The association between asthma and Kawasaki disease

Bong Seok Choi

doi:10.4168/aard.2019.7.4.173

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Choi: The association between asthma and Kawasaki disease

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Allergy Asthma Respir Dis 2019;7(4):173-178.

Published online: 12 October 2019

DOI: https://doi.org/10.4168/aard.2019.7.4.173

The association between asthma and Kawasaki disease

Bong Seok Choi

^¹Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea

Correspondence to: Bong Seok Choi https://orcid.org/0000-0002-2129-7232 Department of Pediatrics, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Korea Tel: +82-53-200-5704, Fax: +82-53-425-6683, E-mail: bschoi@knu.ac.kr

Received 14 March 2019 Revised 11 September 2019 Accepted 11 September 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Kawasaki disease (KD) is a systemic vasculitis and the most common cause of acquired heart disease among preschool-aged children. Asthma is one of the most common chronic illness of childhood. There is increasing interest in the potential link between inflammatory diseases and allergic diseases, and there is increasing epidemiologic evidence for an association of KD and allergic disease. In regards to asthma, 9 studies have been reported about its association with KD; 5 of them showed positive associations between these 2 diseases, while 4 of them showed no association. There are some possible underlying mechanisms for this association. The serum IgE levels are found to be increased and there is a Th2-predominant immune response in KD. These are common findings of asthma. Human leukocyte antigen-G/regT cells and SMAD3/transforming growth factor-beta might also be involved in the pathogenesis of both diseases. Asthma may increase susceptibility to KD and tends to lead to immune dysregulation. Clinician's recognition of the increased risks of KD and other asthma-related comorbidities among patients with asthma may enable early identification and intervention. The early identification and management of comorbidities may ultimately reduce the economic and social burden of these chronic conditions.

Keywords: Kawasaki disease, Mucocutaneous lymph node syndrome, Allergy, Asthma, Comorbidity

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Table 1.

Studies showing an association between asthma and the risk of Kawasaki disease

Type of study	Subjects	Exposure	Outcome	Results	Conclusion
Prospective Cohort Study²²	Patients born between 1997 and 2005 and aged <5 yr, as recorded in the National Health Insurance Research database of Taiwan 1. n=254 cases with KD 2. n=1,012 cases without KD	Allergic diseases (asthma and AR) (ICD-9)	Development of KD (ICD-9 code)	1. KD patients had significantly lower 5-yr allergic disease-free survival rates than comparison cohort (P<0.001). 2. HR of asthma for KD is 1.51 (95% CI, 1.17–1.95).	KD patients were 1.51 times more likely to develop asthma than their comparison cohort.
Case-control study²¹	Patients born between 1976 and 2006, as recorded in the Western Australia Data Linkage System. 1. n=295 cases with KD and 1,636 relatives 2. n=598 cases without KD and 3,780 relatives	Hospitalization for infectious disease, allergy/asthma (ICD-9)	KD (ICD-9, 446.1; ICD-10, M30.3)	Cases more likely to have been admitted at least once for asthma/allergy (16.6% cases vs. 7% controls) (OR, 2.6; 95% CI, 1.7–4.2; P<0.01).	Children with KD were more likely admitted to hospital for allergy/asthma; a majority of these admissions occurred before admission for KD.
Case-control study²⁴	Patients born between 1997 and 2010 and aged <5 yr, as recorded in the National Health Insurance Research Database of Taiwan 1. n=200 with KD 2. n=800 without KD (age- and sex-matched)	Prevalence of atopic dermatitis, allergic rhinitis, asthma (ICD-9)	Development of KD (ICD-9)	Among all subjects, 28% had KD asthma (control: 20.25%, P=0.02). OR was 1.53 (95% CI, 1.08–2.18), with statistical significance. 37.5% of asthma cases were diagnosed after an initial diagnosis of KD.	KD appears to be associated with risk of AD, and most of the atopic diseases occurred after an episode of KD.
Case-control study²⁵	Patients born between 1997 and 2004 and admitted for KD by 2010, as recorded in the National Health Insurance Research Database of Taiwan 1. n=7,072 with KD 2. n=27,275 without KD (zip code-, age- and sex-matched)	Hospitalization for KD (ICD-9)	Manifestations of AD, asthma, urticaria, AR (ICD-9)	1. Asthma rates in KD patients and controls in the first year of life were 5.63% and 4.42% (P<0.001), which peaked at 17.96% and 14.85%, respectively, at the age of 4 yr (P<0.001). 2. Prevalence of AR (OR, 1.30; 95% CI, 1.22–1.38) and asthma (OR, 1.16; 95% CI, 1.05–1.27) was higher in children with KD than in controls.	Higher incidence rates of AD, AR, and asthma were seen in children with KD than in controls.
Cross-sectional study²⁶	Persons aged 16–20 yr, as recorded in the 1998–2013 Israel military preconscription medical data assessment 1. n=70 complicated KD 2. n=74 noncomplicated KD 3. n=1,187,757 general population	Asthma, angioedema/chronic urticaria, allergic rhinitis (questionnaires)	Development of KD (cardiac complicated/noncomplicated, family practitioners' declarations)	1. Complicated KD: Asthma OR, 3.5; P=0.003; angioedema/urticaria OR, 16.48; P<0.001; allergic rhinitis OR, 3.5; P<0.001 2. uncomplicated KD: asthma OR, 2.4; P=0.048	Individuals with a history of KD had a higher prevalence of atopic diseases, and the link between KD and atopic diseases was more significant in complicated KD cases.

