Publications by authors named "Deniz Dogru"

92 Publications

Differentially expressed genes associated with disease severity in siblings with cystic fibrosis.

Pediatr Pulmonol 2020 Dec 23. Epub 2020 Dec 23.

Department of Medical Biology, Hacettepe University Faculty of Medicine, Sıhhiye, Ankara, Turkey.

Cystic fibrosis (CF) is an autosomal recessive disease caused by CFTR gene mutations. Despite having the same mutation, CF patients may demonstrate clinical variability in severity and prognosis of the disease. In this study, we aimed to determine differentially expressed genes between mild and severe siblings with same genotype. We performed targeted real-time polymerase chain reaction based transcriptomic analysis of nasal epithelial cells obtained from two families with two siblings with Class II mutations (F508del/F508del) and (F508del/G85E), one family with three siblings with Class IV mutation (I1234V/I1234V). In severe siblings with Class II mutations, TNFRSF11A, KCNE1, STX1A, SLC9A3R2 were found to be up regulated. CXCL1, CFTR, CXCL2 were found to be down regulated. In the severe sibling with Class IV mutation; mainly genes responsible from complement and coagulation system were identified. Comparison of CF patients to non-CF control; showed that ICAM1 was up regulated whereas EZR, TNFRSF1A, HSPA1A were down regulated in patients. As a result of this study, differentially expressed genes responsible for clinical severity among affected siblings carrying the same mutation were identified. The results will provide an opportunity for the development of novel target molecules for treatment of disease.
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http://dx.doi.org/10.1002/ppul.25237DOI Listing
December 2020

The effect of self-efficacy, social support and quality of life on readiness for transition to adult care among adolescents with cystic fibrosis in Turkey.

J Pediatr Nurs 2020 Dec 2. Epub 2020 Dec 2.

Pediatric Pulmonology Department, Faculty of Medicine, Hacettepe University, Sihhiye, 06100 Ankara, Turkey.

Purpose: The aim of this study is to examine the effects of self-efficacy, social support and quality of life on readiness for transition to adult care in adolescents with cystic fibrosis.

Design And Methods: A descriptive and cross-sectional study design was used. Data were collected from 50 adolescent between 14 and 17 years old with cystic fibrosis, by using The Transition Readiness Assessment Questionnaire, Social Support Appraisals Scale for Children, Self-Efficacy Questionnaire for Children and health-related quality-of-life instrument, the KIDSCREEN-10.

Results: A positive correlation was found between the readiness levels of adolescents for transition to adult care and self-efficacy levels. In path analysis, self-efficacy was found to have a significant effect on the level of readiness for transition to adult care. There was not statistically significant relationship between the level of readiness for transition to adult care and health-related quality of life and perceived social support. Path analysis revealed that health-related quality of life and perceived social support had significant effects on the self-efficacy levels of adolescents.

Conclusions: Self-efficacy were associated with readiness for the transition to adult care. Although perceived social support and quality of life were not related with transition readiness these variables had significant effects on perceived self-efficacy, which was determined as a factor affecting the readiness for the transition to adult care.

Practice Implications: In adolescents with cystic fibrosis, self-efficacy, social support and quality of life levels should be taken into account when planning preparation programs for transition to adult care.
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http://dx.doi.org/10.1016/j.pedn.2020.11.013DOI Listing
December 2020

Risk Factors for Recurrent Pulmonary Exacerbation in Idiopathic Pulmonary Hemosiderosis.

Pediatr Pulmonol 2020 Nov 28. Epub 2020 Nov 28.

Hacettepe University Pediatric Pulmonology, Ankara, Turkey.

Objectives: To evaluate the risk factors of recurrent pulmonary exacerbation and poor prognosis in children with idiopathic pulmonary hemosiderosis (IPH).

Methods: In this multicenter study, 54 patients with a diagnosis of idiopathic pulmonary hemosiderosis were included. Medical records were retrospectively reviewed from three tertiary care hospitals between 1979 and 2019. Also, current information and the long-term progress of patients was determined by contacting the families by telephone.

Results: A total of 54 children were included. The median age of onset of symptoms was 4.5 years (3 months to 15.8 years). The median time from onset to diagnosis was 0.9 years (0.25 months to 12 years). The mean number of recurrent episodes per child in the recurrence-positive group was 3.55 (1-15). Univariate analysis demonstrated that patients presenting with hypoxia or requiring transfusion at the time of presentation had significantly more recurrence episodes (P=0.002). Multivariate analysis showed that the presence of hypoxia at the time of initial presentation was a significant independent predictor of recurrent episodes (P=0.027). The median follow-up was 3.3 years (0.75 months-27 years). There was a significant relationship between the presence of hypoxia, transfusion history, ANA positivity, and elevated transaminases at the time of initial evaluation and treatment response.

Conclusions: The present study provides substantial information regarding factors that may affect recurrent exacerbations and prognosis in children with idiopathic pulmonary hemosiderosis. Demonstrating hypoxia as an independent risk factor in recurrence episodes could guide physicians in the planning of treatment strategies. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ppul.25189DOI Listing
November 2020

Nonmyeloablative hematopoietic stem cell transplantation in a patient with hereditary pulmonary alveolar proteinosis.

Pediatr Pulmonol 2021 Feb 24;56(2):341-343. Epub 2020 Nov 24.

Department of Pediatric Hematology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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http://dx.doi.org/10.1002/ppul.25174DOI Listing
February 2021

Telephone surveillance during 2019 novel coronavirus disease: Is it a helpful diagnostic tool for detecting acute pulmonary exacerbations in children with chronic lung disease?

J Telemed Telecare 2020 Nov 12:1357633X20972008. Epub 2020 Nov 12.

Department of Pediatric Pulmonology, Hacettepe University, Turkey.

Introduction: The global burden of the 2019 novel coronavirus disease pandemic on the healthcare system, as well as the high transmission risk of coronavirus disease has led to the use of alternative strategies for evaluation of children with chronic conditions. In this context, telemedicine has become the effective and affordable choice. In this study we aimed to evaluate the efficiency of telephone visits to determine pulmonary exacerbations and hospitalization rates of children with cystic fibrosis and interstitial lung disease.

Methods: A total of 119 children with cystic fibrosis or interstitial lung disease were enrolled and provided cases in which telephone visits were applied during the peak time of the coronavirus disease pandemic in our country. The recordings of respiratory, gastrointestinal and other symptoms, nutrition status, rate of acute pulmonary exacerbation, treatments initiated by telephone visits, referral to hospital and hospitalization were established from the electronic health reports of the patients.

Results: Thirteen patients (10.9%) were symptomatic, 12 of them (10%) were diagnosed with acute pulmonary exacerbation. One patient was diagnosed with peripheral facial paralysis. Nine patients were recalled to the hospital and seven patients (5.8%) were hospitalised.

