Purpose: Atopic dermatitis (AD) is a common inflammatory skin disease affecting 129 million people worldwide and is characterized by recurrent eczema, severe pruritus, and skin barrier damage. Previous studies on AD-sleep disorder associations were limited by small sample sizes or single-center designs, lacking large-scale epidemiological evidence. This study aimed to investigate the association between AD and sleep disorders using the UK Biobank prospective cohort and to explore effects of sex, race, and obesity on this relationship. Methods: A prospective cohort design was employed, including 329,796 participants for cross-sectional analysis and 330,875 for longitudinal analysis. Multivariable logistic regression and Cox proportional hazards models were used. Subgroup and sensitivity analyses were performed to validate robustness. Results: Cross-sectional analysis showed that AD was significantly associated with increased sleep disorder risk (adjusted odds ratio, 2.84; 95% confidence interval [CI], 2.54-3.18; P < 0.001), while the longitudinal analysis confirmed AD as an independent predictor of sleep disorders (adjusted hazard ratio, 1.51; 95% CI, 1.32-1.73; P < 0.001), with Kaplan-Meier curves further demonstrating a higher cumulative risk of sleep disorders in participants with AD. Subgroup analyses revealed stronger associations in females and participants with moderate body mass index (BMI), and sensitivity analyses validated the robustness of these findings. Conclusions: AD is an independent risk factor for sleep disorders, particularly in women and individuals with moderate BMI. Future research should further explore precision-targeted therapies and management strategies for specific populations.
Purpose: Activation of epidermal growth factor receptor (EGFR) signaling in airway epithelial cells leads to epithelial-mesenchymal transformation (EMT) and airway remodeling in asthma. However, the mechanism regulating EGFR expression is not fully understood. We hypothesized that cadherin-26 (CDH26), a highly expressed cadherin in airway epithelium, promotes airway remodeling via regulating EGFR signaling in asthma. Methods: The expression of CDH26 in airway brush cells of asthmatic patients was examined using quantitative polymerase chain reaction. Airway hyperresponsiveness and remodeling were assessed in the house dust mite (HDM)-sensitized and-challenged Cdh26-deficient mice. The role and mechanism of CDH26 in epidermal growth factor (EGF)-induced EMT were measured in cultured human bronchial epithelial BEAS-2B cells. Results: The expression of CDH26 in airway brush cells was significantly correlated with the thickness of airway basement membrane in asthma patients. Cdh26deficiency significantly reduced airway hyperresponsiveness and remodeling in HDM-sensitized and-challenged mouse model. In cultured human bronchial epithelial BEAS-2B cells, CDH26 knockdown inhibited EGF-induced EMT, whereas overexpression of CDH26 promoted EGF-induced EMT. Furthermore, CDH26 knockdown suppressed EGF-induced activation of EGFR signaling including phosphatidylinositol 3-kinase and AKT phosphorylation. By contrast, CDH26 overexpression intensified EGF-induced activation of EGFR signaling. Mechanistically, CDH26 knockdown promoted the proteasomal degradation of the EGFR. Conclusions: CDH26 promoted airway remodeling via stabilizing the epithelial expression of EGFR and sustaining the activation of EGFR signaling in asthma. Thus, CDH26 can be a potential therapeutic target for airway remodeling in asthma.
Purpose: Iodinated contrast media (ICM) are widely used in diagnostic imaging, but may trigger immediate hypersensitivity reactions, including anaphylaxis. Although human leukocyte antigen (HLA) associations have been proposed, genome-wide evidence remains limited. To identify genetic risk variants associated with ICM-induced anaphylaxis and evaluate their clinical utility. Methods: We conducted a genome-wide association study (GWAS) in 91 Korean patients with confirmed ICM-induced anaphylaxis (discovery, n = 67; replication, n = 24) and 1,565 controls. Genotyping used a Korean-specific single nucleotide polymorphism (SNP) array. Significant variants were replicated. HLA alleles were imputed in the combined dataset. Linkage disequilibrium (LD) among significant loci was analyzed. Cumulative genetic burden was assessed by summing risk alleles per individual. A Least Absolute Shrinkage and Selection Operator-based prediction model incorporated genetic and clinical variables. Results: Nineteen SNPs reached genome-wide significance and were replicated, including rs2229629 in HK2 (odds ratio, 5.02; P = 9.6 & times; 10-23), suggesting altered glycolysis. Additional variants were found near GABBR1, ZNF391, ATAT1, and HLA genes. Imputed HLA-DRB1*15:02 was significantly enriched in patients (41.8% vs. 5.9%, P = 5.21 & times; 10-17). LD analysis showed haplotypic clustering within HLA and non-HLA loci. A gene dosage effect was observed. The combined genetic-clinical model showed the highest predictive performance (area under the curve [AUC] = 0.888), exceeding genetic (AUC = 0.800) and clinical (AUC = 0.835) models. Conclusions: This first GWAS of ICM-induced anaphylaxis identifies susceptibility loci across metabolic, immune, and neuroimmune pathways. HK2 was most strongly associated, and HLA-DRB1*15:02 was robustly replicated.
