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Background: We see increasing evidence that dietary and nutrients factors play a pivotal role in allergic diseases and recent global findings suggest that dietary habits influence the pathogenesis of atopic dermatitis (AD). Frequent consumption of fast food diets is associated with AD development. Despite the rising prevalence of AD in Asia, efforts in investigating the role of dietary habits and AD in adults are still lacking. Methods: We evaluated the association between the dietary intake of 16 food types and AD manifestations using our Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) population. Dietary habits profiles of 11,494 young Chinese adults (1,550 AD cases/2,978 non-atopic controls/6,386 atopic controls) were assessed by an investigator-administered questionnaire. AD cases were further evaluated for their chronicity (550 chronic) and severity (628 moderate-to-severe). Additionally, we derived a novel food index, Quality of Diet based on Glycaemic Index Score (QDGIS), to examine the association between dietary intake of glycaemic index (GI) and various AD phenotypes. Results: The majority of AD subjects are distributed in the good (37.1%) and moderate (36.2%) QDGIS classes. From the multivariable analyses for age and gender, a moderate QDGIS class was significantly associated with a lower odds of AD (adjusted odds ratio (AOR): 0.844; 95% confidence interval (CI): 0.719–0.991; p < 0.05) and moderate-to-severe AD (AOR: 0.839; 95% CI: 0.714–0.985; p < 0.05). A good QDGIS class was only significantly associated with a lower odds of chronic AD (AOR: 0.769; 95% CI: 0.606–0.976; p < 0.05). Among high GI foods, frequent consumption of burgers/fast food was strongly associated with an increased risk of chronic and moderate-to-severe AD. Among low GI foods, increased intake frequencies of fruits, vegetables, and pulses decreased the odds of AD. Finally, we identified significant associations between frequent seafood, margarine, butter, and pasta consumption with an increased odds of AD despite them having little GI values. Conclusion: While genetic components are well-established in their risks associated with increased AD prevalence, there is still a lack of a focus epidemiology study associating dietary influence with AD. Based on the first allergic epidemiology study conducted here in Singapore and Malaysia, it laid the groundwork to guide potential dietary interventions from changing personal dietary habits. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have indicated the ERBB2 genetic variants in the 17q12 locus might be associated with asthma; however, the functional effects of these variants on asthma risk remain inconclusive. This study aimed to characterize the functional roles of asthma-associated ERBB2 single nucleotide polymorphisms (SNPs) in asthma pathogenesis by performing genetic association and functional analysis studies. Methods: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). Genotype-phenotype associations were assessed by performing a genotyping assay on n = 4,348 ethnic Chinese individuals from the SMCSGES cohort. The phosphorylation levels of receptors and signaling proteins in the MAPK signaling cascades, including ErbB2, EGFR, and ERK1/2, were compared across the genotypes of asthma-associated SNPs through in vitro and ex vivo approaches. Results: The ERBB2 tag-SNP rs1058808 was significantly associated with allergic asthma, with the allele "G" identified as protective against the disease (adjusted logistic p = 6.56 × 10−9, OR = 0.625, 95% CI: 0.544–0.718). The allele "G" of rs1058808 resulted in a Pro1170Ala mutation that results in lower phosphorylation levels of ErbB2 in HaCat cells (p < 0.001), whereas the overall ERBB2 mRNA expression and the phosphorylation levels of EGFR remained unaffected. In the SMCSGES cohort, individuals carrying the genotype "GG" of rs1058808 had lower phosphorylated ERK1/2 proteins in the MAPK signaling cascade. A lower phosphorylation level of ERK1/2 was also associated with reduced asthma risk. Conclusions: The present findings highlighted the involvement of a functional exonic variant of ERBB2 in asthma development via modulating the MAPK signaling cascade. [ABSTRACT FROM AUTHOR]

