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.
