Antonios Patelis

Population-based study of multiplexed IgE sensitization in relation to asthma, exhaled nitric oxide, and bronchial responsiveness

BACKGROUND IgE sensitization is an important risk factor for the development of asthma. OBJECTIVE The aim of this study was to investigate the IgE antibody profile for a broad spectrum of allergen molecules in asthmatic patients. METHODS Participants from the European Community Respiratory Health Survey II (n=467) were tested with ImmunoCAP ISAC against 103 allergen molecules. The presence of bronchial hyperresponsiveness was measured with a methacholine challenge test and bronchial inflammation with fraction of exhaled nitric oxide (Feno). RESULTS A total of 38% of the controls and 72% of the asthmatic patients were sensitized against at least 1 of the allergen components (P<.0001). Asthma was independently related to having IgE antibodies against pollen (odds ratio=2.2) and perennial airway allergens (odds ratio=5.6), increased Feno was independently related to having IgE antibodies against food allergens and perennial allergens, while bronchial responsiveness was independently associated with having IgE antibodies against only perennial allergens. Sensitization to food allergens was related to asthma and increased Feno if IgE antibody against pollen allergens was present. Simultaneous sensitization to perennial, pollen, and food allergens involves the highest risk of asthma (odds ratio=18.3), bronchial inflammation, and responsiveness. CONCLUSIONS Feno, bronchial responsiveness, and the risk of asthma increase with multiple sensitizations to different allergen groups. We show for the first time that the presence of IgE antibodies against food allergens is independently associated with increased Feno and increases the risk of asthma in subjects with simultaneous sensitization to pollen allergens.

Aeroallergen and food IgE sensitization and local and systemic inflammation in asthma

We recently reported an independent association between IgE sensitization to food allergens and increased airway inflammation, assessed by fraction of exhaled nitric oxide (FeNO), in a population‐based study (J Allergy Clin Immunol, 130, 2012, 397). Similar studies have not been performed in populations with asthma. The aim of the present study was to investigate the allergic sensitization profile in asthmatics and examine FeNO, airway responsiveness and blood eosinophilia in relation to type and degree of IgE sensitization.

Multiplex component-based allergen microarray in recent clinical studies

During the last decades component‐resolved diagnostics either as singleplex or multiplex measurements has been introduced into the field of clinical allergology, providing important information that cannot be obtained from extract‐based tests. Here we review recent studies that demonstrate clinical applications of the multiplex microarray technique in the diagnosis and risk assessment of allergic patients, and its usefulness in studies of allergic diseases. The usefulness of ImmunoCAP ISAC has been validated in a wide spectrum of allergic diseases like asthma, allergic rhinoconjunctivitis, atopic dermatitis, eosinophilic esophagitis, food allergy and anaphylaxis. ISAC provides a broad picture of a patients sensitization profile from a single test, and provides information on specific and cross‐reactive sensitizations that facilitate diagnosis, risk assessment, and disease management. Furthermore, it can reveal unexpected sensitizations which may explain anaphylaxis previously categorized as idiopathic and also display for the moment clinically non‐relevant sensitizations. ISAC can facilitate a better selection of relevant allergens for immunotherapy compared with extract testing. Microarray technique can visualize the allergic march and molecular spreading in the preclinical stages of allergic diseases, and may indicate that the likelihood of developing symptomatic allergy is associated with specific profiles of sensitization to allergen components. ISAC is shown to be a useful tool in routine allergy diagnostics due to its ability to improve risk assessment, to better select relevant allergens for immunotherapy as well as detecting unknown sensitization. Multiplex component testing is especially suitable for patients with complex symptomatology.

