The effect of inhaled corticosteroid therapy on airway mucosal inflammation was investigated in 10 symptomatic atopic asthmatic patients treated with inhaled albuterol and whose disease severity required preventative antiinflammatory treatment. Endobronchial biopsies were obtained by fiberoptic bronchoscopy before and after 6 wk of therapy with inhaled beclomethasone dipropionate (2,000 µg/day for 2 wk followed by 1,000 µg/day for 4 wk). Following treatment, there was a significant increase in mean morning peak expiratory flow (p < 0.05) and baseline FEV₁ measured on the day of methacholine challenge (p < 0.05) and a decrease in asthma symptoms (p < 0.01), peak expiratory flow variation (p < 0.05), and albuterol usage (p < 0.05). This was accompanied by a sevenfold decrease in airway responsiveness (p = 0.001). The clinical improvement in asthma was associated with a significant (p < 0.05) reduction in epithelial and mucosal mast cells and eosinophils and submucosal T lymphocytes, but electron microscopy did not identify any changes in the extent of mast cell and eosinophil degranulation following treatment. Because of the association between the decrease in inflammatory cell numbers and the improvement in all the measured clinical and physiologic indices of asthma, we suggest that the beneficial effect of inhaled corticosteroids in asthma may be attributed to their antiinflammatory action in the bronchial mucosa.

Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear. We performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients. Sixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed. Significant heterogeneity of T-cell phenotypes was observed, with levels of IL-13-secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and γδ-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine-high) and nonatopic forms. The evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies.