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.
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: 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.
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.
OBJECTIVE: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI.
METHODS: This is a worldwide study, conceived by the World Allergy Organization (WAO) Inborn Errors of Immunity Committee. A questionnaire was developed and pilot-tested and was sent via email to collect data from 61 immunology centers known to treat pediatric and/or adult IEI patients in 41 countries. In addition, a query was submitted to The United States Immunodeficiency Network (USIDNET) at its website.
RESULTS: Thirty centers in 23 countries caring for a total 8450 IEI patients responded. The USIDNET dataset included 2332 patients. Data from responders showed that a median (IQR) of 16.3% (10-28.8%) of patients experienced allergic diseases during the course of their IEI as follows: 3.6% (1.3-11.3%) had bronchial asthma, 3.6% (1.9-9.1%) atopic dermatitis, 3.0% (1.0-7.8%) allergic rhinitis, and 1.3% (0.5-3.3%) food allergy. As per the USIDNET data, the frequency of allergy among IEI patients was 68.8% (bronchial asthma in 46.9%). The percentage of IEI patients who presented initially with allergic disorders was 8% (5-25%) and diagnosis delay was reported in 7.5% (0.9-20.6%). Predominantly antibody deficiencies had the highest frequency of allergic disease followed by combined immunodeficiency with a frequency of 40.3% (19.2-62.5%) and 20.0% (10-32%) respectively. As per the data of centers, anaphylaxis occurred in 25/8450 patients (0.3%) whereas per USIDNET dataset, it occurred in 249/2332 (10.6%); drugs and food allergy were the main causes in both datasets.
CONCLUSIONS: This multinational study brings to focus the relation between allergic diseases and IEI. Major allergies do occur in IEI patients but were less frequent than the general population. Initial presentation with allergy could adversely affect the timely diagnosis of IEI. There is a need for policies to raise awareness and educate primary care and other referring specialties on the association of allergic diseases with IEI. This study provides a network among centers for future prospective studies in the field.
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
METHODS: A group of 11 experts in immunology and otorhinolaryngology from APAC provided information regarding their practices and experiences in the management of AR through an online survey. The group then discussed the barriers and solutions for the implementation of patient-centred care across the patient journey in a face-to-face meeting.
RESULTS: Key barriers to the implementation of patient-centred care for AR in APAC included a lack of patient awareness of the condition and treatment options, low adherence to treatments, financial constraints for patients, and time constraints for physicians. The solutions proposed include improving the knowledge of the patients about their conditions, the use of shared decision-making, the consideration of patient characteristics when choosing treatments, and the use of outcome measures to aid the optimisation of patient care. We provide specific recommendations for clinical practice.
CONCLUSION: A greater focus on patient-centred approaches has the potential to improve the management of AR in APAC. More emphasis should be placed on each patient's specific health needs and desired outcomes.
METHODS: In total, 12 872 individuals, with mean age 22.1 years (SD = 4.8), were recruited from universities in Singapore and Malaysia. Each participant provided epidemiological data based on an investigator-administered questionnaire adapted from the validated International Study of Allergies and Asthma in Childhood (ISAAC) protocol, and atopy status was determined using a skin prick test (SPT) performed by qualified staff. AR was diagnosed according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and a positive SPT result.
RESULTS: Sensitization (determined by SPT) to either Blomia tropicalis or Dermatophagoides pteronyssinus was prevalent in 66.5% of the cohort. Current rhinitis (manifesting ≥2 rhinitis symptoms, within the past 12 months) was observed in 48.9% of our population, while AR, which included atopy status, was estimated at 39.4%. Sneezing and rhinorrhea were the most common symptoms among AR cases. AR prevalence decreased with increasing age (OR: 0.979; 95% CI: 0.969-0.989), while male gender (OR: 2.053; 95% CI: 1.839-2.294), and a parental history of allergic diseases (OR: 2.750; 95% CI: 2.284-3.316) were significant risk factors for AR. Upon adjustment for age, gender, and parental history, housing type (OR: 0.632; 95% CI: 0.543-0.736) and income level (>$6000 vs
METHODS: Information and opinions regarding the barriers and solutions to the implementation of patient-centred approaches to the management of CU were gathered from a group of 13 expert dermatologists and allergist/immunologists from APAC through surveys and a face-to-face meeting.
RESULTS: Barriers identified there included a lack of awareness of CU amongst patients, delays in consulting healthcare providers, financial constraints, and low adherence. Particular issues raised included a lack of suitable online information for patients (83% of experts), and patients accessing oral corticosteroids without a prescription. Compliance issues were also identified as key reasons for inadequate responses to treatments (67% of experts). Solutions proposed by the authors were improving patients' knowledge about their condition (92% strongly agree, 8% agree), physicians' consideration of patient characteristics when choosing treatments (92% strongly agree, 8% agree), implementing shared decision-making (85% strongly agree, 15% agree), and using patient-reported outcome measures (70% strongly agree, 23% agree).
CONCLUSION: Expert opinion within APAC supports the use of patient-centred approaches to improve the management of CU. We provide several recommendations focusing on patient education and involvement in disease management as well as disease monitoring methods that can be implemented by physicians in APAC.
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.
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.
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.
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: Seven- to eight-week old female BALB/c mice were fed either normal (ND) or HP diet and were sensitized with ovalbumin intraperitoneally followed by intranasal challenge. Allergic sensitization was tested by measuring anti-ovalbumin (OVA) IgE, IgG1, and IgG2a antibodies. Cytokine levels were tested by multiplex ELISA in splenocyte supernatants after stimulation. Airway inflammation was tested by measuring total and differential cell counts in bronchoalveolar lavage fluid and by measuring bronchial mucus production, goblet cell hyperplasia and perivascular and peribronchial inflammation severity scores by histologic examination.
RESULTS: Mice fed HP diet had a significant increase in weight and higher levels of OVA-specific IgE and IgG1 antibodies compared to the ND group (P-values 0.002, 0.007 and <0.001, respectively). In addition, they showed a selective Th2 bias in cultured splenocyte supernatants compared to the ND group as demonstrated by higher IL-4 and IL-6 levels (P-values <0.001 and 0.011, respectively) and higher ratios of Th2 to Th1 cytokines. However, the level of airway inflammation was comparable between both groups.
CONCLUSIONS: HP diet increases the risk of allergic sensitization though increase in Th2 cytokines. Efforts should be made to define the upper limit of protein in the diet that does not predispose to allergic sensitization. The effect of diet on health should remain a focus of research for the establishment of optimal health and resilience.