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The Epidemiology of Severe Childhood Asthma

  • Adnan CustovicEmail author
  • Fernando D. Martinez
Chapter

Abstract

Severe asthma affects approximately 1 in 20 asthmatics, and the healthcare resources utilization and mortality are disproportionately high in these patients. Deaths from asthma are relatively rare and correlate poorly with prevalence, and many patients who die from asthma are classified as having a mild/moderate disease based upon their treatment requirements. One of the challenges to understanding the epidemiology, pathophysiology, and etiology of severe asthma is its heterogeneity. Reasons for poor symptom control among patients on maximum treatment range from the wrong diagnosis to nonadherence with prescribed treatments and genuinely therapy-resistant disease. Social and personal circumstances often determine that patients do not adhere to asthma treatments, and this presents to caregivers with uncontrolled asthma. Patients with severe asthma generally start to experience symptoms earlier than those with mild/moderate disease and have early development of atopy and a T2-like diathesis. Severe asthma is often associated with comorbid condition, including obesity, rhinitis, nasal polyps, food allergy, and vocal cord dysfunction. An important determinant of severe asthma is a predisposition to the development of severe exacerbations. Genetic factors and host innate immune responses to viruses may be important determinants of asthma severity and exacerbations. History of sinusitis and of gastroesophageal reflux is associated with proneness for exacerbations. Severe childhood asthma is associated with a loss of lung function during childhood and is a major determinant of early-onset COPD. Therefore, prevention of severe childhood asthma ought to be a major component of the efforts to decrease early mortality due to COPD.

Keywords

Severe asthma Childhood Adults Epidemiology Asthma comorbidities Exacerbations 

References

  1. 1.
    Ellwood P, Asher MI, Beasley R, Clayton TO, Stewart AW, Committee IS. The international study of asthma and allergies in childhood (ISAAC): phase three rationale and methods. Int J Tuberc Lung Dis. 2005;9(1):10–6.PubMedGoogle Scholar
  2. 2.
    Weiland SK, Bjorksten B, Brunekreef B, Cookson WO, von Mutius E, Strachan DP, et al. Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods. Eur Respir J. 2004;24(3):406–12.CrossRefGoogle Scholar
  3. 3.
    Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J. 1995;8(3):483–91.CrossRefGoogle Scholar
  4. 4.
    Variations in the prevalence of respiratory symptoms, self-reported asthma attacks, and use of asthma medication in the European Community Respiratory Health Survey (ECRHS). Eur Respir J. 1996;9(4):687–95.Google Scholar
  5. 5.
    Mitchell EA. International trends in hospital admission rates for asthma. Arch Dis Child. 1985;60(4):376–8.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ebmeier S, Thayabaran D, Braithwaite I, Benamara C, Weatherall M, Beasley R. Trends in international asthma mortality: analysis of data from the WHO Mortality Database from 46 countries (1993–2012). Lancet. 2017;390(10098):935–45.CrossRefGoogle Scholar
  7. 7.
    Guilbert TW, Bacharier LB, Fitzpatrick AM. Severe asthma in children. J Allergy Clin Immunol Pract. 2014;2(5):489–500.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Van Wonderen KE, Van Der Mark LB, Mohrs J, Bindels PJ, Van Aalderen WM, Ter Riet G. Different definitions in childhood asthma: how dependable is the dependent variable? Eur Respir J. 2010;36(1):48–56.CrossRefGoogle Scholar
  9. 9.
    Pavord ID, Beasley R, Agusti A, Anderson GP, Bel E, Brusselle G, et al. After asthma: redefining airways diseases. Lancet. 2018;391(10118):350–400.CrossRefGoogle Scholar
  10. 10.
    Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 2008;372(9643):1107–19.CrossRefGoogle Scholar
  11. 11.
    Lotvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355–60.CrossRefGoogle Scholar
  12. 12.
