Association of FEF25-75% Impairment with Bronchial Hyperresponsiveness and Airway Inflammation in Subjects with Asthma-Like Symptoms

Background: Forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) might be considered as a marker of early airway obstruction. FEF25-75% impairment might suggest earlier asthma recognition in symptomatic subjects even in the absence of other abnormal spirometry values. Objectives: The study was designed in order to verify whether FEF25-75% impairment in a cohort of subjects with asthma-like symptoms could be associated with the risk of bronchial hyperresponsiveness (BHR) and with airway inflammation expressed as fractional exhaled nitric oxide (FeNO) and eosinophil counts in induced sputum. Methods: Four hundred adults with a history of asthma-like symptoms (10.5% allergic) underwent spirometry, determination of BHR to methacholine (PD20FEV1), FeNO analysis and sputum induction. FEF25-75% <65% of predicted or <-1.64 z-score was considered abnormal. Results: All subjects had normal FVC, FEV1 and FEV1/FVC, while FEF25-75% was abnormal in 27.5% of them. FEF25-75% (z-score) was associated with PD20FEV1 (p < 0.001), FeNO (p < 0.001) and sputum eosinophils (p < 0.001). Patients with abnormal FEF25-75% showed higher levels of FeNO and eosinophils in induced sputum than did patients with normal FEF25-75% (p < 0.01 and p < 0.01, respectively). Subjects with abnormal FEF25-75% had an increased probability of being BHR positive (OR = 13.38; 95% CI: 6.7-26.7; p < 0.001). Conclusions: Our data show that abnormal FEF25-75% might be considered an early marker of airflow limitation associated with eosinophilic inflammation and BHR in subjects with asthma-like symptoms, indicating a role for FEF25-75% as a predictive marker of newly diagnosed asthma.