Download PDF
Semin Respir Crit Care Med 2018; 39(01): 036-044
DOI: 10.1055/s-0037-1608707
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Controlling the Risk Domain in Pediatric Asthma through Personalized Care

William C. Anderson III
1   Department of Pediatrics, Section of Allergy and Immunology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
,
Stanley J. Szefler
2   Department of Pediatrics, The Breathing Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
› Author Affiliations
Further Information

Publication History

Publication Date:
10 February 2018 (online)

    Permissions and Reprints

Abstract

Strategies to control the risk domain of NHLBI EPR-3 (National Heart, Lung, and Blood Institute Expert Panel Report-3) asthma guidelines, which includes exacerbations requiring systemic corticosteroids, reduction in lung growth, and progressive loss of lung function, and treatment-related adverse effects, are evolving in children and adolescents. Increasing evidence demonstrates that children and adolescents with asthma are at risk of a reduction in lung growth, leading to lower lung function and potentially chronic obstructive pulmonary disease as adults. Readily available clinical biomarkers for atopy, including aeroallergen testing, total serum IgE, blood eosinophilia, and spirometry, are being utilized to phenotype difficult-to-treat pediatric patients, to assess risk for seasonal exacerbations, and to predict response to controller therapies. The Composite Asthma Severity Index is a novel, freely available scoring system to define asthma control, incorporating NHLBI EPR-3 risk and impairment domains. As new asthma controller therapies, such as tiotropium, are introduced for pediatric use, the safety of established controller therapies including inhaled corticosteroid and long-acting beta-agonist are being reexamined. Macrolide antibiotics may be an oral corticosteroid sparing alternative for the treatment of severe respiratory tract infection in preschool-aged children. Seasonally directed courses of omalizumab may provide an alternative approach to prevent fall asthma exacerbations in children. Combining these pharmaceuticals and biomarker-directed therapies provide potential new options and personalized approaches to gain asthma control in pediatric patients failing current management.

Keywords

risk domain - lung function decline - biomarker - inhaled corticosteroid - long-acting β-agonist - tiotropium - macrolide - omalizumab
 

