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Phenotypes of allergic diseases in children and their application in clinical situations

  • Lee, Eun (Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Hong, Soo-Jong (Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2018.12.31
  • Accepted : 2019.04.18
  • Published : 2019.09.15

Abstract

Allergic diseases, including allergic rhinitis, asthma, and atopic dermatitis, are common heterogeneous diseases that encompass diverse phenotypes and different pathogeneses. Phenotype studies of allergic diseases can facilitate the identification of risk factors and their underlying pathophysiology, resulting in the application of more effective treatment, selection of better treatment responses, and prediction of prognosis for each phenotype. In the early phase of phenotype studies in allergic diseases, artificial classifications were usually performed based on clinical features, such as triggering factors or the presence of atopy, which can result in the biased classification of phenotypes and limit the characterization of heterogeneous allergic diseases. Subsequent phenotype studies have suggested more diverse phenotypes for each allergic disease using relatively unbiased statistical methods, such as cluster analysis or latent class analysis. The classifications of phenotypes in allergic diseases may overlap or be unstable over time due to their complex interactions with genetic and encountered environmental factors during the illness, which may affect the disease course and pathophysiology. In this review, diverse phenotype classifications of allergic diseases, including atopic dermatitis, asthma, and wheezing in children, allergic rhinitis, and atopy, are described. The review also discusses the applications of the results obtained from phenotype studies performed in other countries to Korean children. Consideration of changes in the characteristics of each phenotype over time in an individual's lifespan is needed in future studies.

