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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Rachele Invernizzi has nothing to disclose.
Conflict of interest: Dr Joseph Barnett has nothing to disclose.
Conflict of interest: Bhavin Rawal has nothing to disclose.
Conflict of interest: Poonam Ghai has nothing to disclose.
Conflict of interest: Dr Shaun Kingston has nothing to disclose.
Conflict of interest: Dr Felix Chua has nothing to disclose.
Conflict of interest: Zhe Wu has nothing to disclose.
Conflict of interest: Prof. Athol Wells reports speakers and consultancy fees from Intermune Roche, Boehringer ingelheim and Bayer.
Conflict of interest: Dr Elizabeth Renzoni has received speakers fees from BI, Roche and Mundipharma.
Conflict of interest: Prof. Andrew Nicholson reports personal fees from MEDICAL QUANTITATIVE IMAGE ANALYSIS, personal fees from BOEHRINGER INGELHEIM, personal fees from ROCHE, personal fees from SANOFI, outside the submitted work.
Conflict of interest: Dr Alexandra Rice reports Shareholder in Pfizer.
Conflict of interest: Prof. Clare Lloyd has nothing to disclose.
Conflict of interest: Dr Adam Byrne has nothing to disclose.
Conflict of interest: Prof. Toby Maher has, via his institution, received industry-academic funding from GlaxoSmithKline R&D and UCB and has received consultancy or speakers fees from Apellis, Astra Zeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline R&D, Indalo, Novartis, Pliant, ProMetic, Respivnat, Roche, Samumed and UCB.
Conflict of interest: Dr Anand Devaraj reports personal fees from GSK, personal fees from Roche, personal fees from boehringer ingelheim, outside the submitted work.
Conflict of interest: Dr Philip Molyneaux has, via his institution, received industry-academic funding from Roche, Boehringer Ingelheim and Galapagos and has received speakers fees from Roche.
Conflict of interest: Dr Arjun Nair has nothing to disclose.
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- Received August 1, 2019.
- Accepted December 29, 2019.
- Copyright ©ERS 2020
