Intermittent steroid inhalation for the treatment of childhood asthma

References

• Papers of special note have been highlighted as:
   Google Scholar
• * Of interest
   Google Scholar
• ** Of considerable interest
   Google Scholar
• Global Strategy for Asthma Management and Prevention-Updated 2015. [ cited 2015 May 26]. 2015. Available from: http://www.ginasthma.org/local/uploads/files/GINA_Report_2015.pdf.
   Google Scholar
• Lemanske RF Jr., Jackson DJ, Gangnon RE, et al. Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J Allergy Clin Immunol. 2005;116:571–577.
   PubMed Web of Science ®Google Scholar
• Gern JE, Busse WW. Relationship of viral infections to wheezing illnesses and asthma. Nat Rev Immunol. 2002;2:132–138.
   PubMed Web of Science ®Google Scholar
• Depner M, Fuchs O, Genuneit J, et al. Clinical and epidemiologic phenotypes of childhood asthma. Am J Respir Crit Care Med. 2014;189:129–138.
   PubMed Web of Science ®Google Scholar
• Brand PL, Baraldi E, Bisgaard H, et al. Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J. 2008;32:1096–1110.
   PubMed Web of Science ®Google Scholar
• Suissa S, Ernst P, Kezouh A. Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma. Thorax. 2002;57:880–884.
   PubMed Web of Science ®Google Scholar
• Suissa S, Ernst P, Benayoun S, et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. New England J Med. 2000;343:332–336.
   PubMed Web of Science ®Google Scholar
• Long-term effects of budesonide or nedocromil in children with asthma. The Childhood Asthma Management Program Research Group. N Engl J Med 2000;343:1054–1063.
   PubMed Web of Science ®Google Scholar

** Aids in establishing inhaled corticosteroids as a treatment for childhood asthma

• Castro-Rodriguez JA, Rodrigo GJ. Efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing and asthma: a systematic review with meta-analysis. Pediatrics. 2009;123:e519–25.
   PubMed Web of Science ®Google Scholar
• Bisgaard H, Gillies J, Groenewald M, et al. The effect of inhaled fluticasone propionate in the treatment of young asthmatic children: a dose comparison study. Am J Respir Crit Care Med. 1999;160:126–131.
   PubMed Web of Science ®Google Scholar
• Wilson N, Sloper K, Silverman M. Effect of continuous treatment with topical corticosteroid on episodic viral wheeze in preschool children. Arch Dis Child. 1995;72:317–320.
   PubMed Web of Science ®Google Scholar
• Doull IJ, Lampe FC, Smith S, et al. Effect of inhaled corticosteroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial. BMJ. 1997;315:858–862.
   PubMed Web of Science ®Google Scholar
• Roorda RJ, Mezei G, Bisgaard H, et al. Response of preschool children with asthma symptoms to fluticasone propionate. J Allergy Clin Immunol. 2001;108:540–546.
   PubMed Web of Science ®Google Scholar
• Pao CS, McKenzie SA. Randomized controlled trial of fluticasone in preschool children with intermittent wheeze. Am J Respir Crit Care Med. 2002;166:945–949.
   PubMed Web of Science ®Google Scholar
• Teper AM, Kofman CD, Szulman GA, et al. Fluticasone improves pulmonary function in children under 2 years old with risk factors for asthma. Am J Respir Crit Care Med. 2005;171:587–590.
   PubMed Web of Science ®Google Scholar
• Bibi HS, Feigenbaum D, Hessen M, et al. Do current treatment protocols adequately prevent airway remodeling in children with mild intermittent asthma? Respiratory Medicine. 2006;100:458–462.
   PubMed Web of Science ®Google Scholar
• Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;354:1985–1997.
   PubMed Web of Science ®Google Scholar

** Important in establishing that treatment with inhaled corticosteroids do not seem to have significant disease-modifying effects

