Biomarkers for the Phenotyping and Monitoring of Asthma in Children
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Newacheck PW, Halfon N. Prevalence, impact, and trends in childhood disability due to asthma. Arch Pediatr Adolesc Med. 2000;154(3):287–93.
Mallola J, Crane J, von Mutius E, Odhiambo J, Keil U, Stewart A, the ISAAC Phase Three Study Group. The International Study of Asthma and Allergies in Childhood (ISAAC) phase three: a global synthesis. Allergol Immunopathol (Madr). 2013;41(2):73–85.
Fajt ML, Wenzel SE. Asthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care. J Allergy Clin Immunol. 2015;135:299–310 This review provides new knowledge of biomarkers as a help in finding the right biologic medication to the right patient, and the authors also speculate on the possibility of a more personalized approach to medication of individual patients as opposed to the “one drug fits all” approach that we have today with inhaled corticosteroid and bronchodilators. They also describe limitations to this approach and need for further studies.
Global Initiative for asthma. Global strategy for asthma management and prevention. Updated 2015. http://www.ginasthma.org/lovcal/uploads/files/GINA_Report_2015.pdf.20th May 2015 . This is the latest update on the GINA guidelines—there are many useful overviews of suggested approaches to diagnosis, monitoring, and treatment of asthma in this extensive document.
Buchvald F, Bisgaard H. FeNO measured at fixed exhalation flow rate during controlled tidal breathing in children from the age of 2 yr. Am J Respir Crit Care Med. 2001;163(3 Pt 1):699–704.
Covar RA, Szefler SJ, Martin RJ, Sundstrom DA, Silkoff PE, Murphy J, Young DA, Spahn JD. Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma. J Pediatr. 2003;142:469–75.
Silkoff PE, McClean P, Spino M, Erlich L, Slutsky AS, Zamel N. Dose-response relationship and reproducibility of the fall in exhaled nitric oxide after inhaled beclomethasone dipropionate therapy in asthma patients. Chest. 2001;119:1322–8.
Dweik RA, Sorkness RL, Wenzel S, et al. Use of exhaled nitric oxide measurement to identify a reactive, at-risk phenotype among patients with asthma. Am J Respir Crit Care Med. 2010;181:1033–41.
Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, Plummer AL, Taylor DR, American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. 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 An extensive overview of documented evidence of the applicability of measurement of FeNO in clinical practice including suggested reference values. Includes data from both adult and pediatric studies.
Petsky HL, Cates CJ, Lasserson TJ, et al. A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils). Thorax. 2012;67:199–208.
Gomersal T, Harnan S, Essat M, et al. A systematic review of fractional exhaled nitric oxide in routine managemant of childhood asthma. Ped Pulmonol. 2016;51:316–28 A specific pediatric review and update, it is a useful complement to the ATS guidelines and it includes the most recent studies of pediatric asthma. It includes a thorough review of the benefits and limitations of FeNO in clinical practice.
Stern G, de Jongste J, van der Valk R, et al. Fluctuation phenotyping based on daily fraction of exhaled nitric oxide values in asthmatic children. J Allergy Clin Immunol. 2011;128:293–300.
Konradsen JR, Skantz E, Nordlund B, Lidegran M, James A, Ono J, Ohta S, Izuhara K, Dahlén SE, Alving K, Hedlin G. Predicting asthma morbidity in children using proposed markers of Th2-type inflammation. Pediatr Allergy Immunol. 2015;26(8):772–9.
Malinovschi A, Janson C, Borres M, Alving K. Simultaneously increased fraction of exhaled nitric oxide levels and blood eosinophil counts relate to increased asthma mobidity. J Allergy Clin Immunol 2016.
