Health-Related Quality of Life of Patients and Families with Primary Immunodeficiency in Malaysia: a Cross-Sectional Study.

PURPOSE: Primary immunodeficiency disease (PID) affects various aspects of a patient's life. However, the health-related quality of life (HRQOL) of PID among Malaysian patients is poorly described. This study aimed to determine the quality of life of PID patients and their respective parents. METHOD: This cross-sectional study was performed from August 2020 to November 2020. Patients with PID and their families were invited to answer the PedsQL Malay version (4.0) questionnaire, the tool used to assess the HRQOL. A total of 41 families and 33 patients with PID answered the questionnaire. A comparison was performed with the previously published value of healthy Malaysian children. RESULT: Parents of respondents recorded a lower mean of total score than the parents of healthy children (67.26 ± 16.73 vs. 79.51 ± 11.90, p-value = 0.001, respectively). PID patients reported lower mean total score to healthy children (73.68 ± 16.38 vs. 79.51 ± 11.90, p-value = 0.04), including the psychosocial domain (71.67 ± 16.82 vs. 77.58 ± 12.63, p-value = 0.05) and school functioning (63.94 ± 20.87 vs. 80.00 ± 14.40, p-value = 0.007). No significant difference of reported HRQOL when comparing between subgroup of PID on immunoglobulin replacement therapy and those without immunoglobulin replacement (56.96 ± 23.58 vs. 65.83 ± 23.82, p-value 0.28). Socioeconomic status was found to be predictive of the lower total score of PedsQL in both parent and children reports. CONCLUSION: Parents and children with PID, especially those from middle socioeconomic status, have lower HRQOL and school function impairment than healthy children.

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.

Contribution of early nutrition on the development of malnutrition and allergic diseases in the first year of life: a study protocol for the Mother and Infant Cohort Study (MICOS).

BACKGROUND: Nutrition and environmental factors are essential for the education of the neonatal immune system. Epidemiological evidence has shown that malnutrition and allergic diseases that occur during early childhood share similar protective and risk factors. This paper describes the protocol of the Mother and Infant Cohort Study (MICOS), which aims to determine the contribution of early nutrition to the development of malnutrition and allergic diseases in infants' first year of life. METHODS: MICOS is a prospective cohort study conducted at selected government health clinics in two states, namely Selangor and Wilayah Persekutuan Kuala Lumpur, Malaysia. Women in their third trimester of pregnancy are recruited into the study and their infants will be followed-up at 3, 6, and 12 months of age. Information on prenatal factors including socio-demographic characteristics, obstetric history, pre-pregnancy body mass index, gestational weight gain, smoking, family history of allergic diseases, maternal dietary intake and sunlight exposure during pregnancy are obtained through face-to-face interviews. Postnatal factors including dietary intake, sun exposure, and anthropometric measurements of the mothers, as well as feeding practices, dietary intake, anthropometric measurements, and development of allergic diseases of the infants are assessed at each follow-up. Blood samples are collected from the mothers in the third trimester to determine 25-hydroxyvitamin D levels as well as from the infants at age 12 months to determine atopic sensitisation. DISCUSSION: The concept of developmental origins of health and disease (DOHaD) which emphasises on the role of early life environments in shaping future health and disease susceptibility in adulthood has gained a huge interest in recent years. The DOHaD paradigm has influenced many fields of research including malnutrition and allergic diseases. While findings from the developed countries remain controversial, such studies are scarce in developing countries including Malaysia. The present study will determine the cause and effect relationship between early nutrition and the development of malnutrition and allergic diseases in infants' first year of life.

Accessibility to plasma-derived medicinal products in Malaysia: The challenges faced by patients with inborn errors of immunity.

