Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. COPD frequent exacerbators (FEs) suffer increased morbidity and mortality compared with infrequent exacerbators (IEs). Exacerbations are associated with bacterial infection and lung inflammation. Our overall objective was to determine features that differentiate the oral and sputum microbiota of FEs versus IEs. A total of 11 FEs and 11 IEs provided oral wash and sputum samples. Each sample and control underwent DNA extraction, 16S V4 rRNA amplification, 16S V4 sequencing, and quantitative PCR of 16S rRNA. Data were analyzed using QIIME and R. FEs and IEs demonstrated no significant differences in mean age, FEV1 % predicted, pack-years of tobacco exposure, or St. George's Respiratory Questionnaire score. No differences in oral wash or sputum 16S copy numbers were observed based on phenotype. Shannon diversity was significantly greater in oral samples compared with sputum (P = 0.002), and IE samples were more diverse than FE samples (P = 0.02). No differences in oral wash taxa related to COPD phenotype were observed. The four most common genera in sputum differed by exacerbation phenotype: FE sputum contained Haemophilus, Streptococcus, Veillonella, and Moraxella; IE sputum contained Streptococcus, Veillonella, Prevotella, and Haemophilus. One operational taxonomic unit (Actinomyces) was significantly more abundant in IE versus FE sputum (P = 0.048, Wilcoxon rank-sum test). Principal coordinate analysis using Bray-Curtis distance with permutational multivariate analysis of variance analyses demonstrated clustering by anatomic site (P = 0.016), phenotype (P = 0.025), inhaled corticosteroid use (P = 0.045), current tobacco use (P = 0.024), COPD severity (P = 0.003), and recent dental cleaning (P = 0.006). In conclusion, FEs have less diverse oral and sputum microbiota than IEs. FE sputum contained more Haemophilus and Moraxella compared with IE sputum, but this difference was not statistically significant. The oral and sputum microbiota of subjects with COPD demonstrated clustering based on exacerbation phenotype, inhaled corticosteroid use, tobacco use, severity of obstruction, and dental care habits.
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