Person: KARADAĞ, BÜLENT TANER
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KARADAĞ
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BÜLENT TANER
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Publication Open Access Key paediatric messages from the 2018 European Respiratory Society International Congress(EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2019-04) KARADAĞ, BÜLENT TANER; Nenna, Raffaella; Hunt, Katie A.; Dassios, Theodore; Collins, Jennifer J. P.; Rottier, Robbert J.; Liu, Norrice M.; Rottier, Bart; Goutaki, Myrofora; Karadag, Bulent; Prayle, Andrew; Fernandes, Ricardo M.; Parisi, Giuseppe Fabio; Barben, Jurg; Rubbo, Bruna; Snijders, Deborah; Makrinioti, Heidi; Hall, Graham; Pijnenburg, Marielle W.; Grigg, JonathanIn this article, the Group Chairs and early career members of the European Respiratory Society (ERS) Paediatric Assembly highlight some of the most interesting findings in the field of paediatrics which were presented at the 2018 international ERS Congress.Publication Open Access Sweat Testing and Recent Advances(FRONTIERS MEDIA SA, 2021-05-04) KARADAĞ, BÜLENT TANER; Gokdemir, Yasemin; Karadag, Bulent TanerCystic fibrosis (CF) is the most common fatal genetic disease of the Caucasian population. Sweat testing is the principal diagnostic test for CF, and it is used for the evaluation of infants with positive CF newborn screening (NBS) and in patients with clinical findings suggesting CF. This article describes the classical sweat test method in detail and also provides an overwiew of recent advances.Publication Open Access Respiratory outcome of spinal muscular atrophy type 1 patients treated with nusinersen(2022-01-01) ERGENEKON, ALMALA PINAR; ÖZTÜRK THOMAS, GÜLTEN; ÜNVER, OLCAY; TÜRKDOĞAN, DİLŞAD; KARADAĞ, BÜLENT TANER; ERDEM ERALP, ELA; ERGENEKON A. P., YILMAZ YEĞİT C., Cenk M., GÖKDEMİR Y., ERDEM ERALP E., ÖZTÜRK G., ÜNVER O., Coskun O. K., Saygi E. K., TÜRKDOĞAN D., et al.Background Respiratory failure is the leading cause of mortality in spinal muscular atrophy type 1 (SMA1) children. The current study aims to evaluate the effect of nusinersen treatment on respiratory outcome of the patients with SMA1. Methods In this retrospective, single-center study, 52 SMA1 patients treated with nusinersen were included in the analysis. Patients were divided into two groups based on their age at the time of their first nusinersen treatment (Group 1: 6 months). Respiratory outcome on the 180th day of treatment is defined as the type of ventilation support (spontaneous breathing, noninvasive ventilation (NIV), and tracheostomized or intubated on invasive mechanical ventilation). Demographic data, respiratory outcome, and Children\"s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores were obtained from medical records. Results On the 180th day of treatment, 46 of the 52 (88.4%) children were alive. Prevalence of the mortality was similar in both groups (P = 0.65). The comparison of respiratory outcome in patients between group 1 and group 2 was as follows: spontaneous breathing, 7 (43.7%) versus 4 (13.3%) (P = 0.03); NIV = 16 h/day. There were significant improvements in Children\"s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores of the patients at day 180 in comparison with the baseline (P < 0.001). Conclusions Early initiation of nusinersen treatment in SMA1 patients may alter the disease\"s natural course.Publication Open Access Performance Evaluation of a New Coulometric Endpoint Method in Sweat Testing and Its Comparison With Classic Gibson&Cooke and Chloridometer Methods in Cystic Fibrosis(FRONTIERS MEDIA SA, 2018-05-22) KARADAĞ, BÜLENT TANER; Gokdemir, Yasemin; Vatansever, Pinar; Karadag, Bulent; Seyrekel, Tuncay; Baykan, Ozgur; Ikizoglu, Nilay Bas; Ersu, Refika; Karakoc, Fazilet; Haklar, GoncagulBackground: The objective of the study was to assess the diagnostic efficacy of the coulometric endpoint method and compare it with classic Gibson&Cooke and chloridometer methods. Methods: This study is a prospective clinical study comparing two conventional sweat testing methods with the coulometric endpoint method in previously diagnosed cystic fibrosis (CF) patients and a non-CF control group. All individuals underwent two simultaneous sweat