[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"_public_publisher_byId_726c817a-36c3-42ac-807e-9d4c55c1ab7e":3,"_public_publication_all{\"sortAscending\":false,\"sortField\":\"updateTime\",\"page\":0,\"size\":10,\"facet\":true,\"searchKey\":\"publisherId:726c817a-36c3-42ac-807e-9d4c55c1ab7e,\"}":85},{"code":4,"data":5,"meta":18},"SUCCESS",{"id":6,"createTime":7,"updateTime":8,"relativeEntities":9,"slug":10,"properties":11,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":20,"manageAffiliations":27,"indexDatabases":42,"url":77,"thumbnailPath":18,"statistic":78,"gsStatistic":18,"type":84,"analyzePriority":18},"726c817a-36c3-42ac-807e-9d4c55c1ab7e","2024-04-11T03:41:18.952+00:00","2025-11-21T10:02:47.445+00:00",[],"Respiratory-Research",{"issn":12,"title":14},{"VOID":13},"1465-993X",{"EN":15},"Respiratory Research","PUBLISHER","PENDING",null,0,[21],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":23,"label":24,"description":26,"parentId":18,"standard":18,"scholarHubFieldId":18},"b3b0f9d8-a31a-43cf-9f7d-d2ce7381db6a",[],{"EN":25},"Pulmonary and Respiratory Medicine",{},[28,35],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":30,"slug":18,"properties":31,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":34,"statistic":18},"c5894808-4e99-4047-bbce-594f58821845",[],{"title":32},{"EN":33},"BioMed Central Ltd.",[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":37,"slug":18,"properties":38,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":41,"statistic":18},"67883518-0c98-470e-b6b0-160ab49bb03d",[],{"title":39},{"EN":40},"BMC",[],[43,60],{"id":44,"indexDatabase":45,"url":55,"indexYears":56,"academicFieldIds":57,"indexDatabaseRanking":59},"a002c4bb-471b-494c-8142-a925e39d74ea",{"id":46,"createTime":18,"updateTime":18,"relativeEntities":47,"label":48,"description":50,"key":52,"publicationTags":53,"standard":18},"3c7051d4-eb7d-4c57-a56b-36fc74c5d1e9",[],{"EN":49,"VI":49},"Scopus - Elsevier",{"EN":49,"VI":51},"Cơ sở dữ liệu Scopus thuộc Elsevier","scopus",[54],"SCOPUS","https:\u002F\u002Fwww.scopus.com\u002Fsourceid\u002F18640","2000-2025",[58],"52ed8621-9465-4306-9795-51cbb342ffa8","SCOPUS__Q1",{"id":61,"indexDatabase":62,"url":74,"indexYears":18,"academicFieldIds":75,"indexDatabaseRanking":18},"867b3ac2-a0ce-4dfd-b31a-3f524c2b283e",{"id":63,"createTime":18,"updateTime":18,"relativeEntities":64,"label":65,"description":67,"key":70,"publicationTags":71,"standard":18},"a4921856-b128-4d9f-8f1f-e80813d3bbd4",[],{"EN":66,"VI":66},"ISI\u002FSCIE - Science Citation Index Expanded",{"EN":68,"VI":69},"SCIE database","Cơ sở dữ liệu SCIE","scie",[72,73],"SCIE","ISI","https:\u002F\u002Fwww.scopus.com\u002Fsourceid\u002Fnull",[76],"5a4bdced-b504-414b-926b-133e43a206cf","https:\u002F\u002Flink.springer.com\u002Fjournal\u002F12931",{"impactFactor":19,"impactFactorByYear":79,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":81,"totalCitation":19,"totalCitationByYear":82,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":83,"hindexLast5Year":19,"hindex":19},{},1,{"2004":80},{},{},"JOURNAL",{"meta":86,"data":88},{"total":87},"2899",[89,280,384,596,748,899,1004,1500,1673,1853],{"id":90,"createTime":91,"updateTime":92,"relativeEntities":93,"slug":94,"properties":95,"entityType":106,"verifyStatus":107,"verifyTime":108,"verifyNote":109,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":110,"fullTextUrl":18,"authors":111,"publicationType":222,"publisherRelationship":223,"citationCount":270,"citationInfo":271,"publishDate":275,"publishYear":272,"citationAnalyzeStatus":276,"lastCitationAnalyze":277,"indexDatabases":278,"openAccess":18,"references":18,"isForceReanalyzing":279},"c5052867-a380-41d4-8103-402b460ef878","2024-01-10T07:43:53.086+00:00","2026-08-24T21:20:30.084+00:00",[],"Effects-of-diabetes-on-the-development-of-radiation-pneumonitis",{"abstract":96,"title":98,"gsPaper":100,"references":102,"doi":104},{"EN":97},"Radiation pneumonia (RP) is a common adverse reaction to radiation therapy in patients with chest tumors. Recent studies have shown that diabetes mellitus (DM), which can cause systemic multisystem damage, specifically targets lungs, and the incidence of RP in patients with a history of diabetes is higher than that in other patients with tumors who have undergone radiotherapy. DM is an important risk factor for RP in tumor patients undergoing RT, and patients with DM should be treated with caution. This article reviews research on the clinical aspects, as well as the mechanism, of the effects of diabetes on RP and suggests future research needed to reduce RP.",{"EN":99},"Effects of diabetes on the development of radiation pneumonitis",{"VOID":101},"[\"17755353964976511399\"]",{"VOID":103},"Unnikrishnan R, Anjana RM, Mohan V. Diabetes mellitus and its complications in India. Nat Rev Endocrinol. 2016;12(6):357–70.\nLutz SZ, Staiger H, Fritsche A, et al. Antihyperglycaemic therapies and cancer risk. Diabetes Vasc Dis Res. 2014;11(6):371–89.\nWu D, Hu D, Chen H, et al. Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. Nature. 2018;559(7715):637–41.\nZaorsky NG, Shaikh T, Ruth K, et al. Prostate cancer patients with unmanaged diabetes or receiving insulin experience inferior outcomes and toxicities after treatment with radiation therapy. Clin Genitourin Cancer. 2017;15(2):326–35, e323.\nAlashkham A, Paterson C, Hubbard S, Nabi G. What is the impact of diabetes mellitus on radiation induced acute proctitis after radical radiotherapy for adenocarcinoma prostate? A prospective longitudinal study. Clin Transl Radiat Oncol. 2019;14:59–63.\nPeairs KS, Barone BB, Snyder CF, et al. Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis. J Clin Oncol. 2011;29(1):40–6.\nBledsoe TJ, Nath SK, Decker RH, et al. Radiation pneumonitis. Clin Chest Med. 2017;38(2):201–8.\nChang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol. 2015;16(6):630–7.\nOrton MD, Mukhopadhyay ND, Weiss E. Evaluation of diabetes as a risk factor for the development of clinically symptomatic pneumonitis following Stereotactic Body Radiation Therapy (SBRT). Int J Radiat Oncol Biol Phys. 2013;87(2):S514.\nPopov D, Simionescu M. Alterations of lung structure in ex-perimental diabetes, and diabetes associated with hyperlipidaemia in hamsters. Eur Respir J. 1997;10(18):1850–8.\nLin CC, Chang CT, Li TC, et al. Objective evidence of impair of alveolar integrity in patients with non-insulin-dependent mellitus using radionuclide inhalation lung scan. Lung. 2002;180(3):181–6.\nClore JN, Thurby-Hay L. Glucocorticoid-induced hyperglycemia. Endocr Pract. 2009;15(5):469–74.\nYamashita H, Takahashi W, Haga A, et al. Radiation pneumonitis after stereotactic radiation therapy for lung cancer. World J Radiol. 2014;9(6):708–15.\nHsia WJ, Jan N, Mukhopadhyay ND, Weiss E. Effect of diabetes mellitus and selected medications on the development of radiation pneumonitis in patients with locally advanced non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2015;93(3):403.\nLuo W, Wang Y, Tang SM. Effect of different fractionated radiotherapy modes on radiation pneumonitis after radical mastectomy in patients with diabetes mellitus. J Modern Oncol. 2019;16(27):2879–82.\nGuo F, Du AN, Shi JL, et al. Clinical study of radiation pneumonitis in patients with esophageal cancer and diabetes after intensity-modulated radiotherapy. Chin J Radiol Health. 2018;06(27):628–30.\nZhang X-J, Sun J-G, Sun J, et al. Prediction of radiation pneumonitis in lung cancer patients: a systematic review. J Cancer Res Clin Oncol. 2012;138(12):2103–16.\nKalman Noah S, Hugo Geoffrey D, Mahon Rebecca N, et al. Diabetes mellitus and radiation induced lung injury after thoracic stereotactic body radiotherapy. Radiother Oncol. 2018;129(2):270–6.\nKong M, Lim YJ, Kim Y, et al. Diabetes mellitus is a predictive factor for radiation pneumonitis after thoracic radiotherapy in patients with lung cancer. Cancer Manag Res. 2019;11:7103–10.\nErgen SA, Dincbas FO, Yücel B, et al. Risk factors of radiation pneumonitis in patients with NSCLC treated with concomitant chemoradiotherapy––Are we underestimating diabetes?––Turkish oncology group (TOG)\u002FLung cancer study group. 2020;14(9):871–879.\nHotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87–91.\nDonath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98–107.\nStolecki D. Markers of the progression of complications in patients with type 2 diabetes: a one-year longitudinal study. Exp Clin Endocrinol Diabetes. 2014;122(08):484–90.\nOsborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18(3):363–74.\nGunasekaran MK, Virama-Latchoumy AL, Girard AC, et al. TLR4-dependant pro-inflammatory effects of HMGB1on human adipocyte. Adipocyte. 2016;5(4):384.\nFerrante AW Jr. Macrophages, fat, and the emergence of immunometabolism. J Clin Invest. 2013;123(12):4992–3.\nBeijnum JRV, Buurman WA, Griffioen AW. Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis. 2008;11(1):91–9.\nPark JS, Arcaroli J, Yum HK, et al. Activation of gene expression in human neutrophils by high mobility group BOX 1 protein. Am J Physiol. 2003;284(4):870–9.\nRubinsztajn R, Przybyowski T, Paplińska-Goryca M, et al. Correlation between hyperinflation defined as an elevated RV\u002FTLC ratio and body composition and cytokine profile in patients with chronic obstructive pulmonary disease. Pneumonol Alergol Pol. 2015;83(2):120–5.\nTrott KR, Herrmann T, Kasper M. Target cells in radiation pneumopathy. Int J Radiat Oncol Biol Phys. 2004;58(02):463–9.\nBüttner C, Skupin A, Reimann T, et al. Local production of interleukin-4 during radiation-induced pneumonitis and pulmonary fibrosis in rats: macrophages as a prominent source of interleukin-4. Am J Respir Cell Mol Biol. 1997;17(3):315–25.\nRinne ST, Feemster LC, Collins BF, et al. Thiazolidinediones and the risk of asthma exacerbation among patients with diabetes: a cohort study. Allergy Asthma Clin Immunol. 2014;10(1):1–6.\nTanaka SI, Isoda F, Ishihara Y, et al. T lymphopaenia in relation to body mass index and TNF-alpha in human obesity: adequate weight reduction can be corrective. Clin Endocrinol. 2001;54(3):347–54.\nHotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–7.\nKim JH, Cho TS, Moon JH, et al. Serial changes in serum eosinophil-associated mediators between atopic and non-atopic children after mycoplasma pneumoniae pneumonia. Allergy Asthma Immunol Res. 2014;6(5):428–33.\nHe T, Tao J, Wang X, et al. Effects of cisatracurium in combination with ventilation on inflammatory factors and immune variations in sepsis rats. Exp Ther Med. 2018;15(5):4414–8.\nChen YH, Lee CH, Hsu TH, et al. Submerged-culture mycelia and broth of the maitake medicinal mushroom grifola frondosa (higher basidiomycetes) alleviate type 2 diabetes-induced alterations in immunocytic function. Int J Med Mushrooms. 2015;17(6):541–56.\nCheekatla SS, Tripathi D, Venkatasubramanian S, et al. NK-CD11c+ cell crosstalk in diabetes enhances IL-6-mediated inflammation during Mycobacterium tuberculosis Infection. PLoS Pathog. 2016;12(10):e1005972.\nPiTkiewicz P, Bernat-Karpińska M, et al. NK cell count and glucotransporter 4 (GLUT4) expression in subjects with type 2 diabetes and colon cancer. Diabetol Metab Syndr. 2016;8(1):38.\nNaruishi K, Omori K, Maeda H, et al. Immune responses to porphyromonas gingivalis infection suppress systemic inflammatory response in experimental murine model. J Biol Regul Homeost Agents. 2011;25(2):195–202.\nPark HR, Jo SK. Lasting effects of an impairment of Th1-like immune response inγ-irradiated mice:a resemblance between irradiated mice and aged mice. Cell Immunol. 2011;267(1):1–8.\nTsoutsou PG. The interplay between radiation and the immune system in the field of post-radical pneumonitis and fibrosis and why it is important to understand it. Expert Opin Pharmacother. 2014;15(13):1781–3.\nSinclair AJ, Conroy SP, Bayer AJ. Impact of diabetes on physical function in older people. Diabetes Care. 2008;31(2):233–5.\nBrowne JL, Hooshmand S, Elam M, et al. The relationship between inflammation, oxidative stress, and metabolic risk factors in type 2 diabetic patients. Phytomed Int J Phytother Phytopharmacol. 2012;20(6):470–80.\nEriksson JW. Metabolic stress in insulin’s target cells leads to ROS accumulation-a hypothetical common pathway causing insulin resistance. FEBS Lett. 2007;581(19):3734–42.\nRehman K, Akash MSH. Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: how are they interlinked?: Oxidative stress and diabetes mellitus. J Cell Biochem. 2017;118(11):3577–85.\nButkowski EG, Jelinek HF. Hyperglycaemia, oxidative stress and inflammation markers. Redox Rep. 2017;22:257–64.\nNovakova-Jiresova A, Luijk PV, Goor HV, et al. Changes in expression of injury after irradiation of increasing volumes in rat lung. Int J Radiat Oncol Biol Phys. 2007;67(5):1510–8.\nMa ZC, Hong Q, Wang YG, et al. Ferulic acid protects human umbilical vein endothelial cells from radiation induced oxidative stress by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways. Biol Pharm Bull. 2010;33(1):29–34.\nDeanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction testing and clinical relevance. Circulation. 2007;115(10):1285–95.\nXu F, Liu Y, Zhu X, et al. Protective effects and mechanisms of vaccarin on vascular endothelial dysfunction in diabetic angiopathy. Int J Mol Sci. 2019;20(18):4587–602.\nChen RF, Chang CH, Wang CT, et al. Suppression of oxygen radicals protects diabetic endothelium damage and tissue perfusion in a streptozotocin-induced diabetes rodent mode. Ann Plas Surg. 2019;82(1S):18–22.\nGuzik TJ, Mussa S, Gastaldi D, et al. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation. 2002;105(14):1656–62.\nBasmaeil YS, Al Subayyil AM, Khatlani T, et al. Human chorionic villous mesenchymal stem\u002Fstromal cells protect endothelial cells from injury induced by high level of glucose. Stem Cell Res Ther. 2018;9(1):238–57.\nTonade D, Liu H, Palczewski K, Kern TS. Photoreceptor cells produce inflammatory products that contribute to retinal vascular permeability in a mouse model of diabetes. Diabetologia. 2017;60(10):2111–20.\nIrhimeh MR, Hamed M, Barthelmes D, et al. Identification of novel diabetes impaired miRNA-transcription factor co-regulatory networks in bone marrow-derived Lin-\u002FVEGF-R2+ endothelial progenitor cells. PLoS ONE. 2018;13(7):e0200194.\nFalkevall A, Mehlem A, Palombo I, et al. Reducing VEGF-B signaling ameliorates renal lipotoxicity and protects against diabetic kidney disease. Cell Metab. 2017;25(3):713–26.\nCui X, Chopp M, Zacharek A, et al. Angiopoietin\u002FTie2 pathway mediates type 2 diabetes induced vascular damage after cerebral stroke. Neurobiol Dis. 2011;43(1):285–92.\nAsahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–7.\nTepper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation. 2002;106(22):2781–6.\nTomaiuolo G. Biomechanical properties of red blood cells in health and disease towards microfluidics. Biomicrofluidics. 2014;8(5):89–110.\nChan K, Chen S, Chen P. Astaxanthin attenuated thrombotic risk factors in type 2 diabetic patients. J Funct Foods. 2019;53:22–7.\nOpdenakker G, El-Asrar AA. Metalloproteinases mediate diabetes-induced retinal neuropathy and vasculopathy. Cell Mol Life Sci. 2019;76:3157–66.\nSuzanne M. The full spectrum of Alzheimer’s disease is rooted in metabolic derangements that drive type 3 diabetes. Adv Exp Med Biol. 2019;1128:45–83.\nLong J, He CJ, Ding H, et al. Effect of shock wave on vascular lesions in diabetic rats. Pain Phys. 2019;22(5):505–10.\nLee S, Lee MY, Nam JS, Kang S, Park JS, Shin S, Ahn CW, Kim KR. Hemorheological approach for early detection of chronic kidney disease and diabetic nephropathy in type 2 diabetes. Diabetes Technol Ther. 2015;17(11):808–15.\nDomingueti CP, Dusse LM, Carvalho M, et al. Diabetes mellitus: the linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. J Diabetes Complicat. 2016;30(4):738–45.\nSchuyler M, Niewoehner D, Inkley S, et al. Abnormal lung elasticity in juvenile diabetes mellitus. Am Rev Respir Dis. 1976;113(1):37–41.\nALIMO. Pulmonarycomplications in diabetes mellitus. Mymensingh Med J. 2014; 23(3):603–605.\nMekov EV, Slavova YG, Genova MP, et al. Diabetes mellitus type 2 in hospitalized COPD patients: impact on quality of life and lung function. Folia Med. 2016;58(1):36–41.\nMckeever TM, Weston PJ, Hubbard R, et al. Lung function and glucose metabolism: an analysis of data from the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 2005;161(6):546–56.\nFord ES, Mannino DM, National H, et al. Prospective association between lung function and the incidence of diabetes: findings from the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Diabetes Care. 2004;27(12):2966–70.\nPinnix C, Perkins GH, Strom EA, et al. Topical hyaluronic acid vs standard of care for the prevention of radiation dermatitis after adjuvant radiotherapy for breast cancer: single-blind randomized phase III clinical trial. Int J Radiat Oncol Biol Phys. 2012;83(4):1089–94.\nPlama DA, Senan S, Tsujino K, et al. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2013;87(4):690–6.\nMalenica M, Šilar M, Dujic T, et al. Importance of inflammatory markers and IL-6 for diagnosis and follow up of patients with type 2 diabetes mellitus. Med Glas Ljek Komore Zenicko-doboj Kantona. 2017;14(2):169–75.\nWu HP, Chu CM, Lin CY, et al. Liver cirrhosis and diabetes mellitus are risk factors for staphylococcus aureus infection in patients with healthcare-associated or hospital-acquired pneumonia. Pulm Med. 2016;2016:4706150.\nWalter RE, Beiser A, Giveller RJ, et al. Association between glycemic state and hung function. Am Respir Crit Care Med. 2003;167(5):911.\nNiren K, Shah PD, Wasim E, et al. A novel sodiumglucose cotransporter type 2 inhibitor for the treatment of type 2 diabetes mellitus. Pharmacotherapy. 2012;32(1):80–94.\nBernard L, Reix N, Benabu JC, et al. Breast cancer and diabetes mellitus: complex interactions. Gynecol Obstet Fertil. 2016;44(12):701–11.\nHuang YJ, Huang TW, Lin FH, et al. Radiation therapy for invasive breast cancer increases the risk of second primary lung cancer: a nationwide population-based cohort analysis. J Thorac Oncol. 2017;12(5):782–90.",{"VOID":105},"10.1186\u002Fs12931-021-01754-4","PUBLICATION","VERIFIED","2024-05-16T02:24:16.452+00:00","Auto Verify","https:\u002F\u002Frespiratory-research.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs12931-021-01754-4",[112,137,152,166,180,194,208],{"id":113,"sortIndex":19,"researcher":18,"roles":114,"affiliations":116,"properties":134,"displayName":136,"givenName":18,"familyName":18},"1f51efaf-cfca-4b40-87c7-3086fcfcc9fa",[115],"AUTHOR",[117,125],{"id":118,"sortIndex":19,"affiliation":119,"properties":18},"25e365fc-8c08-4ca6-8f05-735d52406258",{"id":118,"createTime":18,"updateTime":18,"relativeEntities":120,"slug":18,"properties":121,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":124,"statistic":18},[],{"title":122},{"VI":123},"Department of Endocrinology, Guang anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China",[],{"id":126,"sortIndex":80,"affiliation":127,"properties":133},"07fce237-3432-4d36-90e4-7283d5a16d5a",{"id":126,"createTime":18,"updateTime":18,"relativeEntities":128,"slug":18,"properties":129,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":132,"statistic":18},[],{"title":130},{"VI":131},"College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China",[],{},{"title":135},{"VI":136},"Guangtong Dong",{"id":138,"sortIndex":80,"researcher":18,"roles":139,"affiliations":140,"properties":149,"displayName":151,"givenName":18,"familyName":18},"d6c8bdd0-4e6f-4e51-b863-3809ba2421e4",[115],[141],{"id":142,"sortIndex":19,"affiliation":143,"properties":18},"868373fc-599f-40e4-82aa-b5d6d01668fd",{"id":142,"createTime":18,"updateTime":18,"relativeEntities":144,"slug":18,"properties":145,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":148,"statistic":18},[],{"title":146},{"VI":147},"Department of Oncology, Guang’anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China",[],{"title":150},{"VI":151},"Yuxiao Li",{"id":153,"sortIndex":154,"researcher":18,"roles":155,"affiliations":156,"properties":163,"displayName":165,"givenName":18,"familyName":18},"00f34605-32e5-463f-9780-1450422b5ed1",2,[115],[157],{"id":126,"sortIndex":19,"affiliation":158,"properties":18},{"id":126,"createTime":18,"updateTime":18,"relativeEntities":159,"slug":18,"properties":160,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":162,"statistic":18},[],{"title":161},{"VI":131},[],{"title":164},{"VI":165},"Qiyao Zhao",{"id":167,"sortIndex":168,"researcher":18,"roles":169,"affiliations":170,"properties":177,"displayName":179,"givenName":18,"familyName":18},"5dad9d72-d047-4673-aeb1-cc2f4ebcbbc5",3,[115],[171],{"id":118,"sortIndex":19,"affiliation":172,"properties":18},{"id":118,"createTime":18,"updateTime":18,"relativeEntities":173,"slug":18,"properties":174,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":176,"statistic":18},[],{"title":175},{"VI":123},[],{"title":178},{"VI":179},"Bing Pang",{"id":181,"sortIndex":182,"researcher":18,"roles":183,"affiliations":184,"properties":191,"displayName":193,"givenName":18,"familyName":18},"6806f32a-d23c-406c-91f2-2a35156979de",4,[115],[185],{"id":142,"sortIndex":19,"affiliation":186,"properties":18},{"id":142,"createTime":18,"updateTime":18,"relativeEntities":187,"slug":18,"properties":188,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":190,"statistic":18},[],{"title":189},{"VI":147},[],{"title":192},{"VI":193},"Xin Qi",{"id":195,"sortIndex":196,"researcher":18,"roles":197,"affiliations":198,"properties":205,"displayName":207,"givenName":18,"familyName":18},"904d323b-1bad-4ca5-8649-d1aa0572b485",5,[115],[199],{"id":118,"sortIndex":19,"affiliation":200,"properties":18},{"id":118,"createTime":18,"updateTime":18,"relativeEntities":201,"slug":18,"properties":202,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":204,"statistic":18},[],{"title":203},{"VI":123},[],{"title":206},{"VI":207},"Junping Wei",{"id":209,"sortIndex":210,"researcher":18,"roles":211,"affiliations":212,"properties":219,"displayName":221,"givenName":18,"familyName":18},"4891066a-bd59-4878-9721-c336a1dd797d",6,[115],[213],{"id":142,"sortIndex":19,"affiliation":214,"properties":18},{"id":142,"createTime":18,"updateTime":18,"relativeEntities":215,"slug":18,"properties":216,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":218,"statistic":18},[],{"title":217},{"VI":147},[],{"title":220},{"VI":221},"Wei Hou","ARTICLE",{"url":110,"publisher":224,"properties":265},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":225,"slug":10,"properties":226,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":229,"manageAffiliations":234,"indexDatabases":245,"url":77,"thumbnailPath":18,"statistic":260,"gsStatistic":18,"type":84,"analyzePriority":18},[],{"issn":227,"title":228},{"VOID":13},{"EN":15},[230],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":231,"label":232,"description":233,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[235,240],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":236,"slug":18,"properties":237,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":239,"statistic":18},[],{"title":238},{"EN":33},[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":241,"slug":18,"properties":242,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":244,"statistic":18},[],{"title":243},{"EN":40},[],[246,253],{"id":44,"indexDatabase":247,"url":55,"indexYears":56,"academicFieldIds":252,"indexDatabaseRanking":59},{"id":46,"createTime":18,"updateTime":18,"relativeEntities":248,"label":249,"description":250,"key":52,"publicationTags":251,"standard":18},[],{"EN":49,"VI":49},{"EN":49,"VI":51},[54],[58],{"id":61,"indexDatabase":254,"url":74,"indexYears":18,"academicFieldIds":259,"indexDatabaseRanking":18},{"id":63,"createTime":18,"updateTime":18,"relativeEntities":255,"label":256,"description":257,"key":70,"publicationTags":258,"standard":18},[],{"EN":66,"VI":66},{"EN":68,"VI":69},[72,73],[76],{"impactFactor":19,"impactFactorByYear":261,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":262,"totalCitation":19,"totalCitationByYear":263,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":264,"hindexLast5Year":19,"hindex":19},{},{"2004":80},{},{},{"pages":266,"volume":268},{"VOID":267},"1-8",{"VOID":269},"22",24,{"total":270,"publishYear":272,"statisticByYear":273},2021,{"2022":210,"2023":80,"2024":168,"2025":274,"2026":182},10,"2021-05-24","ERROR_IN_ANALYZE_CITATION","2026-08-24T21:20:30.083+00:00",[72,59],false,{"id":281,"createTime":282,"updateTime":283,"relativeEntities":284,"slug":285,"properties":286,"entityType":106,"verifyStatus":107,"verifyTime":297,"verifyNote":109,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":298,"fullTextUrl":18,"authors":299,"publicationType":222,"publisherRelationship":332,"citationCount":19,"citationInfo":378,"publishDate":381,"publishYear":379,"citationAnalyzeStatus":276,"lastCitationAnalyze":382,"indexDatabases":383,"openAccess":18,"references":18,"isForceReanalyzing":279},"10ab5274-ec49-4304-8135-76cf119959f0","2024-01-19T20:00:06.923+00:00","2026-08-20T01:25:04.164+00:00",[],"Idiopathic-pulmonary-fibrosis-an-epithelial-fibroblastic-cross-talk-disorder",{"abstract":287,"title":289,"gsPaper":291,"references":293,"doi":295},{"EN":288},"Idiopathic pulmonary fibrosis is a chronic and usually progressive lung disorder of unknown etiology. A growing body of evidence suggests that, in contrast to other interstitial lung diseases, IPF is a distinct entity in which inflammation is a secondary and non-relevant pathogenic partner. Evidence includes the presence of similar mild\u002Fmoderate inflammation either in early or late disease, and the lack of response to potent anti-inflammatory therapy. Additionally, it is clear from experimental models and some human diseases that it is possible to have fibrosis without inflammation. An evolving hypothesis proposes that IPF may result from epithelial micro-injuries and abnormal wound healing.",{"EN":290},"Idiopathic pulmonary fibrosis: an epithelial\u002Ffibroblastic cross-talk disorder",{"VOID":292},"[\"1439108020782281231\"]",{"VOID":294},"International consensus statement: Idiopathic pulmonary fibrosis: diagnosis and treatment. Am J Respir Crit Care Med. 2000, 161: 646-664.\nPerez-Padilla R, Salas J, Chapela R, Sanchez M, Carrillo G, Perez R, Gaxiola M, Selman M: Mortality in Mexican patients with chronic pigeon breeder's lung compared with those with usual interstitial pneumonia. Am Rev Respir Dis. 1993, 148: 49-53.\nBjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, Offord KP: Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998, 157: 199-203.\nDouglas WW, Ryu JH, Schroeder DR: Idiopathic pulmonary fibrosis. Impact of oxygen and colchicine, prednisone, or no therapy on survival. Am J Respir Crit Care Med. 2000, 161: 1172-1178.\nSelman M, King TE, Pardo A: Idiopathic pulmonary fibrosis: prevaling and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med. 2001, 134: 136-151.\nKatzenstein ALA, Fiorelli RF: Nonspecific interstitial pneumonia\u002Ffibrosis. Histologic features and clinical significance. Am J Surg Pathol. 1994, 18: 136-147.\nBorzone G, Moreno R, Urrea R, Meneses M, Oyarzun M, Lisboa C: Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2001, 163: 1648-1653.\nNicholson AG, Colby TV, du Bois RM, Hansell DM, Wells AU: The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med. 2000, 162: 2213-2217.\nKatzenstein ALA, Myers JL: Idiopathic pulmonary fibrosis. Clinical relevance of pathologic classification. Am J Respir Crit Care Med. 1998, 157: 1301-1315.\nKing TE, Sdchwarz MI, Brown K, Tose JA, Colby TV, Waldron JA, Flint A, Thurlbeck W, Cherniack RM: Extent of fibroblastic foci predict mortality in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2001, 163: A982-\nAdamson IYR, Young L, Bowden DH: Relationship of alveolar epithelial injury and repair to the induction of pulmonary fibrosis. Am J Pathol. 