Plasma P-Selectin Is Inversely Associated with Lung Function and Corticosteroid Responsiveness in Asthma
<b><i>Background:</i></b> Severe asthma has multiple phenotypes for which biomarkers are still being defined. Plasma P-selectin reports endothelial and/or platelet activation. <b><i>Objective:</i></b> To determine if P-selectin is associated with features of asthma in a longitudinal study. <b><i>Methods:</i></b> Plasmas from 70 adult patients enrolled in the Severe Asthma Research Program (SARP) III at the University of Wisconsin-Madison were analyzed for concentration of P-selectin at several points over the course of 3 years, namely, at baseline (BPS), after intramuscular triamcinolone acetonide (TA) injection, and at 36 months after baseline. Thirty-four participants also came in during acute exacerbation and 6 weeks after exacerbation. <b><i>Results:</i></b> BPS correlated inversely with forced expiratory volume in 1 s (FEV<sub>1</sub>) and with residual volume/total lung capacity, an indicator of air trapping. BPS was inversely associated with FEV<sub>1</sub> change after TA, by regression analysis. FEV<sub>1</sub> did not change significantly after TA if BPS was above the median, whereas patients with BPS below the median had significantly increased FEV<sub>1</sub> after TA. BPS was higher in and predicted assignment to SARP phenotype cluster 5 (“severe fixed-airflow asthma”). P-selectin was modestly but significantly increased at exacerbation but returned to baseline within 3 years. <b><i>Conclusions:</i></b> High BPS is associated with airway obstruction, air trapping, the “severe fixed-airflow” cluster, and lack of FEV<sub>1</sub> improvement in response to TA injection. P-selectin concentration, which is a stable trait with only modest elevation during exacerbation, may be a useful biomarker for a severe asthma pheno- or endotype characterized by low pulmonary function and lack of corticosteroid responsiveness.