Tezepelumab in patients with allergic and eosinophilic asthma.

Asthma is a heterogeneous disease commonly driven by allergic and/or eosinophilic inflammation, both of which may be present in severe disease. Most approved biologics for severe asthma are indicated for specific phenotypes and target individual downstream type 2 components of the inflammatory cascade. Tezepelumab, a human monoclonal antibody (immunoglobulin G2λ), binds specifically to thymic stromal lymphopoietin (TSLP), an epithelial cytokine that initiates and sustains allergic and eosinophilic inflammation in asthma. By blocking TSLP, tezepelumab has demonstrated efficacy across known asthma phenotypes and acts upstream of all current clinically used biomarkers. In a pooled analysis of the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies, compared with placebo, tezepelumab reduced the annualized asthma exacerbation rate over 52 weeks by 62% (95% confidence interval [CI]: 53, 70) in patients with perennial aeroallergen sensitization (allergic asthma); by 71% (95% CI: 62, 78) in patients with a baseline blood eosinophil count ≥300 cells/µL; and by 71% (95% CI: 59, 79) in patients with allergic asthma and a baseline blood eosinophil count ≥300 cells/µL. This review examines the efficacy and mode of action of tezepelumab in patients with allergic asthma, eosinophilic asthma and coexisting allergic and eosinophilic phenotypes.

Allergens and thunderstorm asthma.

Thunderstorm-related asthma is increasingly recognized in many parts of the world. This review focuses on important advances in the understanding of the mechanism of the role of allergens, in particular fungal spores such as Alternaria, in asthma epidemics associated with thunderstorms. From our observations, we have proposed that the prerequisites for this phenomenon are as follows: 1) a sensitized, atopic, asthmatic individual; 2) prior airway hyperresponsiveness before a sudden, large allergen exposure; 3) a large-scale thunderstorm with cold outflow occurring at a time and location during an allergen season in which large numbers of asthmatics are outdoors; and 4) sudden release of large amounts of respirable allergenic fragments, particularly fungal spores such as Alternaria.

Epidemic asthma and the role of the fungal mold Alternaria alternata.

BACKGROUND: After July 29, 2002, an epidemic of asthma admissions was associated with a thunderstorm in the United Kingdom. OBJECTIVE: We sought to study the cause of epidemics of asthma associated with thunderstorms. METHODS: We performed a case-control study of 26 patients presenting to Cambridge University Hospital with asthma after the thunderstorm. Control subjects were 31 patients with summer seasonal asthma. Subjects underwent skin tests and specific IgE serology to inhaled aeroallergens. Meteorologic and aerobiologic data correlated with asthma admissions were analyzed. RESULTS: Twenty-three of 26 cases had IgE sensitization to Alternaria species. Eleven of 31 control subjects gave a history of asthma exacerbation during thunderstorms. Ten of these 11 control subjects were sensitive to Alternaria species on skin testing, but Alternaria species sensitivity was only identified in 4 of the 20 remaining control subjects who did not report thunderstorm-related asthma symptoms. The odds ratio of having epidemic thunderstorm-related asthma if sensitive to Alternaria species was 9.31 (95% CI, 2.305-37.601; P = .0008) and 63.966 (95% CI, 3.577-1143.9; P < .0001) if sensitive to Alternaria species, Cladosporium species, or both. Poisson regression analysis showed that counts of broken Alternaria species and Didymella and Cladosporium species were significantly correlated with each other and with asthma admissions. The thunderstorm was associated with increased levels of Alternaria, Cladosporium, and Didymella species. CONCLUSIONS: Alternaria alternata sensitivity is a compelling predictor of epidemic asthma in patients with seasonal asthma and grass pollen allergy and is likely to be the important factor in thunderstorm-related asthma. CLINICAL IMPLICATIONS: Alternaria species sensitization in asthmatic subjects with grass pollen sensitivity predicts susceptibility to thunderstorm-associated asthma.