Discussion: Using telemedicine the health status of patients can be defined, and patients can be guided on proper healthcare that they need, especially during the times of pandemics which we are facing. Communication with patients while minimising the risk of exposure to coronavirus disease is an important advantage of telemedicine. Telemedicine will have to be implemented on our daily medical practice in the near future.
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http://dx.doi.org/10.1177/1357633X20972008DOI Listing
November 2020

Psychiatric and general health effects of COVID-19 pandemic on children with chronic lung disease and parents' coping styles.

Pediatr Pulmonol 2020 12 28;55(12):3579-3586. Epub 2020 Sep 28.

Department of Pediatric Pulmonology, School of Medicine, Ihsan Dogramaci Children's Hospital, Hacettepe University, Ankara, Turkey.

Background: We aim to assess the anxiety and depressive symptoms related to the COVID-19 pandemic in children with chronic lung disease and their parents and also to evaluate parents' coping strategies.

Methods: Parents of children aged 4-18 years, with chronic lung disease (study group n = 113) and healthy control (n = 108) were enrolled in the study. General Health Questionnaire-12, specific COVID-19 related anxiety questions, The Coping Orientation to Problems Experienced inventory, coronavirus-related psychiatric symptom scale in children-parental form were used to analyze the psychiatric effects of COVID-19. Parents were also asked about how online education affected their family life and children. All data were compared between children/parents in the study and control groups. Risk factors related with anxiety scores of children were also analyzed.

Results: Talking about the pandemic, concern about coronavirus transmission, taking precaution to prevent coronavirus transmission, making pressure to protect from COVID-19 were significantly higher in parents within the study group (p < .05). Parents in the study group used more problem-focused coping than parents in the control group (p = .003). Anxiety symptoms score was higher in children of the study group (p = .007). Parents in the study group found online education more useful than parents in the control group.

Conclusion: Children with chronic lung diseases and their parents have more anxiety due to COVID-19 pandemic and these parents use more mature coping strategies to manage the stress of the pandemic. Longitudinal and larger studies should be done in all aspects of online education in children with chronic lung diseases.
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http://dx.doi.org/10.1002/ppul.25082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537125PMC
December 2020

Diverse clinical characteristics of Aspergillus growth in patients with cystic fibrosis.

Turk J Pediatr 2020 ;62(4):560-568

Departments of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Background And Objectives: Patients with cystic fibrosis (CF) have a varying spectrum of clinically significant Aspergillus disease in addition to allergic bronchopulmonary aspergillosis (ABPA). Here we aimed to review the different clinical phenotypes related with Aspergillus growth on the airway culture of patients with CF, we also aimed to investigate the effect of Aspergillus growth on lung function tests.

Method: The medical records of 100 patients with CF who had Aspergillus growth on airway culture within the period of April 2001 and June 2016 were retrospectively analyzed. Age, gender, symptoms, physical examination findings, pulmonary function tests, the diagnosis of ABPA, and airway culture results were recorded for every visit. Patients with Aspergillus growth on airway cultures were classified into different groups as ABPA, Aspergillus sensitization, Aspergillus colonization and Aspergillus bronchitis.

Results: Medical records of 83 patients and 147 sputum cultures were attained from 100 patients. The mean age of the patients was 17.6±7.6 years and the mean age of the first Aspergillus growth in sputum culture was 12.5±6.7 years. At first isolation, Aspergillus fumigatus SC was the most common Aspergillus SC in sputum (76.3%) and 14.5% of these patients required hospitalization. Aspergillus sensitization was diagnosed in 3.6% (n= 3) of the patients. Aspergillus colonization was diagnosed in 18.1% (n= 15) of all patients and led to a decline in FEV1%, FVC% and FEF25-75% which was not statistically significant, furthermore. ABPA was detected in 9.6% (n= 8) of all patients and led to a statistically significant decline in FEV1% (p= 0.02); nonsignificant decline in FVC% and FEF25-75%. Aspergillus bronchitis was detected in 43.4% (n= 36) of all patients and led to nonsignificant decline in FEV1%, FVC% and FEF25-75%.

Conclusion: ABPA is recognized as the most common Aspergillus associated disorder in CF patients and is related to deteriorated pulmonary function tests; however Aspergillus colonization and bronchitis may also be associated with worsening lung function.
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http://dx.doi.org/10.24953/turkjped.2020.04.005DOI Listing
January 2020

Mutations of the CFTR gene and novel variants in Turkish patients with cystic fibrosis: 24-years experience.

Clin Chim Acta 2020 Nov 18;510:252-259. Epub 2020 Jul 18.

Hacettepe University Faculty of Medicine, Department of Pediatric Pulmonology, Ankara, Turkey. Electronic address:

Background: Cystic fibrosis, the most prevalent autosomal recessive genetic disease, is caused by mutations in the CFTR gene. The spectrum and frequency of CFTR mutations in Turkish patients show heterogeneity.

Methods: We investigated CFTR gene mutations in samples from 604 cystic fibrosis patients diagnosed at Hacettepe University, the largest referral CF center in Turkey, by different techniques such as strip assay and direct sequencing. We also analyzed the effects of novel variants and predicted pathogenicity by integrating information from different insilico tools.

Results: We showed that mutation detection rate increased to 76.7% with direct sequencing of the coding region and exon/intron boundaries. Ten variants were described for the first time. All variants except T788R were reported as pathogenic.

Conclusion: Characterization of patients with CFTR mutations that occur at very low frequencies is necessary for mutation-based treatments. Population specific genetic screening panels should be designed since none of them are suitable for Turkish patients due to heterogeneous mutation distribution. The preliminary data obtained from in silico results of novel variants will pave the way for functional analysis by using samples obtained from patients. These observations will facilitate the discovery and development of new targeted and personalized therapies.
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http://dx.doi.org/10.1016/j.cca.2020.07.033DOI Listing
November 2020

Variation in the bombesin staining of pulmonary neuroendocrine cells in pediatric pulmonary disorders-A useful marker for airway maturity.

Pediatr Pulmonol 2020 09 29;55(9):2383-2388. Epub 2020 Jun 29.

Department of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Objectives: Pulmonary neuroendocrine cells (NEC) increase with age due to pulmonary maturity. The aim of this study was to determine whether open lung biopsies from patients with interstitial lung diseases have increased pulmonary NEC compared with neuroendocrine cell hyperplasia of infancy (NEHI). Our second aim was to assess pulmonary NECs in the lung autopsy of children without lung disease who died from different causes.

