Non Type-2 Severe Asthma Has Increased Bronchoalveolar Mast Cell Mediator Release and Health Care Utilization

Rationale: Severe asthma (SA) involves multiple cells. We reported increased epithelial and luminal mast cells (MCs) in severe vs. milder asthma. In response to anti-human IgE, bronchoalveolar lavage (BAL) MCs degranulate and generate eicosanoids. (Flint, 1985; Pearce, 1987) However, functional responses of SA MCs in relation to “Type-2” inflammation have not been explored. We hypothesized that Type-2-high-SA BAL MCs would have increased response to stimulation vs. non-Type-2-SA and greater healthcare utilization. 

Methods: BAL cells from 57 SA (39 on systemic corticosteroids (sCS)) from the Severe Asthma Research Program were analyzed for tryptase mRNA by qPCR. In a subset (n=28), BAL cells in media were stimulated with anti-human IgE (Dako) for 20 minutes. Supernatant PGD2 and tryptase were measured by enzyme immunoassay. Type-2 inflammation was grouped by peripheral blood eosinophilia (≥300/milliliter) and analyzed in relation to health care utilization. Data were analyzed parametrically.

Results: BAL cell tryptase mRNA was increased in Type-2-high vs. non-Type-2-SA (p=0.008). Following anti-IgE stimulation, Type-2-high released less tryptase/mRNA and generated less PGD2/mRNA than non-Type-2-SA [Mean fold change/tryptase mRNA (tryptase:0.07 vs. 0.95, p=0.003); (PGD2:0.04 vs.0.54, p=0.003). Compared to Type-2-high-SA, non-Type-2-SA were more likely to be on sCS and had more hospitalizations/urgent care visits in the past year (p=0.003, p=0.02, p=0.03, respectively). They tended to have lower FEV1%predicted (p=0.15).

Conclusions: Although Type-2-high-SA had more baseline tryptase mRNA, BAL MC tryptase and PDG2 increases following stimulation were significantly greater in non-Type-2-SA, associated with greater health care utilization. Although sCS use may have decreased total MC numbers (non-Type-2), the remaining MCs may be more active.