SERPINB9 is associated with clinical improvement during aspirin therapy in aspirin-exacerbated respiratory disease
In brief
High sputum SERPINB9 levels predict clinical response to aspirin in AERD
In a double-blind crossover trial of 14 aspirin-exacerbated respiratory disease patients, 57% improved on aspirin but the same proportion improved on placebo, showing no overall drug advantage. However, patients with higher baseline SERPINB9 expression in sputum were far more likely to respond to aspirin, suggesting this gene as a potential biomarker pending further validation.
- Journal
- The Journal of allergy and clinical immunology (Q1)
- Published
- 14 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Piotr Szatkowski, Adam Stępień, Anna Gielicz, Adam Ćmiel, Hanna Plutecka, Joanna Szaleniec, et al.
- PMID
- 42600897
- DOI
- 10.1016/j.jaci.2026.07.024
Why clinicians should know about it
- Picked for Immunology and Allergy (top studies of the week, 25 October 2026): Aspirin desensitization therapy and response biomarkers in aspirin-exacerbated respiratory disease
Abstract
RATIONALE: Aspirin therapy after desensitization (ATAD) is a unique treatment option for patients with aspirin-exacerbated respiratory disease (AERD). However, biomarkers predicting response are lacking, and the effects of high-dose aspirin remain unclear. OBJECTIVES: To determine clinical response to ATAD, identify predictive biomarkers, and compare aspirin-related molecular effects between AERD patients and healthy controls. METHODS: We conducted an 18-week, randomized, double-blind, placebo-controlled crossover trial of aspirin (600 mg/day) in patients with AERD (n=14) and controls (n=13). Each treatment arm lasted 8 weeks with a 2-week washout. Blood, induced sputum, nasal lavage [NL] and urine samples were collected at four time points. Clinical outcomes, transcriptional profiles, cytology and levels of eicosanoids, cytokines and chemokines were assessed. RESULTS: At baseline, AERD patients had higher blood eosinophils and elevated leukotriene E4 in plasma, NL, and urine, with reduced eoxin C4 in sputum supernatant and lower prostaglandin E2 and 12-hydroxyeicosatetraenoic acid in NL compared with controls. No differences in sputum gene expression were observed. SERPINB9 expression correlated with IL4RA in both groups and with PTGS2 in AERD. Eight patients (57.1%) responded to aspirin; however, the same number responded to placebo, with substantial overlap between treatments. Higher baseline SERPINB9 expression predicted response (OR, 62.3; padj=0.03). After aspirin, SERPINB9 correlations with IL4RA and PTGS2 were lost in AERD but persisted in controls. No consistent molecular changes were observed after either treatment. CONCLUSION: Clinical improvement during ATAD was comparable to placebo. However, elevated baseline sputum SERPINB9 was associated with clinical improvement, highlighting potential as a candidate biomarker.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.