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Human rhinovirus (HRV) infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD) and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE) modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.

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BACKGROUND: COPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations. METHODS: Data were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18 months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change $ 48 h) and eventbased (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed. RESULTS: A total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score > 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs 5.0 [interquartile range, 2.0-7.0]; P ¼ .01), and they were more likely to have baseline PSQI scores > 5 (50.3% vs 37.3%; P ¼ .01). Higher PSQI scores were associated with increased symptombased exacerbation risk (adjusted rate ratio, 1.09; 95% CI, 1.01-1.18; P ¼ .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95% CI, 1.00-1.21; P ¼ .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95% CI, 1.09-2.03). CONCLUSIONS: Higher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18 months' prospective follow-up.

Background and objectiveLack of consensus on diagnosis of ACO limits our understanding of the impact, management and outcomes of ACO. The present observational study aims to describe the prevalence, clinical characteristics and course of individuals with ACO based on various definitions used in clinical practice.MethodsWe included individuals with COPD from the prospective, multisite CanCOLD study and defined subjects with ACO using seven definitions commonly used in the literature.ResultsData including questionnaires, lung function and CT scans were analysed from 522 individuals with COPD who were randomly recruited from the population. Among them, 264 fulfilled at least one of the seven definitions of ACO. Prevalence of ACO varied from 3.8% to 31%. Regardless of the definition, individuals with ACO had worse outcomes (lung function and higher percentage of fast decliners, symptoms and exacerbations, health‐related quality of life and comorbidities) than the remaining patients with COPD. Conversely, patients with non‐ACO had higher emphysema and bronchiolitis scores. The three definitions that included atopy and/or physician diagnosis of asthma identified subjects who differed significantly from patients with COPD. The two ACO definitions with post‐bronchodilator reversibility were concordant with COPD and were the least stable, with less than 50% of the patients from each group maintaining reversibility over visits.ConclusionAtopy and physician‐diagnosed asthma are more distinguishing characteristics to identify ACO. This finding needs to be validated using measures of airway inflammation and other specific biomarkers.