Drug hypersensitivity reactions in Asia: regional issues and challenges

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.

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

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.

Continued loss of asthma control following epidemic thunderstorm asthma

BACKGROUND: Epidemic thunderstorm asthma (ETSA) severely affected Melbourne, Australia in November 2016. There is scant literature on the natural history of individuals affected by ETSA. OBJECTIVE: A multicentre 12-month prospective observational study was conducted assessing symptomatology and behaviors of ETSA-affected individuals. METHODS: We used a structured phone questionnaire to assess asthma symptom frequency, inhaled preventer use, asthma action plan ownership and healthcare utilization over 12 months since the ETSA. Analysis of results included subgroup analyses of the “current,” “past,” “probable,“ and “no asthma” subgroups defined according to their original 2016 survey responses. RESULTS: Four hundred forty-two questionnaires were analyzed. Eighty percent of individuals reported ongoing asthma symptoms at follow-up, of which 28% were affected by asthma symptoms at least once a week. Risk of persistent asthma symptoms was significantly higher in those with prior asthma diagnosis, current asthma, and probable undiagnosed asthma (all p < 0.01). Of 442 respondents, 53% were prescribed inhaled preventers, of which 51% were adherent at least 5 days a week. Forty-two percent had a written asthma action plan and 16% had sought urgent medical attention for asthma in the preceding year. CONCLUSIONS: Following an episode of ETSA, patients experience a pivotal change in asthma trajectory with both loss of asthma control and persistence of de novo asthma. Suboptimal rates of inhaled preventer adherence and asthma action plan ownership may contribute to asthma exacerbation risk and susceptibility to future ETSA episodes. Longer-term follow-up is needed to determine the extent and severity of this apparent change.

Residential NO₂ exposure is associated with urgent healthcare use in a thunderstorm asthma cohort

BACKGROUND: There is increasing interest in the role of traffic-related air pollution (TRAP) in allergic airway diseases. Few studies investigate the relationship between TRAP exposure and acute exacerbations of asthma. OBJECTIVE: The 2016 Melbourne thunderstorm asthma epidemic provided an opportunity to investigate the relationship between proxies of TRAP exposure and asthma exacerbation requiring urgent healthcare in the previous 12 months. METHODS: Current asthmatics who presented to the 3 Emergency Departments of Melbourne's second-largest health service with epidemic thunderstorm asthma in November 2016 were identified and completed a standard questionnaire. Their residential addresses were geocoded and the annual average nitrogen dioxide (NO2) exposure for each patient was assigned using a validated satellite-based land use regression model. Residential distance to the nearest major road was calculated using ArcGIS. Multivariate logistic regression was used to investigate the relationship between each TRAP proxy and healthcare use, adjusting for potential confounders. RESULTS: From 263 thunderstorm asthma patients, 88 patients identified with current asthma were analysed. Those with higher mean annual residential NO2 exposure had greater odds of urgent healthcare use in the previous year (odds ratio [OR], 3.45 per one interquartile-range increase; 95% confidence interval [CI], 1.31–9.10; p = 0.01), however distance from major road (OR, 0.95 per 100-m increase; 95% CI, 0.80–1.13; p = 0.57) and living < 200 m from a major road (OR, 1.47; 95% CI, 0.29–7.45; p = 0.64) were not significantly associated. CONCLUSION: In current asthmatics who presented during an epidemic thunderstorm asthma event, greater exposure to residential NO2 was significantly associated with greater odds of asthma exacerbations requiring urgent healthcare in the previous 12 months.

