ABSTRACT Background and Objective Non‐invasive ventilation (NIV) and inhaled bronchodilator therapy are foundational in the management of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, optimal drug‐delivery strategies during NIV remain uncertain. This study compared bronchodilator delivery via a pressurized metered‐dose inhaler (pMDI) interface versus standard jet nebulization during NIV. Methods This randomized, open‐label trial enrolled adults with hypercapnic AECOPD requiring NIV. Participants were randomized 1:1 to receive ipratropium bromide via pMDI using a modified NIV mask, or via jet nebulizer integrated into the inspiratory limb. Serum ipratropium concentrations at 30 min constituted the primary bioequivalence endpoint, analysed using geometric mean ratios (GMR) and Bayesian posterior probabilities. Secondary outcomes included changes in physiologic parameters, blood gases, ventilatory asynchrony, duration of stay and cost effectiveness. Results Forty‐four patients were randomized; 41 were included in the intention‐to‐treat analysis (pMDI n = 20, nebulizer n = 21). At 30 min, geometric mean serum ipratropium levels were higher with pMDI (110.9 pg/mL) versus nebulization (51.6 pg/mL), yielding a GMR of 2.15. Bayesian analysis showed a 95.9% probability that GMR exceeded the non‐inferiority threshold (0.80). At 6 h, differences again favoured pMDI (GMR 3.18; p = 0.022; posterior probability 99.8%). Physiologic outcomes, gas exchange, and NIV duration were similar between groups, though ICU stay was shorter in the pMDI arm. No safety concerns or device‐related complications were observed. Post hoc cost analysis showed markedly lower therapy cost with pMDI. Conclusions pMDI‐based bronchodilator delivery during NIV using a customized interface is feasible, safe, cost‐efficient, and achieves higher systemic drug levels than jet nebulization. Larger multicentre trials are warranted to determine clinical impact. Trial Registration Clinical Trials Registry of India CTRI/2023/07/054734
ABSTRACT Background and Objective Whether lifetime lung function trajectories and spirometry patterns are associated with Obstructive Sleep Apnoea (OSA) is unknown. We aimed to investigate this association to widen the understanding of OSA pathophysiology. Methods We previously identified six FEV 1 /FVC (forced expiratory volume in the first second/forced vital capacity) and five FVC trajectories within a population‐based prospective cohort ( n = 2422) using spirometry assessed at ages 7, 13, 18, 43, 50, and 53 years. These trajectories were combined into four lifetime spirometry patterns: restrictive‐only, obstructive‐only, mixed, and reference (normal), which were our exposure variables. Outcomes were medically‐confirmed OSA in midlife and probable‐OSA defined using the STOP‐Bang questionnaire. Associations were assessed using logistic regression models. Results The ‘restrictive‐only’ spirometry pattern was associated with medically‐confirmed OSA (OR = 2.5; 95% CI 1.5, 4.3). In addition, restriction‐confirmatory low total lung capacity and reduced functional residual capacity were associated with increased odds of medically‐confirmed OSA (OR = 1.4; 0.9, 2.1 and OR = 1.7; 1.1, 2.6, respectively, per one SD reduction in volume). The results were similar for probable OSA. These associations held when controlled for BMI and central obesity and were independent of childhood lung function. Neither transfer factor for carbon monoxide (T L co) nor transfer coefficient (Kco) was associated with OSA. Conclusion We provide first evidence that lifetime lung restriction is related to middle‐age OSA. While this information may be used to incidentally flag middle‐age OSA risk and vice versa, further research is encouraged to confirm the underlying pathophysiological mechanisms.
