Occupational and food allergy: focus on allergen extracts

The aim of this thesis is, first, the diagnostic work-up of occupational and food allergies in the absence of well-validated commercially available standardised extracts for Skin Prick Test. Second, to investigate cross-reactivity in occupational and food allergic patients. Third, the treatment of, employees with an occupational allergy in order to enable the continuation of work. The number of work-related symptoms among greenhouse workers is increasing and the prevalence of food allergies is rising. The sequence of diagnostic procedures is the history first, followed by skin tests and RAST tests, and challenge tests as final instruments. Unfortunately, commercial standardised extracts to diagnose the more uncommon allergies caused by relatively unknown allergens are generally not available. Therefore, we made new in house manufactured extracts, for the diagnosis of occupational and food allergies e.g. several flower pollen, A. cucumeris, latex, fruits (peach, kiwi, banana, avocado), and hazelnut

Mono-sensitisation to peanut component Ara h 6: a case series of five children and literature review

Here, we summarise the current clinical knowledge on Ara h 6 sensitisation and clinical relevance of this sensitisation pattern using five illustrative clinical cases. The literature search yielded a total of 166 papers, and an additional relevant article was found by ‘snowballing’. A total of ten articles were considered relevant for this review. Most studies included patients with a sensitisation to Ara h 6 and cosensitisation to Ara h 2. Only three studies showed patients with a mono-sensitisation to Ara h 6. This illustrates that Ara h 6 mono-sensitisation has been neglected in literature. We present a case series of five children with sensitisation to peanut component Ara h 6. Only one of these five patients showed Ara h 8 cosensitivity. Three out of the five children had a positive double-blind placebo-controlled food challenge (DBPCFC), with moderate to strong reactions. Conclusion: A mono-sensitisation to peanut component Ara h 6 is uncommon but can cause severe allergic reactions. Therefore, the determination of sIgE to Ara h 6 is warranted in patients with a suspected peanut allergy, especially in the absence of sensitisation to Ara h 1, 2, 3 and 9.(Table presented.

Occupational allergy in Strawberry Greenhouse workers

Background: Employees in strawberry greenhouses are highly exposed to several (potential) allergenic agents. However, no occupational allergy in this branch has been described before. First, the presence of work-related allergic symptoms in strawberry workers was explored. Second, we aimed to prove the concept that an IgE-mediated allergy could be responsible for work-related symptoms. To test the possibility of an IgE response secondary to cross-reactivity to birch or grass pollen, inhibition experiments were performed. Methods: First, a questionnaire survey concerning work-related allergic symptoms among strawberry workers in the Netherlands was carried out. Second, 3 workers with work-related symptoms were investigated in detail. Skin tests, serum-specific IgE tests with home-made extracts of strawberry pollen and other possible allergenic agents of the strawberry greenhouse environment were executed. Furthermore, immunoblots and nasal provocations with strawberry pollen extract were performed. In addition, inhibition experiments were performed. Results: 29 of 75 questionnaire respondents (38.7%) reported work-related symptoms. Sensitization to strawberry pollen was found in skin tests in all 3 employees with work-related symptoms. ELISA and immunoblotting with strawberry pollen showed positive results in 2 employees. Birch and grass pollen failed to inhibit IgE binding to strawberry pollen in 1 of 2 employees. Partial inhibition was seen in the second employee. Nasal provocation validated clinically relevant allergy to these pollens in 2 of 3 subjects. Conclusions: Allergic symptoms attributable to the workplace are present among a proportion of strawberry greenhouse employees. An IgE-mediated occupational allergy to strawberry pollen may contribute to these symptoms

The effect of birch pollen immunotherapy on apple and rmal d 1 challenges in adults with apple allergy

