Exploring Turkey's mosaic of novel variants and complex alleles in cystic fibrosis genetics.

BACKGROUNDS: Genetic variants in CF transmembrane conductance regulator (CFTR) gene causes cystic fibrosis (CF), a prevalent autosomal recessive disorder. More than 2000 variants in CFTR have been described as disease causative. This study aims to delineate the genotypic and phenotypic landscape of CF among people with CF (pwCF) followed at the largest CF center in Turkey. METHODS: We conducted a descriptive and retrospective analysis of 481 patients registered with the European CF Society Patient Registry and followed at Marmara University Selim Çöremen CF Center from 2015 onwards. Comprehensive CFTR analysis was utilized for genetic diagnosis. Besides the whole cohort, novel variants and complex alleles were also described. RESULTS: Our cohort exhibited a broad spectrum of CFTR variants, with 136 different variants detected, indicating substantial genetic diversity. The F508del variant was less prevalent in our cohort compared to US and European averages, which could reflect unique genetic and demographic characteristics of the Turkish population. Additionally, we identified nine novel variants in 12 alleles, which enhances the understanding of CF's genetic complexity in this region, and complex alleles in 32 pwCF. CONCLUSION: Our research underscores the heterogeneity of CFTR variants in Turkey and highlights the necessity for extensive genetic profiling particularly for diverse populations to provide effective personalized treatment strategies. It is crucial to understand the full spectrum of CFTR variants with the advent of CFTR modulators.

THE ASSOCIATION BETWEEN AMINOGLYCOSIDE EXPOSURE AND OTOTOXICITY IN CHILDREN WITH CYSTIC FIBROSIS.

INTRODUCTION: Pulmonary exacerbations increase the requirement of aminoglycoside (AG) antibiotics in people with cystic fibrosis (pwCF). Several studies have shown that AGs have a cumulative effect on ototoxicity. We aimed to investigate the relationship between AG exposure and ototoxicity by using three different methods in patients with CF. MATERIALS-METHODS: The multicenter study included 121 pwCF aged between 5-18 years with a history of parenteral AG exposure. Standard pure tone audiometry (sPTA), extended high frequency audiometry (EHF-PTA), and distortion-product otoacoustic emissions (DPOAE) tests were performed. Mitochondrial mutation analysis for m1555G>A was performed in 61 patients. RESULTS: Median age was 12.85 years and 52.1% (n=63) were male. 18.2% (n=22) of the patients had received parenteral AGs more than 5 courses/lifetime. Ototoxicity was detected in at least one of the tests in 56.2% (n= 68) of the patients. Only 10.7 % (n=13) of the patients had reported a symptom indicating ototoxicity. 30.3% (n=30) of the patients had ototoxicity in the low-exposure group while it was 45.5% (n=10) in the high-exposure group according to EHF-PTA (p>0.05). Median number of parenteral amikacin courses was significantly higher in the ototoxic group [2(1.25-5.75) vs 2(1-3); p=0.045]. No m1555A>G mutation was detected in 61 patients who screened for mitochondrial mutation analysis. CONCLUSION: As AG ototoxicity occurs primarily at high frequencies, EHF-PTA is important in early detecting otoxicity. EHF-PTA and DPOAE detected ototoxicity in some patients with normal PTA results. All pwCF with a history of AG exposure should be evaluated for hearing loss since symptoms may only be noticed in the late period.

Assessment of patients' baseline cystic fibrosis knowledge levels following translation and adaptation of the CF R.I.S.E translation program into Turkish.

BACKGROUND: Cystic fibrosis (CF) patients have a limited life expectancy, but significant medical advances now highlight the need for successful transition programs from pediatric to adult care. The goal of this project was to introduce the transition program CF R.I.S.E (Responsibility. Independence. Self-care. Education.) to a CF center with limited resources at Marmara University (MU). METHODS: The program was adapted and translated into Turkish with the CF Foundation's permission. A team of experts collaborated to develop educational materials for patients and families. After translation and implementation of the CF S.O.B.E program, 11 Knowledge Assessment Questionnaire (KQA) tests were administered online to the patients aged between 16 and 25 years to assess the lack of patient knowledge. RESULTS: The CF R.I.S.E program was successfully implemented within 6 months. A pilot study showed positive feedback from randomly selected patients, indicating the program's effectiveness and understandability. The mean age of the patients was 19.4 ± 2.9 years, and 42 (52%) were female. The mean forced expiratory volume (FEV1pp) was 76.3 ± 23.2. Fourteen (17.3%) and 4 (4.9%) of the patients colonized with Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA), respectively. Fifteen (18.5%) were on modulator therapy. Eleven Knowledge Assessment Questionnaires (KAQ) surveys were administered to 81 patients. The percentage of correct responses to the KAQs ranged from 47.9% to 68.3%. CONCLUSION: MU CF Center in Turkey implemented the CF S.O.B.E (Responsibility, Self-care, Independence, and Education in Turkish) program. The center aims to make the program a regular practice and expand collaboration with adult clinics. Future studies will assess its long-term impact and applicability in different health settings. The final goal is to disseminate the program's resources and promote structured transition practices across the country.

