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.

Incidence and clinical course of COVID-19 in patients using omalizumab for chronic spontaneous urticaria and/or severe allergic asthma and using mepolizumab for severe eosinophilic asthma: A single center real life experience.

Introduction: To assess the incidence and course of COVID-19 in patients with severe asthma/chronic spontaneous urticaria using biological agents. Materials and Methods: A total of 202 patients (142 with asthma, and 60 with urticaria) were enrolled. The subjects were asked via face-to-face or telephone interview whether they had been diagnosed with COVID-19 and the course of the disease. Result: Study group consisted of 132 women, and 70 men (median age= 48 years). Median omalizumab dose was 300 mg/month in asthma (min-max= 150-1200 mg). The mepolizumab dose of two patients diagnosed with EGPA was 300 mg/month. Thirty one (15.3%) patients were diagnosed with COVID-19, 22 (71%) of whom were receiving omalizumab and nine (29%) were receiving mepolizumab. Asthma or chronic spontaneous urticaria diagnosis, age, sex, smoking, weight, comorbidities, atopy, and biological agent use were not statistically different between patients with or without COVID-19. Nine COVID-19 patients were hospitalized, and three of them required intensive care. Mepolizumab usage was higher in hospitalized patients (5, 55.6%), whereas omalizumab usage was higher in home-treated patients (18, 81%). The mean duration of biological use in home-treated patients was significantly higher than that of the hospitalized patients (35.64 months vs. 22.56 months, p= 0.024). Biological treatment was interrupted in 47 (23%) patients, selfinterruption due to the infection risk was the foremost reason (34%). Conclusions: The incidence of COVID-19 among patients with asthma and urticaria on mepolizumab and omalizumab was higher compared to studies from other countries. The disease course appeared mild in patients receiving long-term biological therapy.

Characteristics of the patients with asthmarhinitis multimorbidity.

Introduction: Asthma and allergic rhinitis frequently coexist and have been regarded as a single airway disease. Clinical features of patients with asthmarhinitis multimorbidity may change depending on the allergic sensitization pattern. The aim of our study is to determine the frequency, type, and characteristics of the patients with asthma-rhinitis multimorbidity. Materials and Methods: Patients who were followed up with a diagnosis of asthma between 2015 and 2020 in our clinic were included in our crosssectional study. Sociodemographic and clinical characteristics of the patients, rhinitis symptoms, and atopy status according to the results of the skin prick test, and sp IgE were recorded from the patient files. Result: Asthma-rhinitis multimorbidity was seen in 138 (113 F/25 M) out of 405 asthmatics and the mean age was 45.51 ± 13.56 years. They were younger and the age of onset of asthma was earlier than asthma patients without rhinitis. The rate of concomitant allergic rhinitis (AR) was 25.9%, and the rate of non-allergic rhinitis (NAR) was 8.1% in the entire group. There was no difference between patients with AR and NAR in terms of comorbidities such as NSAID sensitivity, nasal polyps, chronic rhinosinusitis, and bronchiectasis but, gastroesophageal reflux disease was more common in those with NAR than in those with AR (39.4%, 18.1%, respectively, p= 0.01). Of 105 asthmatic patients accompanied by allergic rhinitis, 41 (39.09%) were monosensitized, and 64 (60.95%) were polysensitized. House dust mites were found to be the most common responsible allergen in monosensitized patients. Sensitization to two allergens was the most common pattern among polysensitized patients, and mites and mold association was the most frequent. Patients with monosensitized allergic rhinitis had more severe asthma and a higher rate of NSAID sensitivity than polysensitized patients (p= 0.03, p= 0.04, respectively). There was no difference in the control level, frequency of eosinophilia, and other comorbidities. Conclusions: Our patients with asthma-rhinitis multimorbidity were mostly polysensitized. The most responsible allergen for the sensitization was house dust mites, regardless of whether the patient was monosensitized or polysensitized.

Effectiveness of Low-Dose Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA): A Real-Life Experience.

INTRODUCTION: Data showing effectiveness of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA) are limited. METHODS: This is a single-center retrospective chart review of patients with EGPA treated with mepolizumab. Clinical, laboratory, functional parameters and asthma, rhinitis control, and quality of life scores (Asthma Control Test [ACT], Asthma Quality of Life Questionnaire [AQLQ], Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ], and SinoNasal Outcome Test [SNOT]-22) were evaluated at the baseline, 6th month, and 12th month. Complete response was defined as the absence of asthma and/or ear, nasal symptoms and exacerbations with a prednisone of ≤7.5 mg/day, partial response if it was achieved with a prednisone of >7.5 mg/day. RESULTS: Overall, 25 patients (18 F/7 M) with a median age of 47 years (23-76) were enrolled. Mepolizumab 100 mg/month was administered (dose increased to 300 mg/month in 3 patients). Mepolizumab significantly decreased daily dose of oral corticosteroid (OCS) from 11.04 mg to 3.65 mg together with a significant improvement in ACT, AQLQ, RQLQ, and SNOT-22 scores and a significant reduction in asthma exacerbations and blood eosinophil count at the 6th and 12th month (all p values <0.05). The mean forced expiratory volume in 1 s increased (at baseline: 1.88 L to 2.46 L at the 12th month [p = 0.037]). Seventy-six percent of patients responded completely at the 6th month and 81.25% at the 12th month. The complete responders at the 6th and 12th month were older than partial responders and nonresponders (p = 0.030 and p = 0.057, respectively). Patients with complete response at the 6th month were on lower doses of OCS than partial responders and nonresponders (p = 0.029). CONCLUSIONS: Low-dose mepolizumab was effective in EGPA patients by improving sinonasal and asthma outcomes, while reducing the need for OCS.

Churg-Strauss syndrome: a new endotype of severe asthma? Results of 14 Turkish patients.

INTRODUCTION: Churg-Strauss syndrome (CSS) is a rare multisystem vasculitis. Considering the variation of autoimmune diseases in different races, it is of interest to determine whether any outstanding features exist for Turkish patients with CSS. OBJECTIVE: The aim of this study was to evaluate the clinical and serological features of the disease, the treatment, and long-term follow-up details, and to investigate possible etiological factors of Turkish CSS patients. METHODS: The study included 14 patients who were diagnosed with CSS, and followed by our department between 2004 and 2012. Possible etiological factors, initial symptoms, clinical presentations, treatment, as well as outcomes were documented. The study was approved by the local ethics. RESULTS: All patients fulfilled the American College of Rheumatology criteria. Initial symptoms were worsening asthma (n = 14; 100%) and skin lesions (n = 6; 43%). All patients had a diagnosis of asthma and nasal polyps, whereas 57.1% had aspirin hypersensitivity at the time of diagnosis. The lungs (100%) and skin (43%) were most commonly involved. Peripheral eosinophilia dominated on initial presentations of all patients. Initial treatments included oral methyl prednisolone in all cases, whereas cyclophosphamide and azathioprine were used in three cases. Relapses were detected in five cases. None of the cases were able to stop the oral corticosteroid treatment. No fatalities were observed. CONCLUSION: We herein describe a new severe asthma endotype in connection with CSS. We suggest that physicians who deal with uncontrolled severe asthma cases should consider CSS in the presence of nasal polyps, aspirin hypersensitivity, and especially peripheral blood eosinophilia over 10%.