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.
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.
METHODS: Participants were recruited as a part of the Singapore and Malaysia cross-sectional genetic and epidemiological study (SMCSGES). Two independent cohorts were recruited: n = 564 serum samples were collected and serological assessment was performed against a panel of 16 crude inhalant allergens including house dust mite, pet, insect, pollen, and fungal allergens; n = 13 652 Singapore/Malaysia Chinese young adults were recruited and skin prick test was used to assess oil palm sensitization, which was tested for its association with the risk and severity of asthma, allergic rhinitis (AR), and atopic dermatitis (AD).
RESULTS: The sensitization rate of oil palm pollen is 9.6% in the n = 564 Singapore/Malaysia cohort. In the n = 13 652 Singapore/Malaysia Chinese cohort, oil palm sensitization significantly associates with increased risks of asthma (p = 1.34x10-4), AR (p = 2.91x10-13), and AD (p = 6.95x10-7). Asthmatic patients with oil palm sensitization have increased risks of wheezing (p = 0.00995), nocturnal cough (p = 0.0122), and exacerbations (p = 0.00139) in the past 12 months. AR patients with oil palm sensitization also have an increased risk of developing moderate-to-severe symptoms (p = 0.00113).
CONCLUSIONS: We have identified significant associations of oil palm sensitization with increased risks, exacerbations, and the severity of symptoms of allergic diseases in the tropical Southeast Asian region (Singapore/Malaysia).
METHODS: A prospective multicentre assessment of stable COPD (n=614) was undertaken in five hospitals across three countries: Singapore, Malaysia and Hong Kong. Clinical and serological assessment was performed against a panel of 35 fungal allergens including crude and recombinant Aspergillus and non-Aspergillus allergens. Unsupervised clustering and topological data analysis (TDA) approaches were employed using the measured sensitisation responses to elucidate if sensitisation subgroups exist and their related clinical outcomes.
RESULTS: Aspergillus fumigatus sensitisation was associated with increased exacerbations in COPD. Unsupervised cluster analyses revealed two "fungal sensitisation" groups. The first was characterised by Aspergillus sensitisation and increased exacerbations, poorer lung function and worse prognosis. Polysensitisation in this group conferred even poorer outcome. The second group, characterised by Cladosporium sensitisation, was more symptomatic. Significant numbers of individuals demonstrated sensitisation responses to only recombinant (as opposed to crude) A. fumigatus allergens f 1, 3, 5 and 6, and exhibited increased exacerbations, poorer lung function and an overall worse prognosis. TDA validated these findings and additionally identified a subgroup within Aspergillus-sensitised COPD of patients with frequent exacerbations.
CONCLUSION: Aspergillus sensitisation is a treatable trait in COPD. Measuring sensitisation responses to recombinant Aspergillus allergens identifies an important patient subgroup with poor COPD outcomes that remains overlooked by assessment of only crude Aspergillus allergens.
METHODS: A total of 1840 subjects (1117 cases/723 controls) completed an investigator-administered questionnaire as part of a cross-sectional study, which include socio-demographics, familial history, lifestyle factors, dietary habits, and acne history. Acne cases were further evaluated for their severity (n = 1051) and scarring (n = 1052) grades by a trained personnel.
RESULTS: Majority of the acne cases (up to 69%) had mild acne or Grade 1/2 scarring, while 21.6% had moderate/severe acne and 5.5% had Grade 3/4 scarring. Males had significantly higher risk of presenting with higher grades of acne scarring. Those who had acne, regardless of severity and scarring grades, had strong positive familial history (either in parents and/or sibling). Frequent consumption (most or all days) of foods that are commonly consumed during breakfast (butter, probiotic drinks, cereals and milk) decreased the risk for acne presentation and higher acne scarring, while periodic consumption (once/twice per week) of nuts and burgers/fast food decreased the risk for higher acne severity. Alcohol drinking was significantly associated with increased risk for acne presentation, while paternal, parental and household smoking were associated with reduced risk of more severe acne.
CONCLUSIONS: In conclusion, positive familial history is a strong predisposing factor in influencing acne presentation, severity and scarring. Frequent consumption of foods that are commonly consumed during breakfast is protective against acne presentation.
METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work.
RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost.
CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.
OBJECTIVES: This study aimed at describing the immunochemical properties of the BN allergens. Comparative studies between 3 commercially available sources (according to the country of origin) of BN were also made.
METHODS: Crude extracts of commercially available processed BN from Sarawak (Malaysia), Thailand, and Indonesia and fresh unprocessed BN from the caves of Sarawak were obtained by means of aqueous extraction. Specific IgE toward these sources were determined by using fluorescence allergosorbent tests (FASTs). Cross-reactivity studies between the 3 sources of commercially available processed BN were carried out by means of FAST inhibition. Immunochemical characterization by means of IgE immunoblot, periodate treatment, and heat stability studies were carried out on fresh unprocessed BN from Sarawak.
RESULTS: Serum from allergic patients showed differences in IgE binding to the 3 sources of commercially available BN, with the highest levels of specific IgE recorded with the Sarawak source (P
RESEARCH QUESTION: What is the occurrence and clinical relevance of Aspergillus sensitization and ABPA in BCO when compared with individuals with COPD or bronchiectasis without overlap?
STUDY DESIGN: Prospective, observational, cross-sectional study.
METHODS: We prospectively recruited 280 patients during periods of clinical stability with bronchiectasis (n = 183), COPD (n = 50), and BCO (n = 47) from six hospitals across three countries (Singapore, Malaysia, and Scotland). We assessed sensitization responses (as specific IgE) to a panel of recombinant Aspergillus fumigatus allergens and the occurrence of ABPA in relationship to clinical outcomes.
RESULTS: Individuals with BCO show an increased frequency and clinical severity of ABPA compared with those with COPD and bronchiectasis without overlap. BCO-associated ABPA is associated with more severe disease, higher exacerbation rates, and lower lung function when compared with ABPA occurring in the absence of overlap. BCO with a severe bronchiectasis severity index (BSI; > 9) is associated significantly with the occurrence of ABPA that is unrelated to underlying COPD severity.
CONCLUSIONS: BCO demonstrates a high frequency of ABPA that is associated with a severe BSI (> 9) and poor clinical outcomes. Clinicians should maintain a high index of suspicion for the potential development of ABPA in patients with BCO with high BSI.