Bacterial burden in the lower airways predicts disease progression in idiopathic pulmonary fibrosis and is independent of radiological disease extent

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 (HR 2.1; 95% CI 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.

Making the case for causality: what role do lung microbiota play in idiopathic pulmonary fibrosis?

“…The correlative significance of the lung microbiome in IPF is now inarguable: lung bacteria correlate with disease status, host genotype, and the alveolar and systemic host response. The current study by INVERNIZZI et al [19] definitively confirms the lung microbiome's prognostic significance: lung microbiota predict disease progression in IPF, independent of radiographic severity. Yet the causal significance of the lung microbiome in IPF, and its status as a therapeutic target, remains a crucial area of ongoing study, requiring both interventional human studies and translational animal modelling.…”

“…An entire kingdom of the tree of life, previously ignored in IPF research, is now a major focus of clinical and experimental study. We have much work left to do, but the current study by INVERNIZZI et al [19] gives us reason to hope that we are on the path towards making a case for causality.…”

“…This core question was the rationale behind an important new study by INVERNIZZI et al [19] in this issue of the European Respiratory Journal. The authors studied a large cohort of patients with IPF who underwent both research bronchoscopy and quantitative interpretations of chest computed tomography (CT) scans.…”

“…Regarding the first embedded claim (the lung microbiome can be altered by interventions), it is now well-established that the community composition of lung bacteria is altered by antibiotics, both in animal models [24] and in human lung conditions other than IPF [25][26][27]. Yet it is unestablished if lung bacterial burden (the most consistently prognostic feature of the lung microbiome in IPF [11,13,19] and other conditions [20,21]) can be altered by antibiotics. In two studies of chronic macrolide therapy (in COPD patients [27] and lung transplant recipients [28]), chronic azithromycin had no effect on lung bacterial burden: the communities changed, but the total bacterial load was unaltered.…”

Lung Microbiome Differentially Impacts Survival of Patients with Non-Small Cell Lung Cancer Depending on Tumor Stroma Phenotype

“…Further in our study, we carried out a quantitative analysis of the general bacterial load in the studied samples to assess its correlations with clinical characteristics. It is known from the literature that an increased bacterial load can be a poor prognostic marker for idiopathic pulmonary fibrosis [35], or contributes to the formation of lung tumors in vivo [36]. On the other hand, it is already known that the use of antibiotics prior to immunotherapy with checkpoint inhibitors significantly reduces the effectiveness of the antitumor treatment of NSCLC [37].…”