• Bacharier LB, Guilbert TW, Zeiger RS, et al. Patient characteristics associated with improved outcomes with use of an inhaled corticosteroid in preschool children at risk for asthma. J Allergy Clin Immunol. 2009;123:1077-1082, 82 e1-5.
   Web of Science ®Google Scholar
• Teper AM, Colom AJ, Kofman CD, et al. Effects of inhaled fluticasone propionate in children less than 2 years old with recurrent wheezing. Pediatr Pulmonol. 2004;37:111–115.
   PubMed Web of Science ®Google Scholar
• Turpeinen M, Raitio H, Pelkonen AS, et al. Skin thickness in children treated with daily or periodical inhaled budesonide for mild persistent asthma. The Helsinki early intervention childhood asthma study. Pediatr Res. 2010;67:221–225.
   PubMed Web of Science ®Google Scholar
• Turpeinen M, Pelkonen AS, Nikander K, et al. Bone mineral density in children treated with daily or periodical inhaled budesonide: the Helsinki early intervention childhood asthma study. Pediatr Res. 2010;68:169–173.
   PubMed Web of Science ®Google Scholar
• Donaldson MD, Morrison C, Lees C, et al. Fatal and near-fatal encephalopathy with hyponatraemia in two siblings with fluticasone-induced adrenal suppression. Acta Paediatr. 2007;96:769–772.
   PubMed Web of Science ®Google Scholar
• Schwartz RH, Neacsu O, Ascher DP, et al. Moderate dose inhaled corticosteroid-induced symptomatic adrenal suppression: case report and review of the literature. Clin Pediatr (Phila). 2012;51:1184–1190.
   PubMed Web of Science ®Google Scholar
• Todd GR, Wright D, Ryan M. Acute adrenal insufficiency in a patient with asthma after changing from fluticasone propionate to budesonide. J Allergy Clin Immunol. 1999;103:956–957.
   PubMed Web of Science ®Google Scholar
• Todd GR, Acerini CL, Buck JJ, et al. Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate. Eur Respir J. 2002;19:1207–1209.
   PubMed Web of Science ®Google Scholar
• Drake AJ, Howells RJ, Shield JP, et al. Symptomatic adrenal insufficiency presenting with hypoglycaemia in children with asthma receiving high dose inhaled fluticasone propionate. BMJ. 2002;324:1081–1082.
   PubMed Web of Science ®Google Scholar
• Zimmerman B, Gold M, Wherrett D, et al. Adrenal suppression in two patients with asthma treated with low doses of the inhaled steroid fluticasone propionate. J Allergy Clin Immunol. 1998;101:425–426.
   PubMed Web of Science ®Google Scholar
• Allen DB. Inhaled corticosteroids and growth: still an issue after all these years. J Pediatr. 2015;166:463–469.
   PubMed Web of Science ®Google Scholar

** Recent commentary on inhaled corticosteroids growth effects

• Sharek PJ, Bergman DA. The effect of inhaled steroids on the linear growth of children with asthma: a meta-analysis. Pediatrics. 2000;106:E8.
   PubMed Web of Science ®Google Scholar
• Pruteanu AI, Chauhan BF, Zhang L, et al. Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth. Cochrane Database Systematic Rev. 2014;7:CD009878.
   PubMed Web of Science ®Google Scholar
• Kelly HW, Sternberg AL, Lescher R, et al. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012;367:904–912.
   PubMed Web of Science ®Google Scholar

** Important study on the persistence of childhood inhaled corticosteroid-related growth suppression into adulthood

• Guilbert TW, Mauger DT, Allen DB, et al. Growth of preschool children at high risk for asthma 2 years after discontinuation of fluticasone. J Allergy Clin Immunol. 2011;128:956-963 e1-7.
   Web of Science ®Google Scholar
• Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med. 2000;343:1064–1069.
   PubMed Web of Science ®Google Scholar

