title: Clinical Implications of Having Reduced Mid Forced Expiratory Flow Rates (FEF25-75), Independently of FEV1, in Adult Patients with Asthma.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Division of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Riley
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri, United States of America.
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.affiliation: Department of Pathobiology, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, George, United States of America.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fitzpatrick
authors.affiliation: Department of Pediatrics, Division of Pediatric Pulmonary Medicine, University Hospitals, Cleveland, Ohio, United States of America.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Immunologic Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Moore
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Immunologic Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
authors.affiliation: Department of Medicine, Division of Allergy and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Immunologic Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.affiliation: Department of Pediatrics, Division of Respiratory Medicine, University of Virginia Children's Hospital, Charlottesville, Virginia, United States of America.
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.affiliation: School of Pharmacy, University of Wisconsin at Madison, Madison, Wisconsin, United States of America.
authors.forename: Ronald
authors.initials: R
authors.lastname: Sorkness
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Fernando
authors.initials: F
authors.lastname: Holguin
mesh_terms: D000328:Adult; D001249:Asthma / Q000150:complications / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000503:physiopathology; D005260:Female; D005540:Forced Expiratory Flow Rates; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D055815:Young Adult
chemical_list: D015415:Biomarkers