collections. One sample of sweat, collected by the CF Delta collector coil system, was analyzed by two methods: the titrimetric Cl- measurement (Sherwood (R) Chloridometer 926S, Sherwood Scientific Ltd., Cambridge, UK) and the coulometric endpoint method (CF Delta Collection System (R), UTSAT/Turkey); the second sample was collected from the other forearm by the Gibson&Cooke method and the collected sweat was analyzed by manual titration in accordance with the Schales&Schales method. Within-run and between-run imprecisions were evaluated via Cl- concentrations of 40, 70, and 130 mmol/L samples. Results: One hundred and seventy (60 CF and 110 controls) subjects were included in the study. All three sweat test methods discriminated CF subjects from the healthy individuals. The mean difference between the coulometric endpoint and titrimetric Cl - measurement methods was -1.5 mmol/L, (95% confidence limits of agreement, ranging from -8.9 to 15.9 mmol/L); the mean difference between manual titration vs. coulometric endpoint methods was 12.8 mmol/L, (95% confidence limits of agreement ranging from -9.7 to 45.3 mmol/L) and the mean difference between the manual titration and titrimetric Cl - measurement methods was 11.3 mmol/L, (95% confidence limits of agreement ranging from -7.8 to 40.5 mmol/L) based on a Bland-Altman analysis. In the Receiver operating characteristic (ROC) analysis, made on the basis that Cl- concentration values <40 mmol/L exclude the CF diagnosis, the coulometric endpoint method resulted in 96.7% sensitivity and 100% specificity for a cut-off value of 58.5 mmol/L (AUC: 0.994; 95% CI = 0.986-1.000; p < 0.001). Conclusions: The coulometric endpoint method can be as reliable as quantitative sweat Cl- analysis and may be considered as a definitive diagnostic tool for CF.Publication Open Access Growth and nutritional status, and their association with lung function: a study from the international Primary Ciliary Dyskinesia Cohort(EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2017-12) KARADAĞ, BÜLENT TANER; Goutaki, Myrofora; Halbeisen, Florian S.; Spycher, Ben D.; Maurer, Elisabeth; Belle, Fabien; Amirav, Israel; Behan, Laura; Boon, Mieke; Carr, Siobhan; Casaulta, Carmen; Clement, Annick; Crowley, Suzanne; Dell, Sharon; Ferkol, Thomas; Haarman, Eric G.; Karadag, Bulent; Knowles, Michael; Koerner-Rettberg, Cordula; Leigh, Margaret W.; Loebinger, Michael R.; Mazurek, Henryk; Morgan, Lucy; Nielsen, Kim G.; Phillipsen, Maria; Sagel, Scott D.; Santamaria, Francesca; Schwerk, Nicolaus; Yiallouros, Panayiotis; Lucas, Jane S.; Kuehni, Claudia E.Chronic respiratory disease can affect growth and nutrition, which can influence lung function. We investigated height, body mass index (BMI), and lung function in patients with primary ciliary dyskinesia (PCD). In this study, based on the international PCD (iPCD) Cohort, we calculated z-scores for height and BMI using World Health Organization (WHO) and national growth references, and assessed associations with age, sex, country, diagnostic certainty, age at diagnosis, organ laterality and lung function in multilevel regression models that accounted for repeated measurements. We analysed 6402 measurements from 1609 iPCD Cohort patients. Height was reduced compared to WHO (z-score -0.12, 95% CI -0.17 to -0.06) and national references (z-score -0.27, 95% CI -0.33 to -0.21) in male and female patients in all age groups, with variation between countries. Height and BMI were higher in patients diagnosed earlier in life (p=0.026 and p<0.001, respectively) and closely associated with forced expiratory volume in 1 s and forced vital capacity z-scores (p<0.001). Our study indicates that both growth and nutrition are affected adversely in PCD patients from early life and are both strongly associated with lung function. If supported by longitudinal studies, these findings suggest that early diagnosis with multidisciplinary management and nutritional advice could improve growth and delay disease progression and lung function impairment in PCD.Publication Open Access Intrinsic Endobronchial Obstructions in Children from Turkey: Evaluation of 2,555 Flexible Bronchoscopic Procedures(KARGER, 2013) KARADAĞ, BÜLENT