Use serum periostin as marker of worsening pediatric allergic asthma

S.S. Masalskiy 1,2, A.S. Kalmykova 2, O.P. Ukhanova 2, Y.S. Smolkin 1, I.V. Markarova 3, F.M. Takushinova 2,3

1 SCCC Allergology and Immunology, Moscow, Russia
2 Stavropol state medical university, Stavropol, Russia
3 City children clinical hospital named G. K. Phillipskiy, Stavropol, Russia

ALLERGOLOGY AND IMMUNOLOGY IN PEDIATRICS, Volume 55 • Number 4 • December 2018, pp. 37 – 48
DOI: 10.24411/2500-1175-2018-00021

The article presents an analysis of the use of periostin, eosinophilia, FEF50 and 25(OH)D, the markers of allergic inflammation in school age patients with uncontrolled asthma.
Traditional markers weren’t associated with severity and worsening of asthma.
Relatively higher serum periostin (SP) values were established in patients with moderate asthma compared with mild asthma. The protein concentration of 5 ng/ml can be used as a cut-off point for patients with ≥2 exacerbation per year.
SP is the only traditional marker (blood eosinophilia, IgE, FEV1) which has showed a relationship with the severity and number of exacerbation of asthma in children. A high level of periostin increases the risk of frequent exacerbation of asthma (OR 1.15, CI 95% 1.01, – 1.295, p = 0.027).
Concentrations of 25(OH)D were found to be lower in bronchial asthma with frequent exacerbation. High concentrations of vitamin D reduced the chances for a moderate-onset asthma (OR, 0.895, 95% CI: 0.830-0.965, p <0.01) and frequent exacerbations (0.927 CI95%: 0.869-0.988, p <0.01).
When using logistic binary regression, the model with 3 predictors (periostin, 25(OH)D, FEF50) is able to predict a mild asthma in 90.2%, and moderate asthma – 60.0% of cases.

