American Journal of Drug Delivery

, Volume 1, Issue 1, pp 61–70 | Cite as

Drug Delivery in Pediatric Patients with Asthma

Spacer Devices vs Nebulizers for β2 Agonists
Technology in Practice


This review discusses published evidence on the use of metered dose inhaler (MDI)/spacer combinations and nebulizers for delivering β2 adrenoeeptor agonists (β2 agonists) in stable and acute severe childhood asthma. Although nebulizers have been the mainstay of inhalation therapy in childhood asthma for many years, these devices are cumbersome, bulky, time-consuming, and expensive to use. As a result, over the past decade the emphasis of inhalation therapy in children has shifted from nebulizers to metered-dose inhalers (MDI) in combination with spacer devices.

MDI/spacer combinations have been shown to be a practical and effective way of delivering medications for inhalation in children with asthma, irrespective of their age. Lung deposition increases with age, being low in young children. This underscores the need for administering relatively high nominal dosages of medication when using an MDI/spacer in young children; the most practical approach is to use the same dose, irrespective of the child’s age or weight.

In children with both stable chronic asthma and acute severe asthma, numerous studies have shown that β2 agonists can be delivered by MDI/spacer at least as effectively and safely as by nebulizer. Although nebulizers may still play a role in status asthmaticus (because they allow combined administration of β2 agonists, anticho-linergic agents, and oxygen in a single procedure), the vast majority of children of all ages with acute severe asthma can be managed effectively and safely by β2 agonists delivered via MDI/spacer. This cost-effective and practical approach should, therefore, be preferred.