TANER; Kut, Arif; Cakir, Erkan; Gokdemir, Yasemin; Midyat, Levent; Ersu, Refika; Erdem, Ela; Karadag, Bulent; Karakoc, FaziletBackground: Endobronchial obstructions are rarely seen in children and are often misdiagnosed resulting in delay of definitive treatment. A variety of diseases can cause endobronchial obstructions in childhood, but data is limited as to the frequency, distribution and clinical characteristics of endobronchial obstructions diagnosed with flexible bronchoscopy (FB). Objective: To document endobronchial obstructions detected by FB. Methods: FB results from three pediatric pulmonology centers in Istanbul were evaluated. Results: A total of 2,555 children underwent an FB procedure during the study period. Endobronchial obstructions were detected in 10% (n = 256) of the patients. Among FB in patients who had endobronchial obstructions, the four most common indications for bronchoscopy were persistent infiltrations (30%, n = 72), persistent wheezing (28%, n = 70), chronic cough (26%, n = 66) and atelectasis (23%, n = 59). The most common endobronchial obstructions detected in the patients were aspirated foreign bodies (35.9%, n = 92), endobronchial tuberculosis (31.6%, n = 81), mucous plugs occluding airway (16.7%, n = 43) and granulation scars (6%, n = 16). Other pathologies included hydatid cysts (n = 5), hemangiomas (n = 5), tumors (n = 5), submucosal nodules (n = 5) and polyps (n = 4). Endobronchial obstructions were most commonly located in the right bronchus (51%, n = 130) followed by the left bronchus (33%, n = 85), bilaterally (8%, n = 21) and trachea (8%, n = 20). Conclusions: Endobronchial obstructions can be caused by a number of different diseases which require various medical or surgical treatments. In the presence of clinical or radiological findings suggesting an endobronchial obstruction, FB should be performed promptly. Copyright (C) 2012 S. Karger AG, BaselPublication Open Access Prevalence and course of disease after lung resection in primary ciliary dyskinesia: a cohort & nested case-control study(BMC, 2019-12) KARADAĞ, BÜLENT TANER; Kouis, Panayiotis; Goutaki, Myrofora; Halbeisen, Florian S.; Gioti, Ifigeneia; Middleton, Nicos; Amirav, Israel; Barbato, Angelo; Behan, Laura; Boon, Mieke; Emiralioglu, Nagehan; Haarman, Eric G.; Karadag, Bulent; Koerner-Rettberg, Cordula; Lazor, Romain; Loebinger, Michael R.; Maitre, Bernard; Mazurek, Henryk; Morgan, Lucy; Nielsen, Kim Gjerum; Omran, Heymut; Ozcelik, Ugur; Price, Mareike; Pogorzelski, Andrzej; Snijders, Deborah; Thouvenin, Guillaume; Werner, Claudius; Zivkovic, Zorica; Kuehni, Claudia E.; Yiallouros, Panayiotis K.Background Lung resection is a controversial and understudied therapeutic modality in Primary Ciliary Dyskinesia (PCD). We assessed the prevalence of lung resection in PCD across countries and compared disease course in lobectomised and non-lobectomised patients. Methods In the international iPCD cohort, we identified lobectomised and non-lobectomised age and sex-matched PCD patients and compared their characteristics, lung function and BMI cross-sectionally and longitudinally. Results Among 2896 patients in the iPCD cohort, 163 from 20 centers (15 countries) underwent lung resection (5.6%). Among adult patients, prevalence of lung resection was 8.9%, demonstrating wide variation among countries. Compared to the rest of the iPCD cohort, lobectomised patients were more often females, older at diagnosis, and more often had situs solitus. In about half of the cases (45.6%) lung resection was performed before presentation to specialized PCD centers for diagnostic work-up. Compared to controls (n = 197), lobectomised patients had lower FVC z-scores (- 2.41 vs - 1.35, p = 0.0001) and FEV1 z-scores (- 2.79 vs - 1.99, p = 0.003) at their first post-lung resection assessment. After surgery, lung function continued to decline at a faster rate in lobectomised patients compared to controls (FVC z-score slope: - 0.037/year Vs - 0.009/year, p = 0.047 and FEV1 z-score slope: - 0.052/year Vs - 0.033/year, p = 0.235), although difference did not reach statistical significance for FEV1. Within cases, females and patients with multiple lobe resections had lower lung function. Conclusions Prevalence of lung resection in PCD varies widely between countries, is often