Risk-Benefit of Asthma Therapy in Children: Topical Corticosteroids

  • Hugo P. Van Bever
  • Lynette P. Shek
  • Daniel Y. T. Goh
Part of the Allergy Frontiers book series (ALLERGY, volume 5)

Inhaled corticosteroids (ICS) are now considered the most effective asthma therapy, and are first-line therapy for control of asthma in both children and adults [1–4]. In the past, ICS were mainly used in children with severe persistent asthma. Nowadays, they are also recommended for the treatment of mild to moderate persistent asthma, and in most countries, ICS have become first-line treatment, even for very young children [5]. However, ICS still fail to enjoy a favorable reputation in terms of safety and tolerability [6]. Many patients (and parents) have a “steroid phobia” that is based on the local and systemic adverse events from high-dose ICS or oral corticosteroids, leading to poor compliance [7– 9]. A number of ICS have been developed and made available to treat asthma over the last 30 years. They include beclomethasone dipro-pionate (BDP), budesonide (BUD), fluticasone propionate (FP), triamcinolone ace-tonide (TA), flunisolide (FLUN), mometasone furoate (MF), and ciclesonide (CIC) [10]. Each has unique physiochemical properties that confer distinct pharmacologic characteristics regarding potency, efficacy, safety, tolerability, lung deposition, receptor binding, lipophilicity, and esterification (Table 1).

In children, the best studied ICS to date are BPD and BUD [11]. Therefore, many of the data and references mentioned in this chapter will be from studies on BPD and BUD. The newest ICS is ciclesonide (CIC), of which many studies in asthmatic children were published [12] recently. A recent study by Pedersen et al. concluded that ciclesonide's safety and efficacy profile in asthmatic children is similar to that of fluticasone propionate [13].


Fluticasone Propionate Allergy Clin Immunol Asthmatic Child Respir Crit Persistent Asthma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Allen DB, Bielory L, Derendorf H, Dluhy R, Colice GL, Szefler SJ (2003) Inhaled corticos-teroids: past lessons and future issues. J Allergy Clin Immunol 112 (3 Suppl):S1–S40PubMedCrossRefGoogle Scholar
  2. 2.
    Pedersen S (2006) Clinical safety of inhaled corticosteroids for asthma in children: an update of long-term trials. Drug Saf 29:599–612PubMedCrossRefGoogle Scholar
  3. 3.
    Donahue JG, Weiss ST, Livingston JM, Goetsch MA, Greineder DK, Platt R (1997) Inhaled steroids and the risk of hospitalization for asthma. JAMA 277:887–891PubMedCrossRefGoogle Scholar
  4. 4.
    Tattersfield AE, Knox AJ, Britton JR, et al. (2002) Asthma. Lancet 360:1313–1322PubMedCrossRefGoogle Scholar
  5. 5.
    White AJ, Richards DH (1997) Inhaled corticosteroid prescribing in very young children. J Allergy Clin Immunol 99:S325.Google Scholar
  6. 6.
    Irwin RS, Richardson ND (2006) Side effects with inhaled corticosteroids: the physician's perception. Chest 130:S41–S53CrossRefGoogle Scholar
  7. 7.
    Jones C, Santanello NC, Boccuzzi SJ, et al. (2003) Adherence to prescribed treatment for asthma: evidence from pharmacy benefits data. J Asthma 40:93–101PubMedCrossRefGoogle Scholar
  8. 8.
    Connett GJ, Lee BW (1994) Treating childhood asthma in Singapore: when West meets East. BMJ 308:1282–1284PubMedGoogle Scholar
  9. 9.
    Chew FT, Goh DYT, Lee BW (1999) Under-recognition of childhood asthma in Singapore: evidence from a questionnaire survey. Ann Trop Paediatr 19:83–91PubMedCrossRefGoogle Scholar
  10. 10.
    Kamada AK, Szefler SJ, Martin RJ, Boushey HA, Chinchilli VM, Drazen JM, et al. (1996) Issues in the use of inhaled glucocorticoids. Am J Respir Crit Care Med 153:1739–1748PubMedGoogle Scholar
  11. 11.
