Cannabis-related allergies: An international overview and consensus recommendations.

Cannabis is the most widely used recreational drug in the world. Cannabis sativa and Cannabis indica have been selectively bred to develop their psychoactive properties. The increasing use in many countries has been accelerated by the COVID-19 pandemic. Cannabis can provoke both type 1 and type 4 allergic reactions. Officially recognized allergens include a pathogenesis-related class 10 allergen, profilin, and a nonspecific lipid transfer protein. Other allergens may also be relevant, and recognition of allergens may vary between countries and continents. Cannabis also has the potential to provoke allergic cross-reactions to plant foods. Since cannabis is an illegal substance in many countries, research has been hampered, leading to challenges in diagnosis since no commercial extracts are available for testing. Even in countries such as Canada, where cannabis is legalized, diagnosis may rely solely on the purchase of cannabis for prick-to-prick skin tests. Management consists of avoidance, with legal issues hindering the development of other treatments such as immunotherapy. Education of healthcare professionals is similarly lacking. This review aimed to summarize the current status of cannabis allergy and proposes recommendations for the future management of this global issue.

Diversity and complexity of mouse allergens in urine, house dust, and allergen extracts assessed with an immuno-allergomic approach.

BACKGROUND: Mouse allergy is an important cause of indoor asthma and allergic rhinoconjunctivitis. The major mouse allergen, Mus m 1, is a complex of homologous pheromone-binding lipocalins called major urinary proteins (MUPs). METHODS: We analyzed the proteome of MUPs in mouse urine, commercial mouse epithelial extracts, and environmental samples using several approaches. These include as follows: two-dimensional electrophoresis and immunoblotting; liquid chromatography-high-resolution mass spectrometry (LC/HRMS); multiple reaction monitoring (MRM) mass spectrometry; and LC/HRMS analysis of glycans at the N-66 residue of MUP3. RESULTS: Albumin is predominant in the extracts, while MUPs are predominant in urine. LC/HRMS of 4 mouse allergen extracts revealed surprising heterogeneity. Of 22 known mouse MUPs, only 6 (MUP3, MUP4, MUP5, MUP13, MUP20, and MUP21) could be identified with MRM using unique peptides. Assessment of MUP content in urine, extracts, and dust samples showed good correlation between MRM and other methods working with different detection principles. All 6 identifiable MUPs were found in electrophoretically separated urine bands, but only MUP3 and MUP20 were above LOQ in unseparated mouse urine, and only MUP3, MUP4, and MUP20 were found in mouse epithelial extracts. Glycan heterogeneity was noted among 4 individual inbred mice: of 13 glycan structures detected, 8 were unique to one mouse, and only 2 glycan modifications were present in all 4 mice. CONCLUSIONS: Using mass spectrometry and MRM, mouse allergen extracts and urine samples are shown to be complex and heterogeneous. The efficacy and safety of commercial mouse allergen extracts will be improved with better controls of allergen content.

Diagnostic accuracy and safety of inhalation challenge tests for bird fancier's lung-Systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic accuracy of inhalation challenge tests for bird fancier's lung and related adverse reactions. DESIGN: We performed a systematic review and meta-analysis for the diagnostic test accuracy of inhalation challenge tests and a systematic review for adverse events of the tests. We evaluated the risk of bias and applicability of the included articles for diagnostic test accuracy with the modified Quality Assessment of Diagnostic Accuracy Studies-2 tool. We used hierarchical summary receiver operating characteristic (HSROC) curve analysis to evaluate the sensitivity and specificity of challenge tests and assessed subjective adverse reactions and steroid treatment use. Sensitivity was calculated by fixing specificity at 99% from the HSROC curve. DATA SOURCES: We searched for articles evaluating the diagnostic accuracy of inhalation challenge tests or describing adverse reactions in Medline, Embase, the Cochrane Library, the International Clinical Trials Registry Platform, and Web of Science. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomized control trials, prospective or retrospective cohort studies, or case-control studies assessing the diagnostic test accuracy of inhalation challenge tests for bird fancier's lung. For adverse effects review, we included the same articles, and case series or case reports reporting adverse reactions of inhalation challenge tests. RESULTS: In our review of 12 articles, the diagnostic accuracy of inhalation challenge tests was substantially high. Point estimate of sensitivity when calculated with a fixed specificity of 99% was 99%. Among 873 patients, 6 needed steroid treatment for adverse reactions; however, no death occurred due to acute exacerbation following a challenge test. CONCLUSIONS: Inhalation challenges for bird fancier's lung could be accurate and safe diagnostic procedures and may be considered both as rule-in and rule-out tests in tertiary care centres. However, caution is required regarding overestimation of diagnostic yield due to risk of bias. Systematic review registration: University hospital Medical Information Network Clinical Trials Registry (UMIN000038799).

