Bronchiectasis in Türkiye: Data from a Multicenter Registry (Turkish Adult Bronchiectasis Database).

Background: Bronchiectasis is a chronic lung disease characterized by permanent bronchial wall dilatation. Although it has been known as an orphan disease, it has recently gained attention because of registry-based studies and drug research. Aims: We aimed to use a multicenter database to analyze and compare data regarding the etiology, associated comorbidities, microbiological characteristics, and preventive strategies of bronchiectasis in Türkiye to those of other countries. Study Design: A multicenter prospective cohort study. Methods: The multicenter, prospective cohort study was conducted between March 2019 and January 2022 using the Turkish Adult Bronchiectasis Database, in which 25 centers in Türkiye participated. Patients aged > 18 years who presented with respiratory symptoms such as cough, sputum, and dyspnea and were diagnosed with non-cystic fibrosis bronchiectasis using computed tomography were included in the study. Demographic information, etiologies, comorbidities, pulmonary functions, and microbiological, radiological, and clinical data were collected from the patients. Results: Of the 1,035 study participants, 518 (50%) were females. The mean age of the patients was 56.1 ± 16.1 years. The underlying etiology was detected in 565 (54.6%) patients. While postinfectious origin was the most common cause of bronchiectasis (39.5%), tuberculosis was identified in 11.3% of the patients. An additional comorbidity was detected in 688 (66.5%) patients. The most common comorbidity was cardiovascular disease, and chronic obstructive pulmonary disease (COPD) and bronchiectasis was identified in 19.5% of the patients. The most commonly detected microbiological agent was Pseudomonas aeruginosa (29.4%). Inhaled corticosteroids (ICS) were used in 70.1% of the patients, and the frequency of exacerbations in the last year was significantly higher in patients using ICS than in nonusers (p < 0.0001). Age [odds ratio (OR): 1.028; 95% confidence interval (CI): 1.005-1.051], cachexia (OR: 4.774; 95% CI: 2,054-11,097), high modified medical research council dyspnea scale score (OR: 1,952; 95% CI: 1,459-2,611), presence of chronic renal failure (OR: 4,172; 95% CI: 1,249-13,938) and use of inhaled steroids (OR: 2,587; 95% CI: 1,098-6,098) were significant risk factors for mortality. Mortality rates were higher in patients with COPD than in those with no COPD (21.7-9.1%, p = 0.016). Patients with bronchiectasis and COPD exhibited more frequent exacerbations, exacerbation-related hospitalizations, and hospitalization in the intensive care unit in the previous year than patients without COPD. Conclusion: This is the first multicenter study of bronchiectasis in Türkiye. The study results will provide important data that can guide the development of health policies in Türkiye on issues such as infection control, vaccination, and the unnecessary use of antibiotics and steroids.

The Role of Sequentially Monitored Laboratory Values and Inflammatory Biomarkers in Assessing the Severity of COVID-19.

With the onset of the pandemic in 2020, COVID-19 pneumonia has become a common cause for hospitalization and is associated with high mortality rates. Inflammatory biomarkers play a crucial role in understanding and monitoring the progression of various diseases, including COVID-19. The objective of this study was to assess the significance of sequentially monitored standard laboratory tests, including complete blood cell count, D-dimer, fibrinogen, ferritin, albumin, C-reactive protein (CRP), as well as newly calculated inflammatory biomarkers in predicting the severity and prognosis of COVID-19 pneumonia. This single-center retrospective study included 194 patients hospitalized due to COVID-19 pneumonia. Patients were grouped based on the severity of their clinical symptoms, with 134 categorized as severe disease and 60 as mild-moderate disease. The patients' demographic data and laboratory values at hospital admission and on the third day of hospitalization were comparatively evaluated. In the severe illness group, there were more complaints about shortness of breath and a significant drop in the SPO2 value was observed at the time of application (p =0.005 and p<0.001, respectively). The overall mortality rate in all patients was 9% (18/194), and all deaths occurred within the severe disease group. All laboratory parameters, with the exception of platelet count and ferritin levels, were significantly associated and correlated with the severity of the disease during the hospitalization period. Among the biomarkers, there was no significant difference in neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) on the first day, a significant increase was observed on the third day of hospitalization in the severe disease group (p=0.050 vs. 0.003 and p=0.073 vs. 0.020, respectively). No significant difference was observed only in the PNR (platelet/neutrophil ratio) value among the inflammatory biomarkers (p=0.090 vs. p=0.354). In conclusion, the SPO2 level of COVID-19 patients at admission and the subsequent laboratory parameters examined show a significant relationship with the severity of the disease. In addition, simple inflammation biomarkers derived from laboratory values have shown a very significant relationship and correlation in the diagnosis and follow-up of the disease. In both admission and follow-up evaluation, a more significant association was observed with CRP-related biomarkers such as CRP/albumin ratio and CRP/lymphocyte ratio rather than NLR and PLR, which are widely used in the literature, in showing the severity of COVID-19. In patients with pneumonia, the laboratory assessment made on the third day of hospitalization reflects the severity of the disease more clearly than on the first day.

