Clinical Implications of Having Reduced Mid Forced Expiratory Flow Rates (FEF _25-75), Independently of FEV1, in Adult Patients with Asthma

Abstract

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.