  1. 1.
    Downs SH, Marks GB, Sporik R, et al. Continued increase in the prevalence of asthma and atopy. Arch Dis Child 2001; 84: 20–3PubMedCrossRefGoogle Scholar
  2. 2.
    Adams RJ, Fuhlbrigge A, Finkelstein JA, et al. Use of inhaled anti-inflammatory medication in children with asthma in managed care settings. Arch Pediatr Adolesc Med 2001; 155: 501–7PubMedGoogle Scholar
  3. 3.
    Lipworth BJ. Modern drug treatment of chronic asthma. BMJ 1999; 318: 380–4PubMedCrossRefGoogle Scholar
  4. 4.
    DeNicola LK, Gayle MO, Blake KV. Drug therapy approaches in the treatment of acute severe asthma in hospitalised children. Pediatr Drugs 2001; 3: 509–37CrossRefGoogle Scholar
  5. 5.
    The British guidelines on asthma management: 1995 review and position statement. The British Thoracic Society, The National Asthma Campaign, The Royal College of Physisicians of London in association with the General Practitioner in Asthma Group, The British Association of Accident and Emergency Medicine, The British Paediatric Respiratory Society, The Royal College of Paediatrics and Child Health. Thorax 1997; 52Suppl. 1: S2–21Google Scholar
  6. 6.
    International consensus report on diagnosis and treatment of asthma. National Heart, Lung, and Blood Institute, National Institutes of Health (publication no. 92-3091, 1992 Mar). EurRespir J 1992; 5: 601–41Google Scholar
  7. 7.
    Bisgaard H. Delivery of inhaled medication to children. J Asthma 1997; 34: 443–67PubMedCrossRefGoogle Scholar
  8. 8.
    O’Callaghan C, Barry PW. How to choose delivery devices for asthma. Arch Dis Child 2000; 82: 185–7PubMedCrossRefGoogle Scholar
  9. 9.
    Child F, Davies S, Clayton S, et al. Inhaler devices for asthma: do we follow the guidelines. Arch Dis Child 2002; 86: 176–9PubMedCrossRefGoogle Scholar
  10. 10.
    Bisgaard H. Aerosol treatment of young children. Eur Respir Rev 1994; 4: 15–20Google Scholar
  11. 11.
    Biggart E, Bush A. Antiasthmatic drug delivery in children. Paediatr Drugs 2002; 4: 85–93PubMedGoogle Scholar
  12. 12.
    Janssens HM, Heijnen EMEW, de Jong VM, et al. Aerosol delivery from spacers in wheezy infants: a daily life study. Eur Respir J 2000; 16: 850–6PubMedCrossRefGoogle Scholar
  13. 13.
    Amirav I, Newhouse MT. Aerosol therapy with valved holding chambers in young children: importance of the facemask seal. Pediatrics 2001; 108: 389–94PubMedCrossRefGoogle Scholar
  14. 14.
    Iies R, Lister P, Edmunds AT. Crying significantly reduces absorption of aerosolized drug in infants. Arch Dis Child 1999; 81: 163–5CrossRefGoogle Scholar
  15. 15.
    Everard ML, Clark AR, Milner AD. Drug delivery from jet nebulisers. Arch Dis Child 1992; 67: 586–91PubMedCrossRefGoogle Scholar
  16. 16.
    Newman SP, Millar AB, Lennard-Jones TR, et al. Improvement of pressurized aerosol deposition with nebuhaler spacer device. Thorax 1984; 39: 935–41PubMedCrossRefGoogle Scholar
  17. 17.
    Piérart F, Wildhaber JH, Vrancken I, et al. Washing plastic spacers in household detergent reduces electrostatic charge and greatly improves delivery. Eur Respir J 1999; 13: 673–8PubMedCrossRefGoogle Scholar
  18. 18.
    Wildhaber JH, Devadason SG, Hayden MJ, et al. Electrostatic charge on a plastic spacer device influences the delivery of salbutamol. Eur Respir J 1996; 9: 1943–6PubMedCrossRefGoogle Scholar
  19. 19.
    Wildhaber JH, Devadason SG, Eber E, et al. Effect of electrostatic charge, flow, delay and multiple actuations on the in vitro delivery of salbutamol from different small volume spacers for infants. Thorax 1996; 51: 985–8PubMedCrossRefGoogle Scholar
  20. 20.
    Bisgaard H. A metal aerosol holding chamber devised for young children with asthma. Eur Respir J 1995; 8: 856–60PubMedCrossRefGoogle Scholar
  21. 21.
    Bisgaard H, Anhoj J, Klug B, et al. A non-electrostatic spacer for aerosol delivery. Arch Dis Child 1995; 73: 226–30PubMedCrossRefGoogle Scholar
  22. 22.
    Berg E, Madsen J, Bisgaard H. In vitro performance of three combinations of spacers and pressurized metered dose inhalers for treatment in children. Eur Respir J 1998; 12: 472–6PubMedCrossRefGoogle Scholar
  23. 23.
    Wildhaber JH, Janssens HM, Piérart F, et al. High-percentage lung delivery in children from detergent-treated spacers. Pediatr Pulmonol 2000; 29: 389–93PubMedCrossRefGoogle Scholar
  24. 24.
