Severe asthma in the spotlights

According to more recent insights, bronchial epithelium plays a key role in the immunopathogenesis of severe asthma. Within the affected airways, epithelial cells can be triggered by e.g. viruses, allergens, or other irritants, causing a subsequent release of pro-inflammatory cytokines, called alarmins, which subsequently induce innate and adaptive immune responses.

Prof. Lena Uller (Lund University, Sweden) explained that novel biologicals targeting the epithelium cell-derived alarmins, i.e. TSLP, IL-33, and IL-25, can inhibit multiple downstream inflammatory pathways, thus offering a broad anti-inflammatory potential for patients with severe uncontrolled asthma. “In the recently published phase 3 study of tezepelumab, targeting TSLP, clinical effectiveness has been shown across both the type2 as well as the non-type2 asthma endotypes [1].” Although the most pronounced clinical improvements occurred in the type2-subpopulation, further research into anti-TSLP effects also includes patients with type2 low (or non-type) asthma [2,3]. Prof. Uller also pointed out that tezepelumab is the first available anti-alarmin biological (in the USA) and that the currently available biologicals in the Nordic countries (and other Western countries) only target more downstream mechanisms of type2-asthma [4].

1. Menzies-Gow A, et al. N Engl J Med. 2021;384:1800-1809.
2. Wechsler ME, et al. Lancet. 2022;10(7):650-660.
3. Menzies-Gow A, et al. Respir Res. 2020 Oct 21;21(1):279.
4. Uller L. Asthma immunopathology as the determinant of biologic target therapy in severe asthma. Nordic Lung Congress 2022, 01–03 June, Copenhagen, Denmark.

 

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Posted on 17 August, 202216 August, 2022