Risk of developing asthma in young children with atopic eczema: A systematic review

doi:10.1016/j.jaci.2007.05.042

Journal of Allergy and Clinical Immunology

Volume 120, Issue 3, September 2007, Pages 565-569

https://doi.org/10.1016/j.jaci.2007.05.042 Get rights and content

Background

It is commonly believed that the majority of infants and young children with early atopic eczema will develop asthma in later childhood. This belief is mainly based on cross-sectional population studies. Recent evidence suggests a more complex relationship between early eczema and asthma.

Objective

This systematic review was conducted to assess the risk of developing asthma in children with atopic eczema during the first 4 years of life.

Methods

A sensitive search was performed to identify all prospective cohort studies on the topic. By pooling the eligible reports, we calculated the risk of developing asthma at 6 years of age or older in children with atopic eczema in the first 4 years of life.

Results

Thirteen prospective cohort studies were included, with 4 representing birth cohort studies and 9 representing eczema cohort studies. The pooled odds ratio for the risk of asthma after eczema, compared with children without eczema, in birth cohort studies was 2.14 (95% CI, 1.67-2.75). The prevalence of asthma at the age of 6 years in eczema cohort studies was 35.8% (95% CI, 32.2% to 39.9%) for inpatients and 29.5% (95% CI, 28.2% to 32.7%) for a combined group of inpatients and outpatients.

Conclusion

Although there is an increased risk of developing asthma after eczema in early childhood, only 1 in every 3 children with eczema develops asthma during later childhood. This is lower than previously assumed.

Clinical implications

Our results may have important consequences for counseling patients with atopic eczema and their parents.

Section snippets

Methods

A sensitive search strategy was designed to retrieve all relevant articles from Medline, Embase (Jan 1, 1950 to August 1, 2006) and the Cochrane library (1966 to August 1, 2006). We searched for ([“asthma” OR “wheeze” OR “bronchial hyperresponsiveness”] AND [“eczema” OR “atopic dermatitis” OR “atopy”]) AND (“prospective study” OR “cohort study” OR “risk factor” OR “epidemiologic study” OR “longitudinal study”) as medical subject headings or as main key words in the title or abstract.

Results

The search yielded 2668 hits in Medline and 2498 hits in Embase, of which 1609 were duplicate hits. Out of this total of 3557 articles, 23 were eligible according to our first set of criteria. Of these 23, two articles were excluded because they showed duplicate data from a study already included.11, 12 The full text of 1 report could not be retrieved through library services.¹³ Following the validity criteria, 7 articles were excluded on the basis of insufficient follow-up figures.14, 15, 16,

Discussion

Our study shows that although the risk of developing asthma in young children with AE is elevated (OR, 2.14; 95% CI, 1.76-2.75), the magnitude of this risk is relatively low, with a prevalence of asthma at the age of 6 years or older of 35.8% (95% CI, 32.2% to 39.9%) in inpatients and of 29.5% (95% CI, 28.2% to 32.7%) in a combined group of inpatients and outpatients. These figures, based on a systematic review of all studies with more than 80% follow-up until the age of 6 years or older, are

