Leukotriene C4 Synthase Expression in Sputum Correlates with Disease Severity Amongst Patients with Different Clinical Phenotypes of Asthma

Rationale: Amongst patients with asthma, clinical presentation and disease severity are well known to be heterogeneous. Recently, three distinct clinical phenotypes of asthmatic patients have been identified based on analysis of the sputum transcriptome. These have been classified as transcriptomic endotype of asthma (TEA) clusters 1-3, with clusters 1 and 2 consisting of patients with severe phenotypes and cluster 3 patients having relatively benign courses. We sought to characterize the expression of arachidonic acid metabolites as contributing factors to the pathophysiology of asthma in these TEA clusters.  

Methods: TEA clusters were identified through previously described methods. Expression of arachidonic acid pathway metabolites in sputum RNA samples was determined for patients in each TEA cluster using Affymetrix HuGene 1.0 ST gene arrays. Comparison of the average expression between TEA clusters was performed with student t-tests and Wilcoxon Rank-Sum tests. 

Results: Patients in different TEA clusters were noted to have statistically different levels of leukotriene C4 synthase (LTC4S) expression in the sputum. The level of LTC4S expression was significantly higher in TEA cluster 1 compared to TEA clusters 2 and 3. The expression of LTC4S was also significantly higher in TEA cluster 2 compared to TEA cluster 3. 

Conclusions: Differences in the expression of LTC4S and, by extrapolation, the level of circulating leukotrienes in sputum appear to correlate with disease severity in patients with different phenotypes of asthma. Further investigation into the expression of inflammatory markers may help elucidate differences in the pathophysiology of asthma in these patients and aid in thoughtful implementation of therapeutic agents.