COMPARABLE EFFICACY OF ADMINISTRATION WITH FACE MASK OR MOUTHPIECE OF NEBULIZED BUDESONIDE SUSPENSION FOR INFANTS AND YOUNG CHILDREN WITH PERSISTANT ASTHMA

To the Editor :

We read with interest the article by Mellon and colleagues in which a retrospective analysis suggested that inhalation of nebulized budesonide is as effective given either via a face mask or mouthpiece to infants and young children with persistent asthma (1). We believe, however, that this conclusion should be interpreted with a degree of caution. This study represents an underpowered retrospective analysis owing to the small numbers of patients in each subgroup at each dose of budesonide and placebo. It is also evident for the primary efficacy variable that there is no evidence of any dose-response effect. This makes it difficult to truly discriminate between the two modes of delivery. Furthermore, for change in nighttime asthma symptoms from baseline there was a significant difference from placebo for budesonide 0.25 mg once daily administered via face mask but not when administered via mouthpiece, suggesting that the mouthpiece may be less effective. In view of the problems of confounding the overall alpha error by subgroup analysis between face mask and mouthpiece, as well as the lack of any dose-response effect, it is not possible to deduce any sensible conclusions about the relative efficacy of delivering budesonide through the face mask or mouthpiece. It is possible that some small difference might be missed, particularly at lower doses. From a pragmatic point of view one could argue that this does not really matter, as it is better to deliver at least some inhaled corticosteroid to an asthmatic child with a face mask rather than none at all if the child is unable to use a mouthpiece.

We have now had experience with using nebulized budesonide in Scotland over the past decade, and given its prohibitive cost, along with the hassle of using a nebulizer, we have never been entirely convinced of its advantages for use in infants and younger children. Our policy in this age group is to first try using a metered dose inhaler with spacer device either via a mouthpiece or mask, or a dry power inhaler in schoolchildren. In terms of cost, even excluding the expense of a compressor and nebulizer, the 28-day drug cost for budesonide nebulizer suspension (500 µg daily) is approximately $69.4, whereas budesonide pMDI via spacer (200 µg daily) is $5.8, and budesonide dry powder via Turbuhaler (200 µg daily) is $8.0 (all calculated from current UK price as 1GBP = 1.55USD).

One could argue the bottom line for clinical therapeutic response is that it does not really matter what nominal dose is delivered via either a mouthpiece or a mask as long as the desired clinical response is obtained using either a spacer or nebulizer, provided that the child and parent are also happy using their chosen device.

University of Dundee, Scotland, United Kingdom

5. Mellon M, Leflein J, Walton-Bowen K, Criz-Rivera M, Fitzpatric S, Smith JA. Comparable efficacy of administration with facemask or mouthpiece of nebulized budesonide inhalation suspension for infants and young children with persistent asthma. Am J Resp Crit Care Med 2000; 162: 593-598 [Abstract/Free Full Text].

From the Authors:

The purpose of our retrospective analysis was to determine if the efficacy with nebulized budesonide inhalation suspension (BIS) observed in the prospective study, in which data were pooled from both younger children, capable of only face mask use, and older children able to use a mouthpiece, resided primarily with one mode of delivery. The results of the retrospective analysis showed statistically significant improvements in nighttime asthma symptoms for BIS at 0.25 mg daily (p = 0.040), 0.25 mg twice daily (p = 0.0008), and 0.5 mg twice daily (p = 0.046) when delivered by face mask as compared with placebo. In patients using mouthpieces, nighttime asthma symptoms improved significantly in the 0.25 mg twice daily (p = 0.005) and 1.0 mg daily (p = 0.035) groups, and daytime asthma symptoms also improved significantly (p = 0.009) in the 0.5 mg twice daily group, compared with placebo. Based on these results, we concluded that "BIS can be administered effectively by either face mask or mouthpiece to young children with persistent asthma," as stated in the paper. Also, we acknowledged that retrospective analyses such as ours are useful to generate hypotheses, but have limitations when study groups are further stratified after completion of the study. To make a more quantitative comparison between the two forms of delivery is not possible because the ages of the two groups are different, and this was not the purpose of either study. In addition, the absence of a dose-response effect for inhaled corticosteroids in the treatment of asthma in young children, when symptoms are the primary efficacy variable, is not unique to our study (1).

We note with much interest the clinical impressions of Professor Lipworth and Dr. Jackson and concur with the principle that when different treatments are proven equally effective and safe, the less expensive and easier-to-deliver treatment is preferable. The proof of efficacy of pressurized metered-dose inhalers with spacers in young children has been best demonstrated with beta agonists in the acute asthma setting (2) and cannot necessarily be extrapolated to inhaled corticosteroid delivery. In addition, pre- school age children often have difficulty with dry powder inhalers.

Currently in the United States, the only approved inhaled corticosteroid for asthma for children under the age of 4 is BIS. Also, some devices (e.g., Babyhaler) and drugs (e.g., budesonide pMDI) that might increase our treatment options are not available even for off-label use. As evidence mounts that asthma is a progressive disease in some children (3, 4) and that early intervention with inhaled corticosteroids can attenuate the deterioration in pulmonary function seen in these children (5), the challenge for us is to increase the appropriate use of inhaled corticosteroids in young children who are currently undertreated with anti-inflammatory medication. To this end, we are in agreement with Professor Lipworth and Dr. Jackson when they say "It does not really matter what nominal dose is delivered via either face mask or mouthpiece as long as the desired clinical response is obtained using either a spacer or a nebulizer, providing the child and the parent are happy using their chosen device."

Kaiser Permanente Medical Offices, San Diego, California

Jeffrey Leflein, MD

Allergy and Immunology Associates of Ann Arbor, P.C.Ann Arbor, Michigan

1. Bisgaard H, Gillies J, Groenwald M, Maden C. on behalf of an International Study Group. The effect of inhaled fluticasone propionate in the treatment of young asthmatic children. Am J Respir Crit Care Med 1999; 160: 126-131 [Abstract/Free Full Text].

2. Schuh S, Johnson DW, Stephens D, Callahan S, Winders P, Canny GJ. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma. J Pediatr 1999; 135: 22-27 [Medline].

3. Zeiger RS, Dawson C, Weiss S. for the Childhood Asthma Management Program (CAMP) Research Group. Relationships between duration of asthma and asthma severity among children in the Childhood Asthma Management Program (CAMP). J Allergy Clin Immunol 1999; 103: 376-387 [Medline].

4. Weiss ST, Van Naita ML, Zeiger RS. for the Childhood Asthma Management Program (CAMP) Research Group. Relationship between increased airway responsiveness and asthma severity in the Childhood Asthma Management Program. Am J Respir Crit Care Med 2000; 162: 50-56 [Abstract/Free Full Text].

5. Agertoft L, Pedersen S. Effects of long-term treatment with inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 1994; 88: 373-381 [Medline].