DTPA clearance test: a sensitive method for detecting radiation-induced lung fibrosis in lung cancer patients.

OBJECTIVE: The aim of this study is to analyze the frequency of lung injury and the sensitivity of the diethylenetriamine penta-acetic acid (DTPA) clearance test in detecting lung injury in patients undergoing radiotherapy (RT) to the thorax. MATERIAL AND METHOD: Twenty individuals scheduled for RT for lung cancer were included as the patient group. The healthy control group consisted of 20 age and gender-matched individuals who were nonsmokers with no history of comorbidities. We conducted follow-up with patients at 0-1-6 months, performing carbon monoxide diffusion test (DLCO), DTPA clearance test (excluding the first month), and high-resolution computed tomography of the thorax. The control group was followed up with DLCO between the baseline and 6th months. RESULTS: Ninety percent of the patient group was male, and the median age was 62 years. Seventy percent of the patients had squamous cell carcinoma and adenocarcinoma. Pneumonitis was detected in the patient group in the first month (100%) and fibrosis in the sixth month (%100) Both at the beginning and in the sixth month, the DLCO values of patients who received RT were lower than those of the control group ( P  = 0.001 and P  < 0.001, respectively). While DTPA clearance was similar between irradiated and non-radiated lungs at the beginning, there was a substantial decrease in the irradiated lung in the sixth month( P  = 0.001). There was no significant correlation between malignancy type, RT dose, and tumor size( P  > 0.05). CONCLUSION: The DTPA clearance test could be an alternative method for demonstrating radiation injury in patients receiving RT.

Evaluation of diaphragm functions with diaphragm ultrasound and pulmonary function tests in individuals with Friedreich's ataxia.

Background/aim: It is known that the correlation of pulmonary function tests (PFT) with muscle dysfunction is insufficient. Here, we aimed to evaluate the diaphragm functions in individuals with Friedreich's ataxia (FRDA) and to examine its relationship with respiratory parameters and disease severity. Materials and methods: This prospective study, conducted between November and December 2022, at Erciyes University, included 14 individuals with genetically confirmed FRDA and an age- and gender-matched healthy control group of eight individuals. We examined pulmonary functions with spirometric methods and evaluated diaphragm excursion, and diaphragm thickness-expiratory (Tde) and - end of inspiration (Tdi) with ultrasonography during calm breathing. Thickening fraction (TF) calculated. Also, we examined PaCO2 at rest. The neurological status of individuals was assessed using the Scale for the Assessment and Rating of Ataxia (SARA). Results: The mean values of FEV1(lt), FEV1(%), FVC (lt), and FVC (%) were higher in the control group (p; <0.001, 0.013, <0.001, and 0.009, respectively). Also, mean Tdi, Tde, excursion and TF were lower in the FRDA group compared to the control group (p = 0.005, 0.294,0.005, and 0.019, respectively). The mean excursion value was 1.13 ± 0.54cm in the FRDA group and 1.71 ± 0.49cm in the control group. There is a strong, negative, and statistically significant correlation between SARA total score with excursion and TF (r = -0.7432, p = 0.002; r = -0.697, p = 0.008). There is no statistically significant relationship between excursion and BMI, standing-to-supine decrease in FVC, FEV1, and PaCO2. Also, the relationship between maximal inspiratory pressure (PImax) and excursion was moderate. Conclusion: Diaphragm ultrasound may reveal respiratory dysfunction better than PFT. Diaphragm excursion and TF are associated with disease scores in individuals with FDRA. Further studies are needed regarding the detection of alveolar hypoventilation.

Discontinuing Omalizumab Treatment in Super-Responder Patients with Allergic Severe Asthma: Can the Baseline Total IgE Level Be Used as a Biological Marker to Decide Discontinuing Omalizumab Treatment?