    Kenyon CJ, Thorsson L, Borgström L, et al. The effects of static charge in spacer devices on glucocorticosteroid aerosol deposition in asthmatic patients. Eur Respir J 1998; 11: 606–10PubMedGoogle Scholar
  25. 25.
    Dompeling E, Oudesluys-Murphy AM, Janssens HM, et al. Randomised controlled study of clinical efficacy of spacer therapy in asthma with regard to electrostatic charge. Arch Dis Child 2001; 84: 178–82PubMedCrossRefGoogle Scholar
  26. 26.
    Tal A, Golan H, Grauer N, et al. Deposition pattern of radiolabeled salbutamol inhaled from a metered-dose inhaler by means of a spacer with mask in young children with airway obstruction. J Pediatr 1996; 128: 479–84PubMedCrossRefGoogle Scholar
  27. 27.
    Anhoj J, Thorsson L, Bisgaard H. Lung deposition of inhaled drugs increases with age. Am J Respir Crit Care Med 2000; 162: 1819–22Google Scholar
  28. 28.
    Wildhaber JH, Devadason SG, Wilson JW, et al. Lung deposition of budesonide from Turbuhaler in asthmatic children. Eur J Pediatr 1998; 157: 1017–22PubMedCrossRefGoogle Scholar
  29. 29.
    Barry PW, O’Callaghan C. In vitro comparison of the amount of salbutamol available for inhalation from different formulations used with different spacer devices. Eur Respir J 1997; 10: 1345–8PubMedCrossRefGoogle Scholar
  30. 30.
    Brand PLP, van der Baan-Slootweg OH, Heynens JWCM, et al. Comparison of handling and acceptability of two spacer devices in young children with asthma. Acta Paediatr 2001; 90: 133–6PubMedCrossRefGoogle Scholar
  31. 31.
    Barry PW, O’Callaghan C. Nebuliser therapy in childhood. Thorax 1997; 52Suppl. 2: S78–88PubMedCrossRefGoogle Scholar
  32. 32.
    Boe J, Dennis JH, O’Driscoll BR. European Respiratory Society guidelines on the use of nebulizers. Eur Respir J 2001; 18: 228–42PubMedCrossRefGoogle Scholar
  33. 33.
    O’Callaghan C, Barry PW. The science of nebulised drug delivery. Thorax 1997; 52Suppl. 2: S31–44PubMedCrossRefGoogle Scholar
  34. 34.
    Struycken VH, Tiddens HA, van den Broek ET, et al. Problems in the use, cleaning and maintenance of nebulization equipment in the home situation [in Dutch]. Ned Tijdschr Geneeskd 1996; 140: 654–8PubMedGoogle Scholar
  35. 35.
    Parkin PC, Saunders NR, Diamond SA, et al. Randomised trial spacer vs nebuliser for acute asthma. Arch Dis Child 1995; 72: 239–40PubMedCrossRefGoogle Scholar
  36. 36.
    Barry PW, O’Callaghan C. The output of budesonide from nebulisers. J Allergy Clin Immunol 2002; 102: 321–2CrossRefGoogle Scholar
  37. 37.
    Loffert DT, Ikle D, Nelson HS. A comparison of commercial jet nebulizers. Chest 1994; 106: 1788–93PubMedCrossRefGoogle Scholar
  38. 38.
    Penna AC, Dawson KP, Manglick P, et al. Systemic absorption of salbutamol following nebulizer delivery in acute asthma. Acta Paediatr 1993; 82: 963–6PubMedCrossRefGoogle Scholar
  39. 39.
    Mallol J, Rattray S, Walker G, et al. Aerosol deposition in infants with cystic fibrosis. Pediatr Pulmonol 1996; 21: 276–81PubMedCrossRefGoogle Scholar
  40. 40.
    Chua HL, Collis GG, Newbury AM, et al. The influence of age on aerosol deposition in children with cystic fibrosis. Eur Respir J 1994; 7: 2185–91PubMedCrossRefGoogle Scholar
  41. 41.
    Mukhopadhyay S, Staddon GE, Eastman C, et al. The quantitative distribution of nebulized antibiotic in the lung in cystic fibrosis. Respir Med 1994; 88: 203–11PubMedCrossRefGoogle Scholar
  42. 42.
    Dubus J-C, Marguet C, Deschildre A, et al. Local side-effects of inhaled corticosteroids in asthmatic children: influence of drug, dose, age, and device. Allergy 2001; 56: 944–8PubMedCrossRefGoogle Scholar
  43. 43.
    Joint Task Force on Practice Parameters. Practice parameters for the diagnosis and treatment of asthma. J Allergy Clin Immunol 1995; 96(5 Pt 2): 858–70Google Scholar
  44. 44.
    Asthma: a follow-up statement from an international paediatric asthma consensus group. Arch Dis Child 1992; 67: 240–8Google Scholar
  45. 45.
    Price JF, Weiler PH. Comparison of fluticasone propionate and sodium cromoglycate for the treatment of childhood asthma (an open parallel group study). Respir Med 1995; 89: 363–8PubMedCrossRefGoogle Scholar
  46. 46.
    Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000; 343: 1054–63CrossRefGoogle Scholar
  47. 47.
    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: 64–77PubMedGoogle Scholar
  48. 48.
    Williams B, Noonan G, Reiss TF, et al. Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older. Clin Exp Allergy 2001; 31: 845–54PubMedCrossRefGoogle Scholar