  • References

  • 1 Szefler SJ. Advancing asthma care: the glass is only half full!. J Allergy Clin Immunol 2011; 128 (03) 485-494
    CrossrefPubMedGoogle Scholar
  • 2 Anderson III WC, Szefler SJ. New and future strategies to improve asthma control in children. J Allergy Clin Immunol 2015; 136 (04) 848-859
    CrossrefPubMedGoogle Scholar
  • 3 National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol 2007; 120 (5, Suppl): S94-S138
    CrossrefPubMedGoogle Scholar
  • 4 Farber HJ, Silveira EA, Vicere DR, Kothari VD, Giardino AP. Oral corticosteroid prescribing for children with asthma in a Medicaid managed care program. Pediatrics 2017; 139 (05) 139
    PubMedGoogle Scholar
  • 5 Sullivan PW, Ghushchyan V, Navaratnam P. , et al. National prevalence of poor asthma control and associated outcomes among school-aged children in the United States. J Allergy Clin Immunol Pract 2017; S2213-2198(17)30525-1
    PubMedGoogle Scholar
  • 6 Sullivan PW, Ghushchyan V, Navaratnam P. , et al. The national cost of asthma among school-aged children in the United States. Ann Allergy Asthma Immunol 2017; 119 (03) 246-252.e1
    CrossrefPubMedGoogle Scholar
  • 7 Belgrave DC, Buchan I, Bishop C, Lowe L, Simpson A, Custovic A. Trajectories of lung function during childhood. Am J Respir Crit Care Med 2014; 189 (09) 1101-1109
    CrossrefPubMedGoogle Scholar
  • 8 Duijts L, Granell R, Sterne JA, Henderson AJ. Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide fraction in adolescence. Eur Respir J 2016; 47 (02) 510-519
    CrossrefPubMedGoogle Scholar
  • 9 Lodge CJ, Lowe AJ, Allen KJ. , et al. Childhood wheeze phenotypes show less than expected growth in FEV1 across adolescence. Am J Respir Crit Care Med 2014; 189 (11) 1351-1358
    CrossrefPubMedGoogle Scholar
  • 10 Lodge CJ, Zaloumis S, Lowe AJ. , et al. Early-life risk factors for childhood wheeze phenotypes in a high-risk birth cohort. J Pediatr 2014; 164 (02) 289-94.e1 , 2
    CrossrefPubMedGoogle Scholar
  • 11 Tai A, Tran H, Roberts M, Clarke N, Wilson J, Robertson CF. The association between childhood asthma and adult chronic obstructive pulmonary disease. Thorax 2014; 69 (09) 805-810
    CrossrefPubMedGoogle Scholar
  • 12 Tagiyeva N, Devereux G, Fielding S, Turner S, Douglas G. Outcomes of childhood asthma and wheezy bronchitis. A 50-year cohort study. Am J Respir Crit Care Med 2016; 193 (01) 23-30
    CrossrefPubMedGoogle Scholar
  • 13 McGeachie MJ, Yates KP, Zhou X. , et al. Patterns of growth and decline in lung function in persistent childhood asthma. N Engl J Med 2016; 374 (19) 1842-1852
    CrossrefPubMedGoogle Scholar
  • 14 Zoratti EM, Krouse RZ, Babineau DC. , et al. Asthma phenotypes in inner-city children. J Allergy Clin Immunol 2016; 138 (04) 1016-1029
    CrossrefPubMedGoogle Scholar
  • 15 Pongracic JA, Krouse RZ, Babineau DC. , et al. Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents. J Allergy Clin Immunol 2016; 138 (04) 1030-1041
    CrossrefPubMedGoogle Scholar
  • 16 Wildfire JJ, Gergen PJ, Sorkness CA. , et al. Development and validation of the Composite Asthma Severity Index--an outcome measure for use in children and adolescents. J Allergy Clin Immunol 2012; 129 (03) 694-701
    CrossrefPubMedGoogle Scholar
  • 17 Krouse RZ, Sorkness CA, Wildfire JJ. , et al. Minimally important differences and risk levels for the Composite Asthma Severity Index. J Allergy Clin Immunol 2017; 139 (03) 1052-1055
    CrossrefPubMedGoogle Scholar
  • 18 Teach SJ, Gergen PJ, Szefler SJ. , et al. Seasonal risk factors for asthma exacerbations among inner-city children. J Allergy Clin Immunol 2015; 135 (06) 1465-73.e5
    CrossrefPubMedGoogle Scholar
  • 19 Hoch HE, Calatroni A, West JB. , et al. Can we predict fall asthma exacerbations? Validation of the seasonal asthma exacerbation index. J Allergy Clin Immunol 2017; 140 (04) 1130.e5-1137.e5
    PubMedGoogle Scholar
  • 20 Gerald JK, Gerald LB, Vasquez MM. , et al. Markers of differential response to inhaled corticosteroid treatment among children with mild persistent asthma. J Allergy Clin Immunol Pract 2015; 3 (04) 540-6.e3
