Abstract

Chronic obstructive pulmonary disease (COPD) is heterogeneous in development, progression, and phenotypes. Little is known about the lung microbiome, sampled by bronchoscopy, in milder COPD and its relationships to clinical features that reflect disease heterogeneity (lung function, symptom burden, and functional impairment). Using bronchoalveolar lavage fluid collected from 181 never-smokers and ever-smokers with or without COPD (GOLD 0-2) enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we find that lung bacterial composition associates with several clinical features, in particular bronchodilator responsiveness, peak expiratory flow rate, and forced expiratory flow rate between 25 and 75% of FVC (FEF25–75). Measures of symptom burden (COPD Assessment Test) and functional impairment (six-minute walk distance) also associate with disparate lung microbiota composition. Drivers of these relationships include members of the Streptococcus, Prevotella, Veillonella, Staphylococcus, and Pseudomonas genera. Thus, lung microbiota differences may contribute to airway dysfunction and airway disease in milder COPD.

Highlights

  • Chronic obstructive pulmonary disease (COPD) is a predominantly smoking-related lung disease, characterized by airflow obstruction, local and systemic inflammatory responses, and phenotypic heterogeneity

  • Using bronchoalveolar lavage fluid (BAL) collected from subjects in the well-characterized SPIROMICS cohort[6,14], we explored the hypotheses that differences in lung bacterial composition are associated with a diagnosis of COPD and/or with clinical features that reflect COPD pathophysiology, including measures of lung function and symptom burden

  • Variation in overall lung bacterial community structure did not associate with a categorical diagnosis of COPD, and only two bacterial taxa were significantly positively associated with COPD status (Streptococcus and Lactobacillales)

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Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a predominantly smoking-related lung disease, characterized by airflow obstruction, local and systemic inflammatory responses, and phenotypic heterogeneity. Inflammation can persist after smoking cessation for reasons not fully understood, and patients vary in disease development, progression and other outcomes. Bacterial colonization of the airways in COPD has long been recognized from culture-based studies, but its role in the pathogenesis or progression of COPD remains unclear. Recent studies, using culture-independent sequencing to profile microbial communities more comprehensively, have reported alterations in airway bacterial composition mostly in more severe COPD1–5. Less is known about the lung microbiome in milder COPD or in smokers without evidence of airflow obstruction and, in particular, whether differences in lung microbiota associate with clinical or biological features in earlier stages of COPD development.

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