    Cerasoli F (2006) Developing the ideal inhaled corticosteroid. Chest 130:54S–64SPubMedCrossRefGoogle Scholar
  12. 12.
    Colice GL (2006) The newly developed inhaled corticosteroid ciclesonide for the treatment of asthma. Expert Opin Pharmacother 15:2107–2117CrossRefGoogle Scholar
  13. 13.
    Pedersen S, Garcia Garcia ML, Manjra A, Theron I, Engelstatter R (2006) A comparative study of inhaled ciclesonide 160 microg/day and fluticasone propionate 176 microg/day in children with asthma. Pediatr Pulmonol 41:954–961PubMedCrossRefGoogle Scholar
  14. 14.
    Barnes PJ (1997) Glucocorticoids. In: Kay AB, editor. Allergy and allergic diseases. Blackwell Science, London, pp. 619–641Google Scholar
  15. 15.
    Schleimer RP, Beck L, Schwiebert L, Stellato C, Bochner BS (1997) Inhibition of inflammatory cell recruitment by glucocorticods: cytokines as primary targets. In: Schleimer RP, Busse WW, O'Byrne P, editors. Topical glucocorticoids in asthma: mechanisms and clinical actions. Marcel Dekker, New York, pp. 203–238Google Scholar
  16. 16.
    Bisgaard H (1998) Automatic actuation of a dry powder inhaler into a non-electrostatic spacer. Am J Respir Crit Care Med 157:518–521PubMedGoogle Scholar
  17. 17.
    Pedersen S (1995) Drug delivery. Am J Respir Crit Care Med 151:S27–S42Google Scholar
  18. 18.
    Agertoft L, Pedersen S (2003) Lung deposition and systemic availability of fluticasone diskus and budesonide turbuhaler in children. Am J Respir Crit Care Med 168:779–782PubMedCrossRefGoogle Scholar
  19. 19.
    Gross G, Chervinsky P, Ramsdell R, Van den Burgt J (1997) Half the daily dose of new CFC-free formulation steroid achieves equivalent pulmonary function in moderate asthma. Am J Respir Crit Care Med 155:A666Google Scholar
  20. 20.
    Anderson PB, Langley SJ, Mooney P, et al. (2002) Equivalent efficacy and safety of a new HFA-134a formulation of BDP compared with the conventional CFC in adult asthmatics. J Investig Allergol Clin Immunol 12:107–113PubMedGoogle Scholar
  21. 21.
    Pedersen S, O'Byrne P (1997) A comparison of the efficacy and safety of inhaled corticoster-oids in asthma. Allergy 52 (suppl 39):1–34PubMedCrossRefGoogle Scholar
  22. 22.
    Simons FER (1998) Benefits and risks of inhaled glucocorticoids in children with persistent asthma. J Allergy Clin Immunol 102:S77–84PubMedCrossRefGoogle Scholar
  23. 23.
    Pedersen S, Hansen OR (1995) Budesonide treatment of moderate and severe asthma in children: a dose-response study. J Allergy Clin Immunol 95:29–33PubMedCrossRefGoogle Scholar
  24. 24.
    Van Essen-Zandvliet EE, Hughes MD, Waalkens HJ, Duiverman EJ, Pocock SJ, Kerrebijn KF, et al. (1992) Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma. Am Rev Respir Dis 146:574–554Google Scholar
  25. 25.
    Verberne AAPH, Frost C, Roorda RJ, van der Laag H, Kerrebijn KF, and the Dutch Paediatric Asthma Study Group (1997) One year treatment with salmeterol compared with beclometha-sone in children with asthma. Am J Respir Crit Care Med 156:688–695PubMedGoogle Scholar
  26. 26.
    Waalkens HJ, Van Essen-Zandvliet EE, Hughes MD, Gerritsen J, Duiverman EJ, Knol K, et al. (1993) Cessation of long-term treatment with inhaled corticosteroids (budesonied) in children with asthma results in deterioration. Am Rev Respir Dis 148:1252–1257PubMedGoogle Scholar
  27. 27.
    Guilbert TW, Morgan WJ, Zeiger RS, et al. (2006) Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med 354:1985–97.PubMedCrossRefGoogle Scholar
  28. 28.