1988, 130: 377-383.\nRegan W, Wold LE, Coonrad R, Morrey BF: Microscopic histopathology of chronic refractory lateral epicondylitis. Am J Sports Med. 1992, 20: 746-749.\nKraushaar BS, Nirschl RP: Tendinosis of the elbow (tennis elbow): clinical features and findings of histological, immunohistochemical, and electron microscopy studies. J Bone Joint Surg Am. 1999, 81: 259-279. 10.1302\u002F0301-620X.81B2.9154.\nKuhn C, Boldt J, King TE, Crouch E, Vartio T, McDonald JA: An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis. Am Rev Respir Dis. 1989, 140: 1693-1703.\nKasper M, Haroske G: Alterations in the alveolar epithelium after injury leading to pulmonary fibrosis. Histol Histopathol. 1996, 11: 463-483.\nKapanci Y, Desmouliere A, Pache JC, Redard M, Gabbiani G: Cytoskeletal protein modulation in pulmonary alveolar myofibroblasts during idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1995, 152: 2163-2169.\nNash JRG, McLaughlin PJ, Butcher D, Corrin B: Expression of tumour necrosis factor-α in cryptogenic fibrosing alveolitis. Histopathology. 1993, 22: 343-347.\nKhalil N, O'Connor RN, Unruh HW, Warren PW, Flanders KC, Kemp A, Bereznay OH, Greenberg AH: Increased production and immunohistochemical localization of transforming growth factor-β in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol. 1991, 5: 155-162.\nKhalil N, O'Connor RN, Flanders KC, Unruh HW: TGF-β1, but not TGF-β2 or TGF-β3, is differentially present in epithelial cells of advanced pulmonary fibrosis: an immunohistochemical study. Am J Respir Cell Mol Biol. 1996, 14: 131-138.\nAntoniades NH, Bravo M, Avila R, Galanopoulus T, Neville J, Selman M: Platelet-derived growth factor in idiopathic pulmonary fibrosis. J Clin Invest. 1990, 86: 1055-1064.\nKuhn C, McDonald JA: The roles of the myofibroblast in idiopathic pulmonary fibrosis. Ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis. Am J Pathol. 1991, 138: 1257-1265.\nFukuda Y, Basset F, Ferrans VJ, Yamanaka N: Significance of early intra-alveolar fibrotic lesions and integrin expression in lung biopsy specimens from patients with idiopathic pulmonary fibrosis. Hum Pathol. 1995, 26: 53-61.\nUhal BD, Joshi I, True AL, Mundle S, Raza A, Pardo A, Selman M: Fibroblasts isolated after fibrotic lung injury induce apoptosis of alveolar epithelial cells in vitro. Am J Physiol. 1995, 269: L819-828.\nWang R, Ramos C, Joshi I, Zagariya A, Pardo A, Selman M, Uhal B: Human lung myofibroblast-derived inducers of alveolar epithelial apoptosis identified as angiotensin peptides. Am J Physiol. 1999, 277: L1158-L1164.\nUhal BD, Joshi I, Hughes WF, Ramos C, Pardo A, Selman M: Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung. Am J Physiol. 1998, 275: L1192-L1199.\nBarbas-Filho JV, Ferreira MA, Sesso A, Kairalla RA, Carvalho CR, Capelozzi VL: Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)\u002Fusual interstitial pneumonia (UIP). J Clin Pathol. 2001, 54: 132-138. 10.1136\u002Fjcp.54.2.132.\nKuwano K, Miyazaki H, Hagimoto N, Kawasaki M, Fujita M, Kuni-take R, Kaneko Y, Hara N: The involvement of Fas-Fas ligand pathway in fibrosing lung diseases. Am J Respir Cell Mol Biol. 1999, 20: 53-60.\nMaeyama T, Kuwano K, Kawasaki M, Kunitake R, Hagimoto N, Matsuba T, Yoshimi M, Inoshima I, Yoshida K, Hara N: Upregulation of Fas-signalling molecules in lung epithelial cells from patients with idiopathic pulmonary fibrosis. Eur Respir J. 2001, 17: 180-189. 10.1183\u002F09031936.01.17201800.\nEhrlich HP, Desmouliere A, Diegelmann RF, Cohen IK, Compton CC, Garner WL, Kapanci Y, Gabbiani G: Morphological and immunochemical differences between keloid and hypertrophic scar. Am J Pathol. 1994, 145: 105-113.\nChodon T, Sugihara T, Igawa HH, Funayama E, Furukawa H: Keloid-derived fibroblasts are refractory to Fas-mediated apoptosis and neutralization of autocrine transforming growth factor-beta 1 can abrogate this resistance. Am J Pathol. 2000, 157: 1661-1669.\nLuo S, Benathan M, Raffoul W, Panizzon RG, Egloff DV: Abnormal balance between proliferation and apoptotic cell death in fibroblasts derived from keloid lesions. Plast Reconstr Surg. 2001, 107: 87-96. 10.1097\u002F00006534-200101000-00014.\nLappi-Blanco E, Soini Y, Paakko P: Apoptotic activity is increased in the newly formed fibromyxoid connective tissue in bronchiolitis obliterans organizing pneumonia. Lung. 1999, 177: 367-376.\nRamos C, Montaño M, García-Alvarez J, Ruiz V, Uhal BD, Selman M, Pardo A: Fibroblasts from idiopathic pulmonary fibrosis and normal lungs differ in growth rate, apoptosis, and TIMPs expresion. Am J Respir Cell Mol Biol. 2001, 24: 591-598.\nJelaska A, Korn JH: Role of apoptosis and transforming growth factor beta1 in fibroblast selection and activation in systemic sclerosis. Arthritis Rheum. 2000, 43: 2230-2239. 10.1002\u002F1529-0131(200010)43:10\u003C2230::AID-ANR10>3.0.CO;2-8.\nJordana M, Schulman J, McSharry C, Irving LB, Newhouse MT, Jordana G, Gauldie J: Heterogeneous proliferative characteristics of human adult lung fibroblast lines and clonally derived fibroblasts from control and fibrotic tissue. Am Rev Respir Dis. 1988, 137: 579-584.\nRaghu G, Chen YY, Rusch V, Rabinovitch PS: Differential proliferation of fibroblasts cultured from normal and fibrotic human Lung. Am Rev Respir Dis. 1988, 138: 703-708.\nLegrand C, Polette M, Tournier JM, de Bentzmann S, Huet E, Monteau M, Birembaut P: UPa\u002Fplasmin system-mediated MMP-9 activation is implicated in bronchial epithelial cell migration. Exp Cell Res. 2001, 264: 326-336. 10.1006\u002Fexcr.2000.5125.\nDavis G, Pintar Allen K, Salazar R, Maxwell S: Matrix metalloproteinase-1 and -9 activation by plasmin regulates a novel endothelial cell-mediated mechanism of collagen gel contraction and capillary tube regression in three-dimensional collagen matrices. J Cell Sci. 2001, 114: 917-930.\nKotani I, Sato A, Hayakawa H, Urano T, Takada Y, Takada A: Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis. Thromb Res. 1995, 77: 493-504. 10.1016\u002F0049-3848(95)00025-9.\nImokawa S, Sato A, Hayakawa H, Kotani M, Urano T, Takada A: Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis. Am J Respir Crit Care Med. 1997, 156: 631-636.\nFujii M, Hayakawa H, Urano T: Relevance of tissue factor and tissue factor pathway inhibitor for hypercoagulable state in the lungs of patients with idiopathic pulmonary fibrosis. Thromb Res. 2000, 99: 111-117. 10.1016\u002FS0049-3848(00)00237-1.\nSaito Y, Suzuki E, Moriyama H, Terada M, Hasegawa T, Ooi H, Kobayashi Y, Tsuchiya T, Geivo F: Decreased ability to generate plasmin in lung tissue of usual interstitial pneumonia compared with bronchiolitis obliterans organizing pneumonia. Am J Respir Crit Care Med. 2000, 161: A826-\nHiggins PJ, Slack JK, Diegelmann RF, Staiano-Coico L: Differential regulation of PAI-1 gene expression in human fibroblasts predisposed to a fibrotic phenotype. Exp Cell Res. 1999, 248: 634-642. 10.1006\u002Fexcr.1999.4466.\nHayashi T, Stetler-Stevenson WG, Fleming MV, Fishback N, Koss MN, Liotta LA, Ferrans VJ, Travis WD: Immunohistochemical study of metalloproteinases and their tissue inhibitors in the lungs of patients with diffuse alveolar damage and idiopathic pulmonary fibrosis. Am J Pathol. 1996, 149: 1241-1256.\nFukuda Y, Ishizaki M, Kudoh S, Kitaichi M, Yamanaka N: Localization of matrix metalloproteinases-1, -2, and -9, and tissue inhibitor of metalloproteinase-2 in interstitial lung diseases. Lab Invest. 1998, 78: 687-698.\nSelman M, Ruiz V, Cabrera S, Segura L, Ramírez R, Barrios R, Pardo A: TIMP 1, 2, 3 and 4 in idiopathic pulmonary fibrosis. A prevailing non-degradative lung microenvironment?. Am J Physiol. 2000, 279: L562-L574.\nZhang K, Rekhter MD, Gordon D, Phan SH: Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. Am J Pathol. 1994, 145: 114-125.\nParks WC, Sudbeck BD, Doyle GR, Saariahlo-Kere UK: Matrix metalloproteinases in tissue repair. In Matrix Metalloproteinases. Edited by Parks WC, Mecham RP. San Diego: Academic Press;. 1998, 263-297.",{"VOID":296},"10.1186\u002Frr175","2024-06-24T05:06:34.534+00:00","https:\u002F\u002Frespiratory-research.biomedcentral.com\u002Farticles\u002F10.1186\u002Frr175",[300,317],{"id":301,"sortIndex":19,"researcher":18,"roles":302,"affiliations":303,"properties":312,"displayName":314,"givenName":18,"familyName":18},"7caec6f1-c01e-4ee8-802f-4820b6e13526",[115],[304],{"id":305,"sortIndex":19,"affiliation":306,"properties":18},"ab49c8da-a9d4-4e22-89b8-fa5a44ca6619",{"id":305,"createTime":18,"updateTime":18,"relativeEntities":307,"slug":18,"properties":308,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":311,"statistic":18},[],{"title":309},{"VI":310},"Instituto Nacional de Enfermedades Respiratorias & Facultad de Ciencias, UNAM, México DF, México",[],{"title":313,"gsAuthor":315},{"VI":314},"Moisés Selman",{"VOID":316},"[\"2-EDU9gAAAAJ\"]",{"id":318,"sortIndex":80,"researcher":18,"roles":319,"affiliations":320,"properties":327,"displayName":329,"givenName":18,"familyName":18},"df66adef-2963-4ecf-8c51-088f6a334571",[115],[321],{"id":305,"sortIndex":19,"affiliation":322,"properties":18},{"id":305,"createTime":18,"updateTime":18,"relativeEntities":323,"slug":18,"properties":324,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":326,"statistic":18},[],{"title":325},{"VI":310},[],{"title":328,"gsAuthor":330},{"VI":329},"Annie Pardo",{"VOID":331},"[\"snoM8VUAAAAJ\"]",{"url":298,"publisher":333,"properties":374},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":334,"slug":10,"properties":335,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":338,"manageAffiliations":343,"indexDatabases":354,"url":77,"thumbnailPath":18,"statistic":369,"gsStatistic":18,"type":84,"analyzePriority":18},[],{"issn":336,"title":337},{"VOID":13},{"EN":15},[339],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":340,"label":341,"description":342,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[344,349],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":345,"slug":18,"properties":346,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":348,"statistic":18},[],{"title":347},{"EN":33},[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":350,"slug":18,"properties":351,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":353,"statistic":18},[],{"title":352},{"EN":40},[],[355,362],{"id":44,"indexDatabase":356,"url":55,"indexYears":56,"academicFieldIds":361,"indexDatabaseRanking":59},{"id":46,"createTime":18,"updateTime":18,"relativeEntities":357,"label":358,"description":359,"key":52,"publicationTags":360,"standard":18},[],{"EN":49,"VI":49},{"EN":49,"VI":51},[54],[58],{"id":61,"indexDatabase":363,"url":74,"indexYears":18,"academicFieldIds":368,"indexDatabaseRanking":18},{"id":63,"createTime":18,"updateTime":18,"relativeEntities":364,"label":365,"description":366,"key":70,"publicationTags":367,"standard":18},[],{"EN":66,"VI":66},{"EN":68,"VI":69},[72,73],[76],{"impactFactor":19,"impactFactorByYear":370,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":371,"totalCitation":19,"totalCitationByYear":372,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":373,"hindexLast5Year":19,"hindex":19},{},{"2004":80},{},{},{"pages":375,"volume":376},{"VOID":267},{"VOID":377},"3",{"total":19,"publishYear":379,"statisticByYear":380},2001,{},"2001-10-11","2026-08-20T01:25:04.161+00:00",[72,59],{"id":385,"createTime":386,"updateTime":387,"relativeEntities":388,"slug":389,"properties":390,"entityType":106,"verifyStatus":107,"verifyTime":401,"verifyNote":109,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":402,"fullTextUrl":18,"authors":403,"publicationType":222,"publisherRelationship":543,"citationCount":19,"citationInfo":590,"publishDate":593,"publishYear":591,"citationAnalyzeStatus":276,"lastCitationAnalyze":594,"indexDatabases":595,"openAccess":18,"references":18,"isForceReanalyzing":279},"07874d68-01e8-441f-8142-f79597ac88c9","2024-01-13T08:07:20.024+00:00","2026-08-17T08:34:35.400+00:00",[],"Thoracic-skeletal-muscle-quantification-low-muscle-mass-is-related-with-worse-prognosis-in-idiopathic-pulmonary-fibrosis-patients",{"abstract":391,"title":393,"gsPaper":395,"references":397,"doi":399},{"EN":392},"Sarcopenia can contribute to negative outcomes in patients with various lung diseases. However, whether sarcopenia affects prognosis in patients with idiopathic pulmonary fibrosis (IPF) has not been reported. Simple measures of muscle mass, derived from chest computed tomography (CT), are increasingly being used to identify patients with sarcopenia. We hypothesized that skeletal muscle mass could be a predictor of prognosis in IPF patients. We retrospectively evaluated 180 patients diagnosed with IPF between January 2010 and December 2015 at a tertiary care hospital in South Korea. We measured thoracic muscle volume by using the cross-sectional area (CSA) of the pectoralis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA) and the erector spinae muscle (ESMCSA) at the 12th vertebral region. CT scans at the time of diagnosis were used for analysis and respective CSA were divided by height squared to normalize for stature. Survival times were estimated with the Kaplan–Meier method and compared with the log-rank test. Multivariate Cox proportional hazards models were performed to investigate relationships between clinical parameters and mortality. Male patients in the lowest quartile of T4CSA divided by height squared (m2) (T4MI) and in the lowest quartile of ESMCSA divided by height squared (m2) (T12MI) were more likely to have higher Gender-Age-Physiology Index scores (T4MI, 3.3 ± 1.3 vs 4.0 ± 1.6, P = 0.012; T12MI, 3.2 ± 1.3 vs 4.1 ± 1.6, P = 0.002). Male patients in the lowest quartile of T4MI exhibited a significantly lower survival rate (P = 0.035). After multivariate Cox proportional hazards analysis, T4MI was a significant risk factor for all-cause mortality (HR, 0.955; 95% CI, 0.913–0.998; P = 0.041), whereas T12MI was not (HR, 0.980; 95% CI, 0.856–1.121; P = 0.766). Low skeletal mass normalized for stature at the level of 4th vertebrae which can be acquired by quantifying thoracic skeletal muscle on single-slice axial chest CT, may be a strong risk factor for all-cause mortality in patients with IPF. The research protocol was approved by the Institutional Review Board of Severance Hospital, South Korea (IRB No.4–2018-0454).",{"EN":394},"Thoracic skeletal muscle quantification: low muscle mass is related with worse prognosis in idiopathic pulmonary fibrosis patients",{"VOID":396},"[\"2464847177297338370\"]",{"VOID":398},"Muscaritoli M, Anker SD, Argiles J, Aversa Z, Bauer JM, Biolo G, Boirie Y, Bosaeus I, Cederholm T, Costelli P, et al. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by special interest groups (SIG) \"cachexia-anorexia in chronic wasting diseases\" and \"nutrition in geriatrics\". Clin Nutr (Edinburgh, Scotland). 2010;29(2):154–9.\nOkumura S, Kaido T, Hamaguchi Y, Kobayashi A, Shirai H, Fujimoto Y, Iida T, Yagi S, Taura K, Hatano E, et al. Impact of skeletal muscle mass, muscle quality, and visceral adiposity on outcomes following resection of intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2017;24(4):1037–45.\nDeluche E, Leobon S, Desport JC, Venat-Bouvet L, Usseglio J, Tubiana-Mathieu N. Impact of body composition on outcome in patients with early breast cancer. Support Care Cancer. 2018;26(3):861-68. https:\u002F\u002Fdoi.org\u002F10.1007\u002Fs00520-017-3902-6. Epub 2017 Sep 25.\nKim EY, Kim YS, Park I, Ahn HK, Cho EK, Jeong YM. Prognostic significance of CT-determined sarcopenia in patients with small-cell lung Cancer. J Thorac Oncol. 2015;10(12):1795–9.\nKim EY, Kim YS, Park I, Ahn HK, Cho EK, Jeong YM, Kim JH. Evaluation of sarcopenia in small-cell lung cancer patients by routine chest CT. Support Care Cancer. 2016;24(11):4721–6.\nTsukioka T, Nishiyama N, Izumi N, Mizuguchi S, Komatsu H, Okada S, Toda M, Hara K, Ito R, Shibata T. Sarcopenia is a novel poor prognostic factor in male patients with pathological stage I non-small cell lung cancer. Jpn J Clin Oncol. 2017;47(4):363–8.\nZuckerman J, Ades M, Mullie L, Trnkus A, Morin JF, Langlois Y, Ma F, Levental M, Morais JA, Afilalo J. Psoas muscle area and length of stay in older adults undergoing cardiac operations. Ann Thorac Surg. 2017;103(5):1498–504.\nFujimoto H, Kobayashi T, Azuma A. Idiopathic pulmonary fibrosis: treatment and prognosis. Clin Med Insights Circ Respir Pulm Med. 2015;9(Suppl 1):179–85.\nHeymsfield SB, Gonzalez MC, Lu J, Jia G, Zheng J. Skeletal muscle mass and quality: evolution of modern measurement concepts in the context of sarcopenia. Proc Nutr Soc. 2015;74(4):355–66.\nJones KI, Doleman B, Scott S, Lund JN, Williams JP. Simple psoas cross-sectional area measurement is a quick and easy method to assess sarcopenia and predicts major surgical complications. Color Dis. 2015;17(1):O20–6.\nRangel EL, Rios-Diaz AJ, Uyeda JW, Castillo-Angeles M, Cooper Z, Olufajo OA, Salim A, Sodickson AD. Sarcopenia increases risk of long-term mortality in elderly patients undergoing emergency abdominal surgery. J Trauma Acute Care Surg. 2017;83(6):1179-1186. https:\u002F\u002Fdoi.org\u002F10.1097\u002FTA.0000000000001657.\nFuseya Y, Hasegawa K, Uemasu K, Sato A, Oguma T, Hirai T, Mishima M, Muro S. Quantitative assessment of erector spinae muscles in patients with chronic obstructive pulmonary disease. Novel chest computed tomography-derived index for prognosis. Ann Am Thorac Soc. 2016;13(3):334-41. https:\u002F\u002Fdoi.org\u002F10.1513\u002FAnnalsATS.201507-446OC.\nMathur S, Rodrigues N, Mendes P, Rozenberg D, Singer LG. Computed tomography–derived thoracic muscle size as an Indicator of sarcopenia in people with advanced lung disease. Cardiopulm Phys Ther J. 2017;28(3):99–105.\nMcDonald ML, Diaz AA, Ross JC, San Jose Estepar R, Zhou L, Regan EA, Eckbo E, Muralidhar N, Come CE, Cho MH, et al. Quantitative computed tomography measures of pectoralis muscle area and disease severity in chronic obstructive pulmonary disease. A cross-sectional study. Ann Am Thorac Soc. 2014;11(3):326–34.\nRozenberg D, Mathur S, Herridge M, Goldstein R, Schmidt H, Chowdhury NA, Mendes P, Singer LG. Thoracic muscle cross-sectional area is associated with hospital length of stay post lung transplantation: a retrospective cohort study. Transplant Int. 2017;30(7):713–24.\nRaghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, et al. An official ATS\u002FERS\u002FJRS\u002FALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.\nLey B, Ryerson CJ, Vittinghoff E, et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012;156(10):684–91.\nCampins L, Camps M, Riera A, Pleguezuelos E, Yebenes JC, Serra-Prat M. Oral drugs related with muscle wasting and sarcopenia. A review. Pharmacology. 2017;99(1–2):1–8.\nDi Marco F, Terraneo S, Roggi MA, Repossi AC, Pellegrino GM, Veronelli A, Santus P, Pontiroli AE, Centanni S. Physical activity impairment in depressed COPD subjects. Respir Care. 2014;59(5):726–34.\nVaz Fragoso CA, Beavers DP, Hankinson JL, Flynn G, Berra K, Kritchevsky SB, Liu CK, McDermott MM, Manini TM, Rejeski WJ, et al. Respiratory impairment and dyspnea and their associations with physical inactivity and mobility in sedentary community-dwelling older persons. J Am Geriatr Soc. 2014;62(4):622–8.\nMarquis K, Debigare R, Lacasse Y, LeBlanc P, Jobin J, Carrier G, Maltais F. Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002;166(6):809–13.\nShen W, Punyanitya M, Wang Z, Gallagher D, St-Onge MP, Albu J, Heymsfield SB, Heshka S. Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. J Applied Physiol (Bethesda, Md : 1985). 2004;97(6):2333–8.\nCollard HR, King TE Jr, Bartelson BB, Vourlekis JS, Schwarz MI, Brown KK. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003;168(5):538–42.\nLey B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(4):431–40.\nKing TE Jr, Tooze JA, Schwarz MI, Brown KR, Cherniack RM. Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Care Med. 2001;164(7):1171–81.\nEl-Gamal H, Khayat A, Shikora S, Unterborn JN. Relationship of dyspnea to respiratory drive and pulmonary function tests in obese patients before and after weight loss. Chest. 2005;128(6):3870–4.\nKruger HS, Micklesfield LK, Wright HH, Havemann-Nel L, Goedecke JH. Ethnic-specific cut-points for sarcopenia: evidence from black south African women. Eur J Clin Nutr. 2015;69(7):843–9.",{"VOID":400},"10.1186\u002Fs12931-019-1001-6","2024-06-26T19:10:47.088+00:00","https:\u002F\u002Frespiratory-research.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs12931-019-1001-6",[404,421,434,447,460,475,488,501,515,529],{"id":405,"sortIndex":19,"researcher":18,"roles":406,"affiliations":407,"properties":416,"displayName":418,"givenName":18,"familyName":18},"6fc5f5c4-56e0-45dc-bca7-53d50eb4ae99",[115],[408],{"id":409,"sortIndex":19,"affiliation":410,"properties":18},"8d31caf4-8947-4c7c-a12a-6e0406c54959",{"id":409,"createTime":18,"updateTime":18,"relativeEntities":411,"slug":18,"properties":412,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":415,"statistic":18},[],{"title":413},{"VI":414},"Division of Pulmonary Medicine Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea",[],{"title":417,"gsAuthor":419},{"VI":418},"Sung Woo Moon",{"VOID":420},"[\"Uf9yaXQAAAAJ\"]",{"id":422,"sortIndex":80,"researcher":18,"roles":423,"affiliations":424,"properties":431,"displayName":433,"givenName":18,"familyName":18},"b58525d9-d653-42ca-af91-36c282925b61",[115],[425],{"id":409,"sortIndex":19,"affiliation":426,"properties":18},{"id":409,"createTime":18,"updateTime":18,"relativeEntities":427,"slug":18,"properties":428,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":430,"statistic":18},[],{"title":429},{"VI":414},[],{"title":432},{"VI":433},"Ji Soo Choi",{"id":435,"sortIndex":154,"researcher":18,"roles":436,"affiliations":437,"properties":444,"displayName":446,"givenName":18,"familyName":18},"5a45f0d6-8731-461d-bbd8-3ff5cbd7c416",[115],[438],{"id":409,"sortIndex":19,"affiliation":439,"properties":18},{"id":409,"createTime":18,"updateTime":18,"relativeEntities":440,"slug":18,"properties":441,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":443,"statistic":18},[],{"title":442},{"VI":414},[],{"title":445},{"VI":446},"Sang Hoon Lee",{"id":448,"sortIndex":168,"researcher":18,"roles":449,"affiliations":450,"properties":457,"displayName":459,"givenName":18,"familyName":18},"af838d0a-0556-4f4b-b9cb-d9346c76bee2",[115],[451],{"id":409,"sortIndex":19,"affiliation":452,"properties":18},{"id":409,"createTime":18,"updateTime":18,"relativeEntities":453,"slug":18,"properties":454,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":456,"statistic":18},[],{"title":455},{"VI":414},[],{"title":458},{"VI":459},"Kyung Soo Jung",{"id":461,"sortIndex":182,"researcher":18,"roles":462,"affiliations":463,"properties":470,"displayName":472,"givenName":18,"familyName":18},"7abf13ca-eb94-4ae9-8e4e-5959a6a0ce77",[115],[464],{"id":409,"sortIndex":19,"affiliation":465,"properties":18},{"id":409,"createTime":18,"updateTime":18,"relativeEntities":466,"slug":18,"properties":467,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":469,"statistic":18},[],{"title":468},{"VI":414},[],{"title":471,"gsAuthor":473},{"VI":472},"Ji Ye Jung",{"VOID":474},"[\"bPRdw2kAAAAJ\"]",{"id":476,"sortIndex":196,"researcher":18,"roles":477,"affiliations":478,"properties":485,"displayName":487,"givenName":18,"familyName":18},"8c72111b-900d-438e-859c-56e2109a0579",[115],[479],{"id":409,"sortIndex":19,"affiliation":480,"properties":18},{"id":409,"createTime":18,"updateTime":18,"relativeEntities":481,"slug":18,"properties":482,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":484,"statistic":18},[],{"title":483},{"VI":414},[],{"title":486},{"VI":487},"Young Ae Kang",{"id":489,"sortIndex":210,"researcher":18,"roles":490,"affiliations":491,"properties":498,"displayName":500,"givenName":18,"familyName":18},"c2de1391-82a2-41d2-abab-06d7d1e4c9f5",[115],[492],{"id":409,"sortIndex":19,"affiliation":493,"properties":18},{"id":409,"createTime":18,"updateTime":18,"relativeEntities":494,"slug":18,"properties":495,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":497,"statistic":18},[],{"title":496},{"VI":414},[],{"title":499},{"VI":500},"Moo Suk Park",{"id":502,"sortIndex":503,"researcher":18,"roles":504,"affiliations":505,"properties":512,"displayName":514,"givenName":18,"familyName":18},"fa298733-862f-4d6e-9fbe-69d303eb4b66",7,[115],[506],{"id":409,"sortIndex":19,"affiliation":507,"properties":18},{"id":409,"createTime":18,"updateTime":18,"relativeEntities":508,"slug":18,"properties":509,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":511,"statistic":18},[],{"title":510},{"VI":414},[],{"title":513},{"VI":514},"Young Sam Kim",{"id":516,"sortIndex":517,"researcher":18,"roles":518,"affiliations":519,"properties":526,"displayName":528,"givenName":18,"familyName":18},"784da596-be28-4365-878d-7120935e57b7",8,[115],[520],{"id":409,"sortIndex":19,"affiliation":521,"properties":18},{"id":409,"createTime":18,"updateTime":18,"relativeEntities":522,"slug":18,"properties":523,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":525,"statistic":18},[],{"title":524},{"VI":414},[],{"title":527},{"VI":528},"Joon Chang",{"id":530,"sortIndex":531,"researcher":18,"roles":532,"affiliations":533,"properties":540,"displayName":542,"givenName":18,"familyName":18},"5889c873-a023-4f07-9fe3-ee9f102aa90b",9,[115],[534],{"id":409,"sortIndex":19,"affiliation":535,"properties":18},{"id":409,"createTime":18,"updateTime":18,"relativeEntities":536,"slug":18,"properties":537,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":539,"statistic":18},[],{"title":538},{"VI":414},[],{"title":541},{"VI":542},"Song Yee Kim",{"url":402,"publisher":544,"properties":585},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":545,"slug":10,"properties":546,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":549,"manageAffiliations":554,"indexDatabases":565,"url":77,"thumbnailPath":18,"statistic":580,"gsStatistic":18,"type":84,"analyzePriority":18},[],{"issn":547,"title":548},{"VOID":13},{"EN":15},[550],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":551,"label":552,"description":553,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[555,560],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":556,"slug":18,"properties":557,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":559,"statistic":18},[],{"title":558},{"EN":33},[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":561,"slug":18,"properties":562,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":564,"statistic":18},[],{"title":563},{"EN":40},[],[566,573],{"id":44,"indexDatabase":567,"url":55,"indexYears":56,"academicFieldIds":572,"indexDatabaseRanking":59},{"id":46,"createTime":18,"updateTime":18,"relativeEntities":568,"label":569,"description":570,"key":52,"publicationTags":571,"standard":18},[],{"EN":49,"VI":49},{"EN":49,"VI":51},[54],[58],{"id":61,"indexDatabase":574,"url":74,"indexYears":18,"academicFieldIds":579,"indexDatabaseRanking":18},{"id":63,"createTime":18,"updateTime":18,"relativeEntities":575,"label":576,"description":577,"key":70,"publicationTags":578,"standard":18},[],{"EN":66,"VI":66},{"EN":68,"VI":69},[72,73],[76],{"impactFactor":19,"impactFactorByYear":581,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":582,"totalCitation":19,"totalCitationByYear":583,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":584,"hindexLast5Year":19,"hindex":19},{},{"2004":80},{},{},{"pages":586,"volume":588},{"VOID":587},"1-9",{"VOID":589},"20",{"total":19,"publishYear":591,"statisticByYear":592},2019,{},"2019-02-15","2026-08-17T08:34:35.399+00:00",[72,59],{"id":597,"createTime":598,"updateTime":599,"relativeEntities":600,"slug":601,"properties":602,"entityType":106,"verifyStatus":107,"verifyTime":613,"verifyNote":109,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":614,"fullTextUrl":18,"authors":615,"publicationType":222,"publisherRelationship":696,"citationCount":18,"citationInfo":18,"publishDate":743,"publishYear":744,"citationAnalyzeStatus":745,"lastCitationAnalyze":746,"indexDatabases":747,"openAccess":18,"references":18,"isForceReanalyzing":279},"380d33cb-6675-4445-8155-d1f3e45e1846","2024-02-09T12:22:14.857+00:00","2026-07-31T01:49:35.480+00:00",[],"Epimorphin-expression-in-interstitial-pneumonia",{"abstract":603,"title":605,"gsPaper":607,"references":609,"doi":611},{"EN":604},"Epimorphin modulates epithelial morphogenesis in embryonic mouse organs. We previously suggested that epimorphin contributes to repair of bleomycin-induced pulmonary fibrosis in mice via epithelium-mesenchyme interactions. To clarify the role of epimorphin in human lungs, we evaluated epimorphin expression and localization in normal lungs, lungs with nonspecific interstitial pneumonia (NSIP), and lungs with usual interstitial pneumonia (UIP); we also studied the effect of recombinant epimorphin on cultured human alveolar epithelial cells in vitro. Northern and Western blotting analyses revealed that epimorphin expression in NSIP samples were significantly higher than those in control lungs and lungs with UIP. Immunohistochemistry showed strong epimorphin expression in mesenchymal cells of early fibrotic lesions and localization of epimorphin protein on mesenchymal cells and extracellular matrix of early fibrotic lesions in the nonspecific interstitial pneumonia group. Double-labeled fluorescent images revealed expression of matrix metalloproteinase 2 in re-epithelialized cells overlying epimorphin-positive early fibrotic lesions. Immunohistochemistry and metalloproteinase activity assay demonstrated augmented expression of metalloproteinase induced by recombinant epimorphin in human alveolar epithelial cells. These findings suggest that epimorphin contributes to repair of pulmonary fibrosis in nonspecific interstitial pneumonia, perhaps partly by inducing expression of matrix metalloproteinase 2, which is an important proteolytic factor in lung remodeling.",{"EN":606},"Epimorphin expression in interstitial pneumonia",{"VOID":608},"[]",{"VOID":610},"Gumbiner BM: Epithelial morphogenesis. Cell 1992, 69:471–482.