    Custovic A, Ainsworth J, Arshad H, Bishop C, Buchan I, Cullinan P, et al. The Study Team for Early Life Asthma Research (STELAR) consortium ‘Asthma e-lab’: team science bringing data, methods and investigators together. Thorax. 2015;70(8):799–801.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Belgrave DC, Custovic A, Simpson A. Characterizing wheeze phenotypes to identify endotypes of childhood asthma, and the implications for future management. Expert Rev Clin Immunol. 2013;9(10):921–36.CrossRefGoogle Scholar
  14. 14.
    Belgrave D, Henderson J, Simpson A, Buchan I, Bishop C, Custovic A. Disaggregating asthma: big investigation versus big data. J Allergy Clin Immunol. 2017;139(2):400–7.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Deliu M, Yavuz TS, Sperrin M, Belgrave D, Sahiner UM, Sackesen C, et al. Features of asthma which provide meaningful insights for understanding the disease heterogeneity. Clin Exp Allergy. 2018;48(1):39–47.CrossRefGoogle Scholar
  16. 16.
    Fitzpatrick AM, Teague WG, Meyers DA, Peters SP, Li X, Li H, et al. Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program. J Allergy Clin Immunol. 2011;127(2):382–9.e1–13.CrossRefGoogle Scholar
  17. 17.
    Just J, Gouvis-Echraghi R, Rouve S, Wanin S, Moreau D, Annesi-Maesano I. Two novel, severe asthma phenotypes identified during childhood using a clustering approach. Eur Respir J. 2012;40(1):55–60.CrossRefGoogle Scholar
  18. 18.
    A plea to abandon asthma as a disease concept. Lancet. 2006;368(9537):705.Google Scholar
  19. 19.
    Harding A. Fernando Martinez: seeking to solve the puzzle of asthma. Lancet. 2006;368(9537):725.CrossRefGoogle Scholar
  20. 20.
    Fitzpatrick AM. Severe asthma in children: lessons learned and future directions. J Allergy Clin Immunol Pract. 2016;4(1):11–9; quiz 20–1CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Bush A, Saglani S. Management of severe asthma in children. Lancet. 2010;376(9743):814–25.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Bush A, Hedlin G, Carlsen KH, de Benedictis F, Lodrup-Carlsen K, Wilson N. Severe childhood asthma: a common international approach? Lancet. 2008;372(9643):1019–21.CrossRefGoogle Scholar
  23. 23.
    Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343–73.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Bush A, Saglani S, Fleming L. Severe asthma: looking beyond the amount of medication. Lancet Respir Med. 2017;5(11):844–6.CrossRefGoogle Scholar
  25. 25.
    Jochmann A, Artusio L, Jamalzadeh A, Nagakumar P, Delgado-Eckert E, Saglani S, et al. Electronic monitoring of adherence to inhaled corticosteroids: an essential tool in identifying severe asthma in children. Eur Respir J. 2017;50(6):1700910.CrossRefGoogle Scholar
  26. 26.
    McDonald VM, Yorke J. Adherence in severe asthma: time to get it right. Eur Respir J. 2017;50(6):1702191.CrossRefGoogle Scholar
  27. 27.
    Puranik S, Forno E, Bush A, Celedon JC. Predicting severe asthma exacerbations in children. Am J Respir Crit Care Med. 2017;195(7):854–9.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Murray CS, Poletti G, Kebadze T, Morris J, Woodcock A, Johnston SL, et al. Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax. 2006;61(5):376–82.CrossRefGoogle Scholar
  29. 29.
    Tunnicliffe WS, Fletcher TJ, Hammond K, Roberts K, Custovic A, Simpson A, et al. Sensitivity and exposure to indoor allergens in adults with differing asthma severity. Eur Respir J. 1999;13(3):654–9.CrossRefGoogle Scholar
  30. 30.
    Osman LM. Psychological factors in asthma control and attack risk. Thorax. 2002;57(3):190–1.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Saglani S, Fleming L. How to manage a child with difficult asthma? Expert Rev Respir Med. 2016;10(8):873–9.CrossRefGoogle Scholar
  32. 32.
    Yorke J, Fleming SL, Shuldham C. A systematic review of psychological interventions for children with asthma. Pediatr Pulmonol. 2007;42(2):114–24.CrossRefGoogle Scholar
  33. 33.
