Clinical and transcriptomic features of persistent exacerbation‐prone severe asthma in U‐BIOPRED cohort

• DOI: 10.1002/ctm2.816
• Publication Date: 2022-04-27T03:31:52Z
• Authors: Uruj Hoda; Stelios Pavlidis; Aruna T. Bansal; Kentaro Takahashi; Sile Hu; Francois Ng Kee K...; Christos Rossios; Kai Sun; Pankaj Bhavsar; Matthew Loza; Frederic Baribaud; Pascal Chanez; Stephen J. Fowler; Ildiko Horvath; Paolo Montuschi; Florian Singer; Jacek Musial; Barbro Dahlen; Norbert Krug; Thomas Sandstrom; Dominic E. Shaw; Rene Lutter; Louise J. Fleming; Peter H. Howarth; Massimo Caruso; Ana R. Sousa; Julie Corfield; Charles Auffray; Bertrand De Meulder; Diane Lefaudeux; Sven‐Erik Dahlen; Ratko Djukanovic; Peter J. Sterk; Yike Guo; Ian M. Adcock; Kian Fan Chung
• Keywords: severe asthma; Medicine (General); Bronchi/pathology; 610; 610 Medicine & health; PHENOTYPES; 1110 Nursing; Bronchi; Sputum/metabolism; Research & Experimental Medicine; Cohort Studies; R5-920; Humans; Asthma/genetics; CEACAM5; Research Articles; Science & Technology; STATEMENT; Research & Experimental; Sputum; Transcriptome/genetics; Asthma; 3. Good health; frequent exacerbators; Oncology; Medicine, Research & Experimental; asthma exacerbations; Medicine; U-BIOPRED study group; Transcriptome; Life Sciences & Biomedicine; persistent frequent exacerbators; LUNG

AbstractBackgroundExacerbation‐prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear.ObjectivesTo determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U‐BIOPRED cohort.MethodsWe 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.ResultsOf 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.ConclusionThe 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.