BACKGROUND: Although there are many studies presenting the efficacy of omalizumab in severe asthma, the data about the optimal treatment duration are still debated. OBJECTIVE: In this study, we aimed to investigate the clinical effects of omalizumab discontinuation after 5 years of treatment in patients with omalizumab super-responders, the persistence of response and to compare the features of patients, whose symptoms are still well controlled and those who relapsed and re-treated with omalizumab. METHODS: Clinical and laboratory data of 100 adult patients diagnosed with allergic severe asthma and treated with omalizumab between 2008 and 2020 were evaluated retrospectively. Demographic, clinical, functional, and laboratory parameters of the patients who were re-treated with omalizumab and those who did not need to be re-treated were compared. RESULTS: There were 14 super-responder patients, who were treated with omalizumab for 5 years, and the treatment was discontinued then. Omalizumab was not restarted in 9 patients (64%) and was restarted in 5 (36%) patients. No significant difference was presented between these two groups in terms of demographic, clinical, functional, and laboratory parameters. The baseline total IgE levels of patients, who were re-treated with omalizumab, was found to be higher than those who were not, but this difference was not statistically significant (440 [229-864] IU/mL vs. 164 [85-293] IU/mL; p = 0.053, respectively). CONCLUSION: One of 3 patients was re-treated with omalizumab due to loss of asthma control after discontinuation of the treatment. Therefore, omalizumab's immunomodulatory effect may seem to persist in a majority of cases after discontinuation. Also, higher baseline total IgE levels might help to predict the cases that need re-treatment after discontinuation.

Frequency of Direct Oral Anticoagulants Usage in Acute Pulmonary Thromboembolism Treatment in Turkey (TUPEDO).

Background: Direct oral anticoagulants (DOACs) have been used in acute pulmonary thromboembolism as an alternative to warfarin due to drug interactions, narrow therapeutic range, and necessary close International Normalized Ratio (INR) monitoring. Phase 3 study results have reported that these drugs are at least as effective as warfarin and beneficial in terms of bleeding; however, studies that present up-to-date life data are necessary. Aims: To evaluate the frequency of using DOACs, which are prescribed with a limited number of indications in our country, and real-life data results. Study Design: Cross-sectional study. Methods: This cross-sectional survey collected the clinical data (history, current treatment, treatment duration, etc.) of patients with pulmonary thromboembolism and who applied to the physician for follow-up between October 15, 2019, and March 15, 2020. The researchers kept the patient records sequentially. Results: Data from 836 patients with acute pulmonary thromboembolism from 25 centers were collected, and DOAC was used in 320 (38.5%) of them. The most preferred DOAC was rivaroxaban (n = 294, 91.9%). DOAC was mostly preferred because it could not provide an effective INR level with warfarin (n=133, 41.6%). Bleeding was observed in 13 (4%) patients. Conclusion: The use of direct oral anticoagulants is becoming almost as widespread as conventional therapy. Real-life data results are important for their contribution to clinical practice.

A prospective observational evaluation of treatment outcomes of patients with chronic obstructive pulmonary disease and peripheral blood eosinophilia.

INTRODUCTION: This study aimed to compare two groups of patients with Chronic Obstructive Lung Disease (COPD) and blood eosinophil values of ≥300 cells/ µL. The patients were followed up for one year in two groups, one receiving inhaled corticosteroids (ICS) and the other not receiving ICS in terms of exacerbation rates, the incidence of pneumonia, mortality rates, FEV1, FVC and FEF25-75 changes, the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scores. MATERIALS AND METHODS: Stable patients, who presented to the University Medical Faculty Chest diseases outpatient clinic and diagnosed with COPD according to pulmonary function test results and GOLD stages 2-4 according to the 2017 GOLD criteria and with blood eosinophil counts of ≥ 300 cells/ µL were included in the study. RESULT: 85 patients were included in the study, of which 76.5% (n= 65) were males. There were no significant differences between the 38 patients receiving ICS and the 47 patients not receiving ICS regarding baseline FEV1, FVC, FEF25- 75 absolute values and percentages, and FEV1, FVC values controlled at month six and month 12, and FEF25-75 absolute values and percentages at month six (p> 0.05). However, the difference between the baseline and month 12 absolute values and percentages of FEF25-75 was statistically significant, and the decrease from baseline was greater in the group receiving ICS (p< 0.05). The difference in CAT and mMRC scores were statistically significant at month six and month nine in favor of the group receiving ICS (p< 0.05). The median number of moderate and severe exacerbations were both one (min: 0, max:3) in the group receiving ICS (n= 38) and in the one not receiving ICS (n= 47). The difference of exacerbation rates in both groups were not statistically significant (p> 0.05). CONCLUSIONS: In this study, it was determined that exacerbation rates of eosinophilic COPD patients did not differ depending on the use of ICS in a one-year period. Nevertheless, the 12-month FEF25-75 values of patients not using ICS were lower to a lesser extent, while the CAT and mMRC scores improved in favor of ICS users at different months in the one-year follow-up.