Background: A proportion of patients allergic to birch pollen are also allergic to pit fruit. The objective of this study was to investigate the effect of immunotherapy with birch pollen on birch-pollen-related apple allergy. Method: Patients with birch pollen immunotherapy underwent a skin-prick test with birch pollen, apple and rMal d 1, global assessments and nasal challenges with birch pollen, open food challenge with apple and a double-blind, placebo-controlled test with rMal d 1 at the start of and during the immunotherapy. Measurements of specific IgE in response to Bet v 1 and rMal d 1 and IgG4 in response to Bet v 1 and rMal d 1 took place. Results: Six of eight patients demonstrated an improvement of nasal challenge test results and all patients improved on global assessment during the immunotherapy. The median oral dose of apple required to elicit a reaction increased but was not statistically significant. The patients showed a decrease in skin-prick test values in response to birch pollen (1.05 to 0.36), apple (0.78 to 0.25) and rMal d 1 (0.51 to 0.10) with p-values of 0.04, 0.03 and 0.06, respectively and a decrease of specific IgE in response to Bet v 1 (10.66 kU/L to 5.19 kU/L) and rMal d 1 (0.99 to 0.61 kU/L) with p-values of 0.01 and 0.05, respectively. Only the median specific IgG4 value to Bet v 1 increased from 0.05 to 1.85 mg/L (p-value of 0.02) and not to IgG4 rMal d 1 (0.07 to 0.08 kU/L). Conclusion: The beneficial effects of immunotherapy for birch pollen were accompanied by a limited effect on apple allergy

A meta-analysis of baseline characteristics in trials on mite allergen avoidance in asthmatics: Room for improvement

Background: Evidence regarding the clinical effectiveness of mite allergen avoidance for the treatment of asthma is lacking. In previous meta-analyses on mite allergen control, the baseline data were not discussed in detail. This study updates and extends the existing Cochrane review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187), with a focus on baseline asthma outcomes and allergen exposures. Methods: We used the existing trials in the original Cochrane review and included newly published studies. The baseline data for the mite allergen load from the mattress, the standardized asthma symptom score (ASS), the forced expiratory volume in 1 s percentage of predicted (FEV1 %pred.), and the histamine provocative concentration causing a 20% drop in FEV1 (PC20) were extracted. First, the mean values of the outcomes were calculated. The influence of the mite allergen load was examined with a random-effect meta-regression using the Metafor package in R. Results: Forty-five trials were included; 39 trials reported strategies for concurrent bedroom interventions, and 6 trails reported strategies for air purification. The mite allergen load ranged from 0.44 to 24.83 μg/g dust, with a mean of 9.86 μg/g dust (95% CI 5.66 to 14.05 μg/g dust, I2 = 99.8%). All health outcomes showed considerable heterogeneity (standardized ASS mean: 0.13, 95% CI 0.08 to 0.18, I2 = 99.9%; FEV1 %pred. mean: 85.3%, 95% CI 80.5 to 90.1%, I2 = 95.8%; PC20 mean: 1.69 mg/mL, 95% CI 0.86 to 2.52 mg/mL, I2 = 95.6%). The covariate mite allergen load did not significantly influence health outcomes. Discussion: This meta-analysis shows that mite avoidance studies are characterized by the inclusion of patients with rather mild to moderate asthma and with varying and sometimes negligible levels of allergen exposure. Future studies should focus on patients with severe asthma and increased levels of allergen exposure

Effectiveness of the Air Purification Strategies for the Treatment of Allergic Asthma: A Meta-Analysis

We updated the meta-analysis published by McDonald et al. [Chest 2002;122;1535-1542] by reviewing the effectiveness of air purification for the treatment of home-related allergic asthma (dust mite, dog, cat, and cockroach). We analysed the trials included by McDonald et al. as well as studies published since 2000. Data on asthma symptoms scores (ASS), medication use, forced expiratory volume in 1 s as a percentage of the predicted value (FEV1 %pred), histamine provocative concentration causing a 20% reduction in FEV1 (PC20), Asthma Quality of Life Questionnaire (AQLQ) scores, and fractional exhaled nitric oxide (FeNO) levels were extracted. The effectiveness was examined using metafor (registered in Prospero CRD42019127227). Ten trials including a total of 482 patients (baseline characteristics: mean FEV1 %pred 83.2%, I2 = 96.7%; mean PC20 4.93 mg/mL, I2 = 44.0%; mean AQLQ 4.67 [max. 7], I2 = 93.7%; mean FeNO 36.5 ppb, I2 = 0%) were included. We assessed the mean differences in the AQLQ scores as +0.36 (95% CI 0.10 to 0.62, p = 0.01, n = 302, I2 = 0%) and the FeNO levels as -6.67 ppb (95% CI -10.56 to -2.77, p = 0.0008, n = 304, I2 = 0%). The standardised mean differences in all other health outcomes were not significant (ASS -0.68, p = 0.20; medication use: -0.01, p = 0.94; FEV1 %pred -0.11, p = 0.34; PC20 +0.24, p = 0.53). We found statistically significant mean differences in the AQLQ scores and FeNO levels in patients with predominantly mild to moderate asthma at baseline. A large trial reported great improvement in the subgroup of patients receiving Global Initiative for Asthma step 4 therapy. We recommend that future studies on air purification focus on patients with severe and poorly controlled allergic asthma

