Atopic dermatitis phenotype with early onset and high serum IL-13 is linked to the new development of bronchial hyperresponsiveness in school children

Sylvia Okoma, Mercer University College of Pharmacy

According to the World Allergy Organization, the term “allergic march” or “atopic march” describes the natural history of atopic manifestations characterized by a sequence of immunoglobulin E (IgE) antibody responses that produce certain clinical symptoms that can appear  early in life, persist for years or decades and will cease spontaneously with time.  [1] It has been identified that atopic dermatitis has its origins from these mechanisms.  [2, 3]

Title:  Atopic dermatitis phenotype with early onset and high serum IL-13 is linked to the new development of bronchial hyperresponsiveness in school children [4]
Design Prospective cohort and follow-up study, N = 242
Objective To define AD phenotypes in children six to eight years, compare them to potential causative factors of AD development, and identify an association with AD phenotype and the development of bronchial hyperresponsiveness (BHR) and asthma
Study Groups Children six to eight years in four study groups:

Group one (n = 64) : early onset of AD with low atopy, low levels of serum IgE and a normal eosinophil percentage

Group two (n = 117):  early onset of AD with high atopy and high eosinophil percentage

Group three (n = 24): late onset of AD with low atopy

Group four (n = 37): late onset with high atopy and normal eosinophil percentage

(Early onset is defined as children six years old and late onset is defined as children who were seven and eight years old.)


Methods Skin prick tests were performed with 13 of the most common inhalant allergens and a mean wheal size of ≥ 3 mm measured after 15 minutes and associated with a measured histamine response of 10 mg/mL was considered a positive response.  Total serum IgE levels were measured using the Immunocap-CAP 1000 system (Aloka, Tokyo, Japan) with a lower detection limit of total serum IgE of 2 kU/L.  Baseline lung function with forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and forced expiratory flow at 25% to 75% of FVC were assessed utilizing the American Thoracic Society (ATS)/ European Respiratory Society (ERS) guidelines.  Bronchial hyperresponsiveness (BHR) for all participants was also measured on the first day of the study.   Bronchial hyperresponsiveness was measured by utilizing a methacholine bronchial challenge that measured the cumulative amount of methacholine utilized to cause a 20% reduction in FEV1 (PC20 concentration) and the change in tidal inhalation when the methacholine doses (0.625, 1.25, 2.5, 5, 10 and 25 mg/mL) were doubled.  Bronchial hyperresponsiveness to methacholine was identified when methacholine PC20 concentration was ≤ 8 mg/mL.


Duration Four years
Primary Outcome Measure Identification of AD phenotype and the development of BHR and asthma during follow up
Baseline Characteristics  Group one , n = 64 Group two , n = 117 Group three , n = 24 Group four , n = 37
Males, n (%) 12 (19%) 87 (74%) 17 (71%) 9 (24%)
Parental history of allergic diseases, n (%) 34 (53%) 65 (56%) 3 (13%) 1 (3%)
Age at AD diagnosis
< 1 year, n (%) 29 (45%) 48 (41%) 1 (4%) 3 (8%)
1-3 years, n (%) 15 (23%) 30 (26%) 9 (38%) 13 (35%)
4-6 years, n (%) 17 (27%) 29 (25%) 13 (54%) 21 (57%)
> 6 years, n (%) 3 (5%) 10 (8%) 1 (4%) 0 (0%)
Positive skin prick tests
≥ 1 allergen, n (%) 2 (3%) 65 (56%) 4 (17%) 4 (11%)
Total serum IgE levels ≥ 100 kU/L, n (%) 8 (13%) 100 (85%) 0 (0%) 31 (84%)
Serum eosinophil ≥ 4%, n (%) 8 (13%) 84 (72%) 0 (0%) 12 (32%)
Results The development of newly developed BHR recorded after the four year follow-up period were:  two new cases for group one, 11 cases in group two (p  = 0.045), none in group three, and one in group four.  Also, the newly diagnosed asthma by physicians during the four year follow-up period were:  three in group one; seven in group two; none in group three, and one in group four.
Adverse Events Common Adverse Events:  At enrollment: atopy (36.1%), positive BHR (18.2%)
Serious Adverse Events:  None reported
Percentage that Discontinued due to Adverse Events:  None reported
Study Author Conclusions The current findings provide information that can help with the identification of the underlying pathophysiology of the allergic march.  The current findings show that eosinophils, serum IL-13, and total serum IgE levels are associated with the allergic march associated phenotypes in school age children.  It has been therefore suggested that eosinophils may contribute to the progression of allergic march.


It is suggested that impairment of epithelial function, resulting in increased sensitization and likewise IgE production, contribute to the association between eczema, asthma, and rhinitis.  This also supports the multi-organ dynamics of allergic sensitization in a systemic reaction rather than a local response.  The relationship between asthma and atopic eczema remains complex involving information from both genetic and clinical aspects for proper assessment.  [4]




  1. Wahn, Ulrich.  The allergic march.   World allergy organization: a world federation of allergy, asthma and clinical  immunology societies.  Sep 2015.  Accessed 28 Jan 2016. Accessed 28 Jan 2015.
  2. Von Kobyletzki LB, Bornehag CG, Hasselgren M, Larsson M, Lindstrom CB, Svensson A. Eczema in early childhood is strongly associated with the development of asthma and rhinitis in a prospective cohort.  BMC Dermatol 2012; 12: 11.  Accessed 28 Jan 2016.
  3. Van der Hulst AE, Klip H, Brand PL. Risk of developing asthma in young children with atopic eczema: a systematic review.  J Allergy Clin Immunol 2007; 120: 565-569.  Accessed 28 Jan 2016.
  4. Lee, Eun, Si Hyeon Lee, Ji-Won Kwon, Yeongho Kim, Hyun-Ju Cho, Song-I Yang, 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, 21 Jan 2016.  Accessed 27 Jan 2016.

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