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.

Diagnosis and management of the drug hypersensitivity reactions in Coronavirus disease 19: An EAACI Position Paper.

Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.

Controversies in Drug Allergy: Radiographic Contrast Media.

The risk for developing immediate or delayed hypersensitivity reactions to radiocontrast media (RCM) interferes with the diagnosis and treatment of a number of patients requiring imaging diagnostic methods for many common diseases. A group of experts met in Orlando, Florida, in March 2018 to analyze the similarities and differences in the management of RCM reactions in different areas of the world. This paper presents a summary of the recommendations provided by this consensus group, highlighting controversial issues and unmet needs that require further research.

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.

[Acute exacerbation in COPD and asthma]. / KOAH ve astimda atak.

Chronic obstructive pulmonary disease (COPD) and asthma are airway diseases with acute exacerbations. Natural course of both disease are affected by exacerbations. COPD exacerbations may be caused by infections and other causes; indoor and outdoor pollution, cardiovascular diseases, asthma-COPD overlap syndrome, COPD- obstructive sleep apnea syndrome, pulmonary embolism, gastro-oesophageal reflux, anxiety-depression, pulmonary hypertension. Exposure to triggering factors, viral infections, treatment insufficiency may cause asthma exacerbations. Smoking cessations, prevention of infections, long-acting anticholinergics, long-acting 2 agonists, inhaled corticosteroids, phosphodiesterase-4 inhibitors, mucolytics, prophilactic antibiotics can be effective on the prevention of COPD exacerbations. Asthma exacerbations may be decreased by the avoidance of allergens, viral infections, occupational exposures, airpollution, treatment of comorbid diseases. Effective treatment of asthma is required to prevent asthma exacerbations. Inhaled steroids and combined treatments are the most effective preventive therapy for exacerbations. Patient education and cooperation is an element of the preventive measures for asthma attacks. Compliance to therapy, inhalation techniques, written asthma plans are required. The essential of COPD and asthma exacerbation treatment is bronchodilator therapy. Steroids are also implemented to the therapy, targeting the inflammation. Specific treatments of the cause (infection, airpollution, pulmonary embolism etc.) should be administered.

Diagnosis of immediate hypersensitivity to ß-lactam antibiotics can be made safely with current approaches.

BACKGROUND: Diagnosing immediate hypersensitivity to ß-lactam antibiotics is still a significant problem. Recently, a new penicillin testing reagent was introduced to the market. In this study, the recommendations of the European Network of Drug Allergy (ENDA) for the diagnosis of immediate reactions to ß-lactams were followed, and the negative predictive value of this approach with currently available reagents was assessed. METHODS: Eighty patients (age range: 6-74 years) with a history of immediate reactions to ß-lactams were included. All cases underwent skin testing with benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM), followed by the culprit drug if necessary. If this step was negative, a drug provocation test was offered. If this step also yielded a negative result, then the patients were recommended to use ß-lactam antibiotics in future whenever their use was indicated. RESULTS: Overall, 29 patients (36.2%) were diagnosed as ß-lactam allergic. The majority of the cases (72.4%) were diagnosed by positive skin tests to either PPL or MDM, whereas 10.3% were diagnosed by skin testing with culprit drugs and 17.2% with drug provocation tests. Regarding the use of the tested drug in the long term, almost half of the contacted patients had had an indication to use the tested drug and the majority had taken the whole course without problems. CONCLUSIONS: Although currently available new penicillin tests provide sufficient allergy data, all the steps recommended by ENDA should be followed in the diagnosis of immediate reactions to ß-lactams. If these steps are negative, the patients usually tolerate ß-lactams and only a few develop mild, non-life-threatening reactions in the long term.

[Therapy with omalizumab in patients with severe persistent allergic asthma: a real life data in Turkey]. / Agir allerjik astimli hastalarda anti-IgE (omalizumab) tedavisi: Gerçek yasam verileri.