\nGoldin GV: Towards a mechanism for morphogenesis in epithelio-mesenchymal organs. Q Rev Biol 1980, 55:251–265.\nMaGowan SE: Extracellular matrix and the regulation of lung development and repair. FASEB J 1992, 6:2895–2904.\nKasper M, Haroske G: Alterations in the alveolar epithelium after leading to pulmonary fibrosis. Histol Histopathol 1996, 11:463–483.\nFukuda Y, Ferrans VJ, Schoenber CI, Rennad SI, Crystal RG: Patterns of pulmonary structural remodeling after experimental paraquat toxicity. Am J Pathol 1985, 118:452–475.\nFukuda Y, Ishizaki M, Masuda Y, Kimura G, Kawanami O, Masugi Y: The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage. Am J Pathol 1987, 126:171–182.\nFukuda Y, Takemura T, Ferrans VJ: Evolution of metaplastic squamous cells of alveolar walls in pulmonary fibrosis produced by paraquat: an ultrastructural and immunohistochemical study. Virchows Arch [Cell Pathol] 1989, 58:27–43.\nEpler GR, Colby TV, McLoud TC, Carrington CB, Gaensler EA: Bronchiolitis obliterans organizing pneumonia. N Engl J Med 1985, 312:152–158.\nBasset F, Ferrans VJ, Soler P, Takemura T, Fukuda Y, Crystal RG: Intraluminal fibrosis in interstitial lung disorders. Am J Pathol 1986, 122:443–461.\nKuhn CD, Boldt J, King TE Jr, Crouch E, Vartio T, McDonald JA: An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis. Am Rev Respir Dis 1989, 140:1693–1703.\nRichard HS: Alveolar epithelial cells in pulmonary fibrosis. In Pulmonary Fibrosis. Lung Biology in Health and Disease. Volume 80. New York: Marcel Dekker; 1989:511–540.\nUsuki J, Fukuda Y: Evolution of three patterns of intra-alveolar fibrosis produced by bleomycin in rats. Pathol Int 1995, 45:552–564.\nFukuda Y, Ishizaki M, Kudoh S, Kitaichi M, Yamanaka N: Localization of matrix metalloproteinases-1,-2, and -9 and tissue inhibitor of metalloproteinase-2 in interstitial lung diseases. Lab Invest 1998, 78:687–698.\nKatzenstein AA, Fiorelli RF: Non-specific interstitial pneumonia\u002Ffibrosis. Histologic pattern and clinical significance. Am J Surg Pathol 1994, 18:136–147.\nHirai Y, Takebe K, Takashina M, Kobayashi S, Takeichi M: Epimorphin: a mesenchymal protein essential for epithelial morphogenesis. Cell 1992, 69:471–481.\nHirose M, Watanabe S, Oide H, Kitamura T, Miyazaki A, Sato N: A new function of Ito cells in liver morphogenesis: evidence using a novel morphogenic protein, epimorphin, in vitro . Biochem Biophys Res Commun 1996, 225:155–160.\nWatanabe S, Hirose M, Wang XE, Ikejima K, Oide H, Kitamura T, Takei Y, Miyazaki A, Sato N: A novel hepatic stellate (Ito) cell-derived protein, epimorphin, plays a key role in the late stages of liver regeneration. Biochem Biophys Res Commun 1998, 250:486–490.\nMori M, Miyazaki K: Factors affecting morphogenesis of rabbit gallbladder epithelial cells cultured in collagen gels. Cell Tissue Res 2000, 300:331–344.\nLehnert L, Lerch MM, Hirai Y, Kruse ML, Schmiegel W, Kalthoff H: Autocrine stimulation of human pancreatic duct-like development by soluble isoforms of epimorphin in vitro . J Cell Biol 2001, 152:911–922.\nGoyal A, Singh R, Swietlicki EA, Levin MS, Rubin DC: Characterization of rat epimorphin\u002Fsyntaxin 2 expression suggests a role in crypt-villus morphogenesis. Am J Physiol 1998, 275:G114-G124.\nHirai Y, Andre L, Sybille G, Koshida S, Niwa S, Bissell JM: Epimorphin functions as a key morphoregulator for mammary epithelial cells. J Cell Biol 1998, 140:159–169.\nHirai Y, Radisky D, Boudreau R, Simian M, Stevens ME, Oka Y, Takebe K, Niwa S, Bissell MJ: Epimorphin mediates mammary luminal morphogenesis through control of C\u002FEBPβ. J Cell Biol 2001, 153:785–794.\nSimian M, Hirai Y, Navre M, Werb Z, Lochter A, Bissell MJ: The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development 2001, 128:3117–3131. breast cancer. Breast Cancer Res. 2002. 4:113–121\nZahnow CA: CCAAT\u002Fenhancer binding proteins in normal mammary development and breast cancer. Breast Cancer Res 2002, 4:113–121.\nFukuda Y, Ishizaki M, Okada Y, Seiki M, Yamanaka N: Matrix metalloproteinases and tissue inhibitor of metalloproteinase-2 in fetal rabbit lung. Am J Physiol Lung Cell Mol Physiol 2000, 279:L555-L561.\nYaguchi T, Fukuda Y, Ishizaki M, Yamanaka N: Immunohistochemical and gelatin zymography studies for matrix metalloproteinases in bleomycin-induced pulmonary fibrosis. Pathol Int 1998, 48:954–963.\nKunugi S, Fukuda Y, Ishizaki M, Yamanaka N: Role of MMP-2 in alveolarepithelial cell repair after bleomycin administration in rabbits. Lab Invest 2001, 81:1309–1318.\nHirai Y: Molecular cloning of human epimorphin. Biochem Biophys Res Commun 1993, 191:1332–1337.\nZah H, Remmers EF, Szpirer C, Szpirer J, Zhang H, Kozak CA, Wilder RL: The epimorphin gene is highly conserved among humans, mice, and rats and maps to human chromosome 7, mouse chromosome 5, and rat chromosome 12. Genomics 1996, 37:386–389.\nAmerican Thoracic Society\u002FEuropean Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial PneumoniasAm J Respir Crit Care Med 2002, 165:277–304.\nZhang L, Ishikawa O, Takeuchi Y, Miyachi Y: Expression of epimorphin in normal and diseased human skin. Immunohistochemical and immunoblot detection. Eur J Dermatol 1996, 6:568–572.\nZhang L, Ishikawa O, Takeuchi Y, Miyachi Y: Immunohistochemical distribution of epimorphin in human and mouse tissues. Histochem J 1998, 30:903–908.\nNagata T, Kumagai F, Hesezawa S: The origin and organization of cortical microtubules during the transition between M and G 1 phases of the cell cycle as observed in highly synchronized cells of tobacco BY-2. Planta 1994, 193:567–572.\nTerasaki Y, Fukuda Y, Ishizaki M, Yamanaka N: Increased expression of epimorphin in bleomycin-induced pulmonary fibrosis in mice. Am J Respir Cell Mol Biol 2000, 23:168–174.\nDrummond HB: Cell turnover in the lung. Am Rev Respir Dis 1983, 128:S46-S48.\nEvans MJ, Shami SG: Lung cell kinetics. In Lung Cell Biology. Lung Biology in Health and Disease. Volume 41. Edited by: Massaro D. Marcel Dekker, New York; 1989:1–36.\nHorikoshi S, Yoshikawa M, Shibata T, Takahashi K, Shirato I, Tomino Y: Protein localization and mRNA expression of epimorphin in mouse and human kidneys. Exp Nephrol 2001, 9:412–419.\nZhang L, Ishikawa O, Takeuchi Y, Yokoyama Y, Miyachi Y: Influences of keratinocyte-fibroblast interaction on the expression of epimorphin by fibroblasts in vitro. J Dermatol Sci 1999, 20:191–196.\nFukuda Y, Basset F, Ferrans VJ, Yamanaka N: Significance of early intraalveolar fibrotic lesions and integrin expression in lung biopsy specimens from patients with idiopathic pulmonary fibrosis. Hum Pathol 1995, 26:53–61.\nPeter DB, Christine HW: The pathogenesis of pulmonary fibrosis. In Pulmonary Diseases and Disorders. Volume 1. third edition. Edited by: Fishman AP. McGraw-Hill, New York; 1997:355.\nLimper AH, Roman J: Fibronectin. A versatile matrix protein with roles in thoracic development, repair and infection. Chest 1992, 101:1663–1673.\nShirasaka T, Iizuka M, Yukawa M, Hirai Y, Horie Y, Itou H, Kon-No S, Fukushima T, Watanabe S: Altered expression of epimorphin in ulcerative colitis. J Gastroenterol Hepatol 2003, 18:570–577.\nAdamson IY, Hedgecock C, Bowden DH: Epithelial cell-fibroblast interactions in lung injury and repair. Am J Pathol 1990, 137:385–392.\nUhal BD, Iravati J, Hughes WF, Ramos C, Pardo A, Selman M: Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung. Am J Physiol 1998, 275:L1192-L1199.\nd' Ortho MP, Clerici C, Yao PM, Delacourt C, Delclaux C, Franco-Montoya ML, Harf A, Lafuma C: Alveolar epithelial cells in vitro produce gelatinases and tissue inhibitor of matrix metalloproteinase-2. Am J Physiol 1997, 273:L663-L675.\nFukuda Y, Nakayama T, Terasaki Y, Kunugi S, Ishizaki M, Itohara S: Retarded alveolar epithelial cell repair after bleomycin treatment in MMP-2 KO mice. Am J Respir Crit Care Med 2002, A482. Abstr\nWoessner JF Jr: Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 1991, 5:2145–2154.",{"VOID":612},"10.1186\u002F1465-9921-6-6","2024-05-31T12:07:42.217+00:00","https:\u002F\u002Frespiratory-research.biomedcentral.com\u002Farticles\u002F10.1186\u002F1465-9921-6-6",[616,640,653,668,683],{"id":617,"sortIndex":19,"researcher":18,"roles":618,"affiliations":619,"properties":637,"displayName":639,"givenName":18,"familyName":18},"f645eb30-eb12-43e3-80ec-6b1869382042",[115],[620,628],{"id":621,"sortIndex":19,"affiliation":622,"properties":18},"85165838-b2a5-45a3-8ffb-8527022dd79c",{"id":621,"createTime":18,"updateTime":18,"relativeEntities":623,"slug":18,"properties":624,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":627,"statistic":18},[],{"title":625},{"VI":626},"Department of Cell Pathology, Postgraduate School of Medicine, Kumamoto University, Kumamoto, Japan",[],{"id":629,"sortIndex":80,"affiliation":630,"properties":636},"7be7a07b-750b-4aca-8eae-464b27977048",{"id":629,"createTime":18,"updateTime":18,"relativeEntities":631,"slug":18,"properties":632,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":635,"statistic":18},[],{"title":633},{"VI":634},"Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan",[],{},{"title":638},{"VI":639},"Yasuhiro Terasaki",{"id":641,"sortIndex":80,"researcher":18,"roles":642,"affiliations":643,"properties":650,"displayName":652,"givenName":18,"familyName":18},"8b91f7c2-5ed5-4205-a21f-383c955de8c9",[115],[644],{"id":629,"sortIndex":19,"affiliation":645,"properties":18},{"id":629,"createTime":18,"updateTime":18,"relativeEntities":646,"slug":18,"properties":647,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":649,"statistic":18},[],{"title":648},{"VI":634},[],{"title":651},{"VI":652},"Yuh Fukuda",{"id":654,"sortIndex":154,"researcher":18,"roles":655,"affiliations":656,"properties":665,"displayName":667,"givenName":18,"familyName":18},"945ef09e-f74f-4a73-aca4-c1581770dedf",[115],[657],{"id":658,"sortIndex":19,"affiliation":659,"properties":18},"f486bf48-2b52-484b-893a-7e1fa2aa6228",{"id":658,"createTime":18,"updateTime":18,"relativeEntities":660,"slug":18,"properties":661,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":664,"statistic":18},[],{"title":662},{"VI":663},"Department of Respiratory Medicine, Postgraduate School of Medicine, Kumamoto University, Kumamoto, Japan",[],{"title":666},{"VI":667},"Moritaka Suga",{"id":669,"sortIndex":168,"researcher":18,"roles":670,"affiliations":671,"properties":680,"displayName":682,"givenName":18,"familyName":18},"a8e81361-6b23-4503-ae1e-7f639055dfd5",[115],[672],{"id":673,"sortIndex":19,"affiliation":674,"properties":18},"fc913a71-5d59-4726-a1b1-17afbffdc674",{"id":673,"createTime":18,"updateTime":18,"relativeEntities":675,"slug":18,"properties":676,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":679,"statistic":18},[],{"title":677},{"VI":678},"Osaka R&D Laboratory (Yokohama-lab), Sumitomo Electric Industries, Yokohama, Japan",[],{"title":681},{"VI":682},"Naoki Ikeguchi",{"id":684,"sortIndex":182,"researcher":18,"roles":685,"affiliations":686,"properties":693,"displayName":695,"givenName":18,"familyName":18},"91c21186-421a-4cd8-8a8b-29c2d3810d28",[115],[687],{"id":621,"sortIndex":19,"affiliation":688,"properties":18},{"id":621,"createTime":18,"updateTime":18,"relativeEntities":689,"slug":18,"properties":690,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":692,"statistic":18},[],{"title":691},{"VI":626},[],{"title":694},{"VI":695},"Motohiro Takeya",{"url":614,"publisher":697,"properties":738},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":698,"slug":10,"properties":699,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":702,"manageAffiliations":707,"indexDatabases":718,"url":77,"thumbnailPath":18,"statistic":733,"gsStatistic":18,"type":84,"analyzePriority":18},[],{"issn":700,"title":701},{"VOID":13},{"EN":15},[703],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":704,"label":705,"description":706,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[708,713],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":709,"slug":18,"properties":710,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":712,"statistic":18},[],{"title":711},{"EN":33},[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":714,"slug":18,"properties":715,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":717,"statistic":18},[],{"title":716},{"EN":40},[],[719,726],{"id":44,"indexDatabase":720,"url":55,"indexYears":56,"academicFieldIds":725,"indexDatabaseRanking":59},{"id":46,"createTime":18,"updateTime":18,"relativeEntities":721,"label":722,"description":723,"key":52,"publicationTags":724,"standard":18},[],{"EN":49,"VI":49},{"EN":49,"VI":51},[54],[58],{"id":61,"indexDatabase":727,"url":74,"indexYears":18,"academicFieldIds":732,"indexDatabaseRanking":18},{"id":63,"createTime":18,"updateTime":18,"relativeEntities":728,"label":729,"description":730,"key":70,"publicationTags":731,"standard":18},[],{"EN":66,"VI":66},{"EN":68,"VI":69},[72,73],[76],{"impactFactor":19,"impactFactorByYear":734,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":735,"totalCitation":19,"totalCitationByYear":736,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":737,"hindexLast5Year":19,"hindex":19},{},{"2004":80},{},{},{"pages":739,"volume":741},{"VOID":740},"1-11",{"VOID":742},"6","2005-01-16",2005,"ERROR_IN_GET_PLATFORM_ID","2026-07-31T01:49:35.479+00:00",[72,59],{"id":749,"createTime":750,"updateTime":751,"relativeEntities":752,"slug":753,"properties":754,"entityType":106,"verifyStatus":107,"verifyTime":765,"verifyNote":109,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":766,"fullTextUrl":18,"authors":767,"publicationType":222,"publisherRelationship":846,"citationCount":19,"citationInfo":892,"publishDate":895,"publishYear":893,"citationAnalyzeStatus":896,"lastCitationAnalyze":897,"indexDatabases":898,"openAccess":18,"references":18,"isForceReanalyzing":279},"129e83ee-6e61-4660-8090-3f28cf63649f","2023-12-09T01:49:55.648+00:00","2026-07-30T12:14:49.221+00:00",[],"Health-status-decline-in-%CE%B1-1-antitrypsin-deficiency-a-feasible-outcome-for-disease-modifying-therapies-",{"abstract":755,"title":757,"gsPaper":759,"references":761,"doi":763},{"EN":756},"Trials of disease modifying therapies in Chronic Obstructive Pulmonary Disease (COPD) provide challenges for detecting physiological and patient centred outcomes. The purpose of the current study was to monitor decline in health status in Alpha-1 antitrypsin deficiency (AATD) and determine its’ relationship to conventional physiology. Patients recruited to the UK-AATD database with a median follow up of 7 years (IQR 5–10) were studied to determine annual change in St George’s Respiratory Questionnaire (SGRQ), FEV1, gas transfer and their feasibility of use in future trials. Annual decline in SGRQ had a wide range, was greater for patients with established COPD and correlated with decline in FEV1 (p \u003C 0.0001). Total score decline was greater (p \u003C 0.05) for those with accelerated FEV1 decline (median = 1.07 points\u002Fyear) compared to those without (median = 0.51). Power calculations indicated effective intervention would not achieve MCID for the SGRQ unless the timeframe was extended for up to 8 years. More than 5000 patients\u002Farm would be required for a statistically significant modest effect over 3 years even in those with rapid FEV1 decline. Despite AATD being a rapidly declining form of COPD, deterioration in SGRQ was slow consistent with ageing and the chronic nature of disease progression. Power calculations indicate the numbers needed to detect a difference with disease modifying therapies would be prohibitive especially in this rare cause of COPD. These data have important implications for future study design of disease modifying therapies even in COPD not associated with AATD.",{"EN":758},"Health status decline in α-1 antitrypsin deficiency: a feasible outcome for disease modifying therapies?",{"VOID":760},"[\"5931323833330935419\"]",{"VOID":762},"Vestbo J, Edwards LD, Scanlon PD, Yates JC, Agusti A, et al. Changes in forced expiratory volume in 1 second over time in COPD. N Engl J Med. 2011;365(13):1184–92.\nNishimura M, Makita H, Nagai K, Konno S, Nasuhara Y, et al. Annual change in pulmonary function and clinical phenotype in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185(1):44–52.\nPark HY, Churg A, Wright JL, Li Y, Tam S, et al. Club cell protein 16 and disease progression in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188(12):1413–9.\nCarter R, Mumford R, Treonze K, Stockley R. Fibrinopeptide AA-VAL360: a footprint of neutrophil elastase activity. COPD: J Chron Obstruct Pulmon Dis. 2011;8(1):50–1.\nDowson LJ, Guest PJ, Hill SL, Holder RL, Stockley RA. High-resolution computed tomography scanning in alpha1-antitrypsin deficiency: relationship to lung function and health status. Eur Respir J. 2001;17(6):1097–104.\nSeemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157(5):1418–22.\nU.S. Food and Drug Administration. Chronic Obstructive Pulmonary Disease: Developing Drugs for Treatment Guidance for Industry (Draft Guidance). 2016 [Available from: http:\u002F\u002Fwww.fda.gov\u002Fdownloads\u002FDrugs\u002FGuidanceComplianceRegulatoryInformation\u002FGuidances\u002FUCM071575.pdf.\nU.S. Food and Drug Administration. In: U.S. Department of Health and Human Services FaDA, Center for Drug Evaluation and Research (CDER), editor. Chronic Obstructive Pulmonary Disease: Use of the St. George’s Respiratory Questionnaire as a PRO Assessment Tool Guidance for Industry; 2018.\nCelli BR, Thomas NE, Anderson JA, Ferguson GT, Jenkins CR, et al. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am J Respir Crit Care Med. 2008;178(4):332–8.\nVestbo J, Anderson JA, Brook RD, Calverley PM, Celli BR, et al. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet. 2016;387(10030):1817–26.\nSchluchter MD, Stoller JK, Barker AF, Buist AS, Crystal RG, et al. Feasibility of a clinical trial of augmentation therapy for alpha1- antitrypsin deficiency. Am J Respir Crit Care Med. 2000;161(3 I):796–801.\nPlasma Protein Therapeutics Association. Clinical and Surrogate Endpoints for Evaluating Efficacy of Alpha 1-Proteinase Inhibitor (Human) Augmentation Therapy: FDA Blood Products Advisory Committee; 2009. [Available from: https:\u002F\u002Fwww.pptaglobal.org\u002F...\u002F954-ppta-statement-on-clinical-and-surrogate-endpoints....\nChapman KR, Burdon JG, Piitulainen E, Sandhaus RA, Seersholm N, et al. Intravenous augmentation treatment and lung density in severe alpha1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(9991):360–8.\nDirksen A, Dijkman JH, Madsen F, Stoel B, Hutchison DCS, et al. A randomized clinical trial of alpha1-antitrypsin augmentation therapy. Am J Respir Crit Care Med. 1999;160(5 I):1468–72.\nDirksen A, Piitulainen E, Parr DG, Deng C, Wencker M, et al. Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency. Eur Respir J. 2009;33(6):1345–53.\nThe Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. A J Respir Crit Care Med. 1998;158(1):49–59.\nDowson LJ, Newall C, Guest PJ, Hill SL, Stockley RA. Exercise capacity predicts health status in alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2001;163(4):936–41.\nVogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, et al. Global strategy for the diagnosis, management and prevention of chronic obstructive lung disease 2017 report. Respirology. 2017;22(3):575–601.\nStockley RA, Edgar RG, Pillai A, Turner AM. Individualized lung function trends in alpha-1-antitrypsin deficiency: a need for patience in order to provide patient centered management? Int J Chron Obstruct Pulmon Dis. 2016;11:1745.\nQuanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, et al. Lung volumes and forced ventilatory flows. Eur Respir J. 1993;6(Suppl 16):5–40.\nWard H, Turner AM, Stockley RA. Spirometric and gas transfer discordance in a alpha1 -antitrypsin deficiency. Patient characteristics and progression. Chest. 2014;145(6):1316–24.\nFerrer M, Villasante C, Alonso J, Sobradillo V, Gabriel R, et al. Interpretation of quality of life scores from the St George's respiratory questionnaire. Eur Respir J. 2002;19(3):405–13.\nPiitulainen E, Mostafavi B, Tanash HA. Health status and lung function in the swedish alpha 1-antitrypsin deficient cohort, identified by neonatal screening, at the age of 37–40 years. Int J Chron Obstruct Pulmon Dis. 2017;12:495.\nNeedham M, Stockley RA. Exacerbations in alpha1-antitrypsin deficiency. Eur Respir J. 2005;25(6):992–1000.\nStolk J, Ng WH, Bakker ME, Reiber JHC, Rabe KF, et al. Correlation between annual change in health status and computer tomography derived lung density in subjects with alpha1-antitrypsin deficiency. Thorax. 2003;58(12):1027–30.\nBernhard N, Lepper PM, Vogelmeier C, Seibert M, Wagenpfeil S, et al. Deterioration of quality of life is associated with the exacerbation frequency in individuals with alpha-1-antitrypsin deficiency–analysis from the german registry. Int J Chron Obstruct Pulmon Dis. 2017;12:1427.\nVincken W, van Noord JA, Greefhorst AP, Bantje TA, Kesten S, et al. Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium. Eur Respir J. 2002;19(2):209–16.\nVestbo J, Anderson JA, Calverley PM, Celli B, Ferguson GT, et al. Adherence to inhaled therapy, mortality and hospital admission in COPD. Thorax. 2009;64(11):939–43.\nCalverley P, Pauwels R, Vestbo J, Jones P, Pride N, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2003;361(9356):449–56.\nWilkinson TM, Donaldson GC, Hurst JR, Seemungal TA, Wedzicha JA. Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004;169(12):1298–303.\nGøtzsche PC, Johansen HK. Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease. Cochrane Libr. 2016; https:\u002F\u002Fdoi.org\u002F10.1002\u002F14651858.CD007851.pub3.\nLinden A. Assessing regression to the mean effects in health care initiatives. BMC Med Res Methodol. 2013;13(1):119.\nStolk J, Cooper BG, Stoel B, Rames A, Rutman O, et al. Retinoid treatment of emphysema in patients on the Alpha-1 international registry. The REPAIR study: study design, methodology and quality control of study assessments. Ther Adv Respir Dis. 2010;4(6):319–32.\nDawkins P, Wood A, Nightingale P, Stockley R. Mortality in alpha-1-antitrypsin deficiency in the United Kingdom. Respir Med. 2009;103(10):1540–7.\nParr DG, Stoel BC, Stolk J, Stockley RA. Validation of computed tomographic lung densitometry for monitoring emphysema in alpha1-antitrypsin deficiency. Thorax. 2006;61(6):485–90.",{"VOID":764},"10.1186\u002Fs12931-018-0844-6","2024-05-10T05:14:14.829+00:00","https:\u002F\u002Frespiratory-research.