    Caroll CL, Bhandari A, Schramm CM, Zucker AR (2006) Chronic inhaled corticosteroids do not affect the course of acute severe asthma exacerbations in children. Pediatr Pulmonol 41:1213–1217CrossRefGoogle Scholar
  29. 29.
    Edmonds MH, Camargo CA Jr, Pollack CV Jr, Rowe BH (2003) Early use of inhaled corti-costeroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev 3:CD002308PubMedGoogle Scholar
  30. 30.
    Smith M, Iqbal S, Elliott TM, Everard M, Rowe BH (2003) Corticosteroids for hospitalised children with acute asthma. Cochrane Database Syst Rev 2003:CD002886Google Scholar
  31. 31.
    Rodrigo GJ (2006) Rapid effects of inhaled corticosteroids in acute asthma: an evidence-based evaluation. Chest 130:1301–1311PubMedCrossRefGoogle Scholar
  32. 32.
    Volovitz B (2007) Inhaled budesonide in the management of acute worsenings and exacerbations of asthma: a review of the evidence. Respir Med 101:685–695PubMedCrossRefGoogle Scholar
  33. 33.
    Schuh S, Reisman J, Alshehri M, Dupuis A, Corey M, Arseneault R, Alothman G, Tennis O, Canny G (2000) A comparison of inhaled fluticasone and oral prednisone for children with severe acute asthma. N Engl J Med 343:689–694PubMedCrossRefGoogle Scholar
  34. 34.
    Schuh S, Dick PT, Hartley M, Khaikin S, Rodrigues L, Coates AL (2006) High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma. Pediatrics 118:644–650PubMedCrossRefGoogle Scholar
  35. 35.
    Nakanishi AK, Klasner AK, Rubin BK (2003) A randomized controlled trial of inhaled fluni-solide in the management of acute asthma in children. Chest 124:790–794PubMedCrossRefGoogle Scholar
  36. 36.
    Agertoft L, Pedersen S (1994) Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 88:373–381PubMedCrossRefGoogle Scholar
  37. 37.
    Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, Ullman A, Lamm CJ, O'Byrne PM, and the START Investigators Group (2003) Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 361:1071–1076PubMedCrossRefGoogle Scholar
  38. 38.
    Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ (1995) Asthma and wheezing in the first six years of life. N Engl J Med 332:133–138PubMedCrossRefGoogle Scholar
  39. 39.
    Van Bever HP, Desager KN, Hagendorens M (2002) Critical evaluation of prognostic factors in childhood asthma. Pediatr Allergy Immunol 12:1–9Google Scholar
  40. 40.
    Illi S, von Mutius E, Lau S, Niggeman B, Gruber C, Wahn U, and the Multicentre Allergy Study (MAS) group (2003) Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. Lancet 368:763–770CrossRefGoogle Scholar
  41. 41.
    Bender B, Milgrom H, Rand C (1997) Nonadherence in asthmatic patients: is there a solution to the problem? Ann Allergy Asthma Immunol 79:177–186PubMedGoogle Scholar
  42. 42.
    Stern L, Berman J, Lumry W, Katz L, Wang L, Rosenblatt L, Doyle JJ (2006) Medication compliance and disease exacerbation in patients with asthma: a retrospective study of managed care data. Ann Allergy Asthma Immunol 97:402–408PubMedCrossRefGoogle Scholar
  43. 43.
    Landwehr LP, Spahn JD, Szefler SJ, Leung DYM (1995) Management of steroid-resistant asthma. Clin Immunother 4:124–137Google Scholar
  44. 44.
    Allen DB (1996) Growth suppression by glucocorticoid therapy. In: Rosenfield RL, editor. Growth and growth disorders. WB Saunders, Philadelphia, pp. 699–718Google Scholar
  45. 45.
    Ferguson AC, Murray AB, Tze W-J (1982) Short stature and delayed skeletal maturation in children with allergic diseases. J Allergy Clin Immunol 69:461–466PubMedCrossRefGoogle Scholar
  46. 46.
    Wolthers OD (1996) Long-, intermediate- and long-term growth studies in asthmatic children treated with inhaled corticosteroids. Eur Respir J 9:821–827PubMedCrossRefGoogle Scholar
  47. 47.
