OBJECTIVES: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.
METHODS: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles ("immunoallertypes"), were determined.
MEASUREMENTS AND MAIN RESULTS: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. "Sensitized bronchiectasis" was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome.
CONCLUSIONS: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a "treatable trait" permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.
RESULTS: Our results indicate that the SHELL markers can theoretically reduce the major losses due to dura contamination of tenera planting material. However, these markers cannot distinguish illegitimate tenera, which reduces the value of having bred elite tenera for commercial planting and in the breeding programme, where fruit form is of limited utility, and incorrect identity could lead to significant problems. We propose an optimised approach using SNPs for routine quality control.
CONCLUSIONS: Both dura and tenera contamination can be identified and removed at or before the nursery stage. An optimised legitimacy assay using SNP markers coupled with a suitable sampling scheme is now ready to be deployed as a standard control for seed production and breeding in oil palm. The same approach will also be an effective solution for other perennial crops, such as coconut and date palm.
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.
METHODS: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47). Longitudinal mycobiome analysis was performed during and following COPD exacerbations (n=34), and examined in terms of exacerbation frequency, 2-year mortality and occurrence of serum specific IgE (sIgE) against selected fungi.
RESULTS: A distinct mycobiome profile is observed in COPD compared with controls as evidenced by increased α-diversity (Shannon index; p<0.001). Significant airway mycobiome differences, including greater interfungal interaction (by co-occurrence), characterise very frequent COPD exacerbators (three or more exacerbations per year) (permutational multivariate ANOVA; adjusted p<0.001). Longitudinal analyses during exacerbations and following treatment with antibiotics and corticosteroids did not reveal any significant change in airway mycobiome profile. Unsupervised clustering resulted in two clinically distinct COPD groups: one with increased symptoms (COPD Assessment Test score) and Saccharomyces dominance, and another with very frequent exacerbations and higher mortality characterised by Aspergillus, Curvularia and Penicillium with a concomitant increase in serum sIgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher 2-year mortality.
CONCLUSION: The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality.
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.
OBJECTIVE: To investigate the functional effect of 4q21 SNPs on AR risk by conducting cohort-based functional genomics and genetic association analyses.
METHODS: The associations between 4q21 SNPs and mRNA expression levels of three 4q21-associated genes (SDAD1, NAAA and CXCL9) in peripheral blood mononuclear cells (PBMCs) were assessed in a Singapore/Malaysia Chinese cohort (n = 291). Exon expression levels of these genes in PBMCs were tested against the tag-SNP genotypes in a Singapore Chinese cohort (n = 30). Serum protein levels of these genes were assessed with tag-SNP genotypes in a Singapore Chinese cohort (n = 193). SNP functions were characterized through luciferase assay. In a Singapore Chinese cohort (n = 1794), we confirmed the associations between functional SNPs and AR.
RESULTS: Forty SNPs in 4q21 showed significant associations with NAAA (but not SDAD1 or CXCL9) mRNA expression in PBMCs, of which were tagged by two tag-SNPs, rs17001237 and rs2242470. Both tag-SNPs rs2242470 and rs12648687 (a proxy for rs17001237) were also significantly associated with the expression level of NAAA exon 1. Tag-SNP rs12648687 was correlated with serum NAAA level. A four promoter SNPs-haplotype tagged by rs17001237 influenced the NAAA promoter activity in HEK293T cells. Lastly, individuals carrying the risk allele A of rs12648687 exhibited significantly higher AR risk in the Singapore Chinese population.
CONCLUSIONS & CLINICAL RELEVANCE: The rs17001237 linkage set SNPs in the 4q21 locus are associated with NAAA expression at both gene and protein levels ex vivo, have functional consequences in vitro and contribute to AR susceptibility in our study population. Our findings provided a better understanding of the genetic mechanism that contributes to AR pathogenesis.
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.
METHODS: There are 3 objectives in our study. We first aim to update the epidemiological status of AD amongst young adults in Singapore and Malaysia, in particular amongst the Chinese ethnic background. Next, we re-evaluated the possible associated risk factors, identified in our previous meta-analysis and review studies, on the current cohort. Finally, we described here a detailed disease presentation and symptoms profile of our Singapore and Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) cohort, which forms the base population for the discovery of associated genetic factors in relation to asthma, allergic diseases and skin conditions. Based on a skin prick test (SPT) and investigator-administered medical history responses, we assessed the AD profiles of 11 494 participants and the significant modifiable and non-modifiable factors associated with disease presentation.