Frequency of peripheral blood eosinophilia and obstructive airway disease in sarcoidosis

Background/aim: There is limited information about peripheral blood eosinophilia (PBE) and airway obstruction in sarcoidosis. Since pulmonary sarcoidosis affects the airways, it is often confused with asthma. The aims of the study are to investigate airway obstruction and PBE in sarcoidosis patients and to examine the similarity of clinical presentation with asthma. Materials and methods: The patients matching the ATS/ERS/WASOG diagnosis criteria and were between 18 and 80 years of age were included consecutively between 2018 and 2020. Other diseases causing granulomas were excluded. Results: A total of 84 patients were included of which 26 (31%) had a PBE level of ≥300 µL with no significant difference seen between sarcoidosis stage and PBE (p > 0.05). A significant (p < 0.05) decrease was only seen in FEV1 as the stage of sarcoidosis progressed. Respectively 31 (36.9%), 12 (14.3%) and 4 (4.8%) patients had an obstructive, restrictive and mixed respiratory function disorder. Twenty-four (28.6%) subjects with sarcoidosis had history of asthma. Spring fever, eczema, and skin/nose allergy were noticed in 17 (20.2%) of the patients. Conclusion: Mild PBE may be seen in sarcoidosis. Patients applying with PBE, airway obstruction, bronchial hyperreactivity along with spring fever, eczema, skin/nose allergy, wheezing, chest tightness, shortness of breath and cough may be also evaluated in terms of sarcoidosis.

Frequency of peripheral blood eosinophilia and obstructive airway disease in sarcoidosis.

BACKGROUND: There is limited information about peripheral blood eosinophilia (PBE) and airway obstruction in sarcoidosis. Since pulmonary sarcoidosis affects the airways, it is often confused with asthma. The aims of the study are to investigate airway obstruction and PBE in sarcoidosis patients and to examine the similarity of clinical presentation with asthma. METHODS: The patients matching the ATS/ERS/WASOG diagnosis criteria and were between 18 and 80 years of age were included consecutively between 2018 and 2020. Other diseases causing granulomas were excluded. RESULTS: A total of 84 patients were included of which 26 (31%) had a PBE level of ≥300 µL with no significant difference seen between sarcoidosis stage and PBE (p > 0.05). A significant (p < 0.05) decrease was only seen in FEV1 as the stage of sarcoidosis progressed. Respectively 31 (36.9%), 12 (14.3%) and 4 (4.8%) patients had an obstructive, restrictive and mixed respiratory function disorder. Twenty-four (28.6%) subjects with sarcoidosis had history of asthma. Spring fever, eczema, and skin/nose allergy were noticed in 17 (20.2%) of the patients. DISCUSSION: Mild PBE may be seen in sarcoidosis. Patients applying with PBE, airway obstruction, bronchial hyperreactivity along with spring fever, eczema, skin/nose allergy, wheezing, chest tightness, shortness of breath and cough may be also evaluated in terms of sarcoidosis.