Voorend-van Bergen S, Vaessen-Verberne AA, Brackel HJ, Landstra AM, van den Berg NJ, Hop WC, de Jongste JC, Merkus PJ, Pijnenburg MW. Monitoring strategies in children with asthma: a randomised controlled trial. Thorax. 2015;70(6):543–50 A very interesting study comparing three different ways of monitoring asthma, one includes symptom reports every fourth week and adjustment of therapy according to an algorithm depending on the symptom report; the other approach is based on visits every fourth month and adjustment of therapy according to the FeNO level and the third regular visits every fourth month. The monthly report and the FeNO both have advantages but differently from the regular follow-up.
Dragonieri S, Schot R, Mertens BJ, et al. An electronic nose in the discrimination of patients with asthma and controls. J Allergy Clin Immunol. 2007;120:856–62.
Fens N, Roldaan AC, van der Schee MP, et al. External validation of exhaled breath profiling using an electronic nose in the discrimination of asthma with fixed airways obstruction and chronic obstructive pulmonary disease. Clin Exp Allergy. 2011;41:1371–8.
Robroeks CM, van Berkel JJ, Jöbsis Q, et al. Exhaled volatile organic compounds predict exacerbations of childhood asthma in a 1-year prospective study. Eur Respir J. 2013;42:98–106.
Van der Schee MP, Hashimoto S, Schuurman AC, et al. Altered exhaled biomarker profiles in children during and after rhinovirus-induced wheeze. Eur Respir J. 2015;45:440–8.
Van der Schee MP, Palmay R, Cowan JO, Taylor DR. Predicting steroid responsiveness in patients with asthma using exhaled breath profiling. Clin Exp Allergy. 2013;43(11):1217–25.
Teng Y, Sun P, Zhang J, Yu R, Bai J, Yao X, Huang M, Adcock IM, Barnes PJ. Hydrogen peroxide in exhaled breath condensate in patients with asthma: a promising biomarker? Chest. 2011;140(1):108–16.
Formanek W, Inci D, Lauener RP, Wildhaber JH, Frey U, Hall GL. Elevated nitrite in breath condensates of children with respiratory disease. Eur Respir J. 2002;19(3):487–91.
Carraro S, Cogo PE, Isak I, Simonato M, Corradi M, Carnielli VP, Baraldi E. EIA and GC/MS analysis of 8-isoprostane in EBC of children with problematic asthma. Eur Respir J. 2010;35(6):1364–9.
Montuschi P, Martello S, Felli M, Mondino C, Barnes PJ, Chiarotti M. Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B4 in asthmatic children. Respir Res. 2005;6:119.
Gaber F, Acevedo F, Delin I, Sundblad BM, Palmberg L, Larsson K, Kumlin M, Dahlén SE. Saliva is one likely source of leukotriene B4 in exhaled breath condensate. Eur Respir J. 2006;28(6):1229–35.
Szefler SJ, Wenzel S, Brown R, Erzurum SC, Fahy JV, Hamilton RG, Hunt JF, Kita H, Liu AH, Panettieri Jr RA, Schleimer RP, Minnicozzi M. Asthma outcomes: biomarkers. J Allergy Clin Immunol. 2012;129(3 Suppl):S9–23.
Nadif R, Siroux V, Oryszczyn MP, Ravault C, Pison C, Pin I, Kauffmann F. Epidemiological study on the Genetics and Environment of Asthma (EGEA). Heterogeneity of asthma according to blood inflammatory patterns. Thorax. 2009;64(5):374–80.
Fahy J. Eosinophilic and neutrophilic inflammation in asthma; insights from clinical studies. Proc Am Thorac Soc. 2009;6:256–9.
Ulrik CS. Peripheral eosinophil counts as a marker of disease activity in intrinsic and extrinsic asthma. Clin Exp Allergy. 1995;25(9):820–7.
Gaillard EA, McNamara PS, Murray CS, Pavord DI, Shields MD. Blood eosinophils as a marker of likely corticosteroid response in children with pre-school wheeze: time for an eosinophil guided clinical trial? Clin Exp Allergy. 2015;45:1384–95.
