Anti-DP effects on airway bacterial load in a phase 2a trial

Abstract

Background: Inflammatory phenotypes in asthma display distinct ecological profiles. Interactions between colonising organisms and inflammatory pathways in the airway are complex and bidirectional, with the specific effects of interventions targeting these poorly understood. Objective: We sought to determine the impact of anti-DP2 antagonism on total and specific sputum bacterial loads. Methods: Sputum supernatant and sputum plugs obtained pre and post-treatment from a previously reported 12 week phase 2a trial of a DP2 antagonist (NCT0154572) underwent quantitative polymerase chain reaction to quantify total 16S, Haemophilus Influenzae (HI) and Streptococcus Pneumoniae (SP). Results: Paired sputum supernatants and plugs were available for 32 and 14 subjects respectively. In the sputum supernatants there was no significant change in total 16S (copies/ml x 107) in those receiving anti-DP2 (ratio post- to pre-treatment 0.60, 95% CI 0.05 to 7.50, p=0.675) or placebo (1.96, 0.10 to 39.04, p=0.634) and no difference between groups (p=0.521). Additionally, there was no significant change within or between groups in the amount of HI or SP. In the sputum plugs there was no significant change in the total or SP bacterial load, but we did observe a reduction in HI following treatment with anti-DP2 (p=0.018). This change was significant compared to placebo (p=0.007). Conclusion: Anti-DP2 did not affect sputum bacterial load. In response to anti-DP2 there was a small reduction in the amount of HI in those subjects that produced adequate sputum plugs. Further longitudinal studies of asthma are required to understand the relationship between airway inflammation and the microbiome, and the effects of interventions.