Natural History of Perceived Food Hypersensitivity and IgE Sensitisation to Food Allergens in a Cohort of Adults

Background No longitudinal studies exist on the natural history of food hypersensitivity and IgE sensitisation to food allergens in adults. Objective To examine the natural history of food hypersensitivity, the natural history of IgE sensitisation to food allergens and to investigate the risk factors for new onset food hypersensitivity. Methods Food hypersensitivity was questionnaire-assessed in 2307 individuals (aged 20–45 years) from Iceland and Sweden during the European Community Respiratory Health Survey both at baseline and follow-up 9 years later. IgE food and aeroallergen sensitisation were assessed in a subgroup of these individuals (n = 807). Values of 0.35 kU/L and above were regarded as positive sensitisation. Results Food hypersensitivity was reported by 21% of the subjects and this proportion remained unchanged at follow-up (p = 0.58). Fruits, nuts and vegetables were the three most common causes of food hypersensitivity, with a similar prevalence at baseline and follow-up. The prevalence IgE sensitisation to food allergens decreased in general by 56% (p<0.001) and IgE sensitisation to peanut decreased in particular by 67% (p = 0.003). The prevalence of timothy grass IgE sensitisation decreased by 15% (p = 0.003) while cat, mite and birch IgE sensitisation did not decrease significantly. Female sex, rhinitis, eczema and presence of IgE sensitisation to aeroallergens were independently associated with new onset food hypersensitivity. Conclusion The prevalence of food hypersensitivity remained unchanged while the prevalence of IgE sensitisation to food allergens decreased in adults over a 9-year follow-up period. The decrease in prevalence of IgE sensitisation to food allergens was considerably larger than the change in prevalence of IgE sensitisation to aeroallergens.

Allergen extract vs. component sensitization and airway inflammation, responsiveness and new‐onset respiratory disease

The absence of IgE sensitization to allergen components in the presence of sensitization to the corresponding extract has been reported, but its clinical importance has not been studied.

New data analysis in a population study raises the hypothesis that particle size contributes to the pro-asthmatic potential of small pet animal allergens.

Abstract Background: The size of inhaled particles influences where they deposit and theoretically should be important for the development of airway inflammation and responsiveness. Our aim was to assess if sensitization to smaller-sized aeroallergens relates to higher prevalence of treated asthma, increased airway responsiveness, and airway and systemic inflammation. Methods: Molecular-based IgE antibody determination was done in 467 subjects. Sensitized subjects were grouped based on the particle size of the aeroallergen: (1) Large particles only (mainly pollen); (2) Medium-sized particles (sensitized to mainly mite and mold and possibly to large particles); and 3) Small particles (sensitized to pet allergens and possibly to medium- and/or large-sized particles). Airway responsiveness to methacholine, exhaled nitric oxide (FENO), and serum eosinophil cationic protein (S-ECP) were measured. Asthma and rhinitis were questionnaire-assessed. Results: Subjects sensitized to small particles had higher prevalence of treated asthma (35% versus 10%, P < 0.001), higher FENO50 (32 versus 17 ppb, P < 0.001), higher S-ECP (10 versus 7.5 ng/mL, P = 0.04), and increased bronchial responsiveness (dose-response slope, 5.6 versus 7.5, P < 0.001) compared with non-atopics. This was consistent after adjusting for potential confounders. Sensitization to only large or to medium and possibly also large aeroallergen particles was not related to any of these outcomes after adjustments. Conclusions: Sensitization to smaller particles was associated with a higher prevalence of asthma under treatment, higher airway responsiveness, and airway and systemic inflammation. Mapping of IgE sensitization to small particles might help to detect subjects having increased airway and systemic inflammation and bronchial responsiveness, indicating increased risk of developing asthma.

IgE sensitisation to food allergens and airborne allergens in relation to biomarkers of type 2 inflammation in asthma.

We have recently reported that sensitization to food allergens and sensitization to airborne allergens had independent associations with increased fraction of exhaled nitric oxide (FeNO) and blood eosinophils in middle‐aged adults and in young subjects with asthma.

