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Observational Study
. 2025 Apr;167(4):945-955.
doi: 10.1016/j.chest.2024.11.045. Epub 2024 Dec 30.

The Role of Bronchial Biopsy in the Prediction of Response to Biologic Therapy in Severe Uncontrolled Asthma: A Prospective Study

Borja G Cosío  1 , Amanda Iglesias  2 , Hanaa Shafiek  3 , Mar Mosteiro  4 , Inés Escribano  5 , Nuria Toledo-Pons  6 , Jose Luis Valera  6 , Cristina Gómez Bellvert  7 , Luis Pérez de Llano  8
Affiliations
Free article
Observational Study

The Role of Bronchial Biopsy in the Prediction of Response to Biologic Therapy in Severe Uncontrolled Asthma: A Prospective Study

Borja G Cosío et al. Chest. 2025 Apr.
Free article

Abstract

Background: Up to two-thirds of patients with severe uncontrolled asthma (SUA) who received biologic therapy do not have a complete response.

Research question: Can bronchial biopsy (BB) play a role in the identification of patients with SUA who have a better response to biologic therapy?

Study design and methods: This prospective multicenter study included consecutive patients with SUA who were candidates for biologic therapy. They underwent bronchoscopy and BB prior to biologic therapy, and clinical response was evaluated 6 months later. BB was evaluated according to a previously validated pathological score (PS) and was compared with a score of type 2 (T2) inflammation (T2 score) that includes blood eosinophil count and fractional exhaled nitric oxide in predicting response to biologic therapy. Response was graded as super-response, good response, and partial/no response according to a composite score that includes exacerbations, oral corticosteroid steroid (OCS) use, asthma control test, and improvement in FEV1.

Results: A total of 92 patients were recruited. Of the 92 patients recruited, 78 completed the study. Among them, 63 received an anti-IL-5 or IL-5 receptor (anti-IL5/5R) (mepolizumab, reslizumab, and benralizumab) while 15 received dupilumab. The proportion of super-responders was 36.5% in the anti-IL5/5R group and 26.6% in the dupilumab group (P = .126). The PS was the only variable independently associated with response; the T2 score was not. Super-responders had a statistically significantly higher PS. Response was better predicted by the PS compared with the T2 score in those receiving OCSs and especially in those taking anti-IL5/5Rs. Reduced eosinophil levels (< 10 eosinophils/field) were associated with poor response to biologic therapy.

Interpretation: Our findings indicate that BB is more precise in the prediction of response to biologic therapy than the T2 score, especially in those requiring OCSs or receiving anti-IL5/5Rs. Tissue eosinophilia is the main driver of this predictive capacity. However, other items in the PS related to bronchial remodeling might contribute to the identification of response to biologic therapy.

Keywords: T2 score; bronchoscopy; pathological score; submucosal eosinophilia; super-response to biologic therapy.

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Conflict of interest statement

Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. G. C. declares participation in Advisory Boards, grant, travel support or speaker fees from AstraZeneca, Chiesi, GSK, Menarini, Sanofi, and Teva. N. T. P. declares speaker fees and travel support from AstraZeneca, Sanofi, and GSK. L. P. d. L. declares participation in Advisory Boards, grants, travel support and speaker fees from AstraZeneca, Gebro, Chiesi, GSK, Bial, Novartis, Rovi, Sanofi, and Teva. None declared (A. I., H. S., M. M., I. E., J. L. V., C. G. B.).

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