  1. Flohr C., Johansson S.G.O., Wahlgren C.F., Williams H.C. How atopic is atopic dermatitis? J Allergy Clin Immunol 2004; 114: 150–158. Roguedas-Contios A.M., Misery L. What is intrinsic atopic dermatitis? Clin Rev Allergy Immunol. 2011; 41(3): 233–236.
  2. Wollenberg A., Feichtner K. Atopic dermatitis and skin allergies – update and outlook. 2013; 68: 1509–1519.
  3. Балаболкин И. И., Булгакова В. А., Елисеева Т. И. Иммунопатогенез и современные возможности терапии атопического дерматита у детей. Аллергология и иммунология в педиатрии. 2017; 2(49): 12–22.
  4. Abuabara K., Yu A.M., Okhovat J.P., Allen E. & Langan S.M. The prevalence of atopic dermatitis beyond childhood: A systematic review and meta-analysis of longitudinal studies. Allergy 2017; 73: 696–704.
  5. Deckers I.A., McLean S., Linssen S., Mommers M., van Schayck C.P., Sheikh A. Investigating international time trends in the incidence and prevalence of atopic eczema 1990-2010: a systematic review of epidemiological studies. PLoS ONE 2012; 7: e39803.
  6. Mallol J., Crane J., von Mutius E., Odhiambo J., Keil U., Stewart A. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis. Allergol Immunopathol (Madr). 2013; 41: 73–85.
  7. Тренева М.С., Мунблит Д.Б., Иванников Н.Ю., Лиханова Л.А., Пампура А. Н. Распространенность атопического дерматита и реакций на пищевые продукты у московских детей в возрасте 2 лет. Педиатрия. Журнал им. Г. Н. Сперанского. 2014; 3: 11–14.
  8. Шахова Н. В., Камалтынова Е. М., Лобанов Ю. Ф., Ардатова Т.С. Атопический дерматит у детей дошкольного возраста: распространенность, клинико-аллергологическая характеристика и факторы риска. Российский аллергологический журнал. 2018; 15(1-1): 55–62.
  9. Мигачева Н.Б., Жестков А. В. Распространенность атопического дерматита у детей раннего возраста г. Самара. Российский аллергологический журнал. 2017; 14(1): 98–101.
  10. Schultz-Larsen F. Atopic dermatitis: a genetic-epidemiologic study in a population-based twin study. J Am Acad Dermatol 1993; 28: 719–23, Taylor B., Wadsworth J., Wadsworth M. et al. Changes in the reported prevalence of childhood eczema since the 1938-45 war. Lancet. 1984; 2: 1255–1257.
  11. Rerknimitr P., Otsuka A., Nakashima C., Kabashima K. The etiopathogenesis of atopic dermatitis: barrier disruption, immunological derangement, and pruritus. Inflamm. Regen. 2017; 37(1): 14.
  12. Levin J., Friedlander S.F., Del Rosso J.Q. Atopic dermatitis and the stratum corneum – Part 1: The role of filaggrin in the stratum corneum barrier and atopic skin. J. Clin. Aesthet. Dermatol. 2013; 6(10): 16–22.
  13. Egawa G., Kabashima K. Multifactorial skin barrier deficiency and atopic dermatitis: essential topics to prevent the atopic march. J Allergy Clin Immunol. 2016; 138: 350–358.
  14. Lyons J.J., Milner J.D., Stone K.D. Atopic Dermatitis in Children: Clinical Features, Pathophysiology, and Treatment. Immunol. Allergy Clin. North Am. 2015; 35(1): 161–183.
  15. Bager P., Wohlfahrt J., Thyssen J.P., Melbye M. Filaggrin genotype and skin diseases independent of atopic dermatitis in childhood. Pediatr. Allergy Immunol. 2016; 27(2): 162–168, Hadson T.J. Skin barrier function and allergic risk. Nature Genetics 2006; 38: 399–400.
  16. McGrath J.A. Filaggrin and skin barrier defects. Australasian Journal of Dermatology (2008) 49, 67–74. Irvine A.D., McLean W.H., Leung D.Y. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011; 365: 1315–1327.
  17. Thyssen J.P., Godoy-Gijon E., Elias P.M. Ichthyosis vulgaris: the filaggrin mutation disease. Br J Dermatol. 2013; 168: 1155–66.
  18. Novak N., Simon D. Atopic dermatitis — from new pathophysiologic insights to individualized therapy. Allergy 2011; 66: 830–839.
