Inhaler Steroid Use Changes Oral and Airway Bacterial and Fungal Microbiome Profile in Asthma Patients.

INTRODUCTION: The full spectrum of bacterial and fungal species in adult asthma and the effect of inhaled corticosteroid use is not well described. The aim was to collect mouthwash and induced sputum samples from newly diagnosed asthma patients in the pretreatment period and in chronic asthma patients while undergoing regular maintenance inhaled corticosteroid therapy, in order to demonstrate the bacterial and fungal microbiome profile. METHODS: The study included 28 asthmatic patients on inhaler steroid therapy, 25 steroid-naive asthmatics, and 24 healthy controls. Genomic DNA was isolated from induced sputum and mouthwash samples. Analyses were performed using bacterial primers selected from the 16S rRNA region for the bacterial genome and "panfungal" primers selected from the 5.8S rRNA region for the fungal genome. RESULTS: Dominant genera in mouthwash samples of steroid-naive asthmatics were Neisseria, Haemophilus, and Rothia. The oral microbiota of asthmatic patients on inhaler steroid treatment included Neisseria, Rothia, and Veillonella species. Abundant genera in induced sputum samples of steroid-naive asthma patients were Actinomyces, Granulicatella, Fusobacterium, Peptostreptococcus, and Atopobium. Sputum microbiota of asthma patients taking inhaler steroids were dominated by Prevotella and Porphyromonas. Mucor plumbeus and Malassezia restricta species were abundant in the airways of steroid-naive asthma patients. Choanephora infundibulifera and Malassezia restricta became dominant in asthma patients taking inhaled steroids. CONCLUSION: The oral and airway microbiota consist of different bacterial and fungal communities in healthy and asthmatic patients. Inhaler steroid use may influence the composition of the oral and airway microbiota.

Evaluation of sinonasal involvement in patients with asthma and chronic obstructive pulmonary disease.

Background: Asthma and chronic obstructive pulmonary disease (COPD) are the most common obstructive diseases. Based on the similarities, we aimed to evaluate sinonasal symptoms in patients with asthma or COPD, and compare the two diseases with regard to upper-airway involvement. Methods: Patients with asthma or with COPD who were followed up at Ankara University Immunology and Allergy or Chest Diseases Departments were included in the study. The participants went through pulmonary function tests, skin-prick tests, and disease severity assessment of either disease. Nasal endoscopic evaluations of all the patients were performed in the Department of Otorhinolaryngology. Lund-Mackay scoring was performed on the computed tomography of the paranasal sinus. Chronic rinosinusitis (CRS) diagnosis was made as recent guidelines. Results: A total of 112 subjects (number of women/men: n = 67/45; median age, 49 years [The range for IQR was 22 years]) were included in the study. Fifty-five patients had asthma, 33 had COPD, and 24 were healthy controls. Nasal symptoms were more frequent in the patients with asthma (patients with asthma, n = 52 [98%]; patients with COPD, n = 17 [52%]; controls, n = 9 [38%]) (p < 0.001). The median (IQR) 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire score was higher in the patients with asthma (33 [20-50]) than in the patients with COPD (8 [1.5-18.7]) and the control group (3.5 [0-18.7]) (p < 0.01). Patients with asthma had significantly higher prevalence rates of rhinosinusitis than did those in the COPD and the control groups (36%, 15.6%, 8.3%, respectively; p < 0.01). The SNOT-22 optimal cutoff score was calculated as ≥11 to detect the score limit for CRS prediction with the best sensitivity and specificity. Conclusion: As a result, patients with both asthma and COPD may have upper-airway symptoms. CRS, was primarily seen in the patients with asthma. Accordingly, SNOT-22 scores were higher in the patients with asthma than in those in the COPD and the control groups. A referral to the Ear Nose Throat department for further evaluation with nasal endoscopy and computed tomography of the paranasal may be required in a subgroup of patients.

Evaluation of adherence and attitudes of patients with allergic rhinitis to nasal steroid treatment.

