Transcriptomic analysis of cellular senescence signatures in severe asthma

Background: Cellular senescence is a potentially important driver of various aging-related diseases. Given the age-related increase in asthma severity, cellular senescence may also be relevant in the pathogenesis of severe asthma. This study aimed to investigate cellular senescence signatures in relation to asthma severity and clinical parameters. Methods: Two gene sets of cellular senescence, p53 signalling pathway and senescence-associated secreted phenotype (SASP), were examined in several cellular compartments of participants in the U-BIOPRED and the Australian Severe Asthma cohorts (GSE147881). For each sample, the enrichment score (ES) of p53 pathway and SASP was calculated using Gene Set Variation Analysis. Produced ESs were examined for statistical associations with categorical and numerical clinical parameters. Results: The ESs of p53 pathway and SASP gene sets were significantly higher in bronchial biopsies of severe asthmatic patients than in those of non-severe patients or healthy volunteers in the U-BIOPRED cohort. They were significantly associated with the number of asthma exacerbations, oral corticosteroid use, serum periostin levels, worse lung function, and comorbid nasal polyps in asthmatics. In nasal brushings, the SASP score was significantly increased in subjects with nasal polyps than those without. The relationships between SASP and asthma severity were validated in bronchial biopsies of the Australian Severe Asthma cohort participants. Conclusions: Cellular senescence may be involved in the pathophysiology of severe asthma, particularly in patients with comorbid nasal polyps. Further studies are warranted to validate the causal relationships.