House dust mite allergen avoidance strategies for the treatment of allergic asthma: A hypothesis-generating meta-analysis.

Background: This study continues the review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187), aiming to systematically generate hypotheses on the effectiveness of (sub)strategies for house dust mite allergen avoidance in the treatment of allergic asthma. Methods: We used the trials previously analysed by Gøtzsche and Johansen and searched recently published studies. Data on asthma symptom scores (ASS), ACQ, number of improved patients, AQLQ-scores, medication use, FEV1%, PC20, and FeNO levels were analysed. The effectiveness of strategies was assessed using Metafor in R. Results: Thirty-five trials involving 2419 patients were included in the final study. The patient-reported outcome number of patients with improved condition following total bedroom control was RR = 3.39 (95% confidence interval: 1.04 to 11.04, P = 0.04). The mean differences in the ASS by nocturnal air purification was -0.7 (95% confidence interval: -1.08 to -0.32, P < 0.001). Other outcomes including partial bedroom control were non-significant or clinically not of importance. Conclusions: Total bedroom control and nocturnal air purification of the breathing zone hypothetically provides clinical benefits in patients with house dust mite-induced allergic asthma. The number of patients with improvements in their condition respectively the asthma symptom score differences showed potential in small subgroups, consisting of single studies. Partial bedroom control is not recommended. Systematic Review Registration: Prospero CRD42022323660.

Comparison of skin prick test and prick-to-prick test with fruits and vegetables in the diagnosis of food allergy.

INTRODUCTION: Prick-to-prick (PTP) test with fresh food is accepted as a reliable tool for measuring sensitization to fruits and vegetables. Not all fruits and vegetables are available throughout the year. The objective of this study was to investigate whether skin prick test (SPT) performed with frozen juice of fruits and vegetables (FJFV) is a good alternative to PTP tests performed with fresh fruits and vegetables (FFV). METHODS: Adult patients suspected of having a food allergy to fruits and/or vegetables were included. A questionnaire was used to score symptoms after consumption of apple, kiwi, peach, tomato, and carrot. SPTs with FJFV, and PTP tests with FFV were performed. Intra-class correlation coefficients (ICC) between the SPT and PTP test results were calculated. The sensitivity and specificity of both diagnostic tests towards food allergen specific symptoms (FASS) were calculated. RESULTS: Thirty-six patients were included. FASS was positive in 75% for apple, 53% for kiwi, 44% for peach, 25% for tomato, and 22% for carrot. ICC between SPT and PTP test results were moderate for apple (0.72) and kiwi (0.71), strong for peach (0.75) and tomato (0.89), and very strong for carrot (0.94). Sensitivity was equal for the SPT and PTP tests for apple (0.93), peach (0.81), and carrot (1.00), and comparable for kiwi (0.50 resp. 0.70), and tomato (0.44 resp. 0.56). Specificity was equal for apple (0.33), peach (0.15), and carrot (0.41), and comparable for kiwi (0.29 resp. 0.21) and tomato (0.80 resp. 0.72). CONCLUSIONS: Results of SPT with FJFV and PTP test with FFV are comparable. SPT with FJFV is a good alternative in the daily practice of the allergists.

COVID-19 Incidence and Disease Course Among Patients at an Allergy Department.

Background: Since the coronavirus pandemic in 2020, there is not much reported about the disease course of COVID-19 in patients with allergic diseases. Objectives: The aim of this study was to investigate the cumulative incidence and severity of COVID-19 among patients from the allergy department compared with the general Dutch population and people from their household. Design: We conducted a comparative longitudinal cohort study. Methods: In this study patients of the allergy department were included with their household members as a control group. Data from the beginning of the pandemic were systematically obtained through questionnaires by telephonic interviews and retrieved from electronic patient files between October 15, 2020 and January 29, 2021. Main outcomes were confirmed SARS-CoV-2 infection, disease duration, hospitalization, intensive care admission, and mortality. Questions regarding applied social distancing measures were inventoried as well. Results: Three hundred and eighty nine patients (median age 39.1 (18.7-84.7) years, 69.9% female) and 441 household members (median age 42.0 (18.0-91.5), 44.1% female) were included. The cumulative COVID-19 incidence in patients was higher compared with the general population (10.5% vs 5.6%, P < .001). In total, 41 (10.5%) patients attending the allergy clinic compared to 38 (8.6%) household members were infected with SARS-CoV-2 (P = .407). Median disease duration was 11.0 (0.0-61.0) days in patients compared to 10.5(1.0-232.0) days in household members (P = .996). Conclusion: The cumulative COVID-19 incidence in patients from the allergy cohort was higher compared with the general Dutch population, but similar compared with household members. There was no difference in symptoms, disease duration, or hospitalization rate between the allergy cohort and their household members.