BACKGROUND: Allergic rhinitis (AR) is defined as an inflammatory disease of the nose. Nasal corticosteroids (NCS) are one of the most effective drugs used in AR treatment. OBJECTIVE: One of the most important issues in the treatment of AR is patient adherence to NCS. We aimed to evaluate the adherence and attitude of patients with AR to NCS treatment. METHODS: One hundred four patients who were prescribed NCS for AR at any time and who used NCS during the study period were included in the study. Morisky Medical Adherence Scale-8 (MMAS-8) was performed on the patients to determine their treatment adherence. RESULTS: The scores of the MMAS-8 were below 6 in 55% of the patients, and the adherence of the patients to the NCS treatment was low. The adherence of the patients to NCS treatment was good in only 19% of the patients. As the duration of the disease increased, the adherence of the patients to the treatment decreased (p = 0.001). Patients who benefited from allergen immunotherapy had statistically significantly higher MMAS-8 scores than those who did not (p = 0.015). As expected, drug adherence was statistically significantly lower in patients with drug-related adverse effects (p = 0.01). Sixty percent of the patients had received NCS training, and MMAS-8 scores were significantly higher in those who received training (p = 0.023). CONCLUSION: Inadequate drug adherence is a challenging problem in the treatment of AR. Frequent evaluation of patients' drug adherence and drug use techniques in daily practice is important for the follow-up and treatment of the disease.

Elderly and aged asthma have different characteristics: results of a multicenter study.

Background/aim: Characteristics of asthma in the elderly population is not well-known. The aim of the present study was to evaluate asthma in the elderly population, to compare disease characteristics between patients diagnosed <60 (aged asthma) and ≥60 (elderly asthma) years of age. Materials and methods: The study was a prospective, multicenter, cross-sectional type. A questionnaire was filled out to patients 60 years of age and over, that have been followed for asthma for at least 3 months. Asthma Control Test (ACT), eight-item Morisky Medication Adherence Scale (MMAS-8) was filled out, inhaler device technique was assessed. Results: A total of 399 patients were included from 17 tertiary care centers across the country. Mean age was 67.11 years and 331 (83%) were female. The age at asthma diagnosis was ≥60 in 146 (36.6%) patients. Patients diagnosed ≥60 years were older (p < 0.001), had higher education level (p < 0.001), more commonly had first-degree relative with asthma (p = 0.038), asthma related comorbidities (p = 0.009) and accompanying rhinitis/rhinosinusitis (p = 0.005), had better asthma control (p = 0.001), were using less controller medications (p = 0.014). Inhaler technique was correct in 37% of the patients with no difference in between the groups. Treatment compliance was better in elderly asthma patients (p < 0.001). In the multivariate logistic regression analysis, having well-controlled asthma (odds ratio = 1.61, CI = 1.04-2.51), and high medication adherence rate (odds ratio = 2.43, CI = 1.48-4.0) were associated with being in the elderly asthma group. Conclusion: The characteristics of asthma are different among patients aged 60 years and over which seems to be related to onset age of asthma. In our cohort, the elderly asthma patients had higher education level, and treatment adherence and asthma control was better. Patients diagnosed ≥60 years of age did not have more severe disease.

Aspirin desensitization following endoscopic sinus surgery is effective in patients with nonsteroidal antiinflammatory drug exacerbated respiratory disease.

INTRODUCTION: Aspirin desensitization (AD) is effective in relieving asthma and sinonasal outcomes in patients with non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD). So far, only a limited number of studies evaluated the effect of AD prospectively in a controlled manner in N-ERD. It is also a current approach to recommend endoscopic sinus surgery (ESS) before AD. This study aimed to prospectively document the clinical effects of AD for 1 year in patients with N-ERD who underwent ESS in the presence of a control group. METHODS: The study included patients with N-ERD who underwent AD (group 1, n = 22) and patients with N-ERD in whom desensitization was indicated but was not performed (group 2, n = 21). All patients had ESS before enrollment in the study. Asthma and rhinosinusitis outcomes were assessed at baseline and after 1 year. RESULTS: The study included a total of 43 subjects (F/M:28/15, mean age: 44.7 ± 2.8 years). Fewer patients had nasal polyp recurrency in group 1 (5/22, 22.7%) than in group 2 (11/21, 52.3%) at the end of the first year (p = 0.035). Smell-test scores were preserved only in group 1 after 1 year. There were significant decreases in the use of both asthma and nasal medications only in group 1. CONCLUSION: Our results strongly support the use of AD for the improvement of both nasal and asthmatic outcomes in patients with N-ERD for 1 year. We also recommend patients undergo ESS before AD. Further controlled studies are necessary to evaluate whether this effect lasts longer.

