Aerodigestive dysbiosis in children with chronic cough.

In pediatric patients with chronic cough, respiratory culture techniques commonly yield negative results. Studies using culture-independent methods have found a high relative abundance of oral microbes in the lower airways, suggesting that the topographical continuity, and dynamics of the intraluminal contents of the aerodigestive system likely influence the lower airway microbiota. We hypothesize that in subjects with chronic cough, clinical diagnosis will correlate with distinct microbial signatures detected using culture-independent methods. STUDY DESIGN AND METHODS: We enrolled 36 pediatric subjects with chronic cough in a cross-sectional study. Subjects were categorized into four clinical groups: asthma, bacterial bronchitis, neurologically impaired-orally fed, and neurologically impaired enterally fed. Samples from the aerodigestive tract were obtained through bronchoscopy and upper endoscopy. 16S rRNA gene sequencing compared the microbiota from bronchoalveolar lavage (BAL), tracheal, supraglottic, esophageal, gastric, and duodenal samples. RESULTS: We observed that the lower airway microbiota of asthma subjects had higher α diversity as compared with the other groups. ß diversity analysis of BAL samples revealed significant differences between the groups. Among the taxonomic differences found, most differentially enriched taxa were upper airway organisms such as Rothia, Gemellaceae (u.g. or uncharacterized genus), and Granulicatella in asthma, Prevotella in bacterial bronchitis, and Veillonella in neurologically impaired orally fed subjects. Greater dissimilarity between the upper airway and lower airway microbiota was associated with increased neutrophilic airway inflammation. CONCLUSIONS: Distinct dysbiotic signatures can be identified in the lower airway microbiota of pediatric subjects with chronic cough that relates to the degree and type of inflammation.

Lung microbiome and host immune tone in subjects with idiopathic pulmonary fibrosis treated with inhaled interferon-γ.

Therapies targeting inflammation reveal inconsistent results in idiopathic pulmonary fibrosis (IPF). Aerosolised interferon (IFN)-γ has been proposed as a novel therapy. Changes in the host airway microbiome are associated with the inflammatory milieu and may be associated with disease progression. Here, we evaluate whether treatment with aerosolised IFN-γ in IPF impacts either the lower airway microbiome or the host immune phenotype. Patients with IPF who enrolled in an aerosolised IFN-γ trial underwent bronchoscopy at baseline and after 6 months. 16S rRNA sequencing of bronchoalveolar lavage fluid (BALF) was used to evaluate the lung microbiome. Biomarkers were measured by Luminex assay in plasma, BALF and BAL cell supernatant. The compPLS framework was used to evaluate associations between taxa and biomarkers. IFN-γ treatment did not change α or ß diversity of the lung microbiome and few taxonomic changes occurred. While none of the biomarkers changed in plasma, there was an increase in IFN-γ and a decrease in Fit-3 ligand, IFN-α2 and interleukin-5 in BAL cell supernatant, and a decrease in tumour necrosis factor-ß in BALF. Multiple correlations between microbial taxa common to the oral mucosa and host inflammatory biomarkers were found. These data suggest that the lung microbiome is independently associated with the host immune tone and may have a potential mechanistic role in IPF.