Clinical Implications of Having Reduced Mid Forced Expiratory Flow Rates (FEF(25-75)), Independently of FEV1, in Adult Patients with Asthma

INTRODUCTION: FEF(25-75) is one of the standard results provided in spirometry reports; however, in adult asthmatics there is limited information on how this physiological measure relates to clinical or biological outcomes independently of the FEV(1) or the FEV(1)/FVC ratio. PURPOSE: To determine the association between Hankinson’s percent-predicted FEF(25-75) (FEF(25-75)%) levels with changes in healthcare utilization, respiratory symptom frequency, and biomarkers of distal airway inflammation. METHODS: In participants enrolled in the Severe Asthma Research Program 1–2, we compared outcomes across FEF(25-75)% quartiles. Multivariable analyses were done to avoid confounding by demographic characteristics, FEV(1), and the FEV(1)/FVC ratio. In a sensitivity analysis, we also compared outcomes across participants with FEF(25-75)% below the lower limit of normal (LLN) and FEV(1)/FVC above LLN. RESULTS: Subjects in the lowest FEF(25-75)% quartile had greater rates of healthcare utilization and higher exhaled nitric oxide and sputum eosinophils. In multivariable analysis, being in the lowest FEF(25-75)% quartile remained significantly associated with nocturnal symptoms (OR 3.0 [95%CI 1.3–6.9]), persistent symptoms (OR 3.3 [95%CI 1–11], ICU admission for asthma (3.7 [1.3–10.8]) and blood eosinophil % (0.18 [0.07, 0.29]). In the sensitivity analysis, those with FEF(25-75)% <LLN had significantly more nocturnal and persistent symptoms, emergency room visits, higher serum eosinophil levels and increased methacholine responsiveness. CONCLUSIONS: After controlling for demographic variables, FEV(1) and FEV(1)/FVC, a reduced FEF(25-75)% is independently associated with previous ICU admission, persistent symptoms, nocturnal symptoms, blood eosinophilia and bronchial hyperreactivity. This suggests that in some asthmatics, a reduced FEF(25-75)% is an independent biomarker for more severe asthma.