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.

Picturing asthma in Turkey: results from the Turkish adult asthma registry.

INTRODUCTION: National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. METHODS: Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. RESULTS: The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3-5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. CONCLUSION: The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.

Diagnostic utility of basophil CD203c expression in ß-lactam allergy.

Background: A diagnosis of immunoglobulin E (IgE) mediated reactions to ß-lactam (BL) antibiotics is still challenging because of the limited availability of skin-prick test (SPT), and standardization issues, particularly with newer BLs, are still ongoing. Because encouraging data are increasingly emerging in the use of basophil activation tests in the diagnosis of IgE-mediated drug hypersensitivity reactions, in this study, we aimed to determine CD203c expression, a basophil surface marker, in the diagnosis of IgE-mediated hypersensitivity to BL antibiotics. Methods: This study included two groups of subjects. The first group (group 1) (n = 20) included patients with a diagnosis of IgE-mediated allergy to BLs as confirmed through STs or drug provocation tests, and the control group consisted of healthy volunteers (group 2) (n = 24). Expression of CD203c by flow cytometry was studied in samples stimulated by two different concentrations of six different BL antibiotics. A stimulation index ≥ 2 was considered a positive response. Results: The study groups had comparable age and sex distribution. In the entire group, the sensitivity and specificity of CD203c were 29.4% (5 out of 17) and 82.6% (19 out of 23), respectively. When considering the single reactors, two among four patients who were allergic to amoxicillin demonstrated upregulation of CD203c with amoxicillin, which makes 50% sensitivity. The specificity was 100%. Conclusion: Our data demonstrated that assessment of CD203c in the diagnosis of IgE-mediated reactions to BLs provided encouraging results, particularly with amoxicillin allergy. However, this finding needs to be verified in a larger number of cases.

Comparison of 300 mg versus 600 mg daily maintenance doses of aspirin treatment after desensitization in N-ERD: A three-year multicentre experience.

Background: Aspirin treatment after desensitization (ATAD) is effective in preventing nasal polyps recurrence as well as respiratory symptoms in patients with nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory diseases (N-ERD). However, there is no consensus on effective daily maintenance doses in ATAD. Therefore, we aimed to compare the effects of two different maintenance doses of aspirin on clinical outcomes for 1-3 years of ATAD. Methods: This was a retrospective, multicenter study that involved four tertiary centers. The maintenance doses of daily aspirin were 300 mg in one center and 600 mg in the remaining three. The data of patients who were on ATAD for 1-3 years were included. Study outcomes (nasal surgeries, sinusitis, asthma attacks, hospitalization, oral corticosteroid use, and medication uses) were assessed in a standardized way and recorded from case files. Results: The study initially included 125 subjects, 38 and 87 were receiving 300 and 600 mg daily aspirin for ATAD, respectively. Number of nasal polyp surgeries decreased after 1 -3 years compared with before ATAD in both groups (group 1, baseline: 0.44 ± 0.07 versus first year: 0.08 ± 0.05; p < 0.001 and baseline: 0.44 ± 0.07 versus 3rd year: 0.01 ± 0.01; p < 0.001; and group 2, baseline 0.42 ± 0.03 versus first year: 0.02 ± 0.02; p < 0.001 and baseline: 0.42 ± 0.03 versus 3rd year: 0.07 ± 0.03; p < 0.001). Conclusion: Given the comparable effects of 300 mg and 600 mg aspirin daily as maintenance treatment of ATAD on both asthma and sinonasal outcomes in N-ERD, our results suggest using 300 mg of aspirin daily in ATAD owing to its better safety profile.

