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Obesity in children with poorly controlled asthma: Sex differences.

Pediatr Pulmonol. 2012 Nov 9;

Authors: Lang JE, Holbrook JT, Wise RA, Dixon AE, Teague WG, Wei CY, Irvin CG, Shade D, Lima JJ, for the American Lung Association-Asthma Clinical Research Centers

Abstract
BACKGROUND: Obesity increases asthma risk, and may alter asthma severity. In adults, sex appears to modify the effect of obesity on asthma. Among children, the effect of sex on the relationship between obesity and asthma severity remains less clear, particularly when considering race. OBJECTIVE: To determine how obesity affects disease characteristics in a diverse cohort of children with poorly controlled asthma, and if obesity effects are altered by sex. DESIGN: We analyzed 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month trial assessing lansoprazole for asthma control. In this secondary analysis, we determined associations between obesity and symptom severity, spirometry, exacerbation risk, airway biomarkers, bronchial reactivity, and airflow perception. We used both a multivariate linear regression and longitudinal mixed-effect model to determine if obesity interacted with sex to affect asthma severity. RESULTS: Regardless of sex, BMI >95th percentile did not affect asthma control, exacerbation risk or airway biomarkers. Sex changed the effect of obesity on lung function (sex × obesity FEV1%, interaction P-value < 0.01, sex × obesity FEV1/FVC, interaction P-value = 0.03). Obese males had significantly worse airflow obstruction compared to non-obese males, while in females there was no obesity effect on airflow obstruction. In females, obesity was associated with significantly greater FEV1 and FVC, and a trend toward reduced airway reactivity. CONCLUSIONS: Obesity did not affect asthma control, airway markers or disease stability; however obesity did affect lung function in a sex-dependent manner. In males, obesity associated with reduced FEV1/FVC, and in females, obesity associated with substantially improved lung function. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

PMID: 23143849 [PubMed - as supplied by publisher]

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Metabolic Pathways of Inhaled Glucocorticoids by the Cyp3a Enzymes.

Drug Metab Dispos. 2012 Nov 9;

Authors: Moore CD, Roberts JK, Orton CR, Murai T, Fidler TP, Reilly CA, Ward RM, Yost GS

Abstract
Asthma is one of the most prevalent diseases in the world, for which the mainstay treatment has been the use of inhaled glucocorticoids. Despite their widespread use, approximately 30% of asthma suffers exhibit some degree of steroid insensitivity, or are refractory to inhaled glucocorticoids. One hypothesis to explain this phenomenon is interpatient variability in the clearance of these compounds. The objective of this research is to determine how metabolism of glucocorticoids by the cytochrome P450 (CYP) 3A family of enzymes could affect their effectiveness in asthmatic patients. In this work, the metabolism of four frequently prescribed inhaled glucocorticoids, triamcinolone acetonide, flunisolide, budesonide, and fluticasone propionate, by the CYP3A family of enzymes was studied to identify differences in their rates of clearance and to identify their metabolites. Both inter-enzyme and inter-drug variability in rates of metabolism and metabolic fate were observed. CYP3A4 was the most efficient metabolic catalyst for all the compounds, and CYP3A7 had the slowest rates. CYP3A5, which is particularly relevant to glucocorticoid metabolism in the lungs, was also shown to efficiently metabolize triamcinolone acetonide, budesonide, and fluticasone propionate. In contrast, flunisolide was only metabolized via CYP3A4, with no significant turnover by CYP3A5 or CYP3A7. Common metabolites included 6β-hydroxylation and Δ6-dehydrogenation for triamcinolone acetonide, budesonide and flunisolide. The structure of Δ6-flunisolide was unambiguously established by NMR analysis. Metabolism also occurred on the D-ring substituents, including the 21-carboxy metabolites for triamcinolone acetonide and flunisolide. The novel metabolite 21-nortriamcinolone acetonide was also identified by LC/MS and NMR analysis.

PMID: 23143891 [PubMed - as supplied by publisher]

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Residential dampness and molds and the risk of developing asthma: a systematic review and meta-analysis.

PLoS One. 2012;7(11):e47526

Authors: Quansah R, Jaakkola MS, Hugg TT, Heikkinen SA, Jaakkola JJ

Abstract
CONTEXT: Studies from different geographical regions have assessed the relations between indoor dampness and mold problems and the risk of asthma, but the evidence has been inconclusive.
OBJECTIVE: To assess the relations between indicators of indoor dampness and mold problems and the risk of developing new asthma, and to investigate whether such relations differ according to the type of exposure.
DATA SOURCES: A systematic literature search of PubMed database from 1990 through March 2012 and the reference lists of recent reviews and of relevant articles identified in our search.
STUDY SELECTION: Cohort/longitudinal and incident case-control studies assessing the relation between mold/dampness and new asthma were included.
DATA EXTRACTION: Three authors independently evaluated eligible articles and extracted relevant information using a structured form.
SYNTHESIS: SIXTEEN STUDIES WERE INCLUDED: 11 cohort and 5 incident case-control studies. The summary effect estimates (EE) based on the highest and lowest estimates for the relation between any exposure and onset of asthma were 1.50 (95% confidence interval [CI] 1.25-1.80, random-effects model, Q-statistic 38.74 (16), P = 0.001) and 1.31 (95% CI 1.09-1.58, random-effects model, Q-statistic 40.08 (16), P = 0.000), respectively. The summary effect estimates were significantly elevated for dampness (fixed-effects model: EE 1.33, 95% CI 1.12-1.56, Q-statistic 8.22 (9), P = 0.413), visible mold (random-effects model; EE 1.29, 95% CI 1.04-1.60, 30.30 (12), P = 0.001), and mold odor (random-effects model; EE 1.73, 95% CI 1.19-2.50, Q-statistics 14.85 (8), P = 0.038), but not for water damage (fixed-effects model; EE 1.12, 95% CI 0.98-1.27). Heterogeneity was observed in the study-specific effect estimates.
CONCLUSION: The evidence indicates that dampness and molds in the home are determinants of developing asthma. The association of the presence of visible mold and especially mold odor to the risk of asthma points towards mold-related causal agents.

PMID: 23144822 [PubMed - in process]

This study sought to characterize effects of clopidogrel on the incidence and severity of community-acquired pneumonia (CAP). A retrospective cohort study was conducted of Kentucky Medicaid patients (2001–2005). The exposed cohort consisted of patients receiving at least six consecutive clopidogrel prescriptions; the non-exposed cohort was comprised of patients not prescribed clopidogrel. Primary endpoints included incidence of CAP and inpatient treatment. Secondary severity endpoints included mortality, intensive care unit admission, mechanical ventilation, sepsis, and acute respiratory distress syndrome/acute lung injury. CAP incidence was significantly greater in the exposed cohort (OR 3.39, 95 % CI 3.27–3.51, p < 0.0001) that remained after adjustment (OR 1....