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Background Chronic obstructive pulmonary disease (COPD) concomitant with obstructive sleep apnea (OSA) is known as overlap syndrome. It has an increased rate of hospitalization due to COPD exacerbation which is believed to indicate a worsening of the underlying chronic airway inflammation. Therefore, the aim of this prospective study was to explore whether OSA exacerbates airway inflammation in subjects with COPD by examining the bronchoalveolar lavage (BAL) fluid. Methods This prospective study included 47 patients with overlap syndrome and 28 patients with moderate-to-severe stage stable COPD. Twenty-five patients with overlap syndrome adhered to the continuous positive airway pressure (CPAP) treatment; the remaining patients either refused CPAP treatment or discontinued it within two weeks owing to adverse effects or other reasons. BAL fluid was collected from all subjects for the evaluation of cell numbers and tumor necrosis factor alpha (TNFα) and interleukin-8 (IL-8) levels. Results The BAL fluid of patients with overlap syndrome showed a significantly increased proportion of neutrophils and higher TNFα concentration and IL-8 levels than that of COPD patients; however, the serum CRP levels were not significantly different. An association was found between the percentage of neutrophils and the TNFα concentration and IL-8 levels. Moreover, the TNFα concentration was significantly correlated with the percentage of nighttime spent with oxygen saturation less than 90%. After CPAP treatment, airway inflammation was found to decrease significantly. Conclusions OSA exacerbates airway inflammation in COPD patients. CPAP treatment can improve nocturnal hypoxemia and decrease airway inflammation. [ABSTRACT FROM AUTHOR]