Acknowledgement

Supported by : Chonnam National University

References

  1. Bieber T. Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine. Allergy 2012;67:1475-82.
  2. Giavina-Bianchi P. Defining phenotypes in rhinitis: a step toward personalized medicine. J Allergy Clin Immunol 2015;135:151-2. https://doi.org/10.1016/j.jaci.2014.10.029
  3. Bieber T, D'Erme AM, Akdis CA, Traidl-Hoffmann C, Lauener R, Schappi G, et al. Clinical phenotypes and endophenotypes of atopic dermatitis: where are we, and where should we go? J Allergy Clin Immunol 2017;139(4S):S58-64. https://doi.org/10.1016/j.jaci.2017.01.008
  4. Vidotto D, Vermunt JK, van Deun K. Bayesian multilevel latent class models for the multiple imputation of nested categorical data. J Educ Behav Stat 2018;43:511-39.
  5. Williams HC, Strachan DP. The natural history of childhood eczema: observations from the British 1958 birth cohort study. Br J Dermatol 1998;139:834-9. https://doi.org/10.1046/j.1365-2133.1998.02509.x
  6. Tokura Y. Extrinsic and intrinsic types of atopic dermatitis. J Dermatol Sci 2010;58:1-7. https://doi.org/10.1016/j.jdermsci.2010.02.008
  7. Pugliarello S, Cozzi A, Gisondi P, Girolomoni G. Phenotypes of atopic dermatitis. J Dtsch Dermatol Ges 2011;9:12-20.
  8. Suarez-Farinas M, Dhingra N, Gittler J, Shemer A, Cardinale I, de Guzman Strong C, et al. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol 2013;132:361-70. https://doi.org/10.1016/j.jaci.2013.04.046
  9. Weidinger S, Novak N. Atopic dermatitis. Lancet 2016;387:1109-22. https://doi.org/10.1016/S0140-6736(15)00149-X
  10. Esaki H, Brunner PM, Renert-Yuval Y, Czarnowicki T, Huynh T, Tran G, et al. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. J Allergy Clin Immunol 2016;138:1639-51. https://doi.org/10.1016/j.jaci.2016.07.013
  11. Czarnowicki T, Esaki H, Gonzalez J, Malajian D, Shemer A, Noda S, et al. Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets. J Allergy Clin Immunol 2015;136:941-51.e3. https://doi.org/10.1016/j.jaci.2015.05.049
  12. Paternoster L, Savenije OEM, Heron J, Evans DM, Vonk JM, Brunekreef B, et al. Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts. J Allergy Clin Immunol 2018;141:964-71. https://doi.org/10.1016/j.jaci.2017.09.044
  13. Czarnowicki T, Gonzalez J, Shemer A, Malajian D, Xu H, Zheng X, et al. Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population. J Allergy Clin Immunol 2015;136:104-15.e7. https://doi.org/10.1016/j.jaci.2015.01.020
  14. Farrell AM, Antrobus P, Simpson D, Powell S, Chapel HM, Ferry BL. A rapid flow cytometric assay to detect CD4+ and CD8+ T-helper (Th) 0, Th1 and Th2 cells in whole blood and its application to study cytokine levels in atopic dermatitis before and after cyclosporin therapy. Br J Dermatol 2001;144:24-33. https://doi.org/10.1046/j.1365-2133.2001.03948.x
  15. Amat F, Saint-Pierre P, Bourrat E, Nemni A, Couderc R, Boutmy-Deslandes E, et al. Early-onset atopic dermatitis in children: which are the phenotypes at risk of asthma? Results from the ORCA cohort. PLoS One 2015;10:e0131369. https://doi.org/10.1371/journal.pone.0131369
  16. Roduit C, Frei R, Depner M, Karvonen AM, Renz H, Braun-Fahrlander C, et al. Phenotypes of atopic dermatitis depending on the timing of onset and progression in childhood. JAMA Pediatr 2017;171:655-62. https://doi.org/10.1001/jamapediatrics.2017.0556
  17. Lee E, Lee SH, Kwon JW, Kim YH, Cho HJ, Yang SI, et al. Atopic dermatitis phenotype with early onset and high serum IL-13 is linked to the new development of bronchial hyperresponsiveness in school children. Allergy 2016;71:692-700. https://doi.org/10.1111/all.12844
  18. Seo E, Yoon J, Jung S, Lee J, Lee BH, Yu J. Phenotypes of atopic dermatitis identified by cluster analysis in early childhood. J Dermatol 2019;46:117-23. https://doi.org/10.1111/1346-8138.14714
  19. Burgess JA, Dharmage SC, Byrnes GB, Matheson MC, Gurrin LC, Wharton CL, et al. Childhood eczema and asthma incidence and persistence: a cohort study from childhood to middle age. J Allergy Clin Immunol 2008;122:280-5. https://doi.org/10.1016/j.jaci.2008.05.018
  20. Bass AM, Anderson KL, Feldman SR. Interventions to increase treatment adherence in pediatric atopic dermatitis: a systematic review. J Clin Med 2015;4:231-42. https://doi.org/10.3390/jcm4020231
  21. Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med 2011;365:1315-27. https://doi.org/10.1056/NEJMra1011040
