Clustering of patients with severe asthma based on long-term percentage of forced expiratory volume in 1 second (FEV1) changes: Real-world evidence.

BACKGROUND

Severe asthma is a heterogeneous disease with variable clinical manifestations and treatment responses. Long-term assessment of lung function trajectories may help define phenotypic and endotypic subgroups.

OBJECTIVE

To identify distinct phenotypic clusters in patients with severe asthma using longitudinal changes in percentage of forced expiratory volume in 1 second (FEV1%) and assess the associated clinical and inflammatory profiles.

METHODS

This single-center, retrospective cohort study analyzed 10-year follow-up data from adult patients with severe asthma. Latent class mixed model analysis was performed using serial FEV1% changes. Baseline characteristics and medication use were compared with analysis of variance and χ2 tests. Linear mixed models assessed longitudinal trends in fractional exhaled nitric oxide (FeNO) levels and blood eosinophil/neutrophil counts.

RESULTS

Altogether, 310 patients (mean age, 44.7 ± 14.4 years; 35.2% were males) were included. The following 3 distinct clusters were identified: group 1 (n = 45) demonstrating a progressive decline in FEV1% despite receiving maintenance therapy (refractory to current treatments); group 2 (n = 211) maintaining stable FEV1% (≥80%); and group 3 (n = 54) demonstrating improvement. Group 1 had higher baseline FeNO and eosinophils than group 2, with eosinophil levels comparable to group 3. Over time, group 1 exhibited persistently elevated FeNO and eosinophil levels than groups 2 and 3, whereas neutrophil and IgE trajectories had no differences. Group 1 also required higher cumulative systemic corticosteroid doses.

CONCLUSION

Three distinct FEV1% trajectories were identified in severe asthma. The treatment-refractory group demonstrated progressive lung function decline despite higher corticosteroid use and persistent T2 inflammation, underscoring the need for biologic therapies than corticosteroid escalation.