Low percentage of clinically relevant pistachio nut and mango co-sensitisation in cashew nut sensitised children

Background: Cashew nut, pistachio nut and mango belong to the Anacardiaceae family and are botanically related. Therefore, cashew nut sensitised children are frequently advised to eliminate cashew nuts and pistachio nuts from their diet. The ‘Improvement of Diagnostic mEthods for ALlergy assessment (IDEAL trial number NTR3572) study showed that cashew nut sensitised children were co-sensitised to pistachio nut in 98% of cases and to mango in 21% of cases. The aim of this follow-up study to IDEAL is to assess the clinical relevance of co-sensitisation to pistachio nut and mango in cashew nut sensitised children. Methods: Children were recruited from the study: ‘Improvement of Diagnostic mEthods for ALlergy assessment (IDEAL trial number NTR3572). Inclusion criterion for the IDEAL study was sensitization to cashew nut as demonstrated by either SPT or sIgE, and a clinical history of reactions to cashew nuts or no previous (known) exposure. Sensitized children who were tolerant to cashew nuts were excluded. Inclusion criterion for this IDEAL follow-up study was co-sensitization to pistachio nut, regardless the result of the DBPCFC with cashew nut. In this follow-up study a double-blind placebo-controlled food challenge with pistachio nut and an open food challenge with mango were performed. Results: Twenty-nine children (mean age of 11.6 years, 62% male) were included. Pistachio nut sensitisation was clinically relevant in only 34% of cashew-sensitised children and only 31% of cashew challenge positive children. None of the children was challenge positive to mango. Conclusion: Although co-sensitisation between cashew nut and pistachio nut was observed in 98%, pistachio nut sensitisation was only clinically relevant in 34% of the children. Therefore, a challenge test with pistachio nut is recommended in children with cashew nut and pistachio nut sensitisation

Allergenic food introduction and risk of childhood atopic diseases

Background: The role of timing and diversity of allergenic food introduction in the development of childhood allergic sensitization and atopic diseases is controversial. Objective: To examine whether timing and diversity of allergenic food introduction are associated with allergic sensitization, allergy and eczema in children until age 10 years. Materials and methods: This study among 5,202 children was performed in a population-based prospective cohort. Timing (age 6 months vs. >6 months) and diversity (0, 1, 2 and 3 foods) of allergenic food (cow’s milk, hen’s egg, peanut, tree nuts, soy and gluten) introduction were assessed by questionnaires at ages 6 and 12 months. At age 10 years, inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by questionnaire. Data on parental-reported physician-diagnosed eczema were obtained from birth until age 10 years. Results: Children introduced to gluten at age 6 months had a decreased risk of eczema (aOR (95% CI): 0.84 (0.72, 0.99)), compared with children introduced to gluten at age >6 months. However, timing of allergenic food introduction was not associated with allergic sensitization or physician-diagnosed allergy. Children introduced to 3 allergenic foods at age 6 months had a decreased risk of physician-diagnosed inhalant allergy (0.64 (0.42, 0.98)), compared with children not introduced to any allergenic food at age 6 months. However, diversity of allergenic food introduction was not associated with allergic sensitization, physician-diagnosed food allergy or eczema. Conclusion: Neither timing nor diversity of allergenic food introduction was consistently associate