Sputum microbiota and inflammation at stable state and during exacerbations in a cohort of chronic obstructive pulmonary disease (COPD) patients.
Tangedal. Solveig S; Nielsen. Rune R; Aanerud. Marianne M; Persson. Louise J LJ; Wiker. Harald G HG; Bakke. Per S PS; Hiemstra. Pieter S PS; Eagan. Tomas M TM
Key Findings
- LL‑37 levels in sputum differ significantly between stable COPD and exacerbation states.
- The composition of lung microbiota changes in many individuals during exacerbations, but these changes are highly individual and not uniform across the cohort.
- Inflammatory markers (IP‑10, MIG, TNF‑α) also vary between stable and exacerbation phases, reflecting an immune response.
Practical Outcomes
- For self‑experimenters, the findings are mainly observational and do not provide actionable steps for using LL‑37 or modifying lung microbiota. The study highlights that COPD flare‑ups involve personal shifts in bacteria and immune proteins, but it offers no clear protocol or dosage guidance for health optimization.
Summary
This study looked at people with COPD and measured how the bacteria in their lungs and certain immune proteins, including the antimicrobial peptide LL‑37, change when they are stable versus when they have a flare‑up. They found that both the bacterial mix and levels of LL‑37 and other inflammation markers shift during flare‑ups, but the patterns are highly personal and not consistent across the group.
Abstract
Exacerbations 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. The 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. Levels 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. Changes 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.
Study Information
pubmed
2019
2019-09-17T00:00:00.000Z
10.1371/journal.pone.0222449
33
37