Midtveisevaluering - -Elise Orvedal Leiten

The airway microbiome of stable COPD: Association to exacerbation frequency and the risks associated with bronchoscopic data collection

Abstract

Acute exacerbations of COPD are an important cause of mortality and morbidity in patients with COPD. It is incompletely understood why some COPD patients experience frequent exacerbations, while others rarely or never exacerbate. Studies have suggested that the microbiome of the lungs is different in patients with different exacerbation frequencies. Most studies use sputum samples prone to contamination from the upper airway. Bronchoscopic sampling could improve the quality of the samples, but is a more invasive approach. The overall aim of the PhD project is to investigate if the airway microbiome in subjects with stable COPD is associated with exacerbation frequency and to assess the complications and discomforts associated with bronchoscopic data collection. This project is a part of the larger Bergen COPD Microbiome Study (MicroCOPD), and consists of three studies.

Study I is a systematic literature review of the complications and discomfort of bronchoscopy. Bronchoscopy is generally a safe procedure with low mortality and few severe complications, but the literature shows a wide range of specific complication rates, and it was not possible to conclude on discomfort or predictors.

Study II is a prospective study of the immediate complications and discomforts associated with bronchoscopy in subjects with COPD, asthma and without lung disease in MicroCOPD. Complications were directly observed during the procedure or in the two-hour observation period, and participants were asked about discomforts and post-procedural fever one week after bronchoscopy. A complication, defined as an unplanned intervention or early termination of bronchoscopy, occurred in 25.9% of bronchoscopies. The rate of potentially severe complications was 1.3%. COPD subjects experienced more dyspnoea than participants without lung disease. Sedation and lower age were associated with less complications. 47.7% reported fever. Discomfort was associated with fever, dread of bronchoscopy, high COPD Assessment Test score, and never-smoking. Complications and fever in a first bronchoscopy were often predictive for complications and fever in a second bronchoscopy.

Study III presents a cross-sectional microbiome study with 1-year prospective follow-up of COPD exacerbations within MicroCOPD. 16S RNA sequencing was performed, and sequences went through extensive pre-processing including identification and removal of contaminants before taxonomic assignment, differential abundance testing and diversity analyses. We found no association between the lung microbiome at stable state and exacerbations of COPD.