Several factors—including β-agonist exposure—influence gene expression in bronchoalveolar lavage (BAL) cells, new research shows. And according to the study authors, BAL cell gene expression in severe asthma reveals mechanisms of severe disease and influences of medications.
To reach this conclusion, the researchers profiled BAL cell expression in 154 patients with and without asthma. In all, 100 of the participants had accompanying airway epithelial cell gene expression.
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The profiles for BAL cell expression were related to participant age, gender, race, and medication use, as well as to the sample trait of cell proportions. Severity-related gene expression was then determined by correlating transcripts and co-expression networks to lung function, emergency department visits or hospitalizations in the last year, medication use, and quality-of-life scores.
Overall, the researchers found that age, gender, race, medications, and cell proportions strongly influenced BAL cell gene expression. And, therefore, by accounting for these influences, the researchers could determine leading severity-related genes.
Participants with severe asthma were most differentiated from the other participants by a BAL cell expression network enriched for cAMP signaling components. According to the study authors, this may be attributable to a robust upregulation in cAMP-related expression among participants with non-severe asthma and those who were β-agonist-naïve who were prescribed a β-agonist prior to cell collection.
Further, based on enzyme-linked immunosorbent assays of BAL lysates, the researchers determined that protein levels may partly disagree with expression changes.
“Gene expression in BAL cells is influenced by factors seldomly considered,” the study authors concluded. “Notably, β-agonist exposure likely had a strong and immediate impact on cellular gene expression, which may not translate to important disease mechanisms or necessarily match protein levels.”
“Leading severity-related genes were discovered in an unbiased, system-wide analysis, revealing new targets that map to asthma susceptibility loci.”
Weathington N, O’Brien ME, Radder J, et al. BAL cell gene expression in severe asthma reveals mechanisms of severe disease and influences of medications. Am J Respir Crit Care Med. 2019;200(7). doi:10.1164/rccm.201811-2221OC.