Beyond the 10%: Unraveling the genetic diversity in Turkish cystic fibrosis patients not eligible for CFTR modulators.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease caused by variants of CFTR gene. Over 2000 variants have been identified, and new drugs called CFTR modulators have been developed to target specific defects in the CFTR protein. However, these drugs are only suitable for patients with certain variants of CFTR, and eligibility rates vary depending on race and geographical region. This study aimed to reveal the detailed genotype and clinical characteristics of people with CF (pwCF) at our center in Turkey, a developing country, who are not eligible for CFTR modulators. METHODS: A total of 445 pwCF followed up at Marmara University were reviewed retrospectively. Variants of the patients ineligible to CFTR modulators were classified based on American College of Medical Genetics guidelines, CFTR classification, the change in the encoded protein, and the variant type. RESULTS: The study revealed that 139 (31.2%) patients weren't eligible for CFTR modulators. There were 60 different variants in the 276 alleles, as two were missing. The majority of patients had missense or nonsense variants, and that the most common variant was c.1545_1546del, which can be said unique to this geography. CONCLUSION: The study highlights the importance of detecting the variants of ineligible patients in detail to guide future approaches for more targeted and effective interventions in CF care. Testing the effectiveness of CFTR modulators for rare or newly occurring variants is crucial to ensure equal access for pwCF to these therapies from different racial backgrounds and ethnic minorities.

Association between upper and lower respiratory disease among patients with primary ciliary dyskinesia: an international study.

Introduction: Nearly all patients with primary ciliary dyskinesia (PCD) report ear-nose-throat (ENT) symptoms. However, scarce evidence exists about how ENT symptoms relate to pulmonary disease in PCD. We explored possible associations between upper and lower respiratory disease among patients with PCD in a multicentre study. Methods: We included patients from the ENT Prospective International Cohort (EPIC-PCD). We studied associations of several reported ENT symptoms and chronic rhinosinusitis (defined using patient-reported information and examination findings) with reported sputum production and shortness of breath, using ordinal logistic regression. In a subgroup with available lung function results, we used linear regression to study associations of chronic rhinosinusitis and forced expiratory volume in 1 s (FEV1) accounting for relevant factors. Results: We included 457 patients (median age 15 years, interquartile range 10-24 years; 54% males). Shortness of breath associated with reported nasal symptoms and ear pain of any frequency, often or daily hearing problems, headache when bending down (OR 2.1, 95% CI 1.29-3.54) and chronic rhinosinusitis (OR 2.3, 95% CI 1.57-3.38) regardless of polyp presence. Sputum production associated with daily reported nasal (OR 2.2, 95% CI 1.20-4.09) and hearing (OR 2.0, 95% CI 1.10-3.64) problems and chronic rhinosinusitis (OR 2.1, 95% CI 1.48-3.07). We did not find any association between chronic rhinosinusitis and FEV1. Conclusion: Reported upper airway symptoms and signs of chronic rhinosinusitis associated with reported pulmonary symptoms, but not with lung function. Our results emphasise the assessment and management of upper and lower respiratory disease as a common, interdependent entity among patients with PCD.

Comparison of refugee patients with cystic fibrosis and their counterpart children from Turkey during the war.

