Persistent FeNO linked to poorer long-term lung function in asthma patients on dupilumab

Asthma patients whose fractional exhaled nitric oxide (FeNO) stays raised during dupilumab treatment may be more likely to see their lung function decline over time, a Japanese study suggests.

The single-centre retrospective study, published in Allergy, Asthma & Clinical Immunology, found that long-term FEV1 trajectories varied widely among patients who stayed on the biologic for three years. Persistently elevated FeNO was associated with a less favourable course.

The authors note that long-term lung function changes during dupilumab treatment have not been well characterised. To explore this, researchers at Niigata University reviewed patients with physician-confirmed asthma who started dupilumab between March 2019 and August 2022. Of 60 patients, 41 continued treatment for three years and were included in the analysis.

Methods

Post-treatment FEV1 slopes were estimated from measurements taken at four months, one year, two years and three years. Patients whose FEV1 fell by more than 30 mL per year were classed as decliners. Persistent FeNO was defined as a reading of 20 ppb or higher at two or more of the one-, two- and three-year visits.

The researchers also tracked maintenance treatment throughout follow-up. In the 38 patients with complete prescription records, they assessed three-year adherence and inhaled corticosteroid (ICS) exposure.

Findings

Seventeen of the 41 patients were classed as decliners. Both groups showed an early rise in FEV1 after starting dupilumab. After that, FEV1 gradually fell in decliners but stayed relatively stable in non-decliners.

Persistent FeNO was associated with a less favourable FEV1 slope. It remained linked to decliner status after adjustment for age and baseline percent-predicted FEV1 (adjusted OR 21.8; 95% CI 2.61–183; p = 0.004). FeNO at one year was also inversely correlated with the post-treatment FEV1 slope (Spearman’s ρ = −0.329; p = 0.036).

The two groups showed no significant differences in prescribed ICS intensity, ICS exposure or prescription-based adherence over three years. This suggests the differences in lung function were not explained by background inhaled therapy.

Conclusions

The authors concluded that in this selected cohort, long-term FEV1 trajectories on dupilumab were heterogeneous. Persistent post-treatment FeNO was associated with a less favourable trajectory.

They describe the findings as exploratory and say they need validating in larger prospective studies. The small sample, retrospective design and selection of patients who stayed on treatment mean the study cannot establish cause and effect. The wide confidence interval around the odds ratio also reflects the small cohort.

Reference: Naramoto S, Ueno H, Aoki A, et al. 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. Published 27 October 2026. https://doi.org/10.1186/s13223-026-01081-7