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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.

Clinical Implications of Having Reduced Mid Forced Expiratory Flow Rates (FEF25-75), Independently of FEV1, in Adult Patients with Asthma