    CrossrefPubMedGoogle Scholar
  • 21 Fitzpatrick AM, Jackson DJ, Mauger DT. , et al; NIH/NHLBI AsthmaNet. Individualized therapy for persistent asthma in young children. J Allergy Clin Immunol 2016; 138 (06) 1608-1618.e12
    CrossrefPubMedGoogle Scholar
  • 22 van Aalderen WM, Grigg J, Guilbert TW. , et al. Small-particle inhaled corticosteroid as first-line or step-up controller therapy in childhood asthma. J Allergy Clin Immunol Pract 2015; 3 (05) 721-31.e16
    CrossrefPubMedGoogle Scholar
  • 23 Kapadia CR, Nebesio TD, Myers SE. , et al; Drugs and Therapeutics Committee of the Pediatric Endocrine Society. Endocrine effects of inhaled corticosteroids in children. JAMA Pediatr 2016; 170 (02) 163-170
    CrossrefPubMedGoogle Scholar
  • 24 Cavkaytar O, Vuralli D, Arik Yilmaz E. , et al. Evidence of hypothalamic-pituitary-adrenal axis suppression during moderate-to-high-dose inhaled corticosteroid use. Eur J Pediatr 2015; 174 (11) 1421-1431
    CrossrefPubMedGoogle Scholar
  • 25 Beigelman A, Bacharier LB. Management of preschool children with recurrent wheezing: lessons from the NHLBI's Asthma Research Networks. J Allergy Clin Immunol Pract 2016; 4 (01) 1-8 , quiz 9–10
    CrossrefPubMedGoogle Scholar
  • 26 Chong J, Haran C, Chauhan BF, Asher I. Intermittent inhaled corticosteroid therapy versus placebo for persistent asthma in children and adults. Cochrane Database Syst Rev 2015; (07) CD011032
    PubMedGoogle Scholar
  • 27 Reddel HK, Busse WW, Pedersen S. , et al. Should recommendations about starting inhaled corticosteroid treatment for mild asthma be based on symptom frequency: a post-hoc efficacy analysis of the START study. Lancet 2017; 389 (10065): 157-166
    CrossrefPubMedGoogle Scholar
  • 28 Lemanske Jr RF, Mauger DT, Sorkness CA. , et al; Childhood Asthma Research and Education (CARE) Network of the National Heart, Lung, and Blood Institute. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med 2010; 362 (11) 975-985
    CrossrefPubMedGoogle Scholar
  • 29 Chauhan BF, Chartrand C, Ni Chroinin M, Milan SJ, Ducharme FM. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev 2015; (11) CD007949
    PubMedGoogle Scholar
  • 30 Butler MG, Zhou EH, Zhang F. , et al. Changing patterns of asthma medication use related to US Food and Drug Administration long-acting β2-agonist regulation from 2005-2011. J Allergy Clin Immunol 2016; 137 (03) 710-717
    CrossrefPubMedGoogle Scholar
  • 31 Stempel DA, Szefler SJ, Pedersen S. , et al; VESTRI Investigators. Safety of adding salmeterol to fluticasone propionate in children with asthma. N Engl J Med 2016; 375 (09) 840-849
    CrossrefPubMedGoogle Scholar
  • 32 Stempel DA, Raphiou IH, Kral KM. , et al; AUSTRI Investigators. Serious asthma events with fluticasone plus salmeterol versus fluticasone alone. N Engl J Med 2016; 374 (19) 1822-1830
    CrossrefPubMedGoogle Scholar
  • 33 Peters SP, Bleecker ER, Canonica GW. , et al. Serious asthma events with budesonide plus formoterol vs. budesonide alone. N Engl J Med 2016; 375 (09) 850-860
    CrossrefPubMedGoogle Scholar
  • 34 Boehringer Ingelheim. Spiriva Respimat: FDA Prescribing Information (updated February 2017). Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Spiriva%20Respimat/spirivarespimat.pdf . Accessed September 25, 2017.
    PubMedGoogle Scholar
  • 35 Hamelmann E, Bateman ED, Vogelberg C. , et al. Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial. J Allergy Clin Immunol 2016; 138 (02) 441-450.e8
    CrossrefPubMedGoogle Scholar
  • 36 Hamelmann E, Bernstein JA, Vandewalker M. , et al. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J 2017; 49 (01) 1601100
    CrossrefPubMedGoogle Scholar
  • 37 Grigg J. Tiotropium in paediatric asthma. Eur Respir J 2017; 49 (01) 1602034
    CrossrefPubMedGoogle Scholar
  • 38 Hamelmann E, Vogelberg C, Szefler SJ. Tiotropium for the treatment of asthma in adolescents. Expert Opin Pharmacother 2017; 18 (03) 305-312
    CrossrefPubMedGoogle Scholar
