Asthma and lower airway disease
Diagnostic accuracy of the bronchodilator response in children

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Background

The bronchodilator response (BDR) reflects the reversibility of airflow obstruction and is recommended as an adjunctive test to diagnose asthma. The validity of the commonly used definition of BDR, a 12% or greater change in FEV1 from baseline, has been questioned in childhood.

Objectives

We sought to examine the diagnostic accuracy of the BDR test by using 3 large pediatric cohorts.

Methods

Cases include 1041 children with mild-to-moderate asthma from the Childhood Asthma Management Program. Control subjects (nonasthmatic and nonwheezing) were chosen from Project Viva and Home Allergens, 2 population-based pediatric cohorts. Receiver operating characteristic curves were constructed, and areas under the curve were calculated for different BDR cutoffs.

Results

A total of 1041 cases (59.7% male; mean age, 8.9 ± 2.1 years) and 250 control subjects (46.8% male; mean age, 8.7 ± 1.7 years) were analyzed, with mean BDRs of 10.7% ± 10.2% and 2.7% ± 8.4%, respectively. The BDR test differentiated asthmatic patients from nonasthmatic patients with a moderate accuracy (area under the curve, 73.3%). Despite good specificity, a cutoff of 12% was associated with poor sensitivity (35.6%). A cutoff of less than 8% performed significantly better than a cutoff of 12% (P = .03, 8% vs 12%).

Conclusions

Our findings highlight the poor sensitivity associated with the commonly used 12% cutoff for BDR. Although our data show that a threshold of less than 8% performs better than 12%, given the variability of this test in children, we conclude that it might be not be appropriate to choose a specific BDR cutoff as a criterion for the diagnosis of asthma.

Section snippets

Subjects

Participants from 3 pediatric cohorts were included in this study. Asthma cases consisted of children enrolled in the Childhood Asthma Management Program (CAMP). The demographics of the CAMP subjects and the study design have been previously reported.15 Briefly, this multicenter trial randomized 1041 children with mild-to-moderate asthma aged 5 to 13 years to budesonide, nedocromil, or placebo. Children were included if they had asthma symptoms 2 or more times per week, used an asthma

Patient demographics

A total of 1041 children with mild-to-moderate asthma were included from the CAMP cohort (cases). Control subjects consisted of 250 children from the Project Viva and Home Allergens cohorts who had no history of wheezing and asthma at the time of the BDR test. Baseline characteristics of the study population by asthma status are presented in Table I. Although their baseline FEV1 percent predicted values were similar and within normal limits (93.7% ± 14.3% in cases and 98.4% ± 12.2% in control

Discussion

In this analysis of the diagnostic accuracy of the BDR test, we found that the commonly used BDR cutoff of 12% was associated with a poor sensitivity and that a BDR cutoff of 8% or lower performed better than 12% at differentiating between children with and without asthma using 3 predominantly white populations.

The BDR test is recommended as an adjunct in the diagnosis of asthma, along with the clinical history and signs of inflammation, such as eosinophilia and increased IgE levels. This test

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      Data from Tse et al28 suggest that a threshold of less than 8% performs better than 12% in younger populations. Given the variability in spirometric testing in children, it might not be appropriate to choose a specific bronchodilator reversibility cutoff as a criterion for the diagnosis of asthma in younger children.28 Response to therapy can be assessed subjectively in terms of symptom control and exercise tolerance.

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    The Childhood Asthma Management Program is supported by contracts NO1-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052 with the National Heart, Lung, and Blood Institute and General Clinical Research Center grants M01RR00051, M01RR0099718-24, M01RR02719-14, and RR00036 from the National Center for Research Resources. Additional support for this research came from grants P50 HL67664, U01 HL65899, and T32 HL07427 from the National Institutes of Health and the National Heart, Lung, and Blood Institute. Home Allergens is funded by National Institute of Allergy and Infectious Diseases/R01 grant AI035786. Project Viva is funded by R01 HL064925 and R01 HD034568.

    Disclosure of potential conflict of interest: S. M. Tse, M. W. Gillman, and K. G. Tantisira have been supported by/have received one or more grants from or have one or more grants pending with the National Institutes of Health (NIH). D. R. Gold has been supported by one or more grants from the National Institute of Allergy and Infectious Diseases. A. L. Fuhlbrigge has been supported by one or more grants from and has received support for travel from the National Heart, Lung, and Blood Institute (NHLBI); is a Board member for Merck; has consultancy arrangements with Merck, GlaxoSmithKline, ICON Medical Imaging, Sunovion, the Lovelace Respiratory Research Institute, and Dmagi; and has received one or more grants from or has one or more grants pending with the NHLBI and the Agency for Healthcare Research and Quality. A. A. Litonjua has been supported by one or more grants from the NIH and has received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest.

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