Introduction: The arachidonic acid (AA) pathway plays a crucial role in allergic inflammatory diseases; however, the functional roles of allergy-associated single nucleotide polymorphisms (SNPs) in this pathway remain incompletely illustrated. Methods: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). We performed population genotyping on n = 2,880 individuals from the SMCSGES cohort to assess the associations of SNPs in the AA pathway genes with asthma and allergic rhinitis (AR). Spirometry assessments were performed to identify associations between SNPs and lung function among n = 74 pediatric asthmatic patients from the same cohort. Allergy-associated SNPs were functionally characterized using in vitro promoter luciferase assay, along with DNA methylome and transcriptome data of n = 237 peripheral blood mononuclear cell (PBMC) samples collected from a subset of the SMCSGES cohort. Results: Genetic association analysis showed 5 tag-SNPs from 4 AA pathway genes were significantly associated with asthma (rs689466 at COX2, rs35744894 at hematopoietic PGD2 synthase (HPGDS), rs11097414 at HPGDS, rs7167 at CRTH2, and rs5758 at TBXA2R, p < 0.05), whereas 3 tag-SNPs from HPGDS (rs35744894, rs11097414, and rs11097411) and 2 tag-SNPs from PTGDR (rs8019916 and rs41312470) were significantly associated with AR (p < 0.05). The asthma-associated rs689466 regulates COX2 promoter activity and associates with COX2 mRNA expression in PBMC. The allergy-associated rs1344612 was significantly associated with poorer lung function, increased risks of asthma and AR, and increased HPGDS promoter activity. The allergy-associated rs8019916 regulates PTGDR promoter activity and DNA methylation levels of cg23022053 and cg18369034 in PBMC. The asthma-associated rs7167 affects CRTH2 expression by regulating the methylation level of cg19192256 in PBMC. Conclusions: The present study identified multiple allergy-associated SNPs that modulate the transcript expressions of key genes in the AA pathway. The development of a "personalized medicine" approach with consideration of genetic influences on the AA pathway may hopefully result in efficacious strategies to manage and treat allergic diseases. [ABSTRACT FROM AUTHOR]

While the IGF1/FoxO1/mTORC1 signalling pathway is a well‐established nutrigenomic link between high glycaemic index (GI)/glycaemic load (GL) diet and acne vulgaris, other signalling pathways remain elusive. Therefore, we aimed to investigate other genes that are involved in the high GI/GL diet‐acne link, using our Singapore/Malaysia population epidemiological, genomics and transcriptomics data. High GI/GL dietary habit of 3207 acne cases (1869 and 1341 further classified into severity and scarring grades, respectively) and 2521 controls were evaluated based on Quality of Diet based on Glycaemic Index Score (QDGIS). Overlapping concordant differentially expressed genes (DEGs) between acne case–controls and QDGIS poor‐moderate/good classes were identified from whole‐transcriptome sequencing data of PBMC of a subset of participants. Finally, we assessed the expression quantitative trait loci (eQTL) association of single nucleotide polymorphisms (SNPs) of the concordant DEGs. Daily intake of fruits significantly reduced the risk of acne presentation, severity and scarring by up to 48.5%. Those with good QDGIS had significantly lower risk of mild and moderate/severe acne, and grade 1/2 acne scarring. Sequential filtering identified four overlapping concordant DEGs that were significantly associated with acne and QDGIS, namely GOLGA7B, SNCB, LOC102723849 and LOC283683. Combining transcriptome and genetic association data, we identified intronic SNP rs1953947 in GOLGA7B as an eQTL for acne. In conclusion, we identified GOLGA7B as a plausible novel gene that links high GI/GL with acne, and hence propose a model for the involvement of Golga7b in high GI/GL diet‐acne pathogenesis, which includes palmitoyl acyltransferase zDHHC5, fatty acid translocase CD36 and palmitic acid. [ABSTRACT FROM AUTHOR]