Omalizumab is a biologic agent, which has been shown to be effective in clinical trials in allergic, severe asthmatics. The aim of this study was to evaluate the clinical, functional effectiveness, and side effects of omalizumab in real-life conditions respectively. A total of 18 patients (female/male: 11/7) were included to the study. The mean ± SD age, total IgE, disease duration were 41.8 ± 11.2 years, 255.1 ± 197.3 kU/L, 12.8 ± 9.4 years, respectively. Eight patients had isolated mite, seven patients had mite + other inhalant allergen, three patients had only other allergen sensitivity. Mean duration of omalizumab treatment (months ± SD) was 15.1 ± 8.6 (min-max 1-29) months. Omalizumab dose was 150 mg/month in five patients, 300 mg/month in five, 300 mg/15 days in three, 375 mg/15 days in four, 225 mg/15 days in one patient. Data at the date of last visit were compared with one year prior to omalizumab treatment. Mean systemic steroid dose reduced by 83% (14.7 ± 14.6 vs. 3.2 ± 8 mg), number of other asthma medications reduced by 28% (3.6 ± 1.3 vs. 2.5 ± 1.3) (p< 0.05). FEV1% values (53.5 ± 21.2 vs. 64.5 ± 23.5) did not significantly change. Mean numbers of exacerbations (20 ± 57.6 vs. 0.4 ± 0.7), emergency visits (16.5 ± 46.1 vs. 0.4 ± 1.2), hospitalizations (2.1 ± 2.6 vs. 0.1 ± 0.3) decreased by 93%, 95%, 86%, respectively (p< 0.05). ACT scores increased by 94% (10.4 ± 3.4 vs. 20.4 ± 5.7) (p< 0.05). Fifteen patients (88%) were stated as responsive to treatment with omalizumab. Eleven patients (64.8%) stated that their expectations are met, three patients (17.6%) stated that their expectations are close to being met, three patients (17.6%) stated that their expectations are not met. A local side effect was seen in one patient. In conclusion, our data has shown that omalizumab is effective, and safe in severe allergic asthmatics under real-life conditions.

Triggers in adult asthma: are patients aware of triggers and doing right?

BACKGROUND: As triggers have a potential to induce asthma exacerbations, awareness of the patients to individual triggers as well as protective measures might be helpful to prevent asthma attacks. Though allergens and allergen avoidance have been studied extensively, there are only few studies on non-allergic triggers and their avoidance for adult patients with asthma. In this study, we wanted to investigate asthma triggers and compliance to the preventive measures in an adult population. METHODS: One hundred and thirty one adult asthma patients were enrolled into the study. A face to face interview was done by using a questionnaire including individual asthma triggers, prevention measures against major modifiable triggers and knowledge sources of the cases. RESULTS: Regardless of asthma severity, 59.5 % of the subjects reported to be triggered by more than 10 factors. The most common triggers were air pollutants (89.3 %) and weather changes (81.7 %). Severe group was more frequently affected by medications, emotional stress, weather changes and indoor pollutants than other severity groups (p=0.017, 0.014, 0.049 and 0.018, respectively) whereas stress was reported more frequently by females than males. Prevention measures were insufficient regarding some major triggers. CONCLUSION: Adult patients are vulnerable to several triggers regardless from underlying severity of the illness. Insufficient compliance to the major preventive measures indicates that new strategies are needed to prevent asthma attacks caused by modifiable triggers.

Triggers in adult asthma: are patients aware of triggers and doing right?

Background: As triggers have a potential to induce asthma exacerbations, awareness of the patients to inividual triggers as well as protective measures might be helpful to prevent asthma attacks. Though allergens and allergen avoidance have been studied extensively, there are only few studies on non-allergic triggers and their avoidance for adult patients with asthma. In this study, we wanted to investigate asthma triggers and compliance to the preventive measures in an adult population. Methods: One hundred and thirty one adult asthma patients were enrolled into the study. A face to face interview was done by using a questionnaire including individual asthma triggers, prevention measures against major modifiable triggers and knowledge sources of the cases. Results: Regardless of asthma severity, 59.5 % of the subjects reported to be triggered by more than 10 factors. The most common triggers were air pollutants (89.3 %) and weather changes (81.7 %). Severe group was more frequently affected by medications, emotional stress, weather changes and indoor pollutants than other severity groups (p = 0.017, 0.014, 0.049 and 0.018,respectively) whereas stress was reported more frequently by females than males. Prevention measures were insufficient regarding some major triggers. Conclusion: Adult patients are vulnerable to several triggers regardless from underlying severity of the illness. Insufficient compliance to the major preventive measures indicates that new strategies are needed to prevent asthma attacks caused by modifiable triggers (AU)

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The prevalence of latex allergy in sixth-year medical students: assessment of knowledge, risk, and attitudes about future specialty direction.