KD, Kawasaki disease; ICD, International Classification of Diseases; CI, confidence interval; OR, odds ratio; AR, allergic rhinitis; AD, atopic dermatitis.

Table 2.

Studies s showing no association between asthma and the risk of Kawasaki disease

Type of study	Subjects	Exposure	Outcome	Results	Conclusion
Prospective Cohort Study²⁷	KD patient cohort (n=58, >5-yr follow-up)	KD	Prevalence of bronchial asthma (1) at onset of KD (2) at follow-up	KD patients had markedly higher total serum IgE level and prevalence of asthma at KD onset than the general children population. The prevalence of bronchial asthma at follow-up was similar to the general children population.	KD patients with atopic bronchial asthma at onset did not develop a severe allergic reaction.
Cross-sectional Study²⁹	103 KD patients and 100 age-matched controls	History of infection, asthma, or allergy; attended daycare/school; have siblings.	Development of KD	Patients with KD were more likely to have had a history of infection in the previous month (21% vs. 2%, P<0.001), have siblings (34% vs. 18%, P=0.02), and attend a full-time daycare facility or school (vs. stay at home) (40% vs. 21%, P=0.004). A similar proportion of patients in both the groups had a previous diagnosis of asthma (5% vs. 4%, P=1.00) and known allergies (5% vs. 4%, P=1.00).	A similar proportion of patients in both groups had known allergies.
Cross-sectional Study²⁸	Patients born between 1998–2008, aged 1–18 yr, and diagnosed with KD, as recorded in the National Health Insurance Research database in Taiwan 1. n=2,748 KD 2. n=10,656 without KD	Allergic conjunctivitis, allergic rhinitis, asthma, atopic dermatitis, urticaria (ICD-9)	Development of KD (ICD-9 with further review and approval by the Bureau of NHI)	In the whole study population, an increased subsequent risk of KD was observed in the children with each of the allergic diseases, except asthma	Children with allergic disease at onset had an increased risk of KD.
Cross-sectional Study (sibling-control study)²⁰	Patients who had KD before the age of 16 yr at least 1 yr after the KD episode. Must have a healthy sibling as control. 1. n=93 KD 2. n=93 sibling pairs	Allergic diseases (AR, eczema, asthma, allergic conjunctivitis) (ISAAC questionnaire and clinical diagnosis)	Development of KD	1. Asthma incidence rate was 14.0% in the KD group and 8.6% in the control group (adjusted OR, 2.56; 95% CI, 0.80–8.23). There was no statistical difference in the incidence of asthma, eczema, and allergic conjunctivitis. 2. Allergic rhinitis was 50.5% in the KD group and 35.5% in the control group (cOR, 2.40; 95% CI, 1.11–5.62, P=0.024)	KD may be a risk factor for AR but not for asthma.

KD, Kawasaki disease; ICD, the international classification of diseases; CI, confidence interval; OR, odds ratio; AR, allergic rhinitis; AD, atopic dermatitis; NHI, National Health Insurance; ISAAC, International Study of Asthma and Allergies in Childhood; cOR, crude odds ratio.

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