Asthma and lower airway disease
Identifying the components of asthma health status in children with mild to moderate asthma

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Background

Weak and inconsistent correlations between measurements of asthma health status suggest that the disease is composed of nonoverlapping components.

Objective

Factor analysis was used to explore the relationships between measures of asthma morbidity and to identify heterogeneous components of asthma health status in children 5 to 12 years old. Results were compared across time (baseline and 48-month visit) and treatment arms.

Methods

Analyses were conducted in 7 different study windows in a database from a large clinical trial of children with mild to moderate asthma (n = 1041). Measurements of lung function, symptoms, and health care utilizations from daily diary cards, serum IgE levels, total eosinophil count, skin test positivity, and airway hyperresponsiveness were included. Data on fractional exhaled nitric oxide and sputum eosinophil cationic protein were included in a subgroup of patients.

Results

In each of the study windows, factor analysis identified 5 factors that explained between 50% and 60% of the common variance. Factors identified included (1) inflammatory markers, (2) symptoms/medication use, (3) asthma exacerbations, and measures of lung function, which subdivided into (4) FEV1 and forced vital capacity, and (5) bronchodilator response and the FEV1/forced vital capacity ratio. Exploratory analyses suggest that fractional exhaled nitric oxide account for the atopy/inflammatory marker factor, and sputum measurements account for a sixth, separate factor.

Conclusion

The consistent identification of a 5-factor structure across time and treatment arms suggests that each of these factors provides independent information in the assessment of asthma.

Section snippets

Methods

Data for this study were taken from the Childhood Asthma Management Program, a double-blind, controlled study designed to evaluate whether the long-term treatment with budesonide or nedocromil produced improvements in lung growth compared with placebo over a period of 5 to 6½ years. Eligible patients were between 5 and 12 years of age with mild or moderate asthma as defined by National Asthma Education and Prevention Program criteria. The protocol for this study was approved by the

Results

Clinical, laboratory, and demographic characteristics of the study population during the screening period before randomization are shown in Table I. Of the 1041 patients enrolled in the trial, 990 had nonmissing values and were used in the analysis at the randomization window. The majority of patients were white and male, and the mean age of this population at baseline was 9.0 ± 2.1. During the randomization window, 40.6% of patients had at least 1 night awakening because of symptoms, and 12.0%

Discussion

Our inclusive analysis has identified a clinically sensible, 5-factor structure explaining between 50% and 60% of the common variance from an inclusive list of variables not previously analyzed together. The factor loading structure remains consistent over the 48-month treatment period and among treatment arms. We believe that this analysis provides further evidence that asthma requires a multicomponent assessment: measurement of 1 or 2 variables alone will not give an adequate picture of the

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    Supported by National Heart, Lung, and Blood Institute grant NO1-HR-16044-16052 and GlaxoSmithKline.

    Disclosure of potential conflict of interest: R. A. Covar has received research support from AstraZeneca, Ross Abbott Laboratories, and Merck. J. Spahn has consulting arrangements with GlaxoSmithKline, has received research support from AstraZeneca and Merck, and is on the speakers' bureau for GlaxoSmithKline and Merck. A. L. Fuhlbrigge is on the speakers' bureau for GlaxoSmithKline and Merck; designed and performed analysis of studies for GlaxoSmithKline, Novartis, and Merck; is on the Data Safety and Monitoring Board for Sepracor; and has received research support from Boehringer Ingelheim, GlaxoSmithKline, and Merck. The rest of the authors have declared that they have no conflict of interest.

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