Pediatric Pulmonology
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Glutathione metabolism in newborns: Evidence for glutathione deficiency in plasma, bronchoalveolar lavage fluid, and lymphocytes in prematures Abstract Respiratory distress in premature newborns is associated with deficiency of surfactant in the bronchoalveolar lining fluid; this may be influenced by a local deficiency of antioxidants. Severe L‐buthionine‐S, R‐sulfoximine‐induced depletion of glutathione (GSH, a major antioxidant) in rodents is associated with lung type 2 cell lamellar body damage and decreased concentrations in lung and bronchoalveolar lavage fluid (BALF) of phosphatidyl choline (a major component of surfactant). At birth, prematurely born newborns (30–34 weeks) had lower peripheral venous plasma GSH concentrations than term (>36 weeks) babies; these levels decreased further with increasing prematurity (>27 weeks, with respiratory distress). On day 2, the peripheral venous plasma GSH concentrations reached a nadir, and the lowest levels were found in the most premature newborns. Lymphocyte GSH concentrations were lowest on day 2 and day 7, and in prematures (< 27 weeks, with respiratory distress) remained below adult lymphocyte GSH levels for at least 4 weeks. At birth, prematures (<27 weeks, with respiratory distress) had a central plasma arterio‐venous (A‐V) GSH gradient across the lung (an estimate of lung uptake of GSH) of 0.72±0.15 (mean ± SD) μ‐mol/L; on day 2, the A‐V gradient did not change significantly (0.49 ± 0.09 μmol/L). At birth, these prematures had markedly decreased BALF GSH concentrations (compared with adult levels), and they were not significantly changed during the first 4 weeks of life. These results suggest that GSH deficiency is present in prematures and that it increases with the degree of prematurity. At birth, GSH deficiency will compromise the lungs' defense against oxidative stress injury. Oxidative stress is likely to increase if hyperoxic treatment is given for respiratory distress in these infants. Pediatr Pulmonol. 1995; 20:160–166 . © 1995 Wiley‐Liss, Inc.
Pediatric Pulmonology - Tập 20 Số 3 - Trang 160-166 - 1995
Predictors of mortality in adults with cystic fibrosis Abstract Assessment of prognostic indicators in patients with cystic fibrosis (CF) is important. The study's aim was to assess the relative contribution of gender, genetics and microbiology on survival in adults with CF. Adult patients were studied from 1995 to 2005 and data collected included FEV1 (%predicted), body mass index (BMI), genetics, and microbiology. Data was available on 183 patients in 1995. Forty‐five patients died in the subsequent 10 years. Patients who died during the study had lower mean (SD) FEV1 %predicted in 1995 when compared to those remaining alive, 41.5 (15.2)% versus 69.8 (23.2)% predicted, respectively, P < 0.001 and they had lower mean (SD) BMI in 1995, 19.2 (3.3) kg/m2 in comparison to those remaining alive, 20.7 (3.4) kg/m2 , P = 0.008. The proportion of patients infected with Pseudomonas aeruginosa and Burkholderia cepacia complex was higher in the group who died during the study compared to those remaining alive, odds ratio 20.9 P < 0.0001 and 7.1 P < 0.0001, respectively. The presence of the ΔF508 homozygous mutation did not alter survival, P = 0.3. Patients infected with either P.aeruginosa or B.cepacia complex had reduced survival compared to those without infection, P = 0.01 and P < 0.0001, respectively. FEV1 % (P < 0.0001), infection with P.aeruginosa (P = 0.005) or B.cepacia complex (P = 0.03) were the only significant predictors of mortality. This study demonstrates adults who died were more likely to have worse lung function and be infected with either P.aeruginosa or B.cepacia complex. FEV1 % and infection with P.aeruginosa or B.cepacia complex were the most significant predictors of survival in adults with CF. Pediatr Pulmonol. 2007; 42:525–532. © 2007 Wiley‐Liss, Inc.