Purpose: This study aimed to investigate the association of exposure to environmental pollutants and surrounding residential environments with the development of respiratory illnesses in 36-month-old children using data from the Korean CHildren's ENvironmental health Study. Methods: Demographic information and anthropometric measurements were obtained from the newborns. At 36 months of age, indoor environmental pollutant levels (particulate matter [PM10 and PM2.5], volatile organic compounds, and house dust mite allergens) were measured during home visits. Concentrations of both heavy metals (lead, mercury, and cadmium) in blood and metabolites of environmental hormones in urine were analyzed. A structured questionnaire was used to assess the presence of 6 common respiratory illnesses (infantile asthma, current asthma, recurrent wheezing, allergic rhinitis, bronchiolitis, and pneumonia) and residential environmental characteristics. Quantile-based g-computation was employed to estimate the joint association of exposure to mixtures of physical and chemical environmental factors with the risk of respiratory illnesses. Results: Among the total of 4,059 children, current allergic rhinitis was the most prevalent respiratory illness at 36 months. Compared with children without respiratory illnesses, those with respiratory illnesses showed significantly higher frequencies of exposure to environmental tobacco smoking and pet ownership. Dust mite concentrations were higher among children with recurrent wheezing and pneumonia. Mixture exposure analysis revealed that overall mixture exposure was positively associated with current allergic rhinitis, largely driven by lead and phthalate metabolites, and with pneumonia, mainly attributable to phthalate metabolites. Exposure to a mixture of multiple chemicals was positively associated with infantile asthma and current asthma. Conclusions: Direct and indirect exposures to environmental pollutants are closely associated with the development of respiratory illnesses in young children, and the surrounding residential environment during early childhood also plays a critical role in determining respiratory disease risk. These findings support the need for systematic and sustainable environmental management at both individual and community levels to protect children who are particularly vulnerable to environmental hazards.
Purpose: This study investigates the association between the C-reactive protein-triglycerideglucose index (CTI), indicative of systemic inflammation and insulin resistance, and all-cause mortality as well as asthma exacerbations in adults with asthma. Methods: Data from eight cycles of the US National Health and Nutrition Examination Survey (1999-2010 and 2015-2018) were analyzed. Adults aged >= 20 years were included, excluding those who were missing key variables. This resulted in 13,972 participants, of whom 1,832 had asthma. Participants were grouped into CTI tertiles. Participants self-reported exacerbations, and survival status was linked with the National Death Index. Complex survey weighting was applied to ensure national representativeness. Weighted multivariate logistic regression and Cox proportional hazards models assessed associations while adjusting for demographics, socioeconomic factors, body mass index, smoking, alcohol consumption, comorbidities, and laboratory indicators. Results: The fully adjusted model revealed no significant association between CTI and asthma prevalence (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.99-1.16; P = 0.078) but showed a strong association with all-cause mortality (hazard ratio [HR], 1.43; 95% CI, 1.12-1.81; P = 0.004). Patients in the highest CTI tertile exhibited a more than two-fold higher risk of mortality compared to those in the lowest tertile (HR, 2.22; 95% CI, 1.24-3.98; P = 0.007). Furthermore, higher CTI was associated with asthma exacerbation (OR, 1.23; 95% Conclusions: In this nationally representative sample, higher CTI was associated with higher all-cause mortality and higher odds of recent asthma exacerbations among adults with asthma, while no significant association with asthma prevalence was observed. CTI may help inform prognostic stratification in asthma and prospective studies are warranted.
