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Background: COPD is associated with nighttime respiratory symptoms, poor sleep quality, and increased risk of nocturnal death. Overnight deterioration of inspiratory capacity (IC) and FEV 1 have been documented previously. However, the precise nature of this deterioration and mechanisms by which evening bronchodilation may mitigate this occurrence have not been studied., Research Question: What is the effect of evening dosing of dual, long-acting bronchodilation on detailed nocturnal respiratory mechanics and inspiratory neural drive (IND)?, Study Design and Methods: A double-blind, randomized, placebo-controlled crossover study assessed the effects of evening long-acting bronchodilation (aclidinium bromide/formoterol fumarate dihydrate: 400/12 μg) or placebo on morning trough IC (12 h after the dose; primary outcome) and serial overnight measurements of spirometry, dynamic respiratory mechanics, and IND (secondary outcomes). Twenty participants with COPD (moderate/severe airway obstruction and lung hyperinflation) underwent serial measurements of IC, spirometry, breathing pattern, esophageal and transdiaphragmatic pressures, and diaphragm electromyography (diaphragmatic electromyography as a percentage of maximum; IND) at 6 time points from 0 to 12 h after the dose and compared with sleeping IND., Results: Compared with placebo, evening bronchodilation was not associated with increased morning trough IC 12 h after the dose (P = .48); however, nadir IC (lowest IC, independent of time), peak IC, area under the curve for 12 h after the dose, and IC for 10 h after the dose were improved (P < .05). During placebo, total airways resistance, lung hyperinflation, IND, and tidal esophageal and transdiaphragmatic pressure swings all increased significantly overnight compared with baseline evening values; however, each of these parameters improved with bronchodilator treatment (P < .05) with no change in ventilation or breathing pattern., Interpretation: Respiratory mechanics significantly deteriorated at night during placebo. Although the morning trough IC was unchanged, evening bronchodilator treatment was associated consistently with sustained overnight improvements in dynamic respiratory mechanics and inspiratory neural drive compared with placebo CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02429765., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Aim: To assess the diagnostic accuracy of common carotid artery intima media thickness (CIMT) for coronary artery disease (CAD) detection in patients with obstructive sleep apnoea (OSA)., Materials & Methods: Patients with clinically suspected OSA prospectively underwent polysomnography (PSG), ultrasound CIMT measurement and coronary computed tomography angiography (CTA). An average CIMT of ≥0.9 mm in either common carotid artery designated as a positive test. Coronary CTA was the reference standard for the presence of CAD. Coronary plaque presence, volume, density and type were correlated with CIMT findings., Results: 35 consecutive male patients were enrolled from sleep clinic. Two patients had no evidence of OSA on PSG (apnoea-hypopnea index [AHI]<5/hr), and were excluded. Of the remaining 33, 18 (54%) had mild-moderate OSA (AHI 5-30/hr) and 15 (46%) had severe OSA (AHI >30/hr). Eight (24%) patients had CAD on coronary CTA. Coronary plaques were predominantly non- or partly calcified, and located in proximal coronary artery segments. Sensitivity, specificity, positive and negative predictive and likelihood ratios for a positive CIMT (≥0.9 mm) in diagnosing CAD were 0.5 (95% confidence interval: 0.76-0.12), 0.96 (1-0.89), 80, 85.7, 12.5 and 0.52 respectively. The adjusted odds ratio was 40.8., Conclusion: In patients with OSA, CIMT is a highly specific but poorly sensitive test for detecting CAD., (Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Introduction: Intermittent hypoxia (IH)-induced activation of pro-inflammatory pathways is a major contributing factor to the cardiovascular pathophysiology associated with obstructive sleep apnea (OSA). Obesity is commonly associated with OSA although it remains unknown whether adipose tissue is a major source of inflammatory mediators in response to IH. The aim of this study was to test the hypothesis that IH leads to augmented inflammatory responses in human adipocytes when compared to cells of non-adipocyte lineages., Methods and Results: Human primary subcutaneous and visceral adipocytes, human primary microvascular pulmonary endothelial cells (HUMEC-L) and human primary small airway epithelial cells (SAEC) were exposed to 0, 6 or 12 cycles of IH or stimulated with tumor necrosis factor (TNF)-α. IH led to a robust increase in NF-κB DNA-binding activity in adipocytes compared with normoxic controls regardless of whether the source of adipocytes was visceral or subcutaneous. Notably, the NF-κB response of adipocytes to both IH and TNF-α was significantly greater than that in HUMEC-L and SAEC. Western blotting confirmed enhanced nuclear translocation of p65 in adipocytes in response to IH, accompanied by phosphorylation of I-κB. Parallel to p65 activation, we observed a significant increase in secretion of the adipokines interleukin (IL)-8, IL-6 and TNF-α with IH in adipocytes accompanied by significant upregulation of mRNA expression. PCR-array suggested profound influence of IH on pro-inflammatory gene expression in adipocytes., Conclusion: Human adipocytes demonstrate strong sensitivity to inflammatory gene expression in response to acute IH and hence, adipose tissue may be a key source of inflammatory mediators in OSA., (Copyright © 2014 Elsevier Inc. All rights reserved.)