    Deliu M, Belgrave D, Simpson A, Murray CS, Kerry G, Custovic A. Impact of rhinitis on asthma severity in school-age children. Allergy. 2014;69(11):1515–21.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Wang R, Custovic A, Simpson A, Belgrave DC, Lowe LA, Murray CS. Differing associations of BMI and body fat with asthma and lung function in children. Pediatr Pulmonol. 2014;49(11):1049–57.CrossRefGoogle Scholar
  35. 35.
    Bush A, Fleming L, Saglani S. Severe asthma in children. Respirology. 2017;22(5):886–97.CrossRefGoogle Scholar
  36. 36.
    Bossley CJ, Fleming L, Ullmann N, Gupta A, Adams A, Nagakumar P, et al. Assessment of corticosteroid response in pediatric patients with severe asthma by using a multidomain approach. J Allergy Clin Immunol. 2016;138(2):413–20.e6.CrossRefGoogle Scholar
  37. 37.
    Fleming L, Koo M, Bossley CJ, Nagakumar P, Bush A, Saglani S. The utility of a multidomain assessment of steroid response for predicting clinical response to omalizumab. J Allergy Clin Immunol. 2016;138(1):292–4.CrossRefGoogle Scholar
  38. 38.
    Pike KC, Levy ML, Moreiras J, Fleming L. Managing problematic severe asthma: beyond the guidelines. Arch Dis Child. 2018;103(4):392–7.CrossRefGoogle Scholar
  39. 39.
    von Bulow A, Backer V, Bodtger U, Soes-Petersen NU, Vest S, Steffensen I, et al. Differentiation of adult severe asthma from difficult-to-treat asthma – outcomes of a systematic assessment protocol. Respir Med. 2018;145:41–7.CrossRefGoogle Scholar
  40. 40.
    Larsson K, Stallberg B, Lisspers K, Telg G, Johansson G, Thuresson M, et al. Prevalence and management of severe asthma in primary care: an observational cohort study in Sweden (PACEHR). Respir Res. 2018;19(1):12.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    von Bulow A, Kriegbaum M, Backer V, Porsbjerg C. The prevalence of severe asthma and low asthma control among Danish adults. J Allergy Clin Immunol Pract. 2014;2(6):759–67.CrossRefGoogle Scholar
  42. 42.
    Bleecker ER. An update on severe asthma. The epidemiology of severe asthma: The TENOR Study and SARP (NIH).World Allergy Organization. XXVII EAACI COngress 9 Jun 2008, Barcelona. https://www.worldallergy.org/educational_programs/world_allergy_forum/barcelona2008/bleecker.php. Accessed 5 May 2019.
  43. 43.
    Mincheva R, Ekerljung L, Bossios A, Lundback B, Lotvall J. High prevalence of severe asthma in a large random population study. J Allergy Clin Immunol. 2018;141(6):2256–64. e2CrossRefGoogle Scholar
  44. 44.
    Rusconi F, Fernandes RM, MWH P, Grigg J, SPACE Clinical Research Collaboration; European Lung Foundation severe asthma patient advisory group. The Severe Paediatric Asthma Collaborative in Europe (SPACE) ERS Clinical Research Collaboration: enhancing participation of children with asthma in therapeutic trials of new biologics and receptor blockers. Eur Respir J. 2018;52(4):1801665.CrossRefGoogle Scholar
  45. 45.
    Bousquet J, Mantzouranis E, Cruz AA, Ait-Khaled N, Baena-Cagnani CE, Bleecker ER, et al. Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma. J Allergy Clin Immunol. 2010;126(5):926–38.CrossRefGoogle Scholar
  46. 46.
    Nordlund B, Melen E, Schultz ES, Gronlund H, Hedlin G, Kull I. Prevalence of severe childhood asthma according to the WHO. Respir Med. 2014;108(8):1234–7.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Lang A, Carlsen KH, Haaland G, Devulapalli CS, Munthe-Kaas M, Mowinckel P, et al. Severe asthma in childhood: assessed in 10 year olds in a birth cohort study. Allergy. 2008;63(8):1054–60.CrossRefGoogle Scholar
  48. 48.