Pediatric Pulmonology - Tập 42 Số 6 - Trang 525-532 - 2007
Correlation between digital clubbing and pulmonary function in cystic fibrosis Abstract The correlation between digital clubbing and certain pulmonary function derangements (hypoxemia and FEV1 ) was previously described. However, the relationship between digital clubbing and other measures of pulmonary function or the presence of liver disease in patients with cystic fibrosis (CF) is poorly defined. Hence we compared the digital clubbing index (CI: ratio of distal phalangeal depth to interphalangeal depth) of 100 patients with CF (43 males, 57 females; mean age, 15.7 ± 7.3 years) with that of 100 age‐ and gender‐matched healthy controls. Digital clubbing was defined as a CI ≥ 1.00 (mean + 2.6 SD; 99% of normal subjects). The CI and its relationship to pulmonary function and to liver disease was then evaluated in the CF patients. Digital clubbing was present in 75/100 (75%) of CF patients but was absent in all controls (P < 0.0001). In CF patients, CI was inversely correlated with PaO2 (r = −0.555; P < 0.001), FEV1 (r = −0.499; P < 0.001), and FEF25–75% (r = −0.404; P < 0.001), and was positively correlated with RV (r = 0.285; P < 0.05) and the slope of phase 3 of single‐breath nitrogen washout (SP3N2 ) (r = 0.532; P < 0.01). There was no significant correlation between CI and age (r = 0.020; P = 0.84), TLC (r = −0.097; P = 0.34), PaCO2 (r = 0.167; P = 0.10), or history of liver disease (P = 0.08). We conclude that in CF, the degree of digital clubbing is related to degree of hypoxemia, airways obstruction, hyperinflation, and nonuniformity of ventilation. Pediatr Pulmonol. 2002; 33:332–338. © 2002 Wiley‐Liss, Inc.
Pediatric Pulmonology - Tập 33 Số 5 - Trang 332-338 - 2002
Familial susceptibility to severe respiratory infection in early life Abstract Lower respiratory tract infections (LRTI) are common in the first year of life and are mostly caused by viruses. Severity of LRTI in infants is associated with early‐life environmental factors. Genetic association studies also suggest a role of heredity in susceptibility to acute bronchiolitis. We designed a case control study to further investigate relative importance of familial influences in risk of LRTI in early childhood compared to environmental factors. From a hospital database, we selected 1,308 children (436 cases; 872 controls) living in Oxfordshire. Cases were children under age 5 years admitted to hospital with LRTI. Parental history and other exposures were recorded in cases and controls by postal questionnaire. Maternal history of asthma increased the risk of severe LRTI in the first year of life, independent of subsequent asthma in a child. History of maternal bronchiolitis also increased the risk of infant LRTI. These results further suppoprt the possibility that genetic factors play an important role in susceptibility to severe viral respiratory infections in early life, and suggest that this effect may be independent of subsequent childhood asthma. Pediatr Pulmonol. 2004; 38:321–328. © 2004 Wiley‐Liss, Inc.
Pediatric Pulmonology - Tập 38 Số 4 - Trang 321-328 - 2004
Airway function measurements and the long-term follow-up of survivors of preterm birth with and without chronic lung disease
Pediatric Pulmonology - Tập 41 Số 6 - Trang 497-508 - 2006
Quantitative CT scans of lung parenchymal pathology in premature infants ages 0–6 years Abstract Background Bronchopulmonary dysplasia (BPD) is a common, heterogeneous disease in premature infants. We hypothesized that quantitative CT techniques could assess lung parenchymal heterogeneity in BPD patients across a broad age range and demonstrate how pathologies change over time. Methods A cross‐sectional, retrospective study of children age 0‐6 years with non‐contrast chest CT scans was conducted. BPD subjects met NICHD/NHLBI diagnostic criteria for BPD and were excluded for congenital lung/airway abnormalities or other known/suspected pulmonary diagnoses; control subjects were not premature and had normal CT scan findings. Radiologic opacities, lucencies, and spatial heterogeneity were quantified via: 1) thresholding using CT‐attenuation (HU); 2) manual segmentation; and 3) Ochiai reader‐scoring system. Clinical outcomes included BPD severity by NICHD/NHLBI criteria, respiratory support at NICU discharge, wheezing, and respiratory exacerbations. Results Heterogeneity (standard deviation) of lung attenuation in BPD was significantly greater than in controls (difference 36.4 HU [26.1‐46.7 HU], P < 0.001); the difference between the groups decreased 0.58 HU per month of age (0.08‐1.07 HU per month, P = 0.02). BPD patients had greater amounts of opacities and lucencies than controls except with automated quantification of lucencies. Cross‐sectionally, lucencies per Ochiai score and opacities per manual segmentation decreased with time. No approach measured a statistically significant relationship to BPD clinical severity. Conclusions Opacities, lucencies, and overall heterogeneity of lungs via quantitative CT can distinguish BPD patients from healthy controls, and these abnormalities decrease with age across BPD patients. Defining BPD severity by clinical outcomes such as respiratory support at several time points (vs a single time point, per current guidelines) may be meaningful.
