Background:
Severe asthma patients with a significant smoking history have airflow obstruction with
reported neutrophilia. We hypothesise that multi1omic analysis will enable the definition of smoking
and ex1smoking severe asthma molecular phenotypes.
Methods
The U1BIOPRED severe asthma patients containing current1smokers (CSA), ex1smokers
(ESA), non1smokers (NSA) and healthy non1smokers (NH) was examined. Blood and sputum cell
counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis
of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells
was performed.
Results
Colony stimulating factor (CSF)2 protein levels were increased in CSA sputum supernatants
with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate
immune pathways were associated with neutrophilic inflammation in ESA. Gene Set Variation
Analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic
metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5
and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes,
mucin 2 and cystatin SN, were downregulated.
Conclusion
Despite little difference in clinical characteristics, CSA were distinguishable from ESA
subjects at the sputum proteomic level with CSA having increased CSF2 expression and ESA
patients showed sustained loss of epithelial barrier processes.