From the Clinical Inquiries Family Physicians Inquiries Network

Brice A. Labruzzo, PharmD What is the preferred Louisiana State University Health Sciences Center, Shreveport Lisa Edgerton, PharmD treatment for a child New Hanover Regional Medical Center, Wilmington, NC with mild persistent asthma? Stacy Rideout, MLIS, MA Wake Area Health Education Center Medical Library, e v i d e n c e b a s e d a n s w e r - Raleigh, NC Low-dose inhaled corticosteroids are the cromil, theophylline, and cromolyn have all preferred treatment for children with mild demonstrated a modest benefit in symptom persistent asthma because they demon- control; leukotriene receptor antagonists strate superior reduction in severity and fre- are also recommended based on data from quency of asthma exacerbations compared older children (SOR: B, cohort study). Unlike with alternatives (strength of recommenda-® treatmentDowden of moderate Health or severe Media asthma, tion [SOR]: A, based on multiple randomized long-acting beta-agonists are not recom- controlled trials). As add-onCopyright therapy, nedoFor- personalmended (SOR: A use, randomized only trials). c l i n i c a l c o m m e n t a r y Clear medication choices for mild Another common clinical scenario asthma are supported by good evidence among children and adolescents is exer- Physicians who routinely treat children cise-induced asthma. Depending on the with asthma are fortunate to have the body sport, the asthma can be classified as of evidence outlined in this review. Clear “mild persistent” or “mild intermittent.” For medication choices are supported in most true intermittent symptoms, my clinical ex- instances by relatively clear comparisons perience (and often parental preference) with alternatives. In my practice, where argues for pre-activity treatment with short many children can be classified in the “mild acting beta-agonists as the most practical persistent” category, I am always surprised therapy. at how many patients’ families lack a clear John Heintzman, MD Oregon Health and Science University, understanding of the factors that trigger a Portland child’s asthma and how to avoid them.

n Evidence summary Low-dose inhaled corticosteroids Mild persistent asthma is defined as Two large randomized trials support us- forced expiratory volume over 1 second ing low-dose inhaled corticosteroids in

(FEV1) ≥80% predicted, with daytime these children. The Childhood Asthma symptoms more than twice per week Management Program (CAMP) study, but less than once daily, and night- which included 1041 children, evalu- time symptoms more often than twice ated treatment with either budesonide monthly.1 or nedocromil vs placebo. Patients

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I taking budesonide had a lower rate of Long-term systemic effects urgent care visits (absolute risk reduc- The potential long-term adverse system- al

c tion [ARR]=10%; number needed to ic effects of inhaled corticosteroids on treat [NNT]=10; P=.02) compared with growth, bone metabolism, and pituitary- children taking nedocromil (ARR=6%; adrenal function call for longer-term Clini NNT=17; P=.02). The urgent care visits studies.4 A systematic review of 15 trials were reported as number of visits per 100 reported that the protective effect of leu- person-years. kotriene receptor antagonists is inferior In practical terms, this means that in to inhaled corticosteroids for adults (rela- order to decrease 1 urgent care visit, 1 tive risk [RR]=1.71; 95% CI, 1.40–2.09); patient would need to take budesonide however, evidence is insufficient to ex- for 10 years. However, because rates are trapolate this to children.5 not necessarily homogenous over time, the number of visits decreased during the first year may be different than the num- Beta-agonists ber of events decreased throughout the Evidence does not support use of long- tenth year. acting beta-agonists as monotherapy or Children taking budesonide experi- in combination with other medications enced 21.5% more episode-free days than for children with mild persistent asthma. those taking placebo (P=.01). No change Although 1 study showed an improve- was observed in the nedocromil group.2 In ment in lung function for children taking the inhaled Steroid Treatment As Regular budesonide plus formoterol compared Therapy (START) in early asthma study, with budesonide alone, the rate of severe budesonide demonstrated a 44% relative exacerbations was lower for those tak- reduction in time to first severe asthma ing budesonide alone (62% decrease vs related event, compared with placebo 55.8% decrease; P=.001). Both groups (95% confidence interval [CI], 0.45–0.71; had a 32% decrease in the number of res- NNT=44; P=.0001).3 cue inhalations per day when compared fast track with placebo (P=.0008).6 Low doses Theophylline of inhaled steroids Theophylline is considered an alterna- Recommendations from others are far better tive to inhaled corticosteroids. One Recommendations are listed in the at reducing study compared beclomethasone with Table.1,7,8 Unlike the NAEPP and GINA exacerbations theophylline in 195 children. This study asthma guidelines, the BTS/SIGN asthma found near-equivalent efficacy in doc- guidelines define no objective measure- of mild persistent tor visits, hospitalizations, monthly peak ment or staging classification to diagnose asthma expiratory flow rates, and FEV1; however, asthma among children. Diagnosis is de- beclomethasone was superior to theoph- termined by a child’s response to medica- ylline in maintaining symptom control tion.8 Independent of any daily controller and decreasing the use of inhaled bron- medication use, all children should have chodilators and systemic steroids. a short acting bronchodilator on hand in When compared with beclometha- case of an acute attack.1,8,9 sone, theophylline was linked to 14% more central nervous system adverse ef- references fects (P<.001) and 17% more gastro- 1. National asthma education and Prevention Pro- gram. Expert Panel Report: Guidelines for the Di- intestinal disturbances (P<.001). Although agnosis and Management of asthma update on beclomethasone induced more oral candi- Selected Topics—2002. National asthma educa- diasis compared with theophylline (8.9% tion and Prevention Program. J Allergy Clin Immu- nol 2002; 110:S141–S219. vs 2.4%; P<.001), the incidence of this in- 2. Long-term effects of budesonide or nedocromil in fection can be reduced by using a spacer. children with asthma. The Childhood Asthma Man-