* Important study of the effects of inhaled corticosteroids on height

• Allen DB, Mullen M, Mullen B. A meta-analysis of the effect of oral and inhaled corticosteroids on growth. J Allergy Clin Immunol. 1994;93:967–976.
   PubMed Web of Science ®Google Scholar
• Bisgaard H, Allen D, Milanowski J, et al. Twelve-month safety and efficacy of inhaled fluticasone propionate in children aged 1 to 3 years with recurrent wheezing. Pediatrics. 2004;113:e87–94.
   PubMed Web of Science ®Google Scholar
• Skoner DP, Maspero J, Banerji D, Ciclesonide Pediatric Growth Study G. Assessment of the long-term safety of inhaled ciclesonide on growth in children with asthma. Pediatrics. 2008;121:e1–14.
   PubMed Web of Science ®Google Scholar
• Pelkonen A, Kari O, Selroos O, et al. Ophthalmologic findings in children with asthma receiving inhaled budesonide. J Allergy Clin Immunol. 2008;122:832–834.
   PubMed Web of Science ®Google Scholar
• Gibson PG, Saltos N, Fakes K. Acute anti-inflammatory effects of inhaled budesonide in asthma: a randomized controlled trial. Am J Respir Crit Care Med. 2001;163:32–36.
   PubMed Web of Science ®Google Scholar
• Wilson NM, Silverman M. Treatment of acute, episodic asthma in preschool children using intermittent high dose inhaled steroids at home. Arch Dis Child. 1990;65:407–410.
   PubMed Web of Science ®Google Scholar
• Connett G, Lenney W. Prevention of viral induced asthma attacks using inhaled budesonide. Arch Dis Child. 1993;68:85–87.
   PubMed Web of Science ®Google Scholar
• Svedmyr J, Nyberg E, Asbrink-Nilsson E, et al. Intermittent treatment with inhaled steroids for deterioration of asthma due to upper respiratory tract infections. Acta Paediatr. 1995;84:884–888.
   PubMed Web of Science ®Google Scholar
• Svedmyr J, Nyberg E, Thunqvist P, et al. Prophylactic intermittent treatment with inhaled corticosteroids of asthma exacerbations due to airway infections in toddlers. Acta Paediatr. 1999;88:42–47.
   PubMed Web of Science ®Google Scholar
• Foresi A, Morelli MC, Catena E. Low-dose budesonide with the addition of an increased dose during exacerbations is effective in long-term asthma control. On behalf of the Italian Study Group. Chest. 2000;117:440–446.
   PubMed Web of Science ®Google Scholar
• McKean M, Ducharme F. Inhaled steroids for episodic viral wheeze of childhood. Cochrane Database Systematic Rev. 2000;CD001107. doi:10.1002/14651858.CD001107.
   Google Scholar

* Meta-analysis of inhaled steroids for intermittent childhood wheeze

• Volovitz B, Nussinovitch M, Finkelstein Y, et al. Effectiveness of inhaled corticosteroids in controlling acute asthma exacerbations in children at home. Clin Pediatr (Phila). 2001;40:79–86.
   PubMed Web of Science ®Google Scholar
• FitzGerald JM, Becker A, Sears MR, et al. Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations. Thorax. 2004;59:550–556.
   PubMed Web of Science ®Google Scholar
• Bisgaard H, Hermansen MN, Loland L, et al. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med. 2006;354:1998–2005.
   PubMed Web of Science ®Google Scholar

* Investigates the long-term effects of inhaled corticosteroids used in very young infants with wheeze

• Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol. 2008;122:1127–35 e8.
   PubMed Web of Science ®Google Scholar

* Investigated episodic steroid and leukotriene receptor antagonist for intermittent wheeze

• Turpeinen M, Nikander K, Pelkonen AS, et al. Daily versus as-needed inhaled corticosteroid for mild persistent asthma (the Helsinki early intervention childhood asthma study). Arch Dis Child. 2008;93:654–659.
   PubMed Web of Science ®Google Scholar
• Zeiger RS, Mauger D, Bacharier LB, et al. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med. 2011;365:1990–2001.
   PubMed Web of Science ®Google Scholar

* Study of intermittent inhaled corticosteroids for childhood asthma

• Martinez FD, Chinchilli VM, Morgan WJ, et al. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet. 2011;377:650–657.
   PubMed Web of Science ®Google Scholar

