Asthma and lower airway disease
Forced expiratory flow between 25% and 75% of vital capacity and FEV1/forced vital capacity ratio in relation to clinical and physiological parameters in asthmatic children with normal FEV1 values

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Background

The assumption that the assessment of forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) does not provide additional information in asthmatic children with normal FEV1 percent predicted has not been adequately tested.

Objective

We sought to determine whether the measurement of FEF25-75 percent predicted offers advantages over FEV1 percent predicted and FEV1/forced vital capacity (FVC) percent predicted for the evaluation of childhood asthma.

Methods

This is a secondary analysis of data from the Pediatric Asthma Controller Trial and the Characterizing the Response to a Leukotriene Receptor Antagonist and Inhaled Corticosteroid trials. Pearson correlation coefficients, Pearson partial correlation coefficients, canonical correlations, and receiver operating characteristic (ROC) curves were constructed.

Results

Among 437 children with normal FEV1 percent predicted, FEF25-75 percent predicted, and FEV1/FVC percent predicted were (1) positively correlated with log2 methacholine PC20, (2) positively correlated with morning and evening peak expiratory flow percent predicted, and (3) negatively correlated with log10 fraction of exhaled nitric oxide and bronchodilator responsiveness. Pearson partial correlations and canonical correlations indicated that FEF25-75 percent predicted was better correlated with bronchodilator responsiveness and log2 methacholine PC20 than were FEV1 percent predicted or FEV1/FVC percent predicted. In the ROC curve analysis, FEF25-75 at 65% of predicted value had a 90% sensitivity and a 67% specificity for detecting a 20% increase in FEV1 after albuterol inhalation.

Conclusion

FEF25-75 percent predicted was well correlated with bronchodilator responsiveness in asthmatic children with normal FEV1. FEF25-75 percent predicted should be evaluated in clinical studies of asthma in children and might be of use in predicting the presence of clinically relevant reversible airflow obstruction.

Section snippets

Methods

We evaluated baseline lung function in relation to clinical and physiological outcome data from 2 National Heart, Lung, and Blood Institute Childhood Asthma Research and Education network studies: the PACT and the CLIC trial. PACT14 enrolled 413 children between the ages of 6 and 14 years with mild-to-moderate persistent asthma. There was a 2- to 4-week run-in period. The CLIC trial15 enrolled 191 children between the ages of 6 and 17 years with mild-to-moderate persistent asthma. There was a

Results

Table I shows the baseline characteristics of the CLIC trial and PACT cohorts. The PACT children were slightly younger and had a shorter duration of asthma, higher FEV1 percent predicted, higher FEF25-75 percent predicted, lower maximum bronchodilator response, lower methacholine response, and lower exhaled nitric oxide than the CLIC trial children.

Discussion

Asthma is characterized by inflammation of the large and small airways.25, 26 Small airway obstruction has been demonstrated in asthmatic subjects.27, 28, 29 FeNO is a measure of airway inflammation in asthma that has been associated with small airway obstruction.30 These 2 features of asthma are believed to be causally related. Air trapping in asthmatic subjects in the presence of normal FEV1 has been documented.3, 4 The midflow rates measured during spirometric testing are believed to

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  • Cited by (0)

    Supported by grants 5U10HL064287, 5U10HL064288, 5U10HL064295, 5U10HL064307, 5U10HL064305, and 5U10HL064313 from the National Heart, Lung, and Blood Institute. This study was carried out in part in the General Clinical Research Centers at Washington University School of Medicine (M01 RR00036) and National Jewish (M01 RR00051).

    Disclosure of potential conflict of interest: C. A. Sorkness is on advisory boards for GlaxoSmithKline, Schering-Plough, AstraZeneca, and Novartis and receives research support from Schering-Plough and Compleware/Sandoz. R. L. Lemanske is on the speakers' bureau for Merck, AstraZeneca, Doembecher Children's Hospital, Washington University, Medicus Group, Park Nicolet Institute, the American College of Allergy, Asthma & Immunology, the LA Allergy Society, Michigan Allergy/Asthma Society, the Medical College of Wisconsin, the Fund for Medical Research and Education (Detroit), Children's Hospital of Minnesota, the Toronto Allergy Society, AAAAI, Beaumont Hospital (Detroit), the University of Illinois, the Canadian Society of Allergy and Clinical Immunology, and New York Presbyterian; is a consultant for AstraZeneca, Map Pharmaceuticals, Gray Consulting, Smith Research, the Merck Childhood Asthma Network, Novartis, Quintiles/Innovax, RC Horowitz & Co, International Meetings and Science, and Scienomics; is an author for Up-to-Date; and is a textbook editor for Elsevier, Inc. S. J. Szelfer has consultant arrangements with GlaxoSmithKline, Genentech, Merck, Boerhinger Ingelheim, Novartis, and Schering-Plough and receives research support from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), NIH/National Institute of Allergy and Infectious Diseases, GlaxoSmithKline, the National Institute of Environmental Health Sciences, and the Environmental Protection Agency. L. B. Bacharier receives honoraria from AstraZeneca and serves on advisory boards for Genentech, GlaxoSmithKline, Merck, Schering-Plough, and Aerocrine. W. Morgan is a consultant for the Cystic Fibrosis Foundation, Genentech, and Novartis and receives research support from the National Institutes of Health/University of Wisconsin, and Novartis. The rest of the authors have declared that they have no conflict of interest.

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