138 vol 56, No 2 / february 2007 The Journal of Family Practice Treatment of mild persistent asthma p

t a b l e Recommendations for treating mild persistent asthma

Guideline Daily controller medication Alternative treatment

National Asthma Education Low-dose inhaled corticosteroids Children <5: cromolyn, LTRAs and Prevention Program Children >5: cromolyn, LTRAs, nedocromil, (NAEPP)1 sustained release theophylline

Global Initiative for Low-dose inhaled corticosteroids All children: Sustained released theophylline, Asthma (GINA)7 Cromone, LTRAs

British Thoracic Society/ Inhaled steroids All children: LTRAs, theophylline Scottish Intercollegiate Children >5: cromones, nedocromil Guidelines Network (BTS/SIGN)8

LRTA, leukotriene receptor antagonists. Sources: NAEPP, J Allergy Clin Immunol 20021; GINA, Guidelines and Resources 2005,7 and BTS/SIGN, Thorax 2003.8

agement Program Research Group. N Engl J Med asthma in adults and children (Cochrane Review). 2000; 343:1054–1063. In: The Cochrane Library 2006 Issue 2. Chichester, 3. Pauwels ra, Pedersen s, busse WW, et al; UK: John Wiley and Sons, Ltd. START Investigators Group. early interven- 6. O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, et al. tion with budesonide in mild persistent asthma: Low dose inhaled budesonide and formoterol in a randomised, double-blind trial. Lancet 2003; mild persistent asthma: the oPTIMA randomized 361:1071–1076. trial. Am J Respir Crit Care Med 2001; 164:1392– 4. Reed CE, Offord KP, Nelson HS, Li JT, Tinkelman 1397. DG. aerosol beclomethasone dipropionate spray 7. The Global Initiative for Asthma. Guidelines and Re- compared with theophylline as primary treatment sources: 2005 Update. Available at: www.ginasth- for chronic mild-to-moderate asthma. The Ameri- ma.com/Guidelineitem.asp??I1=2&I2=1&intId=60. can Academy of Allergy, Asthma and Immunology Accessed January 9, 2007. Beclomethasone Dipropionate-Theophylline Study 8. British Thoracic society scottish Intercollegiate Group. J Allergy Clin Immunol 1998; 101:14–23. Guidelines Network. British guideline on the man- 5. Ducharme FM, Salvio F, Ducharme F. Anti-leukot- agement of asthma. a national clinical guideline. riene agents compared to inhaled corticosteroids Thorax 2003; 58:i1–i94. in the management of recurrent and/or chronic

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