  19. Deleuran M., Hvid M., Kemp K. et al. IL-25 induces both inflammation and skin barrier dysfunction in atopic dermatitis. Chem Immunol Allergy. 2012; 96: 45–49., Howell M.D., Kim B.E., Gao P. et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2009; 124: R7–R12.22.
  20. Morizane S., Yamasaki K., Kajita A. et al. TH2 cytokines increase kallikrein 7 expression and function in patients with atopic dermatitis. J Allergy Clin Immunol. 2012; 130: 259–261.
  21. Danso M.O., van Drongelen V., Mulder A. et al. TNF-a and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents. J Invest Dermatol 2014; 134: 1941–1950.
  22. Kodama A., Horikawa T., Suziki T. et al. Effect of stree on atopic dermatitis: Investigation in patients after the great Hanshin earthquake. J Allergy Clin Immunol. 1999; 104: 173–176, Lifschitz C. The Impact of Atopic Dermatitis on Quality of Life. Ann Nutr Metab. 2015; 66(suppl 1): 34–40.
  23. Wallengren J., Hakanson R. Effects of substance P, neurokinin A and calcitonin gene-related peptide in human skin and their involvment in sensory nerve-mediator responses. Eur. J. Pharmacol. 1987; 143: 267–273.
  24. Флуер Ф.С., Кудрявцева А.В., Нескородова К.А., Титарев С.И. Продукция энтеротоксинов А, В, С и токсина синдрома токсического шока различными видами стафилококков, выделенных с кожи детей больных атопическим дерматитом. Педиатрия. 2017; 96 (6): 87–91.
  25. Leung D.Y., Gately M., Trumble A., Ferguson-Darnell B., Schlievert P.M., Picker L.J. Bacterial superantigens induce T cell expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen, via stimulation of interleukin 12 production. J. Exp. Med. 1995, 181: 747–753.
  26. Li L.B., Goleva E., Hall C.F., Ou L.S., Leung D.Y. Superantigen-induced corticosteroid resistance of human T cells occurs through activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK–ERK) pathway. J. Allergy Clin. Immunol. 114(5), 1059–1069 (2004).
  27. Li L.B., Leung D.Y., Hall C.F., Goleva E. Divergent expression and function of glucocorticoid receptor β in human monocytes and T cells. J. Leukoc. Biol. 79(4), 818–827 (2006).
  28. Kasraie S. Interleukin (IL)-31 induces pro-inflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxins. Allergy. 2010; 65: 712–721.
  29. Sugimoto K., Kitukawa Y., Aotsuka A., Wada T., Kubosawa H. et al. Is Atopic Dermatitis One of the superantigens Diseases? J Dermatolog Clin Res. 2015; 3: 1052–1053.
  30. Reginald K., Westritschnig K., Werfel T. et al. Immunoglobulin E antibody reactivity to bacterial antigens in atopic dermatitis patients. Clin Exp Allergy. 2011; 41: 357–369. Sugimoto K. Staphylococcus-aureus-vs-Atopic-Dermatitis. J Pharm Microbiol. 2016; 2: 8: 1–3.
  31. Broberg A., Faergemann J., Johansson S. et al: Pityrosporum ovale and atopic dermatitis in children and young adults. Acta Derm Venereol. 1992; 72: 187–192.
  32. Nordvall S.L., Lindgren L., Johansson S.G.O. et al. IgE antibodies to Pityrosporum orbiculare and Staphylococcus aureus in patients with very high serum total IgE. Clin Exp Allergy. 1992; 22: 756–761.
  33. Wessels M.W., Doeks G., Van Ieperen-Van Dijk A.G. et al. IgE antibodies to Pityrosporum ovale in atopic dermatitis. Br J Dermatol. 1991; 125: 227–232.
  34. Naik S., Bouladoux N., Wilhelm C., Molloy M.J., Salcedo R., Kastenmuller W. et al. Compartmentalized control of skin immunity by resident commensals. Science (2012) 337: 1115–1119.
  35. A. Capone, S.E. Dowd, G.N. Stamatas, and J. Nikolovski, “Diversity of the human skin microbiome early in life,” Journal of InvestigativeDermatology, vol. 131, no. 10, pp. 2026–2032, 2011.
  36. Murray PR, Turner ML, Segre JA. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012 May; 22(5): 850–9.
  37. Tokura Y. Extrinsic and intrinsic types of atopic dermatitis. J Dermatol Sci. 2010; 58: 1–7., Mori T., Ishida K., Mukumoto S., Yamada Y., Imokawa G., Kabashima K. et al. Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis. Br J Dermatol. 2010; 162: 83–90.