Since the outbreak of the Syrian civil war in 2011, the population of Arab refugees in Turkey has rapidly increased. While cystic fibrosis (CF) is believed to be rare among Arabs, recent studies suggest it is underdiagnosed. This study aims to present the demographic, clinical, and genetic characteristics of CF patients among Arab refugees in Turkey. Additionally, a comparison is made between the findings in the National CF Registry 2021 in Turkey (NCFRT) and the refugee CF patient group. The study included refugee patients between the ages of 0 and 18 years who were diagnosed with CF and received ongoing care at pediatric pulmonology centers from March 2011 to March 2021. The study examined demographic information, age at diagnosis, age of diagnosis of patients through CF newborn screening (NBS), presenting symptoms, CF transmembrane conductance regulator (CFTR) mutation test results, sputum culture results, weight, height, and body mass index (BMI) z score. Their results were compared with the NCFRT results. The study included 14 pediatric pulmonology centers and 87 patients, consisting of 46 (52.9%) boys and 41 (47.1%) girls. All of the patients were Arab refugees, with 80 (92%) being Syrian. All the patients were diagnosed in Turkey. The median age at diagnosis of patients was 22.33 (interquartile range, 1-258) months. The median age of diagnosis of patients through NBS was 4.2 (interquartile range, 1-12) months. The median age of older patients, who were unable to be included in the NBS program, was 32.3 (interquartile range, 3-258) months. Parental consanguinity was observed in 52 (59.7%) patients. The mutation that was most frequently found was F508del, which accounted for 22.2% of the cases. It was present in 20 patients, constituting 32 out of the total 144 alleles. There was a large number of genetic variations. CFTR genotyping could not be conducted for 12 patients. These patients had high sweat tests, and their genetic mutations could not be determined due to a lack of data. Compared to NCFRT, refugee patients were diagnosed later, and long-term follow-up of refugee CF patients had significantly worse nutritional status and pseudomonas colonization.  Conclusion: Although refugee CF patients have equal access to NBS programs and CF medications as well as Turkish patients, the median age at diagnosis of patients, the median age of diagnosis of patients through NBS, their nutritional status, and Pseudomonas colonization were significantly worse than Turkish patients, which may be related to the difficulties of living in another country and poor living conditions. The high genetic heterogeneity and rare mutations detected in the refugee patient group compared to Turkish patients. Well-programmed NBS programs, thorough genetic studies, and the enhancement of living conditions for refugee patients in the countries they relocate to can have several advantages such as early detection and improved prognosis. What is Known: • Children who have chronic diseases are the group that is most affected by wars. • The outcome gets better with early diagnosis and treatment in patients with Cystic Fibrosis (CF). What is New: • Through the implementation of a newborn screening program, which has never been done in Syria previously, refugee patients, the majority of whom are Syrians were diagnosed with cystic fibrosis within a duration of 4 months. • Despite equal access to the newborn screening program and CF medications for both Turkish patients and refugee patients, the challenges of living in a foreign country have an impact on refugees.

Childhood interstitial lung disease in Turkey: first data from the national registry.

The childhood interstitial lung diseases (chILD) Turkey registry (chILD-TR) was established in November 2021 to increase awareness of disease, and in collaboration with the centers to improve the diagnostic and treatment standards. Here, the first results of the chILD registry system were presented. In this prospective cohort study, data were collected using a data-entry software system. The demographic characteristics, clinical, laboratory, radiologic findings, diagnoses, and treatment characteristics of the patients were evaluated. Clinical characteristics were compared between two main chILD groups ((A) diffuse parenchymal lung diseases (DPLD) disorders manifesting primarily in infancy [group1] and (B) DPLD disorders occurring at all ages [group 2]). There were 416 patients registered from 19 centers. Forty-six patients were excluded due to missing information. The median age of diagnosis of the patients was 6.05 (1.3-11.6) years. Across the study population (n = 370), 81 (21.8%) were in group 1, and 289 (78.1%) were in group 2. The median weight z-score was significantly lower in group 1 (- 2.0 [- 3.36 to - 0.81]) than in group 2 (- 0.80 [- 1.7 to 0.20]) (p < 0.001). When we compared the groups according to chest CT findings, ground-glass opacities were significantly more common in group 1, and nodular opacities, bronchiectasis, mosaic perfusion, and mediastinal lymphadenopathy were significantly more common in group 2. Out of the overall study population, 67.8% were undergoing some form of treatment. The use of oral steroids was significantly higher in group 2 than in group 1 (40.6% vs. 23.3%, respectively; p = 0.040).   Conclusion: This study showed that national registry allowed to obtain information about the frequency, types, and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. What is Known: • Childhood interstitial lung diseases comprise many diverse entities which are challenging to diagnose and manage. What is New: • This study showed that national registry allowed to obtain information about the frequency, types and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. Also, our findings reveal that nutrition should be considered in all patients with chILD, especially in A-DPLD disorders manifesting primarily in infancy.

Electronic home monitoring of children with cystic fibrosis to detect and treat acute pulmonary exacerbations and its effect on 1-year FEV1.