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Atopic dermatitis (AD) is thought to induce asthma via the “atopic march,” but the effects of AD on incident asthma and asthma severity have not been fully characterized.
To determine risk of asthma, asthma exacerbations, and asthma-related hospitalizations among patients fwith AD.
A cohort study was conducted using electronic health records data from UK general practices from 1994 to 2015. Children (<18 years old) and adults (≥18 years) with AD were matched on age, practice, and index date to patients without AD. AD severity was categorized using treatments and dermatologist referrals. Outcomes were incident asthma among all patients and asthma exacerbation or hospitalization among patients with asthma.
On comparing 409,341 children with AD (93.2% mild, 5.5% moderate, 1.3% severe) with 1,809,029 unaffected children, those with AD were found to be associated with a 2-fold greater risk of asthma compared with those without AD (hazard ratio, 1.96; 95% CI, 1.93-1.98). On comparing 625,083 adults with AD (65.7% mild, 31.4% moderate, and 2.9% severe) with 2,678,888 unaffected adults, AD was found to be associated with a 38% higher risk of asthma (hazard ratio, 1.38; 95% CI, 1.36-1.40). Asthmatic patients with AD also had a 21% to 63% greater risk of asthma exacerbations and a 20% to 64% greater risk of asthma-related hospitalizations compared with asthmatic patients without AD. Risk of asthma, asthma exacerbation, or asthma-related hospitalization increased with AD severity in a dose-dependent manner in both the pediatric and adult cohorts.
AD, especially in children and when more severe, is associated with greater risk of asthma as well as greater risk of asthma exacerbations and hospitalizations among asthmatic patients.
Beyond the Skin: Reduced Lung Function Associated With Atopic Dermatitis in Infants
2023, Journal of Allergy and Clinical Immunology: In Practice
Very few studies have examined lung function parameters using tidal breath analysis (TBA) in atopic dermatitis (AD) with its high potential for progression to asthma.
To measure lung functions using TBA in infants with AD and in healthy controls (HCs), and to investigate the effects of disease severity, food sensitivity, and history of recurrent wheezing on TBA parameters in infants with AD.
Two hundred thirty infants were included in this prospective cross-sectional study, including an AD group (n = 150) and an HC group (n = 80). Food sensitivity was assessed by means of food-specific IgE or the skin prick test. The severity of the disease was evaluated using the SCORing Atopic Dermatitis. Lung function was assessed using TBA.
The following TBA parameters were significantly lower in the AD group than in the HC group (P < .05): time to peak tidal expiratory flow, exhaled volume to peak tidal expiratory flow, ratio of time to peak tidal expiratory flow to expiratory time, ratio of exhaled volume to peak tidal expiratory flow to total expiratory volume, expiratory flow when 25% of tidal volume remains in the lungs, respiratory rate, and minute ventilation. No difference was observed in the AD group when TBA parameters were compared according to disease severity, food sensitivity, and history of recurrent wheezing (P > .05). The receiver-operating characteristic curve demonstrated by the ratio of time to peak tidal expiratory flow to expiratory time yielded an area under the curve of 0.826 (CI, 0.772-0.879), with a cutoff value of 31.65 or higher in differentiating AD, with a sensitivity of 78.7% and a specificity of 77.5%.
TBA curves can be a useful tool for demonstrating expiratory airway obstruction in AD and for providing objective information for the clinician. Bronchial obstruction was detected in young children with AD irrespective of the severity of the disease, food sensitivity, and history of recurrent wheezing.
Might biologics serve to interrupt the atopic march?
2023, Journal of Allergy and Clinical Immunology
The atopic march was described more than 20 years ago on the basis of initial observations, and it is now seen in prospective studies. The concept has evolved and is now considered to be the progression of atopic dermatitis to other atopic conditions, including asthma, allergic rhinitis, food allergy, and eosinophilic esophagitis in a nonlinear fashion. The progression can include some or all of the aforementioned atopic conditions. The pathogenesis is part of the classic type 2 inflammatory process involving IL-4, IL-5, and IL-13 preceded by induction of the alarmins (thymic stromal lymphopoietin, IL-33, and IL-25), leading to production of IgE in a genetically predisposed individual. The development of new biologics that interact with T2 pathway represent possible ways to prevent or modify the atopic march.
Attenuating the atopic march: Meta-analysis of the dupilumab atopic dermatitis database for incident allergic events
2023, Journal of Allergy and Clinical Immunology
Atopic march refers to the sequential development of allergic diseases from infancy through adolescence, typically beginning with atopic dermatitis (AD), followed by food allergy and then airway diseases, later evolving to broader or worsened spectrum of allergic diatheses. No intervention has shown to alter its course.
We sought to determine the rate of acquisition of new or worsened allergic events for dupilumab versus placebo in patients with AD.
Allergy-associated events from 12 clinical trials were grouped into 17 allergy categories, and IgE changes from baseline were defined. A new/worsened event was considered one step of atopic march. Treatment effect was assessed by incidence rate ratios (IRRs), dupilumab versus placebo, by meta-analysis.