  22. Kabesch M, Carr D, Weiland SK, von Mutius E. Association between polymorphisms in serine protease inhibitor, kazal type 5 and asthma phenotypes in a large German population sample. Clin Exp Allergy 2004;34:340-5. https://doi.org/10.1111/j.1365-2222.2004.01860.x
  23. Ahmad-Nejad P, Mrabet-Dahbi S, Breuer K, Klotz M, Werfel T, Herz U, et al. The toll-like receptor 2 R753Q polymorphism defines a subgroup of patients with atopic dermatitis having severe phenotype. J Allergy Clin Immunol 2004;113:565-7. https://doi.org/10.1016/j.jaci.2003.12.583
  24. Noda S, Suarez-Farinas M, Ungar B, Kim SJ, de Guzman Strong C, Xu H, et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol 2015;136:1254-64. https://doi.org/10.1016/j.jaci.2015.08.015
  25. Cowan K, Guilbert TW. Pediatric asthma phenotypes. Curr Opin Pediatr 2012;24:344-51. https://doi.org/10.1097/MOP.0b013e32835357ab
  26. Rackemann FM. A working classification of asthma. Am J Med 1947;3:601-6. https://doi.org/10.1016/0002-9343(47)90204-0
  27. Walker C, Bode E, Boer L, Hansel TT, Blaser K, Virchow JC Jr. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 1992;146:109-15. https://doi.org/10.1164/ajrccm/146.1.109
  28. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995;332:133-8. https://doi.org/10.1056/NEJM199501193320301
  29. Rusconi F, Galassi C, Corbo GM, Forastiere F, Biggeri A, Ciccone G, et al. Risk factors for early, persistent, and late-onset wheezing in young children. SIDRIA Collaborative Group. Am J Respir Crit Care Med 1999;160(5 Pt 1):1617-22. https://doi.org/10.1164/ajrccm.160.5.9811002
  30. Savenije OE, Granell R, Caudri D, Koppelman GH, Smit HA, Wijga A, et al. Comparison of childhood wheezing phenotypes in 2 birth cohorts: ALSPAC and PIAMA. J Allergy Clin Immunol 2011;127:1505-12.e14. https://doi.org/10.1016/j.jaci.2011.02.002
  31. Henderson J, Granell R, Heron J, Sherriff A, Simpson A, Woodcock A, et al. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax 2008;63:974-80. https://doi.org/10.1136/thx.2007.093187
  32. Ordonez CL, Shaughnessy TE, Matthay MA, Fahy JV. Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma: Clinical and biologic significance. Am J Respir Crit Care Med 2000;161(4 Pt 1):1185-90. https://doi.org/10.1164/ajrccm.161.4.9812061
  33. Fitzpatrick AM, Moore WC. Severe asthma phenotypes - how should they guide evaluation and treatment? J Allergy Clin Immunol Pract 2017;5:901-8. https://doi.org/10.1016/j.jaip.2017.05.015
  34. 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;195:302-13. https://doi.org/10.1164/rccm.201602-0419OC
  35. Sorkness RL, Teague WG, Penugonda M, Fitzpatrick AM; National Institutes of Health, National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Sex dependence of airflow limitation and air trapping in children with severe asthma. J Allergy Clin Immunol 2011;127:1073-4. https://doi.org/10.1016/j.jaci.2010.12.1079
  36. Sendin-Hernandez MP, Avila-Zarza C, Sanz C, Garcia-Sanchez A, Marcos-Vadillo E, Munoz-Bellido FJ, et al. Cluster analysis identifies 3 phenotypes within allergic asthma. J Allergy Clin Immunol Pract 2018;6:955-61.e1. https://doi.org/10.1016/j.jaip.2017.10.006
  37. Terl M, Sedlak V, Cap P, Dvorakova R, Kasak V, Koci T, et al. Asthma management: a new phenotype-based approach using presence of eosinophilia and allergy. Allergy 2017;72:1279-87. https://doi.org/10.1111/all.13165
  38. Desai M, Oppenheimer J. Elucidating asthma phenotypes and endotypes: progress towards personalized medicine. Ann Allergy Asthma Immunol 2016;116:394-401. https://doi.org/10.1016/j.anai.2015.12.024
  39. Schatz M, Hsu JW, Zeiger RS, Chen W, Dorenbaum A, Chipps BE, et al. Phenotypes determined by cluster analysis in severe or difficult-totreat asthma. J Allergy Clin Immunol 2014;133:1549-56. https://doi.org/10.1016/j.jaci.2013.10.006
  40. Lee E, Lee SH, Kwon JW, Kim YH, Yoon J, Cho HJ, et al. Persistent asthma phenotype related with late-onset, high atopy, and low socioeconomic status in school-aged Korean children. BMC Pulm Med 2017;17:45. https://doi.org/10.1186/s12890-017-0387-5
  41. Kim BJ, Lee SY, Kim HB, Lee E, Hong SJ. Environmental changes, microbiota, and allergic diseases. Allergy Asthma Immunol Res 2014;6:389-400. https://doi.org/10.4168/aair.2014.6.5.389
