Allergy, Asthma & Immunology Research最新文献

Purpose: Wheezing in early life is most frequently caused by viral lower respiratory tract illnesses, constituting a significant disease burden in children. This study aimed to investigate the association of wheezing in early life with autoimmune diseases throughout childhood.

Methods: A population-matched retrospective cohort study was conducted in Korea between 2002 and 2017. The cohort comprised 34,959 children admitted with viral wheezing before 2 years of age and an equal number of the matched unexposed children born in 2002 and 2003. Exposed infants were defined as those hospitalized for bronchiolitis or bronchial asthma before the age of 2. Unexposed controls were matched by sex and birth year at a 1:1 ratio, using incidence density sampling. A Cox proportional hazard model controlled for multiple risk factors was employed.

Results: The median age at hospitalization for wheeze was 9 months (interquartile range, 5-15 months), and 63% of the exposed infants were male. Over the mean 15-year follow-up period, the incidence rate of autoimmune diseases was 74.0 and 62.2 per 10,000 person-years in the exposed and matched unexposed cohorts, respectively. The adjusted hazard ratio for any autoimmune disease in the exposed cohort was 1.15 (95% confidence interval, 1.09-1.23) in comparison with the unexposed cohort. The exposed cohort revealed an augmented risk for specific autoimmune diseases, including juvenile idiopathic arthritis, Kawasaki disease, Henoch-Schönlein purpura, psoriasis, idiopathic thrombocytopenic purpura, and immunoglobulin A nephropathy. Risks were heightened for children with multiple wheezing episodes or a persistent wheezing episode after the age of 2 years.

Conclusions: This research identifies associations between early-life wheeze and the development of autoimmune diseases in childhood. Understanding these relationships can aid in recognizing the underlying pathophysiology of early-life wheeze and childhood autoimmune diseases, contributing to management strategies for these conditions.

The diagnostic decision point can help diagnose food allergies while reducing the need for oral food challenge (OFC) tests. We performed a multicenter survey of children aged 0-7 years from January 1, 2018 to March 31, 2022. A total of 231 children were recruited from 18 institutions. Wheat allergy (WA) or non-wheat allergy (NWA) was determined on the basis of OFC results and symptoms. There were no differences in age, sex, family history of allergy or allergic comorbidities between the WA and NWA groups. According to receiver operating characteristic analysis for wheat-specific immunoglobulin E (IgE), the optimal cutoff value, positive decision point, and negative decision point were 10.2, 33.5, and 0.41 kU/L, respectively. For the ω-5 gliadin-specific IgE, their values were 0.69, 3.88, and 0.01 kU/L, respectively. This new diagnostic decision point may be used to diagnose WA in Korean children.

Prurigo nodularis (PN) is a chronic neuroinflammatory dermatosis with severe pruritus that has limited efficacy in various conventional treatments. This study investigated the outcomes of upadacitinib treatment in patients with refractory PN. A prospective study was conducted to screen for potential chronic infections prior to treatment. Upadacitinib was administered at a daily dose of 15 mg for 24 weeks, and the treatment response was assessed using the itch Numeric Rating Scale (NRS), investigator's Global Assessment (IGA), and Dermatology Life Quality Index (DLQI). Adverse events were monitored at each visit. Ten patients, with an average age of 48.8 years, were included in the study. All participants were treated with systemic cyclosporine before receiving upadacitinib, which yielded limited responses. At baseline, the mean prurigo severity scores assessed using the IGA, DLQI, and itch NRS were 3.4, 17.8, and 8.1, respectively; after 24 weeks of treatment, these scores significantly reduced to 1.0, 0.6, and 0.8, respectively. No severe adverse effects were observed. In conclusion, upadacitinib could be considered an alternative therapeutic option with good tolerability for refractory PN.

Purpose: Atopic march is defined as the development of atopic dermatitis in early childhood. We recently developed an atopic march mouse model through skin sensitization with aeroallergens from house dust mites and cockroaches. Using this model, this study aimed to evaluate the oral immunotherapy efficacy of Lactococcus lactis harboring specific antigens on the progression of atopic march.

