What happens to basophils and tryptase, LXA4 and CysLTs during aspirin desensitization?

INTRODUCTION: Aspirin desensitization (AD) is an effective treatment in patients with non-steroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (NERD) by providing inhibitory effect on symptoms and polyp recurrence. However, limited data is available on how AD works. We aimed to study comprehensively the mechanisms underlying AD by examining basophil activation (CD203c upregulation), mediator-releases of tryptase, CysLT, and LXA4, and LTB4 receptor expression for the first 3 months of AD. METHODS: The study was conducted in patients with NERD who underwent AD (group 1: n = 23), patients with NERD who received no desensitization (group 2: n = 22), and healthy volunteers (group 3, n = 13). All participants provided blood samples for flow cytometry studies (CD203c and LTB4 receptor), and mediator releases (CysLT, LXA4, and tryptase) for the relevant time points determined. RESULTS: All baseline parameters of CD203c and LTB4 receptor expressions, tryptase, CysLT, and LXA4 releases were similar in each group (p > 0.05). In group 1, CD203c started to be upregulated at the time of reactions during AD, and continued to be high for 3 months when compared to controls. All other study parameters were comparable with baseline and at the other time points in each group (p > 0.05). CONCLUSION: Although basophils are active during the first 3 months of AD, no releases of CysLT, tryptase or LXA4 exist. Therefore, our results suggest that despite active basophils, inhibition of mediators can at least partly explain underlying the mechanism in the first three months of AD.

The role of component-resolved diagnosis in Hymenoptera venom allergy in clinical practice.

Background: Hymenoptera venom allergy is an immunoglobulin (Ig) E mediated hypersensitivity reaction to Hymenoptera venoms. Obvious identification of the culprit insect that causes the clinical symptoms and, hence, the accurate selection of venom for curative treatment, is of great importance for the effectiveness and safety of venom immunotherapy. Objective: In this study, the contribution of component-resolved diagnostics (CRD) is evaluated in the diagnosis of Hymenoptera venom allergy. Method: Ninety-three patients from four different centers in Turkey were included in the study. Conventional tests, including prick and intradermal skin tests, with commercial venom extracts and serum specific IgE (sIgE) levels for whole venoms were performed. An sIgE analysis for venom allergen components, including rApi m 1, rApi m 2, rApi m 10, rVes v 1, rVes v 5, were evaluated by immunoblotting. Results: In conventional test results, 17 of 35 patients with bee venom allergy were positive to honey bee venom, whereas 18 patients were positive to bee and wasp venoms. In 28 of 35 patients with bee venom allergy, the diagnosis was confirmed with CRD. CRD revealed a sensitivity of 80% in patients with bee venom allergy. According to conventional tests, 7 of 24 patients with vespid venom allergy demonstrated sensitivity only to Vespula species, whereas 17 patients revealed double positivity. The total diagnostic sensitivity of Ves v 1 and Ves v 5 was calculated as 87.5%. Ten of 23 patients with a history of hypersensitivity to both venoms showed double sensitivity with CRD; one patient had cross-reactivity, one patient was found to be sensitive only to bee venom, and, eight patients were sensitive only to Vespula species. Eleven patients had an uncertain history in terms of the culprit insect type and six of them had double sensitivity in CRD. Conclusion: CRD seemed to be more helpful in diagnosing vespid venom allergy than bee venom allergy. It can also discriminate clinically significant sensitizations from irrelevant ones.

Omalizumab in non-allergic Asthma: A report of 13 cases.

BACKGROUND: There are limited data regarding the effectiveness of omalizumab in patients with non-allergic asthma. OBJECTIVE: To evaluate the clinical and functional effectiveness of omalizumab in patients with non-allergic asthma. METHODS: The study was a single-center, retrospective chart review of patients with non-allergic asthma who were treated with add-on omalizumab between February 2014 and March 2016. After omalizumab was started, data of the asthma control test (ACT), pulmonary function test, and daily oral corticosteroid (OCS) dosage were collected at baseline, 16 weeks, 1 year, 2 and 3 years (if available). The number of exacerbations/hospitalizations were collected 1 year prior to and 6 months/1 year after omalizumab. To calculate the total daily dosage of OCS in milligrams, data for 6 months/1 year prior and after omalizumab treatment were recorded. RESULTS: Thirteen patients were included. After omalizumab, the mean ACT was significantly increased at 16 weeks (n = 13, p = 0.002), 1 year (n = 7, p = 0.006), and 2 years (n = 5, p = 0.006). The mean daily OCS dose was significantly decreased at 16 weeks (n = 13, p = 0.001), 1 year (n = 7, p = 0.006), and 2 years (n = 5, p = 0.04). The mean number of exacerbations and hospitalizations were decreased at the 6th month (n = 13; p = 0.001, p = 0.005) and 1st year (n = 7; p = 0.01, p = 0.02). The mean total quantity of OCS decreased 42% from 1.4 to 0.8 g in the six-month period prior to and post-omalizumab treatment (n = 6, p = 0.02) and decreased 76% from 3.8 to 0.9 g at 1 year in the pre vs. post-omalizumab treatment comparison (n = 7, p = 0.01). Six (46.2%) patients responded perfectly and seven (53.8%) partially responded to treatment. CONCLUSION: Omalizumab can be effective in non-atopic severe asthma.

