Tobacco use, self-reported professional dental cleaning habits, and lung adenocarcinoma diagnosis are associated with bronchial and lung microbiome alpha diversity.

RATIONALE: The lung microbiome is an inflammatory stimulus whose role in the development of lung malignancies is incompletely understood. We hypothesized that the lung microbiome associates with multiple clinical factors, including the presence of a lung malignancy. OBJECTIVES: To assess associations between the upper and lower airway microbiome and multiple clinical factors including lung malignancy. METHODS: We conducted a prospective cohort study of upper and lower airway microbiome samples from 44 subjects undergoing lung lobectomy for suspected or confirmed lung cancer. Subjects provided oral (2), induced sputum, nasopharyngeal, bronchial, and lung tissue (3) samples. Pathologic diagnosis, age, tobacco use, dental care history, lung function, and inhaled corticosteroid use were associated with upper and lower airway microbiome findings. MEASUREMENTS AND MAIN RESULTS: Older age was associated with greater Simpson diversity in the oral and nasopharyngeal sites (p = 0.022 and p = 0.019, respectively). Current tobacco use was associated with greater lung and bronchus Simpson diversity (p < 0.0001). Self-reported last profession dental cleaning more than 6 months prior (vs. 6 or fewer months prior) was associated with lower lung and bronchus Simpson diversity (p < 0.0001). Diagnosis of a lung adenocarcinoma (vs. other pathologic findings) was associated with lower bronchus and lung Simpson diversity (p = 0.024). Last professional dental cleaning, dichotomized as ≤ 6 months vs. >6 months prior, was associated with clustering among lung samples (p = 0.027, R2 = 0.016). Current tobacco use was associated with greater abundance of pulmonary pathogens Mycoplasmoides and Haemophilus in lower airway samples. Self-reported professional dental cleaning ≤ 6 months prior (vs. >6 months prior) was associated with greater bronchial Actinomyces and lung Streptococcus abundance. Lung adenocarcinoma (vs. no lung adenocarcinoma) was associated with lower Lawsonella abundance in lung samples. Inhaled corticosteroid use was associated with greater abundance of Haemophilus among oral samples and greater Staphylococcus among lung samples. CONCLUSIONS: Current tobacco use, recent dental cleaning, and a diagnosis of adenocarcinoma are associated with lung and bronchial microbiome α-diversity, composition (ß-diversity), and the abundance of several respiratory pathogens. These findings suggest that modifiable habits (tobacco use and dental care) may influence the lower airway microbiome. Larger controlled studies to investigate these potential associations are warranted.

Sputum microbiome α-diversity is a key feature of the COPD frequent exacerbator phenotype.

Background: The lung microbiome is an inflammatory stimulus whose role in COPD pathogenesis is incompletely understood. We hypothesised that the frequent exacerbator phenotype is associated with decreased α-diversity and increased lung inflammation. Our objective was to assess correlations between the frequent exacerbator phenotype, the microbiome and inflammation longitudinally during exacerbation-free periods. Methods: We conducted a case-control longitudinal observational study of the frequent exacerbator phenotype and characteristics of the airway microbiome. 81 subjects (41 frequent and 40 infrequent exacerbators) provided nasal, oral and sputum microbiome samples at two visits over 2-4 months. Exacerbation phenotype, relevant clinical factors and sputum cytokine values were associated with microbiome findings. Results: The frequent exacerbator phenotype was associated with lower sputum microbiome α-diversity (p=0.0031). This decrease in α-diversity among frequent exacerbators was enhanced when the sputum bacterial culture was positive (p<0.001). Older age was associated with decreased sputum microbiome α-diversity (p=0.0030). Between-visit ß-diversity was increased among frequent exacerbators and those who experienced a COPD exacerbation between visits (p=0.025 and p=0.014, respectively). Sputum cytokine values did not differ based on exacerbation phenotype or other clinical characteristics. Interleukin (IL)-17A was negatively associated with α-diversity, while IL-6 and IL-8 were positively associated with α-diversity (p=0.012, p=0.012 and p=0.0496, respectively). IL-22, IL-17A and IL-5 levels were positively associated with Moraxella abundance (p=0.027, p=0.0014 and p=0.0020, respectively). Conclusions: Even during exacerbation-free intervals, the COPD frequent exacerbator phenotype is associated with decreased sputum microbiome α-diversity and increased ß-diversity. Decreased sputum microbiome α-diversity and Moraxella abundance are associated with lung inflammation.