Saglani S, Lloyd CM. Eosinophils in the pathogenesis of pediatric severe asthma. Curr Opin Allergy Clin Immunol. 2014;14(2):143–8 An update on eosinophils in blood and tissue, strengths, and limitations of measuring eosinophils to characterize asthma in children. They describe children with eosinophilic inflammation and steroid-resistant asthma as a subgroup of severe asthma.
Busse W, Spector S, Rosén K, Wang Y, Alpan O. High eosinophil count: a potential biomarker for assessing successful omalizumab treatement effects. J Allergy Clin Immunol. 2013;132:485–6.
Hanania NA, Wenzel S, Rosén K, et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J respire Crit Care Med. 2013;187(8):804–11.
Konradsen JR, Nordlund B, Lidegran M, Pedroletti C, Grönlund H, van Hage M, Dahlen B, Hedlin G, Swedish Network of Pediatric Allergists, Severe Asthma Network. Problematic severe asthma: a proposed approach to identifying children who are severely resistant to therapy. Pediatr Allergy Immunol. 2011;22(1 Pt 1):9–18.
Burrows B, Martinez FD, Cline MG, Lebowitz MD. The relationship between parental and children’s serum IgE and asthma. Am J Respir Crit Care Med. 1995;152(5 Pt 1):1497–500.
Kulkarni N, Ragazzo V, Costella S, et al. Eosinophilic airway inflammation is increased in children with asthma and food allergies. Pediatr Allergy Immunol. 2012;23:28–33.
Gernez Y, Tirouvanziam R, Yu G, et al. Basophil CD203c levels are increased at baseline and can be used to monitor omalizumab treatment in subjects with nut allergy. Int Arch Allergy Immunol. 2011;154(4):318–27.
Borres MP, Ebisawa M, Eigenmann PA. Use of allergen components begins a new era in pediatric allergology. Pediatr Allergy Immunol. 2011;22:454–61.
Asarnoj A, Moverare R, Ostblom E, et al. IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8-year-olds. Allergy. 2010;65:1189–95.
Nordlund B, Konradsen JR, Kull I, et al. IgE antibodies to animal-derived lipocalin, kallikrein and secretoglobin are markers of bronchial inflammation in severe childhood asthma. Allergy. 2012;67:661–9.
Konradsen JR, Fujisawa T, van Hage M, Hedlin G, Hilger C, Kleine-Tebbe J, Matsui EC, Roberts G, Rönmark E, Platts-Mills T. Allergy towards furry animals: new insights, diagnostic approaches and challenges. J Allergy Clin Immunol. 2015;135(3):616–25 A detailed and up-to-date review of the possibility of refining allergy diagnosis by component resolved analysis of IgE levels in animal allergic children. Some combinations of IgE to components are more common in children with severe asthma.
Dahlen B, Nopp A, Johansson SG, Eduards M, Skedinger M, Adedoyin J. Basophil allergen threshold sensitivity, CD-sens, is a measure of allergen sensitivity in asthma. Clin Exp Allergy. 2011;41:1091–7.
Konradsen JR, Nordlund B, Nilsson OB, et al. High basophil allergen sensitivity (CD-sens) is associated with severe allergic asthma in children. Pediatr Allergy Immunol. 2012;23(4):376–84.
Chapurlat RD, Confavreux CB. Novel biological markers of bone: from bone metabolism to bone physiology. Rheumatology 2016; pii: kev410.
Norris RA, Damon B, Mironov V, Kasyanov V, Ramamurthi A, Moreno-Rodriguez R, et al. Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues. J Cell Biochem. 2007;101:695–711.
Takayama G, Arima K, Kanaji T, Toda S, Tanaka H, Shoji S, et al. Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. J Allergy Clin Immunol. 2006;118:98–104.
Woodruff PG, Boushey HA, Dolganov GM, Barker CS, Yang YH, Donnelly S, et al. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci U S A. 2007;104:15858–63.
Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365:1088–98.
Wagener AH, de Nijs SB, Lutter R, Sousa AR, Weersink EJ, Bel EH, et al. External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015;70:115–20.
Jia G, Erickson RW, Choy DF, Mosesova S, Wu LC, Solberg OD, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol. 2012;130:647–54.
Fingleton J, Braithwaite I, Travers J, Bowles D, Strik R, Siebers R, Holweg C, Matthews J, Weatherall M, Beasley R, NZRHS Study Group. Serum periostin in obstructive airways disease. Eur Respir J. 2016. doi: 10.1183/13993003.01384-2015 .
Kanemitsu Y, Matsumoto H, Izuhara K, Tohda Y, Kita H, Horiguchi T, et al. Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids. J Allergy Clin Immunol. 2013;132:305–12.
Matsusaka M, Kabata H, Fukunaga K, Suzuki Y, Masaki K, Mochimaru T, et al. Phenotype of asthma related with high serum periostin levels. Allergol Int. 2015;64:175–80.
Anderson HM, Lemanske RF Jr, Arron JR, Holweg CT, Rajamanickam V, Gangnon RE, Gern JE, Jackson DJ. Relationships among aeroallergen sensitization, peripheral blood eosinophils, and periostin in pediatric asthma development. J Allergy Clin Immunol. 2016.
Inoue T, Akashi K, Watanabe M, Ikeda Y, Ashizuka S, Motoki T, Suzuki R, Sagara N, Yanagida N, Sato S, Ebisawa M, Ohta S, Ono J, Izuhara K, Katsunuma T. Periostin as a biomarker for the diagnosis of pediatric asthma. Pediatr Allergy Immunol. 2016;27(5):521–6.
Inoue Y, Izuhara K, Ohta S, Ono J, Shimojo N. No increase in the serum periostin level is detected in elementary school-age children with allergic diseases. Allergol Int. 2015;64(3):289–90.
Chupp GL, Lee CG, Jarjour N, Shim YM, Holm CT, He S, Dziura JD, Reed J, Coyle AJ, Kiener P, Cullen M, Grandsaigne M, Dombret MC, Aubier M, Pretolani M, Elias JA. A chitinase-like protein in the lung and circulation of patients with severe asthma. N Engl J Med. 2007;357:2016–27.
Konradsen JR, James A, Nordlund B, Lödrup Carlsen KC, Lidegran M, Verhoek M, Boot RG, Dahlén B, Dahlén SE, Hedlin G. The chitinase-like protein YKL-40: a possible biomarker of inflammation and airway in severe pediatric asthma. J Allergy Clin Immunol. 2013;132:328–35.
James AJ, Reinius LE, Verhoek M, Gomes A, Kupczyk M, Hammar U, Ono J, Ohta S, Izuhara K, Bel E, Kere J, Söderhäll C, Dahlén B, Boot RG, Dahlén SE, BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) Consortium. Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2016;193(2):131–42.
Bara I, Ozier A, Girodet PO, Carvalho G, Cattiaux J, Begueret H, Thumerel M, Ousova O, Kolbeck R, Coyle AJ, Woods J, Tunon de Lara JM, Marthan R, Berger P. Role of YKL-40 in bronchial smooth muscle in asthma. Am J Respir Crit Care Med. 2012;185:715–22.
Tang H, Sun Y, Shi Z, Huang H, Fang Z, Chen J, Xiu Q, Li B. YKL-40 induces IL-8 expression from bronchial epithelium via MAPK (JNK and ERK) and NF-κB pathways, causing bronchial smooth muscle proliferation and migration. J Immunol. 2013;190:438–46.
Furuhashi K, Suda T, Nakamura Y, Inui N, Hashimoto D, Miwa S, Hayakawa H, Kusagaya H, Nakano Y, Nakamura H, Chida K. Increased expression of YKL-40, a chitinase-like protein, in serum and lung of patients with idiopathic pulmonary fibrosis. Respir Med. 2010;104:1204–10.
