Glucocorticoids suppress goblet cell metaplasia in natural and experimental asthma

Abstract

Rationale To determine targets of glucocorticoid treatment in asthma, we examined goblet cell metaplasia and airway hyperreactivity in natural asthma and a mouse model of asthma. Methods For human studies, normal and asthmatic subjects were studied after treatment with fluticasone propionate (FP; 1760 μg/d) for 30 d and then after withdrawal of FP until peak flows decreased by 25%, FEV1 decreased by 15%, or 6 wk elapsed. To control for asthma triggers, genetic background, and treatment (e.g. β2-adrenergic receptor agonists), we studied a mouse model of persistent, asthma-like phenotypes induced by transient paramyxoviral infection (J. Clin. Invest. 110:165-175, 2002). Mice were treated with systemic dexamethasone (DEX), inhaled FP, or inhaled salmeterol xinafoate (SLM). Results In human studies, the group of asthmatic subjects exhibited decreased methacholine PC20 (by 1.2-fold) and increased numbers of endobronchial goblet cells (by 64%) after withdrawal of FP treatment, but the two parameters showed no correlation within individual subjects. In the murine model, systemic DEX or inhaled FP caused little change in airway reactivity, but each agent suppressed goblet cell metaplasia (by 86 and 68%, respectively). Addition of inhaled SLM to FP (or SLM alone) had no significant effect on either asthma-like phenotype. Conclusions Glucocorticoid treatment is sufficient to suppress goblet cell metaplasia but not necessarily airway hyperreactivity in natural and experimental asthma. The effect of glucocorticoids on mucus-producing cells may provide a therapeutic benefit in asthma and other hypersecretory states.