Journal of Asthma and Allergy (May 2022)
Relationship Between Soluble Urokinase Plasminogen Activator Receptor (suPAR) and Disease Outcome in Adult-Onset Asthma
Abstract
Taito Niemelä,1 Hannu Kankaanranta,1– 3 Iida Vähätalo,2 Juho Loponen,1,2 Leena E Tuomisto,2 Onni Niemelä,1,4 Mari Hämäläinen,5 Eeva Moilanen,5 Pinja Ilmarinen1,2 1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 2Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; 3Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 4Department of Laboratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; 5The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, FinlandCorrespondence: Pinja Ilmarinen, Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland, Tel +35 850 420 0596, Email [email protected]: Soluble urokinase plasminogen activator receptor (suPAR) has emerged as a novel biomarker for various inflammatory conditions and has been proposed to associate with the severity of asthma. However, the relationship between suPAR and clinical asthma features is poorly understood.Objective: To examine associations of serum suPAR levels with clinical characteristics of asthma and to define the phenotype with high suPAR levels in patients with adult-onset asthma.Methods: Serum suPAR levels were measured with ELISA from patients with adult-onset asthma participating in the 12-year follow-up visit in the Seinäjoki Adult Asthma Study.Results: In total, 201 patients were divided into quartiles according to suPAR values. High suPAR patients had more severe asthma symptoms and poorer asthma control. They also had higher levels of interleukin 8 (IL-8), interleukin 6 (IL-6), matrix metalloproteinase 9 (MMP-9), and blood neutrophil counts than those with low suPAR levels. The use of high-dose inhaled and oral corticosteroids was more common in patients with elevated suPAR. Such patients also had visited healthcare more frequently during the follow-up period, had more comorbidities, and were physically less active than those with low suPAR levels. The above-mentioned results remained similar after excluding the patients with co-existing COPD; only association to hospitalizations was lost. In multivariable binary regression analyses, the highest suPAR quartile was associated with higher cumulative dispensed oral corticosteroid use, more severe symptoms, and uncontrolled asthma.Conclusion: High suPAR levels occur in uncontrolled adult-onset asthma patients characterized by neutrophilic inflammation, high corticosteroid use, frequent healthcare visits, and multimorbidity with unhealthy lifestyle. This biomarker could be useful in determining asthma phenotypes and target new asthma treatments.Keywords: asthma, adult-onset, neutrophil, phenotypes, suPAR, uncontrolled