Methods: Lung tissue of 5 infants with NEHI; 21 patients with pediatric interstitial lung disease (chILD); 17 lung autopsies of infants at varying age without lung disease were included. The percentage of the airways containing neuroendocrine cells, the average percentage of neuroendocrine cells (NECs) per airway, and the number of neuroendocrine bodies (NEBs) in each case were analyzed.

Results: The mean percentage of the airways containing neuroendocrine cells were 95% in the NEHI group, 30% in the chILD group, 89% under Intrauterine 37 weeks, 70% between intrauterine 37 to 40 weeks, 52% at postnatal 4 days to 6 months of autopsy ages. In the NEHI group, diffuse NE cell distribution and large NEBs were noticed in the lung biopsy. In the chILD group, neuroendocrine cells were dispersed, did not form clusters and NE cells showed solitary distribution. In the lung autopsy group, linear NE cells were detected at younger aged fetuses and solitary distribution of NE cells was detected with the older increasing age.

Conclusions: Our findings confirm that NECs are seen in many other childhood interstitial lung diseases; NE cell hyperplasia may be a marker of decreased pulmonary development and NE cells decrease with the increasing age of the fetus during Intrauterine life.
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http://dx.doi.org/10.1002/ppul.24910DOI Listing
September 2020

Visuomotor reaction time and dynamic balance in children with cystic fibrosis and non-cystic fibrosis bronchiectasis: A case-control study.

Pediatr Pulmonol 2020 09 22;55(9):2341-2347. Epub 2020 Jun 22.

Faculty of Medicine, Department of Pediatric Chest Diseases, Hacettepe University, Ankara, Turkey.

Objective: Extrapulmonary involvement such as balance and reaction time is unclear in cystic fibrosis (CF) patients. The aim of this study was to evaluate visuomotor reaction time (VMRT) and dynamic balance in children with CF and non-CF bronchiectasis compared to healthy children.

Design/methods: Demographic and clinical characteristics were recorded. All children were evaluated with pulmonary function test (PFT) using a spirometer, incremental shuttle walk test (ISWT) for exercise capacity, Fitlight Trainer for VMRT, and functional reach test (FRT) for dynamic balance.

Results: Fourteen children with CF (10.71 ± 2.94 years, 7 females), 17 children with non-CF bronchiectasis (12.75 ± 2.81 years, 8 females), and 21 healthy children (11.36 ± 3.28 years, 11 females) were included. Children with CF had longer total VMRT (P = .027), poorer FRT performance (P = .001), and shorter ISWT distances (P = .03) compared to the children with non-CF bronchiectasis and controls. Although total VMRT was longest in the CF group, there was no significant difference in mean VMRT among the CF, non-CF bronchiectasis, and control groups (P > .05).

Conclusion: Dynamic balance and VMRT show greater impairment in children with CF than in children with non-CF bronchiectasis compared to healthy controls. Our findings suggest that VMRT and dynamic balance should be taken into consideration for assessments and exercise programs in pulmonary rehabilitation.
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http://dx.doi.org/10.1002/ppul.24903DOI Listing
September 2020

Patients eligible for modulator drugs: Data from cystic fibrosis registry of Turkey.

Pediatr Pulmonol 2020 09 26;55(9):2302-2306. Epub 2020 May 26.

Division of Pediatric Pulmonology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background: A better understanding of cystic fibrosis transmembrane conductance regulator biology has led to the development of modulator drugs such as ivacaftor, lumacaftor-ivacaftor, tezacaftor-ivacaftor, and elexacaftor-tezacaftor-ivacaftor. This cross-sectional study evaluated cystic fibrosis (CF) patients eligible for modulator drugs.

Methods: Data for age and genetic mutations from the Cystic Fibrosis Registry of Turkey collected in 2018 were used to find out the number of patients who are eligible for modulator therapy.

Results: Of registered 1488 CF patients, genetic analysis was done for 1351. The numbers and percentages of patients and names of the drugs, that the patients are eligible for, are as follows: 122 (9.03%) for ivacaftor, 156 (11.54%) for lumacaftor-ivacaftor, 163 (11.23%) for tezacaftor-ivacaftor, and 57 (4.21%) for elexacaftor-tezacaftor-ivacaftor. Among 1351 genotyped patients total of 313 (23.16%) patients are eligible for currently licensed modulator therapies (55 patients were shared by ivacaftor and tezacaftor-ivacaftor, 108 patients were shared by lumacaftor-ivacaftor and tezacaftor-ivacaftor, and 22 patients were shared by tezacaftor-ivacaftor and elexacaftor-tezacaftor-ivacaftor groups).

Conclusions: The present study shows that approximately one-fourth of the registered CF patients in Turkey are eligible for modulator drugs. As, frequent mutations that CF patients have in Turkey are different from North American and European CF patients, developing modulator drugs effective for those mutations is necessary. Furthermore, as modulator drugs are very expensive currently, financial support of the government in developing countries like Turkey is noteworthy.
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http://dx.doi.org/10.1002/ppul.24854DOI Listing
September 2020

Factors associated with severe lung disease in an adult population with cystic fibrosis: a single-center experience

Turk J Med Sci 2020 06 23;50(4):945-952. Epub 2020 Jun 23.

Department of Chest Diseases, Medicana Kadıköy, İstanbul, Turkey

Background/aim: The patients with cystic fibrosis (CF) are living longer compared to the past, but respiratory failure is still the most common cause of mortality. The aim of this study is to investigate factors associated with severe lung disease in a cohort of adult patients with CF.

Materials And Methods: Demographic data, clinical and laboratory findings of the patients aged 18 years and more were collected and the patients were grouped according to forced expiratory volume in 1 s (FEV1) as severe group: <40% and nonsevere ≥40%. Associations were investigated between groups and clinical outcomes.

Results: A total of 76 patients were enrolled in the study. The mean age was 24.5 ± 5.25 years and 36 (47.4%) patients were female. In the severe group; the mean age was higher (27.1 ± 6.0 vs 23.6 ± 4.7, P = 0.013), the median Chrispin-Norman score of severe lung disease group was higher (14 (6–22) vs 5.5 (0–20), P < 0.001), hospitalization at least once in a year for intravenous antibiotic was more common (12/18 (66%) vs 19/58 (32%), P = 0.014). There was a positive correlation between body mass index (BMI) and lung function, indicating that lower nutritional status was related to lower FEV1, r2 = 0.21, P < 0.001. The median FEV1% was lower in patients with CF-related diabetes (38 (14–95) vs 66 (13–121), P = 0.042). Dornase alpha use and physiotherapy rate were higher in severe lung disease group (P = 0.008 and P < 0.001, respectively).

Conclusion: Lower BMI, older age, presence of CF-related diabetes, higher radiologic scores, use of dornase alpha and physiotherapy and higher hospitalization rate for intravenous antibiotic therapy are significantly associated with severe lung disease.
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http://dx.doi.org/10.3906/sag-1912-101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379455PMC
June 2020

Clinical features and accompanying findings of Pseudo-Bartter Syndrome in cystic fibrosis.