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.

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.

Mepolizumab Is an Effective Option in Severe Eosinophilic Asthma Regardless of Baseline Features: Single-Center Real-Life Data.

BACKGROUND: Mepolizumab has been approved as a treatment option for severe eosinophilic asthma (SEA) patients in our country. We aimed to evaluate the clinical and functional efficacy of mepolizumab in this group of patients in real life as well as the response rates to mepolizumab and the possible factors affecting the response. METHODS: The study was a retrospective chart review of patients with SEA treated with mepolizumab. The data were collected at baseline, and at the 6th and 12th month. RESULTS: A total of 62 patients (41F/21M) with a mean age of 44.41 ± 13.24 years were included in the study. They had poor symptom control with a mean asthma control test (ACT) score of 16.61 ± 5.59, frequent exacerbations with a mean of 3.4 ± 3.7 in the previous 12 months, and 80.6% required daily oral corticosteroid (OCS) with a median dosage of 8 mg/day as methylprednisolone. The ACT score increased to 22.47 ± 3.18 and 22.03 ± 4.31, respectively, and blood eosinophil count decreased from 1,146/µL to 89/µL and 85/µL at the 6th and 12th month, respectively. The mean FEV1 at baseline was 2.102 L there was an increase of 0.373 L at 6th month and 0.596 L at 12th month. The percentage of regular users of OCS decreased to 66.0% at 6th month with a median dosage of 4 mg and 52.6% at 12th month with a median dosage of 2 mg. Mepolizumab reduced the rate of exacerbations compared with the previous year from a mean of 3.40 to 0.15 at 6th month and 0.36 at 12th month. There was a significant improvement in Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Sino-nasal Outcome Test (SNOT-22) scores at both of time points. The rate of responders and super-responders at 6th month was 60% and 28%, respectively, and consequently, the overall response rate was 88%. At the 12th month, the super-responder rate increased to 44.7% as well as the overall response to 89.4%. The only difference between the nonresponders, responders, and super-responders at the 6th and 12th month was whether regular daily OCS was used pre-mepolizumab. All nonresponders at both 6th and 12th month were using OCS regularly, whereas most of super-responder used the OCS only during exacerbations. CONCLUSION: Mepolizumab effectively reduced asthma exacerbations, steroid requirement, blood eosinophil counts and improved asthma control, pulmonary function, sinonasal symptoms and quality of life. Our data suggest that mepolizumab would be effective in selected patients in real-life settings.

A step-down experience in asthma treatment: a retrospective cohort study.

BACKGROUND: According to recent guidelines; patients with controlled asthma who are stable for at least three months and don't have risk factor should be considered for step down. OBJECTIVE: To evaluate our step down attempts and affecting factors. METHODS: This study was a retrospective-cohort study of patients with asthma who were followed up in our clinic for at least one year. Sociodemographic, phenotypic, clinical features and number of step-down attempts were recorded from the files. Step down was tried in well controlled patients and considered as successful whether descending step was maintained or a lower step was reached until the last visit. RESULTS: A total of 239 patients (196 F/43 M) with a mean age of 51.54 ± 15.29 years were included in the study. Step-down attempt was performed in 44.8% (n = 107) of the patients and % 74.8 (n = 80) of them were successful. Factors related to failure were lower level of education, allergic comorbidity (p = 0.04) and female gender (p = 0.04). Risk of failure was 3.45 and 1.84 times higher than university graduates in high school and primary school graduates, respectively. The probability of failure in step down was 3.38 times higher in patients with allergic comorbidity, and it was 3.92 times more likely in women than men. CONCLUSIONS: Our results showed that the step down attempt could be performed in patients receiving treatment from all steps. In addition, treatment of allergic comorbidities and increased level of education, may make a step down attempt more successful.

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.

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.

[Biological Treatments in patients with ABPA]. / ABPA'li hastalarda biyolojik tedaviler.