Horse allergen sensitivity and respiratory symptoms among horse farm workers

Background/aim: Sensitivity and symptoms related to animal proteins have been investigated in various occupational groups. However, data from horse farm workers are limited. We aimed to determine horse allergen sensitivity in the horse farm workers, and to evaluate its relationship with respiratory symptoms and functional parameters. Materials and methods: A total of 110 subjects were enrolled in the study. The study group consisted of 80 horse farm workers. Face-to-face surveys, skin prick tests (SPT), and pulmonary function tests (PFT) were performed in the study group. Control group consisted of 30 healthy subjects. SPT and PFTs were also performed for control group. The SPT test results of the horse farm workers were compared with the SPT results provided from the medical records of 1376 subjects who admitted to the outpatient clinic with respiratory symptoms. Results: Atopy rate was significantly higher in horse farm workers than in healthy subjects (41% and 13%, respectively; P = 0.008). Horse allergen sensitivity was positive 8/80 (10%) in horse farm workers, 0/30 in healthy subjects, and 32/1376 (2%) in medical records of subjects who were admitted to the outpatient clinic with respiratory symptoms. (P = 0.07, P = 0.001, respectively). There was no statistically significant relationship between respiratory symptoms and horse allergen sensitivity in horse farm workers (P = 0.67). However, mean FEV1 ratios were lower in horse farm workers with horse allergen sensitivity than healthy subjects (88.6% ± 17.9, 103.7 ± 10, P = 0.031, respectively). Conclusion: Atopy and animal allergen sensitization were significantly higher in horse farm workers, suggesting the relationship between the intensity of specific allergen exposure and the sensitization to this specific allergen.

Efficacy of mepolizumab treatment in oral corticosteroid-dependent severe eosinophilic asthma patients with chronic rhinosinusitis with nasal polyps: single center, real life study

Background/aim: Oral corticosteroid (OCS)-dependent severe eosinophilic asthma with chronic rhinosinusitis with nasal polyps (SEA-CRSwNP) would be a suitable phenotype for mepolizumab treatment. This study evaluated the short-term efficacy of mepolizumab treatment in OCS-dependent SEA-CRSwNP. Materials and methods: Baseline and 24th week results [daily OCS doses, asthma exacerbation frequency, asthma control test (ACT) scores, blood eosinophil levels, FEV1 values, and numerical analog scale (NAS) of CRSwNP symptoms] of patients who were treated for at least 24 weeks with mepolizumab were retrospectively evaluated and compared. Results: A total of 16 patients were enrolled in the study. Mepolizumab was discontinued in one patient due to side effects. The daily OCS dosage was reduced from baseline in all patients, and at week 24 OCS was discontinued in 40% of the patients (baseline mean steroid dose: 9.2 ± 5.2 mg, 24th week: 1.3 ± 1.4 mg; P < 0.001). The number of asthma exacerbations within 24 weeks significantly decreased after beginning mepolizumab treatment (2.1 ± 2.7 vs. 0.07 ± 0.26; P = 0.012), and a significant increase in ACT scores (baseline mean ACT: 18 ± 5.7; 24th week mean ACT: 23.3 ± 3; P = 0.006) was observed despite the decrease in daily OCS dosages. There was no significant difference in FEV1 values between baseline and week 24. Evaluation of the general symptoms of CRSwNP, as per NAS, revealed that the baseline mean NAS was 5.6 ± 4.4, and the 24th week mean NAS was 3.2 ± 3.2 (P = 0.021). Conclusion: This is the first real-life study evaluating the short-term efficacy of mepolizumab treatment on OCS-dependent SEA-CRSwNP. This study demonstrates that mepolizumab is an effective and safe biologic for the treatment of this severe asthma subphenotype.

The presence of underlying asthma should be investigated in patients diagnosed with ACE inhibitor induced cough.

INTRODUCTION: Why do only some of patients who are prescribed angiotensin converting enzyme inhibitors (ACE-I) develop cough? The pathogenesis of ACE-I-induced cough remains controversial and requires further studies. OBJECTIVE: We aim to investigate whether asthma is a contributing cause of ACE-I-induced cough. METHODS: Patients attending a cardiology clinic between March 2016 and March 2017 who were diagnosed with ACE-I induced cough were included in this study. ACE-I-induced cough was defined as cough which developed within 4 weeks after initiation of ACE-I therapy and which improved within 4 weeks after discontinuation of the ACE-I. Patients who had received ACE-I treatment for at least 6 months without side effects were included in the study as a control group. Face-to-face questionnaires, pulmonary function tests (PFT) and skin prick tests were applied to all the patients. If there was discordance between asthma history and PFT results, a methacholine bronchial provocation test (BPT) was performed. RESULTS: A total of 43 patients with ACE-I induce cough were compared with 50 controls. Bronchial hyperreactivity (BHR), rhinitis, atopy and family history of asthma were more frequent in patients with ACE-I induced cough (P < .001). Patients with ACE-I-induced cough had significantly higher incidence of diagnosed asthma [OR = 8.28 (95%CI: 3.26-21.03) P < .001]. CONCLUSIONS: Asthma and an atopic background constitute a substantial risk factor for ACE-I induced cough. The presence of underlying asthma should be investigated in patients diagnosed with ACE inhibitor induced cough. However, the fact that most asthma patients tolerate ACE-I therapy, indicates that other cofactors are likely involved.