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs12931-018-0844-6",[768,783,808,823],{"id":769,"sortIndex":19,"researcher":18,"roles":770,"affiliations":771,"properties":780,"displayName":782,"givenName":18,"familyName":18},"71411684-91e5-4c24-8f2f-395ccc786904",[115],[772],{"id":773,"sortIndex":19,"affiliation":774,"properties":18},"b75f3655-9e35-41e7-a63b-ff81e0b4a176",{"id":773,"createTime":18,"updateTime":18,"relativeEntities":775,"slug":18,"properties":776,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":779,"statistic":18},[],{"title":777},{"VI":778},"Lung Investigation Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Edgbaston, UK",[],{"title":781},{"VI":782},"Robert A. Stockley",{"id":784,"sortIndex":80,"researcher":18,"roles":785,"affiliations":786,"properties":803,"displayName":805,"givenName":18,"familyName":18},"a587a8a5-9fd1-47e5-8889-d1babb37cc57",[115],[787,795],{"id":788,"sortIndex":19,"affiliation":789,"properties":18},"b295abbe-4fac-48da-a503-dde04da396c0",{"id":788,"createTime":18,"updateTime":18,"relativeEntities":790,"slug":18,"properties":791,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":794,"statistic":18},[],{"title":792},{"VI":793},"Therapy Services, University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital Birmingham, Edgbaston, UK",[],{"id":796,"sortIndex":80,"affiliation":797,"properties":18},"19a18ea4-eae6-4df4-8216-09a44793505e",{"id":796,"createTime":18,"updateTime":18,"relativeEntities":798,"slug":18,"properties":799,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":802,"statistic":18},[],{"title":800},{"VI":801},"Institute of Applied Health Research, University of Birmingham, Birmingham, UK",[],{"title":804,"gsAuthor":806},{"VI":805},"Ross G. Edgar",{"VOID":807},"[\"3QCq2TUAAAAJ\"]",{"id":809,"sortIndex":154,"researcher":18,"roles":810,"affiliations":811,"properties":820,"displayName":822,"givenName":18,"familyName":18},"51e73512-d927-40fd-b42d-95341caca6d5",[115],[812],{"id":813,"sortIndex":19,"affiliation":814,"properties":18},"5a6d6d6e-4f28-426e-b742-616e0f1394e3",{"id":813,"createTime":18,"updateTime":18,"relativeEntities":815,"slug":18,"properties":816,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":819,"statistic":18},[],{"title":817},{"VI":818},"Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital Birmingham, Edgbaston, UK",[],{"title":821},{"VI":822},"Sian Starkey",{"id":824,"sortIndex":168,"researcher":18,"roles":825,"affiliations":826,"properties":841,"displayName":843,"givenName":18,"familyName":18},"497846d9-32c1-4460-aabb-fb3d8a55b8e7",[115],[827,833],{"id":796,"sortIndex":19,"affiliation":828,"properties":18},{"id":796,"createTime":18,"updateTime":18,"relativeEntities":829,"slug":18,"properties":830,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":832,"statistic":18},[],{"title":831},{"VI":801},[],{"id":834,"sortIndex":80,"affiliation":835,"properties":18},"998bfba4-cb4c-4484-bdf0-a4c70b5c8a4e",{"id":834,"createTime":18,"updateTime":18,"relativeEntities":836,"slug":18,"properties":837,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":840,"statistic":18},[],{"title":838},{"VI":839},"Heart of England NHS Foundation Trust, Respiratory Medicine, Birmingham, UK",[],{"title":842,"gsAuthor":844},{"VI":843},"Alice M. Turner",{"VOID":845},"[\"PxzfT3MAAAAJ\"]",{"url":766,"publisher":847,"properties":888},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":848,"slug":10,"properties":849,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":852,"manageAffiliations":857,"indexDatabases":868,"url":77,"thumbnailPath":18,"statistic":883,"gsStatistic":18,"type":84,"analyzePriority":18},[],{"issn":850,"title":851},{"VOID":13},{"EN":15},[853],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":854,"label":855,"description":856,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[858,863],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":859,"slug":18,"properties":860,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":862,"statistic":18},[],{"title":861},{"EN":33},[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":864,"slug":18,"properties":865,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":867,"statistic":18},[],{"title":866},{"EN":40},[],[869,876],{"id":44,"indexDatabase":870,"url":55,"indexYears":56,"academicFieldIds":875,"indexDatabaseRanking":59},{"id":46,"createTime":18,"updateTime":18,"relativeEntities":871,"label":872,"description":873,"key":52,"publicationTags":874,"standard":18},[],{"EN":49,"VI":49},{"EN":49,"VI":51},[54],[58],{"id":61,"indexDatabase":877,"url":74,"indexYears":18,"academicFieldIds":882,"indexDatabaseRanking":18},{"id":63,"createTime":18,"updateTime":18,"relativeEntities":878,"label":879,"description":880,"key":70,"publicationTags":881,"standard":18},[],{"EN":66,"VI":66},{"EN":68,"VI":69},[72,73],[76],{"impactFactor":19,"impactFactorByYear":884,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":885,"totalCitation":19,"totalCitationByYear":886,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":887,"hindexLast5Year":19,"hindex":19},{},{"2004":80},{},{},{"pages":889,"volume":890},{"VOID":587},{"VOID":891},"19",{"total":19,"publishYear":893,"statisticByYear":894},2018,{},"2018-07-20","DONE_ANALYZE_CITATION","2026-07-30T12:14:49.220+00:00",[72,59],{"id":900,"createTime":901,"updateTime":902,"relativeEntities":903,"slug":904,"properties":905,"entityType":106,"verifyStatus":107,"verifyTime":916,"verifyNote":109,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":917,"fullTextUrl":18,"authors":918,"publicationType":222,"publisherRelationship":951,"citationCount":19,"citationInfo":998,"publishDate":1001,"publishYear":999,"citationAnalyzeStatus":896,"lastCitationAnalyze":1002,"indexDatabases":1003,"openAccess":18,"references":18,"isForceReanalyzing":279},"900c43fe-6523-4b38-8166-d2e2e3a89a07","2024-01-24T21:24:46.869+00:00","2026-07-29T06:00:48.046+00:00",[],"Matrix-metalloproteinases-in-lung-biology",{"abstract":906,"title":908,"gsPaper":910,"references":912,"doi":914},{"EN":907},"Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs) do in tissues. The catalytic activity of these enzymes has been implicated to function in normal lung biology by participating in branching morphogenesis, homeostasis, and repair, among other events. Overexpression of MMPs, however, has also been blamed for much of the tissue destruction associated with lung inflammation and disease. Beyond their role in the turnover and degradation of extracellular matrix proteins, MMPs also process, activate, and deactivate a variety of soluble factors, and seldom is it readily apparent by presence alone if a specific proteinase in an inflammatory setting is contributing to a reparative or disease process. An important goal of MMP research will be to identify the actual substrates upon which specific enzymes act. This information, in turn, will lead to a clearer understanding of how these extracellular proteinases function in lung development, repair, and disease.",{"EN":909},"Matrix metalloproteinases in lung biology",{"VOID":911},"[\"14624124658553993248\"]",{"VOID":913},"Woessner JF Jr: The matrix metalloproteinase family. In Matrix Metalloproteinases. Edited by Parks WC, Mecham RP. New York: Academic Press, Inc., 1998, 1–14.\nNagase H, Woessner JF Jr: Matrix metalloproteinases. J Biol Chem 1999, 274:21491–21494.\nVelasco G, Pendas AM, Fueyo A, Knauper V, Murphy G, Lopez-Otin C: Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members. J Biol Chem 1999, 274:4570–4576.\nWilson CL, Matrisian LM: Matrilysin. In Matrix Metalloproteinases. Edited by Parks WC, Mecham RP. New York: Academic Press, Inc., 1998, 149–184.\nPark HI, Ni J, Gerkema FE, Liu D, Belozerov VE, Sang QX: Identification and characterization of human endometase (matrix metalloproteinase-26) from endometrial tumor. J Biol Chem 2000, 275:20540–20544.\nUria JA, Lopez-Otin C: Matrilysin-2, a new matrix metalloproteinase expressed in human tumors and showing the minimal domain organization required for secretion, latency, and activity. Cancer Res 2000, 60:4745–4751.\nde Coignac AB, Elson G, Delneste Y, Magistrelli G, Jeannin P, Aubry JP, Berthier O, Schmitt D, Bonnefoy JY, Gauchat JF: Cloning of MMP-26. A novel matrilysin-like proteinase. Eur J Biochem 2000, 267:3323–3329.\nKojima S, Itoh Y, Matsumoto S, Masuho Y, Seiki M: Membrane-type 6 matrix metalloproteinase (MT6-MMP, MMP-25) is the second glycosyl-phosphatidylinositol (GPI)-anchored MMP. FEBS Lett 2000, 480:142–148.\nItoh Y, Kajita M, Kinoh H, Mori H, Okada A, Seiki M: Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositol-anchored proteinase. J Biol Chem 1999, 274:34260–34266.\nPei D: CA-MMP: a matrix metalloproteinase with a novel cysteine array, but without the classic cysteine switch. FEBS Lett 1999, 457:262–270.\nShapiro SD: Matrix metalloproteinase degradation of extracellular matrix: biological consequences. Curr Opin Cell Biol 1998, 10:602–608.\nCossins J, Dudgeon TJ, Catlin G, Gearing AJ, Clements JM: Identification of MMP-18, a putative novel human matrix metalloproteinase. Biochem Biophys Res Commun 1996, 228:494–498.\nPei D: Identification and characterization of the fifth membrane-type matrix metalloproteinase MT5-MMP. J Biol Chem 1999, 274:8925–8932.\nPei D: Leukolysin\u002FMMP25\u002FMT6-MMP: a novel matrix metalloproteinase specifically expressed in the leukocyte lineage. Cell Res 1999, 9:291–303.\nTierney GM, Griffin NR, Stuart RC, Kasem H, Lynch KP, Lury JT, Brown PD, Millar AW, Steele RJ, Parsons SL: A pilot study of the safety and effects of the matrix metalloproteinase inhibitor marimastat in gastric cancer. Eur J Cancer 1999, 35:563–568.\nSteward W: Marimastat (BB2516): current status of development. Cancer Chemother Pharmacol 1999, 43 (suppl):S56-S60.\nMucha A, Cuniasse P, Kannan R, Beau F, Yiotakis A, Basset P, Dive V: Membrane type-1 matrix metalloprotease and stromelysin-3 cleave more efficiently synthetic substrates containing unusual amino acids in their P1' positions. J Biol Chem 1998, 273:2763–2768.\nVu TH, Werb Z: Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 2000, 14:2123–2133.\nWilson CL, Ouellette AJ, Satchell DP, Ayabe T, López-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC: Regulation of intestinal α-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 1999, 286:113–117.\nSires UI, Murphy G, Baragi VM, Fliszar CJ, Welgus HG, Senior RM: Matrilysin is much more efficient than other metalloproteinases in the proteolytic inactivation of α-1 antitrypsin. Biochem Biophys Res Commun 1994, 204:613–620.\nPei D, Majmudar G, Weiss SJ: Hydrolytic inactivation of a breast carcinoma cell-derived serpin by human stromelysin-3. J Biol Chem 1994, 269:25849–25855.\nLiu Z, Zhou X, Shapiro SD, Shipley JM, Diaz LA, Senior RM, Werb Z: The serpin α1-proteinase inhibitor is a critical substrate for gelatinase B\u002FMMP-9 in vivo . Cell 2000, 102:647–655.\nHaro H, Crawford HC, Fingleton B, Shinomiya K, Spengler DM, Matrisian LM: Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption. J Clin Invest 2000, 105:143–150.\nLevi E, Fridman R, Miao HQ, Ma YS, Yayon A, Vlodavsky I: Matrix metalloproteinase 2 releases active soluble ectodomain of fibroblast growth factor receptor 1. Proc Natl Acad Sci USA 1996, 93:7069–7074.\nSuzuki M, Raab G, Moses MA, Fernandez CA, Klagsbrun M: Matrix metalloproteinase-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site. J Biol Chem 1997, 272:31730–31737.\nGearing AJH, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson AH, Drummond AH, Galloway WA, Gilbert R, Gordon JL, Leber TM, Mangan M, Miller K, Nayee P, Owen K, Patel S, Thomas W, Wells G, Wood LM, Woolley K: Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature 1994, 370:555–557.\nMcGeehan MG, Becherer JD, Bast RCJ, Boyer CM, Champion B, Connolly KM, Conway JG, Furdon P, Karp S, Kidao S: Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. Nature 1994, 370:558–560.\nYu Q, Stamenkovic I: Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 2000, 14:163–176.\nMcQuibban GA, Gong J-H, Tam EM, McCulloch CAG, Clark-Lewis I, Overall CM: Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 2000, 289:1202–1206.\nMackay AR, Hartzler JL, Pelina MD, Thorgeirsson UP: Studies on the ability of 65-kDa and 92-kDa tumor cell gelatinases to degrade type IV collagen. J Biol Chem 1990, 265:21929–21934.\nHalpert I, Roby JD, Sires UI, Potter-Perigo S, Wight TN, Welgus HG, Shapiro SD, Wickline SA, Parks WC: Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci USA 1996, 93:9748–9753.\nShapiro SD: Elastolytic metalloproteinases produced by human mononuclear phagocytes. Potential roles in destructive lung disease. Am J Respir Crit Care Med 1994, 150:S160-S164.\nBrooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, Quigley JP, Cheresh DA: Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell 1996, 85:683–693.\nYu WH, Woessner JF Jr: Heparan sulfate proteoglycans as extracellular docking molecules for matrilysin (matrix metalloproteinase 7). J Biol Chem 2000, 275:4183–4191.\nWang Z, Juttermann R, Soloway PD: TIMP-2 is required for efficient activation of proMMP-2 in vivo . J Biol Chem 2000, 275:26411–26415.\nCaterina JJ, Yamada S, Caterina NC, Longenecker G, Holmback K, Shi J, Yermovsky AE, Engler JA, Birkedal-Hansen H: Inactivating mutation of the mouse tissue inhibitor of metalloproteinases-2 (TIMP-2) gene alters proMMP-2 activation. J Biol Chem 2000, 275:26416–26422.\nSaarialho-Kere UK, Kovacs SO, Pentland AP, Olerud J, Welgus HG, Parks WC: Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing. J Clin Invest 1993, 92:2858–2866.\nPilcher BK, Dumin JA, Sudbeck BD, Krane SM, Welgus HG, Parks WC: The activity of collagenase-1 is required for keratinocyte migration on a type I collagen matrix. J Cell Biol 1997, 137:1445–1457.\nDunsmore SE, Saarialho-Kere UK, Roby JD, Wilson CL, Matrisian LM, Welgus HG, Parks WC: Matrilysin expression and function in airway epithelium. J Clin Invest 1998, 102:1321–1331.\nLópez-Boado YS, Wilson CL, Hooper LV, Gordon JI, Hultgren SJ, Parks WC: Bacterial exposure induces and activates matrilysin in mucosal epithelial cells. J Cell Biol 2000, 148:1305–1315.\nGanz T: Immunology: defensins and host defense. Science 1999, 286:420–421.\nKarelina TV, Goldberg GI, Eisen AZ: Matrilysin (PUMP) correlates with dermal invasion during appendageal development and cutaneous neoplasia. J Invest Dermatol 1994, 103:482–487.\nWilson CL, Heppner KJ, Rudolph LA, Matrisian LM: The metalloproteinase matrilysin is preferentially expressed by epithelial cells in a tissue-restricted pattern in the mouse. Mol Biol Cell 1995, 6:851–869.\nLochter A, Galosy S, Muschler J, Freedman N, Werb Z, Bissell MJ: Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells. J Cell Biol 1997, 139:1861–1872.\nBetsuyaku T, Fukuda Y, Parks WC, Shipley JM, Senior RM: Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin. Am J Pathol 2000, 157:525–535.\nLegrand C, Gilles C, Zahm J-M, Polette M, Buisson A-C, Kaplan H, Birembaut P, Tournier J-M: Airway epithelial cell migration dynamics: MMP-9 role in cell-extracellular matrix remodeling. J Cell Biol 1999, 146:517–529.\nShapiro SD, Endicott SK, Province MA, Pierce JA, Campbell EJ: Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weaponsrelated radiocarbon. J Clin Invest 1991, 87:1828–1834.\nMercer RR, Crapo JD: Spatial distribution of collagen and elastin fibers in the lungs. J Appl Physiol 1990, 69:756–765.\nD'Armiento J, Dalal SS, Okada Y, Berg RA, Chada K: Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell 1992, 71:955–961.\nFinlay GA, O'Driscoll LR, Russell KJ, D'Arcy EM, Masterson JB, FitzGerald MX, O'Connor CM: Matrix metalloproteinase expression and production by alveolar macrophages in emphysema. Am J Respir Crit Care Med 1997, 156:240–247.\nOhnishi K, Takagi M, Kurokawa Y, Satomi S, Konttinen YT: Matrix metalloproteinase-mediated extracellular matrix protein degradation in human pulmonary emphysema. Lab Invest 1998, 78:1077–1087.\nZheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ, Chapman HA, Shapiro SD, Elias JA: Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J Clin Invest 2000, 106:1081–1093.\nShipley JM, Wesselschmidt RL, Kobayashi DK, Ley TJ, Shapiro SD: Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc Natl Acad Sci USA 1996, 93:3942–3946.\nHautamaki RD, Kobayashi DK, Senior RM, Shapiro SD: Requirement for macrophage elastase for cigarette smoke-induced emphysema. Science 1997, 277:2002–2004.\nSenior RM, Griffin GL, Mecham RP: Chemotactic activity of elastin-derived peptides. J Clin Invest 1980, 66:859–862.\nItoh T, Ikeda T, Gomi H, Nakao S, Suzuki T, Itohara S: Unaltered secretion of beta-amyloid precursor protein in gelatinase A (matrix metalloproteinase 2)-deficient mice. J Biol Chem 1997, 272:22389–22392.\nItoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S: Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res 1998, 58:1048–1051.\nMudgett JS, Hutchinson NI, Chartrain NA, Forsyth AJ, McDonnell J, Singer II, Bayne EK, Flanagan J, Kawka D, Shen CF: Susceptibility of stromelysin 1-deficient mice to collagen-induced arthritis and cartilage destruction. Arthritis Rheum 1998, 41:110–121.\nBullard KM, Lund L, Mudgett JS, Mellin TN, Hunt TK, Murphy B, Ronan J, Werb Z, Banda MJ: Impaired wound contraction in stromelysin-1-deficient mice. Ann Surg 1999, 230:260–265.\nWang M, Qin X, Mudgett JS, Ferguson TA, Senior RM, Welgus HG: Matrix metalloproteinase deficiencies affect contact hypersensitivity: stromelysin-1 deficiency prevents the response and gelatinase B deficiency prolongs the response. Proc Natl Acad Sci USA 1999, 96:6885–6889.\nWilson CL, Heppner KJ, Labosky PA, Hogan BLM, Matrisian LM: Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci USA 1997, 94:1402–1407.\nVu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, Shapiro SD, Senior RM, Werb Z: MMP-9\u002Fgelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 1998, 93:411–422.\nBetsuyaku T, Shipley JM, Liu Z, Senior RM: Neutrophil emigration in the lungs, peritoneum, and skin does not require gelatinase B. Am J Respir Cell Mol Biol 1999, 20:1303–1309.\nLiu Z, Shipley JM, Vu TH, Zhou X, Diaz LA, Werb Z, Senior RM: Gelatinase B-deficient mice are resistant to experimental bullous pemphigoid. J Exp Med 1998, 188:475–482.\nPyo R, Lee JK, Shipley JM, Curci JA, Mao D, Ziporin SJ, Ennis TL, Shapiro SD, Senior RM, Thompson RW: Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J Clin Invest 2000, 105:1641–1649.\nHeymans S, Luttun A, Nuyens D, Theilmeier G, Creemers E, Moons L, Dyspersin GD, Cleutjens JP, Shipley M, Angellilo A, Levi M, Nube O, Baker A, Keshet E, Lupu F, Herbert JM, Smits JF, Shapiro SD, Baes M, Borgers M, Collen D, Daemen MJ, Carmeliet P: Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med 1999, 5:1135–1142.\nDucharme A, Frantz S, Aikawa M, Rabkin E, Lindsey M, Rohde LE, Schoen FJ, Kelly RA, Werb Z, Libby P, Lee RT: Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. J Clin Invest 2000, 106:55–62.\nCoussens LM, Tinkle CL, Hanahan D, Werb Z: MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 2000, 103:481–490.\nMasson R, Lefebvre O, Noel A, Fahime ME, Chenard MP, Wendling C, Kebers F, LeMeur M, Dierich A, Foidart JM, Basset P, Rio MC: In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy. J Cell Biol 1998, 140:1535–1541.\nLijnen HR, Van Hoef B, Vanlinthout I, Verstreken M, Rio MC, Collen D: Accelerated neointima formation after vascular injury in mice with stromelysin-3 (MMP-11) gene inactivation. Arterioscler Thromb Vasc Biol 1999, 19:2863–2870.\nHolmbeck K, Bianco P, Caterina J, Yamada S, Kromer M, Kuznetsov SA, Mankani M, Robey PG, Poole AR, Pidoux I, Ward JM, Birkedal-Hansen H: MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 1999, 99:81–92.",{"VOID":915},"10.1186\u002Frr33","2024-09-13T08:51:03.898+00:00","https:\u002F\u002Frespiratory-research.biomedcentral.com\u002Farticles\u002F10.1186\u002Frr33",[919,936],{"id":920,"sortIndex":19,"researcher":18,"roles":921,"affiliations":922,"properties":931,"displayName":933,"givenName":18,"familyName":18},"ab843af1-910d-4569-9d23-7ee466c0ae55",[115],[923],{"id":924,"sortIndex":19,"affiliation":925,"properties":18},"edecd5dd-f6fc-41b0-a49e-0d9141d6b3a4",{"id":924,"createTime":18,"updateTime":18,"relativeEntities":926,"slug":18,"properties":927,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":930,"statistic":18},[],{"title":928},{"VI":929},"Department of Pediatrics, Department of Medicine, and Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, USA",[],{"title":932,"gsAuthor":934},{"VI":933},"William C Parks",{"VOID":935},"[\"F_f5ZOAAAAAJ\"]",{"id":937,"sortIndex":80,"researcher":18,"roles":938,"affiliations":939,"properties":946,"displayName":948,"givenName":18,"familyName":18},"b1f809f4-abb9-4dbc-a1cb-b46def6a6b5c",[115],[940],{"id":924,"sortIndex":19,"affiliation":941,"properties":18},{"id":924,"createTime":18,"updateTime":18,"relativeEntities":942,"slug":18,"properties":943,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":945,"statistic":18},[],{"title":944},{"VI":929},[],{"title":947,"gsAuthor":949},{"VI":948},"Steven D Shapiro",{"VOID":950},"[\"Ebol0UAAAAAJ\"]",{"url":917,"publisher":952,"properties":993},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":953,"slug":10,"properties":954,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":957,"manageAffiliations":962,"indexDatabases":973,"url":77,"thumbnailPath":18,"statistic":988,"gsStatistic":18,"type":84,"analyzePriority":18},[],{"issn":955,"title":956},{"VOID":13},{"EN":15},[958],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":959,"label":960,"description":961,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[963,968],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":964,"slug":18,"properties":965,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":967,"statistic":18},[],{"title":966},{"EN":33},[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":969,"slug":18,"properties":970,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":972,"statistic":18},[],{"title":971},{"EN":40},[],[974,981],{"id":44,"indexDatabase":975,"url":55,"indexYears":56,"academicFieldIds":980,"indexDatabaseRanking":59},{"id":46,"createTime":18,"updateTime":18,"relativeEntities":976,"label":977,"description":978,"key":52,"publicationTags":979,"standard":18},[],{"EN":49,"VI":49},{"EN":49,"VI":51},[54],[58],{"id":61,"indexDatabase":982,"url":74,"indexYears":18,"academicFieldIds":987,"indexDatabaseRanking":18},{"id":63,"createTime":18,"updateTime":18,"relativeEntities":983,"label":984,"description":985,"key":70,"publicationTags":986,"standard":18},[],{"EN":66,"VI":66},{"EN":68,"VI":69},[72,73],[76],{"impactFactor":19,"impactFactorByYear":989,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":990,"totalCitation":19,"totalCitationByYear":991,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":992,"hindexLast5Year":19,"hindex":19},{},{"2004":80},{},{},{"pages":994,"volume":996},{"VOID":995},"1-10",{"VOID":997},"2",{"total":19,"publishYear":999,"statisticByYear":1000},2000,{},"2000-12-29","2026-07-29T06:00:48.045+00:00",[72,59],{"id":1005,"createTime":1006,"updateTime":1007,"relativeEntities":1008,"slug":1009,"properties":1010,"entityType":106,"verifyStatus":107,"verifyTime":1025,"verifyNote":109,"languages":1026,"translateLanguages":18,"viewCount":19,"primaryUrl":1028,"fullTextUrl":18,"authors":1029,"publicationType":222,"publisherRelationship":1202,"citationCount":1248,"citationInfo":1249,"publishDate":1255,"publishYear":893,"citationAnalyzeStatus":896,"lastCitationAnalyze":1256,"indexDatabases":1257,"openAccess":18,"references":1258,"isForceReanalyzing":279},"ca2ac472-5764-4bb9-8107-6aa1b29ea896","2024-04-18T06:50:40.370+00:00","2026-07-27T01:21:58.390+00:00",[],"Factors-associated-with-bronchiectasis-in-patients-with-uncontrolled-asthma-the-NOPES-score-a-study-in-398-patients",{"mag":1011,"gsPaper":1013,"pmc":1015,"openalex":1017,"title":1019,"pm":1021,"doi":1023},{"VOID":1012},"2799436494",{"VOID":1014},"[\"3428499879561234483\"]",{"VOID":1016},"5857069",{"VOID":1018},"W2799436494",{"EN":1020},"Factors associated with bronchiectasis in patients with uncontrolled asthma; the NOPES score: a study in 398 patients",{"VOID":1022},"29548297",{"VOID":1024},"10.1186\u002Fs12931-018-0746-7","2024-05-16T14:01:30.424+00:00",[1027],"EN","https:\u002F\u002Frespiratory-research.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs12931-018-0746-7",[1030,1047,1068,1083,1100,1117,1132,1151,1168,1183],{"id":1031,"sortIndex":19,"researcher":18,"roles":1032,"affiliations":1033,"properties":1042,"displayName":1044,"givenName":18,"familyName":18},"cf6847b2-35b8-44b7-8a58-494640c00adc",[],[1034],{"id":1035,"sortIndex":19,"affiliation":1036,"properties":18},"189b055d-1135-47dd-ae2d-28bbf269c000",{"id":1035,"createTime":18,"updateTime":18,"relativeEntities":1037,"slug":18,"properties":1038,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1041,"statistic":18},[],{"title":1039},{"EN":1040},"Pneumology Unit. Agencia Sanitaria Costa del Sol, Carretera Nacional 340, Km 187, 29603, Marbella, Málaga, Spain",[],{"title":1043,"openalex":1045},{"EN":1044},"Alicia Padilla-Galo",{"VOID":1046},"A5032982319",{"id":1048,"sortIndex":80,"researcher":18,"roles":1049,"affiliations":1050,"properties":1059,"displayName":1063,"givenName":18,"familyName":18},"2c971fb1-008d-44a2-acb6-6f64451adbdd",[],[1051],{"id":1052,"sortIndex":19,"affiliation":1053,"properties":18},"6b4e34b3-c114-46e0-a1fe-c0a2f2a1f2f1",{"id":1052,"createTime":18,"updateTime":18,"relativeEntities":1054,"slug":18,"properties":1055,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1058,"statistic":18},[],{"title":1056},{"EN":1057},"Pneumology Department, IBIMA (Institute for biomedical research of Málaga), Hospital Regional Universitario de Málaga\u002F University of Málaga, Avenida Carlos Haya, 29010, Málaga, Spain",[],{"orcid":1060,"title":1062,"gsAuthor":1064,"openalex":1066},{"VOID":1061},"https:\u002F\u002Forcid.org\u002F0000-0002-6912-7400",{"EN":1063},"Casilda Olveira",{"VOID":1065},"[\"ywOYloAAAAAJ\"]",{"VOID":1067},"A5064188458",{"id":1069,"sortIndex":154,"researcher":18,"roles":1070,"affiliations":1071,"properties":1078,"displayName":1080,"givenName":18,"familyName":18},"dbc0e83a-3ad1-4c5e-bc1f-bb8752dca356",[],[1072],{"id":1035,"sortIndex":19,"affiliation":1073,"properties":18},{"id":1035,"createTime":18,"updateTime":18,"relativeEntities":1074,"slug":18,"properties":1075,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1077,"statistic":18},[],{"title":1076},{"EN":1040},[],{"title":1079,"openalex":1081},{"EN":1080},"Luis Fernandez de Rota-Garcia",{"VOID":1082},"A5072100405",{"id":1084,"sortIndex":168,"researcher":18,"roles":1085,"affiliations":1086,"properties":1095,"displayName":1097,"givenName":18,"familyName":18},"ec53376e-cbdf-4df2-aa04-82220a4104d6",[],[1087],{"id":1088,"sortIndex":19,"affiliation":1089,"properties":18},"4f198862-f197-4aad-8ea6-9282977e2331",{"id":1088,"createTime":18,"updateTime":18,"relativeEntities":1090,"slug":18,"properties":1091,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1094,"statistic":18},[],{"title":1092},{"EN":1093},"Radiology Deparment. Hospital de Alta Resolución de Benalmádena, Arroyo Hondo s\u002Fn, 29639, Benalmádena, Málaga, Spain",[],{"title":1096,"openalex":1098},{"EN":1097},"I. Marco-Galve",{"VOID":1099},"A5040007033",{"id":1101,"sortIndex":182,"researcher":18,"roles":1102,"affiliations":1103,"properties":1112,"displayName":1114,"givenName":18,"familyName":18},"947f1c72-4aa5-460b-a3d6-c5a03f1bd7fe",[],[1104],{"id":1105,"sortIndex":19,"affiliation":1106,"properties":18},"7034996f-082e-4b52-86b0-033f2ec1cb95",{"id":1105,"createTime":18,"updateTime":18,"relativeEntities":1107,"slug":18,"properties":1108,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1111,"statistic":18},[],{"title":1109},{"EN":1110},"Infectious Diseases Department, Hospital Regional Universitario de Málaga, Avenida Carlos Haya, 29010, Málaga, Spain",[],{"title":1113,"openalex":1115},{"EN":1114},"Antonio Plata",{"VOID":1116},"A5037234764",{"id":1118,"sortIndex":196,"researcher":18,"roles":1119,"affiliations":1120,"properties":1127,"displayName":1129,"givenName":18,"familyName":18},"10749a8a-df45-409f-bf16-85b0f9668fe6",[],[1121],{"id":1088,"sortIndex":19,"affiliation":1122,"properties":18},{"id":1088,"createTime":18,"updateTime":18,"relativeEntities":1123,"slug":18,"properties":1124,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1126,"statistic":18},[],{"title":1125},{"EN":1093},[],{"title":1128,"openalex":1130},{"EN":1129},"Antonio Álvarez",{"VOID":1131},"A5079359277",{"id":1133,"sortIndex":210,"researcher":18,"roles":1134,"affiliations":1135,"properties":1144,"displayName":1148,"givenName":18,"familyName":18},"3e58bafb-0ac9-4d70-99fa-dda820afade2",[],[1136],{"id":1137,"sortIndex":19,"affiliation":1138,"properties":18},"5de6d95e-0c41-47ee-b9b6-b8a043eb1aa4",{"id":1137,"createTime":18,"updateTime":18,"relativeEntities":1139,"slug":18,"properties":1140,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1143,"statistic":18},[],{"title":1141},{"EN":1142},"Research Unit. Red de Investigación en Servicios de Salud en Enfermedades Crónicas, REDISSEC (Spanish healthcare network for chronic diseases), Agencia Sanitaria Costa del Sol, Carretera Nacional 340, Km 187, 29603, Marbella, Málaga, Spain",[],{"orcid":1145,"title":1147,"openalex":1149},{"VOID":1146},"https:\u002F\u002Forcid.org\u002F0000-0002-8894-0501",{"EN":1148},"Francisco Rivas-Ruiz",{"VOID":1150},"A5075256303",{"id":1152,"sortIndex":503,"researcher":18,"roles":1153,"affiliations":1154,"properties":1163,"displayName":1165,"givenName":18,"familyName":18},"902da619-0fd4-4510-b966-986f9c9cd774",[],[1155],{"id":1156,"sortIndex":19,"affiliation":1157,"properties":18},"536e31b0-db49-464a-adae-014b2d0ee3cb",{"id":1156,"createTime":18,"updateTime":18,"relativeEntities":1158,"slug":18,"properties":1159,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1162,"statistic":18},[],{"title":1160},{"VI":1161},"Faculty of Medicine, University of Málaga, Málaga, Spain",[],{"title":1164,"openalex":1166},{"EN":1165},"A. Carmona-Olveira",{"VOID":1167},"A5076790696",{"id":1169,"sortIndex":517,"researcher":18,"roles":1170,"affiliations":1171,"properties":1178,"displayName":1180,"givenName":18,"familyName":18},"2b52491d-94ff-4e26-9c31-3f5de80f8926",[],[1172],{"id":1035,"sortIndex":19,"affiliation":1173,"properties":18},{"id":1035,"createTime":18,"updateTime":18,"relativeEntities":1174,"slug":18,"properties":1175,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1177,"statistic":18},[],{"title":1176},{"EN":1040},[],{"title":1179,"openalex":1181},{"EN":1180},"Jose Joaquin Cebrian-Gallardo",{"VOID":1182},"A5006761869",{"id":1184,"sortIndex":531,"researcher":18,"roles":1185,"affiliations":1186,"properties":1195,"displayName":1199,"givenName":18,"familyName":18},"7d02bdf7-3c7e-48b7-aa6a-9ed8d1bd3cf7",[],[1187],{"id":1188,"sortIndex":19,"affiliation":1189,"properties":18},"a9d592c7-831c-49f2-9cd0-4dd541d31861",{"id":1188,"createTime":18,"updateTime":18,"relativeEntities":1190,"slug":18,"properties":1191,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1194,"statistic":18},[],{"title":1192},{"EN":1193},"Pneumology Department, Hospital Universitario La Fe, Valencia, Spain",[],{"orcid":1196,"title":1198,"openalex":1200},{"VOID":1197},"https:\u002F\u002Forcid.org\u002F0000-0002-7321-1891",{"EN":1199},"Miguel Ángel Martínez-García",{"VOID":1201},"A5011481509",{"url":18,"publisher":1203,"properties":1244},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1204,"slug":10,"properties":1205,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":1208,"manageAffiliations":1213,"indexDatabases":1224,"url":77,"thumbnailPath":18,"statistic":1239,"gsStatistic":18,"type":84,"analyzePriority":18},[],{"issn":1206,"title":1207},{"VOID":13},{"EN":15},[1209],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":1210,"label":1211,"description":1212,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[1214,1219],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":1215,"slug":18,"properties":1216,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1218,"statistic":18},[],{"title":1217},{"EN":33},[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":1220,"slug":18,"properties":1221,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1223,"statistic":18},[],{"title":1222},{"EN":40},[],[1225,1232],{"id":44,"indexDatabase":1226,"url":55,"indexYears":56,"academicFieldIds":1231,"indexDatabaseRanking":59},{"id":46,"createTime":18,"updateTime":18,"relativeEntities":1227,"label":1228,"description":1229,"key":52,"publicationTags":1230,"standard":18},[],{"EN":49,"VI":49},{"EN":49,"VI":51},[54],[58],{"id":61,"indexDatabase":1233,"url":74,"indexYears":18,"academicFieldIds":1238,"indexDatabaseRanking":18},{"id":63,"createTime":18,"updateTime":18,"relativeEntities":1234,"label":1235,"description":1236,"key":70,"publicationTags":1237,"standard":18},[],{"EN":66,"VI":66},{"EN":68,"VI":69},[72,73],[76],{"impactFactor":19,"impactFactorByYear":1240,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":1241,"totalCitation":19,"totalCitationByYear":1242,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":1243,"hindexLast5Year":19,"hindex":19},{},{"2004":80},{},{},{"issue":1245,"volume":1247},{"VOID":1246},"1",{"VOID":891},104,{"total":1248,"publishYear":893,"statisticByYear":1250},{"2018":154,"2019":1251,"2020":1252,"2021":1251,"2022":1253,"2023":274,"2024":517,"2025":1254,"2026":531},13,16,18,12,"2018-12-01","2026-07-27T01:21:58.389+00:00",[72,59],[1259,1262,1266,1270,1274,1278,1282,1286,1290,1294,1298,1302,1306,1310,1314,1318,1322,1325,1329,1333,1336,1340,1344,1348,1352,1356,1360,1364,1368,1372,1376,1380,1384,1388,1392,1396,1400,1404,1408,1412,1416,1419,1423,1427,1431,1435,1439,1443,1446,1450,1453,1457,1461,1465,1469,1473,1477,1481,1484,1488,1492,1496],{"id":18,"text":1260,"url":18,"identifiers":1261},"Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA), 2016. http:\u002F\u002Fwww.ginasthma.org\u002F .",{},{"id":18,"text":1263,"url":18,"identifiers":1264},"Bousquet J, Clark TJH, Hurd S, Khaltaev N, Lenfant C, O'byrne P, et al. GINA guidelines on asthma and beyond. Allergy. 