D2.154 - Small airway dysfunction defined by reduced FEF25–75% identifies a distinct clinical phenotype in children with preserved FEV1

Small airway dysfunction may be overlooked in pediatric asthma when forced expiratory volume in one second (FEV1) is preserved. In children with asthma and preserved FEV1, the clinical significance of reduced forced expiratory flow at 25–75% of vital capacity (FEF25–75%) remains insufficiently characterized in routine clinical practice.

We conducted a retrospective chart review of children aged 6–18 years with a clinical diagnosis of asthma at a university-affiliated hospital between January 2019 and June 2025. Asthma was diagnosed based on typical symptoms and/or evidence of airway hyperresponsiveness, irrespective of baseline spirometric values. Among 507 children diagnosed with asthma during the study period, 345 children with preserved lung function (FEV1 ≥80% predicted) were included. Spirometry was analyzed at the time of asthma diagnosis or at the earliest available pulmonary function test.

Small airway dysfunction was defined as FEF25–75% <65% predicted, based on pediatric normative data used in previous studies. Patients were categorized into a normal small airway group (FEF25–75% ≥65%) and a reduced small airway group (FEF25–75% <65%).

Clinical characteristics, biomarkers of airway inflammation (fractional exhaled nitric oxide [FeNO], blood eosinophils), airway hyperresponsiveness assessed by methacholine challenge test (PC20), and asthma outcomes including systemic corticosteroid–requiring exacerbations within 12 months were compared between groups. Pulmonary function testing was performed in all included patients. FeNO and methacholine challenge data were available in 98% and 75% of patients, respectively.

Among 345 children with preserved FEV1 (mean age 10.8 ± 3.0 years, 58% male), reduced FEF25–75% was observed in 87 patients (25.2%).

Children with reduced FEF25–75% demonstrated higher FeNO levels (median 29 ppb [IQR 21–44] vs 19 ppb [IQR 12–30], p<0.001) and greater airway hyperresponsiveness reflected by lower methacholine PC20 values (median 0.85 mg/mL [IQR 0.40–1.80] vs 1.80 mg/mL [IQR 0.95–3.50], p=0.03) compared with those with normal FEF25–75%.

Asthma exacerbations requiring systemic corticosteroids within 12 months were more frequent in the reduced FEF25–75% group (35% vs 18%, p=0.009), whereas emergency department visits showed a similar trend without reaching statistical significance. FEV1 values were comparable between groups (p=0.30).

In multivariable analysis adjusted for age, sex, atopic status, and inhaled corticosteroid use, reduced FEF25–75% remained independently associated with systemic corticosteroid–requiring exacerbations (adjusted odds ratio 2.4, 95% CI 1.3–4.5, p=0.008).

In children with asthma and preserved FEV1, reduced FEF25–75% identifies a clinically relevant small airway phenotype associated with increased airway inflammation, enhanced airway hyperresponsiveness, and a higher risk of clinically significant exacerbations. Assessment of small airway function may provide additional value for risk stratification and closer monitoring beyond conventional spirometric indices in real-world pediatric asthma care.