BACKGROUND: In the prevention of latex allergy, knowledge levels and risk determination for latex allergy of medical students gain importance. OBJECTIVES: To evaluate the latex allergy knowledge levels of sixth-year medical students and their latex allergy risk. METHODS: Students completed a questionnaire that assessed basic knowledge of latex allergy and that evaluated latex-related symptoms and latex exposure. The specialty branch students were going to choose in the Medical Specialty Examination was also asked. Skin prick tests (SPTs) with latex and inhalant allergens and patch tests with latex-related products were then performed. Finally, students were asked again about any changes in branch selection after learning their individual risks. RESULTS: Two hundred twenty sixth-year students were enrolled. Forty-four percent of the students gave the right answer for description of latex. Correct identification of at least 1 latex-related product used outside and inside hospitals was 55.5% and 95.5%, respectively. The prevalence of latex sensitization was 4.4% according to SPT results. The positivity of SPT to any inhalant allergen was 35% (n = 64). None of the students changed their mind about their specialty branch after learning their latex allergy risk. CONCLUSIONS: Last-year medical students have a remarkably low latex allergy knowledge level, which imposes a serious professional risk. Training strategies based on the benefit to this risk group and reevaluation are strongly recommended before graduation from medical school.

Fasting: an important issue in asthma management compliance.

BACKGROUND: Fasting, neither eating nor drinking anything between dawn (sahur time) and sundown (iftar time), may have an important role in the treatment and follow-up of asthmatic patients in countries where most of the population is Muslim. OBJECTIVE: To analyze the effects of fasting on outpatient asthmatic patients. METHODS: One hundred twenty-one fasting patients were evaluated for attendance at follow-up visits, attitudes about undergoing diagnostic investigations, and opinions and practices regarding medication use during fasting. Their sources of knowledge about asthma, fasting, and medication consumption were also evaluated. RESULTS: Ninety percent of fasting patients reported no harm with respect to religion of visiting physicians while fasting. Although 96% of the patients stated that inhaled medication could be used, only 13% continued to use medication in the same manner as when they were not fasting. Most patients rearranged their medication-consumption hours. Although 96% of the patients received general information about asthma from their physicians, rates of receiving information about the fasting-medication use relationship from physicians and religious sources were similar (37% and 32%, respectively). CONCLUSION: Most Muslim asthmatic patients do not consider asthma to be a drawback to fasting, and they continue fasting by rearranging their medication consumption times. During Ramadan, patients should be questioned about this subject and should be followed up carefully for asthma control at regular visits.

Direct medical cost of asthma in Ankara, Turkey.

BACKGROUND: There has been no documented data regarding the cost of asthma in our country. OBJECTIVE: In this 1-year prospective study, we aimed to determine the annual cost of asthma in Ankara, Turkey. METHODS: Direct medical cost analysis was performed in 118 patients. RESULTS: Mean annual direct medical costs of asthma were USD 1,465.7 +/- 111.8 per capita. Medication cost comprised the majority (81%) of the total direct cost. Mean direct medical costs according to the stage of disease were USD 172.5 +/- 51.7, 860.7 +/- 70.2, 1,671.6 +/- 141.8 and 3,491.9 +/- 417.6 for stage 1 (n = 4), 2 (n = 54), 3 (n = 46) and 4 (n = 14) patients, respectively. CONCLUSIONS: In this first study to document the cost of asthma for our region, direct cost of asthma was found to be increased with the severity of the illness. Considering the fact that medication cost comprises the major fraction of the direct cost, cost-effectiveness trials to determine the effective treatment with optimal cost for different asthma stages should be the next step.