Pediatr Pulmonol 2020 08 4;55(8):2011-2016. Epub 2020 May 4.

Department of Pediatric Pulmonology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background: Pseudo-Bartter syndrome (PBS) is a rare complication of cystic fibrosis (CF) and there are limited data in the literature about it. We aimed to compare clinical features and accompanying findings of patients with PBS in a large patient population.

Methods: The data were collected from the Cystic Fibrosis Registry of Turkey where 1170 CF patients were recorded in 2017. Clinical features, diagnostic test results, colonization status, complications, and genetic test results were compared in patients with and without PBS.

Results: Totally 1170 patients were recorded into the registry in 2017 and 120 (10%) of them had PBS. The mean age of diagnosis and current age of patients were significantly younger and newborn screening positivity was lower in patients with PBS (P < .001). There were no differences between the groups in terms of colonization status, mean z-scores of weight, height, BMI, and mean FEV percentage. Types of genetic mutations did not differ between the two groups. Accompanying complications were more frequent in patients without PBS.

Conclusion: PBS was detected as the most common complication in the registry. It could be due to warm weather conditions of our country. It is usually seen in younger ages regardless of mutation phenotype and it could be a clue for early diagnosis of CF.
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http://dx.doi.org/10.1002/ppul.24805DOI Listing
August 2020

Cystic fibrosis in Turkey.

Lancet Respir Med 2020 04;8(4):e17

Division of Pediatric Pulmonology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.

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http://dx.doi.org/10.1016/S2213-2600(20)30055-2DOI Listing
April 2020

Respiratory viruses: What is their role in acute exacerbations in children with cystic fibrosis?

Pediatr Pulmonol 2020 07 30;55(7):1646-1652. Epub 2020 Mar 30.

Department of Pediatrics, Division of Pediatric Pulmonology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background: Respiratory viruses (RVs) are frequently present in the airways of patients with cystic fibrosis (CF) during pulmonary exacerbations (PEx).

Method And Objectives: This prospective, longitudinal study was performed to examine the role of RVs in acute exacerbations in children with CF. Sputum samples or additional midturbinate swabs were tested from all children using a polymerase chain reaction panel. The primary aims of the study were to determine the prevalence and etiologic role of RVs in exacerbations of CF and to compare changes with RV-positive and RV-negative infections. The secondary aims were to determine the predictive factors for RV-related exacerbations.

Results: From 50 patients with PEx, 23 (48.9%) sputum samples were virus-positive. With a combination of sputum and swab, viral positivity increased to 56%. The virus-positive group presented more frequently with hypoxia (oxygen saturation <93%) than the virus-negative group (P = .048). Virus-positive exacerbations were not associated with an increase in colonization rates or greater lung function decline over 12 months.

Conclusions: RVs frequently present during PEx of CF. However, predicting viral infections is difficult in this group. Only the presence of hypoxia may raise the suspicion of an accompanying viral agent. The combination of sputum and nasal swab samples increases the diagnostic yield in viral infections of CF. Despite their high frequency, the presence of RVs had no impact on clinical outcomes, such as a decline in lung function and increased colonization rates.
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http://dx.doi.org/10.1002/ppul.24750DOI Listing
July 2020

Impact of mannose-binding lectin 2 gene polymorphisms on disease severity in noncystic fibrosis bronchiectasis in children.

Pediatr Pulmonol 2020 05 2;55(5):1190-1198. Epub 2020 Mar 2.

Department of Pediatrics, Division of Pediatric Pulmonology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background: Mannose-binding lectin (MBL) is a complement protein involved in the innate immune system, and is associated with some chronic respiratory diseases including noncystic fibrosis (non-CF) bronchiectasis in adults. The aim of this study was to investigate the frequency of MBL2 gene polymorphisms in children with non-CF bronchiectasis, and the effect of MBL deficiency on disease severity.

Methods: Fifty children with non-CF bronchiectasis (bronchiectasis group) and 50 healthy controls (control group) were included. The demographic findings, number of acute pulmonary exacerbations in the previous year, airway cultures, pulmonary function tests, and radiologic scores of the bronchiectasis group were recorded. DNA extraction was performed in both groups and MBL2 gene polymorphisms in codons 52, 54, 57 in exon 1 and H/L, Y/X in the promoter region were studied using real-time polymerase chain reaction. Haplotypes were made by genotypes, and MBL serum expression was classified according to the genotypes in the literature.

Results: The bronchiectasis group consisted of 23 (46%) patients with primary ciliary dyskinesia, 5 (10%) with primary immunodeficiency diseases, and 22 (44%) with idiopathic bronchiectasis. There were no statistically significant differences between the bronchiectasis and control groups in terms of allele and genotype frequencies of polymorphisms in codons 52, 54, 57 in exon 1 and promoter H/L. However, the YX heterozygote genotype was more frequent in the control group (82%) compared with the bronchiectasis group (50%) (P = .002). The frequency of patients with intermediate serum MBL expression genotype was higher in the bronchiectasis group (20%) than in the control group (0%) (P = .001). In the bronchiectasis group, there were no significant differences in growth, annual pulmonary exacerbation rates in the last year, pulmonary function tests, radiologic scores, and microbiologic findings between low, intermediate, and high-expressing genotypes.

Conclusions: In children with non-CF bronchiectasis, MBL genotype was different from healthy controls. MBL deficiency associated only with MBL genotype was not related to disease severity in this group of patients.
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http://dx.doi.org/10.1002/ppul.24711DOI Listing
May 2020

From Diagnosis to Treatment of Pediatric Tuberculosis: Ten Years Experience in a Single Institution.

Clin Pediatr (Phila) 2020 05 22;59(4-5):476-482. Epub 2020 Feb 22.

Department of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

. To describe the patient characteristics, clinical-epidemiologic-microbiologic profile, and treatment outcomes, and to draw attention to tuberculosis (TB) in Turkey. . A retrospective, descriptive study was undertaken of 93 children aged 0 to 18 years who were admitted to Hacettepe University Pediatric Pulmonology Department for treatment from January 2005 to December 2015. Review of hospital records was performed for all children diagnosed as having TB. . Pulmonary TB was detected in 51.6% of the patients, extrapulmonary involvement in 33.3%, and pulmonary TB with extrapulmonary involvement in 15.1%. The history of contact with an adult with TB was found in 29% of cases. The most common extrapulmonary TB was TB lymphadenitis. The most common symptom was cough followed by fever and night sweats. One fifth of the patients had normal physical examinations at the time of diagnosis. One fifth (20.4%) of the patients had culture, 17.2% had polymerase chain reaction, and 15% had acid-resistant bacillus positivity. In 21.4% of patients with culture growth, at least one anti-TB drug resistance was found. The mean duration of treatment of patients treated according to the national guideline was 8.6 months (range = 6-36 months). Recovery was seen in 91.4% of patients. . The most important way to prevent childhood TB is to fight adult TB through early diagnosis and effective treatment. The presence of contact history must direct us to search for TB. While evaluating children with persisted nonspecific symptoms, TB must be kept in mind even if physical examinations are normal.
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http://dx.doi.org/10.1177/0009922820906488DOI Listing
May 2020

Genotype and phenotype evaluation of patients with primary ciliary dyskinesia: First results from Turkey.