Inborn errors of immunity (IEI) (also known as primary immunodeficiencies) is an umbrella term for a growing group of over 450 different disorders that are characterized by defects in some of the components of the immune system. IEI are chronic diseases of genetic origin that render individuals suffering from them susceptible to infections. The mainstay of treatments for most patients with IEI, that is, predominantly antibody deficiencies is immunoglobulin replacement therapy (IRT), which is commonly delivered intravenously. Immunoglobulin (IG) therapy contains antibodies to compensate for the defective immune system's inability to produce them. Individuals with IEI need IRT regularly throughout their lives to help combat infections and prevent organ damage. Without IRT, they are in danger of suffering from morbidity, poor quality of life, and reduced life expectancy. In the last 20 years, the use of IG preparation has tripled and this is partly attributed to the growing awareness and improved diagnoses of IEI cases. IG preparations are also used for the treatment of other medical conditions including secondary immunodeficiencies and autoimmune diseases. As IG is derived from human plasma, there are concerns about the availability of supply, particularly to treat life-threatening conditions that cannot be improved with other medications. It is estimated that 75% to 80% of IEI patients do not have access to adequate IG therapy throughout the world. This concern of supply and other challenges faced by patients with IEI in Malaysia are described from the patients' perspective.

Newborn screening for severe combined immunodeficiency in Malaysia: current status, challenges and progress.

Introduction: Early diagnosis of Severe Combined Immunodeficiency (SCID) increases survival outcomes and quality of life while significantly minimizing healthcare burden and costs. Despite growing evidence supporting the benefits and cost-effectiveness of SCID detection through newborn screening (NBS), it has yet to be implemented in Malaysia. This study aims to explore experts' opinions on the current status, challenges, and crucial strategies needed for the successful implementation of SCID NBS. Methodology: A guided, structured interview was employed to explore opinions on the current status, barriers, and strategies for implementing SCID NBS in Malaysia. All 13 invited experts participated in this study, indicating complete participation from the entire Malaysian immunology fraternity (consisting of eight clinical immunologists and five immunopathologists). Key findings: Several initiatives are ongoing to establish SCID NBS in Malaysia. Hindrances such as low immunologist-to-patient ratio, unequal placements of immunologists throughout Malaysia, society's low disease awareness, national health prioritization, lack of stakeholder engagement, and inadequacy of local study/data were highlighted. Pilot research on SCID NBS, advocacy workshops, and promotion materials are among the ongoing activities outlined in the blueprint, paving the way for this nationwide NBS program to be achievable in the near future. Conclusion: This article provides recommendations to policymakers in mandating SCID NBS. Strategies by key stakeholders are underway, particularly in advocacy programs and efforts to increase awareness among clinicians and the public.

Air pollution and allergy in Malaysia: The need for evidence and action.

There is a scarcity in both epidemiological studies and forecast models on the impact of air pollution on respiratory allergic responses in Malaysia. The quantification of baseline allows for an understanding of the severity of the impact and target areas for intervention. High-quality forecasts not only provide information for the assessment of potential outcomes but also the dissemination of public health warnings, such as the application of mobile-based early warning systems. There is a need for a data repository system that facilitates research on such studies. However, a call for more evidence should not put a pause on actions and future plans that will help reduce pollution emission and exposure to air pollutants as there are sufficient evidence to indicate that air pollutants impact health.

Evaluating immune responses to pneumococcal vaccines.

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.

Malaysian Society of Allergy and Immunology Consensus Statement on Sublingual Immunotherapy in Allergic Rhinitis.

Allergic rhinitis (AR) is an IgE-mediated inflammatory disease of the upper airway. AR affects the patients' quality of life, is a known risk factor for asthma and a socio-economic burden. Allergen-specific immunotherapy (AIT), comprising sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT), involves administering increasing doses of the causative allergen to induce clinical and immunologic tolerance to the allergens. It is the only currently available treatment for AR that has been proven to induce disease-modifying effects (i.e., long-term remission of allergic symptoms or potential prevention of asthma and new sensitizations). Although AIT is conventionally recommended for patients who are non-responsive to symptom-relieving pharmacotherapy, it is presently recommended as a first-line treatment for patients with moderate to severe AR who prefer a treatment with the potential for long-term remission. In light of the relatively recent implementation of AIT in Malaysia, guidelines on its appropriate indication and application are important to attain optimal outcomes. This consensus statement was developed by an expert group formed by the Malaysian Society of Allergy and Immunology to provide evidence-based recommendations for the practice of AIT in Malaysia. Patient and product selection, choice of AIT, and strategy towards an effective treatment outcome in AIT are presented.