    Belgrave DCM, Simpson A, Semic-Jusufagic A, Murray CS, Buchan I, Pickles A, et al. Joint modeling of parentally reported and physician-confirmed wheeze identifies children with persistent troublesome wheezing. J Allergy Clin Immunol. 2013;132(3):575–83.e12.CrossRefGoogle Scholar
  49. 49.
    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(9):1101–9.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Why asthma still kills: the National Review of Asthma Deaths (NRAD) Confidential Enquiry report. London: Royal College of Physicians; 2014.Google Scholar
  51. 51.
    Levy ML, Winter R. Asthma deaths: what now? Thorax. 2015;70(3):209–10.CrossRefGoogle Scholar
  52. 52.
    Fitzpatrick AM, Gaston BM, Erzurum SC, Teague WG, National Institutes of Health/National Heart L, Blood Institute Severe Asthma Research P. Features of severe asthma in school-age children: atopy and increased exhaled nitric oxide. J Allergy Clin Immunol. 2006;118(6):1218–25.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Stern DA, Morgan WJ, Halonen M, Wright AL, Martinez FD. Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study. Lancet. 2008;372(9643):1058–64.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Bossley CJ, Saglani S, Kavanagh C, Payne DN, Wilson N, Tsartsali L, et al. Corticosteroid responsiveness and clinical characteristics in childhood difficult asthma. Eur Respir J. 2009;34(5):1052–9.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Chipps BE, Szefler SJ, Simons FE, Haselkorn T, Mink DR, Deniz Y, et al. Demographic and clinical characteristics of children and adolescents with severe or difficult-to-treat asthma. J Allergy Clin Immunol. 2007;119(5):1156–63.CrossRefGoogle Scholar
  56. 56.
    Lowe LA, Simpson A, Woodcock A, Morris J, Murray CS, Custovic A, et al. Wheeze phenotypes and lung function in preschool children. Am J Respir Crit Care Med. 2005;171(3):231–7.CrossRefGoogle Scholar
  57. 57.
    Payne DN, Wilson NM, James A, Hablas H, Agrafioti C, Bush A. Evidence for different subgroups of difficult asthma in children. Thorax. 2001;56(5):345–50.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Haland G, Carlsen KC, Sandvik L, Devulapalli CS, Munthe-Kaas MC, Pettersen M, et al. Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med. 2006;355(16):1682–9.CrossRefGoogle Scholar
  59. 59.
    Stern DA, Morgan WJ, Wright AL, Guerra S, Martinez FD. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet. 2007;370(9589):758–64.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Childhood Asthma Management Program Research G, Szefler S, Weiss S, Tonascia J, Adkinson NF, Bender B, et al. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med. 2000;343(15):1054–63.CrossRefGoogle Scholar
  61. 61.
    Shrine N, Portelli MA, John C, Soler Artigas M, Bennett N, Hall R, et al. Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study. Lancet Respir Med. 2018;7(1):20–34.CrossRefGoogle Scholar
  62. 62.
    Bonnelykke K, Sleiman P, Nielsen K, Kreiner-Moller E, Mercader JM, Belgrave D, et al. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet. 2014;46(1):51–5.CrossRefGoogle Scholar
  63. 63.
    Bochkov YA, Watters K, Ashraf S, Griggs TF, Devries MK, Jackson DJ, et al. Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication. Proc Natl Acad Sci U S A. 2015;112(17):5485–90.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Bonnelykke K, Coleman AT, Evans MD, Thorsen J, Waage J, Vissing NH, et al. Cadherin-related family member 3 genetics and rhinovirus C respiratory illnesses. Am J Respir Crit Care Med. 2018;197(5):589–94.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Bonnelykke K, Ober C. Leveraging gene-environment interactions and endotypes for asthma gene discovery. J Allergy Clin Immunol. 2016;137(3):667–79.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Koo S, Gupta A, Fainardi V, Bossley C, Bush A, Saglani S, et al. Ethnic variation in response to IM triamcinolone in children with severe therapy-resistant asthma. Chest. 2016;149(1):98–105.CrossRefGoogle Scholar
  67. 67.
