Open AccessClinical and transcriptomic features of persistent exacerbation‐prone severe asthma in U‐BIOPRED cohort
Author(s) -
Hoda Uruj,
Pavlidis Stelios,
Bansal Aruna T.,
Takahashi Kentaro,
Hu Sile,
Ng Kee Kwong Francois,
Rossios Christos,
Sun Kai,
Bhavsar Pankaj,
Loza Matthew,
Baribaud Frederic,
Chanez Pascal,
Fowler Stephen J.,
Horvath Ildiko,
Montuschi Paolo,
Singer Florian,
Musial Jacek,
Dahlen Barbro,
Krug Norbert,
Sandstrom Thomas,
Shaw Dominic E.,
Lutter Rene,
Fleming Louise J.,
Howarth Peter H.,
Caruso Massimo,
Sousa Ana R.,
Corfield Julie,
Auffray Charles,
De Meulder Bertrand,
Lefaudeux Diane,
Dahlen SvenErik,
Djukanovic Ratko,
Sterk Peter J.,
Guo Yike,
Adcock Ian M.,
Chung Kian Fan
Publication year - 2022
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.816
Subject(s) - medicine , asthma , transcriptome , cohort , exacerbation , sinusitis , endotype , eosinophil , immunology , gene expression , gene , biology , genetics
Background Exacerbation‐prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear. Objectives To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U‐BIOPRED cohort. Methods We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures. Results Of 317 patients, 62.4% had FE, of whom 63.6% had PFE, while 37.6% had IE, of whom 61.3% had PIE. Using multivariate analysis, FE was associated with short‐acting beta‐agonist use, sinusitis and daily oral corticosteroid use, while PFE was associated with eczema, short‐acting beta‐agonist use and asthma control index. CEA cell adhesion molecule 5 ( CEACAM5) was the only differentially expressed transcript in bronchial biopsies between PE and IE. There were no differentially expressed genes in the other four compartments. There were higher expression scores for type 2, T‐helper type‐17 and type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while there were higher expression scores of type 2, type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE. Conclusion The FE group and its PFE subgroup are associated with poor asthma control while expressing higher type 1 and type 2 activation pathways compared to IE and PIE, respectively.