Occupational respiratory allergy to lettuce in lettuce farmers.

BACKGROUND: Lettuce-associated respiratory allergy has never been reported before. The aim of this study was to clarify the clinical condition of lettuce-associated respiratory allergy and to identify the lettuce antigen which induces allergic symptoms. METHODS: We distributed questionnaires to 1168 lettuce farmers and performed medical examinations in those who exhibited respiratory symptoms related to occupational exposure to lettuce. We analysed specific IgE-binding proteins in the sera of patients through immunoblotting analysis and determined molecular characterization of the IgE-binding bands using liquid chromatography-mass spectrometry. RESULTS: A total of 932 farmers (80%) responded to the questionnaire. Of those, 7% exhibited lettuce-associated respiratory symptoms, during harvesting and packaging. Thirteen patients were diagnosed with allergy to lettuce and agreed to undergo further examinations. The percentage of activated basophils in these patients was significantly higher compared with that reported in negative controls (P < .05). Lettuce-specific IgE (ImmunoCAP® ) and skin prick testing was positive in 46% and 62% of patients, respectively. Notably, occupational lettuce-allergic asthma was detected in one patient through specific bronchial provocation testing. The IgE-binding bands recognized in the sera of >50% of patients were identified as epidermis-specific secreted glycoprotein EP1-like (51 kDa). CONCLUSION: The present analysis identified a novel lettuce allergen. This allergen may have clinically useful applications, such as specific IgE testing and allergen-specific immunotherapy.

Immunological methods for diagnosis and monitoring of IgE-mediated allergy caused by industrial sensitizing agents (IMExAllergy).

Industrial sensitizing agents (allergens) in living and working environments play an important role in eliciting type 1 allergic disorders including asthma and allergic rhinitis. Successful management of allergic diseases necessitates identifying their specific causes (ie, identify the causative agent(s) and the route of contact to allergen: airborne, or skin contact) to avoid further exposure. Identification of sensitization by a sensitive and validated measurement of specific IgE is an important step in the diagnosis. However, only a limited number of environmental and occupational allergens are available on the market for use in sIgE testing. Accordingly, specific in-house testing by individual diagnostic and laboratory centers is often required. Currently, different immunological tests are in use at various diagnostic centers that often produce considerably divergent results, mostly due to lack of standardized allergen preparation and standardized procedures as well as inadequate quality control. Our review and meta-analysis exhibited satisfactory performance of sIgE detection test for most high molecular weight (HMW) allergens with a pooled sensitivity of 0.74 and specificity of 0.71. However, for low molecular weight (LMW) allergens, pooled sensitivity is generally lower (0.28) and specificity higher (0.89) than for HMW tests. Major recommendations based on the presented data include diagnostic use of sIgE to HMW allergens. A negative sIgE result for LMW agents does not exclude sensitization. In addition, the requirements for full transparency of the content of allergen preparations with details on standardization and quality control are underlined. Development of standard operating procedures for in-house sIgE assays, and clinical validation, centralized quality control and audits are emphasized. There is also a need for specialized laboratories to provide a custom service for the development of tests for the measurement of putative novel occupational allergens that are not commercially available.

Allergic sensitization to laboratory animals is more associated with asthma, rhinitis, and skin symptoms than sensitization to common allergens.