2007;62(2):102–12.",{"doi":1265},"10.1111\u002Fj.1398-9995.2006.01305.x",{"id":18,"text":1267,"url":18,"identifiers":1268},"Martínez-García MÁ, Máiz L, Olveira C, Girón RM, de la Rosa D, Blanco M, et al. Spanish guidelines on the evaluation and diagnosis of bronchiectasis in adults. Arch Bronconeumol. 2017;(17):30272–7. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.arbres.2017.07.015 .",{"doi":1269},"10.1016\u002Fj.arbres.2017.07.015",{"id":18,"text":1271,"url":18,"identifiers":1272},"Seitz AE, Olivier KN, Adjemian J, Holland SM, Prevots R. Trends in bronchiectasis among Medicare beneficiaries in the United States, 2000 to 2007. Chest. 2012;142:432–9.",{"doi":1273},"10.1378\u002Fchest.11-2209",{"id":18,"text":1275,"url":18,"identifiers":1276},"Martínez-García MA, Máiz-Carro L, Catalán-Serra P. Tratamiento de las bronquiectasias no debidas a fibrosis quística. Arch Bronconeumol. 2011;47(12):599–609.",{"doi":1277},"10.1016\u002Fj.arbres.2011.06.003",{"id":18,"text":1279,"url":18,"identifiers":1280},"Quint JK, Millett ER, Joshi M, Navaratnam V, Thomas SL, Hurst JR, et al. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004-2013: a population-based cohort study. Eur Respir J. 2016;47(1):186–93.",{"doi":1281},"10.1183\u002F13993003.01033-2015",{"id":18,"text":1283,"url":18,"identifiers":1284},"Patel I, Seemungal T, Wilks M, Lloyd-Owen S, Donaldson G, Wedzicha J. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax. 2002;57(9):759–64.",{"doi":1285},"10.1136\u002Fthorax.57.9.759",{"id":18,"text":1287,"url":18,"identifiers":1288},"Martínez-García M, Soler-Cataluña JJ, Donat Sanz Y, Catalán Serra P, Agramunt Lerma M, Ballestín Vicente J, et al. Factors associated with bronchiectasis in patients with COPD. Chest. 2011;140(5):1130–7.",{"doi":1289},"10.1378\u002Fchest.10-1758",{"id":18,"text":1291,"url":18,"identifiers":1292},"Martínez-García MA, de la Rosa Carrillo D, Soler-Cataluña JJ, Donat-Sanz Y, Serra PC, Lerma MA, et al. Prognostic value of bronchiectasis in patients with moderate-to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187(8):823–31.",{"doi":1293},"10.1164\u002Frccm.201208-1518OC",{"id":18,"text":1295,"url":18,"identifiers":1296},"Gupta S, Siddiqui S, Haldar P, Raj JV, Entwisle JJ, Wardlaw AJ, et al. Qualitative analysis of high-resolution CT scans in severe asthma. Chest. 2009;136(6):1521–8.",{"doi":1297},"10.1378\u002Fchest.09-0174",{"id":18,"text":1299,"url":18,"identifiers":1300},"Bisaccioni C, Aun MV, Cajuela E, Kalil J, Agondi RC, Giavina-Bianchi P. Comorbidities in severe asthma: frequency of rhinitis, nasal polyposis, gastroesophageal reflux disease, vocal cord dysfunction and bronchiectasis. Clinics (Sao Paulo). 2009;64:769–73.",{"doi":1301},"10.1590\u002FS1807-59322009000800010",{"id":18,"text":1303,"url":18,"identifiers":1304},"Menzies D, Holmes L, McCumesky G, Prys-Picard C, Niven R. Aspergillus sensitization is associated with airflow limitation and bronchiectasis in severe asthma. Allergy. 2011;66(5):679–85.",{"doi":1305},"10.1111\u002Fj.1398-9995.2010.02542.x",{"id":18,"text":1307,"url":18,"identifiers":1308},"Oguzulgen K, Kervan F, Ozis T, Turktas H. The impact of bronchiectasis in clinical presentation of asthma. South Med J. 2007;100(5):468–71.",{"doi":1309},"10.1097\u002FSMJ.0b013e31802fa16f",{"id":18,"text":1311,"url":18,"identifiers":1312},"Kang HR, Choi GS, Park SJ, Song YK, Kim JM, Ha J, et al. The effects of bronchiectasis on asthma exacerbations. Tuberc Respir Dis. 2014;77(5):209–14.",{"doi":1313},"10.4046\u002Ftrd.2014.77.5.209",{"id":18,"text":1315,"url":18,"identifiers":1316},"Paganin F, Trussard V, Seneterre E, Chanez P, Giron J, Godard P, et al. Chest radiography and high resolution computed tomography of the lungs in asthma. Am Rev Respir Dis. 1992;146(4):1084–7.",{"doi":1317},"10.1164\u002Fajrccm\u002F146.4.1084",{"id":18,"text":1319,"url":18,"identifiers":1320},"Khadadah M, Jayakrishnan B, Muquim A, Roberts O, Sinan T, Maradny N, et al. High resolution computed tomography in asthma. Oman Med J. 2012;27(2):145–50.",{"doi":1321},"10.5001\u002Fomj.2012.30",{"id":18,"text":1323,"url":18,"identifiers":1324},"Machado D, Pereira C, Teixeira L, Canelas A, Tavares B, Loureiro G, et al. Thoracic high resolution computed tomography (HRCT) in asthma. Eur Ann Allergy Clin Immunol. 2009;41(5):139–45.",{},{"id":18,"text":1326,"url":18,"identifiers":1327},"Grenier P, Mourey-Gerosa I, Benali K, Brauner MW, Leung AN, Lenoir S, et al. Abnormalities of the airways and lung parenchyma in asthmatics: CT observations in 50 patients and inter- and intraobserver variability. Eur Radiol. 1996;6(2):199–206.",{"doi":1328},"10.1007\u002FBF00181147",{"id":18,"text":1330,"url":18,"identifiers":1331},"Lynch DA, Newell JD, Tschomper BA, Cink TM, Newman LS, Bethel R. Uncomplicated asthma in adults: comparison of CT appearance of the lungs in asthmatic and healthy subjects. Radiology. 1993;188(3):829–33.",{"doi":1332},"10.1148\u002Fradiology.188.3.8351357",{"id":18,"text":1334,"url":18,"identifiers":1335},"Guía Española para el manejo del asma (GEMA 4.1). http:\u002F\u002Fwww.gemasma.com .",{},{"id":18,"text":1337,"url":18,"identifiers":1338},"Naidich DP, McCauley DI, Khouri NF, Stitik FP, Siegelman SS. Computed tomography of bronchiectasis. J Comput Assist Tomogr. 1982;6(3):437–44.",{"doi":1339},"10.1097\u002F00004728-198206000-00001",{"id":18,"text":1341,"url":18,"identifiers":1342},"Bhalla M, Turcios N, Aponte V, Jenkins M, Leitman BS, McCauley DI, et al. Cystic fibrosis: scoring system with thin-section CT. Radiology. 1991;179(3):783–8.",{"doi":1343},"10.1148\u002Fradiology.179.3.2027992",{"id":18,"text":1345,"url":18,"identifiers":1346},"Shah RM, Sexauer W, Ostrum BJ, Fiel SB, Friedman AC. High resolution CT in the acute exacerbation of cystic fibrosis: evaluation of acute findings, reversibility of those findings, and clinical correlation. AJR Am J Roentgenol. 1997;169(2):375–80.",{"doi":1347},"10.2214\u002Fajr.169.2.9242738",{"id":18,"text":1349,"url":18,"identifiers":1350},"Murray MP, Pentland JL, Turnbull K, MacQuarrie S, Hill AT. Sputum colour: a useful clinical tool in non-cystic fibrosis bronchiectasis. Eur Respir J. 2009;34(2):361–4.",{"doi":1351},"10.1183\u002F09031936.00163208",{"id":18,"text":1353,"url":18,"identifiers":1354},"Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999;54(7):581–6.",{"doi":1355},"10.1136\u002Fthx.54.7.581",{"id":18,"text":1357,"url":18,"identifiers":1358},"Martinez-Garcia MA, de Gracia J, Vendrell M, Girón RM, Máiz Carro L, de la Rosa Carrillo D, et al. Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score. Eur Respir J. 2014;43(5):1357–67.",{"doi":1359},"10.1183\u002F09031936.00026313",{"id":18,"text":1361,"url":18,"identifiers":1362},"Natham RA, Sorkness Ch A, Kosinski M, Schatz M, Li J, Marcus PH. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004;113:59–65.",{"doi":1363},"10.1016\u002Fj.jaci.2003.09.008",{"id":18,"text":1365,"url":18,"identifiers":1366},"Vega JM, Badia X, Badiola C, López-Viña A, Olaguíbel JM, Picado C. Validation of the Spanish version of the asthma control test (ACT). J Asthma. 2007;44:867–72.",{"doi":1367},"10.1080\u002F02770900701752615",{"id":18,"text":1369,"url":18,"identifiers":1370},"Rodrigo GJ, Arcos JP, Nannini LJ, Neffen H, González Broin M, Contrera M. Reability and factor analysis of the Spanish version of the asthma control test. Ann Allergy Asthma Immunol. 2008;100:17–22.",{"doi":1371},"10.1016\u002FS1081-1206(10)60399-7",{"id":18,"text":1373,"url":18,"identifiers":1374},"Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63(Suppl 86):8–160.",{"doi":1375},"10.1111\u002Fj.1398-9995.2007.01620.x",{"id":18,"text":1377,"url":18,"identifiers":1378},"Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.",{"doi":1379},"10.1016\u002F0021-9681(87)90171-8",{"id":18,"text":1381,"url":18,"identifiers":1382},"Chalmers JD, Goeminne P, Aliberti S, McDonnell MJ, Lonni S, Davidson J, et al. The bronchiectasis severity index. An international derivation and validation study. Am J Respir Crit Care Med. 2014;189(5):576–85.",{"doi":1383},"10.1164\u002Frccm.201309-1575OC",{"id":18,"text":1385,"url":18,"identifiers":1386},"American Thoracic Society. Recommendations for standardized procedures for the on-line and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children. Am J Respir Crit Care Med. 2005;171(8):912–30.",{"doi":1387},"10.1164\u002Frccm.200406-710ST",{"id":18,"text":1389,"url":18,"identifiers":1390},"Standardization of spirometry. Statement of the American thoracic society. Am Rev Respir Dis. 1987;136(5):1285–98.",{"doi":1391},"10.1164\u002Fajrccm\u002F136.5.1285",{"id":18,"text":1393,"url":18,"identifiers":1394},"Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, et al. An official American Thoracic Society\u002FEuropean Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59–99.",{"doi":1395},"10.1164\u002Frccm.200801-060ST",{"id":18,"text":1397,"url":18,"identifiers":1398},"Martínez-García MA, Perpiñá-Tordera M, Román-Sánchez P, Soler-Cataluña JJ. Quality of life determinants in patients with clinically stable bronchiectasis. Chest. 2005;128:739–45.",{"doi":1399},"10.1378\u002Fchest.128.2.739",{"id":18,"text":1401,"url":18,"identifiers":1402},"Murphy TF, Brauer AL, Schiffmacher AT, Sethi S. Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004;170(3):266–72.",{"doi":1403},"10.1164\u002Frccm.200403-354OC",{"id":18,"text":1405,"url":18,"identifiers":1406},"Sethi S, Evans N, Grant BJ, Murphy TF. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 2002;347(7):465–71.",{"doi":1407},"10.1056\u002FNEJMoa012561",{"id":18,"text":1409,"url":18,"identifiers":1410},"Park H, Shin JW, Park SG, Kim W. Microbial communities in the upper respiratory tract of patients with asthma and chronic obstructive pulmonary disease. PLoS One. 2014;9(10):e109710.",{"doi":1411},"10.1371\u002Fjournal.pone.0109710",{"id":18,"text":1413,"url":18,"identifiers":1414},"Cantón R, Máiz L, Escribano A, Olveira C, Oliver A, Asensio O, et al. Spanish consensus on the prevention and treatment of Pseudomonas aeruginosa bronchial infections in cystic fibrosis patients. Arch Bronconeumol. 2015;51(3):140–50.",{"doi":1415},"10.1016\u002Fj.arbres.2014.09.021",{"id":18,"text":1417,"url":18,"identifiers":1418},"R statistical: Department of Statistics, University of Auckland, Auckland, NZ; http:\u002F\u002Fwww.r-project.org\u002F .",{},{"id":18,"text":1420,"url":18,"identifiers":1421},"Swets JA. Measuring the accuracy of diagnostic systems. Science. 1988;240:1285–93.",{"doi":1422},"10.1126\u002Fscience.3287615",{"id":18,"text":1424,"url":18,"identifiers":1425},"Altman DG, Bland JM. Statistics notes: diagnostic tests 1: sensitivity and specificity. BMJ. 1994;308:1552.",{"doi":1426},"10.1136\u002Fbmj.308.6943.1552",{"id":18,"text":1428,"url":18,"identifiers":1429},"Altman DG, Bland JM. Statistics notes: diagnostic tests 2: predictive values. BMJ. 1994;309:102.",{"doi":1430},"10.1136\u002Fbmj.309.6947.102",{"id":18,"text":1432,"url":18,"identifiers":1433},"Luján M, Gallardo X, Amengual MJ, Bosque M, Mirapeix RM, Domingo C. Prevalence of bronchiectasis in asthma according to oral steroid requirement: influence of immunoglobulin levels. Biomed Res Int. 2013;2013:109219.",{"doi":1434},"10.1155\u002F2013\u002F109219",{"id":18,"text":1436,"url":18,"identifiers":1437},"Paganin F, Sénetérre E, Chanez P, Daurés JP, Bruel JM, Michel FB, et al. Computed tomography of the lungs in asthma: influence of disease severity and etiology. Am J Respir Crit Care Med. 1996;153(1):110–4.",{"doi":1438},"10.1164\u002Fajrccm.153.1.8542102",{"id":18,"text":1440,"url":18,"identifiers":1441},"Neeld DA, Goodman LR, Gurney JW, Greenberger PA, Fink JN. Computerized tomography in the evaluation of allergic bronchopulmonary aspergillosis. Am Rev Respir Dis. 1990;142(5):1200–5.",{"doi":1442},"10.1164\u002Fajrccm\u002F142.5.1200",{"id":18,"text":1444,"url":18,"identifiers":1445},"Sánchez Cuellar S, Girón RM, Cisneros C, Caballero P, Tejerina A, Ancochea J. Valoración de bronquiectasias en pacientes con asma. Rev Patol Respir. 2015;18(2):57–62.",{},{"id":18,"text":1447,"url":18,"identifiers":1448},"Goeminne PC, Vandooren J, Moelants EA, Decraene A, Rabaey E, Pauwels A, et al. The Sputum colour chart as a predictor of lung inflammation, proteolysis and damage in non-cystic fibrosis bronchiectasis: a case-control analysis. Respirology. 2014;19(2):203–10.",{"doi":1449},"10.1111\u002Fresp.12219",{"id":18,"text":1451,"url":18,"identifiers":1452},"Royce BF, Victor RG. Bronchiectasis following atypical pneumonia. Bull U S Army Med Dep. 1948;8(1):61–8.",{},{"id":18,"text":1454,"url":18,"identifiers":1455},"Jatakanon A, Lim S, Kharitonov SA, Chung KF, Barnes PJ. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax. 1998;53(2):91–5.",{"doi":1456},"10.1136\u002Fthx.53.2.91",{"id":18,"text":1458,"url":18,"identifiers":1459},"Lim S, Jatakanon A, Meah S, Oates T, Chung KF, Barnes PJ. Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in mild to moderately severe asthma. Thorax. 2000;55(3):184–8.",{"doi":1460},"10.1136\u002Fthorax.55.3.184",{"id":18,"text":1462,"url":18,"identifiers":1463},"Silkoff PE, Lent AM, Busacker AA, Katial RK, Balzar S, Strand M, et al. Exhaled nitric oxide identifies the persistent eosinophilic phenotype in severe refractory asthma. J Allergy Clin Immunol. 2005;116:1249–55.",{"doi":1464},"10.1016\u002Fj.jaci.2005.09.029",{"id":18,"text":1466,"url":18,"identifiers":1467},"Berry MA, Shaw DE, Green RH, Brightling CE, Wardlaw AJ, Pavord ID. The use of exhaled nitric oxide concentration to identify eosinophilic airway inflammation: an observational study in adults with asthma. Clin Exp Allergy. 2005;35:1175–9.",{"doi":1468},"10.1111\u002Fj.1365-2222.2005.02314.x",{"id":18,"text":1470,"url":18,"identifiers":1471},"Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J. 1993;6:1368–70.",{"doi":1472},"10.1183\u002F09031936.93.06091368",{"id":18,"text":1474,"url":18,"identifiers":1475},"Kharitonov SA, Wells AU, O'Connor BJ, Cole PJ, Hansell DM, Logan-Sinclair RB, et al. Elevated levels of exhaled nitric oxide in bronchiectasis. Am J Respir Crit Care Med. 1995;151(6):1889–93.",{"doi":1476},"10.1164\u002Fajrccm.151.6.7767536",{"id":18,"text":1478,"url":18,"identifiers":1479},"Cho YJ, Lim HJ, Park JS, Lee JH, Lee CT, Yoon HI. Measurement of fractional exhaled nitric oxide in stable bronchiectasis. Tuberc Respir Dis (Seoul). 2013;74(1):7–14.",{"doi":1480},"10.4046\u002Ftrd.2013.74.1.7",{"id":18,"text":1482,"url":18,"identifiers":1483},"Cole PJ. Inflammation: a two-edged sword-the model of bronchiectasis. Eur J Respir Dis Suppl. 1986;147:6–15.",{},{"id":18,"text":1485,"url":18,"identifiers":1486},"Fuschillo S, De Felice A, Balzano G. Mucosal inflammation in idiopathic bronchiectasis: celular and molecular mechanisms. Eur Respir J. 2008;31(2):396–406.",{"doi":1487},"10.1183\u002F09031936.00069007",{"id":18,"text":1489,"url":18,"identifiers":1490},"Tsikrika S, Dimakou K, Papaioannou AI, Hillas G, Thanos L, Kostikas K, et al. The role of non-invasive modalities for assessing inflammation in patients with non-cystic fibrosis bronchiectasis. Cytokine. 2017;99:281–6.",{"doi":1491},"10.1016\u002Fj.cyto.2017.08.005",{"id":18,"text":1493,"url":18,"identifiers":1494},"Chen FJ, Liao H, Huang XY, Xie CM. Importance of fractional exhaled nitric oxide in diagnosis of bronchiectasis accompanied with bronchial asthma. J Thorac Dis. 2016;8(5):992–9.",{"doi":1495},"10.21037\u002Fjtd.2016.03.72",{"id":18,"text":1497,"url":18,"identifiers":1498},"Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602–15.",{"doi":1499},"10.1164\u002Frccm.9120-11ST",{"id":1501,"createTime":1502,"updateTime":1503,"relativeEntities":1504,"slug":1505,"properties":1506,"entityType":106,"verifyStatus":107,"verifyTime":1517,"verifyNote":109,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":1518,"fullTextUrl":18,"authors":1519,"publicationType":222,"publisherRelationship":1621,"citationCount":19,"citationInfo":1667,"publishDate":1670,"publishYear":1668,"citationAnalyzeStatus":896,"lastCitationAnalyze":1671,"indexDatabases":1672,"openAccess":18,"references":18,"isForceReanalyzing":279},"317d5215-1b93-45d9-813b-8c044296c9e4","2024-01-27T19:49:56.638+00:00","2026-07-26T14:57:03.687+00:00",[],"Cigarette-smoke-differentially-modulates-dendritic-cell-maturation-and-function-in-time",{"abstract":1507,"title":1509,"gsPaper":1511,"references":1513,"doi":1515},{"EN":1508},"Dendritic cells (DCs) as professional antigen presenting cells (APCs) play a critical role in the regulation of host immune responses. DCs evolve from immature, antigen-capturing cells, to mature antigen-presenting cells. The relative contribution of DCs to cigarette smoke-induced inflammation is not well documented. In the current study, we investigated a modulatory effect of cigarette smoke extract (CSE) on differentiation, maturation and function of DCs. Primary murine DCs were grown from bone marrow cells with GM-CSF. Development of DC was analyzed by expression of CD11c, MHCII, CD86, CD40 and CD83 using flow cytometry. Murine DC’s and human L428 cells were co-cultured with CSE for various periods of time. Functional activity was analyzed by measuring FITC-dextran uptake, cytokine production and the ability to stimulate T cell activation in a mixed lymphocyte reaction. Our results show that short-term CSE stimulation (~24 h) influence the maturation status of newly differentiated and immature DCs towards more mature cells as revealed by upregulation of MHCII, CD83, CD86, CD40, reduction in antigen up-take capacity and enhanced secretion of pro-inflammatory (IL-12, IL-6 and TNF-α) cytokines. Interestingly, long-term CSE exposure, time- and concentration-dependently, suppressed the development of functional DCs. This suppression was demonstrated by a decline in CD11c\u002FMHCII, CD83, CD86 and CD40 expression, the production of cytokines and ability to stimulate T lymphocytes. Moreover, CSE significantly suppressed the endocytosis function of mouse DCs which was not due to diminished DC viability. Similar to mouse DCs, long-term co-culturing of the human L428 DC cell line with CSE time-dependently suppressed the expression of CD54. The present study provides evidence that CSE modulates DC-mediated immune responses via affecting both the function and maturation of DCs. The suppressive effects of cigarette smoke on DC function might lead to impaired immune responses to various infections.",{"EN":1510},"Cigarette smoke differentially modulates dendritic cell maturation and function in time",{"VOID":1512},"[\"13481150260193143579\"]",{"VOID":1514},"Gershon AS, Warner L, Cascagnette P, Victor JC, To T. Lifetime risk of developing chronic obstructive pulmonary disease: a longitudinal population study. Lancet. 2011;378:991–6.\nLarsson L, Pehrson C, Dechen T, Crane-Godreau M. Microbiological components in mainstream and sidestream cigarette smoke. Tob Induc Dis. 2012;10:13.\nTanaka H, Demeure CE, Rubio M, Delespesse G, Sarfati M. Human monocyte-derived dendritic cells induce naive T cell differentiation into T helper cell type 2 (Th2) or Th1\u002FTh2 effectors. Role of stimulator\u002Fresponder ratio. J Exp Med. 2000;192:405–12.\nBothelo FM, Nikota JK, Bauer CMT, Morissette MC, Iwakura Y, Kolbeck R, et al. Cigarette-smoke induced accumulation of lung dendritic cells is interleukin-1α dependent in mice. Respir Res. 2012;6:e28457.\nSanarico N, Ciaramella A, Sacchi A, Bernasconi D, Bossù P, Mariani F, et al. Human monocyte-derived dendritic cells differentiated in the presence of IL-2 produce proinflammatory cytokines and prime Th1 immune response. J Leukoc Biol. 2006;80:555–62.\nDesch AN, Randolph GJ, Murphy K, Gautier EL, Kedl RM, Lahoud MH, et al. CD103+ pulmonary dendritic cells preferentially acquire and present apoptotic cell-associated antigen. J Exp Med. 2011;208(9):1789–97.\nHashimoto M, Yanagisawa H, Minagawa S, Sen D, Ma R, Murray LA, et al. TGF-β-Dependent Dendritic Cell Chemokinesis in Murine Models of Airway Disease. J Immunol. 2015;195:1182–90.\nMacDonald KP, Munster DJ, Clark GJ, Dzionek A, Schmitz J, Hart DN. Characterization of human blood dendritic cell subsets. Blood. 2002;100:4512–20.\nWikstrom ME, Stumbles PA. Mouse respiratory tract dendritic cell subsets and the immunological fate of inhaled antigens. Immunol Cell Biol. 2007;85:182–8.\nInaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte\u002Fmacrophage colony-stimulating factor. J Exp Med. 1992;176:1693–702.\nInaba K, Steinman RM, Pack MW, Aya H, Inaba M, Sudo T, et al. Identification of proliferating dendritic cell precursors in mouse blood. J Exp Med. 1992;175:1157–67.\nScheicher C, Mehlig M, Zecher R, Reske K. Dendritic cells from mouse bone marrow: in vitro differentiation using low doses of recombinant granulocyte-macrophage colony-stimulating factor. J Immunol Methods. 1992;154:253–64.\nPeters JH, Xu H, Ruppert J, Ostermeier D, Friedrichs D, Gieseler RK. Signals required for differentiating dendritic cells from human monocytes in vitro. Adv Exp Med Biol. 1993;329:275–80.\nVassallo R, Tamada K, Lau JS, Kroening PR, Chen L. Cigarette smoke extract suppresses human dendritic cell function leading to preferential induction of Th-2 priming. J Immunol. 2005;175:2684–91.\nNouri-Shirazi M, Guinet E. A possible mechanism linking cigarette smoke to higher incidence of respiratory infection and asthma. Immunol Lett. 2006;103:167–76.\nAicher A, Heeschen C, Mohaupt M, Cooke JP, Zeiher AM, Dimmeler S. Nicotine strongly activates dendritic cell-mediated adaptive immunity: potential role for progression of atherosclerotic lesions. Circulation. 2003;107:604–11.\nMortaz E, Kraneveld AD, Smit JJ, Kool M, Lambrecht BN, Kunkel SL, et al. Effect of cigarette smoke extract on dendritic cells and their impact on T-cell proliferation. PLoS One. 2009;4:e4946.\nBlue ML, Janoff A. Possible mechanisms of emphysema in cigarette smokers. Release of elastase from human polymorphonuclear leukocytes by cigarette smoke condensate in vitro. Am Rev Respir Dis. 1978;117:317–25.\nLutz MB, Kukutsch N, Ogilvie AL, Rossner S, Koch F, Romani N, et al. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods. 1999;223:77–92.\nSheikh NA, Jones LA. CD54 is a surrogate marker of antigen presenting cell activation. Cancer Immunol Immunother. 2008;57:1381–90.\nRobbins CS, Franco F, Mouded M, Cernadas M, Shapiro SD. Cigarette smoke exposure impairs dendritic cell maturation and T cell proliferation in thoracic lymph nodes of mice. J Immunol. 2008;180:6623–8.\nWilson NS, El-Sukkari D, Villadangos JA. Dendritic cells constitutively present self antigens in their immature state in vivo and regulate antigen presentation by controlling the rates of MHC class II synthesis and endocytosis. Blood. 2004;103:2187–95.\nMcKenzie JL, Egner W, Calder VL, Hart DN. Hodgkin’s disease cell lines: a model for interleukin- 1-independent accessory cell function. Immunology. 1992;77:345–53.\nKennedy IC, Hart DN, Colls BM, Nimmo JC, Willis DA, Angus HB. Nodular sclerosing, mixed cellularity and lymphocyte-depleted variants of Hodgkin’s disease are probable dendritic cell malignancies. Clin Exp Immunol. 1989;76:324–31.\nKandasamy M, Ying PC, Ho AW, Sumatoh HR, Schlitzer A, Hughes TR, et al. Complement mediated signaling on pulmonary CD103(+) dendritic cells is critical for their migratory function in response to influenza infection. PLoS Pathog. 2013;9:e1003115.\nKroening PR, Barnes TW, Pease L, Limper A, Kita H, Vassallo R. Cigarette smoke-induced oxidative stress suppresses generation of dendritic cell IL-12 and IL-23 through ERK-dependent pathways. J Immunol. 2008;181(2):1536–47.\nVassallo R, Kroening PR, Parambil J, Kita H. Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses. Mol Immunol. 2008;45:3321–9.\nNouri-Shirazi M, Guinet E. Evidence for the immunosuppressive role of nicotine on human dendritic cell functions. Immunology. 2003;109:365–73.\nNouri-Shirazi M, Tinajero R, Guinet E. Nicotine alters the biological activities of developing mouse bone marrow-derived dendritic cells (DCs). Immunol Lett. 2007;109:155–64.\nFeldman C1, Anderson R. Cigarette smoking and mechanisms of susceptibility to infections of the respiratory tract and other organ systems. J Infect. 2013:67:169-84.\nGivi ME, Peck MJ, Boon L, Mortaz E. The role of dendritic cells in the pathogenesis of cigarette smoke-induced emphysema in mice. Eur J Pharmacol. 2013;721(1-3):259–66.\nLiao S, Ding T, Rao X-M, Sun D-S, Sun P-P, Wang Y-J, et al. Cigarette smoke affects dendritic cell maturation in the small airways of patients with chronic obstructive pulmonary disease. Mol Med Rep. 2015;11:219–25.\nStoll P, Heinz AS, Bratke K, Bier A, Garbe K, Kuepper M, et al. Impact of smoking on dendritic cell phenotypes in the airway lumen of patients with COPD. Respir Res. 2014;15:48.