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  1. El-Sayed ZA, Abramova I, Aldave JC, Al-Herz W, Bezrodnik L, Boukari R, et al.
    World Allergy Organ J, 2019;12(3):100018.
    PMID: 30937141 DOI: 10.1016/j.waojou.2019.100018
    Background: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features.

    Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries.

    Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16%) and reflected the ongoing need for education of both patients and referring physicians.

    Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications.

  2. Lim JJ, Lim YYE, Ng JY, Malipeddi P, Ng YT, Teo WY, et al.
    World Allergy Organ J, 2022 Dec;15(12):100722.
    PMID: 36438192 DOI: 10.1016/j.waojou.2022.100722
    BACKGROUND: Atopic Dermatitis (AD) is a highly pruritic, chronic-recurrent inflammatory skin condition associated with erythematous lesions that affect a significant proportion of the population. Although AD is a non-communicable disease, it can cause pain, unbearable itchiness, sleep disturbance, loss of work productivity, and reduced quality of life. As a heterogeneous disease, AD is influenced by multiple genes and environmental triggers. As such, it is imperative to gain a deeper insight into the intricate gene-environment relationship that results in the manifestation of AD.

    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.

  3. Wong QYA, Lim JJ, Ng JY, Malipeddi P, Lim YYE, Sio YY, et al.
    World Allergy Organ J, 2023 Mar;16(3):100757.
    PMID: 36968625 DOI: 10.1016/j.waojou.2023.100757
    BACKGROUND: Asthma is a chronic inflammatory disease of the airway characterized by respiratory symptoms: wheezing, shortness of breath, coughing, and chest tightness. Globally, asthma affects over 300 million individuals and carries high morbidity and mortality burden. Previous studies have estimated the prevalence of asthma; however, prevalence estimates have been changing over time. Here, in a population of young Chinese adults from Singapore, we aimed to obtain an updated prevalence of asthma and its phenotypes, and identify potential associated risk factors.

    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.

  4. Soh JY, Chiang WC, Huang CH, Woo CK, Ibrahim I, Heng K, et al.
    World Allergy Organ J, 2017;10(1):3.
    PMID: 28232856 DOI: 10.1186/s40413-016-0136-x
    BACKGROUND: Galacto-oligosaccharides (GOS) are prebiotics added to commercial milk formula of infants and mothers. In recent years, cases of allergy related to GOS in atopic children have been reported in the South East Asian region.

    CASE PRESENTATIONS: We describe a series of pregnant (n = 4) and lactating mothers (n = 2) who developed anaphylactic reactions after consumption of maternal milk formula containing GOS. All six subjects had pre-existing atopy and a positive skin prick test to GOS and 5/5 of the subjects who were tested had positive basophil activation tests to GOS. All of the mothers and their babies had normal neonatal outcomes after the reactions.

    CONCLUSIONS: The supplementation of GOS into milk and beverages in the Asian region should take into account the rare chance of allergenicity of GOS in the atopic population.

  5. Maspero J, De Paula Motta Rubini N, Zhang J, Sanclemente G, Amador JR, El Sayed MH, et al.
    World Allergy Organ J, 2023 Mar;16(3):100724.
    PMID: 37033301 DOI: 10.1016/j.waojou.2022.100724
    BACKGROUND: There are gaps in our understanding of the epidemiology of atopic dermatitis (AD) in adults.

    OBJECTIVE: To evaluate the prevalence and severity of AD in adults from countries/regions within Asia, Eurasia, Latin America, Middle East, and Russia.

    METHODS: This international, web-based survey was performed in Argentina, Brazil, China, Colombia, Egypt, Hong Kong, Israel, Malaysia, Mexico, Russia, Kingdom of Saudi Arabia (KSA), Singapore, Taiwan, Thailand, Turkey, and United Arab Emirates. Questionnaires were sent to adult members of online respondent panels for determination of AD and assessment of severity. A diagnosis of AD required respondents to meet the modified United Kingdom (UK) Working Party criteria and to self-report they had a physician diagnosis of AD. Severity of AD was determined using Patient-Oriented Scoring of Atopic Dermatitis (PO-SCORAD), Patient-Oriented Eczema Measure (POEM), and Patient Global Assessment (PGA).

    RESULTS: Among respondents by country/region the prevalence of AD ranged from 3.4% in Israel to 33.7% in Thailand. The prevalence was generally higher in females versus males. Severity varied by scale, although regardless of scale the proportion of respondents with mild and moderate disease was higher than severe disease. PGA consistently resulted in the lowest proportion of severe AD (range 2.4% China - 10.8% Turkey) relative to PO-SCORAD (range 13.4% China - 41.6% KSA) and POEM (range 5.1% China - 16.6% Israel).

    CONCLUSIONS: This survey highlights the importance of AD in adults, with high prevalence and high morbidity among respondents and emphasizes that AD is not just a disease of childhood-there is disease persistence and chronicity in adults.

  6. Wang HC, Djajalaksana S, Sharma L, Theerakittikul T, Lim HF, Yoo KH, et al.
    World Allergy Organ J, 2023 Oct;16(10):100823.
    PMID: 37869560 DOI: 10.1016/j.waojou.2023.100823
    BACKGROUND: The extent of short-acting Beta-2-agonist (β2-agonist) (SABA) use across Asian countries is not well documented. As part of the SABA use IN Asthma (SABINA) III study, we assessed SABA prescriptions and clinical outcomes in patients with asthma from Asia.

    METHODS: This cross-sectional study recruited patients (aged ≥12 years) with asthma from 8 Asian countries. Data on disease characteristics and asthma treatments were collected using electronic case report forms. Patients were classified by practice type (primary or specialist care) and investigator-defined asthma severity (per Global Initiative for Asthma [GINA] 2017 recommendations). The association of SABA prescriptions with clinical outcomes was analyzed using multivariable regression models.