BACKGROUND: We aimed to investigate the effect of the use of electronic home spirometry in children with cystic fibrosis (CF) on 1-year FEV1 (% predicted, pp) change. METHODS: This is a randomised, one-year prospective study including children with CF between 6 and 18 years of age. Subjects were randomised into home spirometry group (HSG) and usual care group (UCG). Children in HSG performed two pulmonary function tests (PFT) per week. Data regarding acute pulmonary exacerbations (PEx) was obtained from patients' records. At baseline and 12th month, health related quality of life questionnaire for CF patients (CFQ-R) and lung clearance index (LCI) were performed. RESULTS: Sixty children were recruited with a median (IQR) age of 13.3 (11.4-15.4) years. Absolute change in FEV1pp from baseline to 12th month as median (IQR) was +1% (-6.75-9.75) in HSG and -2.50% (-7.50-3.25) in UCG (p = 0.10). Sensitivity analysis including only adherent children in HSG (n = 22), yielded an increase of 5% (-3.50-12) in HSG and a decrease of 2.50% (-7.50-3.25) in UCG (p = 0.009). A total of 29 (96.7%) subjects in HSG and 23 (76.7%) in UCG had PEx (p = 0.05). Absolute change in median (IQR) LCI2.5 from baseline to the 12th month was -1.6 [-2.9-0] (p<0.001) in HSG and -1.5 [-2.8-(-0.6)] (p<0.001) in UCG (p = 0.94). There was a significant increase in the social domain of the CFQ-R in HSG (from 59.1 to 76.2, p = 0.01). CONCLUSIONS: Electronic home monitoring of children with CF by spirometry may result in improvement in lung function.

Medical Treatment of Obstructive Sleep Apnea in Children.

Obstructive sleep apnea (OSA) is characterized by recurrent complete or partial obstruction of the upper airway. The prevalence is 1-4% in children aged between 2 and 8 years and rising due to the increase in obesity rates in children. Although persistent OSA following adenotonsillectomy is usually associated with obesity and underlying complex disorders, it can also affect otherwise healthy children. Medical treatment strategies are frequently required when adenotonsillectomy is not indicated in children with OSA or if OSA is persistent following adenotonsillectomy. Positive airway pressure treatment is a very effective modality for persistent OSA in childhood; however, adherence rates are low. The aim of this review article is to summarize medical treatment options for OSA in children.

Sinonasal disease among patients with primary ciliary dyskinesia: an international study.

Background: Sinonasal symptoms are a common feature of primary ciliary dyskinesia (PCD); however, literature about their severity and frequency, particularly during the life course, is scarce. Using baseline data from the Ear, nose and throat (ENT) Prospective International Cohort of PCD patients, we describe sinonasal disease in PCD. Methods: We included participants who had a routine sinonasal examination during which they completed a symptoms questionnaire. We compared frequency of reported symptoms and examination findings among children and adults, and identified characteristics potentially associated with higher risk of sinonasal disease using ordinal regression. Results: 12 centres contributed 384 participants; median age was 16 years (IQR 9-22), and 54% were male. Chronic nasal problems were the most common feature, reported by 341 (89%). More adults (33; 24%) than children (10; 4%) described hyposmia. Quality of life was moderately affected by rhinosinusitis among 136 participants with completed SNOT-22 questionnaires (median score 31; IQR 23-45). Examinations revealed nasal polyps among 51 of 345 participants (15%) and hypertrophic inferior nasal turbinates among 127 of 341 participants (37%). Facial pain was detected in 50 of 342 participants (15%). Nasal polyps, hypertrophic turbinates, deviated septum and facial pain were found more commonly in adults than children. The only characteristic associated with higher risk of sinonasal disease was age 10 years and older. Conclusions: Based on our findings, regular sinonasal examinations are relevant for patients with PCD of all ages. There is a need for improved management of sinonasal disease supported by evidence-based guidelines.

Implementation of standardized cystic fibrosis care algorithm to improve the center data-quality improvement project international collaboration.