Comparison of two diagnostic criteria in the diagnosis of anaphylaxis in a tertiary adult allergy clinic.

Background: Anaphylaxis is a very dynamic issue with its incidence and trigger profile changing over the years. We aimed to compile the characteristics of anaphylaxis cases diagnosed in our clinic prospectively and to make a comparison between diagnostic criteria proposed by National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) and World Allergy Organization (WAO). Method: Three-item diagnostic criteria recommended by NIAID/FAAN (2006) were used in the diagnosis of anaphylaxis. The clinical features of the cases, risk factors, etiologies, severity of anaphylaxis, and treatment approach were determined. The same patients were also classified by current WAO diagnostic criteria. Results: A total of 204 patients (158F/46 M, median age 45.3 years) were included. Drugs (65.2%), venom (9.8%) and food allergies (9.3%) were the top 3 etiologies. Among drug triggers, chemotherapeutics were the most common (17.7%), followed by antibiotics (15.3%) and non-steroidal anti-inflammatory drugs (14.2%). The patients were mostly diagnosed with the second criterion (84.8%), followed by the first criterion (11.8%) and the third criterion (3.4%) of the NIAID/FAAN criteria. In terms of WAO criteria, 82.8% of the patients were diagnosed with the first criterion, and 14.3% with the second criterion while 2.9% of the patients did not meet the WAO criteria. The severity of anaphylaxis was evaluated as grade-2, 3 and 4 in 30.9%, 64.2%, and 4.9% of the patients, respectively. Adrenaline was administered to 31.9% of the patients especially who had angioedema and bronchospasm (p = 0.04). Conclusion: Our data suggest that covering more details in patient's history may prevent possible underdiagnosis and WAO diagnostic criteria seem to be insufficient in some patients. We believe that our results will contribute to the literature on anaphylaxis and would be groundwork for future studies.

Reliability of basophil activation test using CD203c expression in diagnosis of pollen allergy.

BACKGROUND: CD203c is a basophil surface marker and its expression is rapidly up-regulated after cross-linking of high-affinity immunoglobulin E (IgE) receptor (FcepsilonR1) by an allergen. CD203c basophil activation tests have been studied for the in vitro diagnosis of several allergic conditions. However, there is limited data about its diagnostic usefulness. The optimum allergen concentrations for stimulation and allergen specific cutoff values remain unknown for a number of allergens. This study was designed to investigate the efficacy of basophil activation test via CD203c in the diagnosis of pollen allergy. METHODS: The CD203c basophil activation was determined in 31 allergic rhinitis patients with pollen allergy and 9 healthy nonatopic controls during the off-season. CD203c expression was evaluated using three-color staining protocol by flow cytometry. RESULTS: After an in vitro stimulation with grass pollen extract, the CD203c assay clearly discriminated pollen-allergic patients from controls (p < 0.001). A dose-dependent increase in the percentages of CD203c-activated basophils was shown in rhinitis patients with pollen allergy (p < 0.001). The sensitivity and specificity was 100% and optimal cutoff values were 14.05 and 10.05% with 45.1 and 4.5 µg/mL Phl p 5 stimulation, respectively. Although the specificity was also 100%, the sensitivity was 93 and 87% and the cutoff values were 5.40 and 5.35% with 4.5 × 10(-4) and 4.5 × 10(-5) micrograms/mL Phl p 5 stimulation, respectively. CONCLUSION: The CD203c basophil activation test seems to be a reliable tool in the diagnosis of grass pollen allergy. It could be used when conventional diagnostic tests fail or can not be performed.