Allergic Bronchopulmonary Aspergillosis (ABPA) is a pulmonary disease characterized by recurrent pulmonary opacities and bronchiectasis caused by Type 1 hypersensitivity to A. fumigatus. Asthma is an important part of the disease and is generally in severe form. It is thought that immunoglobulins against A. fumigatus, Th2-derived cytokines such as IL-4, IL-5 and IL-13 and eosinophilic inflammation play a role in the pathogenesis of the disease. Monoclonal antibody treatments targeting IL-4, IL-5, IL-13 and IgE, which are involved in pathogenesis, have been used in asthmatic patients before. The main treatment of ABPA for exacerbations and remissions is oral corticosteroids (OCS). However, in cases where the corticosteroid dose cannot be reduced or side effects develop, monoclonal agents may be added to the treatment. Monoclonal agents such as omalizumab, mepolizumab, benralizumab and dupilumab targeting cytokines involved to the patogenesis have been used in patients with ABPA. Omalizumab has shown a reduction in exacerbations and OCS requirements, improvement in asthma symptoms and improvement in pulmonary function parameters. With mepolizumab, a decrease in OCS dose, decrease in blood eosinophil count, clinical improvement and radiological improvement were observed. Benralizumab reduced, the number of eosinophil or even almost nullified as well as clinical recovery alongside with radiological improvement. With dupilumab, improvement in symptoms, discontinuation of OCS, but increase in eosinophil count at the beginning of treatment was reported. As a result, monoclonal antibodies were generally found to be successful and safe in patients with ABPA.

Using RV/LV ratio and cardiac biomarkers to define the risk of mortality from pulmonary embolism.

INTRODUCTION: Acute pulmonary thromboembolism (PTE) is a common cause of cardiovascular mortality. Right ventricular (RV) dysfunction is the most important cause of mortality. Computed Tomography Pulmonary Angiography (CTPA) can detect right ventricular enlargement which is an indicator of RV dysfunction at the time of diagnosis. This study aimed to determine the parameters indicating RV dysfunction in CTPA and correlation of early mortality findings. MATERIALS AND METHODS: In this retrospective study, electronic files of patients diagnosed PTE with CTPA between January 2012 and December 2017 were evaluated. Measurements of heart chambers, IVC reflux, and IVS morphology were calculated. In-hospital mortality of the patients after acute PTE diagnosis was evaluated. RESULT: There were 206 eligible patients. Among the evaluated radiological parameters, right atrium (RA) size (p= 0.002), PA size (p= 0.003), Ao size (p= 0.006), and the presence of IVC reflux (p= 0.001) were associated with mortality. No significant relationship was found between RV/LV ≥1 and mortality (p= 0.908). All patients with PTE-related mortality had RV/LV ratio ≥1 in CTPA and had IVC reflux. Patients with an RV/LV ratio of ≥1 had statistically significantly higher troponin levels (p= 0.004) and IVC reflux (p= 0.025) compared to patients with an RV/LV ratio of <1. CONCLUSIONS: In conclusion, RV/LV ratio should be evaluated together with cardiac biomarkers to define mortality risk.

The relationship between hemoglobin A1c levels and thrombus load in patients with type 2 diabetes mellitus and non-ST-segment elevation myocardial infarction.

BACKGROUND: We aimed to investigate the relationship between hemoglobin A1c (HbA1c) and coronary thrombus load in type-2 diabetes mellitus (T2DM) patients with non-ST segment elevation myocardial infarction (NSTEMI). MATERIALS AND METHODS: Ninety diabetic patients with NSTEMI were recruited for the study. They were separated into two groups according to HbA1c levels. Forty-seven patients having HbA1c ≤6.5% formed Group-I (35 male, mean age 58 ± 10.5 years) and the remaining 43 patients with HbA1c >6.5% formed Group-II (23 male, mean age 58 ± 11.1 years). Both the groups were evaluated in terms of thrombolysis in myocardial infarction (TIMI) thrombus score and Syntax score. RESULTS: Baseline patient characteristics were comparable in both the groups. TIMI thrombus score and Syntax score were higher in Group II than in Group I (3.2 ± 1.4 vs. 4.7 ± 0.5 and 20.2 ± 3.4 vs. 26.3 ± 3.0 respectively, P < 0.05). No significant difference was found in other parameters. In stepwise linear regression analysis, prepercutaneous coronary intervention (PCI) and post-PCI TIMI frame number and HbA1c were significantly related to the coronary thrombus scale. However, no significant relationship has been found between thrombus formation and hypertension, previous PCI history, pre-PCI heart rate, pre-PCI cholesterol status, and high-sensitive troponin T. CONCLUSION: In NSTEMI with T2DM, increased HbA1c (HbA1c >6.5%) is related with coronary thrombus in the target vessel. In those patient population, strict anticoagulation should be considered to prevent potential adverse events.