ARIA Care Pathways 2019: Next-Generation Allergic Rhinitis Care and Allergen Immunotherapy in Malaysia.

An increase in the prevalence of allergic rhinitis (AR) worldwide presents a significant burden to the health care system. An initiative was started in Europe designated as Allergic Rhinitis and Its Impact on Asthma (ARIA) to develop internationally applicable guidelines by utilising an evidence-based approach to address this crucial issue. The efforts are directed at empowerment of patients for self-management, the use of digital mobile technology to complement and personalise treatment, and establishment of real-life integrated care pathways (ICPs). This guideline includes aspects of patients' and health care providers' management and covers the main areas of treatment for AR. The model provides better real-life health care than the previous traditional models. This review summarises the ARIA next-generation guideline in the context of the Malaysian health care system.

APAAACI clinical pathway on direct provocation testing for penicillin allergy delabeling.

Background: Allergy to penicillin is commonly reported in many countries and is an overwhelming global public health concern. Penicillin allergy labels can lead to the use of less effective antibiotics and can be associated with antimicrobial resistance. Appropriate assessment of suspected penicillin allergy (often including skin testing, followed by drug provocation testing [DPT] performed by allergists) can prevent the unnecessary restriction of penicillin or delabelling. Many countries in the Asia Pacific (AP) have very limited access to allergy services, and there are significant disparities in the methods of evaluating penicillin allergy. Therefore, a clinical pathway for the management of penicillin allergy is essential. Objectives: To develop a risk-stratified clinical pathway for delabeling penicillin allergy, taking into account the distinct epidemiology, patient/sensitization profiles, and disparities of allergy services or facilities within the AP. Methods: A risk-stratified penicillin allergy delabeling clinical pathway was formulated by the Drug Allergy Committee of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. and members of the Penicillin Allergy Disparities survey in AP each representing one country/region of the AP. The clinical pathway was tested based on a database of anonymized patients who were sequentially referred for and completed penicillin allergy evaluation in Hong Kong. Results: The clinical pathway was piloted employing a "hub-and-spoke" approach to foster multidisciplinary collaboration between allergists and nonallergists. A simulation run of the algorithm on a retrospective Hong Kong cohort of 439 patients was performed. Overall, 367 (84%) of patients were suitable for direct DPT and reduced the need for skin testing or specialist's care for 357 (97%) skin test-negative individuals. Out of the skin test-negative patients, 345 (94%) patients had a negative DPT. Conclusions: This risk-stratification strategy for direct oral DPT can reduce the need for unnecessary skin testing in patients with low-risk penicillin allergy histories. The hub and spoke model of care may be considered for further piloting and validation in other AP populations that lack adequately trained allergists.

Epidemiology, Management, and Treatment Access of Hereditary Angioedema in the Asia Pacific Region: Outcomes From an International Survey.

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.

COVID-19 in the Asia Pacific: Impact on climate change, allergic diseases and One Health.

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.

Transition practice for primary immunodeficiency diseases in Southeast Asia: a regional survey.

Introduction: With increased diagnostic capabilities and treatment modalities in the field of primary immunodeficiencies (PID), many pediatric patients survive beyond childhood and experience a change of care to the adult-oriented healthcare system. Unfortunately, the transition pathways for PID are less clearly defined, resulting in deterioration of quality of care in adulthood. Hence, this is the first regional study to address PID clinicians' opinions on practices and challenges of transition care in 7 Southeast Asia (SEA) countries. Methods: We adopted a cross-sectional study design through an online survey platform to enquire opinions of transition practices from expert representatives in 7 SEA countries. Results: Regionally, 3 out 7 countries reported having no practice of transition care. Among cited challenges were reluctant adaptation by patients and caregivers to unfamiliarized adult healthcare systems, inadequate ratio of adult immunologists to patients and lack of facilities for transfer. Discussion and conclusion: Our study provides evidence to advocate policy makers on the importance of standardized integration of transition practice towards betterment of transiting PID patients into adulthood.

