Original Articles: Asthma Lower Airway Diseases
Exhaled nitric oxide as a predictor of exacerbation in children with moderate-to-severe asthma: a prospective, 5-month study

https://doi.org/10.1016/S1081-1206(10)60183-4Get rights and content

Background

Inhaled corticosteroids (ICSs) are recommended as the first line of treatment in children with moderate-to-severe asthma. Exhaled nitric oxide (ENO) has been proposed as a clinically useful marker of control that might help identify patients in whom ICS dose may be safely reduced.

Objective

To evaluate the ability of ENO to predict future asthma exacerbations in children with moderate-to-severe asthma undergoing ICS tapering.

Methods

This is an observational study with no control group. ENO was measured biweekly for 14 weeks in 32 children with moderate-to-severe asthma who were undergoing ICS tapering. Clinical evaluations and spirometry were performed concomitantly, and families kept daily diaries to record symptoms between visits. We used generalized estimating equations to model the ln (odds) of an asthma exacerbation in the subsequent 2-week interval as a function of ENO level at the start of the interval while adjusting for age, sex, asthma severity, and current medication use.

Results

We were able to successfully lower ICS doses in 10 (56%) of the 18 children with moderate asthma and in 3 (21%) of the 14 children with severe asthma. In 83 of the 187 follow-up clinical evaluations, children were determined to have had an exacerbation during the preceding 2 weeks. ENO levels, whether expressed as a continuous variable or dichotomized, were not associated with future risk for exacerbations in either unadjusted or adjusted models.

Conclusion

ENO was not a useful clinical predictor of future asthma exacerbations for children with moderate-to-severe asthma undergoing ICS tapering.

Section snippets

INTRODUCTION

Although inhaled corticosteroids (ICSs) are the recommended first-line treatment for asthma in children,1, 2, 3 long-term use can lead to systemic effects,4, 5 and, therefore, the lowest dose needed to maintain good asthma control should be used. Because of the great variability of the dose required both between children and within individual children, safe methods to guide titration are highly desirable. Once a patient has achieved control over a period, the health care provider can carefully

Study Population

We examined all 104 children aged 7 to 14 years who met the criteria for moderate-to-severe asthma1 (based on current history, stability of disease in the previous year, rates of exacerbation, medication needs, and pulmonary function) and, as of the start of the study protocol in October 2004, had been receiving care from us at the outpatient clinic of Hospital Infantil Darcy Vargas, Sao Paulo, Brazil, for at least 12 months. From this group, we excluded 72 children: 34 who had not been

RESULTS

Of the 32 children who began the study, 27 completed all 7 follow-up visits after the initiation of tapering; the other 5 completed all but the last follow-up visit. All are included in the analysis. Study participants averaged 10.3 years of age, and 66% were male (Table 1).

At the beginning of tapering, the average FEV1 was 90.0% of the predicted value and the average ENO level was 38 ppb. As expected, the clinical indicators were worse for the 14 children with severe asthma compared with the

DISCUSSION

Our results showed that ENO measurements were not a predictor of future exacerbation in children with atopic, moderate-to-severe asthma undergoing a period of steroid tapering.

Prior studies addressing the utility of ENO as a predictor of asthma exacerbations have shown conflicting results. Several studies failed to prove that ENO was a good predictor of loss of control or future exacerbation in adult9, 22, 37 patients while tapering the ICS dose. More recently, Menzies et al22 evaluated the

ACKNOWLEDGMENTS

We acknowledge the contribution of the American Thoracic Society’s Methods in Epidemiologic, Clinical and Operations Research course in the development of this article.

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    Disclosures: Authors have nothing to disclose.

    Funding Sources: This study was supported by the following Brazilian scientific agencies: Fundação de Amparo à Pesquisa do Estado de São Paulo and Conselho Nacional de Desenvolvimento Científico e Tecnológico.

    Previous Presentation: Presented in part at the International Meeting of the American Thoracic Society; San Francisco, California; May 22, 2007.

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