    The Childhood Asthma Management Program Research Group (CAMP) (2000) Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 343:1054–1063CrossRefGoogle Scholar
  48. 48.
    Wolthers OD, Hansen M, Juul A, Nielsen HK, Pedersen S (1997) Knemometry, urine cortisol excretion, and measures of the insulin-like growth factor axis and collagen turnover in children treated with inhaled glucocorticoids. Pediatr Res 41:44–50PubMedCrossRefGoogle Scholar
  49. 49.
    Tinkelman DG, Reed CE, Nelson HS, Offord KP (1993) Aerosol beclomethasone dipropi-onate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children. Pediatrics 92:64–77PubMedGoogle Scholar
  50. 50.
    Simons FER, and the Canadian Beclomethasone Dipropionate-Salmeterol Xinofoate Study Group (1997) A comparison of beclomethasone, salmeterol, and placebo in children with asthma. N Engl J Med 337:1659–1665PubMedCrossRefGoogle Scholar
  51. 51.
    Wales JKH, Barnes ND, Swift PGF (1991) Growth retardation in children on steroids for asthma. Lancet 338:1535PubMedCrossRefGoogle Scholar
  52. 52.
    Thomas BC, Stanhope R, Grant DB (1994) Impaired growth in children with asthma during treatment with conventional doses of inhaled corticosteroids. Acta Paediatr 83:196–199PubMedCrossRefGoogle Scholar
  53. 53.
    Littelwood JM, Johnson AW, Edwards PA, Littlewood AE. Growth retardation in asthmatic children treated with inhaled beclomethasone dipropionate. Lancet 1:115–116Google Scholar
  54. 54.
    Saha M-T, Laippala P, Lenko HL (1997) Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids. Acta Paediatr 86:138–142PubMedCrossRefGoogle Scholar
  55. 55.
    Hunt GJJ, Edmunds ATE, Kelnar CJH (1994) Height velocity standard deviation scores in 162 prepubertal children receiving beclomethasone dipropionate, budesonide, or sodium cromo-glycate. Thorax 49:399PGoogle Scholar
  56. 56.
    Inoue T, Soi S, Takamatsu I, Murayama N, Kameda M, Hayashida M, et al. (1995) Effects of inhaled beclomethasone on height growth and bone metabolism in children with asthma. Arerugi 44:678–684PubMedGoogle Scholar
  57. 57.
    Crowley S, Hindmarsh PC, Matthews DR, Brook CGD (1995) Growth and the growth hormone axis in prepubertal children with asthma. J Pediatr 126:297–303PubMedCrossRefGoogle Scholar
  58. 58.
    Doull IJM, Freezer NJ, Holgate ST (1995) Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate. Am J Respir Crit Care Med 151:1715–1719PubMedGoogle Scholar
  59. 59.
    Le Bourgeois M, Benoist MR, de Blic J, Allaire JM, Scheinmann P (1993) One year treatment with two doses of inhaled flunisolide (250 and 500 mcg bid): effects on growth of asthmatic children. Am Rev Respir Dis 147:A265Google Scholar
  60. 60.
    Allen DB, Bronsky EA, LaForce CF, Nathan RA, Tinkelman DG, Vandewalker ML, et al. (1998) Growth in asthmatic children treated with fluticasone propionate. J Pediatr 132:472–477PubMedCrossRefGoogle Scholar
  61. 61.
    Price JF, Russell G, Hindmarsh PC, Weller P, Heaf DP, Williams J (1997) Growth during one year of treatment with fluticasone propionate or sodium cromoglycate in children with asthma. Pediatr Pulmonol 24:178–186PubMedCrossRefGoogle Scholar
  62. 62.
    Anhoj J, Bisgaard AM, Bisgaard H (2002) Systemic activity of inhaled steroids in 1-to 3-year-old children with asthma. Pediatrics, 109:40.CrossRefGoogle Scholar
  63. 63.
    Bisgaard H, Allen D, Miles EA, et al. (2004) Long-term safety and efficacy of inhaled fluti-casone propionate in children aged 1 to 3 years old with recurrent wheezing. Pediatrics, 113:e87–94PubMedCrossRefGoogle Scholar
  64. 64.