  49. 49.
    Simons FER, Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. N Engl J Med 1997; 337: 1659–65CrossRefGoogle Scholar
  50. 50.
    Verberne AAPH, Frost C, Roorda RJ, et al. One year treatment with salmeterol compared with beclomethasone in children with asthma. Am J Respir Crit Care Med 1997; 156: 688–95PubMedGoogle Scholar
  51. 51.
    Calpin C, Macarthur C, Stephens D, et al. Effectiveness of prophylactic inhaled steroids in childhood asthma: a systematic review of the literature. J Allergy Clin Immunol 1997; 100: 452–7PubMedCrossRefGoogle Scholar
  52. 52.
    Allen DB. Safety of inhaled corticosteroids in children. Pediatr Pulmonol 2002; 33: 208–20PubMedCrossRefGoogle Scholar
  53. 53.
    Brand PLP. Inhaled corticosteroids reduce growth: or do they. Eur Respir J 2001; 17: 287–94PubMedCrossRefGoogle Scholar
  54. 54.
    Pedersen S. Do inhaled corticosteroids inhibit growth in children. Am J Respir Crit Care Med 2001; 164: 521–35PubMedGoogle Scholar
  55. 55.
    Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med 1999; 159: 941–55PubMedCrossRefGoogle Scholar
  56. 56.
    Russell G, Ninan TK. Inhaled corticosteroid toxicity, growth and asthma. In: David TJ, editor. Recent advances in paediatrics. 17th ed. London: Churchill Livingstone, 1999: 1–15Google Scholar
  57. 57.
    Brand PLP. Inhalation therapy in children with asthma. Minerva Pediatr 2000; 52: 137–42PubMedGoogle Scholar
  58. 58.
    Ram FSF, Wright J, Brocklebak D, et al. Systematic review of clinical effectiveness of pressurized metered dose inhalers versus other hand held inhaler devices for delivering β2 agonist bronchodilators in asthma. National Health Technology Assessment Inhaler Review Group. BMJ 2001; 323: 901–5PubMedCrossRefGoogle Scholar
  59. 59.
    Blackhall MI, O’Donnell SR. A dose-response study of inhaled terbutaline administered via Nebuhaler or nebuliser to asthmatic children. Eur J Respir Dis 1987; 71: 96–101PubMedGoogle Scholar
  60. 60.
    Pierce RJ, McDonald CF, Le Souef PN, et al. Nebuhaler vs wet aerosol for domiciliary bronchodilator therapy. Med J Aust 1992; 156: 771–4PubMedGoogle Scholar
  61. 61.
    Uhlig T, Eber E, Devadason SG, et al. Aerosol delivery to spontaneously breathing neonates: spacer or nebulizer. Pediatr Asthma Allergy Immunol 1997; 11: 111–7CrossRefGoogle Scholar
  62. 62.
    Fitzgerald M. Extracts from clinical evidence: acute asthma. BMJ 2000; 323: 841–5CrossRefGoogle Scholar
  63. 63.
    Bentur L, Canny GJ, Shields MD, et al. Controlled trial of nebulized albuterol in children younger than 2 years of age with acute asthma. Pediatrics 1992; 89: 133–7PubMedGoogle Scholar
  64. 64.
    Robertson CF, Smith F, Beck R, et al. Response to frequent low doses of nebulized salbutamol in acute asthma. J Pediatr 1985; 106: 672–4PubMedCrossRefGoogle Scholar
  65. 65.
    Katz RW, Kelly W, Crowley MR, et al. Safety of continuously nebulized albuterol for bronchospasm in infants and children. Pediatrics 1993; 92: 666–9PubMedGoogle Scholar
  66. 66.
    Moler FW, Hurwitz E, Custer JR. Improvement in clinical asthma score and PaCO2 in children with severe asthma treated with continuously nebulized terbutaline. J Allergy Clin Immunol 1988; 81: 1101–9PubMedCrossRefGoogle Scholar
  67. 67.
    Craig VL, Bigos D, Brilli RJ. Efficacy and safety of continuous albuterol nebulization in children with severe status asthmaticus. Pediatr Emerg Care 1996; 12: 1–5PubMedGoogle Scholar
  68. 68.
    Montgomery VL, Eid NS. Low-dose beta-agonist continuous nebulization therapy for status asthmaticus in children. J Asthma 1994; 31: 201–7PubMedCrossRefGoogle Scholar
  69. 69.
    Papo MC, Frank J, Thompson AE. A prospective, randomized study of continuous vs intermittent nebulized albuterol for severe status asthmaticus in children. Crit Care Med 1993; 21: 1479–86PubMedCrossRefGoogle Scholar
  70. 70.
    Pedersen S. Aerosol treatment of bronchoconstriction in children, with or without a tube spacer. N Engl J Med 1983; 308: 1328–30PubMedCrossRefGoogle Scholar
  71. 71.
    Pedersen S. Treatment of acute bronchoconstriction in children with use of a tube spacer aerosol and a dry powder inhaler. Allergy 1985; 40: 300–4PubMedCrossRefGoogle Scholar
  72. 72.
    Benton G, Thomas RC, Nickerson BG, et al. Experience with a metered-dose inhaler with a spacer in the pediatric emergency department. Am J Dis Child 1989; 143: 678–81PubMedGoogle Scholar
