Moderate to severe atopic dermatitis in children: focus on systemic Th2 cytokine receptor antagonists and Janus kinase inhibitors.

Atopic dermatitis (AD) is a lifelong disease that markedly impairs quality of life. AD is considered a starting point of the "atopic march," which begins at a young age and may progress to systemic allergic diseases. Moreover, it is strongly associated with comorbid allergic and inflammatory diseases including arthritis and inflammatory bowel disease. Understanding the pathogenesis of AD is essential for the development of targeted therapies. Epidermal barrier dysfunction, immune deviation toward a T helper 2 proinflammatory profile, and microbiome dysbiosis play important roles via complex interactions. The systemic involvement of type 2 inflammation, wheather acute or chronic, and whether extrinsic or intrinsic, is evident in any type of AD. Studies on AD endotypes with unique biological mechanisms have been conducted according to clinical phenotypes, such as race or age, but the endotype for each phenotype, or endophenotype, has not yet been clearly identified. Therefore, AD is still being treated according to severity rather than endotype. Infancy-onset and severe AD are known risk factors leading to atopic march. In addition, up to 40% of adult AD are cases of infancy-onset AD that persist into adulthood, and these are often accompanied by other allergic diseases. Therefore, early intervention strategies to identify high-risk infants and young children, repair an impaired skin barrier, and control systemic inflamation may improve long-term outcomes in AD patients. However, to the best of our knowledge, no study has evaluated the effectiveness of early intervention on atopic march using systemic therapy in high-risk infants. This narrative review addresses the latest knowledge of systemic treatment, including Th2 cytokine receptor antagonists and Janus kinase inhibitors, for children with moderate to severe AD that is refractory to topical treatment.

Current Asthma Prevalence Using Methacholine Challenge Test in Korean Children from 2010 to 2014.

BACKGROUND: Most epidemiological studies depend on the subjects' response to asthma symptom questionnaires. Questionnaire-based study for childhood asthma prevalence may overestimate the true prevalence. The aim of this study was to investigate the prevalence of "Current asthma" using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and methacholine challenge test in Korean children. METHODS: Our survey on allergic disease included 4,791 children (age 7-12 years) from 2010 to 2014 in Korean elementary schools. Bronchial hyperresponsiveness (BHR) was defined as provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) ≤ 16 mg/mL. "Current asthma symptoms" was defined as positive response to "Wheezing, current," "Treatment, current," or "Exercise, current." "Current asthma" was defined when the subjects with "Current asthma symptoms" showed BHR on the methacholine challenge test or had less than 70% of predicted FEV1 value. RESULTS: The prevalence of "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," "Exercise, current," and "Current asthma symptoms" was 19.6%, 6.9%, 10.0%, 3.3%, 3.5%, and 9.6%, respectively, in our cross-sectional study of Korean elementary school students. The prevalence of BHR in elementary school students was 14.5%. The prevalence of BHR in children with "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," and "Exercise, current" was 22.3%, 30.5%, 22.4%, 28.8%, and 29.9%, respectively. BHR was 26.1% in those with "Current asthma symptoms." The prevalence of "Current asthma" was 2.7%. CONCLUSIONS: Our large-scale study provides 2.7% prevalence of current asthma in Korean elementary school children. Since approximately one third of the children who have "Current asthma symptoms" present BHR, both subjective and objective methods are required to accurately predict asthma in subjects with asthma symptoms.

Bacterial Microbiota-derived Extracellular Vesicles in Children With Allergic Airway Diseases: Compositional and Functional Features.

PURPOSE: Bacterial extracellular vesicles (EVs) play crucial roles in bacteria-host interactions. Due to their cargo, EVs are considered fingerprints of the parent cell, which are detectable in body fluids. We studied the composition and function of bacterial microbiota-derived EVs genes in urine to evaluate whether they have specific characteristics concerning allergic airway disease. METHODS: Subjects were from elementary school surveys and classified into 3 groups according to questionnaires and sensitization to aeroallergens: the allergic airway group (AA, n = 16), atopic controls (AC, n = 7) and healthy controls (HC, n = 26). The bacterial EVs were isolated from voided urine samples, their nucleic acid was extracted for 16S ribosomal RNA pyrosequencing and then characterized using α-diversity, ß-diversity, network analysis, intergroup comparison of bacterial composition and predicted functions, and correlation with total immunoglobulin E (IgE), eosinophils% and fractional exhaled NO. RESULTS: The compositional α-diversity was the highest in AA, while functional α-diversity was the highest in HC. AA had a distinct clustering with the least intersample variation. Klebsiella, Haemophilus, members from Lachnospiraceae and Ruminococcaceae, and the pathways of sphingolipid and glycerolipid metabolism, and biosynthesis of peptidoglycan and lysine were the highest in AA and positively correlated with total IgE or eosinophil%. Genetic information processing function contributed to 48% of the intergroup variance and was the highest in AA. Diaphorobacter, Acinetobacter, and the pathways of short-chain fatty acids and anti-oxidants metabolism, lysine and xenobiotic degradation, and lipopolysaccharide biosynthesis were the lowest in AA and negatively correlated with total IgE or eosinophil%. The bacterial composition and function in AC were closer to those in HC. The bacterial network was remarkably dense in HC. CONCLUSIONS: The bacterial microbiota-derived EVs in urine possess characteristic features in allergic airway disease with a remarkable correlation with total IgE and eosinophil%. These findings suggest that they may play important roles in allergic airway diseases.