Bacterial load is associated with neutrophilic sputum in severe asthmatics

Abstract

Background: Asthma is a heterogeneous disease. A sputum neutrophilia is observed in approximately 30% of severe asthmatics, but its aetiology remains unclear. Aims and Objectives: We aimed to determine in sputum samples whether bacterial colonisation and transcriptomic profiles consistent with infection are more common in neutrophilic asthma (≥61% neutrophils). Methods: Subjects with severe asthma were recruited from a single centre and underwent detailed clinical characterisation. Bacterial load determined by16S ribosomal (r)RNA by qPCR was assessed in 123 stable samples from 80 asthmatics. In an independent group of asthmatics (n=46) and healthy controls (n=6) the sputum transcriptome was analysed using a whole genome array. Differential gene expression (>2-fold and p Results: Bacterial load was increased in neutrophilic versus non-neutrophilic asthma (16SrRNA 4.2x109 versus 2.1x109; p=0.041). The sputum neutrophil count was associated with log 16S rRNA (β=0.011 [SE=0.004], p=0.008) using a mixed effect model. The number of differentially expressed genes between neutrophilic and non-neutrophilic asthma or healthy controls was 479 and 321 respectively. Of these the commonest gene function was infectious disease with the proportion of differentially expressed genes up-regulated in neutrophilic versus non-neutrophilic asthma (82%; p Conclusions: Neutrophilic asthma is associated with increased bacterial colonisation and sputum gene expression consistent with persistent infection.