The Dutch Working Party on Antibiotic Policy (SWAB) guideline for the approach to suspected antibiotic allergy.

OBJECTIVES: Prudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy. METHODS: The guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak. RESULTS: Sixty recommendations were provided for suspected allergy to ß-lactam antibiotics (BLAs) and non-ß-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team. CONCLUSIONS: Accumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non-ß-lactam antibiotics, thereby strongly supporting antimicrobial stewardship.

Allergen immunotherapy for allergic asthma: The future seems bright.

Allergen specific immunotherapy (AIT) is the only causal therapeutic option for allergic airway diseases including asthma and allergic rhinitis. AIT has been shown to restore the allergen immune tolerance, can modify both the early and late-onset allergen-specific airway hyperreactivity, helps to achieve disease control/remission and prevents new sensitisations. Recent real life data on long-term effectiveness of house dust mite (HDM) AIT in a large group of patients with HDM-driven asthma further underscored its unique therapeutic potential as well as confirmed previous data with pollen AIT. More widespread use of this causal treatment in select patient populations should further move this promising therapeutic field. In this mini-review, we discuss updates on new insights based on real world patient data.

Homemade Food Allergen Extracts for Use in Skin Prick Tests in the Diagnosis of IgE-Mediated Food Allergy: A Good Alternative in the Absence of Commercially Available Extracts?

INTRODUCTION: The skin prick test (SPT) is the first step in the diagnosis of an immunoglobulin E (IgE)-mediated food allergy. The availability of commercial food allergen extracts is very limited, resulting in a need for alternative extraction methods of food allergens. The objective of this study was to compare the SPT results of homemade food allergen extracts with commercially available extracts. METHODS: Adult patients with a suspected food allergy were included. Food allergen-specific symptoms were scored using a questionnaire. SPTs were performed with homemade and commercially available extracts (ALK-Abelló, Kopenhagen, Denmark) from almond, apple, hazelnut, peach, peanut, and walnut. Serum-specific IgE was measured with ISAC or ImmunoCAP™. Intra-class correlation coefficients (ICC) between the SPT results of both extract methods were calculated. The proportion of agreement with food allergen-specific symptoms was analyzed. RESULTS: Fifty-four patients (mean age 36; range 19-69 years; female/male: 42/12) were included. The intra-class correlation coefficient (ICC) between the SPT results of both extract methods were strong for hazelnut 0.79 (n = 44) and walnut 0.78 (n = 31), moderate for apple 0.74 (n = 21) and peanut 0.66 (n = 28), and weak for almond 0.36 (n = 27) and peach 0.17 (n = 23). The proportion of agreement between SPT results and food allergen-specific symptoms was comparable for homemade and commercially available extracts, except for peach; 0.77 versus 0.36, respectively. CONCLUSION: In the diagnostic procedures to identify an IgE-mediated food allergy, homemade extracts from hazelnut and walnut appear to be a good alternative in the absence of commercially available food allergen extracts.

Allergen provocation tests in respiratory research: building on 50†years of experience.

The allergen provocation test is an established model of allergic airway diseases, including asthma and allergic rhinitis, allowing the study of allergen-induced changes in respiratory physiology and inflammatory mechanisms in sensitised individuals as well as their associations. In the upper airways, allergen challenge is focused on the clinical and pathophysiological sequelae of the early allergic response, and is applied both as a diagnostic tool and in research settings. In contrast, bronchial allergen challenge has almost exclusively served as a research tool in specialised research settings with a focus on the late asthmatic response and the underlying type 2 inflammation. The allergen-induced late asthmatic response is also characterised by prolonged airway narrowing, increased nonspecific airway hyperresponsiveness and features of airway remodelling including the small airways, and hence allows the study of several key mechanisms and features of asthma. In line with these characteristics, allergen challenge has served as a valued tool to study the cross-talk of the upper and lower airways and in proof-of-mechanism studies of drug development. In recent years, several new insights into respiratory phenotypes and endotypes including the involvement of the upper and small airways, innovative biomarker sampling methods and detection techniques, refined lung function testing as well as targeted treatment options further shaped the applicability of the allergen provocation test in precision medicine. These topics, along with descriptions of subject populations and safety, in line with the updated Global Initiative for Asthma 2021 document, will be addressed in this review.

Assessment of immediate and non-immediate hypersensitivity contrast reactions by skin tests and provocation tests: A review.

