LSC Abstract – Changes in the respiratory microbiome during acute exacerbations of Idiopathic Pulmonary Fibrosis

Abstract

Introduction: The diagnosis of an acute exacerbation of IPF (AE-IPF) requires the exclusion of infective triggers, suggesting infection plays no role in the pathogenesis of these events. Following the recent characterisation of the respiratory microbiome in IPF this study aimed to assess for changes in the respiratory microbiome during an AE-IPF. Methods: Eighteen patients with AE-IPF and 14 stable IPF patients undergoing bronchoscopy were enrolled at the University of Ulsan, Korea. Patients had a negative lavage bacterial culture and respiratory virus screen. Bacterial DNA was extracted and a hyper-variable region of the 16S ribosomal RNA gene (16S rRNA) amplified, quantified and pyrosequenced. Results: Subjects had a mean age of 66 years and on average mild disease (DLco 68±13% predicted; FVC 78±16% predicted). AE-IPF subjects had on average 1.4x10 9 copies of the 16S rRNA gene per ml of BAL, more than four times higher than stable IPF subjects (3.1x10 8 ) ( P =0.012). The microbiota of the stable Korean IPF subjects is dominated by Firmicutes (34%), Proteobacteria (32%) and Bacteroidetes (16%). The same phyla predominate in the AE-IPF subjects, but proteobacteria account for over 40% of the total reads, with a higher relative abundance of two potentially pathogenic OTUs. Within paired samples there were clear changes in an individual9s microbiota during an exacerbation. Conclusions: AE-IPF is associated with an increased BAL bacterial burden compared to stable disease. There are detectable changes in the composition of the respiratory microbiome during an AE-IPF, an event that current guidelines would lead us to believe is non-infective.