Clustering of patients with severe asthma based on long-term percentage of forced expiratory volume in 1 second...

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.

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.

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.

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.

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.