Author’s response: Dysfunction of small airways and prevalence, airway responsiveness and inflammation in asthma: much more than small particle size of pet animal allergens

Authors response : Dysfunction of small airways and prevalence, airway responsiveness and inflammation in asthma: much more than small particle size of pet animal allergens

Clinical relevance of measuring IgE to cat allergen components

Background: Although pretreatment is not routinely used before immunotherapy, it has been shown to reduce the reactions in patients using rush, cluster and conventional schedules. Our aim is to determine the possible preventive effects of various premedication usage on systemic and local reactions during cluster immunotherapy. Method: One hundred and eighteen patients receiving a total of 137 cluster immunotherapy protocols to mites, pollens, bee and wasp venoms were recruited in the study. Patients were randomized into 5 different groups according to premedication status as shown here below: Group 1: daily levosetirizine, Group 2: levosetirizine only 2 h prior to injections, Group 3: daily montelukast, Group 4: combinations of montelukast and levosetirizine and, Group 5: no premedication Patients were followed during build up and maintenance phase of immunotherapy, systemic and local reactions were reported. Reactions are reported according to World Allergy Organization Subcutaneous Systemic Reaction Grading System. Results: Most of the patients were female (%64.2), the most frequent allergen was house dust mites (50.4%). Of 69.3% of patients took premedication and 19.7% of patients had reactions during the build up phase. Reactions were more frequent in patients who have pollen allergy and have received pollen immunotherapy [P = 0.034; OR = 2.65 CI:95%, 1.05–6.63)]. The total frequency of the hypersensitivity reaction was significantly higher in patients not receiving premedication [14 (14.7%) vs 13 (31.0%), P = 0.028 ]. However no difference was detected between groups taking various drugs for premedication. The patients in the premedication group significantly experienced less local reactions (P = 0.033) although no difference in the frequency of systemic reactions was seen between the groups. Conclusion: These preliminary results suggest that the reaction risk is increased in pollen immunotherapy and premedication does not seem to prevent the frequency or severity of systemic reactions although it decreases the frequency of local reactions. As the number of patients recruited in the study increases, the effect of premedication on reactions may be clearer.A three year follow-up of asthma, respiratory symptoms and self-reported allergy, among pilots and cabin attendants

IgE sensitisation to food allergens is independently associated with exhaled nitric oxide and blood eosinophils in asthmatics - results from the MIDAS study

Background: It was reported in two studies that inhalation challenges with HDM aggravated skin lesions in patients with atopic dermatitis, especially in those with concomitant allergic asthma. The effect of HDM inhalation on aggravating skin responses in patients with hand eczema had never been investigated. Method: Of 18 patients with vesicular hand eczema and HDM allergy (positive SPT to D. pteronyssinus) were investigated in a randomised, double-blind, placebocontrolled, cross-over study. Increasing concentrations of standardised HDM (80, 400, 2000, 10 000 BU/ml) were inhaled for 1 min at intervals of 15 min. The FEV1 was measured immediately before and after each dose, after the last challenge every 10 min for 1 h, and thereafter every hour for 7 h. The placebo challenge procedure was the same as described for the active suspension. The time interval between HDM and placebo was 2-4 weeks. Early asthmatic reactions and late asthmatic reactions (LAR) were defined as a placebocorrected fall of 15% or more from baseline of FEV1. Hand eczema was scored according to the Dyshidrotic eczema Area and Severity Index (DASI) at baseline, 1, 6, 24 and 48 h. Total IgE was measured at the start of the first provocation day and serum eosinophils on both provocation days before the first challenge and 24 h later. Results: Significant increases in median DASI score and median DASI sub-scores were seen only after HDM provocation. After placebo provocation, no significant differences from baseline were seen. The median DASI increased significantly as compared with baseline at 6 and 48 h after HDM inhalation. This increase was significantly different between the provocations at 6 h. The median vesicles score increased significantly from baseline at 24 and 48 h. Patients with a placebo-corrected increase of vesicles at 24 and 48 h had significantly more often a LAR than those without an increase of vesicles. Patients with a placebo- corrected increase of the DASI at 24 h had as a group a higher mean total IgE level than those without an increase of the DASI. The increase in serum eosinophils 24 h after HDM provocation was not significantly different between the placebocorrected skin responders and non-skin responders. Conclusion: Hand eczema increased significantly more after HDM provocation than after placebo provocation. An increase of vesicles was preceded by a LAR. The group patients with an increase of hand eczema tended to have a higher mean total IgE level.