\nZanini A, Spanevello A, Baraldo S, Majori M, Della Patrona S, Gumiero F, et al. Decreased Maturation of Dendritic Cells in the Central Airways of COPD Patients Is Associated with VEGF, TGF-β and Vascularity. Respiration. 2014;87(3):234–42.\nRogers AV, Adelroth E, Hattotuwa K, Dewar A, Jeffery PK. Bronchial mucosal dendritic cells in smokers and ex smokers with COPD: an electron microscopic study. Thorax. 2008;63:108–14.",{"VOID":1516},"10.1186\u002Fs12931-015-0291-6","2024-08-30T20:31:04.139+00:00","https:\u002F\u002Frespiratory-research.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs12931-015-0291-6",[1520,1545,1560,1575,1590],{"id":1521,"sortIndex":19,"researcher":18,"roles":1522,"affiliations":1523,"properties":1540,"displayName":1542,"givenName":18,"familyName":18},"24e6083f-6752-48ba-876e-954236d4fda1",[115],[1524,1532],{"id":1525,"sortIndex":19,"affiliation":1526,"properties":18},"8869d554-0bbf-46e0-b4ee-c46dcd283844",{"id":1525,"createTime":18,"updateTime":18,"relativeEntities":1527,"slug":18,"properties":1528,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1531,"statistic":18},[],{"title":1529},{"VI":1530},"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands",[],{"id":1533,"sortIndex":80,"affiliation":1534,"properties":18},"e5b1cd77-3037-4f25-8ca9-e9ec8585c109",{"id":1533,"createTime":18,"updateTime":18,"relativeEntities":1535,"slug":18,"properties":1536,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1539,"statistic":18},[],{"title":1537},{"VI":1538},"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Shahid Chamran University, Ahvaz, Iran",[],{"title":1541,"gsAuthor":1543},{"VI":1542},"Masoumeh Ezzati Givi",{"VOID":1544},"[\"RefezxEAAAAJ\"]",{"id":1546,"sortIndex":80,"researcher":18,"roles":1547,"affiliations":1548,"properties":1555,"displayName":1557,"givenName":18,"familyName":18},"d891710b-b678-4407-a0df-952798d78604",[115],[1549],{"id":1525,"sortIndex":19,"affiliation":1550,"properties":18},{"id":1525,"createTime":18,"updateTime":18,"relativeEntities":1551,"slug":18,"properties":1552,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1554,"statistic":18},[],{"title":1553},{"VI":1530},[],{"title":1556,"gsAuthor":1558},{"VI":1557},"Gert Folkerts",{"VOID":1559},"[\"SOLIKbIAAAAJ\"]",{"id":1561,"sortIndex":154,"researcher":18,"roles":1562,"affiliations":1563,"properties":1572,"displayName":1574,"givenName":18,"familyName":18},"fa41e66e-7d2f-42a4-8dc5-c023c0001f98",[115],[1564],{"id":1565,"sortIndex":19,"affiliation":1566,"properties":18},"34f53cfb-8631-432b-b679-13e7b92f44a4",{"id":1565,"createTime":18,"updateTime":18,"relativeEntities":1567,"slug":18,"properties":1568,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1571,"statistic":18},[],{"title":1569},{"VI":1570},"Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, Leiden, The Netherlands",[],{"title":1573},{"VI":1574},"Gerry T. M. Wagenaar",{"id":1576,"sortIndex":168,"researcher":18,"roles":1577,"affiliations":1578,"properties":1585,"displayName":1587,"givenName":18,"familyName":18},"1ff4fd22-5068-4c42-b7ba-3af0cb037058",[115],[1579],{"id":1525,"sortIndex":19,"affiliation":1580,"properties":18},{"id":1525,"createTime":18,"updateTime":18,"relativeEntities":1581,"slug":18,"properties":1582,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1584,"statistic":18},[],{"title":1583},{"VI":1530},[],{"title":1586,"gsAuthor":1588},{"VI":1587},"Frank A. Redegeld",{"VOID":1589},"[\"HBbKWqMAAAAJ\"]",{"id":1591,"sortIndex":182,"researcher":18,"roles":1592,"affiliations":1593,"properties":1618,"displayName":1620,"givenName":18,"familyName":18},"8f9153ab-5b1f-4c30-a23e-6deb8b000dfb",[115],[1594,1600,1609],{"id":1525,"sortIndex":19,"affiliation":1595,"properties":18},{"id":1525,"createTime":18,"updateTime":18,"relativeEntities":1596,"slug":18,"properties":1597,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1599,"statistic":18},[],{"title":1598},{"VI":1530},[],{"id":1601,"sortIndex":80,"affiliation":1602,"properties":1608},"e102b103-402a-4995-a3d8-25c2f29599d7",{"id":1601,"createTime":18,"updateTime":18,"relativeEntities":1603,"slug":18,"properties":1604,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1607,"statistic":18},[],{"title":1605},{"VI":1606},"Chronic Respiratory Diseases Research Center and National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Department of Immunology, Shahid Beheshti University of Medical Sciences, Tehran, Iran",[],{},{"id":1610,"sortIndex":154,"affiliation":1611,"properties":1617},"693d3e6d-48c4-49fe-a11c-393f5a9059ce",{"id":1610,"createTime":18,"updateTime":18,"relativeEntities":1612,"slug":18,"properties":1613,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1616,"statistic":18},[],{"title":1614},{"VI":1615},"Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK",[],{},{"title":1619},{"VI":1620},"Esmaeil Mortaz",{"url":1518,"publisher":1622,"properties":1663},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1623,"slug":10,"properties":1624,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":1627,"manageAffiliations":1632,"indexDatabases":1643,"url":77,"thumbnailPath":18,"statistic":1658,"gsStatistic":18,"type":84,"analyzePriority":18},[],{"issn":1625,"title":1626},{"VOID":13},{"EN":15},[1628],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":1629,"label":1630,"description":1631,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[1633,1638],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":1634,"slug":18,"properties":1635,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1637,"statistic":18},[],{"title":1636},{"EN":33},[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":1639,"slug":18,"properties":1640,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1642,"statistic":18},[],{"title":1641},{"EN":40},[],[1644,1651],{"id":44,"indexDatabase":1645,"url":55,"indexYears":56,"academicFieldIds":1650,"indexDatabaseRanking":59},{"id":46,"createTime":18,"updateTime":18,"relativeEntities":1646,"label":1647,"description":1648,"key":52,"publicationTags":1649,"standard":18},[],{"EN":49,"VI":49},{"EN":49,"VI":51},[54],[58],{"id":61,"indexDatabase":1652,"url":74,"indexYears":18,"academicFieldIds":1657,"indexDatabaseRanking":18},{"id":63,"createTime":18,"updateTime":18,"relativeEntities":1653,"label":1654,"description":1655,"key":70,"publicationTags":1656,"standard":18},[],{"EN":66,"VI":66},{"EN":68,"VI":69},[72,73],[76],{"impactFactor":19,"impactFactorByYear":1659,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":1660,"totalCitation":19,"totalCitationByYear":1661,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":1662,"hindexLast5Year":19,"hindex":19},{},{"2004":80},{},{},{"pages":1664,"volume":1665},{"VOID":995},{"VOID":1666},"16",{"total":19,"publishYear":1668,"statisticByYear":1669},2015,{},"2015-10-24","2026-07-26T14:57:03.686+00:00",[72,59],{"id":1674,"createTime":1675,"updateTime":1676,"relativeEntities":1677,"slug":1678,"properties":1679,"entityType":106,"verifyStatus":107,"verifyTime":1689,"verifyNote":109,"languages":18,"translateLanguages":18,"viewCount":196,"primaryUrl":1690,"fullTextUrl":18,"authors":1691,"publicationType":222,"publisherRelationship":1804,"citationCount":18,"citationInfo":18,"publishDate":1850,"publishYear":272,"citationAnalyzeStatus":745,"lastCitationAnalyze":1851,"indexDatabases":1852,"openAccess":18,"references":18,"isForceReanalyzing":279},"be420b95-dc23-49ee-8159-c7841351d9da","2023-12-01T07:04:03.440+00:00","2026-07-23T17:50:39.340+00:00",[],"Duration-and-determinants-of-delayed-tuberculosis-diagnosis-and-treatment-in-high-burden-countries-a-mixed-methods-systematic-review-and-meta-analysis",{"abstract":1680,"title":1682,"gsPaper":1684,"references":1685,"doi":1687},{"EN":1681},"Thirty countries with the highest tuberculosis (TB) burden bear 87% of the world’s TB cases. Delayed diagnosis and treatment are detrimental to TB prognosis and sustain TB transmission in the community, making TB elimination a great challenge, especially in these countries. Our objective was to elucidate the duration and determinants of delayed diagnosis and treatment of pulmonary TB in high TB-burden countries. We conducted a systematic review and meta-analysis of quantitative and qualitative studies by searching four databases for literature published between 2008 and 2018 following PRISMA guidelines. We performed a narrative synthesis of the covariates significantly associated with patient, health system, treatment, and total delays. The pooled median duration of delay and effect sizes of covariates were estimated using random-effects meta-analyses. We identified key qualitative themes using thematic analysis. This review included 124 articles from 14 low- and lower-middle-income countries (LIC and LMIC) and five upper-middle-income countries (UMIC). The pooled median duration of delays (in days) were—patient delay (LIC\u002FLMIC: 28 (95% CI 20–30); UMIC: 10 (95% CI 10–20), health system delay (LIC\u002FLMIC: 14 (95% CI 2–28); UMIC: 4 (95% CI 2–4), and treatment delay (LIC\u002FLMIC: 14 (95% CI 3–84); UMIC: 0 (95% CI 0–1). There was consistent evidence that being female and rural residence was associated with longer patient delay. Patient delay was also associated with other individual, interpersonal, and community risk factors such as poor TB knowledge, long chains of care-seeking through private\u002Fmultiple providers, perceived stigma, financial insecurities, and poor access to healthcare. Organizational and policy factors mediated health system and treatment delays. These factors included the lack of resources and complex administrative procedures and systems at the health facilities. We identified data gaps in 11 high-burden countries. This review presented the duration of delays and detailed the determinants of delayed TB diagnosis and treatment in high-burden countries. The gaps identified could be addressed through tailored approaches, education, and at a higher level, through health system strengthening and provision of universal health coverage to reduce delays and improve access to TB diagnosis and care. PROSPERO registration: CRD42018107237.",{"EN":1683},"Duration and determinants of delayed tuberculosis diagnosis and treatment in high-burden countries: a mixed-methods systematic review and meta-analysis",{"VOID":608},{"VOID":1686},"World Health Organization. TB: a global emergency, WHO report on the TB epidemic [Internet]. Geneva: World Health Organization; 1994. Available from: https:\u002F\u002Fapps.who.int\u002Firis\u002Fhandle\u002F10665\u002F58749.\nWorld Health Organization. Global tuberculosis report 2019. Geneva: World Health Organization; 2019.\nStop TB Partnership, United Nations Office for Project Services (UNOPS). Global plan to end TB. The paradigm shift 2016–2020. Geneva: STOP TB Partnership and UNOPS; 2016.\nGolub JE, Bur S, Cronin WA, Gange S, Baruch N, Comstock GW, et al. Delayed tuberculosis diagnosis and tuberculosis transmission. Int J Tuberc Lung Dis. 2006;10:24–30.\nGetnet F, Demissie M, Assefa N, Mengistie B, Worku A. Delay in diagnosis of pulmonary tuberculosis in low-and middle-income settings: systematic review and meta-analysis. BMC Pulm Med. 2017. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12890-017-0551-y.\nde Vries SG, Cremers AL, Heuvelings CC, Greve PF, Visser BJ, Bélard S, et al. Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature. Lancet Infect Dis. 2017;17:e128–43.\nSullivan BJ, Esmaili BE, Cunningham CK. Barriers to initiating tuberculosis treatment in sub-Saharan Africa: a systematic review focused on children and youth. Glob Health Action. 2017;10:1290317.\nSreeramareddy CT, Panduru KV, Menten J, Van den Ende J. Time delays in diagnosis of pulmonary tuberculosis: a systematic review of literature. BMC Infect Dis. 2009;9:91.\nStorla DG, Yimer S, Bjune GA. A systematic review of delay in the diagnosis and treatment of tuberculosis. BMC Public Health. 2008;8:15.\nBarnabishvili M, Ulrichs T, Waldherr R. Role of acceptability barriers in delayed diagnosis of Tuberculosis: literature review from high burden countries. Acta Trop. 2016;161:106–13.\nSreeramareddy CT, Qin ZZ, Satyanarayana S, Subbaraman R, Pai M. Delays in diagnosis and treatment of pulmonary tuberculosis in India: a systematic review. Int J Tuberc Lung Dis. 2014;18:255–66.\nPage MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021. https:\u002F\u002Fdoi.org\u002F10.1136\u002Fbmj.n160.\nTeo AKJ, Singh SR, Prem K, Hsu LY, Yi S. Delayed diagnosis and treatment of pulmonary tuberculosis in high-burden countries: a systematic review protocol. BMJ Open. 2019;9:e029807.\nCASP - Critical Appraisal Skills Programme. CASP Checklists [Internet]. CASP - Critical Appraisal Skills Programme. [cited 2019 Jan 26]. Available from: https:\u002F\u002Fcasp-uk.net\u002Fcasp-tools-checklists\u002F.\nNoyes J, Booth A, Flemming K, Garside R, Harden A, Lewin S, et al. Cochrane Qualitative and Implementation Methods Group guidance series—paper 3: methods for assessing methodological limitations, data extraction and synthesis, and confidence in synthesized qualitative findings. J Clin Epidemiol. 2018;97:49–58.\nWells G, Shea B, O’connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [Internet]. [cited 2019 Jan 27]. Available from: http:\u002F\u002Fwww.ohri.ca\u002Fprograms\u002Fclinical_epidemiology\u002Foxford.asp.\nMunn Z, Porritt K, Lockwood C, Aromataris E, Pearson A. Establishing confidence in the output of qualitative research synthesis: the ConQual approach. BMC Med Res Methodol. 2014;14:108.\nThe World Bank. World Bank country and lending groups [Internet]. 2019 [cited 2019 Dec 29]. Available from: https:\u002F\u002Fdatahelpdesk.worldbank.org\u002Fknowledgebase\u002Farticles\u002F906519-world-bank-country-and-lending-groups.\nMcGrath S, Zhao X, Qin ZZ, Steele R, Benedetti A. One-sample aggregate data meta-analysis of medians. Stat Med. 2019;38:969–84.\nLin X, Chongsuvivatwong V, Geater A, Lijuan R. The effect of geographical distance on TB patient delays in a mountainous province of China. Int J Tuberc Lung Dis. 2008;12:288–93.\nLin Y, Enarson DA, Chiang C-Y, Rusen ID, Qiu L-X, Kan X-H, et al. Patient delay in the diagnosis and treatment of tuberculosis in China: findings of case detection projects. Public Health Action. 2015;5:65–9.\nCochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–29.\nHiggins JPT, Thompson SG, Spiegelhalter DJ. A re-evaluation of random-effects meta-analysis. J R Stat Soc A. 2009;172:137–59.\nBelay M, Bjune G, Ameni G, Abebe F. Diagnostic and treatment delay among tuberculosis patients in Afar Region, Ethiopia: a cross-sectional study. BMC Public Health. 2012. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-12-369.\nBogale S, Diro E, Shiferaw AM, Yenit MK. Factors associated with the length of delay with tuberculosis diagnosis and treatment among adult tuberculosis patients attending at public health facilities in Gondar town, Northwest, Ethiopia. BMC Infect Dis. 2017. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12879-017-2240-0.\nGebeyehu E, Azage M, Abeje G. Factors associated with patient’s delay in tuberculosis treatment in Bahir Dar City Administration, Northwest Ethiopia. BioMed Res Int. 2014;2014:1–6.\nSeid A, Metaferia Y. Factors associated with treatment delay among newly diagnosed tuberculosis patients in Dessie city and surroundings, Northern Central Ethiopia: a cross-sectional study. BMC Public Health. 2018. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12889-018-5823-9.\nFuge TG, Bawore SG, Solomon DW, Hegana TY. Patient delay in seeking tuberculosis diagnosis and associated factors in Hadiya Zone, Southern Ethiopia. BMC Res Notes. 2018. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs13104-018-3215-y.\nAdenager GS, Alemseged F, Asefa H, Gebremedhin AT. Factors associated with treatment delay among pulmonary tuberculosis patients in public and private health facilities in Addis Ababa, Ethiopia. Tuberc Res Treat. 2017;2017:1–9.\nAsres M, Gedefaw M, Kahsay A, Weldu Y. Patients’ delay in seeking health care for tuberculosis diagnosis in east Gojjam Zone, Northwest Ethiopia. Am J Trop Med Hyg. 2017;96:1071–5.\nGebreegziabher SB, Bjune GA, Yimer SA. Patients’ and health system’s delays in the diagnosis and treatment of new pulmonary tuberculosis patients in West Gojjam Zone, Northwest Ethiopia: a cross-sectional study. BMC Infect Dis. 2016. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12879-016-1995-z.\nMesfin MM, Newell JN, Walley JD, Gessessew A, Madeley RJ. Delayed consultation among pulmonary tuberculosis patients: a cross sectional study of 10 DOTS districts of Ethiopia. BMC Public Health. 2009. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-9-53.\nHussen A, Biadgilign S, Tessema F, Mohammed S, Deribe K, Deribew A. Treatment delay among pulmonary tuberculosis patients in pastoralist communities in Bale Zone, Southeast Ethiopia. BMC Res Notes. 2012. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1756-0500-5-320.\nYimer SA, Bjune GA, Holm-Hansen C. Time to first consultation, diagnosis and treatment of TB among patients attending a referral hospital in Northwest, Ethiopia. BMC Infect Dis. 2014. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2334-14-19.\nGele AA, Bjune G, Abebe F. Pastoralism and delay in diagnosis of TB in Ethiopia. BMC Public Health. 2009. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-9-5.\nYirgu R, Lemessa F, Hirpa S, Alemayehu A, Klinkenberg E. Determinants of delayed care seeking for TB suggestive symptoms in Seru district, Oromiya region, Ethiopia: a community based unmatched case-control study. BMC Infect Dis. 2017. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12879-017-2407-8.\nAbebe G, Deribew A, Apers L, Woldemichael K, Shiffa J, Tesfaye M, et al. Knowledge, health seeking behavior and perceived stigma towards tuberculosis among tuberculosis suspects in a rural community in southwest Ethiopia. Mokrousov I, editor. PLoS ONE. 2010;5:e13339.\nSenbeto M, Tadesse S, Tadesse T, Melesse T. Appropriate health-seeking behavior and associated factors among people who had cough for at least two weeks in northwest Ethiopia: a population-based cross-sectional study. BMC Public Health. 2013. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-13-1222.\nYimer S, Holm-Hansen C, Yimaldu T, Bjune G. Health care seeking among pulmonary tuberculosis suspects and patients in rural Ethiopia: a community-based study. BMC Public Health. 2009. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-9-454.\nEngeda EH, Dachew BA, Kassa Woreta H, Mekonnen Kelkay M, Ashenafie TD. Health seeking behaviour and associated factors among pulmonary tuberculosis suspects in Lay Armachiho District, Northwest Ethiopia: a community-based study. Tuberc Res Treat. 2016;2016:1–7.\nAddisu Y, Birhanu Z, Tilahun D, Assefa T. Predictors of treatment seeking intention among people with cough in East Wollega, Ethiopia based on the theory of planned behavior: a community based cross-sectional study. Ethiop J Health Sci. 2014;24:131.\nSaifodine A, Gudo PS, Sidat M, Black J. Patient and health system delay among patients with pulmonary tuberculosis in Beira city, Mozambique. BMC Public Health. 2013. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-13-559.\nMfinanga SG, Mutayoba BK, Kahwa A, Kimaro G, Mtandu R, Ngadaya E, et al. The magnitude and factors associated with delays in management of smear positive tuberculosis in Dar es Salaam, Tanzania. BMC Health Serv Res. 2008. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1472-6963-8-158.\nNgadaya ES, Mfinanga GS, Wandwalo ER, Morkve O. Delay in tuberculosis case detection in Pwani region, Tanzania. A cross sectional study. BMC Health Serv Res. 2009. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1472-6963-9-196.\nSenkoro M, Hinderaker SG, Mfinanga SG, Range N, Kamara DV, Egwaga S, et al. Health care-seeking behaviour among people with cough in Tanzania: findings from a tuberculosis prevalence survey. Int J Tuberc Lung Dis. 2015;19:640–6.\nSegagni Lusignani L, Quaglio G, Atzori A, Nsuka J, Grainger R, Da Conceiçao Palma M, et al. Factors associated with patient and health care system delay in diagnosis for tuberculosis in the province of Luanda, Angola. BMC Infect Dis. 2013. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2334-13-168.\nRifat M, Rusen ID, Islam MdA, Enarson DA, Ahmed F, Ahmed SM, et al. Why are tuberculosis patients not treated earlier? A study of informal health practitioners in Bangladesh. Int J Tuberc Lung Dis. 2011;15:647–51.\nLorent N, Choun K, Malhotra S, Koeut P, Thai S, Khun KE, et al. Challenges from tuberculosis diagnosis to care in community-based active case finding among the urban poor in Cambodia: a mixed-methods study. PLoS ONE. 2015;10:e0130179.\nPurty A, Chauhan R, Natesan M, Cherian J, Singh Z, Sharma Y. Patient and health system delays among adult smear-positive tuberculosis patients diagnosed at medical colleges of Puducherry in south India. Indian J Public Health. 2016;60:77.\nThakur R, Murhekar M. Delay in diagnosis and treatment among tb patients registered under RNTCP mandi, Himachal Pradesh, India, 2010. Indian J Tuberc. 2013;60:37–45.\nTamhane A, Ambe G, Vermund S, Kohler CL, Karande A, Sathiakumar N. Pulmonary tuberculosis in Mumbai, India: factors responsible for patient and treatment delays. Int J Prev Med. 2012;3:13.\nBasa S, Venkatesh S. Patient and healthcare system delays in the start of pulmonary tuberculosis treatment among tribal patients registered under DOTS, Odisha. J Clin Diagn Res [Internet]. 2016 [cited 2019 Nov 22]; Available from: http:\u002F\u002Fjcdr.net\u002Farticle_fulltext.asp?issn=0973-709x&year=2016&volume=10&issue=9&page=LC21&issn=0973-709x&id=8567.\nKalra A. Care seeking and treatment related delay among childhood tuberculosis patients in Delhi, India. Int J Tuberc Lung Dis. 2017;21:645–50.\nSatyanarayana S, Nair SA, Chadha SS, Sharma G, Yadav S, Mohanty S, et al. Healthcare seeking among people with cough of 2 weeks or more in India. Is passive TB case finding sufficient? Public Health Action. 2012;2:157–61.\nLock WA, Ahmad RA, Ruiter RAC, van der Werf MJ, Bos AER, Mahendradhata Y, et al. Patient delay determinants for patients with suspected tuberculosis in Yogyakarta province, Indonesia: TB patients delay determinants. Trop Med Int Health. 2011;16:1501–10.\nAhmad RA, Richardus JH, de Vlas SJ. Care-seeking behaviour among individuals with TB symptoms in Jogjakarta Province, Indonesia: a community-based study. Int Health. 2013;5:51–7.\nAyuo P, Diero L, Owino-Ong’or W, Mwangi A. Causes of delay in diagnosis of pulmonary tuberculosis in patients attending a referral hospital in Western Kenya. East Afr Med J. 2008. https:\u002F\u002Fdoi.org\u002F10.4314\u002Feamj.v85i6.9623.\nNjau IW, Karanja SM, Wanzala P, Omolo JO. Factors associated with late presentation of suspected tuberculosis cases to tuberculosis management facilities: the case in Dagoretti district, Nairobi, Kenya. Pan Afr Med J. 2012;12:93.\nBiya O, Gidado S, Abraham A, Waziri N, Nguku P, Nsubuga P, et al. Knowledge, care-seeking behavior, and factors associated with patient delay among newly-diagnosed pulmonary tuberculosis patients, Federal Capital Territory, Nigeria, 2010. Pan Afr Med J. 2014. https:\u002F\u002Fdoi.org\u002F10.11604\u002Fpamj.supp.2014.18.1.4166.\nUkwaja KN, Alobu I, Nweke CO, Onyenwe EC. Healthcare-seeking behavior, treatment delays and its determinants among pulmonary tuberculosis patients in rural Nigeria: a cross-sectional study. BMC Health Serv Res. 2013. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1472-6963-13-25.\nFatiregun AA, Ejeckam CC. Determinants of patient delay in seeking treatment among pulmonary tuberculosis cases in a government specialist hospital in Ibadan, Nigeria. Tanzania J Health Res. 2010. https:\u002F\u002Fdoi.org\u002F10.4314\u002Fthrb.v12i2.56398.\nChanda-Kapata P, Kapata N, Masiye F, Maboshe M, Klinkenberg E, Cobelens F, et al. Health seeking behaviour among individuals with presumptive tuberculosis in Zambia. van Zyl-Smit R, editor. PLoS ONE. 2016;11:e0163975.\nTakarinda KC, Harries AD, Nyathi B, Ngwenya M, Mutasa-Apollo T, Sandy C. Tuberculosis treatment delays and associated factors within the Zimbabwe national tuberculosis programme. BMC Public Health. 2015. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12889-015-1437-7.\nde Almeida CPB, Skupien EC, Silva DR. Health care seeking behavior and patient delay in tuberculosis diagnosis. Cadernos de Saúde Pública. 2015;31:321–30.\nDeponti GN, Silva DR, Coelho AC, Muller AM, de Dalcin PTR. Delayed diagnosis and associated factors among new pulmonary tuberculosis patients diagnosed at the emergency department of a tertiary care hospital in Porto Alegre, South Brazil: a prospective patient recruitment study. BMC Infect Dis. 2013. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2334-13-538.\nWysocki AD, Ponce MAZ, Scatolin BE, Andrade RL de P, Vendramini SHF, Netto AR, et al. Atraso na procura pelo primeiro atendimento para o diagnóstico da tuberculose. Revista da Escola de Enfermagem da USP. 2013;47:440–7.\nTrigueiro DRSG, Nogueira J de A, Sá LD de, Monroe AA, Anjos UU dos, Villa TCS, et al. The influence of individual determinants in the delay of the tuberculosis diagnosis. Texto & Contexto - Enfermagem. 2014;23:1022–31.\nMaior M de L, Guerra RL, Cailleaux-Cezar M, Golub E, Conde MB. Time from symptom onset to the initiation of treatment of pulmonary tuberculosis in a city with a high incidence of the disease. J Bras Pneumol. 2012;38:202–9.\nMachado AC de FT, Steffen RE, Oxlade O, Menzies D, Kritski A, Trajman A. Fatores associados ao atraso no diagnóstico da tuberculose pulmonar no estado do Rio de Janeiro. Jornal Brasileiro de Pneumologia. 2011;37:512–20.\nMaciel ELN, Golub JE, Peres RL, Hadad DJ, Fávero JL, Molino LP, et al. Delay in diagnosis of pulmonary tuberculosis at a primary health clinic in Vitoria, Brazil. Int J Tuberc Lung Dis. 2010;14:1403–10.\nNogueira BMF, Rolla VC, Akrami KM, Kiene SM. Factors associated with tuberculosis treatment delay in patients co-infected with HIV in a high prevalence area in Brazil. Hasnain SE, editor. PLoS ONE. 2018;13:e0195409.\nZhou C, Tobe RG, Chu J, Gen H, Wang X, Xu L. Detection delay of pulmonary tuberculosis patients among migrants in China: a cross-sectional study. Int J Tuberc Lung Dis. 2012;16:1630–6.\nChen H-G, Liu M, Jiang S-W, Gu F-H, Huang S-P, Gao T-J, et al. Impact of diabetes on diagnostic delay for pulmonary tuberculosis in Beijing. Int J Tuberc Lung Dis. 2014;18:267–71.\nWang Q, Ma A, Han X, Zhao S, Cai J, Kok FJ, et al. Hyperglycemia is associated with increased risk of patient delay in pulmonary tuberculosis in rural areas: 高血糖与农村地区肺结核患者延误就诊风险增加相关. J Diabetes. 2017;9:648–55.\nChimbatata NBW, Zhou C, Chimbatata CM, Mhango L, Diwan VK, Xu B. Barriers to prompt TB diagnosis—a comparative study between northern Malawi and eastern rural China. Trans R Soc Trop Med Hyg. 2017;111:504–11.\nDuan Q, Wang P, Lv J, Zhong R, Wang W. Health care seeking among pulmonary tuberculosis suspects in Wuhan: a community-based study. Int J Med Med Sci. 2013;5:273–8.\nTobe RG, Xu L, Zhou C, Yuan Q, Geng H, Wang X. Factors affecting patient delay of diagnosis and completion of Direct Observation Therapy, Short-course (DOTS) among the migrant population in Shandong, China. BioSci Trends [Internet]. 2013 [cited 2019 Nov 22]; Available from: http:\u002F\u002Fwww.biosciencetrends.com\u002Fgetabstract.php?id=678.\nLi X, Jiang S, Li X, Mei J, Zhong Q, Xu W, et al. Predictors on delay of initial health-seeking in new pulmonary tuberculosis cases among migrants population in east China. Pai M, editor. PLoS ONE. 2012;7:e31995.\nZhao X, Yang P, Gai R, Mei L, Wang X, Xu L. Determinants of health care-seeking delay among tuberculosis patients in Shandong Province, China. Eur J Public Health. 