    Allen DB, Mullen M, Mullen B (1994) A meta-analysis of the effcet of oral and inhaled cor-ticosteroids on growth. J Allergy Clin Immunol 93:967–976PubMedCrossRefGoogle Scholar
  65. 65.
    Godfrey S, König P (1974) Treatment of childhood asthma for 13 months and longer with beclomethasone dipropionate aerosol. Arch Dis Child 49:591–596PubMedCrossRefGoogle Scholar
  66. 66.
    Balfour-Lynn L (1986) Growth and childhood asthma. Arch Dis Child 61:1049–1055PubMedCrossRefGoogle Scholar
  67. 67.
    Volovitz B, Amir J, Malik H, Kauschansky A, Varsano I (1993) Growth and pituitary-adrenal function in children severe asthma treated with inhaled budesonide. N Engl J Med 329:1703–1708PubMedCrossRefGoogle Scholar
  68. 68.
    Merkus PJFM, van Essen-Zandvliet EEM, Duiverman EJ, van Houwelingen HC, Kerrebijn KF, Quanjer PH (1993) Long-term effect of inhaled corticosteroids on growth rate in adolescents with asthma. Pediatrics 91:1121–1226PubMedGoogle Scholar
  69. 69.
    Silverstein MD, Yunginger JW, Reed CE, Petterson T, Zimmerman D, Li JTC, et al. (1997) Attained adult height after childhood asthma: effect of glucocorticoid therapy. J Allergy Clin Immunol 99:466–474PubMedCrossRefGoogle Scholar
  70. 70.
    Agertoft L, Pedersen S (2000) Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 343:1064–1069PubMedCrossRefGoogle Scholar
  71. 71.
    Van Bever HP, Desager KN, Lijssen N, Weyler JJ, Du Caju MV (1999) Does treatment of asthmatic children with inhaled corticosteroids affect their adult height? Pediatr Pulmonol 27:369–375PubMedCrossRefGoogle Scholar
  72. 72.
    Allen DB (2005) Inhaled steroids for children: effects on growth, bone, and adrenal function. Endocrinol Metab Clin N Am 34:555–564CrossRefGoogle Scholar
  73. 73.
    Birkebaek NH, Esberg G, Andersen K, Wolthers O, Hassager C (1995) Bone and collagen turnover during treatment with inhaled dry powder budesonide and beclomethasone dipropi-onate. Arch Dis Child 73:524–527PubMedCrossRefGoogle Scholar
  74. 74.
    Rao R, Gregson RK, Jones AC, Murrils AJ, Warner JA, Warner JO (1997) Inhaled steroids in standard dose do not affect bone architecture or turnover with long term use in childhood asthma. Am J Respir Crit Care Med 155:A267Google Scholar
  75. 75.
    Agertoft L, Pedersen S (1998) Bone mineral density in children with asthma receiving longterm treatment with inhaled budesonide. Am J Respir Crit Care Med 157:178–183PubMedGoogle Scholar
  76. 76.
    Konig P, Hillman L, Cervantes C, et al. (1993) Bone metabolism in children with asthma treated with inhaled beclomethasone dipropionate. J Pediatr 122:219–226PubMedCrossRefGoogle Scholar
  77. 77.
    Kelly HW, Strunk RC, Donithan M, et al. (2003) Growth and bone density in children with mild-moderate asthma: a cross-sectional study in children entering the Childhood Asthma Management Program (CAMP). J Pediatr 142:286–291PubMedCrossRefGoogle Scholar
  78. 78.
    Roux C, Kolta S, Desfougeres JL, et al. (2003) Long-term safety of fluticasone propionate and nedocromil sodium on bone in children with asthma. J Pediatr 142:286–291CrossRefGoogle Scholar
  79. 79.
    van Staa TP, Cooper C, Leufkens HG, et al. (2003) Children and the risk of fractures caused by oral corticosteroids. J Bone Miner Res 18:913–918PubMedCrossRefGoogle Scholar
  80. 80.
    Bisgaard H, Nielsen MDD, Andersen B, Andersen P, Foged N, Fuglsang G, et al. (1988) Adrenal function in children with bronchial asthma treated with beclomethasone or budes-onide. J Allergy Clin Immunol 81:1088–1095PubMedCrossRefGoogle Scholar
  81. 81.
    Prahl P (1991) Adrenocortical suppression following treatment with beclomethasone dipro-pionate and budesonide. Clin Exp Allergy 21:145–146PubMedCrossRefGoogle Scholar
  82. 82.
    Nicolaizik WH, Marchant JL, Preece MA, Warner JO (1994) Endocrine and lung function in asthmatic children on inhaled corticosteroids. Am J Respir Crit Care Med 150:624–628PubMedGoogle Scholar
  83. 83.
    Philip M, Aviram M, Lieberman E, Zadik Z, Giat Y, Levy J, et al. (1992) Integrated plasma cortisol concentration in children with asthma receiving long-term inhaled corticosteroids. Ped Pulmonol 12:84–89CrossRefGoogle Scholar
  84. 84.
    Todd GR, Acerini CL, Buck JJ, et al. (2002) Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate. Eur Respir J 19:1207–1209PubMedCrossRefGoogle Scholar
  85. 85.
    Simons FER, Persaud MP, Gillespie CA, Cheang M, Shuckett EP (1993) Absence of posterior subcapsular cataracts in young patients treated with inhaled corticosteroids. Lancet 342:776–778PubMedCrossRefGoogle Scholar
  86. 86.
    Geller DE (2007) Clinical side effects during aerosol therapy: cutaneous and ocular effects. J Aerosol Med 20 (suppl 1):S100–S109PubMedCrossRefGoogle Scholar
  87. 87.
    Connett G, Lenney W. Inhaled budesonide and behavioural disturbances. Lancet 338:634–635Google Scholar
  88. 88.
    Choong K, Zwaigenbaum L, Onyett H (1995) Severe varicella after low dose inhaled corti-costeroids. Pediatr Infect Dis J 14:809–811PubMedGoogle Scholar
  89. 89.
    Turpeinen M, Sorva R, Juntunen-Backman K (1991) Changes in carbohydrate and lipid metabolism in children with asthma inhaling budesonide. J Allergy Clin Immunol 88:384–389PubMedCrossRefGoogle Scholar
  90. 90.
    de Vries TW, de Langen-Wouterse JJ, de Jong-Van den Berg LT, Duiverman EJ (2007) Hypertrichosis as a side effect of inhaled steroids in children. Pediatr Pulmonol 42:370–373PubMedCrossRefGoogle Scholar
  91. 91.
    Bousquet J, Clark TJ, Hurd S, Khaltaey N, Lenfant C, O'byrne P, Sheffer A (2007) GINA guidelines on asthma and beyond. Allergy 62:102–112PubMedGoogle Scholar
  92. 92.
    Taussig LM, Wright AL, Holberg CJ, Halonen M, Morgan WJ, Martinez FD (2003) Tucson Children's Respiratory Study: 1980 to present. J Allergy Clin Immunol 111:661–675PubMedCrossRefGoogle Scholar
  93. 93.
    Tan TN, Lim DLC, Chong YS, Lee BW, Van Bever HP (2005) Prevalence of allergy-related symptoms in the second year of life. Ped Allergy Immunol 16:151–156CrossRefGoogle Scholar
  94. 94.
    Martinez FD (2002) What have we learned from the Tucson Children's Respiratory Study? Paediatr Respir Rev 3:193–7PubMedCrossRefGoogle Scholar
  95. 95.
    Chavasse RJ, Bastian-Lee Y, Seddon P (2002) How do we treat wheezing infants? Evidence or anecdote. Arch Dis Childh 87:546–7PubMedCrossRefGoogle Scholar
  96. 96.
    Devulapalli CS, Haaland G, Pettersen M, Carlsen KH, Lodrup Carlsen KC (2004) Effect of inhaled steroids on lung function in young children: a cohort study. Eur Respir J 23:869–75PubMedCrossRefGoogle Scholar
  97. 97.
    Chavasse RJ, Bastian-Lee Y, Richter H, et al. (2001) Persistent wheezing in infants with an atopic tendency responds to inhaled fluticasone. Arch Dis Childh 85:143–8PubMedCrossRefGoogle Scholar
  98. 98.
