Bacterial burden in the lower airways predicts disease progression in idiopathic pulmonary fibrosis and is independent of radiological disease extent
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Published version
Author(s)
Type
Journal Article
Abstract
Increasing bacterial burden in the lower airways of patients with idiopathic pulmonary fibrosis confers an increased risk of disease progression and mortality. However, it remains unclear whether this increased bacterial burden directly influences progression of fibrosis or simply reflects the magnitude of the underlying disease extent or severity.
We prospectively recruited 193 patients who underwent bronchoscopy and received a multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Quantification of the total bacterial burden in bronchoalveolar lavage fluid was performed by 16S rRNA gene qPCR. Imaging was independently evaluated by two readers assigning quantitative scores for extent, severity and topography of radiographic changes and relationship of these features with bacterial burden was assessed.
Increased bacterial burden significantly associated with disease progression (hazard ratio 2.1; 95% confidence interval 1.287–3.474; p=0.0028). Multivariate stepwise regression demonstrated no relationship between bacterial burden and radiological features or extent of disease. When specifically considering patients with definite or probable usual interstitial pneumonia there was no difference in bacterial burden between these two groups. Despite a postulated association between pleuroparenchymal fibroelastosis and clinical infection, there was no relationship between either the presence or extent of pleuroparenchymal fibroelastosis and bacterial burden.
We demonstrate that bacterial burden in the lower airways is not simply secondary to the extent of the underlying architectural destruction of the lung parenchyma seen in idiopathic pulmonary fibrosis. The independent nature of this association supports a relationship with the underlying pathogenic mechanisms and highlights the urgent need for functional studies.
We prospectively recruited 193 patients who underwent bronchoscopy and received a multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Quantification of the total bacterial burden in bronchoalveolar lavage fluid was performed by 16S rRNA gene qPCR. Imaging was independently evaluated by two readers assigning quantitative scores for extent, severity and topography of radiographic changes and relationship of these features with bacterial burden was assessed.
Increased bacterial burden significantly associated with disease progression (hazard ratio 2.1; 95% confidence interval 1.287–3.474; p=0.0028). Multivariate stepwise regression demonstrated no relationship between bacterial burden and radiological features or extent of disease. When specifically considering patients with definite or probable usual interstitial pneumonia there was no difference in bacterial burden between these two groups. Despite a postulated association between pleuroparenchymal fibroelastosis and clinical infection, there was no relationship between either the presence or extent of pleuroparenchymal fibroelastosis and bacterial burden.
We demonstrate that bacterial burden in the lower airways is not simply secondary to the extent of the underlying architectural destruction of the lung parenchyma seen in idiopathic pulmonary fibrosis. The independent nature of this association supports a relationship with the underlying pathogenic mechanisms and highlights the urgent need for functional studies.
Date Issued
2020-04-03
Date Acceptance
2019-12-29
Citation
European Respiratory Journal, 2020, 55 (4), pp.1-9
ISSN
0903-1936
Publisher
European Respiratory Society
Start Page
1
End Page
9
Journal / Book Title
European Respiratory Journal
Volume
55
Issue
4
Copyright Statement
©ERS 2020 http://creativecommons.org/licenses/by/4.0/
This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
Sponsor
Action for Pulmonary Fibrosis
British Lung Foundation
Wellcome Trust
National Institute for Health Research
British Lung Foundation
Wellcome Trust
Identifier
https://erj.ersjournals.com/content/55/4/1901519
Grant Number
n/a
BLF-RMF 15-16
107059/Z/15/Z
CS-2013-13-017
C17-3
205949/Z/17/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Respiratory System
PLEUROPARENCHYMAL FIBROELASTOSIS
PROMOTER POLYMORPHISM
SYSTEMIC-SCLEROSIS
MICROBIOME
EXACERBATION
PATHOGENESIS
MUC5B
Respiratory System
11 Medical and Health Sciences
Publication Status
Published
Date Publish Online
2020-04-03