Abstract
During the last 30 years, a significant rise in wheezing illness has occurred in the child population. Despite its high prevalence there is no clear definition of the disease, which includes a heterogeneous group of syndromes ranging from transient wheezing in infancy to atopic asthma with persistence into adult life. Molecular advances and further epidemiological information from well characterised individuals and their families are likely to clarify the different subtypes of wheezing illness and inform therapeutic options. With the recognition that chronic airway inflammation is a feature of persistent disease, at least in adults, there has been a trend towards the early introduction of anti-inflammatory treatment and particularly inhaled corticosteroids (ICS). However, the natural resolution of much wheezing illness, particularly in young children and in children with viral-induced episodes, suggests that newly presenting children should remain on symptomatic therapy alone while the severity of the disease is being assessed. Although ICS have become a cornerstone of management of chronic persistent disease, their ability to protect against exacerbations in young and mildly affected children is questionable. Alongside concerns about long term use of ICS and possible systemic adverse effects, there remains a need for alternative approaches to the control of the disease in children. Extrapolation of the findings of large multicentre adult studies into childhood, particularly for doubling the doses of ICS and long-acting β2-agonists, may be unsound. Other approaches include the early introduction of inhaled cromones, use of second generation antihistamines, low dose theophyllines and, more recently, leukotriene modifiers. As the majority of preschool children will become asymptomatic by mid-childhood, there is an urgent need to identify those in whom chronic airway inflammation is developing, as it is in this group that early introduction of ICS may be of maximum benefit. In the remainder, other approaches, including use of corticosteroid-sparing long-acting β2-agonists and leukotriene modifying drugs, may be more appropriate. Safe and effective oral preparations such as leukotriene modifying drugs are likely to establish a significant role in the management of symptoms in children of all ages and with all types of asthma and wheezing illness.
Similar content being viewed by others
References
Ninan TK, Russell G. Respiratory symptoms and atopy in Aberdeen schoolchildren: evidence from two surveys 25 years apart. BMJ 1992; 304: 873–5
Burr ML, Butland BK, King S, et al. Changes in asthma prevalence: two surveys 15 years apart. Arch Dis Child 1989; 64: 1452–6
Robertson CF, Heycock E, Bishop J, et al. Prevalence of asthma in Melbourne schoolchildren: changes over 26 years. BMJ 1991; 302: 1116–8
Warner JO, Gotz M, Landau LI, et al. Management of asthma: a consensus statement. Arch Dis Child 1989; 64: 1065–79
Wilson NM. Wheezy bronchitis revisited. Arch Dis Child 1989; 64: 1194–9
Christie G, Helms P. Childhood asthma: what is it and where is it going? Thorax 1995; 50: 1027–30
Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995; 332: 133–8
Brooke AM, Lambert PC, Burton PR, et al. The natural history of respiratory symptoms in preschool children. Am J Respir Crit Care Med 1995; 152 (6 Pt 1): 1872–8
Silverman M. Out of the mouths of babes and sucklings: lessons from early childhood asthma. Thorax 1993; 48(12): 1200–4
Martinez FD, Morgan WJ, Wright AL, et al. Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N Engl J Med 1988; 319: 1112–7
Wang X, Wypij D, Gold DR, et al. A longitudinal study of the effects of parental smoking on pulmonary function in children 6–18 years. Am J Respir Crit Care Med 1994; 149: 1420–5
Pattemore PK, Asher MI, Harrison AC, et al. The interrelationship among bronchial hyperresponsiveness, the diagnosis of asthma, and asthma symptoms. Am Rev Respir Dis 1990; 142: 549–54
Peat JK, Britton WJ, Salome CM, et al. Bronchial hyperresponsiveness in two populations of Australian schoolchildren. II. Relative importance of associated factors. Clin Allergy 1987; 17: 283–90
Burrows B, Marinez FD, Halonen M, et al. Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med 1989; 320(5): 271–7
Kelly WJ, Hudson I, Phelan PD, et al. Atopy in subjects with asthma followed to the age of 28 years. J Allergy Clin Immunol 1990; 85(3): 548–57
Martin AJ, Landau LI, Phelan PD. Asthma from childhood at age 21: the patient and his disease. BMJ 1982; 284: 380–2