RESULTS: The prevalence of AD in the combined population was 13.5%. Chronic and moderate/severe AD were observed in 35.5% and 40.5% of the individuals with AD, respectively. Family history of atopic diseases, prior history of drug allergies, a history of acne, increased household family monthly income, higher number of individuals in the shared household, parental education, sedentary lifestyle, physical activities, alcoholic consumption, and even quality of diet was significantly associated with AD presentation, chronicity, and severity. Among all the factors evaluated, family and personal history of atopic diseases imposed the strongest associated risk.
CONCLUSIONS: These findings supported our previous review studies and affirmed that familial history or genetic factors critically influence the development of AD in our population and environment. Environmental and other modifiable factors can also trigger AD throughout the lifetime of individuals who have especially inherited the atopic disease disposition. A better understanding of how these risk factors affect AD individuals in our population can facilitate disease surveillance, monitor disease control, and serve as a description for our future genetic epidemiology studies.
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: The Singapore/Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) is an ongoing study which uses established ISAAC guidelines to collect epidemiological data and information pertaining to allergic diseases such as asthma. Responses from young Chinese adults recruited in the National University of Singapore were analyzed.
RESULTS: Lifetime asthma prevalence rate was estimated at 19.1% (2049/10,736), while current asthma prevalence rate was estimated at 6.3% (679/10,736). For ever asthma, the most important risk factor was a parental history of asthma. Increased consumption of pulses (aOR: 0.822, 95% CI: 0.706-0.958) was associated with a lowered odds of ever asthma, but cereals (aOR: 1.256, 95% CI: 1.006-1.580), pasta (aOR: 1.265, 95% CI: 1.027-1.553), butter (aOR: 1.350, 95% CI: 1.113-1.632), and margarine (aOR: 1.343, 95% CI: 1.081-1.660) were associated with a higher risk of ever asthma. Increased television/computer usage was associated with a decreased risk of ever asthma (aOR: 0.448, 95% CI: 0.367-0.545). Conversely, genetic factors had a lower strength of effect on current asthma (parental history of asthma - OR: 1.465, 95% CI: 1.135-1.888) as compared to ever asthma. Only increased potato consumption was significantly associated with an increased risk of current asthma (most or all days per week vs never or only occasionally - aOR: 1.577, 95% CI: 1.145-2.180). Physical activity (aOR: 0.693, 95% CI: 0.542-0.885) was associated with a lower odds of asthma, while second-hand smoke exposure was associated with an increased risk for current asthma (aOR: 1.435, 95% CI: 1.001-2.047).
CONCLUSION: Overall, the prevalence of lifetime asthma and current asthma among young Chinese adults was 19.1% and 6.3%, higher than that of previous studies. Our results suggested a stronger association between genetic factors and ever asthma as compared to current asthma. Parental asthma was the most important intrinsic epidemiological factor for asthma manifestation, while various foods, physical activity levels, and television or computer usage were also significantly associated with asthma. Future studies should consider risk factors in conjunction with other accompanying variables given the potential interactions between them, to discern the effects of environment and lifestyle on asthma more distinctly.
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.
SUMMARY: Cockroach allergy is an important risk factor for allergic rhinitis in the tropics, that disproportionately affects children and young adults and those living in poor socio-economic environments. Immunotherapy would provide long-lasting improvement in quality of life, with reduced medication intake. However, the present treatment regime is long and has a risk of adverse effects. In addition, cockroach does not seem to have an immuno-dominant allergen, that has been traditionally used to treat allergies from other sources. Future trends of cockroach immunotherapy involve precision diagnosis, to correctly identify the offending allergen. Next, precision immunotherapy with standardized allergens, which have been processed in a way that maintains an immunological response without allergic reactions. This approach can be coupled with modern adjuvants and delivery systems that promote a Th1/Treg environment, thereby modulating the immune response away from the allergenic response.