Rapid Drug Desensitization with Chemotherapeutics (Platins, Taxanes, and Others): A Single-Center Retrospective Study.

BACKGROUND: Rapid drug desensitization (RDD) induces a temporary tolerance to chemotherapeutics that induce hypersensitivity reactions (HSRs). PURPOSE: Our objective is to report our experience with RDD to platins, taxanes, etoposide, doxorubicin, and irinotecan. METHODS: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to chemotherapeutics. HSRs were classified as grade I, II, or III, based on their severity. Skin prick/intradermal tests were performed with implicated chemotherapeutics. A 12-step RDD protocol was used. RESULTS: The study consisted of 38 women and 3 men (mean age 53.3 ± 11.6 years). Patients had ovarian (n = 13, 31.8%), breast (n = 10, 24.4%), colon (n = 7, 17%), lung (n = 4, 9.8%), and other cancers (n = 7; endometrial sarcoma, testicular cancer, uterine cancer, ampulla of Vater tumor, choledochal tumor, peritonitis carcinomatosa, and Merkel cell carcinoma, n = 1, respectively). Twenty-two patients experienced HSRs to platins, 15 to taxanes, and 4 to other chemotherapeutics (doxorubicin, irinotecan, and etoposide). A total of 122 RDDs (47 to platins, 52 to taxanes, 23 to other chemotherapeutics) were performed. In 25 (61%) patients no reactions occurred during RDD, but breakthrough reactions developed in 16 patients (39%) with platins (n = 11), taxanes (n = 3), doxorubicin (n = 1), and irinotecan (n = 1). RDD procedures could not be completed in only 2 patients with grade II breakthrough reactions to carboplatin and oxaliplatin. CONCLUSION: In our experience, 98.3% of 122 RDDs were completed. We found that RDD was safe and effective in this the largest series of RDD with chemotherapeutics in our country.

Long-Term Omalizumab Treatment: A Multicenter, Real-Life, 5-Year Trial.

BACKGROUND: Omalizumab has demonstrated therapeutic benefits both in controlled clinical trials and real-life studies. However, research concerning the long-term effects and tolerability of omalizumab is needed. The main objective of this study was to evaluate the effectiveness and tolerability of treatment with omalizumab for up to 5 years. METHODS: A multicenter, retrospective, chart-based study was carried out to compare documented exacerbations, hospitalizations, systemic steroid requirement, FEV1, and asthma control test (ACT) results during 1 year prior to omalizumab treatment versus at 1, 3, and 5 years of treatment. Adverse events and reasons for discontinuation were also recorded at each time point. RESULTS: Four hundred and sixty-five patients were enrolled in the study. Outcome variables had improved after the 1st year and were sustained after the 3rd and 5th years of treatment with omalizumab. Omalizumab treatment reduced the asthma exacerbation rate by 71.3% (p < 0.001) at 1 year, 64.3% (p < 0.001) at 3 years, and 54.8% (p = 0.002) at 5 years. The hospitalization rate also decreased; by the 5th year of the treatment no patients were hospitalized. ACT results had also improved significantly: 12 (p < 0.001) at 1 year, 12 (p < 0.001) at 3 years, and 12 (p = 0.002) at 5 years. Overall, 12.7% of patients reported adverse events (most of these were mild-to-moderate) and the overall dropout rate was 9.0%. CONCLUSION: Omalizumab had a significant effect on asthma outcomes and this effect was maintained over 5 years. The drug was found to be generally safe and treatment compliance was good.