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Airway Mast Cells on a Type-2 Inflammatory Background Confer a More Clinically Severe Asthma Phenotype Than Isolated Type-2 Inflammation
Sunday, March 5, 2017: 2:00 PM
Rooms B303-B304 (Georgia World Congress Center, Building B)
Merritt L. Fajt, MD FAAAAI, , ,
Rationale: Both mast cells (MC) and Type-2 (T2) inflammation have been implicated in asthma pathogenesis. We hypothesized that the presence of airway luminal MCs on a background Type-2 inflammatory process would confer a more clinically severe asthma phenotype than either biomarker alone.

Methods: Bronchoalveolar lavage (BAL) cells from 100 University of Pittsburgh asthmatics in NHLBI trials were analyzed for tryptase mRNA by qPCR and BAL fluid for prostaglandin D2 (PGD2) by ELISA. Subjects were divided into MC and T2 Hi or Lo by BAL cell tryptase median split and peripheral blood eosinophilia (≥300/microliter)  to develop  MCHi/T2Hi, MCHi/T2Lo, MCLo/T2Hi and MCLo/T2Lo quadrants. Their relation to BAL fluid PGD2, lung function, and health care utilization was  analyzed.

Results: BAL fluid PGD2 was highest in the MCHi/T2Hi quadrant  (overall p=0.0036) and significantly higher than in the MCLo/T2Hi  and MCLo/T2Lo quadrants. The MCHi/T2Hi  asthmatics had the lowest FEV1%p (overall p=0.03). The MCLo/T2Lo quadrant had significantly higher FEV1%p than the MCHi/T2Hi and MCHi/T2Lo quadrants. The MCHi/T2Hi quadrant had the most asthma exacerbations in the previous year (overall p=0.003), with significantly more exacerbations than in both the MCLo/T2HI and MCLo/T2Lo  quadrants.   Of note, tryptase mRNA was higher in the MCHi/T2Hi quadrant than in the MCHi/T2Lo quadrant.

Conclusions: In this population, evidence for an active airway MC population in addition to Type-2 (eosinophilic) inflammation identified patients with more severe disease than those with evidence for Type-2 inflammation alone. Non-invasive MC biomarkers, in combination with T2 biomarkers could identify a population at greater risk than those identified by T2 biomarkers alone.