The protective effects of thymoquinone on lung damage caused by cigarette smoke.

Chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation that usually is caused by exposure to noxious particles or gases. Thymoquinone (TQ) prevents the production of inflammatory mediators, such as thromboxane B2 and leukotriene, by altering arachidonic acid metabolism. We investigated the preventive and curative effects of TQ on lung damage in rats caused by cigarette smoke (CS). We used 50 adult male rats, 30 of which were exposed to CS every day for 3 months. TQ in dimethylsulfoxide (DMSO) was administered intraperitoneally (i.p.) every day to ten animals to investigate the protective effects of TQ, and to ten other animals during the last 21 days to investigate the curative effect. Ten rats received saline for the last 21 days. Ten subjects were untreated controls. Ten controls that were not exposed to CS received TQ for the last ten days. Serum IL-8, IL-6, IL-1ß and MMP-9 levels were measured using ELISA. IL-1ß and IL-8 levels were elevated in the group exposed to CS compared to controls. IL-8 levels were decreased in the group that received only TQ compared to controls, which indicated the anti-inflammatory effect of TQ. The apoptotic index (AI) was increased in all groups that were exposed to CS compared to controls. The AI index was decreased in the group that received TQ for the last 21 days compared to the other CS groups. AI was increased in the group that received TQ daily compared to the other CS groups. Our findings indicate that TQ exerts curative effects for the inflammation caused by CS and may prevent apoptosis if administered in appropriate doses; however, long term TQ or DMSO exposure may produce cumulative toxic effects.

Regional distribution of genetic mutation in lung cancer in Turkey (REDIGMA).

INTRODUCTION: The results of standard chemotherapy in lung cancer are not very satisfactory, so it is important to identify genetic mutations that provide targeted therapies. Recent reports have suggested influences of racial difference on the frequency of mutation in lung cancer. We aimed to determine the frequency and regional distribution of genetic mutations of non-small cell lung cancer (NSCLC) in Turkey. MATERIALS AND METHODS: Regional distribution of genetic mutations in lung cancer in Turkey (REDIGMA) study was carried out as a prospective, cross-sectional, observational study in a large number of centers in which lung cancer patients were followed and could perform genetic mutation analysis on patients' biopsy materials. RESULT: The 703 patients (77.7% male, mean age 63.3 ± 12.5 years) who were diagnosed as NSCLC from 25 different centers were included in the study. Tumor samples from patients were reported as 87.1% adenocarcinoma, 6.4% squamous cell carcinoma and 6.5% other. Mutation tests were found to be positive in 18.9% of these patients. The mutations were 69.9% EGFR, 26.3% ALK, 1.6% ROS and 2.2% PDL. Mutations were higher in women and non-smokers (p<0.000, p<0.001). Again, the frequency of mutations in adenocarcinoma was higher in metastatic disease. There was no difference between the patient's age, area of residence, comorbidity and clinical stage and mutation frequency. CONCLUSIONS: Our study revealed that the EGFR mutation rate in Turkey with NSCLC was similar to East European, African-American and Caucasian patients, and was lower than in East Asia.

Last station in the eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis march: Eosinophilic asthma with radiological findings associated with blood eosinophilia.

OBJECTIVE: Eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis (EA-CRS/NP) is a subphenotype of adult-onset eosinophilic asthma. Blood eosinophil levels are shown to be highly elevated in patients with EA-CRS/NP and have potential for tissue infiltration. We aimed to demonstrate the clinical features of the patients who have a blood eosinophil level above 10% and have thorax computed tomography findings due to blood eosinophilia. METHODS: Patients who were followed up in our clinic between 2012 and 2017 were retrospectively evaluated. Inclusion criteria were as follows: 1) Eosinophilic severe asthma, 2) eosinophilia >10%, 3) chronic sinusitis and/or nasal polyps, 4) patients with pathologic findings on thorax computed tomography, 5) regular follow-up for at least 1 year. RESULTS: We identified 36 patients who met the above criteria. We defined this group as "Eosinophilic Asthma with chronic Rhinosinusitis and/or nasal polyposis with Radiological findings related to blood eosinophilia" (EARR). The mean age was 44.9 ± 11 years and 64% were females. Nasal polyps, aspirin exacerbated respiratory disease, and atopy, were present in 81%, 47%, and 25% of the patients, respectively. The mean blood eosinophil count was 1828.6 cells/mm3 (19%). The majority of EARR patients had upper lobe dominant ground-glass opacities. The mean follow-up period was 3.2 ± 2.5 years. EARR patients did not evolve into eosinophilic granulomatous polyangiitis in the follow-up. CONCLUSIONS: This phenotype is the first eosinophilic asthma sub-phenotype reported in the literature. EARR is the final stage of the allergic march of EA-CRS/NP.