Pediatr Pulmonol 2020 02 25;55(2):383-393. Epub 2019 Nov 25.

Department of Pediatric Pulmonology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background And Objective: Primary ciliary dyskinesia (PCD) is a rare and genetically heterogeneous disease and the severity of the disease related with genetic analysis has been described in some previous studies. The main aim of our study was to describe the clinical characteristics and laboratory findings of patients with genetically diagnosed PCD and to investigate the correlation between clinical, radiologic, and laboratory findings and genetic analyses of these patients.

Method: This is a cohort study in which we analyzed the clinical characteristics, laboratory findings, and genetic results of 46 patients with genetically diagnosed PCD through whole-exome sequencing at our single center from a total of 265 patients with PCD within a 5-year period.

Results: Genetic analysis revealed pathogenic variants in DNAH5 (n = 12 individuals, 12 families), CCDC40 (n = 9 individuals, six families), RSPH4A (n = 5 individuals, three families), DNAH11 (n = 4 individuals, four families), HYDIN (n = 5 individuals, five families), CCNO (n = 4 individuals, four families), DNAI1 (n = 2 individuals, one family), ARMC4 (n = 2 individuals, two families), TTC25 (n = 1), DNAH1 (n = 1), and CCDC39 (n = 1) genes. Although not statistically significant, the age at diagnosis was lower (median: 3 years; range, 6 months-4 years) in patients with CCNO pathogenic variants due to the early reporting of symptoms, and the median body mass index (BMI) and BMI z scores were lower in patients at 18.7 and 16 kg/m , and -0.78 and -1.2 with CCDC40 and CCNO pathogenic variants, respectively. The median forced expiratory flow in 1 second (FEV1%), forced vital capacity (FVC%), and forced expiratory flow (FEF)25-75% were 53%, 64%, and 28%, respectively; these parameters were also lower in the CCDC40 group than in the other groups. There was no significant correlation between the genetic results and symptoms, radiologic findings, and microbiologic data of patients with PCD.

Conclusion: In PCD, there was significant heterogeneity of lung disease, patients who had pathogenic variants in CCNO presented earlier, and those with CCDC40 and CCNO had worse lung disease, and poorer nutritional status compared with the other subgroups. We hope that whole genotype-phenotype and clinical relationships will be identified in PCD.
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http://dx.doi.org/10.1002/ppul.24583DOI Listing
February 2020

Childhood diffuse parenchymal lung diseases: We need a new classification.

Clin Respir J 2020 Feb 8;14(2):102-108. Epub 2019 Dec 8.

Faculty of Medicine, Radiology Department, Hacettepe University, Ankara, Turkey.

Introduction: Childhood diffuse parenchymal lung diseases (DPLD) are a heterogeneous group of respiratory disorders of both known and unknown causes that share common histological features. To date, there is not an exact consensus about the terminology, classification, therapy and follow up of this disease because of its rarity and wide clinical spectrum.

Objectives: In this study, we tried to classify our DPLD patients according to the last classification scheme (chILD Network Classification).

Methods: The files of the children diagnosed with DPLD at our university hospital between 1974 and 2012 were retrospectively investigated. Clinical features, laboratory, radiological and histopathological findings, therapy and follow-up outcomes of these patients were recorded and evaluated according to the actual information and definitions.

Results: We described 130 DPLD patients, the largest childhood DPLD series from a single center, classified in 16 distinct groups according to their diagnosis. Our largest group in this serie is pulmonary hemosiderosis (28.5%); idiopathic interstitial pneumonias, pulmonary hemosiderosis, sarcoidosis and lipid storage diseases with lung involvement represent the 70% of the diagnoses. When we classified our patients according to the chILD Network Classification; patients with idiopathic interstitial pneumonia older than 2 years, idiopathic pulmonary hemosiderosis, pulmonary alveolar microlithiasis and diffuse chondroid malformation of the lung stayed out of this classification.

Conclusion: To ensure a consensus about the therapy and follow up, we have to make revisions and reorganisations on the DPLD classification which was proposed in 2007. We need a new childhood DPLD classification that will cover all these disease groups.
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http://dx.doi.org/10.1111/crj.13106DOI Listing
February 2020

Cystic fibrosis in Turkey: First data from the national registry.

Pediatr Pulmonol 2020 02 11;55(2):541-548. Epub 2019 Nov 11.

Division of Pediatric Pulmonology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background: Cystic fibrosis (CF) care has been implemented in Turkey for a long time; however, there had been no patient registry. For this purpose, the Turkish National CF Registry was established. We present the first results of registry using data collected in 2017.

Methods: The data were collected using a data-entry software system, which was accessed from the internet. Demographic and annually recorded data consisted of 15 and 79 variables, respectively.

Results: There were 1170 patients registered from 23 centers; the estimated coverage rate was 30%. The median age at diagnosis was 1.7 years (median current age: 7.3 years); 51 (4.6%) patients were aged over 18 years. Among 293 patients who were under 3 years of age, 240 patients (81.9%) were diagnosed through newborn screening. Meconium ileus was detected in 65 (5.5%) patients. Genotyping was performed in 978 (87.4%) patients and 246 (25.2%) patients' mutations were unidentified. The most common mutation was deltaF508 with an allelic frequency of 28%, followed by N1303K (4.9%). The median FEV1% predicted was 86. Chronic colonization with Pseudomonas aeruginosa was seen in 245 patients. The most common complication was pseudo-Bartter syndrome in 120 patients. The median age of death was 13.5 years in a total of 15 patients.

Conclusions: Low coverage rate, lack of genotyping, unidentified mutations, and missing data of lung functions are some of our greatest challenges. Including data of all centers and reducing missing data will provide more accurate data and help to improve the CF care in Turkey in the future.
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http://dx.doi.org/10.1002/ppul.24561DOI Listing
February 2020

BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immuneosseous- dysplasia.

