To the Editor:
Data from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study reported by Kolmert and colleagues (1) have highlighted the potential value of urinary eicosanoids in identifying type 2 inflammation in asthma. Urinary metabolites of prostaglandin D2 (PGD2), tetranor PGD2 (PGDM) and 2,3-dinor-11β-PGF2α, were elevated in severe asthma compared with mild to moderate asthma, and urinary cysteinyl leukotriene E4 (LTE4) concentrations were elevated in mild to severe asthma compared with healthy nonsmoking control subjects. Importantly, high concentrations of urinary PGD2 and LTE4 metabolites were associated with markers of type 2 high inflammation in the UBIOPRED cohort and in validation populations of severe asthma and adolescents with asthma. Although metabolite concentrations were unrelated to several demographic factors, the study does not report on the effects of current smoking status or exposure to passive smoke on urinary metabolite eicosanoid concentrations.
Previous studies have found that PGD2 urinary metabolite PGDM concentrations are increased in current smokers with asthma compared with never-smokers with asthma (2) and that LTE4 urinary metabolite concentrations are elevated in healthy smokers (2, 3), current smokers with asthma compared with never-smokers (2, 4), and children with asthma exposed to passive smoke and at risk of severe exacerbations (5). Collectively, these findings indicate that exposure to tobacco smoke is an important variable to consider when interpreting urinary PGDM and LTE4 concentrations as a biomarker of type 2 inflammatory status. Interestingly, urinary LTE4 (2, 4) and PGDM concentrations (2) are directly associated with sputum eosinophils among current smokers with asthma, suggesting a potential link between urinary eicosanoids and type 2 eosinophilic inflammation, at least in a proportion of this subgroup of smokers. Although the UBIOPRED study included a “smoking” group of 109 current and former smokers with severe asthma, in whom urinary eicosanoid concentration did not differ from the nonsmokers with severe asthma, urinary biomarker results are not reported in the subgroup of current smokers with asthma. It would also be helpful to know whether exposure to passive smoke altered urinary eicosanoid concentrations in the UBIOPRED and validation populations.
Type 2 inflammation occurs in adults with severe asthma and a smoking history (6), although non–type 2 inflammation is a more frequently found phenotype. Current cigarette smoking can alter several biomarkers of type 2 inflammation, for example, by reducing fractional exhaled nitric oxide and serum periostin concentrations, which may hinder stratification of current smokers with asthma for targeted treatments. Further assessment of the role of urinary eicosanoids in identifying and monitoring type 2 inflammation in adults and adolescents with asthma should include data on the effects of exposure to active and passive tobacco smoke on urinary eicosanoids in relevant asthma populations.
Footnotes
Originally Published in Press as DOI: 10.1164/rccm.202101-0011LE on February 23, 2021
Author disclosures are available with the text of this letter at www.atsjournals.org.
References
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