performed before PCD diagnosis and overall is more frequent in patients with delayed diagnosis. After lung resection, compared to controls most lobectomised patients have poorer and continuing decline of lung function despite lung resection. Further studies benefiting from prospective data collection are needed to confirm these findings.Publication Open Access The international primary ciliary dyskinesia cohort (iPCD Cohort): methods and first results(EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2017-01) KARADAĞ, BÜLENT TANER; Goutaki, Myrofora; Maurer, Elisabeth; Halbeisen, Florian S.; Amirav, Israel; Barbato, Angelo; Behan, Laura; Boon, Mieke; Casaulta, Carmen; Clement, Annick; Crowley, Suzanne; Haarman, Eric; Hogg, Claire; Karadag, Bulent; Koerner-Rettberg, Cordula; Leigh, Margaret W.; Loebinger, Michael R.; Mazurek, Henryk; Morgan, Lucy; Nielsen, Kim G.; Omran, Heymut; Schwerk, Nicolaus; Scigliano, Sergio; Werner, Claudius; Yiallouros, Panayiotis; Zivkovic, Zorica; Lucas, Jane S.; Kuehni, Claudia E.Data on primary ciliary dyskinesia (PCD) epidemiology is scarce and published studies are characterised by low numbers. In the framework of the European Union project BESTCILIA we aimed to combine all available datasets in a retrospective international PCD cohort (iPCD Cohort). We identified eligible datasets by performing a systematic review of published studies containing clinical information on PCD, and by contacting members of past and current European Respiratory Society Task Forces on PCD. We compared the contents of the datasets, clarified definitions and pooled them in a standardised format. As of April 2016 the iPCD Cohort includes data on 3013 patients from 18 countries. It includes data on diagnostic evaluations, symptoms, lung function, growth and treatments. Longitudinal data are currently available for 542 patients. The extent of clinical details per patient varies between centres. More than 50% of patients have a definite PCD diagnosis based on recent guidelines. Children aged 10-19 years are the largest age group, followed by younger children (<= 9 years) and young adults (20-29 years). This is the largest observational PCD dataset available to date. It will allow us to answer pertinent questions on clinical phenotype, disease severity, prognosis and effect of treatments, and to investigate genotype-phenotype correlations.Publication Open Access Access to medicines for rare diseases: beating the drum for primary ciliary dyskinesia(EUROPEAN RESPIRATORY SOC JOURNALS LTD) KARADAĞ, BÜLENT TANER; Crowley, Suzanne; Azevedo, Ines; Boon, Mieke; Bush, Andrew; Eber, Ernst; Haarman, Eric; Karadag, Bulent; Kotz, Karsten; Leigh, Margaret; Moreno-Galdo, Antonio; Mussaffi, Huda; Nielsen, Kim G.; Omran, Heymut; Papon, Jean-Francois; Pohunek, Petr; Priftis, Kostas; Rindlisbacher, Bernhard; Santamaria, Francesca; Valiulis, Arunas; Witt, Michal; Yiallouros, Panayiotis; Zivkovic, Zorica; Kuehni, Claudia E.; Lucas, Jane S.Publication Open Access Management of primary ciliary dyskinesia in European children: recommendations and clinical practice(EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2012-06) KARADAĞ, BÜLENT TANER; Strippoli, Marie-Pierre F.; Frischer, Thomas; Barbato, Angelo; Snijders, Deborah; Maurer, Elisabeth; Lucas, Jane S. A.; Eber, Ernst; Karadag, Bulent; Pohunek, Petr; Zivkovic, Zorica; Escribano, Amparo; O'Callaghan, Chris; Bush, Andrew; Kuehni, Claudia E.The European Respiratory Society Task Force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe. Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median (interquartile range) of 4 (2-9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosa! biopsy. Samples were analysed by electron microscopy (77%) and ciliary function tests (57%). Nasal nitric oxide was used for screening in 46% of centres and saccharine tests in 36%. Treatment approaches varied widely, both within and between countries. European region, size of centre and the country's general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments. In conclusion, we found substantial heterogeneity in management of PCD within and between countries, and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries. Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.