Turk J Pediatr 2019;61(1):111-116

Department of Pediatrics Division of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Düzova A, Gülhan B, Topaloğlu R, Özaltın F, Cengiz AB, Yetimakman AF, Doğru D, Güçer Ş, Beşbaş N. BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immune-osseous-dysplasia. Turk J Pediatr 2019; 61: 111-116. Patients with juvenile onset Schimke immune-osseous-dysplasia (SIOD) have less severe symptoms and can survive in the second and third decade of life. We present an 18 year-old adolescent with juvenile onset SIOD who was diagnosed after renal transplantation and developed BK virus associated nephropathy (BKVAN) and severe pneumonia during follow-up. The patient developed nephrotic syndrome, unresponsive to immunosuppressives, at the age of 8 years. He had a history of meningitis, short stature, microcephaly, prominent ears, and bilateral cryptorchidism. A renal transplantation was performed at the age of 15 years. During follow-up, he suffered from leucopenia, urinary tract infections, herpes labialis, and candida esophagitis. Sanger sequencing of SMARCAL1 revealed a missense mutation on exon 11 (R586W). A renal biopsy performed after a sharp increase in serum creatinine (without significant viremia) revealed BKVAN which responded to sirolimus monotherapy and cidofovir. Three months later, he suffered from productive cough and dyspnea with diffuse ground glass pulmonary infiltrates. His clinical situation deteriorated and non-invasive mechanical ventilation was started. Cidofovir (2 mg/kg) was re-started weekly for a possible BKV pneumonia with intravenous immunoglobulin. After 5 doses of cidofovir and intense antibiotic regime, his dyspnea resolved with stable graft functions. In our case; BKVAN, which developed without significant viremia, and possibly associated pneumonia were treated successfully with cidofovir and sirolimus monotherapy.
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http://dx.doi.org/10.24953/turkjped.2019.01.018DOI Listing
January 2020

Pulmonary complications following hematopoietic stem cell transplantation in children.

Turk J Pediatr 2019 ;61(1):59-60

Departments of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Çıkı K, Doğru D, Kuşkonmaz B, Emiralioğlu N, Yalçın E, Özçelik U, Uçkan-Çetinkaya D, Kiper N. Pulmonary complications following hematopoietic stem cell transplantation in children. Turk J Pediatr 2019; 61: 59-70. Pediatric data about early or long-term pulmonary complications of hematopoietic stem cell transplantation (HSCT) are limited. Here we aimed to evaluate children who were treated with HSCT in the last 10 years and developed pulmonary complications following HSCT and to determine their risk factors associated with pulmonary complications. In this retrospective study, we evaluated 195 patients for the development of pulmonary complications after HSCT within a 10 years of period. Pulmonary complications developed in 71 (36.4%) patients. Of the 71 patients who had pulmonary complications, 60 had one pulmonary complication, 11 had two pulmonary complications. Pulmonary complications were diagnosed as early in 42 (51.2%) and late in 40 (48.8%) episodes. Pulmonary complications were infectious in 28 (34.1%), noninfectious in 20 (24.4%) and both infectious and nonfectious in 34 (41.5%) episodes. Pulmonary complications developed significantly more frequently in patients with malignancy, congenital immune deficiency and with at least one pulmonary disease before HSCT. The number of patients who had myeloablative conditioning regimen was significantly higher in the group of patients without pulmonary complications than the group with pulmonary complications. However, in multivariate analysis, none of these variables were shown to be effective in predicting pulmonary complications after HSCT (p > 0.05). During follow up, 54 (65.8%) episodes recovered, 20 (24.3%) episodes resulted with death due to pulmonary complications, 6 (7.3%) episodes had chronic pulmonary disease (bronchiolitis obliterans (BO) and bronchiolitis obliterans organizing pneumonia (BOOP)); 2 patients (each patient with one episode) were lost to follow up. In conclusion; identifying children who are at risk for severe pulmonary complications and close longitudinal follow-up after HSCT by pediatric pulmonologists is mandatory to increase survival and life quality of these patients.
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http://dx.doi.org/10.24953/turkjped.2019.01.010DOI Listing
January 2020

Nasal nitric oxide levels in primary ciliary dyskinesia, cystic fibrosis and healthy children.

Turk J Pediatr 2019 ;61(1):20-25

Division of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Güney E, Emiralioğlu N, Cinel G, Yalçın E, Doğru D, Kiper N, Özçelik HU. Nasal nitric oxide levels in primary ciliary dyskinesia, cystic fibrosis and healthy children. Turk J Pediatr 2019; 61: 20-25. Primary ciliary dyskinesia (PCD) is a rare, inherited disorder characterized by recurrent respiratory tract infections. The measurement of nasal nitric oxide (nNO) is an important test for the diagnosis of PCD. In this study, we aim to evaluate NIOX-MINOÒ, which is an easily applicable method for measuring nNO, in the diagnosis of patients with PCD and define diagnostic cut-off levels. Furthermore, determining the normal limits of nNO in healthy children and investigating nNO levels of children with cystic fibrosis (CF) are the other aims of this study. The children included in this study were 5 to 18.5 years old, 46 of them had PCD, 44 had CF and 200 were healthy children. To our knowledge, this work contains the widest population compared to previous studies. Subjects receiving steroids or antibiotics or those with any acute respiratory tract infection, asthma or allergic rhinitis were not included in the study. Mean nNO levels were found as 10.4, 22.8 and 21.0 ppb in PCD, CF and healthy children, respectively. The nNO levels for PCD patients were found significantly lower than children with CF and the control groups (p < 0.05). In this study, the diagnostic nNO cut-off level between PCD and the other two groups was determined to be < 11.5 ppb with %83.6 specificity and %67.4 sensitivity. The screening of nNO with NIOX-MINO method provides early diagnose before mucosal biopsy of patients who are suspected to have PCD and therefore, prevents co-morbidities and prolongs survival with early treatment.
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http://dx.doi.org/10.24953/turkjped.2019.01.004DOI Listing
January 2020

The relationship between oxidative stress markers in exhaled breath condensate and respiratory problems in patients with repaired esophageal atresia.

J Pediatr Surg 2020 Aug 21;55(8):1516-1521. Epub 2019 Jun 21.

Hacettepe University Faculty of Medicine, Department of Pediatric Surgery, Ankara, Turkey.

Aim: To evaluate the relationship between respiratory problems and oxidative stress markers in exhaled breath condensate (EBC) of patients with esophageal atresia (EA).

Methods: EA cases with respiratory problems were evaluated retrospectively for age, gender, the type of atresia, surgical treatment, outcome and respiratory symptoms. The results of gastroesophageal reflux (GER) treatment including the use of proton pump inhibitor (PPI) and fundoplication were also documented. EBC samples of 500-1000 μl were obtained by Ecoscreen machine in all cases. The levels of Glutathione (Glut), 8-isoprostane (8-iso), cysteinyl-leukotriene (Cys-LT) were measured with ELISA. Results were compared with healthy control subjects (CG, n = 26) and the relationship between oxidative stress markers and respiratory symptoms was evaluated. The results of GER treatment and oxidative stress markers in EBC were also correlated.

