Molecular T2 asthma phenotypes are stable but heterogeneous: the usefulness of periostin for endotyping

Front Allergy. 2023 Sep 8:4:1205115. doi: 10.3389/falgy.2023.1205115. eCollection 2023.

Abstract

Background: The stability of molecular T2/non-T2 phenotypes remains uncertain. The objectives of this study were to assess the stability of these phenotypes and the correlation between serum periostin and asthma T2 phenotypes and endotypes.

Methods: Demographics, clinical data, and blood samples were collected. Patients diagnosed with moderate-to-severe asthma were classified into T2 or non-T2 according to previously defined thresholds of blood eosinophilia and serum total IgE levels. Asthma endotype was also determined. After at least 1 year of follow-up, the stability of T2 phenotypes and endotypes was assessed.

Results: A total of 53 patients (72% women), mean age 47 years (range 16-77), were included. In the initial and second evaluations, the T2 phenotype was found in 41.5% and 43.4% of patients and the non-T2 phenotype was found in 58.4% and 56.7%, respectively. The mean [standard deviation (SD), range] serum periostin level was 52.7 (26.2, 22.6-129.7) ng/mL in patients with T2 phenotype, and 39.3 (25.6, 7.7-104.) ng/mL in non-T2 patients (P = 0.063). Periostin levels correlated to endotypes (P = 0.001): 45.7 (27.9) ng/mL in allergic asthma (n = 16 patients), 64.7 (24.9) in aspirin-exacerbated respiratory disease (n = 14), 59.0 (27.6) ng/mL in late-onset eosinophilic asthma (n = 4), and 28.3 (13.3) ng/mL in non-eosinophilic asthma (n = 18).

Conclusions: T2 and non-T2 asthma phenotypes assessed by accessible methods in daily practice are stable over time yet widely heterogeneous. Serum periostin does not discriminate between T2 and non-T2 phenotypes. Nevertheless, its correlation to asthma endotypes may contribute to guide therapies targeting T2 cytokines in a more personalized approach.

Keywords: asthma; endotypes; molecular phenotype; periostin; phenotypes.

Grants and funding

This study was funded by a grant from the Health Research Fund (Fondo de Investigación Sanitaria—FIS) of Instituto de Salud Carlos III (FIS PI14/00711). The funding sources were used to cover fungible expenses and had no influence on the results whatsoever. The research activity of IB was partly supported by the Instituto de Salud Carlos III—AES 2013, Programme Juan Rodés JR13/012. The research activities of DBG-G and NC-M were supported by competitive grants financed by the Institute for Health Research 12 de octubre (i + 12), Madrid, Spain and by MINECO—Spanish Ministry of Economy and Competitiveness, respectively.