Correspondence

Budesonide in Preschool-Age Children with Recurrent Wheezing

N Engl J Med 2012; 366:570-571February 9, 2012

Article

To the Editor:

In the Maintenance and Intermittent Inhaled Corticosteroids in Wheezing Toddlers (MIST) trial (ClinicalTrials.gov number, NCT00675584), Zeiger et al. (Nov. 24 issue)1 suggest that intermittent high-dose budesonide was equal in efficacy to daily low-dose budesonide in preschool-age children with recurrent wheezing. This conclusion requires some further clarification. The study involved children with episodic, mild, and moderate asthma. Children with more severe asthma, with either more than six courses of oral glucocorticoids or more than two hospitalizations for wheezing during the previous year, were excluded. Mild episodic asthma constitutes the vast majority of cases and, at least in Australia, these children are not routinely prescribed preventive inhaled low-dose glucocorticoids.2 These children, by definition, are asymptomatic for most of the time and would have little scope for improvement on treatment. Can the authors please clarify what proportion of their study cohort had episodic asthma?

Alison Poulton, M.D.
Anthony Liu, M.P.H., M.Med.Ed.
Ralph Nanan, Dr.Med., Habil.
University of Sydney, Sydney, NSW, Australia
alison.poulton@sydney.edu.au

No potential conflict of interest relevant to this letter was reported.

2 References

1. 1

   Zeiger RS, Mauger D, Bacharier LB, et al. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med 2011;365:1990-2001
   Full Text | Web of Science | Medline

2. 2

   Asthma management handbook 2006. Melbourne: National Asthma Council Australia, 2006.
   

To the Editor:

In the study by Zeiger et al., the use of intermittent budesonide and the use of daily budesonide resulted in an equal number of exacerbations that required oral glucocorticoid therapy. If these findings are true, it could be possible to avoid unnecessary medication use. An important precondition with respect to the effectiveness of intermittent budesonide use is the ability of the parents to make the right decisions about when to start the budesonide treatment. Do the authors think that the intermittent treatment regimen of budesonide is suitable for every parent with a child with asthma? And do the authors have information about characteristics of the parents that were related to successfully administered intermittent budesonide treatment?

Lisette van den Bemt, Ph.D.
Lotte van den Nieuwenhof, M.D., Ph.D.
Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
l.vandenbemt@elg.umcn.nl

No potential conflict of interest relevant to this letter was reported.

To the Editor:

Zeiger et al. report that early intermittent high-dose inhaled glucocorticoid treatment effectively reduced asthma exacerbations in preschool-age children with wheezing. Applying this strategy in clinical practice poses a problem. In this study and in the previous Acute Intervention Management Strategies (AIMS) study (NCT00000622) by the same CARE Network,1 patients were treated with an inhaled budesonide suspension delivered by means of a nebulizer, which may not reflect its delivery when a similar metered-dose inhaler is used for delivery. International guidelines on asthma management in preschool-age children recommend a metered-dose inhaler with a dedicated spacer and mask as the preferred device for delivering inhaled drugs2; despite this recommendation, nebulizers are widely used.3 With the currently available evidence,1,4 should we consider that the same results would have been obtained if a metered-dose inhaler and spacer, which are more portable than a nebulizer, had been used?

Eugenio Baraldi, M.D.
University of Padua, Padua, Italy
baraldi@pediatria.unipd.it

Giovanni A. Rossi, M.D.
Gaslini Institute, Genoa, Italy

Attilio L. Boner, M.D.
University of Verona, Verona, Italy

for the Beclomethasone and Salbutamol Treatment (BEST) for Children Study Group (NCT00497523)

No potential conflict of interest relevant to this letter was reported.

4 References

1. 1

   Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol 2008;122:1127-1135
   CrossRef | Web of Science | Medline

2. 2

   Global Initiative for Asthma (GINA). Global strategy for the diagnosis and management of asthma in children 5 years and younger. 2009 (http://www.ginasthma.org).
   

3. 3

   Bisgaard H, Szefler S. Prevalence of asthma-like symptoms in young children. Pediatr Pulmonol 2007;42:723-728
   CrossRef | Web of Science | Medline

4. 4

   Papi A, Nicolini G, Boner AL, et al. Short term efficacy of nebulized beclomethasone in mild-to-moderate wheezing episodes in pre-school children. Ital J Pediatr 2011;37:39-39
   CrossRef | Web of Science

Author/Editor Response

Poulton et al. request additional information about the proportion of the study cohort that had an episodic wheezing phenotype. We specifically studied a subgroup of preschool-age children with recurrent wheezing who had an increased risk of future persistent asthma as determined by a positive value on the modified asthma predictive index (API).1 Eligibility required that all patients in the cohort had episodic, rather than persistent, symptoms and at least one significant wheezing exacerbation in the prior year. We previously found that preschool-age children with a positive value on the API and a recurrent wheezing phenotype benefited from daily inhaled glucocorticoids with a reduced illness burden.1,2

Van den Bemt and van den Nieuwenhof correctly note that the success of an intermittent treatment regimen clearly depends on the ability of parents to know when and how to administer such a regimen. As we noted, parents require careful, individualized instruction on when to start the intermittent regimen to ensure the appropriate use of this approach. We used a previously reported successful educational program that taught parents when to initiate the intermittent regimen.3 Parents did not have difficulty in following the intermittent regimen.

Baraldi et al. question whether high-dose inhaled glucocorticoids administered by means of a metered-dose inhaler delivery system with spacer and mask would lead to results that are similar to those shown for high-dose budesonide delivered by means of a nebulizer, as in the MIST study. It would be anticipated that similar results would be derived if equipotent doses of inhaled glucocorticoids were administered by means of the metered-dose inhaler system. Although the clinical effects of intermittent therapy with high-dose budesonide may be associated with a class effect of inhaled glucocorticoids, our data cannot be extended with confidence beyond the inhaled glucocorticoid product and delivery system used in our study.

Robert S. Zeiger, M.D., Ph.D.
University of California, La Jolla, CA

David Mauger, Ph.D.
Pennsylvania State University, Hershey, PA

Leonard B. Bacharier, M.D.
Washington University, St. Louis, MO

Since publication of their article, the authors report no further potential conflict of interest.

3 References

1. 1

   Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med 2006;354:1985-1997
   Full Text | Web of Science | Medline

2. 2

   Bacharier LB, Guilbert TW, Zeiger RS, et al. Patient characteristics associated with improved outcomes with use of an inhaled corticosteroid in preschool children at risk for asthma. J Allergy Clin Immunol 2009;123:1077-1082
   CrossRef | Web of Science | Medline

3. 3

   Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol 2008;122:1127-1135
   CrossRef | Web of Science | Medline