부산대학교 도서관

IntroductionCOPD exacerbations are the main cause of hospital admission and death in COPD. Respiratory viruses are identified in over half COPD exacerbations with human rhinovirus (HRV) being the most commonly detected. Secondary bacterial infection is associated with prolonged exacerbations, higher rates of hospital admission and increased symptom severity. Our group have previously shown that secondary bacterial infection in HRV induced COPD exacerbations is driven by an outgrowth of Haemophilus influenzae.HypothesisWe hypothesised that HRV may impair phagocytosis of bacteria by alveolar macrophages which may lead to secondary bacterial outgrowth in COPD exacerbations.MethodsBronchoscopy was performed on participants of the London COPD cohort and healthy controls. Alveolar macrophages were obtained by bronchoalveolar lavage. Alveolar macrophages were incubated with HRV at a multiplicity of infection (MOI) of 5 for 24 hours or media control. Phagocytic capacity was assessed by incubating with fluorescently labelled heat killed Haemophilus influenzaeor Streptococcus pneumoniaefor 4 hours. Uptake was measured in Relative Fluorescent Units (RFU) using a fluorimeter.ResultsAlveolar macrophages were obtained from 14 COPD patients and 9 healthy controls. HRV significantly impaired phagocytosis of H. influenzaeby alveolar macrophages in patients with COPD (HRV median 0.97 (0.50–2.17 interquartile range) RFU x103vs media control median 1.38 (0.70–2.50 interquartile range) RFU x103p<0.05) but did not impair phagocytosis of S. pneumoniae. HRV did not impair phagocytosis in alveolar macrophages from healthy controls. Baseline phagocytic capacity of H. influenzae was impaired in COPD patients compared to healthy controls (COPD 1.59+/-1.31 RFU x103vs healthy control 3.81+/-1.82 RFU x103). Phagocytosis of H. influenzae correlated with worsening FEV1 percent predicted in COPD (R²=0.452 p<0.05).ConclusionsThe presence of HRV impaired phagocytosis of H. influenzaein alveolar macrophages from patients with COPD but not healthy controls. This may contribute to secondary bacterial infection in COPD exacerbations.