Results: Twenty-nine patients with a mean age of 8.8 years (3-14 years) were included. The male/female ratio was 16:13. The EA presented with distal fistula in 27 cases. While no fistula was observed in 1 case, both proximal and distal fistulae were present in another single case. Associated anomalies, most of which were cardiovascular anomalies, were observed in 65.5% (n = 19) of cases. The median Glut level was 1.03 mM/ml (0.93-1.15), iso-8 was 38.8 pg/mL (32.03-76.2) and Cys-LT was 0.44 pg/mL (20.17-61.3) in patients with EA. The median levels of oxidative markers in CG were 1.23 mM/mL (1.13-1.36), 66.3 pg/mL (33.5-106.7), and 56.9 pg/mL (27.4-80.1), respectively. Glut levels were significantly lower in EA cases compared to CG (p = 0.01). There was no significant difference between the groups regarding 8-iso and CYS-LT levels (p = 0.9, p = 1.0). Cys-LT levels were significantly lower in patients with PPI treatment [21.7 pg/mL (18.6-48.1)], when compared to patients without PPI treatment [41.1 pg/mL (22.5-83.1)] (p = 0.04) and healthy subjects [56.9 pg/mL (27.4-80.1)] (p = 0.017). The 8-iso levels were significantly decreased in cases with fundoplication compared to the patients without fundoplication (p = 0.02).

Conclusion: Glut - an antioxidant agent - levels were significantly lower in EBC of EA cases. The decrease in Cys-LT levels in cases with PPI treatment and in 8-iso levels in patients with fundoplication suggests that the oxidative damage in EBC of EA cases may be correlated with GER and its management.

Type Of Study: Case control study LEVEL OF EVIDENCE: Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.06.007DOI Listing
August 2020

Bilateral Pulmonary Langerhans's Cell Histiocytosis is Surgical Challenge in Children: A Case Report.

European J Pediatr Surg Rep 2019 Jan 23;7(1):e8-e11. Epub 2019 May 23.

Department of Pediatric Oncology, Hacettepe University, Faculty of Medicine, Ankara, Turkey.

 Pulmonary Langerhans's cell histiocytosis (PLCH) is a rare cause of interstitial lung disease in children and more than half of the cases are bilateral. Persistent respiratory distress due to spontaneous pneumothorax (SP) in bilateral PLCH may refractory to conservative treatment and posed a great challenge to surgical modalities. A 3-year-old boy with SP due to bilateral PLCH is presented to discuss the surgical options of recurrent and refractory PLCH cases in children.  The patient was admitted to the emergency department with severe respiratory distress and SP. After chest tube insertion, biopsy from neck mass revealed Langerhans's cell histiocytosis. Chemotherapy including vinblastine and prednisone was initiated. Due to persistent respiratory difficulty and air leaks, talc pleurodesis and thoracoscopic bullae excision with pleural decortication were performed. Two months after the admission, due to nosocomial infection and severe respiratory distress, extracorporeal membranous oxygenation (ECMO) support was initiated. The patient was died of ECMO complications on 24th day of ECMO.  Despite the use of chemotherapy and surgical excision of cystic lesions, bilateral PLCH in children may have lethal outcome. Other treatment options including respiratory support with ECMO and lung transplantation should be considered as last resort of treatment alternative in persistent cases.
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http://dx.doi.org/10.1055/s-0039-1688771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533102PMC
January 2019

A review of the etiology and clinical presentation of non-cystic fibrosis bronchiectasis: A tertiary care experience.

Respir Med 2018 04 24;137:35-39. Epub 2018 Feb 24.

Hacettepe University Faculty of Medicine, Department of Pediatric Pulmonology, Ankara, Turkey.

Introduction: Non-cystic fibrosis(CF) bronchiectasis has been recognized in children for the past 200 years. Early childhood pneumonia and underlying conditions such as immunodeficiency, primary ciliary dyskinesia(PCD), and congenital lung pathology should be considered in the etiology. The aim of our study was to describe the clinical characteristics, laboratory, and radiological findings of a large population of patients with non-CF bronchiectasis at a tertiary center.

Methods: We analyzed the clinical findings of 187 patients diagnosed with non-CF bronchiectasis over a period of 10 years (January 2005-December 2015) at the Hacettepe University Faculty of Medicine Department of Pediatric Pulmonology.

Results: The median age at the time of diagnosis of non-CF bronchiectasis was 8 years (1-18 years). Consanguinity was positive in 59.4% (n = 111) of patients and 19.8% (n = 37) of patients had a positive family history for non-CF bronchiectasis. Common causes were PCD in 51.3% (n = 96), immunodeficiency in 15% (n = 28), history of tuberculosis in 5.9% (n = 11), post-infectious complication in 3.2% (n = 6) and other anomalies in 2.1% (n = 4) of patients. The frequency of pulmonary lobe involvement was as follows: 71.1% left-lower lobe, 59.4% right lower lobe, 54% right-middle lobe, 26.8% left lingula, 13.9% right upper lobe, and 9.6% left upper lobe.

Conclusions: Diagnosis of non-CF bronchiectasis is often delayed because of a failure to recognize the significance of symptoms. Through clinical investigation, including a HRCT scan of the chest, sweat test, studies of immune function, and ciliary function in a child with a prolonged suppurative cough, remains important. In Turkey, the most common causes of non-CF bronchiectasis are PCD and immunodeficiency, related to a high frequency of consanguinity.
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http://dx.doi.org/10.1016/j.rmed.2018.02.013DOI Listing
April 2018

Impact of Surgery on Growth, Pulmonary Functions, and Acute Pulmonary Exacerbations in Children with Non-Cystic Fibrosis Bronchiectasis.

Thorac Cardiovasc Surg 2019 01 12;67(1):58-66. Epub 2017 Dec 12.

Hacettepe University Faculty of Medicine, Department of Pediatric Pulmonology, Ankara, Turkey.

Background: Treatment decisions for the management of bronchiectasis include medical treatment, such as antibiotics, chest physiotherapy, and surgical procedures. Here, we aimed to review the effect of lung resection on longitudinal growth, clinical course of patients depending on annual exacerbation rates, and pulmonary function tests (PFTs) and compare them with the results of only medically treated children with non-cystic fibrosis (non-CF) bronchiectasis.

Methods: The medical records of patients with non-CF bronchiectasis were retrospectively analyzed. Patients who underwent lobectomy/segmentectomy/pneumonectomy were categorized as "surgery group" ( = 29). Age- and gender-matched patients who were only medically treated were selected as "medical group" ( = 33). Annual data of patients were included till the end of postoperative second year in the surgery group and third year of medical treatment in the medical group.