James A, Konradsen J, Nordlund B, Ebersjo C, Henckel E, Dahlen SE, Bergren Bostrom E, Hedlin G. Serum YKL-40 is increased in children with bronchopulmonary dysplasia compared to children with asthma. Am J Respir Crit Care Med. 2013;187:A2536.
Hinks TS, Brown T, Lau LC, Rupani H, Barber C, Elliott S, Ward JA, Ono J, Ohta S, Izuhara K, Djukanović R, Kurukulaaratchy RJ, Chauhan A, Howarth PH. Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1. J Allergy Clin Immunol. 2016;138:61–75.
Mitchell PD, O’Byrne PM. Biologics and the lung: TSLP and other epithelial cell-derived cytokines in asthma. Pharmacol Ther. 2016.
Chauhan A, Singh M, Agarwal A, Paul N. Correlation of TSLP, IL-33, and CD4 + CD25 + FOXP3 + T regulatory (Treg) in pediatric asthma. J Asthma. 2015;52(9):868–72.
Checkley W, Robinson CL, Baumann LM, Hansel NN, Romero KM, Pollard SL, Wise RA, Gilman RH, Mougey E, Lima JJ, PURA Study Investigators. 25-hydroxy vitamin D levels are associated with childhood asthma in a population-based study in Peru. Clin Exp Allergy. 2015;45(1):273–82.
Stenberg Hammar K, Hedlin G, Konradsen JR, Nordlund B, Kull I, Giske CG, Pedroletti C, Söderhäll C, Melén E. Subnormal levels of vitamin D are associated with acute wheeze in young children. Acta Paediatr. 2014;103(8):856–61.
Brehm JM et al. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J Allergy Clin Immunol. 2010;126(1):52–8.
Hamsten C, Häggmark A, Grundström J, Mikus M, Lindskog C, Konradsen JR, Eklund A, Pershagen G, Wickman M, Grunewald J, Melén E, Hedlin G, Nilsson P, van Hage M. Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma. Allergy. 2016;71(9):1357–61.
Lex C, Payne DN, Zacharasiewicz A, et al. Sputum induction in children with difficult asthma: safety, feasibility, and inflammatory cell pattern. Pediatr Pulmonol. 2005;39:318–24.
Fleming L, Tsartsali L, Wilson N, Regamey N, Bush A. Sputum inflammatory phenotypes are not stable in children with asthma. Thorax. 2012;67:675–81.
Vizmanos-Lamotte G, Moreno-Galdó A, Muñoz X, Gómez-Ollés S, Gartner S, Cruz MJ. Induced sputum cell count and cytokine profile in atopic and non-atopic children with asthma. Pediatr Pulmonol. 2013;48(11):1062–9.
Bossley CJ, Fleming L, Gupta A, Regamey N, Frith J, Oates T, Tsartsali L, Lloyd CM, Bush A, Saglani S. Pediatric severe asthma is characterized by eosinophilia and remodeling without T(H)2 cytokines. J Allergy Clin Immunol. 2012;129(4):974–82.
Konradsen JR, Nordlund B, Levänen B, Hedlin G, Linden A. The cytokine interleukin-26 as a biomarker in pediatric asthma. Respir Res. 2016;17:32.
Fleming L, Wilson N, Regamey N, Bush A. Use of sputum eosinophil counts to guide management in children with severe asthma. Thorax. 2012;67:193–8.
Regamey N, Ochs M, Hilliard TN, et al. Increased airway smooth muscle mass in children with asthma, cystic fibrosis, and non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2008;177:837–43.
Okunishi K, Peters-Golden M. Leukotrienes and airway inflammation. Biochim Biophys Acta. 2011;1810(11):1096–102.
Claar D, Hartert TV, Peebles Jr RS. The role of prostaglandins in allergic lung inflammation and asthma. Expert Rev Respir Med. 2015;9(1):55–72.
