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Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma.

ABSTRACT: BACKGROUND:Although pre-puberty asthma is more prevalent in males, after puberty through middle-age, asthma is more prevalent in females. The surge of sex hormones with puberty might explain this gender switch. METHODS:To examine the effects of sex hormones on lung function and symptoms with puberty, Tanner stage was assessed in 187 children 6-18 years of age (59% severe) enrolled in the NIH/NHLBI Severe Asthma Research Program (SARP). The effects of circulating sex hormones (n?=?68; testosterone, dehydroepiandrosterone sulfate (DHEA-S), estrogen, and progesterone) on lung function and 4 week symptom control (ACQ6) in cross-section were tested by linear regression. RESULTS:From pre-/early to late puberty, lung function did not change significantly but ACQ6 scores improved in males with severe asthma. By contrast females had lower post-BD FEV1% and FVC% and worse ACQ6 scores with late puberty assessed by breast development. In males log DHEA-S levels, which increased by Tanner stage, associated positively with pre- and post-BD FEV1%, pre-BD FVC %, and negatively (improved) with ACQ6. Patients treated with high-dose inhaled corticosteroids had similar levels of circulating DHEA-S. In females, estradiol levels increased by Tanner stage, and associated negatively with pre-BD FEV1% and FVC %. CONCLUSIONS:These results support beneficial effects of androgens on lung function and symptom control and weak deleterious effects of estradiol on lung function in children with asthma. Longitudinal data are necessary to confirm these cross-sectional findings and to further elucidate hormonal mechanisms informing sex differences in asthma features with puberty. TRIAL REGISTRATION:ClinicalTrials.gov registration number: NCT01748175 .

SUBMITTER: DeBoer MD

PROVIDER: S-EPMC5891903 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma.

DeBoer Mark D MD Phillips Brenda R BR Mauger David T DT Zein Joe J Erzurum Serpil C SC Fitzpatrick Anne M AM Gaston Benjamin M BM Myers Ross R Ross Kristie R KR Chmiel James J Lee Min Jie MJ Fahy John V JV Peters Michael M Ly Ngoc P NP Wenzel Sally E SE Fajt Merritt L ML Holguin Fernando F Moore Wendy C WC Peters Stephen P SP Meyers Deborah D Bleecker Eugene R ER Castro Mario M Coverstone Andrea M AM Bacharier Leonard B LB Jarjour Nizar N NN Sorkness Ronald L RL Ramratnam Sima S Irani Anne-Marie AM Israel Elliot E Levy Bruce B Phipatanakul Wanda W Gaffin Jonathan M JM Gerald Teague W W

BMC pulmonary medicine 20180410 1

<h4>Background</h4>Although pre-puberty asthma is more prevalent in males, after puberty through middle-age, asthma is more prevalent in females. The surge of sex hormones with puberty might explain this gender switch.<h4>Methods</h4>To examine the effects of sex hormones on lung function and symptoms with puberty, Tanner stage was assessed in 187 children 6-18 years of age (59% severe) enrolled in the NIH/NHLBI Severe Asthma Research Program (SARP). The effects of circulating sex hormones (n = ...[more]

PMID: 29631584

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Project description:BackgroundExtracellular DNA (e-DNA) and neutrophil extracellular traps (NETs) are linked to asthmatics airway inflammation. However, data demonstrating the characterization of airway inflammation associated with excessive e-DNA production and its impact on asthma outcomes are limited.ObjectiveTo characterize the airway inflammation associated with excessive e-DNA production and its association with asthma control, severe exacerbations and pulmonary function, particularly, air trapping and small airway dysfunction.MethodsWe measured e-DNA concentrations in induced sputum from 134 asthma patients and 28 healthy controls. We studied the correlation of e-DNA concentrations with sputum neutrophils, eosinophils and macrophages and the fractional exhaled nitric oxide (FeNO). Lung function was evaluated using spirometry, body plethysmography, impulse oscillometry and inert gas multiple breath washout. We stratified patients with asthma into low-DNA and high-DNA to compare lung function impairments and asthma outcomes.ResultsPatients with severe asthma had higher e-DNA concentration (54.2 ± 42.4 ng/µl) than patients with mild-moderate asthma (41.0 ± 44.1 ng/µl) or healthy controls (26.1 ± 16.5 ng/µl), (all p values < 0.05). E-DNA concentrations correlated directly with sputum neutrophils (R = 0.49, p < 0.0001) and negatively with sputum macrophages (R = - 0.36, p < 0.0001), but neither with sputum eosinophils (R = 0.10, p = 0.26), nor with FeNO (R = - 0.10, p = 0.22). We found that 29% of asthma patients (n = 39) had high e-DNA concentrations above the upper 95th percentile value in healthy controls (55.6 ng /μl). High-DNA was associated with broad lung function impairments including: airflow obstruction of the large (FEV1) and small airways (FEF50%, FEF25-75), increased air trapping (RV, RV/TLC), increased small airway resistance (R5-20, sReff), decreased lung elasticity (X5Hz) and increased ventilation heterogeneity (LCI), (all P values < 0.05). We also found that high e-DNA was associated with nearly three-fold greater risk of severe exacerbations (OR 2·93 [95% CI 1.2-7.5]; p = 0·012), worse asthma control test (p = 0.03), worse asthma control questionnaire scores (p = 0.01) and higher doses of inhaled corticosteroids (p = 0.026).ConclusionIncreased production of extracellular DNA in the airway characterizes a subset of neutrophilic asthma patients who have broad lung function impairments, poor symptom control and increased risk of severe exacerbations.

Dataset Information

Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma.

Publications

Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma.

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