Results: Mean baseline height -score was lower in the surgery group, and mean baseline PFT values were all lower in the surgery group than those in the medical group ( < 0.05). In the surgery group, mean values of height -score were -1.68 ± 0.92 at the time of surgery and improved to -1.42 ± 1.22 and -1.34 ± 1.05 in the first and second postoperative years, respectively, and annual intravenous antibiotic requirements decreased significantly ( < 0.05); however, mean body mass index (BMI) -score values and PFT parameters did not change significantly. In the medical group, height -score mean values and PFT parameters showed nonsignificant improvement but annual exacerbation frequency, annual intravenous, and oral antibiotic requirements decreased significantly.

Conclusion: Surgical management of non-CF bronchiectasis has no significant effect on BMI -scores, annual exacerbation frequencies, oral antibiotic requirements and lung function tests; but can lead to significant improvement on height -scores and decrease need of annual intravenous antibiotic requirements for acute severe exacerbations despite small number of patients in this study.
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http://dx.doi.org/10.1055/s-0037-1608922DOI Listing
January 2019

Genotypic-phenotypic features and enzyme replacement therapy outcome in patients with mucopolysaccharidosis VI from Turkey.

Am J Med Genet A 2017 Nov 8;173(11):2954-2967. Epub 2017 Sep 8.

Hacettepe University Children Hospital, Division of Metabolism, Ankara, Turkey.

Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD) characterized by a chronic, progressive course with multiorgan involvement. In our study, clinical, biochemical, molecular findings, and response to enzyme replacement therapy (ERT) for at least 6 months were evaluated in 20 patients with MPS VI. Treatment effects on clinical findings such as liver and spleen sizes, cardiac and respiratory parameters, visual and auditory changes, joints' range of motions, endurance tests and changes in urinary glycosaminoglycan excretions, before and after ERT were analyzed. ERT caused increased physical endurance and decreased urinary dermatan sulfate/chondroitin sulfate ratios. Changes in growth parameters, cardiac, respiratory, visual, auditory findings, and joint mobility were not significant. All patients and parents reported out an increased quality of life, which were not correlated with clinical results. The most prevalent mutation was p.L321P, accounting for 58.8% of the mutant alleles and two novel mutations (p.G79E and p.E390 K) were found. ERT was a safe but expensive treatment for MPS VI, with mild benefits in severely affected patients. Early treatment with ERT is mandatory before many organs and systems are involved.
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http://dx.doi.org/10.1002/ajmg.a.38459DOI Listing
November 2017

Long term azithromycin therapy in patients with cystic fibrosis.

Turk J Pediatr 2016 ;58(1):34-40

Division of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Inflammation is a central contributor to the pathogenesis of cystic fibrosis (CF) pulmonary disease; so limiting the excessive production of inflammatory mediators represents a major therapeutic strategy for slowing the decline in lung function and improving survival. The macrolide antibiotic azithromycin (AZM) has anti-inflammatory properties and immunomodulatory effects that may be beneficial in CF. The aim of this study was to document the long term use of AZM effect on pulmonary function, nutritional status and number of pulmonary exacerbations in patients with CF. Twenty four patients with CF aged 4-23 years followed at Hacettepe University Department of Pediatric Pulmonology between May 2007- December 2014 enrolled in the study from 630 CF patients. They received 10 mg/kg/day of AZM three times a week. Pulmonary function parameters, sputum cultures, body mass index (BMI) Z scores and number of pulmonary exacerbations were analyzed at different time intervals (at the visits at months 6, 9 and 12). Median age of the patients was 14.7 (range 4-23 years) years and median treatment duration was 14 months (range 6-60 months). Initially, median FEV1% was found 68% (range 30%-100%), BMI was found 17.05 (range 13.3-26.5) and oxygen saturation was found 95% (range 84%-99%). At the end of the 6th, 9th and 12th months of the AZM therapy; no significant differences in FEV1% and oxygen saturation parameters were found compared to the initial time, however BMI increased significantly (p=0.03), also the number of pulmonary exacerbations (p < 0.001) and severe exacerbations (p < 0.001) needing intravenous antibiotic treatment were significantly reduced at the 6th and 12th month. At the end of the 12th month of AZM; Methicillin sensitive S. aureus (MSSA) colonization was significantly increased (p=0.005) and increased macrolide resistance was detected (p=0.008). Although, this study could not be designed as a placebo controlled study, the results showed that at least 6 months of AZM treatment led to a significiant reduction in the number of pulmonary exacerbations requiring antibiotics and improvement on nutritional status. Despite increased P. aeruginosa antibiotic resistance and MSSA colonization rates, the lower incidence of acute exacerbations in patients receiving AZM is an important and clinically relevant measure of beneficial effect. Therefore, long term use of AZM may be considered to slow pulmonary deterioration in CF patients with P. aeruginosa colonization.
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http://dx.doi.org/10.24953/turkjped.2016.01.005DOI Listing
May 2017

Diagnosis of cystic fibrosis with chloride meter (Sherwood M926S chloride analyzer®) and sweat test analysis system (CFΔ collection system®) compared to the Gibson Cooke method.

Turk J Pediatr 2016 ;58(1):27-33

Division of Pediatric Pulmonology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Sweat test with Gibson Cooke (GC) method is the diagnostic gold standard for cystic fibrosis (CF). Recently, alternative methods have been introduced to simplify both the collection and analysis of sweat samples. Our aim was to compare sweat chloride values obtained by GC method with other sweat test methods in patients diagnosed with CF and whose CF diagnosis had been ruled out. We wanted to determine if the other sweat test methods could reliably identify patients with CF and differentiate them from healthy subjects. Chloride concentration was measured with GC method, chloride meter and sweat test analysis system; also conductivity was determined with sweat test analysis system. Forty eight patients with CF and 82 patients without CF underwent the sweat test, showing median sweat chloride values 98.9 mEq/L with GC method, 101 mmol/L with chloride meter, 87.8 mmol/L with sweat test analysis system. In non-CF group, median sweat chloride values were 16.8 mEq/L with GC method, 10.5 mmol/L with chloride meter, and 15.6 mmol/L with sweat test analysis system. Median conductivity value was 107.3 mmol/L in CF group and 32.1 mmol/L in non CF group. There was a strong positive correlation between GC method and the other sweat test methods with a statistical significance (r=0.85) in all subjects. Sweat chloride concentration and conductivity by other sweat test methods highly correlate with the GC method. We think that the other sweat test equipments can be used as reliably as the classic GC method to diagnose or exclude CF.
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http://dx.doi.org/10.24953/turkjped.2016.01.004DOI Listing
May 2017