2014;24:757–61.\nXia D, Zhang Z, Li X, Jiang C, Ma J, Ding S, et al. Factors associated with patient delay among new tuberculosis patients in Anqing, China. Biomed Res. 2016;27:8.\nShu W, Chen W, Zhu S, Hou Y, Mei J, Bai L, et al. Factors causing delay of access to tuberculosis diagnosis among new, active tuberculosis patients: a prospective cohort study. Asia Pac J Public Health. 2014;26:33–41.\nXu X, Liu J-H, Cao S-Y, Zhao Y, Dong X-X, Liang Y, et al. Delays in care seeking, diagnosis and treatment among pulmonary tuberculosis patients in Shenzhen, China. Int J Tuberc Lung Dis. 2013;17:615–20.\nWang Y, Long Q, Liu Q, Tolhurst R, Tang S. Treatment seeking for symptoms suggestive of TB: comparison between migrants and permanent urban residents in Chongqing, China: delay in treatment seeking for symptoms suggestive of TB. Trop Med Int Health. 2008;13:927–33.\nWoith WM, Larson JL. Delay in seeking treatment and adherence to tuberculosis medications in Russia: a survey of patients from two clinics. Int J Nurs Stud. 2008;45:1163–74.\nMøller V, Erstad I, Cramm JM, Nieboer AP, Finkenflügel H, Radloff S, et al. Delays in presenting for tuberculosis treatment associated with fear of learning one is HIV-positive. Afr J AIDS Res. 2011;10:25–36.\nMeintjes G, Schoeman H, Morroni C, Wilson D, Maartens G. Patient and provider delay in tuberculosis suspects from communities with a high HIV prevalence in South Africa: a cross-sectional study. BMC Infect Dis. 2008. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2334-8-72.\nOtwombe KN, Variava E, Holmes CB, Chaisson RE, Martinson N. Predictors of delay in the diagnosis and treatment of suspected tuberculosis in HIV co-infected patients in South Africa. Int J Tuberc Lung Dis. 2013;17:1199–205.\nButsorn A, Suggaravetsiri P, Tesama N. Delay of treatment among new smear-positive pulmonary tuberculosis patients in Thai-Cambodia border: cases study in Surin and Sisaket Province, Thailand. Res J Med Sci. 2010;4:340–5.\nRattananupong T, Hiransuthikul N, Lohsoonthorn V, Chuchottaworn C. Factors associated with delay in tuberculosis treatment at 10 tertiary level care hospitals in Thailand. Southeast Asian J Trop Med Public Health. 2015;46:8.\nAdejumo OA, Daniel OJ, Otesanya AF, Adejumo EN. Determinants of health system delay at public and private directly observed treatment, short course facilities in Lagos State, Nigeria: a cross-sectional study. Int J Mycobacteriol. 2016;5:257–64.\nRossato Silva D, Müller AM, de Tarso Roth Dalcin P. Factors associated with delayed diagnosis of tuberculosis in hospitalized patients in a high TB and HIV burden setting: a cross-sectional study. BMC Infect Dis. 2012. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2334-12-57.\nBoniface R, Moshabela M, Zulliger R, MacPherson P, Nyasulu P. Correlates of delayed diagnosis among human immunodeficiency virus-infected pulmonary tuberculosis suspects in a rural HIV Clinic, South Africa. Tuberc Res Treat. 2012;2012:1–7.\nHinderaker SG, Madland S, Ullenes M, Enarson DA, Rusen I, Kamara D. Treatment delay among tuberculosis patients in Tanzania: data from the FIDELIS initiative. BMC Public Health. 2011. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-11-306.\nHtike W, Islam MA, Hasan MT, Ferdous S, Rifat M. Factors associated with treatment delay among tuberculosis patients referred from a tertiary hospital in Dhaka City: a cross-sectional study. Public Health Action. 2013;3:317–22.\nThomas BE, Subbaraman R, Sellappan S, Suresh C, Lavanya J, Lincy S, et al. Pretreatment loss to follow-up of tuberculosis patients in Chennai, India: a cohort study with implications for health systems strengthening. BMC Infect Dis. 2018. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12879-018-3039-3.\nPaul D, Busireddy A, Nagaraja SB, Satyanarayana S, Dewan PK, Nair SA, et al. Factors associated with delays in treatment initiation after tuberculosis diagnosis in two districts of India. Pai M, editor. PLoS ONE. 2012;7:e39040.\nKant S, Singh A, Parmeshwaran G, Haldar P, Malhotra S, Kaur R. Delay in initiation of treatment after diagnosis of pulmonary tuberculosis in primary health care setting: eight year cohort analysis from district Faridabad, Haryana, North India. Rural Remote Health. 2017. https:\u002F\u002Fdoi.org\u002F10.22605\u002FRRH4158.\nIlangovan K, Nagaraja SB, Ananthakrishnan R, Jacob AG, Tripathy JP, Tamang D. TB Treatment delays in Odisha, India: is it expected even after these many years of RNTCP implementation? Mistry N, editor. PLoS ONE. 2015;10:e0125465.\nMugauri H, Shewade HD, Dlodlo RA, Hove S, Sibanda E. Bacteriologically confirmed pulmonary tuberculosis patients: loss to follow-up, death and delay before treatment initiation in Bulawayo, Zimbabwe from 2012–2016. Int J Infect Dis. 2018;76:6–13.\nZhou C, Chu J, Geng H, Wang X, Xu L. Pulmonary tuberculosis among migrants in Shandong, China: factors associated with treatment delay. BMJ Open. 2014;4:e005805.\nVan Wyk SS, Enarson DA, Beyers N, Lombard C, Hesseling AC. Consulting private health care providers aggravates treatment delay in urban South African tuberculosis patients. Int J Tuberc Lung Dis. 2011;15:1069–76.\nAsefa A, Teshome W. Total delay in treatment among smear positive pulmonary tuberculosis patients in five primary health centers, southern Ethiopia: a cross sectional study. Pai M, editor. PLoS ONE. 2014;9:e102884.\nBronner Murrison L, Ananthakrishnan R, Swaminathan A, Auguesteen S, Krishnan N, Pai M, et al. How do patients access the private sector in Chennai, India? An evaluation of delays in tuberculosis diagnosis. Int J Tuberc Lung Dis. 2016;20:544–51.\nVan Ness SE, Chandra A, Sarkar S, Pleskunas J, Ellner JJ, Roy G, et al. Predictors of delayed care seeking for tuberculosis in southern India: an observational study. BMC Infect Dis. 2017. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12879-017-2629-9.\nMahendradhata Y, Syahrizal BM, Utarini A. Delayed treatment of tuberculosis patients in rural areas of Yogyakarta province, Indonesia. BMC Public Health. 2008. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-8-393.\nBassili A, Seita A, Baghdadi S, AlAbsi A, Abdilai I, Agboatwalla M, et al. Diagnostic and treatment delay in tuberculosis in 7 countries of the eastern Mediterranean region. Infect Dis Clin Pract. 2008;16:23–35.\nSaqib MA, Awan IN, Rizvi SK, Shahzad MI, Mirza ZS, Tahseen S, et al. Delay in diagnosis of tuberculosis in Rawalpindi, Pakistan. BMC Res Notes. 2011. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1756-0500-4-165.\nSaqib SE, Ahmad MM, Amezcua-Prieto C, Virginia M-R. Treatment delay among pulmonary tuberculosis patients within the Pakistan National Tuberculosis Control Program. Am J Trop Med Hyg. 2018;99:143–9.\nCoimbra I, Maruza M, de Militão-Albuquerque MFP, Moura LV, Diniz GTN, de Miranda-Filho DB, et al. Associated factors for treatment delay in pulmonary tuberculosis in HIV-infected individuals: a nested case-control study. BMC Infect Dis. 2012. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2334-12-208.\nSagbakken M, Frich JC, Bjune GA. Perception and management of tuberculosis symptoms in Addis Ababa, Ethiopia. Qual Health Res. 2008;18:1356–66.\nTadesse T, Demissie M, Berhane Y, Kebede Y, Abebe M. Long distance travelling and financial burdens discourage tuberculosis DOTs treatment initiation and compliance in Ethiopia: a qualitative study. BMC Public Health. 2013. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-13-424.\nGele AA, Sagbakken M, Abebe F, Bjune GA. Barriers to tuberculosis care: a qualitative study among Somali pastoralists in Ethiopia. BMC Res Notes. 2010. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1756-0500-3-86.\nMindu C, López-Varela E, Alonso-Menendez Y, Mausse Y, Augusto OJ, Gondo K, et al. Caretakers’ perspectives of paediatric TB and implications for care-seeking behaviours in Southern Mozambique. Graham SM, editor. PLoS ONE. 2017;12:e0182213.\nVerhagen LM, Kapinga R, van Rosmalen-Nooijens KAWL. Factors underlying diagnostic delay in tuberculosis patients in a rural area in Tanzania: a qualitative approach. Infection. 2010;38:433–46.\nGosoniu GD, Ganapathy S, Kemp J, Auer C, Somma D, Karim F, et al. Gender and socio-cultural determinants of delay to diagnosis of TB in Bangladesh, India and Malawi. Int J Tuberc Lung Dis. 2008;12:848–55.\nBam K, Bhatt LP, Thapa R, Dossajee HK, Angdembe MR. Illness perception of tuberculosis (TB) and health seeking practice among urban slum residents of Bangladesh: a qualitative study. BMC Res Notes. 2014. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1756-0500-7-572.\nSundaram N, James R, Sreynimol U, Linda P, Yoong J, Saly S, et al. A strong TB programme embedded in a developing primary healthcare system is a lose-lose situation: insights from patient and community perspectives in Cambodia. Health Policy Plan. 2017;32:ii32–42.\nPurohit MR, Sharma M, Rosales-Klintz S, Lundborg CS. ‘Multiple-test’ approach to the laboratory diagnosis of tuberculosis-perception of medical doctors from Ujjain, India. BMC Infect Dis. 2015. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12879-015-1037-2.\nMistry N, Rangan S, Dholakia Y, Lobo E, Shah S, Patil A. Durations and delays in care seeking, diagnosis and treatment initiation in uncomplicated pulmonary tuberculosis patients in Mumbai, India. Hozbor DF, editor. PLoS ONE. 2016;11:e0152287.\nKapoor SK, Raman AV, Sachdeva KS, Satyanarayana S. How did the TB patients reach DOTS services in Delhi? A study of patient treatment seeking behavior. Neyrolles O, editor. PLoS ONE. 2012;7:e42458.\nMcArthur E, Bali S, Khan A. Socio-cultural and knowledge-based barriers to tuberculosis diagnosis for women in Bhopal, India. Indian J Community Med. 2016;41:62.\nYellappa V, Lefèvre P, Battaglioli T, Devadasan N, Van der Stuyft P. Patients pathways to tuberculosis diagnosis and treatment in a fragmented health system: a qualitative study from a south Indian district. BMC Public Health. 2017. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12889-017-4627-7.\nRintiswati N, Mahendradhata Y, Suharna, Susilawati, Purwanta, Subronto Y, et al. Journeys to tuberculosis treatment: a qualitative study of patients, families and communities in Jogjakarta, Indonesia. BMC Public Health. 2009. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-9-158.\nDewi C, Barclay L, Passey M, Wilson S. Improving knowledge and behaviours related to the cause, transmission and prevention of Tuberculosis and early case detection: a descriptive study of community led Tuberculosis program in Flores, Indonesia. BMC Public Health. 2016. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12889-016-3448-4.\nOshi DC, Oshi SN, Alobu IN, Ukwaja KN. Gender-related factors influencing women’s health seeking for tuberculosis care in Ebonyi State, Nigeria. J Biosoc Sci. 2016;48:37–50.\nHu A, Loo E, Winch PJ, Surkan PJ. Filipino women’s tuberculosis care seeking experience in an urban poor setting: a socioecological perspective. Health Care Women Int. 2012;33:29–44.\nCremers AL, Gerrets R, Kapata N, Kabika A, Birnie E, Klipstein-Grobusch K, et al. Tuberculosis patients’ pre-hospital delay and non-compliance with a longstanding DOT programme: a mixed methods study in urban Zambia. BMC Public Health. 2016. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12889-016-3771-9.\nMavhu W, Dauya E, Bandason T, Munyati S, Cowan FM, Hart G, et al. Chronic cough and its association with TB-HIV co-infection: factors affecting help-seeking behaviour in Harare, Zimbabwe. Trop Med Int Health. 2010. https:\u002F\u002Fdoi.org\u002F10.1111\u002Fj.1365-3156.2010.02493.x.\nde Sa LD, Barreto AJR, de Nogueira JA, Cunha FTS, Palha PF, Villa TCS. The discourse of health managers on aspects related to the delay in tuberculosis diagnosis. Revista da Escola de Enfermagem da USP. 2013;47:1165–71.\nFurlan MCR, Silva RLST, Marcon SS. Factors associated with early and late diagnosis of tuberculosis: a descriptive study. Online Braz J Nurs. 2014;13:62–71.\nde Andrade SLE, de Souza Rodrigues DC, Barreto AJR, de Oliveira AAV, do Nascimento Santos ARB, de Sa LD. Tuberculosis among the elderly: health care system gateway and late diagnosis. Revista Enfermagem UERJ. 2016. https:\u002F\u002Fdoi.org\u002F10.12957\u002Freuerj.2016.5702.\nOliveira AAV de, Sá LD de, Nogueira J de A, Andrade SLE de, Palha PF, Villa TCS. Diagnóstico da tuberculose em pessoas idosas: barreiras de acesso relacionadas aos serviços de saúde. Revista da Escola de Enfermagem da USP. 2013;47:145–51.\nStrand MA, Duan X, Johnson R, Li Y. Social determinants of delayed diagnosis of tuberculosis in a North China urban setting. Int Q Community Health Educ. 2011;31:279–90.\nWei X, Chen J, Chen P, Newell JN, Li H, Sun C, et al. Barriers to TB care for rural-to-urban migrant TB patients in Shanghai: a qualitative study. Trop Med Int Health. 2009;14:754–60.\nLong Q, Li Y, Wang Y, Yue Y, Tang C, Tang S, et al. Barriers to accessing TB diagnosis for rural-to-urban migrants with chronic cough in Chongqing, China: a mixed methods study. BMC Health Serv Res. 2008. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1472-6963-8-202.\nHutchison C, Khan MS, Yoong J, Lin X, Coker RJ. Financial barriers and coping strategies: a qualitative study of accessing multidrug-resistant tuberculosis and tuberculosis care in Yunnan, China. BMC Public Health. 2017. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12889-017-4089-y.\nKuznetsov VN, Grjibovski AM, Mariandyshev AO, Johansson E, Enarson DA, Bjune GA. Hopelessness as a basis for tuberculosis diagnostic delay in the Arkhangelsk region: a grounded theory study. BMC Public Health. 2013. https:\u002F\u002Fdoi.org\u002F10.1186\u002F1471-2458-13-712.\nKuznetsov VN, Grjibovski AM, Mariandyshev AO, Johansson E, Bjune GA. Two vicious circles contributing to a diagnostic delay for tuberculosis patients in Arkhangelsk. Emerg Health Threats J. 2014;7:24909.\nAdams LV, Basu D, Grande SW, Craig SR, Patridge MT, Panth N, et al. Barriers to tuberculosis care delivery among miners and their families in South Africa: an ethnographic study. Int J Tuberc Lung Dis. 2017;21:571–8.\nFinnie RKC, Mabunda T, Khoza LB, van den Borne B, Selwyn B, Mullen PD. Pilot study to develop a rapid assessment of tuberculosis care-seeking and adherence practices in rural Limpopo Province, South Africa. Int Q Community Health Educ. 2011;31:3–19.\nSkinner D, Claassens M. It’s complicated: why do tuberculosis patients not initiate or stay adherent to treatment? A qualitative study from South Africa. BMC Infect Dis. 2016. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12879-016-2054-5.\nKerrigan D, West N, Tudor C, Hanrahan CF, Lebina L, Msandiwa R, et al. Improving active case finding for tuberculosis in South Africa: informing innovative implementation approaches in the context of the Kharitode trial through formative research. Health Res Policy Syst. 2017. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12961-017-0206-8.\nMurray EJ, Bond VA, Marais BJ, Godfrey-Faussett P, Ayles HM, Beyers N. High levels of vulnerability and anticipated stigma reduce the impetus for tuberculosis diagnosis in Cape Town, South Africa. Health Policy Plan. 2013;28:410–8.\nSkordis-Worrall J, Hanson K, Mills A. Confusion, caring and tuberculosis diagnostic delay in Cape Town, South Africa. Int J Tuberc Lung Dis. 2010;14:171–80.\nTschirhart N, Nosten F, Foster AM. Access to free or low-cost tuberculosis treatment for migrants and refugees along the Thailand-Myanmar border in Tak province, Thailand. Int J Equity Health. 2016. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs12939-016-0391-z.\nWingfield T, Boccia D, Tovar M, Gavino A, Zevallos K, Montoya R, et al. Defining catastrophic costs and comparing their importance for adverse tuberculosis outcome with multi-drug resistance: a prospective cohort study, Peru. PLoS Med. 2014;11:e1001675.\nWilliams E, Cheng AC, Lane GP, Guy SD. Delays in presentation and diagnosis of pulmonary tuberculosis: a retrospective study of a tertiary health service in Western Melbourne, 2011–2014. Intern Med J. 2018;48:184–93.\nAbbara A, Collin SM, Kon OM, Buell K, Sullivan A, Barrett J, et al. Time to diagnosis of tuberculosis is greater in older patients: a retrospective cohort review. ERJ Open Res. 2019;5:00228–2018.\nLönnroth K, Castro KG, Chakaya JM, Chauhan LS, Floyd K, Glaziou P, et al. Tuberculosis control and elimination 2010–50: cure, care, and social development. Lancet. 2010;375:1814–29.\nWatts K. Is Australia neglecting the local topography when it comes to catastrophic costs and ending tuberculosis? Trop Med Infect Dis. 2018;3:126.\nPareek M, Greenaway C, Noori T, Munoz J, Zenner D. The impact of migration on tuberculosis epidemiology and control in high-income countries: a review. BMC Med. 2016;14:48.\nLönnroth K, Migliori GB, Abubakar I, D’Ambrosio L, de Vries G, Diel R, et al. Towards tuberculosis elimination: an action framework for low-incidence countries. Eur Respir J. 2015;45:928–52.\nDurrani H. Healthcare and healthcare systems: inspiring progress and future prospects. Mhealth. 2016. https:\u002F\u002Fdoi.org\u002F10.3978\u002Fj.issn.2306-9740.2016.01.03.\nOlaru ID, Albert H, Zallet J, Werner U-E, Ahmed N, Rieder HL, et al. Impact of quality improvement in tuberculosis laboratories in low- and lower-middle-income countries: a systematic review. Int J Tuberc Lung Dis. 2018;22:309–20.\nSulis G, Centis R, Sotgiu G, D’Ambrosio L, Pontali E, Spanevello A, et al. Recent developments in the diagnosis and management of tuberculosis. npj Prim Care Respir Med. 2016. https:\u002F\u002Fdoi.org\u002F10.1038\u002Fnpjpcrm.2016.78.\nHorton KC, MacPherson P, Houben RMGJ, White RG, Corbett EL. Sex differences in tuberculosis burden and notifications in low- and middle-income countries: a systematic review and meta-analysis. PLoS Med. 2016. https:\u002F\u002Fdoi.org\u002F10.1371\u002Fjournal.pmed.1002119.\nCazabon D, Alsdurf H, Satyanarayana S, Nathavitharana R, Subbaraman R, Daftary A, et al. Quality of tuberculosis care in high burden countries: the urgent need to address gaps in the care cascade. Int J Infect Dis. 2017;56:111–6.\nWorld Health Organization. Addressing poverty in TB control: options for national TB control programs. Geneva: World Health Organization; 2005.\nFuady A, Houweling TAJ, Mansyur M, Richardus JH. Catastrophic total costs in tuberculosis-affected households and their determinants since Indonesia’s implementation of universal health coverage. Infect Dis Poverty. 2018;7:3.\nPrasanna T, Jeyashree K, Chinnakali P, Bahurupi Y, Vasudevan K, Das M. Catastrophic costs of tuberculosis care: a mixed methods study from Puducherry, India. Glob Health Action. 2018. https:\u002F\u002Fdoi.org\u002F10.1080\u002F16549716.2018.1477493.\nVerguet S, Riumallo-Herl C, Gomez GB, Menzies NA, Houben RMGJ, Sumner T, et al. Catastrophic costs potentially averted by tuberculosis control in India and South Africa: a modelling study. Lancet Glob Health. 2017;5:e1123–32.\nAljassim N, Ostini R. Health literacy in rural and urban populations: a systematic review. Patient Educ Couns. 2020;103:2142–54.\nvon Wagner C, Steptoe A, Wolf MS, Wardle J. Health literacy and health actions: a review and a framework from health psychology. Health Educ Behav. 2009;36:860–77.\nKuddus MA, Tynan E, McBryde E. Urbanization: a problem for the rich and the poor? Public Health Rev. 2020;41:1.\nLi Y, Ehiri J, Tang S, Li D, Bian Y, Lin H, et al. Factors associated with patient, and diagnostic delays in Chinese TB patients: a systematic review and meta-analysis. BMC Med. 2013;11:156.\nWorld Health Organization. Systematic screening for active tuberculosis: an operational guide. Geneva: World Health Organization; 2015.\nEsmail H, Dodd PJ, Houben RMGJ. Tuberculosis transmission during the subclinical period: could unrelated cough play a part? Lancet Respir Med. 2018;6:244–6.\nHouben RMGJ, Esmail H, Emery JC, Joslyn LR, McQuaid CF, Menzies NA, et al. Spotting the old foe—revisiting the case definition for TB. Lancet Respir Med. 2019;7:199–201.\nAyles H, Schaap A, Nota A, Sismanidis C, Tembwe R, Haas PD, et al. Prevalence of tuberculosis, HIV and respiratory symptoms in two Zambian communities: implications for tuberculosis control in the era of HIV. PLoS ONE. 2009;4:e5602.\nTurner RD, Bothamley GH. Cough and the transmission of tuberculosis. J Infect Dis. 2015;211:1367–72.\nBisallah CI, Rampal L, Lye M-S, Mohd Sidik S, Ibrahim N, Iliyasu Z, et al. Effectiveness of health education intervention in improving knowledge, attitude, and practices regarding Tuberculosis among HIV patients in General Hospital Minna, Nigeria—a randomized control trial. PLoS ONE. 2018. https:\u002F\u002Fdoi.org\u002F10.1371\u002Fjournal.pone.0192276.\nJaramillo E. The impact of media-based health education on tuberculosis diagnosis in Cali, Colombia. Health Policy Plan. 2001;16:68–73.\nZwarenstein M, Fairall LR, Lombard C, Mayers P, Bheekie A, English RG, et al. Outreach education for integration of HIV\u002FAIDS care, antiretroviral treatment, and tuberculosis care in primary care clinics in South Africa: PALSA PLUS pragmatic cluster randomised trial. BMJ. 2011. https:\u002F\u002Fdoi.org\u002F10.1136\u002Fbmj.d2022.\nGonzalez-Angulo Y, Geldenhuys H, Van As D, Buckerfield N, Shea J, Mahomed H, et al. Knowledge and acceptability of patient-specific infection control measures for pulmonary tuberculosis. Am J Infect Control. 2013;41:717–22.\nCraig GM, Daftary A, Engel N, O’Driscoll S, Ioannaki A. Tuberculosis stigma as a social determinant of health: a systematic mapping review of research in low incidence countries. Int J Infect Dis. 2017;56:90–100.\nMeershoek A, Zwerling A, Daftary A, Citro B, Smyth C, Lewis D, et al. TB stigma measurement guidance. Den Haag: KNCV Tuberculosis Foundation; 2018.\nSommerland N, Wouters E, Mitchell EMH, Ngicho M, Redwood L, Masquillier C, et al. Evidence-based interventions to reduce tuberculosis stigma: a systematic review. Int J Tuberc Lung Dis. 2017;21:S81-86.\nBerendes S, Heywood P, Oliver S, Garner P. Quality of private and public ambulatory health care in low and middle income countries: systematic review of comparative studies. Jenkins R, editor. PLoS Med. 2011;8:e1000433.\nTeo AKJ, Ork C, Eng S, Sok N, Tuot S, Hsu LY, et al. Determinants of delayed diagnosis and treatment of tuberculosis in Cambodia: a mixed-methods study. Infect Dis Poverty. 2020;9:49.\nJohansson E, Winkvist A. Trust and transparency in human encounters in tuberculosis control: lessons learned from Vietnam. Qual Health Res. 2002;12:473–91.\nDeber RB, Kraetschmer N, Irvine J. What role do patients wish to play in treatment decision making? Arch Intern Med. 1996;156:1414–20.\nBodnar O, Link A, Arendacká B, Possolo A, Elster C. Bayesian estimation in random effects meta-analysis using a non-informative prior. Stat Med. 2017;36:378–99.\nHartung J, Knapp G. A refined method for the meta-analysis of controlled clinical trials with binary outcome. Stat Med. 2001;20:3875–89.\nTeo AKJ, Prem K, Tuot S, Ork C, Eng S, Pande T, et al. Mobilising community networks for early identification of tuberculosis and treatment initiation in Cambodia: an evaluation of a seed-and-recruit model. ERJ Open Res. 2020;6:00368–2019.\nDaftary A, Frick M, Venkatesan N, Pai M. Fighting TB stigma: we need to apply lessons learnt from HIV activism. BMJ Global Health. 2017;2:e000515.\nWorld Health Organization. Same-day diagnosis of tuberculosis by microscopy: policy statement. [Internet]. Geneva: World Health Organization; 2011 [cited 2020 Jan 29]. Available from: http:\u002F\u002Fwhqlibdoc.who.int\u002Fpublications\u002F2011\u002F9789241501606_eng.pdf.\nDavis JL, Dowdy DW, den Boon S, Walter ND, Katamba A, Cattamanchi A. Test and treat: a new standard for smear-positive tuberculosis. J Acquir Immune Defic Syndr. 2012;61:e6-8.\nLönnroth K, Glaziou P, Weil D, Floyd K, Uplekar M, Raviglione M. Beyond UHC: monitoring health and social protection coverage in the context of tuberculosis care and prevention. PLoS Med. 2014. https:\u002F\u002Fdoi.org\u002F10.1371\u002Fjournal.pmed.1001693.",{"VOID":1688},"10.1186\u002Fs12931-021-01841-6","2024-06-25T05:26:36.049+00:00","https:\u002F\u002Frespiratory-research.