PT - JOURNAL ARTICLE AU - Scott Tebbutt AU - Sarah Kam AU - Amrit Singh AU - Louis-Philippe Boulet AU - Mark FitzGerald AU - Gail Gauvreau AU - Paul O'Byrne TI - Late-breaking abstract: Changes in cortisol levels in the plasma of asthmatic individuals undergoing allergen inhalation challenge differentiate isolated early from dual responders DP - 2011 Sep 01 TA - European Respiratory Journal PG - 3408 VI - 38 IP - Suppl 55 4099 - http://erj.ersjournals.com/content/38/Suppl_55/3408.short 4100 - http://erj.ersjournals.com/content/38/Suppl_55/3408.full SO - Eur Respir J2011 Sep 01; 38 AB - Allergen inhalation challenge in mild asthmatic subjects induces airflow obstruction, airway hyperresponsiveness and inflammation, and provides a model for hypothesis-generating experiments to understand molecular regulation of these responses. Adult asthmatic subjects (18-55 years of age, with stable, mild allergic asthma, n=14) underwent cat allergen inhalation challenges. All subjects had an early asthmatic response of ≥20% fall in FEV1, and six individuals also had a late phase response of ≥15% fall in FEV1 (dual responders). Blood samples were collected just prior to, and two hours after allergen challenge. We have evaluated the differential changes in genome-wide gene expression in peripheral blood cells and changes in the plasma metabolome, post-challenge compared to pre-challenge. Amongst other findings, we have demonstrated significantly reduced cortisol levels in the plasma of mild asthmatic subjects post-challenge, compared to pre-challenge (p=0.013). Importantly, this reduction in plasma cortisol was only significant in subjects who had an isolated early asthmatic reaction, rather than in subjects who also went on to develop a late phase asthmatic reaction. Interestingly, this is consistent with gene expression data demonstrating that in isolated early responders only, there is a significant increase in RNA transcript levels for the hydroxysteroid (11-beta) dehydrogenase 2 gene (HSD11B2), post-challenge compared to pre- (p=0.026). The HSD11B2 enzyme converts cortisol to inactive cortisone. Thus, allergen inhalation challenge may improve understanding of pathways and underlying genes associated with asthma.