* Comparison of intermittent and daily inhaled corticosteroid therapy

• Calhoun WJ, Ameredes BT, King TS, et al. Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial. Jama. 2012;308:987–997.
   PubMed Web of Science ®Google Scholar

** Aids in establishing that patient, symptom-based therapy modification is not superior to physician-based dosage adjustment

• Thomas A, Lemanske RF Jr., Jackson DJ. Approaches to stepping up and stepping down care in asthmatic patients. J Allergy Clin Immunol. 2011;128:915–924. quiz 25-6.
   PubMed Web of Science ®Google Scholar

* Summary of approaches to stepping up and stepping down asthma care

• Ducharme FM, Lemire C, Noya FJ, et al. Preemptive use of high-dose fluticasone for virus-induced wheezing in young children. N Engl J Med. 2009;360:339–353.
   PubMed Web of Science ®Google Scholar
• Papi A, Nicolini G, Baraldi E, et al. Regular vs prn nebulized treatment in wheeze preschool children. Allergy. 2009;64:1463–1471.
   PubMed Web of Science ®Google Scholar
• Papi A, Canonica GW, Maestrelli P, et al. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N Engl J Med. 2007;356:2040–2052.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Martinez CE, Nino G, Castro-Rodriguez JA. Cost-utility analysis of daily versus intermittent inhaled corticosteroids in mild-persistent asthma. Pediatr Pulmonol. 2015;50(8):735–746.
   PubMed Web of Science ®Google Scholar
• Nelson HS, Weiss ST, Bleecker ER, et al. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15–26.
   PubMed Web of Science ®Google Scholar

* Study of LABA therapy that raises concerns for asthma-related deaths

• Salpeter SR, Buckley NS, Ormiston TM, et al. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006;144:904–912.
   PubMed Web of Science ®Google Scholar

* Meta-analysis of LABA therapy that raises concerns for asthma-related deaths

• FitzGerald JM, Sears MR, Boulet LP, et al. Adjustable maintenance dosing with budesonide/formoterol reduces asthma exacerbations compared with traditional fixed dosing: a five-month multicentre Canadian study. Can Respir J. 2003;10:427–434.
   PubMedGoogle Scholar
• Aalbers R, Backer V, Kava TT, et al. Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma. Curr Med Res Opin. 2004;20:225–240.
   PubMed Web of Science ®Google Scholar
• FitzGerald JM, Boulet LP, Follows RM. The CONCEPT trial: a 1-year, multicenter, randomized, double-blind, double-dummy comparison of a stable dosing regimen of salmeterol/fluticasone propionate with an adjustable maintenance dosing regimen of formoterol/budesonide in adults with persistent asthma. Clin Ther. 2005;27:393–406.
   PubMed Web of Science ®Google Scholar

* Describes that there may be a minimum daily therapy needed with dynamic dosing

• Vogelmeier C, D’Urzo A, Pauwels R, et al. Budesonide/formoterol maintenance and reliever therapy: an effective asthma treatment option? Eur Respir J. 2005;26:819–828.
   PubMed Web of Science ®Google Scholar
• O’Byrne PM, Bisgaard H, Godard PP, et al. Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Am J Respir Crit Care Med. 2005;171:129–136.
   PubMed Web of Science ®Google Scholar

* Important study of dynamic dosing in children

• Bisgaard H, Le Roux P, Bjamer D, et al. Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. Chest. 2006;130:1733–1743.
   PubMed Web of Science ®Google Scholar

* Another important study of dynamic dosing in children

• Bousquet J, Boulet LP, Peters MJ, et al. Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs high-dose salmeterol/fluticasone. Respiratory Medicine. 2007;101:2437–2446.
   PubMed Web of Science ®Google Scholar
• Kew KM, Karner C, Mindus SM, et al. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database Systematic Rev. 2013;12:CD009019.
   PubMedGoogle Scholar

* Cochrane review of dynamic dosing strategies in adults and children