  38. Suarez-Farinas M., Dhingra N., Gittler J., Shemer A., Cardinale I., de Guzman S.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.
  39. Gray C.L., Levin M.E., Zar H.J., Potter P.C., Khumalo N.P., Volkwyn L. et al. Food allergy in South African children with atopic dermatitis. Pediatr Allergy Immunol. 2014; 25: 572–579.
  40. Boyce J.A., Assa’ad A.H., Burks A.W. et al. Guidelines for the Diagnosis and Management of Food Allergy in the United States. Report of the NIAID-sponsored Expert Panel. J Allergy Clin Immunol. 2010; 126(6 Suppl): S1–S
  41. Flohr C., Perkin M., Logan K., Marrs T., Radulovic S., Campbell L.E. et al. Atopic dermatitis and disease severity are the main risk factors for food sensitization in exclusively breastfed infants. J Invest Dermatol. 2014; 134: 345–350.
  42. Toit du G., Roberts G., Sayre P.H., Plaut M., Bahnson H.T., Mitchell H. et al. Identifying infants at high risk of peanut allergy: the Learning Early About Peanut Allergy (LEAP) screening study. J Allergy Clin Immunol. 2013; 131: 135–143.
  43. Venkataraman D., Soto-Ramirez N., Kurukulaaratchy R.J., Holloway J.W., Karmaus W., Ewart S.L. et al. Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence. J Allergy Clin Immunol. 2014; 134: 876–882.
  44. Fallon P.G., Sasaki T., Sandilands A., Campbell L.E., Saunders S.P., Mangan N.E. et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet. 2009; 41: 602–608.
  45. Sampson H.A. The evaluation and management of food allergy in atopic dermatitis. Clin Dermatol. 2003; 21: 183–192.
  46. Breuer K., Heratizadeh A., Wulf A., Baumann U., Constien A., Tetau D. et al. Late eczematous reactions to food in children with atopic dermatitis. Clin Exp Allergy. 2004; 34: 817–824.
  47. Sampson H.A., Aceves S., Bock S.A., James J., Jones S. et al. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol. 2014 Nov. 134 (5): 1016-1025.
  48. Celik-Bilgili S., Mehl A., Verstege A., Staden U., Nocon M., Beyer K. et al. The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges. Clin Exp Allergy. 2005; 35: 268–273.
  49. Werfel T., Ballmer-Weber B., Eigenmann P.A., Niggemann B., Rance F., Turjanmaa K. et al. Eczematous reactions to food in atopic eczema: position paper of the EAACI and GA2LEN. Allergy. 2007; 62: 723–728.
  50. Ono E., Murota H., Mori Y., Yoshioka Y., Nomura Y., Munetsugu T. et al. Sweat glucose and GLUT2 expression in atopic dermatitis: Implication for clinical manifestation and treatment. PLoS ONE (2018) 13(4): e0195960.
  51. Murota H., Yamaga K., Ono E., Katayama I. Sweat in the pathogenesis of atopic dermatitis. Allergol Int. 2018, Oct; 67(4): 455–459.
  52. Swerev M. What dermatologists should know about textiles. Textiles and the skin Curr Probl Dermatol. 2003; 31: 1–23.
  53. Höfer D. A Real-Life Based Evaluation of the Effectiveness of Antibacterial Fabrics in Treating Atopic Dermatitis. Dermatology Research and Practice. Volume 2018, Article ID 7043438, 8 p.
  54. Ricci G., Patrizi A., Bendandi B. et al. Clinical effectiveness of a silk fabric in the treatment of atopic dermatitis Br J Dermatol 2004; 150: 127–131.
  55. Faleide A.O., Galtung V.K., Unger S., Watten R.G. Children at risk of allergic development: the parents’ dyadic relationship. Psychother Psychosom. 1988, 49(3-4): 223–229.
  56. Letourneau N.L., Kozyrskyj A.L., Cosic N., Ntanda H.N., Anis L., Hart M.J., Campbell T.S., Giesbrecht G.F. Maternal sensitivity and social support protect against childhood atopic dermatitis. APrON Team. Allergy Asthma Clin Immunol. 2017 May; 26: 13–26.
  57. Williams H.C., Burney P.G., Pembroke A.C. et al. The U.K. Working Party’s diagnostic criteria for atopic dermatitis. III. Independent hospital validation. Br J Dermatol. 1994; 131: 406–416.