BACKGROUND: Workers exposed to laboratory animals have a high risk of developing laboratory animal allergy (LAA). Atopy seems to be the main risk factor for LAA. We hypothesized that occupational sensitization is a better predictor for the development of asthma, rhinitis, and bronchial hyperresponsiveness (BHR) than common sensitization. OBJECTIVE: To investigate the association between occupational sensitization to laboratory animals and clinical outcomes. METHODS: This was a cross-sectional study performed at two universities on students and employees dealing with small rodents. The subjects were allocated in groups: non-sensitized, common sensitization, or occupational sensitization, according to the results of the skin prick test (SPT). All subjects answered a questionnaire about animal exposures, symptoms, allergic diseases, and underwent spirometry and bronchial challenge test with mannitol. Multivariate analysis was performed using Poisson regression to estimate the prevalence ratio (PR). RESULTS: Data from 453 volunteers were analysed. Non-sensitized group comprised 237 subjects; common sensitization group, 142 subjects; and occupational sensitization group, 74 subjects. Occupational sensitization was associated with greater risk for all outcomes studied. When the common sensitization group was reference, skin symptoms had PR of 1.36, 95% confidence interval (CI): 1.01-1.85; wheezing had PR of 1.75, CI 95%: 1.21-2.53; rhinitis had PR of 1.25, 95%: 1.11-1.40; nocturnal dyspnoea had PR of 2.40, 95% CI: 1.31-4.40; bronchial hyperresponsiveness (BHR) had PR of 2.47, 95% CI: 1.50-4.09; and confirmed asthma had PR of 2.65, 95% CI: 1.45-4.85. In addition, the overlap of asthma, rhinitis, and skin symptoms in a same subject was significantly more prevalent in the occupational sensitization group, 16.2% versus 4.9% in the common sensitization group. CONCLUSION AND CLINICAL RELEVANCE: Occupational sensitization is associated with allergic symptoms and respiratory diseases. SPT with occupational allergens along with other parameters may contribute to detection of risk for allergic and respiratory diseases associated with exposure to laboratory animals.

Respiratory allergies among veterinarians: two cross-sectional surveys from 2006 to 2012.

PURPOSE: Animal-related allergy is known to be an occupational hazard among veterinarians; however, there is a lack of data showing to which extent these are affected. We aimed at describing the prevalence of respiratory allergies in this population. METHODS: In two repeated cross-sectional surveys in 2006 and 2012 in Bavaria, we examined the prevalence of wheezing, asthma and allergic rhinitis by questionnaires. We additionally performed multiple regression analysis to identify associated factors. RESULTS: Overall participation rate was above 60%, leading to sample sizes of 512 in 2006 and 596 in 2012, respectively. Prevalences of allergic symptoms ranged from 5.1 to 5.6% for asthma, 17.0 to 20.2% for rhinitis, and 11.4 to 14.3% for wheezing, as well as 7.2 to 11.3% for wheezing without having a cold. The percentage of women in this occupation grew between the first and second survey. There were gender differences in both surveys concerning age and practice type (p < 0.0001). Women had a lower mean age (42.1 vs. 53.0 years in 2012) and worked much more often exclusively with small animals (50.2 vs. 15.9% in 2012). There was a borderline significantly higher prevalence for allergic rhinitis in women than in men in 2012 (20.1 vs. 13.7, p = 0.052). Having allergic rhinitis was clearly associated with wheezing, wheezing without cold and asthma. CONCLUSIONS: In a repeated cross-sectional survey at an interval of 6 years among veterinarians, we found a relatively stable overall prevalence of wheeze, wheeze without having a cold, asthma and allergic rhinitis.

Occupational anaphylaxis--an EAACI task force consensus statement.

Anaphylaxis is a systemic allergic reaction, potentially life-threatening that can be due to nonoccupational or, less commonly, to occupational triggers. Occupational anaphylaxis (OcAn) could be defined as anaphylaxis arising out of triggers and conditions attributable to a particular work environment. Hymenoptera stings and natural rubber latex are the commonest triggers of OcAn. Other triggers include food, medications, insect/mammal/snake bites, and chemicals. The underlying mechanisms of anaphylactic reactions due to occupational exposure are usually IgE-mediated and less frequently non-IgE-mediated allergy or nonallergic. Some aspects of work-related allergen exposure, such as route and frequency of exposure, type of allergens, and cofactors may explain the variability of symptoms in contrast to the nonoccupational setting. When assessing OcAn, both confirmation of the diagnosis of anaphylactic reaction and identification of the trigger are required. Prevention of further episodes is important and is based on removal from further exposure. Workers with a history of OcAn should immediately be provided with a written emergency management plan and an adrenaline auto-injector and educated to its use. Immunotherapy is recommended only for OcAn due to Hymenoptera stings.

