Background:Current guidelines for the evaluation of chronic obstructive pulmonary disease (COPD) do not recommend screening for pulmonary hypertension (PH), despite the high prevalence and impact on outcomes. A simple screening tool to identify patients with an elevated pulmonary vascular resistance (PVR) is urgently needed, as they may benefit from PH-specific therapy and more urgent referral for lung transplantation.Research Question:We sought to examine whether a ratio of forced expiratory volume in one second (FEV1) to diffusing capacity (DLCO) predicts hemodynamic patterns in COPD.Study Design and Methods:Individuals with COPD who underwent right heart catheterization from two academic medical centers were included. Adjusted multinomial models tested associations between FEV1/DLCO and hemodynamic patterns. Receiver operating curves were generated to assess the discriminative performance of the FEV1/DLCO ratio in predicting PH with an elevated PVR.Results:Approximately 40% of the 411 individuals included had PH with an elevated PVR. For every 0.1 increase in the FEV1/DLCO ratio, there was a 12-14% increased rate of PH with an elevated PVR compared to No PH. FEV1/DLCO ratio had moderate discriminative performance (C-statistic 0.68-0.72) which was strengthened when combined in a model with elevated tricuspid regurgitant jet velocity on echocardiography (C-statistic 0.78-0.82). Above a threshold of 1.4, FEV1/DLCO demonstrated good specificity (75%) in predicting PH with an elevated PVR.Interpretation:These findings suggest that disproportionate reductions in DLCO predict PH with an elevated PVR in a COPD population. The FEV1/DLCO ratio should be considered in evaluation of PH in COPD.

Obstructive sleep apnoea (OSA) is a prevalent disorder with major health consequences for which there is no approved pharmacological therapy targeting upper airway muscle pathophysiology. A combination of a noradrenergic (atomoxetine) and antimuscarinic (oxybutynin) (AtoOxy) may meaningfully reduce apnoea-hypopnoea index (AHI), but further repeated-dose intervention data are needed. 58 participants with moderate-to-severe OSA were randomised to receive AtoOxy (80/5 mg) and placebo in a 1-month cross-over study. Primary analysis quantified the effect of AtoOxy versus placebo on AHI (percent change from baseline). Individual pathophysiology was characterised at baseline in a stand-alone gold-standard physiology study to determine whether OSA traits (collapsibility per 'Pcrit'; arousal threshold and muscle effectiveness per intraoesophageal catheter; loop gain) modified AtoOxy effectiveness. AHI was lowered by -23.8 (-35.2, -10.6)%baseline (estimate (95% CI)) with AtoOxy versus by -11.7 (-24.3, 2.9)%baseline with placebo; the treatment difference of -12.1 (-22.4, -0.5)%baseline was significant (p=0.041). Only arousal threshold was a significant modifier of response: AtoOxy treatment effect was greater in high versus low arousal threshold (-25 vs +3 %baseline treatment difference from placebo). Point-estimate treatment differences were observed within low but not high muscle effectiveness (-20 vs -4 %baseline) and mild but not severe collapsibility (-17 vs -7 %baseline). Sensitivity analysis suggested a twofold greater treatment difference using AHI4 (4% hypopnoea criteria). AtoOxy reduced AHI over 1 month; although the average response was not clinically meaningful, greater improvements were observed in participants with a higher arousal threshold, lower muscle effectiveness and milder collapsibility, which could enable targeted pharmacological intervention.

Lung-function outcomes among preterm-born children referred for pulmonology care are highly heterogeneous, and early determinants remain incompletely defined. We aimed to identify early-life factors associated with school-age lung function after preterm birth and to examine whether school-age spirometry patterns relate to subsequent lung-function trajectories. Early-life analyses (n=511) examined predictors of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) z-scores at ages 6-8 years using multivariable regression. Spirometry-based phenotypes included prematurity-associated preserved-ratio impaired spirometry (pPRISm), prematurity-associated obstructive lung disease (POLD) and prematurity-associated dysanapsis. Longitudinal mixed-effects models assessed lung-function trajectories from ages 8 to 21 years. Parallel analyses were conducted in the National Health and Nutrition Examination Survey (NHANES). Lower weight-for-height at 4 years was non-linearly associated with both FEV1 and FVC at school age. Invasive ventilation in the first year of life was associated with lower FEV1 (β -0.62, 95% CI -0.96 to -0.28) and FVC (β -0.54, 95% CI -0.92 to -0.18). In exploratory analyses, pPRISm was inversely associated with neighbourhood income (risk ratio (RR) 0.63 per SD increase, 95% CI 0.46 to 0.88), and POLD was associated with invasive ventilation (RR 8.07, 95% CI 3.33 to 19.5). Similar subtypes and associations were observed in NHANES. School-age pPRISm was associated with progressive FEV1 z-score decline (age x pPRISm β -0.08 SD/year, 95% CI -0.15 to -0.02), while POLD was associated with improving FVC z-score (age x POLD β 0.13 SD/year, 95% CI 0.07 to 0.20). Early-childhood growth, neonatal respiratory exposures and school-age spirometry patterns help stratify long-term pulmonary risk among preterm-born children referred for pulmonary care.