P144 Changes in the lung microbiota in response to IV therapy for pulmonary exacerbations and relation to clinical outcomes

Abstract

Objectives: To determine how changes in the lung microbiota relate to response to IV antibiotics (IV abs) for pulmonary exacerbations (PEx) and to later clinical outcomes. Methods: A single centre observational study assessed response to IV abs on day 0, day 5 and end of treatment (EOT) using clinical (ppFEV1, 24hr sputum volume), inflammatory (CRP) and symptom measures (CFRSD-CRISS). The relationship between these outcomes and ecological parameters defining the airway microbiota (taxonomic richness, Shannon diversity, evenness, dominance, relative abundance [RA]) were determined using Spearman's rank correlation (r) and Survival analysis. Results: 31 participants (13M:18F), mean(SD), age 30(7)yrs and mean ppFEV1 61(25)% were enrolled. Significant individual variation, both positive and negative, in bacterial RA was observed between day 0, 5 and EOT (p < 0.03). Diversity (r = 0.51;p = 0.003), RA of Staphylococcus spp. (r = 0.41;p = 0.04) and Fusobacterium (r = 0.40;p = 0.04) correlated positively and dominance negatively with CRP (r = −0.57;p = 0.002). RA of Staphylococcus (r = 0.54;p = 0.03) and Burkholderia spp. (r = 0.42;p = 0.08) correlated positively with 24hr sputum volume. No correlation with CFRSD-CRISS was seen. Richness, diversity, RA of Haemophilus and Veillonella spp. correlated positively (r ≥ 0.40;p < 0.05), dominance correlated negatively (r = −0.43; p = 0.01) with ppFEV1. Richness (83 vs 179 days (HR = 0.27;p = 0.006), diversity (81 vs 179 days (HR = 0.26;p = 0.0006) and RA of Staphylococcus spp. (65 vs 166 days (HR = 0.17;p = 0.0006) below linear regression defined cut offs (y), plus dominance ≥y (84 vs 176 days (HR = 3.47;p = 0.0013) all associated with significantly longer time to next exacerbation (TUNE). Conclusion: Significant individual variation in bacterial RA aids understanding of individual PEx response. Ecological microbiota parameters relate to clinical outcomes, including TUNE. In future, microbiota analysis may assist in guiding treatment for PEx as part of multi-dimensional assessment.