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Evaluating immune responses to pneumococcal vaccines

Thong BY, Pawankar R, Park HS, Abdul Latiff AH

Asia Pac Allergy, 2023 Sep;13(3):127-131.
PMID: 37744960 DOI: 10.5415/apallergy.0000000000000114

Streptococcus pneumoniae (pneumococcus) is a significant cause of bacterial infections ranging from mild infections affecting the respiratory tract such as otitis media and sinusitis to severe diseases including bacteremia, pneumonia, and invasive pneumococcal disease (IPD) (eg, meningitis, septic arthritis, and endocarditis). Pneumococcal vaccines were first developed in the 1970s as capsular pneumococcal polysaccharide vaccines, which were T-cell independent and hence lacked immunologic memory. Subsequently in the year 2000, pneumococcal conjugate vaccines (PCV) conjugated to a protein to increase immunogenicity were developed and made commercially available. The increasing number of pneumococcal serotypes identified and the expanding pipeline of PCV vaccines with improved immunogenicity have significantly reduced the morbidity and mortality associated with IPD in high-risk patients. Pneumococcal vaccines also play an important role in the diagnosis and immunophenotyping of children and adults with inborn errors of immunity (IEI) given the increasing diversity/heterogeneity of IEI presenting with primary and/or specific antibody deficiency. Other than the quantitation of serotype levels in routine clinical care, other measurements of immune response including the functional activity of antibodies, antibody avidity, cell-mediated immunity, and immunological memory remain limited to clinical trials during vaccine development.
Fulltext Methotrexate-associated nonalcoholic fatty liver disease with transaminitis in rheumatoid arthritis

Sakthiswary R, Chan GY, Koh ET, Leong KP, Thong BY

ScientificWorldJournal, 2014;2014:823763.
PMID: 24971392 DOI: 10.1155/2014/823763

BACKGROUND: The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore.
METHODS: Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis.
RESULTS: Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512).
CONCLUSION: The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

Study site: Tan Tock Seng Hospital, Singapore
Fulltext Asia-Pacific perspectives on the COVID-19 pandemic

Pawankar R, Thong BY, Tiongco-Recto M, Wang JY, Abdul Latiff AH, Thien F, et al.

Allergy, 2021 09;76(9):2998-2901.
PMID: 33948966 DOI: 10.1111/all.14894
Epidemiology, Management, and Treatment Access of Hereditary Angioedema in the Asia Pacific Region: Outcomes From an International Survey

Li PH, Pawankar R, Thong BY, Fok JS, Chantaphakul H, Hide M, et al.

J Allergy Clin Immunol Pract, 2023 Apr;11(4):1253-1260.
PMID: 36584968 DOI: 10.1016/j.jaip.2022.12.021

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease with significant morbidity and mortality for which early diagnosis and effective therapy are critical. Many Asia Pacific (AP) countries still lack access to diagnostic tests and evidence-based therapies. Epidemiologic data from the AP is needed to formulate regional guidelines to improve standards of care for HAE.
OBJECTIVE: To investigate the estimated minimal prevalence, needs, and potential interventions for the diagnosis and management of HAE in the AP.
METHODS: A structured questionnaire was distributed to representative experts from member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. Patient profiles and the presence of diagnostic facilities or tests, regional and national HAE guidelines, and patient support groups were reported and compared.
RESULTS: Completed questionnaires were received from 14 representatives of 12 member countries and territories, representing 46% of the world population. Overall minimal prevalence of HAE in the AP region was 0.02/100,000 population, with significant heterogeneity across different centers. Only one-half and one-third had registered on-demand and prophylactic medications, respectively. Few had patient support groups (58%) or regional guidelines (33%), and their existence was associated with the availability of HAE-specific medications. Availability of C1-inhibitor level testing was associated with a lower age at HAE diagnosis (P = .017).
CONCLUSIONS: Hereditary angioedema in the AP differs from that in Western countries. Hereditary angioedema-specific medications were registered in only a minority of countries and territories, but those with patient support groups or regional guidelines were more likely to have better access. Asia Pacific-specific consensus and guidelines are lacking and urgently needed.
Fulltext COVID-19 in the Asia Pacific: Impact on climate change, allergic diseases and One Health

Pawankar R, Thong BY, Recto MT, Wang JY, Abdul Latiff AH, Leung TF, et al.

