Innate and adaptive immune cells are increased in the airways associated with allergic asthmatic responses. Total and type 2 cytokine-positive ILC2 are increased only within the airways, whereas CD4 T lymphocytes demonstrated local and systemic increases. Steroid sensitivity of both cells may explain effectiveness of this therapy in those with mild asthma.

Environmental allergens are an important cause of asthma and can contribute to loss of asthma control and exacerbations. Allergen inhalation challenge has been a useful clinical model to examine the mechanisms of allergen-induced airway responses and inflammation. Allergen bronchoconstrictor responses are the early response, which reaches a maximum within 30 min and resolves by 1-3 h, and late responses, when bronchoconstriction recurs after 3-4 h and reaches a maximum over 6-12 h. Late responses are followed by an increase in airway hyperresponsiveness. These responses occur when IgE on mast cells is cross-linked by an allergen, causing degranulation and the release of histamine, neutral proteases and chemotactic factors, and the production of newly formed mediators, such as cysteinyl leukotrienes and prostaglandin D 2 . Allergen-induced airway inflammation consists of an increase in airway eosinophils, basophils and, less consistently, neutrophils. These responses are mediated by the trafficking and activation of myeloid dendritic cells into the airways, probably as a result of the release of epithelial cell-derived thymic stromal lymphopoietin, and the release of pro-inflammatory cytokines from type 2 helper T-cells. Allergen inhalation challenge has also been a widely used model to study potential new therapies for asthma and has an excellent negative predictive value for this purpose. @ERSpublications Environmental allergens are an important cause of asthma

Asthma is characterized by discordant responses among cells of the adaptive and innate immune systems. This interplay involves a complex pattern of cytokine-driven processes resulting in cell migration and recruitment, inflammation, and proliferative states. The significant majority of asthmatic patients respond well to conventional inhaled treatments. However, about 5% of asthmatics have severe refractory asthma and account for 50% of the health expenditure on asthma. Human(ized) monoclonal antibodies (hMabs) targeting inflammatory pathways are promising therapeutic agents in asthma management. The anti-IgE hMab omalizumab was the first biologic treatment approved for the treatment of allergic asthma. Potential future strategies and targets include interleukin (IL)-5, IL-4, and IL-13, anti-TSLP, IL-25, and IL-33. hMabs targeting IL-5 have shown great promise in severe refractory asthma with a persisting eosinophilia, and clinical trials with hMabs against IL-13 and IL4Rα have also shown clinical benefit. Studies of hMabs against other cytokines in severe asthma are under way.

Glucagon-like peptide-1 receptor is expressed on human eosinophils and neutrophils. A GLP-1 analog attenuates LPS-stimulated eosinophil activation. GLP-1 agonists may have additional adjunctive indications in treating persons with concomitant type 2 diabetes mellitus and asthma.