    Van Bever HP, Schuddinck L, Wojciechowski M, Stevens WJ (1990) Aerosolized budes-onide in asthmatic infants: a double blind study. Pediatr Pulmonol 9:177–180PubMedCrossRefGoogle Scholar
  99. 99.
    Bisgaard H, Northman Hermansen B, Loland L, et al. (2006) Intermittent inhaled corticos-teroids in infants with episodic wheezing. N Engl J Med 354:1998–2005PubMedCrossRefGoogle Scholar
  100. 100.
    Murray CS, Woodcock A, Langley SJ, Morris J, Custovic A (2006) Secondary prevention of asthma by the use of Inhaled Fluticasone propionate in Wheezy Infants (IFWIN): doubleblind, randomised, controlled study. Lancet 368:754–762PubMedCrossRefGoogle Scholar
  101. 101.
    Schokker S, Kooi EM, de Vries TW, Brand PL, Mulder PG, Duiverman EJ, van der Molen T (2007) Inhaled corticosteroids for recurrent respiratory symptoms in preschool children in general practice: randomized controlled trial. Pulm Pharmacol Ther Jan 23 (in press)Google Scholar
  102. 102.
    Blom D, Ermers M, Bont L, van Aalderen W, van Woensel J (2007) Inhaled corticosteroids during acute bronchiolitis in the prevention of post-bronchiolitic wheezing. Cochrane Database Syst Rev 24, CD004881.Google Scholar
  103. 103.
    Sorkness CA, Lemanske RF Jr, Mauger DT, Boehmer SJ, Chinchilli VM, Martinez FD, Strunk RC, Szefler SJ, Zeiger RS, Bacharier LB, Bloomberg GR, Covar RA, Guilbert TW, Heldt G, Larsen G, Mellon MH, Morgan WJ, Moss MH, Spahn JD, Taussig LM, and the Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute (2007) Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. J Allergy Clin Immunol 119:64–72PubMedCrossRefGoogle Scholar
  104. 104.
    Verberne AAPH, Frost C, Duiverman EJ, Grol MH, Kerribijn KF (1998) Addition of salme-terol versus doubling the dose of beclomethasone in children with asthma. Am J Respir Crit Care Med 158:213–219PubMedGoogle Scholar
  105. 105.
    Pohunek P, Kuna P, Jorup C, De Boeck K (2006) Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma. Pediatr Allergy Immunol 17:458–65PubMedCrossRefGoogle Scholar
  106. 106.
    Bisgaard H (2003) Effect of long-acting b2 agonists on exacerbation rates of asthma in children. Pediatr Pulmonol 36:391–8PubMedCrossRefGoogle Scholar
  107. 107.
    Lee DK, Currie GP, Hall IP, Lima JJ, Lipworth BJ (2004) The arginine-16 beta2-adrenocep-tor polymorphism predisposes to bronchoprotective subsensitivity in patients treated with formoterol and salmeterol. Br J Clin Pharmacol 57:68–75PubMedCrossRefGoogle Scholar
  108. 108.
    Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM; SMART Study Group (2006) The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 129:15–26PubMedCrossRefGoogle Scholar
  109. 109.
    Martinez FD (2005) Safety of long-acting beta-agonists--an urgent need to clear the air. N Engl J Med 353:2637–9PubMedCrossRefGoogle Scholar
  110. 110.
    Todd G, Dunlop K, McNaboe J, Ryan MF, Carson D, Shields MD (1996) Growth and adrenal suppression in asthmatic children treated with high-dose fluticasone propionate. Lancet 348:27–29PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Hugo P. Van Bever
    • 1
    • 2
  • Lynette P. Shek
    • 3
  • Daniel Y. T. Goh
    • 4
    • 5
  1. 1.Department of PaediatricsYong Loo Lin School of Medicine, National University of SingaporeSingapore
  2. 2.Department of PaediatricsNational University HospitalSingapore
  3. 3.Department of PaediatricsYong Loo Lin School of Medicine, National University of SingaporeSingapore
  4. 4.Department of PaediatricsYong Loo Lin School of Medicine, National University of SingaporeSingapore
  5. 5.University Children's Medical Institute, National University HospitalSingapore

Personalised recommendations