Omalizumab Treatment for Atopic Severe Persistant Asthma: A Single-Center, Long-Term, Real-Life Experience with 38 Patients.

OBJECTIVES: Omalizumab is a monoclonal antibody that is used as add-on therapy for treating moderate-to-severe persistant atopic asthma in patients with persistant symptoms and frequent exacerbations, despite step 4 treatment according to GINA guidelines. Real-life studies on omalizumab treatment are limited in Turkey. Thus, the present study aims to assess the clinical efficacy and treatment outcomes of omalizumab in patients with atopic severe persistant asthma. MATERIALS AND METHODS: Patients with atopic severe persistant asthma who were treated with omalizumab between 2009 and 2017 were retrospectively evaluated. Baseline and last results of the following variables were compared: symptom scores (GINA categorical), controller medications, blood eosinophil counts, forced expiratory volume in 1 second (FEV1) values, and the number of exacerbations that were treated with systemic corticosteroids for at least 3 days within the last 1 year. The effect of coexisting aspirin-exacerbated respiratory disease (AERD) on these parameters was also analyzed. Step-down of other asthma medications was attempted in patients with symptom control and in those without an exacerbation history within the last 6 months. RESULTS: Thirty-eight patients (mean age, 50 years; females, 30) were included in this study, of whom four showed AERD. After treating with a mean time of 30±22.1 (min: 6, max: 92) months, 26 (68%) patients showed complete controlled disease and 12 (32%) showed partly controlled disease, of whom all had uncontrolled disease before. Mean exacerbation rates within the last 1 year decreased by approximately 76% (9.4±8.4 vs. 1.8±1.5; p<0.001) and FEV1 values increased by approximately 14% (2075±729 vs. 2321±800 cc; p=0.001) compared with baseline levels. Although the reduction in eosinophil count was not significant in all patients (503.8±524.8 vs. 370.8±314.5; p=0.134), repeated measures analysis of variance revealed a more prominent reduction in eosinophil count in the AERD group than in the non-AERD group, independent from the treatment period (F: 4.23, p=0.049). The mean inhaled corticosteroid dose (budesonide eq., 1063±397 vs. 958±439 mcg; p=0.084), the number of other controller medications, and the number of patients with long-term systemic steroid use decreased after omalizumab treatment. No serious adverse events were recorded during the follow-up period. CONCLUSION: Our results confirm that omalizumab significantly improves disease control and is a safe add-on therapy. In addition, in suitable patients with controlled disease over time, the step-down of other asthma medications will be appropriate.

The role of endobronchial and endoscopic ultrasound guided fine needle aspiration for mediastinal nodal staging of non-small-cell lung cancer.

INTRODUCTION: Mediastinal and hilar nodal staging is one of the key points for differentiating treatment modalities in patients with non-small-cell lung cancer (NSCLC). The aim of the present study was to determinate the diagnostic yields of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and combined EBUS-TBNA and EUS-FNA modalities for nodal staging in potentially operable NSCLC patients. MATERIALS AND METHODS: Twenty consecutive patients were prospectively enrolled in the study between March 2014 and November 2015. All patients had a potentially operable NSCLC diagnosis before endosonographic procedures. RESULT: Thirty lymph nodes were sampled by EBUS-TBNA and 17 lymph nodes were sampled by EUS-FNA in all 20 patients. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of F-18 fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT), EBUS-TBNA, EUS-FNA and combined EBUS-TBNA and EUS-FNA were 100%, 33.3%, 64.7%, 100% and 70.0%; 81.8%, 100%, 100%, 81.8% and 90%; 81.8%, 100%, 100%, 75% and 88.2%; 90.9%, 100%, 100%, 90.0% and 95.0%, respectively. CONCLUSIONS: The combined EBUS-TBNA and EUS-FNA technique is a successful procedure for nodal staging in potentially operable NSCLC patients.