Roorda RJ, Gerritsen J, Van Aalderen WMC, et al. Risk factors for the persistence of respiratory symptoms in childhood asthma. Am Rev Respir Dis 1993; 148 (6 Pt 1): 1490–5
Gottlieb DJ, Sparrow D, O'Connor GT, et al. Skin test reactivity to common aeroallergens and decline in lung function: the Normative Aging Study. Am J Respir Crit Care Med 1996; 153: 561–6
Sporik R, Holgate ST, Cogswell JJ. Natural history of asthma in childhood — a birth cohort study. Arch Dis Child 1991; 66: 1050–3
Donahue JG, Weiss ST, Livingston JM, et al. Inhaled steroids and the risk of hospitalization for asthma. JAMA 1997; 277: 887–91
Wennergren G, Kristjansson S, Strannegard IL. Decrease in hospitalization for treatment of childhood asthma with increased use of antiinflammatory treatment, despite an increase in the prevalence of asthma. J Allergy Clin Immunol 1996; 97: 742–8
Paterson NAM, Peat JK, Mellis CM, et al. Accuracy of asthma treatment in schoolchildren in NSW, Australia. Eur Respir J 1997; 10: 658–64
British Asthma Guidelines coordinating committee. The British guidelines on asthma management 1995 review and position statement. Thorax 1997; 52: S1–21
International consensus report on diagnosis and treatment of asthma. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Publication no. 92-3091, March 1992. Eur Respir J 1992; 5: 601–41
National Heart, Lung, and Blood Institute and World Health Organization. Global Initiative for Asthma. Global strategy for asthma management and prevention. NIH Publication no. 95-3659. Bethesda, MD: National Institutes of Health, 1995: 1–48
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 2: guidelines for the diagnosis and management of asthma. NIH Publication no. 97-4051. Bethesda, MD: National Institutes of Health, 1997: 1–50
Silverman M, Wilson N. Asthma — time for a change of name? Arch Dis Child 1997; 77: 62–5
Clifford RD, Howell JB, Radford M, et al. Associations between respiratory symptoms, bronchial response to methacholine, and atopy in two age groups of schoolchildren. Arch Dis Child 1989; 64: 1133–9
De Gooijer A, Brand PLP, Gerritsen J, et al. Changes in respiratory symptoms and airway hyperresponsiveness after 27 years in a population-based sample of school children. Eur Respir J 1993; 6: 848–54
Reijonen TM, Korppi M. One-year follow-up of young children hospitalized for wheezing: the influence of early anti-inflammatory therapy and risk factors for subsequent wheezing and asthma. Pediatr Pulmonol 1998; 26: 113–9
Agertoft L, Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 1994; 88: 373–81
Baxter-Jones ADG, Helms PJ. Effect of early introduction of inhaled steroids in wheezing children presenting in primary care. Eur Respir J 1999; 14: S30–280
Doull DM, Lampe FC, Smith S, et al. Effect of inhaled cortico-steroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial. BMJ 1997; 315: 858–62
Kamada AK, Parks DP, Szefler SJ. Inhaled glucocorticoid therapy in children: how much is safe? Pediatr Pulmonol 1992; 12: 71–2
Cade A, Butler GE, Morrison JF, et al. High-dose inhaled steroids in asthmatic children. Lancet 1996; 348: 819
Doull DM, Freezer NJ, Holgate ST. Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate. Am J Respir Crit Care Med 1995; 151: 1715–9
Ninan TK, Russell G. Asthma, inhaled corticosteroid treatment, and growth. Arch Dis Child 1992; 67: 703–5
Saha MT, Laippala P, Lenko HL. Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids. Acta Paediatr 1997; 86: 138–42
Phillip K. Integrated plasma Cortisol concentration in children with asthma receiving long-term inhaled corticosteroids. Pediatr Pulmonol 1992; 12: 84–9
Tabachnik E, Zadik Z. Diurnal Cortisol secretion during therapy with inhaled beclomethasone dipropionate in children with asthma. J Pediatr 1991; 118: 294–7
Wolthers OD, Pedersen S. Measures of systemic activity of inhaled glucocorticosteroids in children: a comparison of urine Cortisol excretion and knemometry. Respir Med 1995; 89: 347–9
Wolthers OD, Pedersen S. Short-term growth during treatment with inhaled fluticasone propionate and beclomethasone diproprionate. Arch Dis Child 1993; 68: 673–6
MacKenzie CA, Wales JKH, Crowley S, et al. Growth of asthmatic children. BMJ 1991; 303: 416
Tinkelman DG, Reed CE, Nelson HS, et al. Aerosol beclomethasone dipropionate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children. Pediatrics 1993; 92: 64–77
Russell G, Eastell R, MacKenzie C, et al. Childhood asthma and growth — a review of the literature. Respir Med 1994; 88: 31–7
Robins SP, Black D, Patterson CR, et al. Evaluation of urinary hydroxypyridinium crosslink measurements as resorption markers in metabolic bone diseases. Eur J Clin Invest 1991; 21: 310–5