  58. Атопический дерматит: рекомендации для практических врачей. Российский национальный согласительный документ по атопическому дерматиту (Р.М. Хаитов и А.А. Кубанова, ред). М., Фармарус Принт, 2002, 58–77.
  59. Bernstein I., Li J.T., Bernstein D.I., Hamilton R., Spector S., Tan R. et al. Allergy Diagnostic Testing: An Updated Practice ParameterI. Ann Allergy Asthma Immunol. 2008; 100(3 Suppl 3): S1–148.
  60. Bousquet J., Heinzerling L., Bachert C., Papadopoulos N.G., Bousquet P.J., Burney P.G. et al. Practical guide to skin prick tests in allergy to aeroallergens. Allergy. 2012; 67: 18–24.
  61. Sampson H.A., Albergo R. Comparison of results of prick skin tests, RAST, and double-blind placebo-controlled food challenges in children with atopic dermatitis. J Allergy Clin Immunol 1984; 74: 26–33.
  62. Cox L., Williams B., Sicherer S., Oppenheimer J., Sher L., Hamilton R. et al. American College of Allergy, Asthma and Immunology Test Task Force; American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force. Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force. Ann Allergy Asthma Immunol. 2008; 101(6): 580–592.
  63. Castelain M., Birnbaum J., Castelain P.Y. et al. Patch test reactions to mite antigens: A GERDA multicentre study. Contact Dermatitis 1993; 29: 246–250.
  64. Simonsen A.B., Johansen J.D., Deleuran M., Mortz C.G., Sommerlund M. Contact allergy in children with atopic dermatitis: a systematic review. Br J Dermatol. 2017 Aug; 177(2): 395–405.
  65. Jacob S.E., McGowan M., Silverberg N.B., Pelletier J.L., Fonacier L., Mousdicas N. et al. Pediatric Contact Dermatitis Registry Data on Contact Allergy in Children With Atopic Dermatitis. JAMA Dermatol. 2017. 153: 765–770.
  66. Leung D.Y., Hanifin J.M., Charlesworth E.N. et al. Disease management of atopic dermatitis: A practice parameter. Ann Allergy Asthma Immunol. 1997; 79: 197–211.
  67. Probiotics for treating eczema Areti Makrgeorgou, Jo Leonardi-Bee et al. Cochrane Database of Systematic Reviews, 2018, 11, 11 2018.
  68. Chinthrajah R.S., Tupa D., Prince B.T., Block W.M., Rosa J.S., Singh A.M., Nadeau K. Diagnosis of Food Allergy. Pediatr Clin North Am. 2015; 62(6): 1393–1408.
  69. Sampson H., Gerthvan Wijk R., Bindslev-Jensen C., Sicherer S., Teuber S.S., Burks A.W., Dubois A.E.J., Beyer K., Eigenmann P.A., Spergel J.M., Werfel T., Chinchilli V.M. Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol. 2012; 130: 1260–1274.
  70. Pettersson M.E., Koppelman G.H., Flokstra-de Blok B.M.J., Kollen B.J., Dubois A.E.J. Prediction of the severity of allergic reactions to foods. Allergy. 2018; 73(7): 1532–1540.
  71. Anagnostou K. Safety of Oral Food Challenges in Early Life. Children (Basel). 2018; 5(6): 65.
  72. Федеральные клинические рекомендации по оказанию медицинской помощи детям с пищевой аллергией. Союз педиатров России. 2015, 27 с. Аллергия к белкам коровьего молока у детей. Клинические рекомендации. Союз педиатров России. 2016, 52 с.
  73. «Атопический дерматит у детей: обновление 2019 (на правах руководства)» Согласительный документ Ассоциации детских аллергологов и иммунологов России Москва: АДАИР, 2019; Cамара: ООО «Полиграфическое объединение «Стандарт», 2019. – 222 с.

Masalskiy SS, Kalmykova AS, Ukhanova OP, Smolkin YS, Markarova IV, Takushinova FM. Use serum periostin as marker of worsening pediatric allergic asthma. Allergology and Immunology in Pediatrics. 2018;55(4):37-48. (In Russ.) https://doi.org/10.24411/2500-1175-2018-00021

For correspondense

S.S. Masalskiy
e-mail: masalsky@live.com.

A.S. Kalmykova
email: kangeline@mail.ru.

O.P. Ukhanova
email: uhanova_1976@mail.ru.

Y.S. Smolkin
e-mail: smolkinyury@hotmail.com.

I.V. Markarova
email: markarova.inna@yandex.ru.

F.M. Takushinova
email: Tfm85@mail.ru.

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