  • 39 Vogelberg C, Moroni-Zentgraf P, Leonaviciute-Klimantaviciene M. , et al. A randomised dose-ranging study of tiotropium Respimat® in children with symptomatic asthma despite inhaled corticosteroids. Respir Res 2015; 16: 20
    Google Scholar
  • 40 Vogelberg C. Emerging role of long-acting anticholinergics in children with asthma. Curr Opin Pulm Med 2016; 22 (01) 74-79
    PubMedGoogle Scholar
  • 41 Beigelman A, King TS, Mauger D. , et al; Childhood Asthma Research and Education Network of National Heart, Lung, and Blood Institute. Do oral corticosteroids reduce the severity of acute lower respiratory tract illnesses in preschool children with recurrent wheezing?. J Allergy Clin Immunol 2013; 131 (06) 1518-1525
    CrossrefPubMedGoogle Scholar
  • 42 Kloepfer KM, Lee WM, Pappas TE. , et al. Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations. J Allergy Clin Immunol 2014; 133 (05) 1301-1307 , 1307.e1–1307.e3
    CrossrefPubMedGoogle Scholar
  • 43 Wong EHC, Porter JD, Edwards MR, Johnston SL. The role of macrolides in asthma: current evidence and future directions. Lancet Respir Med 2014; 2 (08) 657-670
    CrossrefPubMedGoogle Scholar
  • 44 Gielen V, Johnston SL, Edwards MR. Azithromycin induces anti-viral responses in bronchial epithelial cells. Eur Respir J 2010; 36 (03) 646-654
    CrossrefPubMedGoogle Scholar
  • 45 Bacharier LB, Guilbert TW, Mauger DT. , et al. Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: a randomized clinical trial. JAMA 2015; 314 (19) 2034-2044
    CrossrefPubMedGoogle Scholar
  • 46 Stokholm J, Chawes BL, Vissing NH. , et al. Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2016; 4 (01) 19-26
    CrossrefPubMedGoogle Scholar
  • 47 Metsälä J, Lundqvist A, Virta LJ, Kaila M, Gissler M, Virtanen SM. Prenatal and post-natal exposure to antibiotics and risk of asthma in childhood. Clin Exp Allergy 2015; 45 (01) 137-145
    CrossrefPubMedGoogle Scholar
  • 48 Sun W, Svendsen ER, Karmaus WJ, Kuehr J, Forster J. Early-life antibiotic use is associated with wheezing among children with high atopic risk: a prospective European study. J Asthma 2015; 52 (07) 647-652
    CrossrefPubMedGoogle Scholar
  • 49 Chipps BE, Lanier B, Milgrom H. , et al. Omalizumab in children with uncontrolled allergic asthma: Review of clinical trial and real-world experience. J Allergy Clin Immunol 2017; 139 (05) 1431-1444
    CrossrefPubMedGoogle Scholar
  • 50 Busse WW, Morgan WJ, Gergen PJ. , et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med 2011; 364 (11) 1005-1015
    CrossrefPubMedGoogle Scholar
  • 51 Rodrigo GJ, Neffen H. Systematic review on the use of omalizumab for the treatment of asthmatic children and adolescents. Pediatr Allergy Immunol 2015; 26 (06) 551-556
    CrossrefPubMedGoogle Scholar
  • 52 Deschildre A, Marguet C, Salleron J. , et al. Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey. Eur Respir J 2013; 42 (05) 1224-1233
    CrossrefPubMedGoogle Scholar
  • 53 Deschildre A, Marguet C, Langlois C. , et al. Real-life long-term omalizumab therapy in children with severe allergic asthma. Eur Respir J 2015; 46 (03) 856-859
    CrossrefPubMedGoogle Scholar
  • 54 Sullivan PW, Campbell JD, Ghushchyan VH, Globe G. Outcomes before and after treatment escalation to Global Initiative for Asthma steps 4 and 5 in severe asthma. Ann Allergy Asthma Immunol 2015; 114 (06) 462-469
    CrossrefPubMedGoogle Scholar
  • 55 Teach SJ, Gill MA, Togias A. , et al. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol 2015; 136 (06) 1476-1485
    CrossrefPubMedGoogle Scholar
  • 56 Baena-Cagnani CE, Teijeiro A, Canonica GW. Four-year follow-up in children with moderate/severe uncontrolled asthma after withdrawal of a 1-year omalizumab treatment. Curr Opin Allergy Clin Immunol 2015; 15 (03) 267-271
    CrossrefPubMedGoogle Scholar
  • 57 Molimard M, Mala L, Bourdeix I, Le Gros V. Observational study in severe asthmatic patients after discontinuation of omalizumab for good asthma control. Respir Med 2014; 108 (04) 571-576
    CrossrefPubMedGoogle Scholar