Interleukin-4Ralpha Blockade by Dupilumab Decreases Staphylococcus Aureus Colonization and Increases Microbial Diversity in Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP)
University of Virginia
Summary
Hypothesis: The investigators hypothesize that in patients with CRSwNP who demonstrate sinus colonization with staphylococcus aureus, the administration of dupilumab will be associated with decreased staph colonization and an increase in microbial diversity. Primary Objective will be to demonstrate that dupilumab reduces staphylococcus aureus (phyla firmicutes) abundance while increasing microbial diversity in patients with CRSwNPs who are culture positive for staph aureus at enrollment. Secondary Objectives will be to correlate reduction in Staph aureus abundance and improved bacterial diversity with increased expression of anti-microbial proteins (ß-defensins1-4) and cathelicidin LL-37. In addition, the investigators will correlate improvements in microbial diversity/decreased staph abundance with clinical improvements as assessed via questionnaires and objective/subjective smell function and also as improvements in cellular/immune T2 inflammation as assessed by reduced expression of T2 cytokines/chemokines and eosinophil/eosinophil-derived proteins.
Description
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an important clinical problem and is associated with profound unmet medical needs given the absence - until recently - of adequate medical therapies. It has an estimated prevalence of 2-4% in the USA and Europe but also has disproportionate burden on quality of life and economic burden. CRSwNPs is predominantly (in 62-85% of patients) a type 2 (T2) disease, as demonstrated by an IL-4high, IL-5high, IL-13high cytokine signature and prominent infiltration with eosinophils, basophils, and newly recruited mast cells. Another characteristic f…