Lung immune challenge study protocol: controlled exposure to inhaled resiquimod (R848) to study mechanisms of inflammation

Abstract

This study aims to develop a human lung immune challenge model using inhaled Resiquimod (R848), a Toll-like receptor 7/8 agonist, to investigate inflammatory mechanisms involved in the human respiratory mucosa in health and disease. This approach seeks to induce innate immune anti-viral responses in the lungs and blood, with a suitable dose of inhaled R848 that is clinically tolerable. The study will include healthy volunteers and individuals with asthma. The primary outcome is a change in CXCL10, a biomarker representative of anti-viral responses, at 24 hours post-exposure. Secondary outcomes include changes in lung function, physiological parameters, and inflammatory markers, including C-reactive protein and eosinophil counts. This trial involves a single ascending dose, randomized, single-blind, placebo-controlled design. Participants will receive R848 via nebulization in escalating doses from 0.1 to 100 µg/ml or saline placebo. Safety assessments include spirometry, vital signs, and blood samples to monitor systemic and lung-specific immune responses. The study will contribute to understanding immune pathways in asthma and provide a platform for testing novel anti-inflammatory therapeutics. The protocol has been approved by relevant ethics committees and will be disseminated via peer-reviewed publications and open-access data repositories.