Robins SP. Pyridinium crosslink as markers of bone resorption. Lancet 1992; 340: 278–9
Doull I, Freezer N, Holgate S. Osteocalcin, growth, and inhaled corticosteroids: a prospective study. Arch Dis Child 1996; 74: 497–501
Crowley S, Trivedi P, Risteli L, et al. Collagen metabolism and growth in prepubertal children with asthma treated with inhaled steroids. J Pediatr 1998; 132: 409–13
Jonsson J, Bousquet J, Jones PW, et al. Treating asthma: health economic aspects. Eur Respir Rev 1995; 5(30): 270–96
Wisniewski AF, Lewis SA, Green DJ, et al. Cross sectional investigation of the effects of inhaled corticosteroids on bone density and bone metabolism in patients with asthma. Thorax 1997; 52: 853–60
Packe GE, Douglas JG, McDonald AF, et al. Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids. Thorax 1992; 47: 414–7
Agertoft L, Pedersen S. Bone mineral density in children with asthma receiving long-term treatment with inhaled budesonide. Am J Respir Crit Care Med 1998; 157: 178–83
Crowley S, Trivedi P, Risteli L, et al. Collagen metabolism and growth in prepubertal children with asthma treated with inhaled steroids. J Pediatr 1998; 132: 409–13
Greening AP, Ind PW, Northfield M, et al. Added salmeterol versus higher dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroids. Lancet 1994; 344: 219–24
Woolcock A, Lundback B, Ringdal N, et al. Comparison of addition of salmeterol to inhaled steroid with doubling of inhaled steroids. Am Respir Crit Care Med 1996; 153: 1481–8
Verberne AAPH, Frost C, Duiverman EJ, et al. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. Am J Respir Crit Care Med 1998; 158: 213–9
Kimata H, Yoshida A, Ishioka C, et al. Disodium cromoglycate (DSCG) selectively inhibits IgE production and enhances IgG4 production by human B cell in vitro. Clin Exp Immunol 1991; 84(3): 395–9
Iikura Y, Naspitz CK, Mikawa H, et al. Prevention of asthma by ketotifen in infants with atopic dermatitis. Ann Allergy 1992; 68: 233–6
Bustos GJ, Bustos D, Romero O. Prevention of asthma with ketotifen in preasthmatic children: a three-year follow-up study. Clin Exp Allergy 1995; 25: 568–73
Tasche MJ, van der Wouden JC, Uijen JH, et al. Randomised placebo-controlled trial of inhaled sodium cromoglycate in 1–4-year-old children with moderate asthma. Lancet 1997; 350: 1060–4
ETAC Study Group. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC. Pediatr Allergy Immunol 1998; 9: 116–24
Ward AIM, McKenniff M, Evans JM, et al. Theophylline: an immunomodulatory role in asthma. Am Rev Respir Dis 1993; 147: 518–23
Sullivan O, Bekir S, Jaffar Z, et al. Anti-inflammatory effects of low dose oral theophylline in atopic asthma. Lancet 1994; 343: 1006–8
Warner JO, Naspitz CK. Third International Pediatric Consensus Statement on the management of childhood asthma. International Pediatric Asthma Consensus Group. Pediatr Pulmonol 1998; 25: 1–17
Balfour-Lynn IM, Valman HB, Wellings R, et al. Tumour necrosis factor-alpha and leukotriene E4 production in wheezy infants. Clin Exp Allergy 1994; 24: 121–6
Volovitz B, Faden H, Ogra PL. Release of leukotriene C4 in respiratory tract during acute viral infection. J Pediatr 1988; 112(2): 218–22
Knorr B, Matz J, Bernstein JA, et al. Montelukast for chronic asthma in 6 to 14 year old children. JAMA 1998; 279: 1181–6
Lofdahl CG, Reiss TF, Leff JA, et al. Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist Montelukast on tapering inhaled corticosteroids in asthmatic patients. BMJ 1999; 319: 87–90
Kemp JP, Dockhorn RJ, Shapiro GG, et al. Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma. J Pediatr 1998; 133: 424–8
Arshad SH, Matthews S, Gant C, et al. Effect of allergen avoidance on development of allergic disorders in infancy. Lancet 1992; 339: 1493–7
Custovic A, Simpson A, Chapman MD, et al. Allergen avoidance in the treatment of asthma and atopic disorders. Thorax 1998; 53: 63–72
Gotzsche PC, Hammarquist C, Burr M. House dust mite control measures in the management of asthma: meta-analysis. BMJ 1998; 317: 1105–10
Walsh LJ, Wong CA, Cooper S, et al. Morbidity from asthma in relation to regular treatment: a community based study. Thorax 1999; 54: 296–300
Kelloway JS, Wyatt RA, Aldis SA. Comparison of patients' compliance with prescribed oral and inhaled asthma medications. Arch Intern Med 1994; 154: 1349–52
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Helms, P.J. Corticosteroid-Sparing Options in the Treatment of Childhood Asthma. Drugs 59 (Suppl 1), 15–22 (2000). https://doi.org/10.2165/00003495-200059001-00003
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-200059001-00003