Methods: Dust mite major allergen Der p 2 and cockroach Per a 2-372 were expressed in L. lactis as a fusion recombinant clone (D2P2). L. lactis-D2P2 was administered intragastrically to Aeroallergen patch-sensitized mice once a day for a total of 35 times. The immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of lungs and skin were evaluated.

Results: Our data showed that L. lactis-D2P2 significantly lowered total immunoglobulin E levels, decreased scratch bouts, and relieved AHR compared with the control mice. Histological analysis of the skin and lung tissue demonstrated the therapeutic effects of L. lactis-D2P2 to modulate immune responses via decreased eosinophil infiltration and reduced expression of key cytokines, interleukin (IL)-31 and IL-13, respectively.

Conclusions: The results imply that mucosal allergen-specific immunotherapy of L. lactis-D2P2 is a more cost-effective alternative to conventional subcutaneous allergen-specific immunotherapy. This study provides a promising platform for the development of novel oral protein-based vaccines in the early prevention of allergies.

Airway remodeling is a key characteristic of allergic asthma. Epithelial-mesenchymal transition (EMT) induced by various factors, particularly transforming growth factor (TGF)-β1, orchestrates airway remodeling. Protein phosphatase 2A (PP2A), an important serine-threonine phosphatase, is involved in TGF-β1 production and EMT. Long noncoding RNAs (lncRNAs) have emerged as novel players in regulating EMT. Here, we aimed to explore the effects and mechanisms of action of lincR-PPP2R5C, a lncRNA that affects PP2A activity, on airway remodeling in a mouse model of chronic allergic asthma. LincR-PPP2R5C knockout (KO) alleviated inflammatory responses in house dust mite (HDM)-induced chronic allergic asthma. Moreover, airway remodeling and EMT were reduced in lung tissues of lincR-PPP2R5C KO mice. HDM extract induced EMT in airway epithelial cells, which was decreased following lincR-PPP2R5C KO. Mechanistically, lincR-PPP2R5C deficiency enhanced PP2A activity, which inhibited TGF-β1 production in epithelial cells. In conclusion, lincR-PPP2R5C deficiency prevented HDM-induced airway remodeling in mice by reversing EMT, which was mediated by the PP2A/TGF-β1 signaling pathway. Thus, lncRNAs, i.e., lincR-PPP2R5C, may be potential targets to prevent airway remodeling in allergic asthma.

The pathogenesis of atopic dermatitis (AD) is multifactorial, involving a dynamic interplay between genetic susceptibility, skin-barrier dysfunction, microbiome alterations, and immune dysregulation, whereas food allergy (FA) arises from the interplay of transcutaneous sensitization to food allergens and failure in the induction of oral tolerance. Skin epicutaneous sensitization is commonly involved in the development of AD and FA. Although clinical trials have been conducted to prevent AD or FA by applications of emollients on the skin after birth, the results are not consistent. For more effective preventive strategies, reliable biomarkers are required to identify high-risk individuals. Skin tape stripping (STS) is a non-invasive technique for identifying these biomarkers in the skin. By analyzing the stratum corneum collected via STS, researchers can gain molecular or cellular insights into the early pathogenesis and potential progression of AD and FA. This review aims to elucidate the critical aspects of AD and FA, underlying their pathogenesis, early manifestations, and STS's potential as a tool for identifying predictive non-invasive biomarkers in infants prior to onset of clinical disease.

Purpose: Limited knowledge exists regarding the psychosocial characteristics of young Asian children affected by food allergies (FAs) and their caregivers. This study aims to assess the usefulness of the Food Allergy Severity Score (FASS) system in evaluating the risk of emotional impacts on young children and caregivers who are dealing with severe FA.

Methods: Children between 2 and 10 years of age who were diagnosed with FA and following an elimination diet were enrolled in the study. The FASS, Korean Parenting Stress Index, and Korean Behavior Assessment System for Children-2 were used for evaluating the above mentioned risk.

