Sputum microbiota and inflammation at stable state and during exacerbations in a cohort of chronic obstructive pulmonary disease (COPD) patients

Abstract

BackgroundExacerbations of chronic obstructive pulmonary disease (COPD) are debilitating events and spur disease progression. Infectious causes are frequent; however, it is unknown to what extent exacerbations are caused by larger shifts in the airways’ microbiota. The aim of the current study was to analyse the changes in microbial composition between stable state and during exacerbations, and the corresponding immune response.MethodsThe study sample included 36 COPD patients examined at stable state and exacerbation from the Bergen COPD Cohort and Exacerbations studies, and one patient who delivered sputum on 13 different occasions during the three-year study period. A physician examined the patients at all time points, and sputum induction was performed by stringent protocol. Only induced sputum samples were used in the current study, not spontaneously expectorated sputum. Sputum inflammatory markers (IL-6, IL-8, IL-18, IP-10, MIG, TNF-α) and antimicrobial peptides (AMPs, i.e. LL-37/hCAP-18, SLPI) were measured in supernatants, whereas target gene sequencing (16S rRNA) was performed on corresponding cell pellets. The microbiome bioinformatics platform QIIME2TM and the statistics environment R were applied for bioinformatics analyses.ResultsLevels of IP-10, MIG, TNF-α and AMPs were significantly different between the two disease states. Of 36 sample pairs, 24 had significant differences in the 12 most abundant genera between disease states. The diversity was significantly different in several individuals, but not when data was analysed on a group level. The one patient case study showed longitudinal dynamics in microbiota unrelated to disease state.ConclusionChanges in the sputum microbiota with changing COPD disease states are common, and are accompanied by changes in inflammatory markers. However, the changes are highly individual and heterogeneous events.

Lung Microbiome Participation in Local Immune Response Regulation in Respiratory Diseases

“…The main bacteria implicated are Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis [62]. During the stable phase, longitudinal studies have identified a decrease in bacterial diversity and alteration in the systemic inflammatory response in pathways dependent on the bacterial response, such as TNF-α, IP-10, and MIG [63]. The use of antibiotics, such as azithromycin, usually used in COPD therapy to decrease the number of exacerbations, generates a decrease in bacterial diversity and an increase in microbial metabolites (glycolic acid, linoleic acid, and indole-3-acetate), resulting in altered expression of cytokines that regulate the immune response, such as IL-12, IL-13, CXCL-1, and TNF-α [40,45,64].…”

Compare the Effect of Inhaled Corticosteroids and Systemic Corticosteroids on Sputum Microbiome of AECOPD

“…One-year treatment with ICS increases the total bacterial load in the sputum of COPD patients and changes the microbiome composition (13). Local inflammation in AECOPD is related to changes in the microbiota, characterized by reduced microbial diversity (14,15). Treatment with SCS alone decreased microbial alpha diversity in AECOPD (1).…”

The airway microbiota and exacerbations of COPD

“…Some previous studies comparing sputum microbiota between stable and exacerbated state in COPD indicate there are differences between disease states, but the findings are inconsistent [ 7 – 12 ]. And, two previous retrospective studies indicated that the sputum microbiota in the stable state was different in patients prone to exacerbations compared to patients who do not exacerbate [ 13 , 14 ].…”