    RESULTS: Overall, 3066 patients were analyzed, with a mean (standard deviation) age of 51.8 (16.7) years; of these patients, 2116 (69%) were female, 2517 (82.1%) had moderate-to-severe asthma and 2498 (81.5%) and 559 (18.2%) were treated in specialist and primary care, respectively. In total, 1423 (46.4%) patients had partly controlled/uncontrolled asthma, with 1149 (37.5%) patients experiencing ≥1 severe asthma exacerbation in the previous year. Overall, 800 (26.7%) patients were prescribed ≥3 SABA canisters in the previous year, which is regarded as overprescription and was associated with a significantly decreased odds of at least partly controlled asthma and increased incidence rates of severe exacerbations (P 

  7. Abdullah B, Kandiah R, Hassan NFHN, Ismail AF, Mohammad ZW, Wang Y
    World Allergy Organ J, 2020 Dec;13(12):100482.
    PMID: 33294114 DOI: 10.1016/j.waojou.2020.100482
    BACKGROUND: Primary care practitioners (PCPs), being the front liners, play an important role in treating allergic rhinitis (AR). As there is no proper tool to assess their perception, attitude, and practice in utilizing the guidelines, we aimed to develop and validate a new questionnaire for such purpose.

    METHODS: The development phase consists of both literature and expert panel review. The validation phase consists of content validity, face validity, and construct validity. Cronbach's alpha was used to verify internal consistency. The development phase produced a questionnaire with 3 domains: perception, attitude, and practice consisting of 60 items (PAP-PCP questionnaire). Item response theory analysis for perception demonstrated the difficulty and discrimination values were acceptable except for 3 items. Exploratory factor analysis for attitude and practice domains showed the psychometric properties were good except for 3 items in practice domain. Experts judgement was used to decide on the final selection of questionnaire which consists of 59 items.

    RESULTS: The final validated questionnaire has 3 domains with 59 items. All domains had Cronbach's alpha above 0.65 which was reliable. 302 physicians completed the questionnaire. 98% PCPs diagnosed AR based on clinical history. Although, majority agree AR guidelines is useful (67%), they had difficulty in using it to classify AR (54.9%) and determine AR severity (73.9%). Oral anti-histamines (first and second generation) were the most prescribed (>75%) followed by intranasal corticosteroids (59%) and combined intranasal corticosteroid and oral anti-histamine (51%). Majority agreed that treatment efficacy (81.8%), adverse effects (83.8%), fear of adverse effects (73.5%), route of administration (69.4%), dosing frequency (72.5%), taste (64.6%) and cost (73.5%) affect treatment compliance.

    CONCLUSIONS: The newly developed and validated questionnaire is a promising instrument in understanding the treatment gap in AR. Although further testing and refinement are needed, it provides an initial means for evaluating knowledge and understanding of PCPs in treating AR.

  8. Teo WY, Lim YYE, Sio YY, Say YH, Reginald K, Chew FT
    World Allergy Organ J, 2024 Feb;17(2):100869.
    PMID: 38298829 DOI: 10.1016/j.waojou.2023.100869
    BACKGROUND: Atopic dermatitis (AD) is a complex inflammatory disease with a strong genetic component. A singular approach of genome wide association studies (GWAS) can identify AD-associated genetic variants, but is unable to explain their functional relevance in AD. This study aims to characterize AD-associated genetic variants and elucidate the mechanisms leading to AD through a multi-omics approach.

    METHODS: GWAS identified an association between genetic variants at 6p21.32 locus and AD. Genotypes of 6p21.32 locus variants were evaluated against LOC100294145 expression in peripheral blood mononuclear cells (PBMCs). Their influence on LOC100294145 promoter activity was measured in vitro via a dual-luciferase assay. The function of LOC100294145 was then elucidated through a combination of co-expression analyses and gene enrichment with g:Profiler. Mendelian randomization was further used to assess the causal regulatory effect of LOC100294145 on its co-expressed genes.

    RESULTS: Minor alleles of rs116160149 and rs115388857 at 6p21.32 locus were associated with increased AD risk (p = 2.175 × 10-8, OR = 1.552; p = 2.805 × 10-9, OR = 1.55) and higher LOC100294145 expression in PBMCs (adjusted p = 0.182; 8.267 × 10-12). LOC100294145 expression was also found to be increased in those with AD (adjusted p = 3.653 × 10-2). The genotype effect of 6p21.32 locus on LOC100294145 promoter activity was further validated in vitro. Co-expression analyses predicted LOC100294145 protein's involvement in interleukin-27 and type 1 interferon signaling, which was further substantiated through mendelian randomization.

    CONCLUSION: Genetic variants at 6p21.32 locus increase AD susceptibility through raising LOC100294145 expression. A multi-omics approach enabled the deduction of its pathogenesis model comprising dysregulation of hub genes involved in type 1 interferon and interleukin 27 signaling.

  9. Sio YY, Victoria Nanong GA, Lim JA, Matta SA, Say YH, Teh KF, et al.
    World Allergy Organ J, 2024 Jan;17(1):100853.
    PMID: 38235258 DOI: 10.1016/j.waojou.2023.100853
    BACKGROUND: Elaeis guineensis (Ela g, oil palm) pollen is one of the most predominant species of inhalant allergens in the tropical Southeast Asia region; however, its association with the manifestation of allergic diseases remains largely unexplored. This study aimed to determine the sensitization pattern of oil palm pollen and associate this with the risk and severity of 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).

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