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American Journal of Respiratory and Critical Care Medicine Vol 172. pp. 1058-1059, (2005)
© 2005 American Thoracic Society

Correspondence

Inhaled Corticosteroids in Wheezy Infants

To the Editor:

With considerable interest we read the article by Teper and colleagues (1), who suggested that till now, the efficacy of inhaled corticosteroids (ICS) in children with recurrent wheeze had been mainly studied on clinical endpoints, but that the effect of ICS on ventilatory function measurements had not been fully addressed. To our knowledge, at least 11 other publications now exist on this topic (1–11), of which 5 included lung function tests as endpoint (1, 2, 6, 9, 11), but these were not discussed by Teper and coworkers.

Studies are still inconclusive as regards efficacy in infants with chronic/recurrent wheeze on symptoms and/or lung function (see Table 1). Strikingly, the studies describing a beneficial effect were mostly performed in older preschool children, and the studies in which ICS was not superior to placebo were all performed in children < 2 yr of age. Also, in our own recent study in wheezing infants treated with fluticasone for 3 mo, no effect on lung function was observed (11). Therefore, the most interesting aspect of the study of Teper and coworkers is that they observed lung function improvement in a relatively small group of 26 infants who had been selected because of significant airway obstruction and clinical improvement after bronchodilators out of 102 children < 2 yr of age with risk factors for asthma. This means that a special selection was made, since bronchodilators are effective in a minority of infants (12). It is possible that they included the infants with early-onset asthma by this selection procedure.


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  		TABLE 1. Details of randomized controlled trials of inhaled steroids in preschool children with wheeze

 
Because of the various phenotypes of infant wheeze, it is especially difficult to assess what characteristics predict a beneficial ICS response in the youngest age group. In addition, because the contribution of children with transient or viral wheeze becomes progressively smaller with age, this will reduce the "contamination" of wheeze due to causes other than asthma in children over 2 yr of age. These aspects were not considered fully previously and should be taken into account in future studies with infants to optimally characterize those wheezy infants who will respond to ICS treatment, to minimize possible side effects of this treatment (13).

Peter J. F. M. Merkus and Johan C. de Jongste

Erasmus Medical Centre, Sophia Children's Hospital, Rotterdam, the Netherlands

FOOTNOTES

Conflict of Interest Statement: Neither of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

  1. Teper AM, Kofman CD, Szulman GA, Vidaurreta SM, Maffey AF. Fluticasone improves pulmonary function in children under 2 years old with risk factors for asthma. Am J Respir Crit Care Med 2005;171:587–590.[Abstract/Free Full Text]
  2. Maayan C, Itzhaki T, Bar-Yishay E, Gross S, Tal A, Godfrey S. The functional response of infants with persistent wheezing to nebulized beclomethasone dipropionate. Pediatr Pulmonol 1986;2:9–14.[Medline]
  3. Bisgaard H, Munck SL, Nielsen JP, Petersen W, Ohlsson SV. Inhaled budesonide for treatment of recurrent wheezing in early childhood. Lancet 1990;336:649–651.[CrossRef][Medline]
  4. Noble V, Ruggins RN, Everard ML, Milner AD. Inhaled budesonide for chronic wheezing under 18 months of age. Arch Dis Child 1992;67:285–288.[Abstract]
  5. Connett GJ, Warde C, Wooler E, Lenney W. Use of budesonide in severe asthmatics aged 1–3 years. Arch Dis Child 1993;69:351–355.[Abstract]
  6. Kraemer R, Graf Bigler U, Casaulta Aebischer C, Weder M, Birrer P. Clinical and physiological improvement after inhalation of low-dose beclomethasone dipropionate and salbutamol in wheezy infants. Respiration (Herrlisheim) 1997;64:342–349.
  7. Bisgaard H, Gillies J, Groenewald M, Maden C. The effect of inhaled fluticasone propionate in the treatment of young asthmatic children: a dose comparison study. Am J Respir Crit Care Med 1999;160:126–131.[Abstract/Free Full Text]
  8. Van Bever HP, Schuddinck L, Wojciechowski M, Stevens WJ. Aerosolized budesonide in asthmatic infants: a double blind study. Pediatr Pulmonol 1990;9:177–180.[Medline]
  9. Stick SM, Burton PR, Clough JB, Cox M, LeSouef PN, Sly PD. The effects of inhaled beclomethasone dipropionate on lung function and histamine responsiveness in recurrently wheezy infants. Arch Dis Child 1995;73:327–332.[Abstract]
  10. Barrueto L, Mallol J, Figueroa L. Beclomethasone dipropionate and salbutamol by metered dose inhaler in infants and small children with recurrent wheezing. Pediatr Pulmonol 2002;34:52–57.[CrossRef][Medline]
  11. Hofhuis W, van der Wiel EC, Nieuwhof EM, Hop WCJ, Affourtit MJ, Smit FJ, Vaessen-Verberne AAPH, Versteegh FGA, de Jongste JC, Merkus PJFM on behalf of the Anti-Inflammatory Treatment in Infants with Recurrent Wheeze (AIR) Study Group. Efficacy of fluticasone propionate on lung function and symptoms in wheezy infants. Am J Respir Crit Care Med 2005;171:328–333.[Abstract/Free Full Text]
  12. Chavasse R, Seddon P, Bara A, McKean M. Short acting beta agonists for recurrent wheeze in children under 2 years of age. Cochrane Database Syst Rev 2002;3:CD002873.
  13. Kovar J, Willet KE, Hislop A, Sly PD. Impact of postnatal glucocorticoids on early lung development. J Appl Physiol 2005;98:881–888.[Abstract/Free Full Text]




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