Pediatric Pulmonology - Tập 53 Số 3 - Trang 316-323 - 2018
Predictors of asthma following severe respiratory syncytial virus (RSV) bronchiolitis in early childhood
Pediatric Pulmonology - Tập 51 Số 12 - Trang 1382-1392 - 2016
Respiratory syncytial virus is an “opportunistic” killer Abstract Respiratory syncytial virus (RSV), responsible for more than three million yearly hospitalizations and up to 118 000 deaths in children under 5 years, is the leading pulmonary cause of death for this age group that lacks a licensed vaccine. Ninety‐nine percent of deaths due to the virus occur in developing countries. In‐hospital RSV fatalities affect previously healthy term infants in association with bacterial sepsis, clinically significant pneumothoraxes and, to a lesser extent, comorbid conditions. Community deaths affect low‐income children from socially vulnerable families and appear to be as frequent as inpatient fatalities. In industrialized countries, RSV deaths occur almost exclusively in children with premorbid conditions. In a sense, RSV is an “opportunistic” killer. It needs a synergistic premorbid, medical practice‐related, infectious, or social co‐factor to cause a fatal outcome. But while the complex problems associated with these co‐factors await solutions, candidate vaccines, long‐lived monoclonal antibodies and antivirals against RSV are under clinical evaluation. It seems reasonable to predict that the landscape of RSV infections will look different in the next decade.
Pediatric Pulmonology - Tập 53 Số 5 - Trang 664-667 - 2018
Tracheostomy in children: A population‐based experience over 17 years Abstract Introduction Tracheostomy is a lifesaving intervention with numerous complications. Objectives We describe the natural history of tracheostomy in children in a defined geographical area over a 17‐year period. Our primary aim is to stress the need for a consensus on pediatric tracheostomy care. Methods This retrospective study reviewed the charts of 72 children who had tracheostomy between January 1990 and January 2007. Indications for the procedure were divided into 3 groups: (1) upper airway obstruction at a well‐defined anatomic site (32 patients); (2) upper airway obstruction with a complex medical condition (24 patients); and (3) need for an access to the lower airway for long‐term ventilation and pulmonary care with normal airway anatomy (16 patients). Results The most common indication for tracheostomy was upper airway obstruction due to subglottic stenosis (15 patients, 21%) or as part of a complex craniofacial syndrome (15 patients, 21%). The duration of intubation prior to tracheostomy and the duration of hospitalization after tracheostomy varied markedly. Tracheocutaneous fistulae complicated 15 of the 38 (37%) decannulated patients. Tracheostomy infection occurred in 90% of the patients and tracheal granulation in 56%. Eleven (15%) deaths occurred, 10 were due to the underlying medical illness and 1 to a mucous plug. Conclusion The complications of tracheostomy in children are substantial. Surveillance and prompt interventions are necessary to overcome life‐threatening sequelae. A multidisciplinary (medical–surgical) approach provides better care for these highly vulnerable children. A consensus on pediatric tracheostomy care is needed. Pediatr Pulmonol. 2010; 45:487–493. © 2010 Wiley‐Liss, Inc.
Pediatric Pulmonology - Tập 45 Số 5 - Trang 487-493 - 2010
Hypercarbic ventilatory responses of infants at risk for SIDS Abstract We examined the hypercarbic ventilatory responses (HVR) of 143 infants at risk for sudden infant death syndrome (SIDS) and 34 normal control infants. Sixty‐five of the atrisk infants had experienced apparent life‐threatening events (ALTE), and 78 were siblings of SIDS victims. Twenty‐three (35%) of the ALTE infants experienced subsequent apnea; one died of SIDS. Seven (9%) of the SIDS siblings experienced subsequent apnea; two ultimately died of SIDS. In the HVR studies, we measured tidal volume (VT ), minute ventilation (VE ), frequency of breathing (f), and end‐tidal PCO 2 (PETCO 2 ) at rest and while breathing 2% and 4% CO2 . Mean HVR values for the ALTE, sibling, and control groups were all similar. The mean HVR values for those at‐risk infants who experienced subsequent apnea were not different from those who did not experience subsequent apnea. However, those infants experiencing subsequent apnea had higher mean VT /kg values (P < 0.01) and lower mean PETCO 2 values (P < 0.001) than those who did not. The SIDS siblings had significantly lower resting VT /kg values than either the near‐miss infants or normal controls (P < 0.01). We did not find depressed HVR values in infants at risk for SIDS. On the contrary, those infants who experienced subsequent apnea had evidence suggesting relative hyper ventilation. SIDS siblings had evidence suggesting relative hypo ventilation. These findings are interesting and thought‐provoking. However, HVR studies do not appear to be sensitive, specific, or appropriate for the general screening of infants at risk for SIDS.
Pediatric Pulmonology - Tập 3 Số 4 - Trang 226-230 - 1987
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