  42. Lee E, Lee SH, Kwon JW, Kim Y, Cho HJ, Yang SI, et al. A rhinitis phenotype associated with increased development of bronchial hyperresponsiveness and asthma in children. Ann Allergy Asthma Immunol 2016;117:21-8.e1. https://doi.org/10.1016/j.anai.2016.04.016
  43. Brozek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol 2017;140:950-8. https://doi.org/10.1016/j.jaci.2017.03.050
  44. Bousquet J, Van Cauwenberge P, Khaltaev N; Aria Workshop Group; World Health Organization. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108(5 Suppl):S147-334. https://doi.org/10.1067/mai.2001.118891
  45. Papadopoulos NG, Bernstein JA, Demoly P, Dykewicz M, Fokkens W, Hellings PW, et al. Phenotypes and endotypes of rhinitis and their impact on management: a PRACTALL report. Allergy 2015;70:474-94. https://doi.org/10.1111/all.12573
  46. Kurukulaaratchy RJ, Zhang H, Patil V, Raza A, Karmaus W, Ewart S, et al. Identifying the heterogeneity of young adult rhinitis through cluster analysis in the Isle of Wight birth cohort. J Allergy Clin Immunol 2015;135:143-50. https://doi.org/10.1016/j.jaci.2014.06.017
  47. Togias A, Gergen PJ, Hu JW, Babineau DC, Wood RA, Cohen RT, et al. Rhinitis in children and adolescents with asthma: Ubiquitous, difficult to control, and associated with asthma outcomes. J Allergy Clin Immunol 2019;143:1003-11.e10. https://doi.org/10.1016/j.jaci.2018.07.041
  48. Tran MM, Lefebvre DL, Dharma C, Dai D, Lou WYW, Subbarao P, et al. Predicting the atopic march: Results from the Canadian Healthy Infant Longitudinal Development Study. J Allergy Clin Immunol 2018;141:601-7.e8. https://doi.org/10.1016/j.jaci.2017.08.024
  49. Lee E, Lee SH, Kim YH, Cho HJ, Yoon J, Yang SI, et al. Association of atopy phenotypes with new development of asthma and bronchial hyperresponsiveness in school-aged children. Ann Allergy Asthma Immunol 2017;118:542-50.e1. https://doi.org/10.1016/j.anai.2017.02.008
  50. Havstad S, Johnson CC, Kim H, Levin AM, Zoratti EM, Joseph CL, et al. Atopic phenotypes identified with latent class analyses at age 2 years. J Allergy Clin Immunol 2014;134:722-7.e2. https://doi.org/10.1016/j.jaci.2014.01.022
  51. Schoos AM, Chawes BL, Melen E, Bergstrom A, Kull I, Wickman M, et al. Sensitization trajectories in childhood revealed by using a cluster analysis. J Allergy Clin Immunol 2017;140:1693-9. https://doi.org/10.1016/j.jaci.2017.01.041
  52. Boulet LP, Turcotte H, Laprise C, Lavertu C, Bedard PM, Lavoie A, et al. Comparative degree and type of sensitization to common indoor and outdoor allergens in subjects with allergic rhinitis and/or asthma. Clin Exp Allergy 1997;27:52-9. https://doi.org/10.1111/j.1365-2222.1997.tb00672.x
  53. Huss K, Adkinson NF Jr, Eggleston PA, Dawson C, Van Natta ML, Hamilton RG. House dust mite and cockroach exposure are strong risk factors for positive allergy skin test responses in the Childhood Asthma Management Program. J Allergy Clin Immunol 2001;107:48-54. https://doi.org/10.1067/mai.2001.111146
  54. Schoos AM, Chawes BL, Rasmussen MA, Bloch J, Bonnelykke K, Bisgaard H. Atopic endotype in childhood. J Allergy Clin Immunol 2016;137:844-51.e4. https://doi.org/10.1016/j.jaci.2015.10.004
  55. 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;181:1200-6. https://doi.org/10.1164/rccm.200907-1101OC
  56. von Mutius E, Martinez FD, Fritzsch C, Nicolai T, Roell G, Thiemann HH. Prevalence of asthma and atopy in two areas of West and East Germany. Am J Respir Crit Care Med 1994;149(2 Pt 1):358-64. https://doi.org/10.1164/ajrccm.149.2.8306030
  57. Arshad SH, Tariq SM, Matthews S, Hakim E. Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study. Pediatrics 2001;108:E33. https://doi.org/10.1542/peds.108.2.e33
  58. Dharma C, Lefebvre DL, Tran MM, Lou WYW, Subbarao P, Becker AB, et al. Patterns of allergic sensitization and atopic dermatitis from 1 to 3 years: Effects on allergic diseases. Clin Exp Allergy 2018;48:48-59. https://doi.org/10.1111/cea.13063
  59. Czarnowicki T, He H, Krueger JG, Guttman-Yassky E. Atopic dermatitis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol 2019;143:1-11. https://doi.org/10.1016/j.jaci.2018.10.032
  60. Khanna P, Shah A. Categorization of patients with allergic rhinitis: a comparative profile of "sneezers and runners" and "blockers". Ann Allergy Asthma Immunol 2005;94:60-4. https://doi.org/10.1016/S1081-1206(10)61287-2
  61. 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;68:764-70. https://doi.org/10.1111/all.12134