An epidemic of thunderstorm asthma in Melbourne 2016: asthma, rhinitis, and other previous allergies

BACKGROUND: On 21st November 2016, Melbourne experienced an epidemic of ‘thunderstorm asthma.’ Although previously described in the literature, risk factors and natural history remain incompletely understood. OBJECTIVE: Our aim was to follow up those presenting to the 3 Emergency Departments (EDs) in our health service during the epidemic, and assess their history for previous asthma, rhinitis, and allergies. METHODS: ED notes of all respiratory presentations within 48 hours of the thunderstorm event were reviewed and patients with acute asthma included. A standardised questionnaire was devised encompassing asthma diagnosis, undiagnosed asthma symptoms and rhinitis severity. Patients were contacted by phone within 30 days of the event. RESULTS: Three hundred forty-four patients were identified overall; 263 patients were contactable and completed a phone or mail questionnaire. The mean age was 32.7 ± 19.2 years (range, 6 months–87 years; 25% < 18 years) with 58% male sex. A previous diagnosis of asthma was present in 42% (n = 111), and there was no previous asthma diagnosis in 58% (n = 152). Of those who had no asthma diagnosis 53% had probable undiagnosed asthma. Overall, rhinitis prevalence was 88%, of which 72% were moderate or severe (Allergic Rhinitis and its Impact on Asthma guidelines) and 51% (n = 133) reported a history of grass pollen allergy. CONCLUSION: Our data highlights the importance of atopy and rhinitis as risk factors for epidemic thunderstorm asthma. Better identification of undiagnosed asthma, and implementing treatment of asthma and rhinitis may be important.

Thunderstorm asthma: potential danger but a unique opportunity

No abstract available.

Eosinophilic esophagitis: current understanding and evolving concepts

Eosinophilic esophagitis (EoE) is now considered to represent a form of food allergy and this is demonstrated by a response to elimination diet in many patients. A critical additional factor may be an inherent impairment in epithelial barrier integrity, possibly worsened by reflux of gastric contents and improved with proton pump inhibitor (PPI) use. Key clinic challenges are posed by the absence of reliable allergy tests to guide elimination diet, and the subsequent need for invasive endoscopic assessment following empirical food challenge, meaning that corticosteroids will remain the mainstay of therapy for many. From a research standpoint, determining if impairments in barrier integrity are innate, and how PPIs address this deficit (which may be pH independent) are important questions that when answered may allow future therapeutic advancement.

Oral antiplatelet agent hypersensitivity and cross-reactivity managed by successful desensitisation

Oral platelet aggregation inhibitors are widely used for the treatment and prevention of cardiovascular diseases, including coronary stent thrombosis. Premature discontinuation following percutaneous coronary intervention would pose a grave risk of in-stent thrombosis, acute myocardial infarction and eventual death. Although they share the same mechanism of adenosine diphosphate P2Y12 platelet receptor inhibition, they belong to either the chemical class of thienopyridines (clopidogrel, prasugrel, and ticlopidine) or cyclopentyl-triazolo-pyrimidines (ticagrelor and cangrelor). This case describes the first documented cross-reactive hypersensitivity of clopidogrel towards both its fellow thienopyridine, prasugrel, as well as the structurally dissimilar ticagrelor, and its subsequent successful desensitisation.

Measuring and imaging small airways dysfunction in asthma

Asthma is a chronic inflammatory disorder of the airways causing typical symptoms, and the diagnosis is supported by evidence of airflow obstruction which is variable, reversible or inducible. However, standard assessment of lung function with spirometry does not measure dysfunction in small airways which are < 2 mm in diameter towards the periphery of the lung. These airways make only a small contribution to airway resistance under normal circumstances. Nevertheless, there is mounting evidence that pathology and dysfunction in these small airways are implicated in the pathogenesis and natural history of asthma. Using forced oscillation and the multibreath nitrogen washout techniques, uneven ventilation (ventilation heterogeneity) due to small airways dysfunction has been shown to be an important marker of asthma disease activity, even in the absence of abnormalities in standard spirometric measurements. Recent advances in imaging research, particularly with hyperpolarised gas magnetic resonance imaging, have also given insights into the significance and dynamic nature of ventilation heterogeneity in asthma. The challenge is to integrate these new physiological and imaging insights to further our understanding of asthma and facilitate potential new treatments.