Clinical and Serological Features of Eosinophilic and Vasculitic Phases of Eosinophilic Granulomatosis with Poliangiitis: a Case Series of 15 Patients.

OBJECTIVES: Eosinophilic granulomatosis with poliangiitis (EGPA) which was previously called Churg-Strauss Syndrome, is classified into eosinophilic and vasculitic phases. To characterize the eosinophilic and vasculitic phases of the disease in terms of clinical findings, serology, and treatment. MATERIALS AND METHODS: We included 15 EGPA patients in the study. The clinical, serological, and therapeutic characteristics and the treatment responses of the patients were recorded. RESULTS: Thirteen patients were classified as being in the eosinophilic phase and two were classified as being in the vasculitic phase of EGPA. Initial symptoms were worsening asthma in all patients (n=15; 100%). All patients had rhinosinusitis, and 66.6% had hypersensitivity to nonsteroidal anti-inflammatory drugs. The two patients in the vasculitic phase did not have nasal polyposis. Pulmonary and nervous system involvement were the most common symptoms. The erythrocyte sedimentation rates (ESRs) of the two patients in the vasculitic phase were 65 mm/h and 55 mm/h, while ESR was normal in eosinophilic-phase patients. Antineutrophil cytoplasmic antibodies (ANCA) was detected in one patient (6.6%) who was in the vasculitic phase (Case 15). The disease was under control with higher doses of methylprednisolone in the vasculitic phase (Case 14: 12 mg/day, Case 15: 10 mg/day) than in the eosinophilic phase. Relapse was detected in the two patients in the vasculitic phase. Oral corticosteroid was not discontinued in any case, and no mortality was reported. CONCLUSION: Patients with eosinophilic phase or vasculitic phase EGPA had similar clinical onset. However, higher ESR, ANCA positivity, and extrapulmonary organ involvement were only found in patients in the vasculitic phase. Corticosteroid responsiveness was very good in all patients in the eosinophilic phase, and the disease could be controlled with a very low maintenance dose of a corticosteroid.

The Association of Brain-Derived Neurotrophic Factor Gene Polymorphism with Obstructive Sleep Apnea Syndrome and Obesity.

BACKGROUND: Obesity represents a major risk factor for Obstructive Sleep Apnea Syndrome (OSAS). Brain-derived neurotrophic factor (BDNF) affects the mechanisms that regulate weight, eating behavior, and metabolism. This project aims to investigate the possible association of BDNF gene polymorphism with obesity and OSAS, and to contribute knowledge to the understanding of the pathophysiology of OSAS. METHODS: The subjects included in this study were selected among the individuals who were hospitalized in the Erciyes University Medical School Chest Diseases Sleep Medicine Laboratory. Subjects were divided into four groups based on the presence of OSAS and/or obesity. Group 1 included OSAS+ obesity+ patients, Group 2 included OSAS+ obesity- patients, Group 3 included OSAS- obesity+ patients, and Group 4 included OSAS- obesity- patients. The targeted patient number per each study group was 45, but only 32 patients could be enrolled into Group 3. RESULTS: Out of a total number of 167 subjects, 117 (70.1 %) had BDNF 196G/G, 48 (28.7 %) had BDNF 196G/A, and 2 (1.2 %) had BDNF 196A/A genotype. Of 48 subjects having BDNF 196G/A genotype, 32 (66.6 %) were obese, and 16 (33.3 %) were non-obese. Out of 90 subjects with OSAS, 64 (71.1 %) had BDNF 196G/G, and 25 (27.8 %) had BDNF 196G/A genotype. Out of 77 subjects without OSAS, BDNF 196G/G, and BDNF 196G/A genotypes were detected in 53 (68.8 %) and 23 (29.9 %) subjects, respectively. A statistically significant difference was demonstrated between the four study groups in terms of BDNF rs6265 polymorphism (p = 0.013). This difference was attributed to OSAS+ obesity- Group, in which BDNF 196G/G genotype was more common and BDNF 196G/A polymorphism was less common than the patients in other groups. CONCLUSION: In conclusion, BDNF 196G/A genotype was found to be more frequent among obese patients compared to the non-obese individuals, but it was not significantly related to OSAS in the present study. BDNF196G/G genotype was more common and BDNF 196G/A polymorphism was less common among OSAS+ obesity- subjects compared to the other study groups.