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs12931-021-01841-6",[1692,1716,1729,1751,1773],{"id":1693,"sortIndex":19,"researcher":18,"roles":1694,"affiliations":1695,"properties":1713,"displayName":1715,"givenName":18,"familyName":18},"d9b43c18-5d7d-482a-ba58-be35a46f8292",[115],[1696,1704],{"id":1697,"sortIndex":19,"affiliation":1698,"properties":18},"f8dad48c-085c-4566-a723-56618900af9b",{"id":1697,"createTime":18,"updateTime":18,"relativeEntities":1699,"slug":18,"properties":1700,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1703,"statistic":18},[],{"title":1701},{"VI":1702},"Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore, Singapore",[],{"id":1705,"sortIndex":80,"affiliation":1706,"properties":1712},"913c0fdb-ddd3-46cd-864c-6db3c27a16df",{"id":1705,"createTime":18,"updateTime":18,"relativeEntities":1707,"slug":18,"properties":1708,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1711,"statistic":18},[],{"title":1709},{"VI":1710},"Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore",[],{},{"title":1714},{"VI":1715},"Alvin Kuo Jing Teo",{"id":1717,"sortIndex":80,"researcher":18,"roles":1718,"affiliations":1719,"properties":1726,"displayName":1728,"givenName":18,"familyName":18},"01d2d71d-3a7a-4603-803d-c9d982697450",[115],[1720],{"id":1697,"sortIndex":19,"affiliation":1721,"properties":18},{"id":1697,"createTime":18,"updateTime":18,"relativeEntities":1722,"slug":18,"properties":1723,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1725,"statistic":18},[],{"title":1724},{"VI":1702},[],{"title":1727},{"VI":1728},"Shweta R. Singh",{"id":1730,"sortIndex":154,"researcher":18,"roles":1731,"affiliations":1732,"properties":1748,"displayName":1750,"givenName":18,"familyName":18},"92d083e6-be56-400d-bd08-4f2e6a2e8575",[115],[1733,1739],{"id":1697,"sortIndex":19,"affiliation":1734,"properties":18},{"id":1697,"createTime":18,"updateTime":18,"relativeEntities":1735,"slug":18,"properties":1736,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1738,"statistic":18},[],{"title":1737},{"VI":1702},[],{"id":1740,"sortIndex":80,"affiliation":1741,"properties":1747},"9e62ebb2-6d0f-46c9-8656-fddac32abc92",{"id":1740,"createTime":18,"updateTime":18,"relativeEntities":1742,"slug":18,"properties":1743,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1746,"statistic":18},[],{"title":1744},{"VI":1745},"Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK",[],{},{"title":1749},{"VI":1750},"Kiesha Prem",{"id":1752,"sortIndex":168,"researcher":18,"roles":1753,"affiliations":1754,"properties":1770,"displayName":1772,"givenName":18,"familyName":18},"c8235ed0-aa67-4d72-8f71-fb2b3e622d4f",[115],[1755,1761],{"id":1697,"sortIndex":19,"affiliation":1756,"properties":18},{"id":1697,"createTime":18,"updateTime":18,"relativeEntities":1757,"slug":18,"properties":1758,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1760,"statistic":18},[],{"title":1759},{"VI":1702},[],{"id":1762,"sortIndex":80,"affiliation":1763,"properties":1769},"1f1c1365-e093-4d83-9c6b-30ac972cdd32",{"id":1762,"createTime":18,"updateTime":18,"relativeEntities":1764,"slug":18,"properties":1765,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1768,"statistic":18},[],{"title":1766},{"VI":1767},"Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore",[],{},{"title":1771},{"VI":1772},"Li Yang Hsu",{"id":1774,"sortIndex":182,"researcher":18,"roles":1775,"affiliations":1776,"properties":1801,"displayName":1803,"givenName":18,"familyName":18},"b0926adf-5de6-4815-ab20-63fb2f91b10c",[115],[1777,1783,1792],{"id":1697,"sortIndex":19,"affiliation":1778,"properties":18},{"id":1697,"createTime":18,"updateTime":18,"relativeEntities":1779,"slug":18,"properties":1780,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1782,"statistic":18},[],{"title":1781},{"VI":1702},[],{"id":1784,"sortIndex":80,"affiliation":1785,"properties":1791},"64d65cc4-bc24-4bbc-b870-f33284e27845",{"id":1784,"createTime":18,"updateTime":18,"relativeEntities":1786,"slug":18,"properties":1787,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1790,"statistic":18},[],{"title":1788},{"EN":1789},"KHANA Center for Population Health Research, Phnom Penh, Cambodia",[],{},{"id":1793,"sortIndex":154,"affiliation":1794,"properties":1800},"58e829c1-f6a0-41e0-b4ed-1589b2984951",{"id":1793,"createTime":18,"updateTime":18,"relativeEntities":1795,"slug":18,"properties":1796,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1799,"statistic":18},[],{"title":1797},{"VI":1798},"Center for Global Health Research, Touro University California, Vallejo, USA",[],{},{"title":1802},{"VI":1803},"Siyan Yi",{"url":1690,"publisher":1805,"properties":1846},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1806,"slug":10,"properties":1807,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":1810,"manageAffiliations":1815,"indexDatabases":1826,"url":77,"thumbnailPath":18,"statistic":1841,"gsStatistic":18,"type":84,"analyzePriority":18},[],{"issn":1808,"title":1809},{"VOID":13},{"EN":15},[1811],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":1812,"label":1813,"description":1814,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[1816,1821],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":1817,"slug":18,"properties":1818,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1820,"statistic":18},[],{"title":1819},{"EN":33},[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":1822,"slug":18,"properties":1823,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1825,"statistic":18},[],{"title":1824},{"EN":40},[],[1827,1834],{"id":44,"indexDatabase":1828,"url":55,"indexYears":56,"academicFieldIds":1833,"indexDatabaseRanking":59},{"id":46,"createTime":18,"updateTime":18,"relativeEntities":1829,"label":1830,"description":1831,"key":52,"publicationTags":1832,"standard":18},[],{"EN":49,"VI":49},{"EN":49,"VI":51},[54],[58],{"id":61,"indexDatabase":1835,"url":74,"indexYears":18,"academicFieldIds":1840,"indexDatabaseRanking":18},{"id":63,"createTime":18,"updateTime":18,"relativeEntities":1836,"label":1837,"description":1838,"key":70,"publicationTags":1839,"standard":18},[],{"EN":66,"VI":66},{"EN":68,"VI":69},[72,73],[76],{"impactFactor":19,"impactFactorByYear":1842,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":1843,"totalCitation":19,"totalCitationByYear":1844,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":1845,"hindexLast5Year":19,"hindex":19},{},{"2004":80},{},{},{"pages":1847,"volume":1849},{"VOID":1848},"1-28",{"VOID":269},"2021-09-23","2026-07-23T17:50:39.339+00:00",[72,59],{"id":1854,"createTime":1855,"updateTime":1856,"relativeEntities":1857,"slug":1858,"properties":1859,"entityType":106,"verifyStatus":107,"verifyTime":1870,"verifyNote":109,"languages":1871,"translateLanguages":18,"viewCount":19,"primaryUrl":1872,"fullTextUrl":18,"authors":1873,"publicationType":222,"publisherRelationship":1997,"citationCount":2039,"citationInfo":2040,"publishDate":2043,"publishYear":2041,"citationAnalyzeStatus":17,"lastCitationAnalyze":2044,"indexDatabases":2045,"openAccess":18,"references":2046,"isForceReanalyzing":279},"5c842a74-d7b8-4861-80bf-e34f5ec7bb60","2024-04-11T08:20:39.557+00:00","2026-07-23T16:19:31.774+00:00",[],"Adenosine-metabolized-from-extracellular-ATP-ameliorates-organ-injury-by-triggering-A2BR-signaling",{"abstract":1860,"title":1862,"gsPaper":1864,"keywords":1866,"doi":1868},{"EN":1861},"Trauma and a subsequent hemorrhagic shock (T\u002FHS) result in insufficient oxygen delivery to tissues and multiple organ failure. Extracellular adenosine, which is a product of the extracellular degradation of adenosine 5’ triphosphate (ATP) by the membrane-embedded enzymes CD39 and CD73, is organ protective, as it participates in signaling pathways, which promote cell survival and suppress inflammation through adenosine receptors including the A2BR. The aim of this study was to evaluate the role of CD39 and CD73 delivering adenosine to A2BRs in regulating the host’s response to T\u002FHS. T\u002FHS shock was induced by blood withdrawal from the femoral artery in wild-type, global knockout (CD39, CD73, A2BR) and conditional knockout (intestinal epithelial cell-specific deficient VillinCre-A2BRfl\u002Ffl) mice. At 3 three hours after resuscitation, blood and tissue samples were collected to analyze organ injury. T\u002FHS upregulated the expression of CD39, CD73, and the A2BR in organs. ATP and adenosine levels increased after T\u002FHS in bronchoalveolar lavage fluid. CD39, CD73, and A2BR mimics\u002Fagonists alleviated lung and liver injury. Antagonists or the CD39, CD73, and A2BR knockout (KO) exacerbated lung injury, inflammatory cytokines, and chemokines as well as macrophage and neutrophil infiltration and accumulation in the lung. Agonists reduced the levels of the liver enzymes aspartate transferase and alanine transaminase in the blood, whereas antagonist administration or CD39, CD73, and A2BR KO enhanced enzyme levels. In addition, intestinal epithelial cell-specific deficient VillinCre-A2BRfl\u002Ffl mice showed increased intestinal injury compared to their wild-type VillinCre controls. In conclusion, the CD39-CD73-A2BR axis protects against T\u002FHS-induced multiple organ failure.",{"EN":1863},"Adenosine metabolized from extracellular ATP ameliorates organ injury by triggering A2BR signaling",{"VOID":1865},"[\"4098981668781046780\"]",{"EN":1867},"",{"VOID":1869},"10.1186\u002Fs12931-023-02486-3","2024-05-12T22:44:32.910+00:00",[1027],"https:\u002F\u002Frespiratory-research.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs12931-023-02486-3",[1874,1899,1920,1937,1952,1967,1982],{"id":1875,"sortIndex":19,"researcher":18,"roles":1876,"affiliations":1877,"properties":1894,"displayName":1896,"givenName":18,"familyName":18},"4cec1cb9-e672-4eed-8646-8dd21e578789",[],[1878,1886],{"id":1879,"sortIndex":19,"affiliation":1880,"properties":18},"88c2c809-e48d-4c46-b204-fb2025d19d97",{"id":1879,"createTime":18,"updateTime":18,"relativeEntities":1881,"slug":18,"properties":1882,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1885,"statistic":18},[],{"title":1883},{"EN":1884},"Department of Anesthesiology, Columbia University, New York City, USA",[],{"id":1887,"sortIndex":19,"affiliation":1888,"properties":18},"cb2c4f01-5408-4cd9-8f61-0be43ce21ff0",{"id":1887,"createTime":18,"updateTime":18,"relativeEntities":1889,"slug":18,"properties":1890,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1893,"statistic":18},[],{"title":1891},{"EN":1892},"Department of Physiology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey",[],{"title":1895,"gsAuthor":1897},{"EN":1896},"Taha Kelestemur",{"VOID":1898},"[\"vvHNVFcAAAAJ\"]",{"id":1900,"sortIndex":80,"researcher":18,"roles":1901,"affiliations":1902,"properties":1917,"displayName":1919,"givenName":18,"familyName":18},"7d52c9b8-598e-429d-ae0f-e75104ccad5d",[],[1903,1911],{"id":1904,"sortIndex":19,"affiliation":1905,"properties":18},"9a43021c-1bf5-4e29-85c4-28a13b7b60b9",{"id":1904,"createTime":18,"updateTime":18,"relativeEntities":1906,"slug":18,"properties":1907,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1910,"statistic":18},[],{"title":1908},{"EN":1909},"Department of Surgery, Morristown Medical Center, Morristown, USA",[],{"id":1879,"sortIndex":19,"affiliation":1912,"properties":18},{"id":1879,"createTime":18,"updateTime":18,"relativeEntities":1913,"slug":18,"properties":1914,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1916,"statistic":18},[],{"title":1915},{"EN":1884},[],{"title":1918},{"EN":1919},"Zoltán H. Németh",{"id":1921,"sortIndex":154,"researcher":18,"roles":1922,"affiliations":1923,"properties":1932,"displayName":1934,"givenName":18,"familyName":18},"003243fe-5f1b-49b9-8480-1e64132a6b12",[],[1924],{"id":1925,"sortIndex":19,"affiliation":1926,"properties":18},"7e36afc1-5d39-4b83-9276-0fa9447725a5",{"id":1925,"createTime":18,"updateTime":18,"relativeEntities":1927,"slug":18,"properties":1928,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1931,"statistic":18},[],{"title":1929},{"VI":1930},"Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute On Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, USA",[],{"title":1933,"gsAuthor":1935},{"EN":1934},"Pal Pacher",{"VOID":1936},"[\"XNRjTvcAAAAJ\"]",{"id":1938,"sortIndex":168,"researcher":18,"roles":1939,"affiliations":1940,"properties":1949,"displayName":1951,"givenName":18,"familyName":18},"a84fb089-cad2-4815-9caf-47da4c19baf4",[],[1941],{"id":1942,"sortIndex":19,"affiliation":1943,"properties":18},"8ef9e9cf-4ba9-4b13-bbad-877edbce0e64",{"id":1942,"createTime":18,"updateTime":18,"relativeEntities":1944,"slug":18,"properties":1945,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1948,"statistic":18},[],{"title":1946},{"EN":1947},"Daresbury Proteins Ltd, Sci-Tech Daresbury, Warrington, UK",[],{"title":1950},{"EN":1951},"Jennet Beesley",{"id":1953,"sortIndex":182,"researcher":18,"roles":1954,"affiliations":1955,"properties":1964,"displayName":1966,"givenName":18,"familyName":18},"59c9f98f-7836-4307-bfc1-b5b1f80b1b80",[],[1956],{"id":1957,"sortIndex":19,"affiliation":1958,"properties":18},"4e8dd56b-2dcc-4d85-80a6-d7528d31b403",{"id":1957,"createTime":18,"updateTime":18,"relativeEntities":1959,"slug":18,"properties":1960,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1963,"statistic":18},[],{"title":1961},{"VI":1962},"Department of Anesthesia, Beth Israel Deaconess Medical Center, Boston, USA",[],{"title":1965},{"EN":1966},"Simon C. Robson",{"id":1968,"sortIndex":196,"researcher":18,"roles":1969,"affiliations":1970,"properties":1979,"displayName":1981,"givenName":18,"familyName":18},"b3e86b29-b668-41cc-8066-6a9a96eb6d10",[],[1971],{"id":1972,"sortIndex":19,"affiliation":1973,"properties":18},"bc653c06-e58e-46e6-8b29-fd11b4c17b6f",{"id":1972,"createTime":18,"updateTime":18,"relativeEntities":1974,"slug":18,"properties":1975,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1978,"statistic":18},[],{"title":1976},{"EN":1977},"Department of Anesthesiology, The University of Texas Health Science Center at Houston, Houston, USA",[],{"title":1980},{"EN":1981},"Holger K. Eltzschig",{"id":1983,"sortIndex":210,"researcher":18,"roles":1984,"affiliations":1985,"properties":1992,"displayName":1996,"givenName":18,"familyName":18},"ac6fd4b5-7cfd-48ef-907c-37befa228d5d",[],[1986],{"id":1879,"sortIndex":19,"affiliation":1987,"properties":18},{"id":1879,"createTime":18,"updateTime":18,"relativeEntities":1988,"slug":18,"properties":1989,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1991,"statistic":18},[],{"title":1990},{"EN":1884},[],{"email":1993,"title":1995},{"VOID":1994},"gh2503@cumc.columbia.edu",{"EN":1996},"György Haskó",{"url":18,"publisher":1998,"properties":18},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1999,"slug":10,"properties":2000,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":2003,"manageAffiliations":2008,"indexDatabases":2019,"url":77,"thumbnailPath":18,"statistic":2034,"gsStatistic":18,"type":84,"analyzePriority":18},[],{"issn":2001,"title":2002},{"VOID":13},{"EN":15},[2004],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":2005,"label":2006,"description":2007,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},[2009,2014],{"id":29,"createTime":18,"updateTime":18,"relativeEntities":2010,"slug":18,"properties":2011,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2013,"statistic":18},[],{"title":2012},{"EN":33},[],{"id":36,"createTime":18,"updateTime":18,"relativeEntities":2015,"slug":18,"properties":2016,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2018,"statistic":18},[],{"title":2017},{"EN":40},[],[2020,2027],{"id":44,"indexDatabase":2021,"url":55,"indexYears":56,"academicFieldIds":2026,"indexDatabaseRanking":59},{"id":46,"createTime":18,"updateTime":18,"relativeEntities":2022,"label":2023,"description":2024,"key":52,"publicationTags":2025,"standard":18},[],{"EN":49,"VI":49},{"EN":49,"VI":51},[54],[58],{"id":61,"indexDatabase":2028,"url":74,"indexYears":18,"academicFieldIds":2033,"indexDatabaseRanking":18},{"id":63,"createTime":18,"updateTime":18,"relativeEntities":2029,"label":2030,"description":2031,"key":70,"publicationTags":2032,"standard":18},[],{"EN":66,"VI":66},{"EN":68,"VI":69},[72,73],[76],{"impactFactor":19,"impactFactorByYear":2035,"i10Index":19,"i10IndexLast5Year":19,"totalPublication":80,"totalPublicationByYear":2036,"totalCitation":19,"totalCitationByYear":2037,"totalCitationPerPublication":19,"totalCitationPerPublicationByYear":2038,"hindexLast5Year":19,"hindex":19},{},{"2004":80},{},{},11,{"total":2039,"publishYear":2041,"statisticByYear":2042},2023,{"2024":80,"2025":503,"2026":154},"2023-07-13","2026-07-23T16:19:31.773+00:00",[72,59],[2047,2049,2051,2053,2055,2057,2059,2061,2063,2065,2067,2069,2071,2073,2075,2077,2079,2081,2083,2085,2087,2089,2091,2093,2095,2097,2099,2101,2103,2105,2107,2109,2111,2113,2115,2117,2119,2121,2123,2125,2127,2129,2131,2133,2135,2137,2139,2141,2143,2145,2147,2149,2151,2153,2155,2157,2159,2161,2163],{"id":18,"text":2048,"url":18,"identifiers":18},"Cannon JW, Hemorrhagic Shock. N Engl J Med. 2018;19:1852–3.",{"id":18,"text":2050,"url":18,"identifiers":18},"Huan Z, Tang Y, Xu C, Cai J, Yao H, Wang Y, Bu F, Ge X. PTPRO knockdown protects against inflammation in hemorrhage shock-induced lung injury involving the NF-kappaB signaling pathway. Respir Res. 2022;1:195.",{"id":18,"text":2052,"url":18,"identifiers":18},"Kao RL, Xu X, Xenocostas A, Parry N, Mele T, Martin CM, Rui T. Induction of acute lung inflammation in mice with hemorrhagic shock and resuscitation: role of HMGB1. J Inflamm (Lond). 2014;1:30.",{"id":18,"text":2054,"url":18,"identifiers":18},"Valade G, Libert N, Martinaud C, Vicaut E, Banzet S, Peltzer J. Therapeutic potential of mesenchymal stromal cell-derived extracellular vesicles in the Prevention of Organ Injuries Induced by Traumatic hemorrhagic shock. Front Immunol. 2021. https:\u002F\u002Fdoi.org\u002F10.3389\u002Ffimmu.2021.749659.",{"id":18,"text":2056,"url":18,"identifiers":18},"Hasko G, Xu DZ, Lu Q, Nemeth ZH, Jabush J, Berezina TL, Zaets SB, Csoka B, Deitch EA. Adenosine A2A receptor activation reduces lung injury in trauma\u002Fhemorrhagic shock. Crit Care Med. 2006;4:1119–25.",{"id":18,"text":2058,"url":18,"identifiers":18},"Koscso B, Trepakov A, Csoka B, Nemeth ZH, Pacher P, Eltzschig HK, Hasko G. Stimulation of A2B adenosine receptors protects against trauma-hemorrhagic shock-induced lung injury. Purinergic Signal. 2013;3:427–32.",{"id":18,"text":2060,"url":18,"identifiers":18},"Chen Y, Bao Y, Zhang J, Woehrle T, Sumi Y, Ledderose S, Li X, Ledderose C, Junger WG. Inhibition of neutrophils by Hypertonic saline involves Pannexin-1, CD39, CD73, and other Ectonucleotidases. Shock. 2015;3:221–7.",{"id":18,"text":2062,"url":18,"identifiers":18},"Ham PB, Raju R. Mitochondrial function in hypoxic ischemic injury and influence of aging. Prog Neurobiol. 2017. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.pneurobio.2016.06.006.",{"id":18,"text":2064,"url":18,"identifiers":18},"Wang Y, Copeland J, Shin M, Chang Y, Venton BJ. CD73 or CD39 deletion reveals different mechanisms of formation for spontaneous and mechanically stimulated Adenosine and Sex Specific Compensations in ATP degradation. ACS Chem Neurosci. 2020;6:919–28.",{"id":18,"text":2066,"url":18,"identifiers":18},"Antonioli L, Pacher P, Vizi ES, Hasko G. CD39 and CD73 in immunity and inflammation. Trends Mol Med. 2013;6:355–67.",{"id":18,"text":2068,"url":18,"identifiers":18},"Di Virgilio F, Sarti AC, Coutinho-Silva R. Purinergic signaling, DAMPs, and inflammation. Am J Physiol Cell Physiol. 2020;5:C832–5.",{"id":18,"text":2070,"url":18,"identifiers":18},"Hasko G, Linden J, Cronstein B, Pacher P. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov. 2008;9:759–70.",{"id":18,"text":2072,"url":18,"identifiers":18},"Zhang X, Du P, Luo K, Li Y, Liu Z, Wang W, Zeng C, Ye Q, Xiao Q. Hypoxia-inducible factor-1alpha protects the liver against ischemia-reperfusion injury by regulating the A2B adenosine receptor. Bioengineered. 2021;1:3737–52.",{"id":18,"text":2074,"url":18,"identifiers":18},"Tiwari-Heckler S, Lee GR, Harbison J, Ledderose C, Csizmadia E, Melton D, Zhang Q, Junger W, Chen G, Hauser CJ, Otterbein LE. Longhi, and SC Robson. Extracellular mitochondria drive CD8 T cell dysfunction in trauma by upregulating CD39. Thorax. 2023;2:151–9.",{"id":18,"text":2076,"url":18,"identifiers":18},"Eltzschig HK, Sitkovsky MV, Robson SC. Purinergic signaling during inflammation. N Engl J Med. 2012;24:2322–33.",{"id":18,"text":2078,"url":18,"identifiers":18},"Chen JF, Eltzschig HK, Fredholm BB. Adenosine receptors as drug targets—what are the challenges? Nat Rev Drug Discovery. 2013;4:265–86.",{"id":18,"text":2080,"url":18,"identifiers":18},"Reutershan J, Vollmer I, Stark S, Wagner R, Ngamsri KC, Eltzschig HK. Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs. Faseb J. 2009;2:473–82.",{"id":18,"text":2082,"url":18,"identifiers":18},"Wang S, Gao S, Zhou D, Qian X, Luan J, Lv X. The role of the CD39-CD73-adenosine pathway in liver disease. J Cell Physiol. 2021;2:851–62.",{"id":18,"text":2084,"url":18,"identifiers":18},"Junger WG. Immune cell regulation by autocrine purinergic signalling. Nat Rev Immunol. 2011;3:201–12.",{"id":18,"text":2086,"url":18,"identifiers":18},"Rai R. Cross talk of purinergic and immune signaling: implication in inflammatory and pathogenic diseases, in purinergic system, Bagatini MD, Ed., 2022, IntechOpen: United Kingdom. 2022; p. 1–29.",{"id":18,"text":2088,"url":18,"identifiers":18},"Sun Y, Huang PB. Adenosine A(2B) receptor: from cell biology to human diseases. Front Chem. 2016. https:\u002F\u002Fdoi.org\u002F10.3389\u002Ffchem.2016.00037.",{"id":18,"text":2090,"url":18,"identifiers":18},"Xu XT, Zhu QW, Niu FF, Zhang R, Wang Y, Wang WY, Sun DW, Wang XT, Wang AZ. A2BAR activation attenuates acute lung injury by inhibiting alveolar epithelial cell apoptosis both in vivo and in vitro. Am J Physiol-Cell Ph. 2018;4:C558–70.",{"id":18,"text":2092,"url":18,"identifiers":18},"Csoka B, Selmeczy Z, Koscso B, Nemeth ZH, Pacher P, Murray PJ, Kepka-Lenhart D, Morris SM Jr, Gause WC, Leibovich SJ, Hasko G. Adenosine promotes alternative macrophage activation via A2A and A2B receptors. FASEB J. 2012;1:376–86.",{"id":18,"text":2094,"url":18,"identifiers":18},"Koscso B, Csoka B, Selmeczy Z, Himer L, Pacher P, Virag L, Hasko G. Adenosine augments IL-10 production by microglial cells through an A2B adenosine receptor-mediated process. J Immunol. 2012;1:445–53.",{"id":18,"text":2096,"url":18,"identifiers":18},"Csoka B, Koscso B, Toro G, Kokai E, Virag L, Nemeth ZH, Pacher P, Bai P, Hasko G. A2B Adenosine Receptors prevent insulin resistance by inhibiting adipose tissue inflammation via maintaining alternative macrophage activation. Diabetes. 2014;3:850–66.",{"id":18,"text":2098,"url":18,"identifiers":18},"Nemeth ZH, Lutz CS, Csoka B, Deitch EA, Leibovich SJ, Gause WC, Tone M, Pacher P, Vizi ES, Hasko G. Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. J Immunol. 2005;12:8260–70.",{"id":18,"text":2100,"url":18,"identifiers":18},"Patel N, Wu W, Mishra PK, Chen F, Millman A, Csoka B, Koscso B, Eltzschig HK, Hasko G, Gause WC. A2B adenosine receptor induces protective antihelminth type 2 Immune responses. Cell Host Microbe. 2014;3:339–50.",{"id":18,"text":2102,"url":18,"identifiers":18},"Hasko G, Kuhel DG, Chen JF, Schwarzschild MA, Deitch EA, Mabley JG, Marton A. Szabo. Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms. Faseb J. 2000;13:2065–74.",{"id":18,"text":2104,"url":18,"identifiers":18},"Csoka B, Nemeth ZH, Virag L, Gergely P, Leibovich SJ, Pacher P, Sun CX, Blackburn MR, Vizi ES, Deitch EA, Hasko G. A2A adenosine receptors and C\u002FEBPbeta are crucially required for IL-10 production by macrophages exposed to Escherichia coli. Blood. 2007;7:2685–95.",{"id":18,"text":2106,"url":18,"identifiers":18},"Csoka B, Himer L, Selmeczy Z, Vizi ES, Pacher P, Ledent C, Deitch EA, Spolarics Z, Nemeth ZH, Hasko G. Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function. FASEB J. 2008;10:3491–9.",{"id":18,"text":2108,"url":18,"identifiers":18},"Hasko G, Szabo C, Nemeth ZH, Kvetan V, Pastores SM, Vizi ES. Adenosine receptor agonists differentially regulate IL-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages and in endotoxemic mice. J Immunol. 1996;10:4634–40.",{"id":18,"text":2110,"url":18,"identifiers":18},"Hasko G, Nemeth ZH, Vizi ES, Salzman AL, Szabo C. An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-gamma production and prevents lethality in endotoxemic mice. Eur J Pharmacol. 1998;3:261–8.",{"id":18,"text":2112,"url":18,"identifiers":18},"Szabo C, Scott GS, Virag L, Egnaczyk G, Salzman AL, Shanley TP, Hasko G. Suppression of macrophage inflammatory protein (MIP)-1alpha production and collagen-induced arthritis by adenosine receptor agonists. Br J Pharmacol. 1998;2:379–87.",{"id":18,"text":2114,"url":18,"identifiers":18},"Kelestemur T, Nemeth ZH, Pacher P, Antonioli L, Hasko G. A 2a Adenosine Receptors regulate multiple organ failure after hemorrhagic shock in mice. Shock. 2022;4:321–31.",{"id":18,"text":2116,"url":18,"identifiers":18},"Beker MC, Caglayan AB, Altunay S, Ozbay E, Ates N, Kelestemur T, Caglayan B, Kilic U, Doeppner TR, Hermann DM, Kilic E. Phosphodiesterase 10A is a critical target for Neuroprotection in a mouse model of ischemic stroke. Mol Neurobiol. 2022;1:574–89.",{"id":18,"text":2118,"url":18,"identifiers":18},"Matute-Bello G, Downey G, Moore BB, Groshong SD, Matthay MA, Slutsky AS, Kuebler WM. Acute Lung Injury in Animals Study. An official american thoracic society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011;5:725–38.",{"id":18,"text":2120,"url":18,"identifiers":18},"Enjyoji K, Sevigny J, Lin Y, Frenette PS, Christie PD, Esch JS, Imai M, Edelberg JM, Rayburn H, Lech M, Beeler DL, Csizmadia E, Wagner DD, Robson SC, Rosenberg RD. Targeted disruption of cd39\u002FATP diphosphohydrolase results in disordered hemostasis and thromboregulation. Nat Med. 1999;9:1010–7.",{"id":18,"text":2122,"url":18,"identifiers":18},"Mizumoto N, Kumamoto T, Robson SC, Sevigny J, Matsue H, Enjyoji K, Takashima A. CD39 is the dominant Langerhans cell associated ecto-NTPDase: modulatory roles in inflammation and immune responsiveness. Nat Med. 2002;4:358–65.",{"id":18,"text":2124,"url":18,"identifiers":18},"Eltzschig HK, Kohler D, Eckle T, Kong T, Robson SC, Colgan SP. Central role of Sp1-regulated CD39 in hypoxia\u002Fischemia protection. Blood. 2009;1:224–32.",{"id":18,"text":2126,"url":18,"identifiers":18},"Eltzschig HK, Thompson LF, Karhausen J, Cotta RJ, Ibla JC, Robson SC, Colgan SP. Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism. Blood. 2004;13:3986–92.",{"id":18,"text":2128,"url":18,"identifiers":18},"Grenz A, Zhang H, Hermes M, Eckle T, Klingel K, Huang DY, Muller CE, Robson SC. Osswald, and HK Eltzschig. Contribution of E-NTPDase1 (CD39) to renal protection from ischemia-reperfusion injury. FASEB J. 2007;11:2863–73.",{"id":18,"text":2130,"url":18,"identifiers":18},"Hart ML, Gorzolla IC, Schittenhelm J, Robson SC, Eltzschig HK. SP1-dependent induction of CD39 facilitates hepatic ischemic preconditioning. J Immunol. 2010;7:4017–24.",{"id":18,"text":2132,"url":18,"identifiers":18},"Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;2:138–50.",{"id":18,"text":2134,"url":18,"identifiers":18},"Kohler D, Eckle T, Faigle M, Grenz A, Mittelbronn M, Laucher S, Hart ML, Robson SC, Muller CE, Eltzschig HK. CD39\u002Fectonucleoside triphosphate diphosphohydrolase 1 provides myocardial protection during cardiac ischemia\u002Freperfusion injury. Circulation. 2007;16:1784–94.",{"id":18,"text":2136,"url":18,"identifiers":18},"Leite RO, Pods CB, Haas F, da Silveira KR, Mohr APS, Bertoni MS, Soares JH, Azambuja M, Dal Prá LLP, da Cruz NE, Gelsleichter K, Begnini G, Hasko MR, Wink RM, Spanevello E. Braganhol ATPergic signaling disruption in human sepsis as a potential source of biomarkers for clinical use. Clin Exp Med. 2023. https:\u002F\u002Fdoi.org\u002F10.1007\u002Fs10238-023-01045-w.",{"id":18,"text":2138,"url":18,"identifiers":18},"Riedemann NC, Guo RF, Ward PA. The enigma of sepsis. J Clin Invest. 2003;4:460–7.",{"id":18,"text":2140,"url":18,"identifiers":18},"Sayegh MN, Cooney KA, Han WM, Cicka M, Strobel F, Wang L, Garcia AJ, Levit RD. Hydrogel delivery of purinergic enzymes improves cardiac ischemia\u002Freperfusion injury. J Mol Cell Cardiol. 2023. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.yjmcc.2023.02.001.",{"id":18,"text":2142,"url":18,"identifiers":18},"Hart ML, Henn M, Kohler D, Kloor D, Mittelbronn M, Gorzolla IC, Stahl GL, Eltzschig HK. Role of extracellular nucleotide phosphohydrolysis in intestinal ischemia-reperfusion injury. FASEB J. 2008;8:2784–97.",{"id":18,"text":2144,"url":18,"identifiers":18},"Handa M, Guidotti G. Purification and cloning of a soluble ATP-diphosphohydrolase (apyrase) from potato tubers (Solanum tuberosum). Biochem Biophys Res Commun. 1996;3:916–23.",{"id":18,"text":2146,"url":18,"identifiers":18},"Thompson LF, Eltzschig HK, Ibla JC, Van De Wiele CJ, Resta R, Morote-Garcia JC, Colgan SP. Crucial role for ecto-5’-nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med. 2004;11:1395–405.",{"id":18,"text":2148,"url":18,"identifiers":18},"Lennon PF, Taylor CT, Stahl GL, Colgan SP. Neutrophil-derived 5’-adenosine monophosphate promotes endothelial barrier function via CD73-mediated conversion to adenosine and endothelial A2B receptor activation. J Exp Med. 1998;8:1433–43.",{"id":18,"text":2150,"url":18,"identifiers":18},"Eltzschig HK, Ibla JC, Furuta GT, Leonard MO, Jacobson KA, Enjyoji K, Robson SC, Colgan SP. Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors. J Exp Med. 2003;5:783–96.",{"id":18,"text":2152,"url":18,"identifiers":18},"Synnestvedt K, Furuta GT, Comerford KM, Louis N, Karhausen J, Eltzschig HK, Hansen KR, Thompson LF, Colgan SP. Ecto-5’-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J Clin Invest. 2002;7:993–1002.",{"id":18,"text":2154,"url":18,"identifiers":18},"Beavis PA, Stagg J, Darcy PK, Smyth MJ. CD73: a potent suppressor of antitumor immune responses. Trends Immunol. 2012;5:231–7.",{"id":18,"text":2156,"url":18,"identifiers":18},"Regateiro FS, Howie D, Nolan KF, Agorogiannis EI, Greaves DR, Cobbold SP, Waldmann H. Generation of anti-inflammatory adenosine by leukocytes is regulated by TGF-beta. Eur J Immunol. 2011;10:2955–65.",{"id":18,"text":2158,"url":18,"identifiers":18},"Hasko G, Csoka B, Koscso B, Chandra R, Pacher P, Thompson LF, Deitch EA, Spolarics Z, Virag L, Gergely P, Rolandelli RH, Nemeth ZH. Ecto-5’-nucleotidase (CD73) decreases mortality and organ injury in sepsis. J Immunol. 2011;8:4256–67.",{"id":18,"text":2160,"url":18,"identifiers":18},"Zhao N, Xia G, Cai J, Li Z, Lv XW. Adenosine receptor A2B mediates alcoholic hepatitis by regulating cAMP levels and the NF-KB pathway. Toxicol Lett. 2022. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.toxlet.2022.01.012.",{"id":18,"text":2162,"url":18,"identifiers":18},"Tavares LP, Negreiros-Lima GL, Lima KM, Pinho ES, Teixeira MM, Sousa LP. Blame the signaling: role of cAMP for the resolution of inflammation. Pharmacol Res. 2020. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.phrs.2020.105030.",{"id":18,"text":2164,"url":18,"identifiers":18},"Csoka B, Nemeth ZH, Rosenberger P, Eltzschig HK, Spolarics Z, Pacher P, Selmeczy Z, Koscso B, Himer L, Vizi ES, Blackburn MR, Deitch EA, Hasko G. A2B adenosine receptors protect against sepsis-induced mortality by dampening excessive inflammation. J Immunol. 2010;1:542–50."]