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.

Comparison of perennial and preseasonal allergoid immunotherapy in grass pollen allergic patients.

BACKGROUND: The clinical and immunological efficacy of preseasonal allergoid immunotherapy has been previously investigated, however, studies comparing the effectiveness of the two protocols are limited in the literature. OBJECTIVE: The aim of this study is to compare the clinical and immunological efficacy of pre-seasonal and perennial allergoid immunotherapy. METHODS: This is a prospective cross sectional two-arm study. During the season; symptom and medication scores were filled. Before and at the end of the season; RQLQ was applied, Phl p sIgE, sIgG4 and IL-10 levels were measured. RESULTS: In preseasonal group patients had better symptom control for most of the weeks, particularly during the peak pollen period (April: w-2 & w-4, p = 0.04; May: w-2, p = 0.02; June: w-1, w-2, p = 0.02; w-3, w-5, p = 0.03; July: w-2, p = 0.01; w-3, p = 0.02; w-4, p = 0.04). In the perennial group, sIgG4 [1st time point: preseasonal 0.02 mgA/L vs perennial 0.13 mgA/L (p < 0.0001); 2nd time point: preseasonal 0.52 mgA/L vs perennial 0.33 mgA/L; 3rd time point: preseasonal 0.04 mgA/L vs perennial 0.12 mgA/L (p < 0.0001)] and IL-10 (1st time point: preseasonal 1.45 pg/ml vs perennial 2.03 pg/ml; 2nd time point: preseasonal 2.29 pg/ml vs perennial 2.19 pg/ml; 3rd time point: preseasonal 2.32 pg/ml vs perennial 2.16 pg/ml) levels were higher and more stable. CONCLUSIONS: Preseasonal immunotherapy provided better control of symptoms throughout the pollen season. However, the blocking antibody response was stronger and more permanent in the perennial immunotherapy group.

Baker's asthma in bread factory workers.

Background: Baker's asthma (BA) is one of the most common causes of occupational asthma. Prevalence of BA varies from 3 to 24% in various studies; however, in our country, there are not enough data on its prevalence. Objective: The aim of this study was to evaluate wheat flour sensitivity and to determine the rate of BA in workers at a large bread factory in Ankara. Methods: All steps of the study were carried out in the workplace by the research team who made regular visits to the bread factory. A questionnaire was used to determine the presence of respiratory symptoms and its relation with the occupation. Skin-prick tests and specific immunoglobulin E measurements were performed. Pulmonary function tests and specific inhalation challenges (SIC) were performed to confirm the BA diagnosis. Results: A total of 162 workers (women/men, 3/159; mean ±standard error age, 38.25 ± 7.8 years) were included in the study. Of the 99 workers who described symptoms, 88 (88.8%) had nasal and 57 (57.5%) had lower respiratory symptoms. Sensitivity to wheat flour was present in 23 of the workers (14.2%) among all the workers. Among all the workers, seven (4.32%) were diagnosed with BA and SICs were positive in four (2.46%). Conclusion: Wheat sensitivity was high among the bakers who were exposed to wheat flour; however, the prevalence of BA was quite lower than the previous data in the literature.

Immunologic alterations and efficacy of subcutaneous immunotherapy with Dermatophagoides pteronyssinus in monosensitized and polysensitized patients.

BACKGROUND: There is a continuing debate about whether monoallergen subcutaneous immunotherapy (SCIT) is able to modulate immune and clinical responses toward main causal allergen in polysensitized patients. OBJECTIVE: To investigate short-term immunologic changes and clinical effectiveness of SCIT with Dermatophagoides pteronyssinus in monosensitized and polysensitized patients who have rhinitis with or without asthma. METHODS: Nineteen monosensitized and 24 polysensitized patients participated in this prospective, self-placebo-controlled, interventional study. Cluster immunotherapy with D pteronyssinus was administered after 2 months of placebo in both groups. Immunologic parameters, including CD203c expression on basophils after allergen stimulation, total IgE, specific IgE, and specific IgG4, were evaluated at baseline, after placebo, and after immunotherapy. Clinical effectiveness was assessed using monthly symptom-medication scores, visual analog scale, quality-of-life questionnaire, and nasal allergen provocation test. RESULTS: At baseline, polysensitized patients had higher CD203c expression on basophils than monosensitized patients (P = .007). Activated basophils expressing CD203c, total IgE, and specific IgG4 were significantly increased after immunotherapy compared with baseline and placebo in the polysensitized group (P < .025). After immunotherapy, specific IgE and D pteronyssinus-induced CD203c expression were significantly higher in polysensitized than monosensitized patients (P < .05). The total symptom scores and the Mini Rhinoconjunctivitis Quality of Life Questionnaire scores in polysensitized patients and the visual analog scale scores in both groups were lower after immunotherapy compared with baseline and placebo (P < .025). Titrated nasal allergen provocation test with D pteronyssinus increased after immunotherapy in the monosensitized group (P < .05). CONCLUSION: This study indicates that monosensitized and polysensitized patients have distinct humoral response and basophil behavior to SCIT. However, a single-allergen immunotherapy corresponding to the most clinically troublesome allergy in polysensitized patients can lead to early clinical efficacy comparable to that seen in monosensitized patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01795846.

Evaluation of vascular endothelial growth factor A and endostatin levels in induced sputum and relationship to bronchial hyperreactivity in patients with seasonal allergic rhinitis.

BACKGROUND: Studies about the pathogenesis of bronchial hyperreactivity (BHR) in patients with allergic rhinitis (AR) and its relationship with lower airway remodeling are extremely limited. In this study, bronchial vascular remodeling and its relationship with BHR were evaluated by measurement of vascular endothelial growth factor A (VEGF-A) and endostatin in patients with seasonal AR (SAR). METHODS: The study group consisted of 30 patients with SAR (positive skin test to grass pollens) and 14 healthy controls. Induced sputum and bronchial provocation test (BPT) to methacholine (M) were performed in season. VEGF-A and endostatin levels were measured by ELISA in induced sputum supernatant. RESULTS: The percentages of eosinophils in induced sputum were significantly increased in BHR+ patients (n = 10) with SAR compared with BHR(-) patients (n = 20) with SAR (p < 0.001). There was no correlation between eosinophils and provocative concentration of M required to produce a 20% decrease in forced expiratory volume in 1 second. The levels of VEGF-A were significantly higher in SAR patients with BHR than in SAR patients without BHR and healthy controls (respectively, p = 0.014 and p = 0.04). The levels of endostatin were significantly lower in SAR patients with BHR than in SAR patients without BHR and healthy controls (respectively, p = 0.020 and p = 0.014). The ratio of VEGF-A/endostatin was significantly higher in SAR patients with BHR than in SAR patients without BHR and healthy controls (respectively, p = 0.009 and p = 0.019). CONCLUSION: In this first study comparing the VEGF-A and endostatin levels of patients with SAR in sputum supernatant, the presence of BHR was shown to be associated with the vascular component of remodeling "angiogenesis."