Ann Allergy Asthma Immunol. 2025 Dec 5:S1081-1206(25)01371-7. doi: 10.1016/j.anai.2025.12.002. Online ahead of print.
ABSTRACT
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 severe asthma patients using longitudinal changes in 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 usage were compared with analysis of variance and chi-square 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 three 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) showing 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 showed 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 showed progressive lung function decline despite higher corticosteroid use and persistent T2 inflammation, underscoring the need for biologic therapies over corticosteroid escalation.
PMID:41354271 | DOI:10.1016/j.anai.2025.12.002