Impact of Primary Immunodeficiency Diseases on the Life Experiences of Patients in Malaysia From the Caregivers' Perspective: A Qualitative Study.

Introduction: Primary immunodeficiency diseases (PIDs) are chronic diseases that affect the various aspects of a patient's life. However, the impact of living with PIDs is poorly described. Objective: This study aimed to explore the living experience challenges among the Malaysian caregivers of the patients with PID who underwent a follow-up in the Universiti Sains Malaysia or those registered members of the Malaysian PIDs Society. Methodology: The study was conducted from March 1 to May 30, 2021. The parents of children with PIDs were invited to participate for a semi-structured in-depth interview at the PID clinics in the USM. The estimated time of each interview was 30 min. The semi-structured interview was performed via a telephone call because of COVID-19 pandemic restrictions. The audio recording of each interview was transcribed and translated from Malay to English. Subsequently, a thematic analysis utilizing the ATLAS.ti software was performed. Results: The thematic analysis revealed five main themes, which are living with fear and anxiety with four sub-themes (sickness, psychological issues, fear of infections and hereditary issues), PID healthcare support struggles with four sub-themes (PID health system, treatment, diagnosis and financial issues), knowledge with two sub-themes (educational issues and disease understanding), social constraint with two sub-themes (relationships and social isolations) and coping with three sub-themes (acceptance, child health improvement and emotional hygiene). Conclusion: Living with fear and anxiety is a major theme impacting the living experiences of Malaysian patients with PIDs. Improvements in healthcare delivery and disease education are needed to ensure optimal quality of life.

Pharmacological Management of Allergic Rhinitis: A Consensus Statement from the Malaysian Society of Allergy and Immunology.

The goal of allergic rhinitis (AR) management is to achieve satisfactory symptom control to ensure good quality of life. Most patients with AR are currently treated with pharmacotherapy. However, knowledge gaps on the use of pharmacotherapy still exist among physicians, particularly in the primary care setting, despite the availability of guideline recommendations. Furthermore, it is common for physicians in the secondary care setting to express uncertainty regarding the use of new combination therapies like intranasal corticosteroid plus antihistamine combinations. Inadequate treatment leads to significant reduction of quality of life that affects daily activities at home, work, and school. With these concerns in mind, a practical consensus statement was developed to complement existing guidelines on the rational use of pharmacotherapy in both the primary and secondary care settings.

Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity.

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.

Adaptation, Translation and Validation of the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF): The Malay Version.

Food allergy has a significant impact on the quality of life (QoL) of children and can be measured using The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF). This study aimed to adapt, translate the FAQLQ-PF into Malay and determine the validity and reliability of the translated version. This cross-sectional questionnaire validation study was conducted among parents of children (0 to 12 years old) with food allergies across five sites in Selangor and Kuala Lumpur, Malaysia. The FAQLQ-PF-Malay underwent cross-cultural adaptation, translation, validation (content, face and construct) and reliability assessment. Exploratory factor analysis, internal consistency and test-retest reliability analyses were used to examine its construct validity and reliability. Out of 150 children, the majority were between the age of 7 to 12 years old (41%) and were female (81%). Three subscales were identified, which were: (i) social and dietary implication, (ii) food anxiety and (iii) emotional and physical impact. Four items were eliminated because of weak factor loadings. The Cronbach's alpha for each subscale ranged from 0.88 to 0.94, with an overall Cronbach's alpha of 0.95. The intra-class correlation coefficient ranged from 0.54 (95% CI: 0.10-0.77) to 0.97 (95% CI: 0.90-0.99). The 26-item FAQLQ-PF-Malay retained the three-factor structure of the original FAQLQ-PF. The FAQLQ-PF-Malay is a valid and reliable tool to assess the QoL of Malaysian children with food allergies.