    Jackson DJ, Johnston SL. The role of viruses in acute exacerbations of asthma. J Allergy Clin Immunol. 2010;125(6):1178–87; quiz 88–9CrossRefGoogle Scholar
  68. 68.
    Kim CK, Callaway Z, Gern JE. Viral infections and associated factors that promote acute exacerbations of asthma. Allergy Asthma Immunol Res. 2018;10(1):12–7.CrossRefGoogle Scholar
  69. 69.
    Edwards MR, Regamey N, Vareille M, Kieninger E, Gupta A, Shoemark A, et al. Impaired innate interferon induction in severe therapy resistant atopic asthmatic children. Mucosal Immunol. 2013;6(4):797–806.CrossRefGoogle Scholar
  70. 70.
    Custovic A, Belgrave D, Lin L, Bakhsoliani E, Telcian AG, Solari R, et al. Cytokine responses to rhinovirus and development of asthma, allergic sensitization and respiratory infections during childhood. Am J Respir Crit Care Med. 2018;197(10):1265–74.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Porsbjerg C, Menzies-Gow A. Co-morbidities in severe asthma: clinical impact and management. Respirology. 2017;22(4):651–61.CrossRefGoogle Scholar
  72. 72.
    Del Giacco SR, Bakirtas A, Bel E, Custovic A, Diamant Z, Hamelmann E, et al. Allergy in severe asthma. Allergy. 2017;72(2):207–20.CrossRefGoogle Scholar
  73. 73.
    Ullmann N, Mirra V, Di Marco A, Pavone M, Porcaro F, Negro V, et al. Asthma: differential diagnosis and comorbidities. Front Pediatr. 2018;6:276.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Frith J, Fleming L, Bossley C, Ullmann N, Bush A. The complexities of defining atopy in severe childhood asthma. Clin Exp Allergy. 2011;41(7):948–53.CrossRefGoogle Scholar
  75. 75.
    Holt PG, Strickland D, Bosco A, Belgrave D, Hales B, Simpson A, et al. Distinguishing benign from pathologic TH2 immunity in atopic children. J Allergy Clin Immunol. 2016;137(2):379–87.CrossRefGoogle Scholar
  76. 76.
    Konradsen JR, Nordlund B, Onell A, Borres MP, Gronlund H, Hedlin G. Severe childhood asthma and allergy to furry animals: refined assessment using molecular-based allergy diagnostics. Pediatr Allergy Immunol. 2014;25(2):187–92.CrossRefGoogle Scholar
  77. 77.
    Sylvestre L, Jegu J, Metz-Favre C, Barnig C, Qi S, de Blay F. Component-based allergen-microarray: Der p 2 and Der f 2 dust mite sensitization is more common in patients with severe asthma. J Investig Allergol Clin Immunol. 2016;26(2):141–3.CrossRefGoogle Scholar
  78. 78.
    Green RM, Custovic A, Sanderson G, Hunter J, Johnston SL, Woodcock A. Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. BMJ. 2002;324(7340):763.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Fitzpatrick AM, Jackson DJ, Mauger DT, Boehmer SJ, Phipatanakul W, Sheehan WJ, et al. Individualized therapy for persistent asthma in young children. J Allergy Clin Immunol. 2016;138(6):1608–18. e12CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Sharples J, Gupta A, Fleming L, Bossley CJ, Bracken-King M, Hall P, et al. Long-term effectiveness of a staged assessment for paediatric problematic severe asthma. Eur Respir J. 2012;40(1):264–7.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Oksel C, Custovic A. Development of allergic sensitization and its relevance to paediatric asthma. Curr Opin Allergy Clin Immunol. 2018;18(2):109–16.CrossRefGoogle Scholar
  82. 82.
    Simpson A, Tan VY, Winn J, Svensen M, Bishop CM, Heckerman DE, et al. Beyond atopy: multiple patterns of sensitization in relation to asthma in a birth cohort study. Am J Respir Crit Care Med. 2010;181(11):1200–6.CrossRefGoogle Scholar
  83. 83.