INTRODUCTION: Allergic and nonallergic hypersensitivity reactions to iodinated contrast media (ICM) and gadolinium-based contrast media are classified as immediate or non-immediate hypersensitivity reactions (IHR and NIHR), respectively. Skin tests and provocation tests are recommended for the evaluation of hypersensitivity reactions to contrast agents; however provocations are not common in clinical practice. METHODS: A MEDLINE search was conducted to investigate studies comprising both skin tests and provocation tests that evaluated hypersensitivity reactions to ICM. RESULTS: Nineteen studies were identified that reported on skin tests, followed by provocations. In the case of IHR to ICM, 65/69 (94%) patients with a positive skin test for the culprit media tolerated a challenge with a skin-test-negative alternative ICM. In IHR to ICM with a negative skin test for the culprit media, provocations were positive in 3.2%-9.1% patients. In the case of a NIHR to ICM with a positive skin test, provocation with a skin-test-negative agent was tolerated in 75/105 (71%) of cases. In NIHR with a negative skin test for the culprit agent, re-exposure to the culprit or an alternative was positive in 0%-34.6% patients. Provocations with the same ICM in skin test positive patients with IHR or NIHR were positive for a majority of the patients, although such provocation tests were rarely performed. Data on hypersensitivity reactions, skin tests and provocations with gadolinium-based contrast media were limited; however, they exhibited a pattern similar to that observed in ICM. CONCLUSION: In both ICM and gadolinium-based contrast media, the risk of an immediate repeat reaction is low when skin tests are negative. In contrast, a provocation with a skin-test-positive contrast medium showed a high risk of an immediate repeat hypersensitivity reaction. Therefore, a thorough medical history is necessary, followed by skin tests. A provocation is recommended, for diagnostic work-up, when the diagnosis is uncertain.

Characteristics of COVID-19 infection and antibody formation in patients known at a tertiary immunology department.

BACKGROUND: Knowledge about COVID-19 infections is expanding, although knowledge about the disease course and antibody formation in patients with an auto-immune disease or immunodeficiency is not fully unraveled yet. It could be hypothesized that immunodeficient patients, due to immunosuppressive drugs or their disease, have a more severe disease course due to their immunocompromised state. However, it could also be hypothesized that some of the immunosuppressive drugs protect against a hyperinflammatory state. METHODS: We collected data on the incidence of COVID-19, disease course and SARS-CoV-2 antibody formation in COVID-19 positive patients in a cohort of patients (n â€‹= â€‹4497) known at the Clinical Immunology outpatient clinic in a tertiary care hospital in the Netherlands. RESULTS: In the first six months of the pandemic, 16 patients were identified with COVID-19, 14 by nasal swab PCR, and 2 patients by SARS-CoV-2 antibodies. Eight patients were admitted to the hospital. SARS-CoV-2 antibodies were measured in 8 patients and were detectable in all, including one patient on B-cell ablative therapy and one patient with Common Variable Immunodeficiency Disorder. CONCLUSION: This study indicates that the disease course differs among immunocompromised patients, independently of (dis)continuation of immunosuppressive drugs. Antibody production for SARS-CoV-2 in immunocompromised patients was shown. More research needs to be conducted to confirm these observations and guidelines regarding (dis)continuation of immunosuppressive drugs in COVID-19 positive immunocompromised patients should be developed.

Small percentage of anaphylactic reactions treated with epinephrine during food challenges in Dutch children.

BACKGROUND: Severe allergic reactions, including anaphylaxis, occur during oral food challenges (OFCs) and the first-line treatment of anaphylaxis is epinephrine. OBJECTIVE: To evaluate the percentage of anaphylactic reactions treated with epinephrine during OFCs and to identify associated factors for the administration of epinephrine. METHODS: Children who underwent an OFC with peanut, hazelnut, cow's milk, hen's egg, or cashew nut from 2005 through 2015 in the Netherlands were evaluated. Children with reactions meeting the criteria for anaphylaxis according to the European Academy of Allergy and Clinical Immunology guidelines for food allergy and anaphylaxis were included. Children with an anaphylactic reaction treated with vs without epinephrine were compared. Possible factors associated with the administration of epinephrine, such as age, sex, symptoms consistent with asthma, history of an allergic reaction to the tested allergen, and symptom types during the anaphylactic reaction, were evaluated using logistic regression analysis. RESULTS: Eighty-three children in clinical and research settings (43% boys; median age, 7 years; range, 1-17) who met the criteria for anaphylaxis were included in this study. Thirty-two of 83 children (39%) with anaphylaxis were treated with epinephrine. Respiratory symptoms during the OFC were treated significantly more often with epinephrine than gastrointestinal symptoms (P = .01). CONCLUSION: Only 39% of children with anaphylaxis, according to the guideline criteria, were treated with epinephrine during the OFC and most of these children had respiratory symptoms. There is need for an easy-to-use international guideline for the treatment of allergic symptoms during OFCs.