Samuelsson B, Granström E, Green K, Hamberg M, Hammarström S. Prostaglandins. Annu Rev Biochem. 1975;44:669–95.
Lewis GP. Biochemistry, pathophysiology and pharmacology of slow-reacting substances/leukotrienes. Agents Actions. 1981;11(6–7):569–71.
Balgoma D, Larsson J, Rokach J, Lawson JA, Daham K, Dahlén B, Dahlén SE, Wheelock CE. Quantification of lipid mediator metabolites in human urine from asthma patients by electrospray ionization mass spectrometry: controlling matrix effects. Anal Chem. 2013;85(16):7866–74.
O’Shaughnessy KM, Wellings R, Gillies B, R.W F. Differential effects of fluticasone propionate on allergen-evoked bronchoconstriction and increased urinary leukotriene E4 excretion. Am Rev Respir Dis. 1993;147(6 Pt 1):1472–6.
Kumlin M, Dahlen B, et al. Urinary excretion of leukotriene E4 and 11-dehydro-thromboxane B2 in response to bronchial provocations with allergen, aspirin, leukotriene D4, and histamine in asthmatics. Am Rev Respir Dis. 1992;146(1):96–103.
Green SA, Malice MP, Tanaka W, Tozzi CA, Reiss TF. Increase in urinary leukotriene LTE4 levels in acute asthma: correlation with airflow limitation. Thorax. 2004;59(2):100–4.
Liu MC, Dube LM, Lancaster J. Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group. J Allergy Clin Immunol. 1996;98(5 Pt 1):859–71.
Liston TE, Roberts 2nd LJ. Metabolic fate of radiolabeled prostaglandin D2 in a normal human male volunteer. J Biol Chem. 1985;260(24):13172–80.
Dahlen SE, Kumlin M. Monitoring mast cell activation by prostaglandin D2 in vivo. Thorax. 2004;59(6):453–5.
Schleimer RP, Schulman ES, MacGlashan Jr DW, Peters SP, Hayes EC, Adams 3rd GK, Lichtenstein LM, Adkinson Jr NF. Effects of dexamethasone on mediator release from human lung fragments and purified human lung mast cells. J Clin Invest. 1983;71(6):1830–5.
Kippelen P, Larsson J, Anderson SD, Brannan JD, Dahlén B, Dahlén SE. Effect of sodium cromoglycate on mast cell mediators during hyperpnea in athletes. Med Sci Sports Exerc. 2010;42(10):1853–60.
Konradsen JR, Bood J, Nordlund B, Venge P, Alving K, Dahlen B, Dahlen SE, Hedlin G. Urinary biomarkers identify a sub-phenotype of severe childhood asthma driven by mast cells and eosinophils. Am J Respir Crit Care Med. 2014;189:A3832.
Klonoff-Cohen H, Polavarapu M. Eosinophil protein X and childhood asthma: a systematic review and meta-analysis. Immunity, Inflammation and Disease. 2016;4:114–34.
Moeller A, Carlsen KH, Sly PD, et al. ERS Task Force. Monitoring asthma in children: lung function, bronchial responsiveness and inflammation. Eur Respir Rev. 2015;24(136):204–15 A thorough review of the evidence for different monitoring strategies. It is one of three reports from the ERS Task force on monitoring asthma. This one includes also an overview of currently available biomarkers like FeNO and biomarkers measured in exhaled breath condensate. There is also a section on bronchial hyper-responsiveness.
Andersen WC, Szefler SJ. New and future strategies to improve asthma control in children. J Allergy Clin Immunol. 2015;136(4):848–59 For several years, Szefler has published a summary of new knowledge on asthma in children that has been achieved during the previous year in the Journal of Allergy and Clinical Immunology. This is the latest and includes, among other useful updates, also an update of current views on biomarkers to improve asthma control in children.