    Lazic N, Roberts G, Custovic A, Belgrave D, Bishop CM, Winn J, et al. Multiple atopy phenotypes and their associations with asthma: similar findings from two birth cohorts. Allergy. 2013;68(6):764–70.CrossRefGoogle Scholar
  84. 84.
    Simpson A, Lazic N, Belgrave DCM, Johnson P, Bishop C, Mills C, et al. Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years. J Allergy Clin Immunol. 2015;136(5):1224–31.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Custovic A, Sonntag H-J, Buchan IE, Belgrave D, Simpson A, Prosperi MCF. Evolution pathways of IgE responses to grass and mite allergens throughout childhood. J Allergy Clin Immunol. 2015;136(6):1645–52.e8.CrossRefGoogle Scholar
  86. 86.
    Howard R, Belgrave D, Papastamoulis P, Simpson A, Rattray M, Custovic A. Evolution of IgE responses to multiple allergen components throughout childhood. J Allergy Clin Immunol. 2018;142(4):1322–30.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Fontanella S, Frainay C, Murray CS, Simpson A, Custovic A. Machine learning to identify pairwise interactions between specific IgE antibodies and their association with asthma: a cross-sectional analysis within a population-based birth cohort. PLoS Med. 2018;15(11):e1002691.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Castro-Rodríguez JA, Holberg CJ, Morgan WJ, Wright AL, Martinez FD. Increased incidence of asthmalike symptoms in girls who become overweight or obese during the school years. Am J Respir Crit Care Med. 2001;163(6):1344–9.CrossRefGoogle Scholar
  89. 89.
    Papoutsakis C, Priftis KN, Drakouli M, Prifti S, Konstantaki E, Chondronikola M, et al. Childhood overweight/obesity and asthma: is there a link? A systematic review of recent epidemiologic evidence. J Acad Nutr Diet. 2013;113(1):77–105.CrossRefGoogle Scholar
  90. 90.
    Lang JE, Bunnell HT, Hossain MJ, Wysocki T, Lima JJ, Finkel TH, et al. Being overweight or obese and the development of asthma. Pediatrics. 2018;142(6):e20182119.CrossRefGoogle Scholar
  91. 91.
    Chen Z, Salam MT, Alderete TL, Habre R, Bastain TM, Berhane K, et al. Effects of childhood asthma on the development of obesity among school-aged children. Am J Respir Crit Care Med. 2017;195(9):1181–8.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Contreras ZA, Chen Z, Roumeliotaki T, Annesi-Maesano I, Baiz N, von Berg A, et al. Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts. Eur Respir J. 2018;52(3):1800504.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Ross MK, Romero T, Sim MS, Szilagyi PG. Obese- and allergic-related asthma phenotypes among children across the United States. J Asthma. 2019;56(5):512–21.CrossRefGoogle Scholar
  94. 94.
    Guerra S, Wright AL, Morgan WJ, Sherrill DL, Holberg CJ, Martinez FD. Persistence of asthma symptoms during adolescence: role of obesity and age at the onset of puberty. Am J Respir Crit Care Med. 2004;170(1):78–85.CrossRefGoogle Scholar
  95. 95.
