The sputum microbiome, airway inflammation, and mortality in chronic obstructive pulmonary disease

Abstract

Microbiome, Airway Inflammation and Mortality in COPD n=253 n=96 n=135Background: The sputum microbiome has a potential role in disease phenotyping and risk stratification in chronic obstructive pulmonary disease (COPD), but few large longitudinal cohort studies exist. Objective: Our aim was to investigate the COPD sputum microbiome and its association with inflammatory phenotypes and mortality. Methods: 16S ribosomal RNA gene sequencing was performed on sputum from 253 clinically stable COPD patients (4-year median follow-up). Samples were classified as Proteobacteria or Firmicutes (phylum level) and Haemophilus or Streptococcus (genus level) dominant. Alpha diversity was measured by using Shannon-Wiener diversity and Berger-Parker dominance indices. Survival was modeled by using Cox proportional hazards regression. A subset of 78 patients had label-free liquid chromatography with tandem mass spectrometry performed, with partial least square discriminant analysis integrating clinical, microbiome, and proteomics data. Results: Proteobacteria dominance and lower diversity was associated with more severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease classification system (P 5 .0015), more frequent exacerbations (P 5 .0042), blood eosinophil level less than or equal to 100 cells/mL (P < .0001), and lower FEV 1 (P 5 .026). Blood eosinophil counts showed a positive relationship with percent of Firmicutes and Streptococcus and a negative association with percent Proteobacteria and Haemophilus. Proteobacteria dominance was associated with increased mortality compared with Firmicutes-dominated or balanced microbiome profiles (hazard ratio 5 2.58; 95% CI 5 1.43-4.66; P 5 .0017 and hazard From a the

A Refined View of Airway Microbiome in Chronic Obstructive Pulmonary Disease at Species and Strain-Levels

“…There was an overall decreased alpha diversity (Shannon index) and non-significantly increased relative abundance of Haemophilus in patients with increased severity measured using both spirometry-based GOLD I-IV and new GOLD A-D classification scheme based on exacerbation frequency, CAT and mMRC scores [ Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2019 ], consistent with previous findings ( Mayhew et al, 2018 ; Dicker et al, 2020 ) ( Supplementary Figures S4A,B ). No species-level taxa reached statistical significance in association with GOLD classification, CAT or mMRC scores (FDR P < 0.05).…”

“…Nevertheless, both our results (increased Ralstonia mannitolilytica in frequent exacerbators) and those of Leitao Filho et al supported the notion that identification of rare opportunistic pathogens may be associated with worse clinical outcome and prognosis of COPD patients. A recent study by Dicker et al showed that Haemophilus dominance at COPD clinical stability was linked to increased severity, frequent exacerbations and increased mortality ( Dicker et al, 2020 ). This is also consistent with our finding that increased relative abundance of Haemophilus , in particular H. influenzae species, was observed in patients with enhanced GOLD status.…”

Chronic infection by nontypeable Haemophilus influenzae fuels airway inflammation

“…It has been reported that the presence of NTHi can be associated with acute exacerbation episodes in CF [15]. Similar observations have been made in COPD patients, although in this case the NTHi infection was also associated with a worse clinical prognosis [16,17]. However, there are no observations on the effect of chronic NTHi infection in the progression of CF chronic airway disease, due to the presence of several clinical and microbiological cofounding factors, such as concomitant infections [15,19] and lack of available human cohorts.…”

The airway microbiome in COPD, bronchiectasis and bronchiectasis‐COPD overlap

“…45 Increased abundance of Haemophilus, Moraxella and Pseudomonas are described in COPD FE while non-FEs appear to associate with increased Actinomyces. 12,14,17,46 The stability of the COPD microbiome through longitudinal assessment remains inconsistent, with high variability reported in the AERIS study as compared to COPDMAP which found lower variability of beta-diversity in FE. 14,20 During AECOPD, a decreased alpha diversity associates with higher mortality and abundance of Staphylococcus, however, an absence of Veillonella is also a poor prognostic indicator.…”

“…13 In addition, diversity is further reduced as disease progresses, and is also reported during acute exacerbations (AECOPD). [13][14][15][16][17] The dominant microbial phyla in stable COPD include Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria while predominant genera include Haemophilus, Moraxella, Streptococcus, Veillonella, Pseudomonas and Prevotella. 2,16,18 Important microbial alteration occurs with COPD treatments, including during and following AECOPD.…”