The duration of pooled AD studies was 4 to 52 weeks (1359 patient-years; n = 2296 dupilumab, n = 1229 placebo, median age 35 years). The median age at AD onset was 2 years. Baseline allergic disease burden was comparable between groups. Dupilumab reduced the risk of new/worsening allergies by 34% (IRR 0.66; 95% confidence interval [CI], 0.52-0.84) and new allergies by 37% (IRR 0.63; 95% CI, 0.48-0.83) versus placebo. Including IgE category shift, the IRR for combined new/worsening allergies was reduced by 54% (IRR 0.46; 95% CI, 0.36-0.57). These treatment benefits did not reverse on treatment discontinuation in off-treatment follow-up.
The acquisition/worsening of allergic conditions suggestive of atopic march was observed in a pooled adult/adolescent AD study population with inadequately controlled AD. Treatment with dupilumab reduced new/worsened allergy events versus placebo; inclusion of IgE category change increased the apparent benefit.
Allergen immunotherapy for allergic airway diseases: Use lessons from the past to design a brighter future
2022, Pharmacology and Therapeutics
Allergic respiratory diseases, such as allergic dermatitis, food allergy, allergic rhino conjunctivitis and allergic asthma, are chronic inflammatory diseases with increasing prevalence. Symptoms include such as watery or itchy itching of the mouth, skin, or the eyes, swelling of the face or throat, sneezing, congestion or vomiting, wheezing, shortness of breath and coughing. For allergic asthma, additional symptoms include tightness of chest, cough, wheezing, and reversible airflow limitation. These symptoms can be triggered by inhalation of allergens such as food allergens or airborne allergens such as those from tree- or grass pollen and house dust mites. Pharmacological intervention in allergic disease includes the use of antihistamines, immune suppressive drugs and in case of asthma, the use of (long acting) beta-agonists for relaxation of the constricted airways. These treatment options merely suppress symptoms and do not cure the disease. Allergen immunotherapy (AIT), in contrast, has the capacity of inducing long-term tolerance, with symptom relief persisting decennia after discontinuation of treatment, despite recurrent re-exposure to the allergen. However, AIT is not effective for all allergic disorders, and treatment for several years is required to obtain long-term protection. Moreover, some forms of AIT have safety concerns, with risk of mild to severe allergic reactions. To improve safety and efficacy of AIT, the underlying mechanisms have been studied extensively in the clinic as well as in experimental models of allergic airway inflammation.
Despite more than a century of clinical experience and a vast body of experimental and translational studies into the immunological and cellular mechanisms underpinning its therapeutic potential, AIT is still not implemented in routine clinical care for allergic asthma. This review provides an overview of the substantial developments that contribute to our knowledge of the pathogenesis of allergic airway diseases, the mechanism of action of AIT, its treatment routes and schedules, the standardization of extracts and use of adjuvantia. Moreover, the main conclusions from experimental models of AIT with regard to the safety and effectiveness of the treatment are summarized, and future directions for further improvements are outlined. AIT urgently requires further improvements in order to increase its efficiency and shorten the treatment duration while remaining safe and cost-effective.
Prevalence of type 2 inflammatory diseases in pediatric patients with atopic dermatitis: Real-world evidence
2022, Journal of the American Academy of Dermatology
Patients with atopic dermatitis (AD) are considered at increased risk of developing other type 2 inflammatory diseases. However, real-world evidence based on large commercially insured pediatric populations in the United States is scarce.
To use a large claims database (IBM MarketScan 2013-2017) in the United States to assess prevalence and incidence of type 2 inflammatory diseases in pediatric patients with AD.
Pediatric patients with AD were matched 1:1 to patients without AD. Prevalence was assessed for conjunctivitis, rhinitis, urticaria, asthma, eosinophilic esophagitis, and chronic rhinosinusitis/nasal polyps at the 12 months' post-index date (the first AD diagnosis date for patients with AD; a randomly selected outpatient visit for control patients). The incidence of other type 2 inflammatory diseases post-index was assessed among patients 0-2 years of age.
A total of 244,776 AD and matched non-AD patients were selected. The prevalence and incidence of type 2 inflammatory diseases were higher among patients with AD. Overall, the prevalence more than doubled for asthma, eosinophilic esophagitis, urticaria, and rhinitis, and increased with AD severity.
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The burden of type 2 inflammatory diseases in pediatric patients with AD is substantial, highlighting the need to optimize management of AD and its numerous associated morbidities.

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: Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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Asthma diagnosis and treatmentRisk of developing asthma in young children with atopic eczema: A systematic review

Background

Objective

Methods

Results

Conclusion

Clinical implications

Section snippets

Methods

Results

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Cont Clin Trials

J Allergy Clin Immunol

Chest

J Am Acad Dermatol

J Allergy Clin Immunol

Natural history of allergic diseases and asthma

Atopic dermatitis (atopic eczema)

Allergy

Allergy, asthma and immunology from infancy to adulthood

Asthma and wheezing in the first six years of life

N Engl J Med

Atopic dermatitis in early infancy predicts allergic airway disease at 5 years

Clin Exp Allergy

A clinical index to define the risk of asthma in young children with recurrent wheezing

Am J Respir Crit Care Med

Prognosis in infantile eczema

Ir J Med Sci

Long-term prognosis in infantile eczema

BMJ

Evolution of atopic dermatitis

Dermatologica

Asthma diagnosis and treatment
Risk of developing asthma in young children with atopic eczema: A systematic review