Identification of a 17 kDa protein that is a potentially novel antigen of lettuce-associated respiratory allergy in farmers.

BACKGROUND: We have identified and reported a novel antigen, nonprotein-specific secreted EP1-like glycoprotein (51 kDa), for lettuce-related respiratory allergy. OBJECTIVE: We aimed to identify a novel antigen for lettuce-related respiratory allergy that is different from epidermis-specific secreted EP1-like glycoprotein. METHODS: Immunoblotting was performed using an immunoglobulin E-specific antibody. The antigen-antibody reaction was confirmed by means of enzyme-linked immunosorbent assaying. LC-MS/MS analysis was carried out to detect a novel protein found in sera from 3 of 13 patients with lettuce-related respiratory allergy. Finally, we purified a novel protein from Escherichia coli. RESULTS: Immunoblotting assays showed common bands of 17 kDa in the sera of 3 of 13 patients. An enzyme-linked immunosorbent assay confirmed that the patient sera reacted with lettuce latex juice. A 17 kDa protein band that showed antigenic reactivity in 3 of 13 patient sera was identified as a kirola-like protein by LC-MS/MS. In addition, although we purified this protein, we failed to show the inhibitory effect. CONCLUSION: A 17 kDa protein that is a potentially novel antigen of lettuce-associated respiratory allergy was identified. In further studies, we will focus on purifying this novel protein to diagnose lettuce allergy.

Exposição prolongada a animais de laboratório está associada ao aumento de casos de asma / Prolonged exposure to laboratory animals is associated with increasing asthma cases

Resumo Objetivo: descrever o resultado do acompanhamento de trabalhadores sensibilizados a animais de laboratório que prolongaram sua exposição. Métodos: após um período de aproximadamente 7 anos, entramos em contato com todos os indivíduos com sensibilização alérgica ocupacional detectada em estudo anterior. Um questionário foi aplicado para situação ocupacional atual, relação entre alergia e a decisão de deixar o trabalho ou exposição e para asma, sibilância, rinite, sintomas cutâneos e dispneia noturna. Resultados: dos 74 indivíduos com sensibilização ocupacional, 45 responderam ao questionário na segunda avaliação e 37 ainda estavam expostos. Ao comparar os dados da primeira avaliação com os da avaliação atual, observou-se um aumento na frequência de asma. Na primeira avaliação, entre todos os sensibilizados (n = 74), 27,0% responderam sim a ambas as questões "Você tem ou já teve asma?" e "A asma foi diagnosticada por um médico?". Na segunda avaliação, 7 anos depois, dos 37 sujeitos que ainda estavam expostos, 51,3% responderam sim a essas questões (OR: 2,80; IC95%: 1,23-6,38; p = 0,013). Não houve mudança na frequência de respostas positivas às outras perguntas. Conclusão: os dados demonstram aumento da frequência de asma entre trabalhadores com sensibilização ocupacional que prolongam a exposição a animais de laboratório.

Abstract Objective: to describe the follow-up evaluation of sensitized workers who prolonged their occupational exposure to laboratory animals. Methods: after a follow-up period of approximately 7 years, we contacted all individuals with occupational allergic sensitization detected in a previous study. A questionnaire was employed to assess present occupational status, relationship between allergy and decision on quitting job or exposure, and to assess asthma, wheezing, rhinitis, skin symptoms, and nocturnal dyspnea. Results: of the 74 individuals with occupational sensitization, 45 volunteers completed the questionnaire at the second evaluation and 37 were still exposed. By comparing the data from the first evaluation with data from the current evaluation, we observed an increase in asthma frequency. In the first evaluation, among all sensitized subjects (n=74), 27.0% answered yes to both questions "Do you have or have you ever had asthma?" and "Was the asthma diagnosed by a doctor?" In the second evaluation, 7 years later, among the 37 subjects who were still exposed, 51.3% answered yes to these questions (OR: 2.80; 95%CI: 1.23-6.38; p=0.013). There was no change in the frequency of positive responses to the other questions. Conclusion: data demonstrate increasing frequency of asthma among workers with occupational sensitization who prolong exposure to laboratory animal.