  73. 73.
    Goren A, Noviski N, Avital A, et al. Assessment of the ability of young children to use a powder inhaler device (Turbuhaler). Pediatr Pulmonol 1994; 18: 77–80PubMedCrossRefGoogle Scholar
  74. 74.
    Laberge S, Spier S, Drblik SP, et al. Comparison of inhaled terbutaline administered by either the Turbuhaler dry powder inhaler or a metered-dose inhaler with spacer in preschool children with asthma. J Pediatr 1994; 124: 815–7PubMedCrossRefGoogle Scholar
  75. 75.
    Ruggins NR, Milner AD, Swarbrick A. An assessment of a new breath actuated inhaler device in acutely wheezy children. Arch Dis Child 1993; 68: 477–80PubMedCrossRefGoogle Scholar
  76. 76.
    Closa RM, Ceballos JM, Gómez-Papí A, et al. Efficacy of bronchodilators administered by nebulizers versus spacer devices in infants with acute wheezing. Pediatr Pulmonol 1998; 26: 344–8PubMedCrossRefGoogle Scholar
  77. 77.
    Dewar AL, Stewart A, Cogswell JJ, et al. A randomised controlled trial to assess the relative benefits of large volume spacers and nebulizers to treat acute asthma in hospital. Arch Dis Child 1999; 80: 421–3PubMedCrossRefGoogle Scholar
  78. 78.
    Ploin D, Chapuis FR, Stamm D, et al. High-dose albuterol by metered-dose inhaler plus a spacer device vs nebulization in preschool children with recurrent wheezing: a double-blind, randomized equivalence trial. Pediatrics 2000; 106: 311–7PubMedGoogle Scholar
  79. 79.
    Leversha AM, Campanella SG, Aickin RP, et al. Costs and effectiveness of spacer vs nebulizer in young children with moderate and severe acute asthma. J Pediatr 2000; 136: 497–502PubMedCrossRefGoogle Scholar
  80. 80.
    Mandelberg A, Tschori S, Houri S, et al. Is nebulized aerosol treatment necessary in the pediatric emergency department: comparison with a metal spacer device for metered-dose inhaler. Chest 2000; 117: 1309–13PubMedCrossRefGoogle Scholar
  81. 81.
    Rubilar L, Castro-Rodriguez JA, Girardi G. Randomized trial of salbutamol via metered-dose inhaler with spacer vs nebulizer for acute wheezing in children less than 2 years of age. Pediatr Pulmonol 2000; 29: 264–9PubMedCrossRefGoogle Scholar
  82. 82.
    Fuglsang G, Pedersen S. Comparison of Nebuhaler and nebulizer treatment of acute severe asthma in children. Eur J Respir Dis 1986; 69: 109–13PubMedGoogle Scholar
  83. 83.
    Kerem E, Levison H, Schuh S, et al. Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma. J Pediatr 1993; 123: 313–7PubMedCrossRefGoogle Scholar
  84. 84.
    Lin Y-Z, Hsieh K-H. Metered dose inhaler and nebuliser in acute asthma. Arch Dis Child 1995; 72: 214–8PubMedCrossRefGoogle Scholar
  85. 85.
    Williams JR, Bothner JP, Swanton RD. Delivery of albuterol in a pediatric emergency department. Pediatr Emerg Care 1996; 12: 263–7PubMedCrossRefGoogle Scholar
  86. 86.
    Schuh S, Johnson DW, Stephens D, et al. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma. J Pediatr 1999; 135: 22–7PubMedCrossRefGoogle Scholar
  87. 87.
    Chou KJ, Cunningham SJ, Crain EF. Metered-dose inhalers with spacers vs nebulizers for pediatric asthma. Arch Pediatr Adolesc Med 1995; 149: 201–5PubMedCrossRefGoogle Scholar
  88. 88.
    Robertson CF, Norden MA, Fitzgerald DA, et al. Treatment of acute asthma: salbutamol via jet nebuliser vs spacer and metered dose inhaler. J Paediatr Child Health 1998; 34: 142–6PubMedCrossRefGoogle Scholar
  89. 89.
    Cates CJ, Rowe BH, Bara A. Holding chambers vs nebulisers for beta-agonist treatment of acute asthma (Cochrane review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2002Google Scholar
  90. 90.
    Turner MO, Patel A, Ginsburg S, et al. Bronchodilator delivery in acute airflow obstruction: a meta-analysis. Arch Intern Med 1997; 157: 1736–44PubMedCrossRefGoogle Scholar
  91. 91.
    Zar HJ, Brown G, Donson H, et al. Home-made spacers for bronchodilator therapy in children with acute asthma: a randomised trial. Lancet 1999; 354: 979–82PubMedCrossRefGoogle Scholar
  92. 92.
    Powell CVE, Maskell GR, Marks MK, et al. Successful implementation of spacer treatment guidelines for acute asthma. Arch Dis Child 2001; 84: 142–6PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2003

Authors and Affiliations

  1. 1.Department of Paediatrics, Division of Paediatric PulmonologyIsala Klinieken/Weezenlanden HospitalZwolleThe Netherlands

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