Browsing by Subject "lung function"

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    Cumulative Effects of Neonatal Hyperoxia on Murine Alveolar Structure and Function
    (Wiley, 2017-05) Cox, Angela M.; Gao, Yong; Perl, Anne-Karina T.; Tepper, Robert S.; Ahlfeld, Shawn K.; Pediatrics, School of Medicine
    Background Bronchopulmonary dysplasia (BPD) results from alveolar simplification and abnormal development of alveolar and capillary structure. Survivors of BPD display persistent deficits in airflow and membrane and vascular components of alveolar gas diffusion. Despite being the defining feature of BPD, various neonatal hyperoxia models of BPD have not routinely assessed pulmonary gas diffusion. Methods To simulate the most commonly-utilized neonatal hyperoxia models, we exposed neonatal mice to room air or ≥90% hyperoxia during key stages of distal lung development: through the first 4 (saccular), 7 (early alveolar), or 14 (bulk alveolar) postnatal days, followed by a period of recovery in room air until 8 weeks of age when alveolar septation is essentially complete. We systematically assessed and correlated the effects of neonatal hyperoxia on the degree of alveolar–capillary structural and functional impairment. We hypothesized that the degree of alveolar–capillary simplification would correlate strongly with worsening diffusion impairment. Results Neonatal hyperoxia exposure, of any duration, resulted in alveolar simplification and impaired pulmonary gas diffusion. Mean Linear Intercept increased in proportion to the length of hyperoxia exposure while alveolar and total lung volume increased markedly only with prolonged exposure. Surprisingly, despite having a similar effect on alveolar surface area, only prolonged hyperoxia for 14 days resulted in reduced pulmonary microvascular volume. Estimates of alveolar and capillary structure, in general, correlated poorly with assessment of gas diffusion. Conclusion Our results help define the physiological and structural consequences of commonly-employed neonatal hyperoxia models of BPD and informtheir clinical utility.
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    Use of continuous positive airway pressure reduces airway reactivity in adults with asthma
    (European Respiratory Journal, 2013-02) Busk, Michael; Busk, Nancy; Puntenney, Paula; Hutchins, Janet; Yu, Zhangsheng; Gunst, Susan J.; Tepper, Robert S.; Department of Pediatrics, IU School of Medicine
    Asthma is characterised by airway hyperreactivity, which is primarily treated with β-adrenergic bronchodilators and anti-inflammatory agents. However, mechanical strain during breathing is an important modulator of airway responsiveness and we have previously demonstrated in animal models that continuous positive airway pressure (CPAP) resulted in lower in vivo airway reactivity. We now evaluated whether using nocturnal CPAP decreased airway reactivity in clinically-stable adults with asthma. Adults with stable asthma and normal spirometry used nocturnal CPAP (8-10 cmH(2)O) or sham treatment (0-2 cmH(2)O) for 7 days. Spirometry and bronchial challenges were obtained before and after treatment. The primary outcome was the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC(20)). The CPAP group (n=16) had a significant decrease in airway reactivity (change in (Δ)logPC(20) 0.406, p<0.0017) while the sham group (n=9) had no significant change in airway reactivity (ΔlogPC(20) 0.003, p=0.9850). There was a significant difference in the change in airway reactivity for the CPAP versus the sham group (ΔlogPC(20) 0.41, p<0.043). Our findings indicate that chronic mechanical strain of the lungs produced using nocturnal CPAP for 7 days reduced airway reactivity in clinically stable asthmatics. Future studies of longer duration are required to determine whether CPAP can also decrease asthma symptoms and/or medication usage.