Background and Objective: Sleep disruption has been shown to affect immune function and thus influence allergic disease manifestation. The specific effects of sleep on allergic diseases, however, are less well-established; hence, in a unique population of young Chinese adults, we investigated the association between sleep and allergic disease., Methods: Young Chinese adults recruited from Singapore in the Singapore/Malaysia Cross-Sectional Genetic Epidemiology Study (SMCGES) were analyzed. We used the International Study of Asthma and Allergies in Childhood (ISAAC) protocol and a skin prick test to determine atopic dermatitis (AD), allergic rhinitis (AR), and asthma status. Information regarding total sleep time (TST) and sleep quality (SQ) was also obtained., Results: Of 1558 participants with a mean age of 25.0 years (SD = 7.6), 61.4% were female, and the mean total sleep time (TST) was 6.8 h (SD = 1.1). The proportions of AD, AR, and asthma were 24.5% (393/1542), 36.4% (987/1551), and 14.7% (227/1547), respectively. 59.8% (235/393) of AD cases suffered from AD-related sleep disturbances, 37.1% (209/564) of AR cases suffered from AR-related sleep disturbances, and 25.1% (57/227) of asthma cases suffered from asthma-related sleep disturbances. Only asthma cases showed a significantly lower mean TST than those without asthma (p = 0.015). Longer TST was significantly associated with lower odds of AR (OR = 0.905, 95% CI = 0.820-0.999) and asthma (OR = 0.852, 95% CI = 0.746-0.972). Linear regression analyses showed that lower TST was significantly associated with asthma (β =  - 0.18, SE = 0.076, p-value = 0.017), and AR when adjusted for AR-related sleep disturbances (β =  - 0.157, SE = 0.065, p-value = 0.016). Only sleep disturbances due to AR were significantly associated with a poorer SQ (OR = 1.962, 95% CI = 1.245-3.089)., Conclusions: We found that sleep quality, but not sleep duration was significantly poorer among AD cases, although the exact direction of influence could not be determined. In consideration of the literature coupled with our findings, we posit that TST influences allergic rhinitis rather than vice versa. Finally, the association between TST and asthma is likely mediated by asthma-related sleep disturbances, since mean TST was significantly lower among those with nighttime asthma symptoms. Future studies could consider using objective sleep measurements coupled with differential expression analysis to investigate the pathophysiology of sleep and allergic diseases., (© 2024. The Author(s).)

Introduction: Allergic sensitisation to fungi such as Aspergillus are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear., Methods: Patients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD. We identified key fungi in outdoor air and developed specific-IgE assays against the top culturable fungi, linking sensitisation responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of 11 COPD patients and linked to clinical outcome., Results: High frequencies of sensitisation to a broad range of allergens occur in COPD. Fungal sensitisation associates with frequent exacerbations, and unsupervised clustering reveals a "highly sensitised fungal predominant" subgroup demonstrating significant symptomatology, frequent exacerbations and poor lung function. Outdoor and indoor environments serve as important reservoirs of fungal allergen exposure in COPD and promote a sensitisation response to outdoor air fungi. Indoor (home) environments with high fungal allergens associate with greater COPD symptoms and poorer lung function, illustrating the importance of environmental exposures on clinical outcomes in COPD., Conclusion: Fungal sensitisation is prevalent in COPD and associates with frequent exacerbations representing a potential treatable trait. Outdoor and indoor (home) environments represent a key source of fungal allergen exposure, amenable to intervention, in "sensitised" COPD., Competing Interests: Conflict of interest: P.Y. Tiew has nothing to disclose. Conflict of interest: F.W.S. Ko has nothing to disclose. Conflict of interest: S.L. Pang has nothing to disclose. Conflict of interest: S.A. Matta has nothing to disclose. Conflict of interest: Y.Y. Sio has nothing to disclose. Conflict of interest: M.E. Poh has nothing to disclose. Conflict of interest: K.J.X. Lau has nothing to disclose. Conflict of interest: M. Mac Aogain has nothing to disclose. Conflict of interest: T.K. Jaggi has nothing to disclose. Conflict of interest: F.X. Ivan has nothing to disclose. Conflict of interest: N.E. Gaultier has nothing to disclose. Conflict of interest: A. Uchida has nothing to disclose. Conflict of interest: D.I. Drautz-Moses has nothing to disclose. Conflict of interest: H. Xu has nothing to disclose. Conflict of interest: M.S. Koh has nothing to disclose. Conflict of interest: D.S.C. Hui has nothing to disclose. Conflict of interest: A. Tee has nothing to disclose. Conflict of interest: J.A. Abisheganaden has nothing to disclose. Conflict of interest: S.C. Schuster has nothing to disclose. Conflict of interest: F.T. Chew has nothing to disclose. Conflict of interest: S.H. Chotirmall has nothing to disclose., (Copyright ©ERS 2020.)

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a "research priorities" consensus statement for bronchiectasis.Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S-28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes.The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus , Cryptococcus and Clavispora Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus- associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations.The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus -associated disease should be considered even in apparently stable patients., Competing Interests: Conflict of interest: F.T. Chew reports personal fees from Sime Darby Technology Center, Olam International and First Resources Ltd, outside the submitted work. J.D. Chalmers reports grants from AstraZeneca, grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Bayer Healthcare and Grifols, and personal fees from Napp, outside the submitted work., (Copyright ©ERS 2018.)