Persistent airway inflammation on dupilumab linked to steeper lung function decline in asthma study

Patients with asthma who stayed on the biologic drug dupilumab for three years did not all follow the same lung function path, according to a single-center retrospective study published in Allergy, Asthma & Clinical Immunology. While many maintained the gains in breathing capacity achieved early in treatment, a substantial minority saw their lung function slowly erode over time, and a simple, measurable sign of ongoing airway inflammation appeared to flag who was at risk.

The research team, led by Shun Naramoto and colleagues at Niigata University, set out to address a gap in the evidence. Although dupilumab is widely used for moderate-to-severe asthma, long-term lung function trajectories during treatment have remained insufficiently characterized.

The study drew on patients with physician-confirmed asthma who initiated dupilumab for asthma at Niigata University between March 2019 and August 2022. Of 60 such patients, 41 continued the treatment for the full three years and formed the analysis cohort. Because the design was retrospective and the cohort was selected on treatment persistence, the findings are exploratory and the authors themselves note that they require validation in larger prospective studies.

To track lung function, the team estimated post-treatment FEV1 slopes using measurements taken at four months, one year, two years and three years after starting dupilumab. Patients whose annual FEV1 slope was more negative than minus 30 milliliters per year were classified as decliners. Persistent FeNO was defined as a value of 20 parts per billion or higher at two or more of the one-, two- and three-year visits.

Seventeen of the 41 patients met the criteria for decliners. Both groups showed an early increase in FEV1 after starting dupilumab, reflecting the initial improvement many patients experience on the drug. Thereafter, the trajectories diverged: FEV1 gradually decreased in the decliners but remained relatively stable in the non-decliners. This heterogeneity in long-term post-treatment trajectories is the study’s central observation.

Persistent FeNO emerged as the key correlate of that divergence. Patients with persistently elevated FeNO had a less favorable FEV1 slope, and the association with decliner status held after statistical adjustment for age and baseline percent-predicted FEV1, with an adjusted odds ratio of 21.8 (95 percent confidence interval, 2.61 to 183; p = 0.004). FeNO measured at one year was also inversely correlated with the post-treatment FEV1 slope, with a Spearman’s rho of minus 0.329 (p = 0.036), meaning higher early inflammation scores tended to accompany steeper subsequent decline.

Importantly, the link was not explained by differences in standard therapy. The researchers assessed maintenance treatment throughout follow-up and, in the 38 patients with complete prescription records, evaluated three-year prescription-based adherence and inhaled corticosteroid exposure. No significant between-group differences were observed in three-year prescribed ICS intensity, prescription-based ICS exposure, or prescription-based adherence. That strengthens the case that persistent FeNO reflects something beyond undertreatment, although the wide confidence interval around the odds ratio reflects the small sample size.

The authors conclude that in this selected cohort of patients who continued dupilumab for three years, long-term post-treatment FEV1 trajectories were heterogeneous, and that persistent post-treatment FeNO was associated with a less favorable trajectory. As a single-center retrospective analysis of 41 patients, the study cannot establish causation, and the definition of decliners and of persistent FeNO were chosen by the investigators. Still, the results suggest that monitoring FeNO during biologic therapy may help identify patients whose lung function continues to slip despite treatment, a hypothesis that now needs testing in larger, prospective cohorts.

Subject of Research: Long-term lung function trajectories and persistent FeNO in asthma patients treated with dupilumab

Article Title: Persistent post-treatment FeNO and long-term FEV1 trajectories in patients with asthma treated with dupilumab: a single-center retrospective study

Article References: Naramoto, S., Ueno, H., Aoki, A., Shima, K., Kimura, Y., Aoki, N., Ohshima, Y., Watanabe, S., Hasegawa, T., Kikuchi, T., & Koya, T. (2026). Persistent post-treatment FeNO and long-term FEV1 trajectories in patients with asthma treated with dupilumab: a single-center retrospective study. Allergy, Asthma & Clinical Immunology. https://doi.org/10.1186/s13223-026-01081-7

Image Credits: AI Generated

DOI: 10.1186/s13223-026-01081-7

Keywords: asthma, dupilumab, FeNO, FEV1, lung function, biologics, type 2 inflammation, retrospective study, inhaled corticosteroids, Niigata University, Persistent, post-treatment