Asia Pac Allergy, 2023 Mar;13(1):44-49.
PMID: 37389098 DOI: 10.5415/apallergy.0000000000000021

Climate change and environmental factors such as air pollution and loss of biodiversity are known to have a major impact not only on allergic diseases but also on many noncommunicable diseases. Coronavirus disease 2019 (COVID-19) resulted in many environmental changes during the different phases of the pandemic. The use of face masks, enhanced hand hygiene with hand rubs and sanitizers, use of personal protective equipment (gowns and gloves), and safe-distancing measures, reduced the overall incidence of respiratory infections and other communicable diseases. Lockdowns and border closures resulted in a significant reduction in vehicular traffic and hence environmental air pollution. Paradoxically, the use of personal protective equipment and disposables contributed to an increase in environmental waste disposal and new problems such as occupational dermatoses, especially among healthcare workers. Environmental changes and climate change over time may impact the exposome, genome, and microbiome, with the potential for short- and long-term effects on the incidence and prevalence of the allergic disease. The constant use and access to mobile digital devices and technology disrupt work-life harmony and mental well-being. The complex interactions between the environment, genetics, immune, and neuroendocrine systems may have short- and long-term impact on the risk and development of allergic and immunologic diseases in the future.
Asia Pacific Association of Allergy Asthma and Clinical Immunology White Paper 2020 on climate change, air pollution, and biodiversity in Asia-Pacific and impact on allergic diseases

Pawankar R, Wang JY, Wang IJ, Thien F, Chang YS, Latiff AHA, et al.

Asia Pac Allergy, 2020 Jan;10(1):e11.
PMID: 32099833 DOI: 10.5415/apallergy.2020.10.e11

Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on a variety of chronic noncommunicable diseases in particular respiratory and cardiovascular diseases. The extent of air pollution both outdoor and indoor air pollution and climate change including global warming is increasing-to alarming proportions particularly in the developing world especially rapidly industrializing countries worldwide. In recent years, Asia has experienced rapid economic growth and a deteriorating environment and increase in allergic diseases to epidemic proportions. Air pollutant levels in many Asian countries especially in China and India are substantially higher than are those in developed countries. Moreover, industrial, traffic-related, and household biomass combustion, indoor pollutants from chemicals and tobacco are major sources of air pollutants, with increasing burden on respiratory allergies. Here we highlight the major components of outdoor and indoor air pollutants and their impacts on respiratory allergies associated with asthma and allergic rhinitis in the Asia-Pacific region. With Asia-Pacific comprising more than half of the world's population there is an urgent need to increase public awareness, highlight targets for interventions, public advocacy and a call to action to policy makers to implement policy changes towards reducing air pollution with interventions at a population-based level.
Fulltext Diagnostic procedures & practices in drug allergy/hypersensitivity: a survey of 13 Asian countries

Tang MM, Fok JS, Thong BY, Yun J, Li PH, Kang HR, et al.

Asia Pac Allergy, 2020 Oct;10(4):e36.
PMID: 33178561 DOI: 10.5415/apallergy.2020.10.e36

Background: The issues and challenges in the diagnosis of drug allergy/hypersensitivity among children and adults in Asia are likely to be different from non-Asian countries.
Objective: To study the diagnostic modalities used in the evaluation and management of drug allergy/drug hypersensitivity reactions (DHRs) among member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI).
Methods: A questionnaire comprising 41 questions was circulated electronically to member societies and individual members of APAAACI between January 23, 2020 and March 6, 2020.
Results: Twenty-six respondents from 15 member societies and 1 individual member responded. European DHR guidelines were most commonly used. Skin prick and intradermal testing was used by 100%, with only 60% having access to commercial penicillin skin test reagents. In vitro-speciﬁc IgE tests were used by 75%, and basophil activation test by 56.3% for immediate DHR. Patch tests were used by 75% in contrast to lymphocyte transformation tests by 25% for nonimmediate DHR. Drug provocation tests were used by 68.8%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (93.3%). Human leukocyte antigen (HLA) genotype testing was mandatory among 25% respondents before new carbamazepine prescriptions, and 8.3% for allopurinol prescriptions.
Conclusions: There was increased use of skin testing for iodinated contrast media hypersensitivity and patch testing for nonimmediate DHR. HLA genotype testing prior to new carbamazepine, allopurinol and abacavir prescriptions remain variable despite strong associations for severe cutaneous adverse reactions with Asian ethnicity. Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across APAAACI member societies.
Drug hypersensitivity reactions in Asia: regional issues and challenges

Thong BY, Lucas M, Kang HR, Chang YS, Li PH, Tang MM, et al.

Asia Pac Allergy, 2020 Jan;10(1):e8.
PMID: 32099830 DOI: 10.5415/apallergy.2020.10.e8

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.