Results: Among the 75 participants, 64.0% had a history of anaphylaxis, and 56.0% reported multiple FAs. A total of 160 cases of FASS was documented across 21 types of food and classified as mild (n = 5, 1.07), moderate (n = 100, 2.01-4.01), or severe (n = 55, 4.24-6.84). The concordance of calculated- and stakeholder interpreted-FASS was moderate (kappa 0.587). Children with severe FASS (sFASS) showed increased risk for functional communication (relative risk [RR], 1.57; 95% confidence interval [CI], 0.99-2.48) and increased parental reinforcement (RR, 1.40; 95% CI, 0.91-2.14). Their caregivers exhibited reduced levels of demandingness (RR, 0.59; 95% CI, 0.37-0.94) and role restriction (RR, 0.62; 95% CI, 0.39-0.98). Receiver operating characteristic curves suggested that functional communication (numeric FASS cutoff, 3.47; area under the curve [AUC], 0.695), withdrawal (cutoff, 3.40; AUC, 0.657), developmental social disorders (cutoff, 3.96; AUC, 0.648), and reinforces parent (cutoff, 3.15; AUC, 0.646) were possibly be affected.

Conclusions: The FASS provides an objective tool to assess pediatric FA severity. Early psychosocial intervention for young children with severe FASS and their caregivers may improve prognosis by identifying possible adaptive skill deficiencies and excessive parenting stresses.

Pregnancy is a risk factor for asthma exacerbation and may trigger new-onset asthma in nonasthmatics. This study evaluated the epidemiology of newly diagnosed asthma during pregnancy and the associated risk factors among previously nonasthmatic women. Twelve-year medical data from the Korean National Health Insurance claims database (from January 2007 to December 2018) of Korean women who gave birth between January 2012 and December 2015 were collected. Previously nonasthmatic women were defined as those who had not been diagnosed with asthma for at least 4 years before pregnancy. Asthma flare-up was defined as asthma diagnosed three times or more and treated at least once with an oral corticosteroid. A nested case-control study was performed, and then the derived risk factors were applied to whole study population. Among the nonasthmatic women, 7.5% experienced asthma during pregnancy including episodes requiring hospitalization and 18.6% of them visited emergency room. Older age, primiparity, multi-fetal pregnancy, and rhinitis were identified as the risk factors. Among the entire study population, moderate to severe rhinitis was a significant risk factor across all age groups, while primiparity with multi-fetal pregnancy was one for older pregnant women; 22.7% in those ≥ 34 years old experienced asthma flare-ups compared to only 3.5% in the < 34 age group. A substantial portion of pregnant women with no history of asthma experienced an asthma flare-up during pregnancy. Multi-fetal pregnancy as primiparity at a later age and moderate to severe rhinitis are risk factors for the new development of asthma.

Purpose: Asthma is a clinical syndrome with various underlying pathomechanisms and clinical phenotypes. Genetic, ethnic, and geographic factors may influence the differences in clinical presentation, severity, and prognosis. We compared the characteristics of asthma based on the geographical background by analyzing representative cohorts from the United States, Europe, South America, and Asia using the Severe Asthma Research Program (SARP), Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED), Program for Control of Asthma in Bahia (ProAR), and Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), respectively.

Methods: The clinical characteristics and medications for the SARP (n = 669), U-BIOPRED (n = 509), ProAR (n = 996), and COREA (n = 3,748) were analyzed. Subgroup analysis was performed for severe asthma.

Results: The mean age was highest and lowest in the COREA and SARP, respectively. The asthma onset age was lowest in the ProAR. The mean body mass index was highest and lowest in the SARP and COREA, respectively. Baseline pulmonary function was lowest and highest in the U-BIOPRED and COREA, respectively. The number of patients with acute exacerbation in the previous year was highest in U-BIOPRED. The mean blood eosinophil count was highest in COREA. The total immunoglobulin E was highest in the ProAR. The frequency of atopy was highest in the SARP. The principal component analysis plot revealed differences among all cohorts.

Conclusions: The cohorts from 4 different continents exhibited different clinical and physiological characteristics, probably resulting from the interplay between genetic susceptibility and geographical factors.