    Borrell LN, Nguyen EA, Roth LA, Oh SS, Tcheurekdjian H, Sen S, et al. Childhood obesity and asthma control in the GALA II and SAGE II studies. Am J Respir Crit Care Med. 2013;187(7):697–702.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Forno E, Weiner DJ, Mullen J, Sawicki G, Kurland G, Han YY, et al. Obesity and airway dysanapsis in children with and without asthma. Am J Respir Crit Care Med. 2017;195(3):314–23.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Forno E, Lescher R, Strunk R, Weiss S, Fuhlbrigge A, Celedon JC, et al. Decreased response to inhaled steroids in overweight and obese asthmatic children. J Allergy Clin Immunol. 2011;127(3):741–9.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Forno E, Han YY, Muzumdar RH, Celedon JC. Insulin resistance, metabolic syndrome, and lung function in US adolescents with and without asthma. J Allergy Clin Immunol. 2015;136(2):304–11.e8.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Rastogi D, Fraser S, Oh J, Huber AM, Schulman Y, Bhagtani RH, et al. Inflammation, metabolic dysregulation, and pulmonary function among obese urban adolescents with asthma. Am J Respir Crit Care Med. 2015;191(2):149–60.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Covar RA, Szefler SJ, Zeiger RS, Sorkness CA, Moss M, Mauger DT, et al. Factors associated with asthma exacerbations during a long-term clinical trial of controller medications in children. J Allergy Clin Immunol. 2008;122(4):741–7.e4.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Kljaic-Bukvic B, Blekic M, Aberle N, Curtin JA, Hankinson J, Semic-Jusufagic A, et al. Genetic variants in endotoxin signalling pathway, domestic endotoxin exposure and asthma exacerbations. Pediatr Allergy Immunol. 2014;25(6):552–7.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Sharma S, Raby BA, Hunninghake GM, Soto-Quiros M, Avila L, Murphy AJ, et al. Variants in TGFB1, dust mite exposure, and disease severity in children with asthma. Am J Respir Crit Care Med. 2009;179(5):356–62.CrossRefGoogle Scholar
  103. 103.
    Bukvic BK, Blekic M, Simpson A, Marinho S, Curtin JA, Hankinson J, et al. Asthma severity, polymorphisms in 20p13 and their interaction with tobacco smoke exposure. Pediatr Allergy Immunol. 2013;24(1):10–8.CrossRefGoogle Scholar
  104. 104.
    Denlinger LC, Phillips BR, Ramratnam S, Ross K, Bhakta NR, Cardet JC, et al. Inflammatory and comorbid features of patients with severe asthma and frequent exacerbations. Am J Respir Crit Care Med. 2017;195(3):302–13.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Chang EH, Willis AL, McCrary HC, Noutsios GT, Le CH, Chiu AG, et al. Association between the CDHR3 rs6967330 risk allele and chronic rhinosinusitis. J Allergy Clin Immunol. 2017;139(6):1990–2.e2.CrossRefGoogle Scholar
  106. 106.
    Martinez FD, Vercelli D. Asthma Lancet. 2013;382(9901):1360–72.CrossRefGoogle Scholar
  107. 107.
    Berry CE, Billheimer D, Jenkins IC, Lu ZJ, Stern DA, Gerald LB, et al. A distinct low lung function trajectory from childhood to the fourth decade of life. Am J Respir Crit Care Med. 2016;194(5):607–12.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Belgrave DCM, Granell R, Turner SW, Curtin JA, Buchan IE, Le Souef PN, et al. Lung function trajectories from pre-school age to adulthood and their associations with early life factors: a retrospective analysis of three population-based birth cohort studies. Lancet Respir Med. 2018;6(7):526–34.CrossRefGoogle Scholar
  109. 109.
    Sears MR, Greene JM, Willan AR, Wiecek EM, Taylor DR, Flannery EM, et al. A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med. 2003;349(15):1414–22.CrossRefGoogle Scholar
  110. 110.
    Tai A, Tran H, Roberts M, Clarke N, Gibson AM, Vidmar S, et al. Outcomes of childhood asthma to the age of 50 years. J Allergy Clin Immunol. 2014;133(6):1572–8.e3.CrossRefGoogle Scholar
  111. 111.
    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(9):805–10.CrossRefGoogle Scholar
  112. 112.
    Martinez FD. Early-life origins of chronic obstructive pulmonary disease. N Engl J Med. 2016;375(9):871–8.CrossRefGoogle Scholar
  113. 113.
    Szefler SJ. Asthma across the lifespan: Time for a paradigm shift. J Allergy Clin Immunol. 2018;142(3):773–80.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Paediatrics, Imperial College London, St Mary’s Campus Medical SchoolLondonUK
  2. 2.Asthma & Airway Disease Research Center, University of ArizonaTucsonUSA

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