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

• Authors: Craig M. Riley, University of Pittsburgh Medical Center; Sally E. Wenzel, University of Pittsburgh Medical Center; Mario Castro, Washington University School of Medicine in St. Louis; Serpil C. Erzurum, Cleveland Clinic Foundation; Kian Fan Chung, Imperial College London; Anne Fitzpatrick, Emory University; Benjamin Gaston, University Hospitals, Cleveland; Elliot Israel, Brigham and Women’s Hospital; Wendy C. Moore, Wake Forest University; Eugene R. Bleecker, Wake Forest University; William J. Calhoun, University of Texas Medical Branch; Nizar N. Jarjour, University of Wisconsin; William W. Busse, University of Wisconsin; Stephen P. Peters, Wake Forest University; W. Gerald Teague, University of Virginia Children’s Hospital; Ronald Sorkness, University of Wisconsin at Madison; Fernando Holguin, University of Pittsburgh School of Medicine
• Journal Title: PLoS ONE
• Volume: Volume 10, Number 12
• Publisher: Public Library of Science | 2015-12-30, Pages e0145476-e0145476
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0145476
• Subjects: Health Sciences, General; Health Sciences, Health Care Management
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; LUNG; STANDARDIZATION; OBSTRUCTION; SPIROMETRY

Abstract

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction: FEF25-75 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 FEV1 or the FEV1/FVC ratio. Purpose: To determine the association between Hankinson's percent-predicted FEF25-75 (FEF25-75%) 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 FEF25-75% quartiles. Multivariable analyses were done to avoid confounding by demographic characteristics, FEV1, and the FEV1/FVC ratio. In a sensitivity analysis, we also compared outcomes across participants with FEF25-75% below the lower limit of normal (LLN) and FEV1/FVC above LLN. Results: Subjects in the lowest FEF25-75% quartile had greater rates of healthcare utilization and higher exhaled nitric oxide and sputum eosinophils. In multivariable analysis, being in the lowest FEF25-75% 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 FEF25-75% <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, FEV1 and FEV1/FVC, a reduced FEF25-75% is independently associated with previous ICU admission, persistent symptoms, nocturnal symptoms, blood eosinophilia and bronchial hyperreactivity. This suggests that in some asthmatics, a reduced FEF25-75% is an independent biomarker for more severe asthma.