BACKGROUND: A collaboration between the University of Michigan (U of M) Cystic Fibrosis Center (CFC) and Marmara University (MU) CFC was initiated to improve the health status of people with cystic fibrosis (pwCF) at MU through implementing Quality Improvement (QI) initiatives. The main aim was to improve lung function in children with FEV1pp <80. The secondary aim was to assess the changes in health related quality of life. METHODS: Included in the project were pwCF who received cystic fibrosis (CF) care at the MU CFC and were 6-18 years of age with an FEV1pp <80. Flow charts were created and a standardized CF care algorithm was implemented. Weekly case review were done to develop individualized treatment plans. Appropriate intervention was applied and patient data were assessed at baseline, 3, 6, 9 and 12 months. The Cystic Fibrosis Revised Questionnaire (CFQ-R) was completed. RESULTS: 55 pwCF were included (mean age:11.8 ± 3.3 years). Mean FEV1pp (SD) at baseline, 6 and 12 month was 63.7 (14.6), 66.9 (16.6), 70.4 (19.2), respectively, with a relative increase of 5.0% in 6 months (p:0.002) and 10.5% in 12 months compared to baseline (p<0.001). Physical functioning, eating problems and respiratory symptoms domains of the CFQ-R questionnaire were improved at the end of the one year for 6-13 (p = 0.024, p = 0.009, p = 0.002) and 13-18 year olds (p = 0.013, p = 0.002, p = 0.038). CONCLUSION: There was significant improvement in pwCF with FEV1<80%pp after implementing this QI project. The processes and assessments used can be adopted by other low-middle income countries to improve similar measures.

Clinical and Functional Characteristics of the E92K CFTR Gene Variant in the Russian and Turkish Population of People with Cystic Fibrosis.

The pathogenic variant E92K (c.274G > A) of the CFTR gene is rare in America and Europe, but it is common for people with cystic fibrosis from Russia and Turkey. We studied the effect of the E92K genetic variant on the CFTR function. The function of the CFTR channel was studied using the intestinal current measurements (ICM) method. The effects of CFTR modulators on the restoration of the CFTR function were studied in the model of intestinal organoids. To assess the effect of E92K on pre-mRNA splicing, the RT-PCR products obtained from patients' intestinal organoid cultures were analyzed. Patients with the genetic variant E92K are characterized by an older age of diagnosis compared to homozygotes F508del and a high frequency of pancreatic sufficiency. The results of the sweat test and the ICM method showed partial preservation of the function of the CFTR channel. Functional analysis of CFTR gene expression revealed a weak effect of the E92K variant on mRNA-CFTR splicing. Lumacaftor (VX-809) has been shown to restore CFTR function in an intestinal organoid model, which allows us to consider the E92K variant as a promising target for therapy with CFTR correctors.

Improvements in body mass index of children with cystic fibrosis following implementation of a standardized nutritional algorithm: A quality improvement project.

BACKGROUND: A collaboration between the University of Michigan (UM) Cystic Fibrosis Center (CFC) and Marmara University (MU) CFC was initiated in MU through conducting Quality Improvement projects (QIP). The global aim was to improve nutritional status of children with CF (cwCF), with a specific aim to increase the mean BMI percentile (BMIp) for cwCF by 10 percentile points in 12 months. METHODS: Body mass index (BMI) percentiles of cwCF were categorized as: nutritionally adequate (BMIp ≥ 50%); at risk (BMIp 25%-49%); urgently at risk (BMIp 10%-25%); critically at risk (BMIp < 10%). Appropriate interventions were made according to BMIp category every three months. Forced expiratory volume in one-second percent predicted (FEV1pp), and health-related quality of life (HRQoL) were evaluated. RESULTS: One hundred and eight-two cwCF with a mean age of 9.1 ± 4.3 years were included in the project. Baseline BMIp increased from 25.6 to 37.2 at the 12th month (p < 0.001). In the critically at-risk group BMIp increased from 3.6 to 20.5 (p < 0.001), in the urgently at risk group from 15.9 to 30.8 (p < 0.001), in the at risk group from 37.0 to 44.2 (p < 0.079) and in the nutritionally adequate group the increase was from 66.8 to 69.5 (p < 0.301). FEV1pp also improved significantly, from 81.3 ± 20.6 to 85.9 ± 20.8 (p < 0.001). Physical functioning, eating problems, and respiratory symptoms domains of the HRQoL evaluation improved (p < 0.05). CONCLUSION: This project has led to significant improvements in BMIp, FEV1pp and HRQoL of cwCF; similar projects could easily be implemented by centers in other developing countries.

The safety and sustainability of bottle-pep therapy in pediatric patients with cystic fibrosis.

INTRODUCTION: Airway clearance techniques, which include positive expiratory pressure (PEP) devices, are essential in the pulmonary rehabilitation of cystic fibrosis (CF). Bottle-PEP is a low-cost but an effective alternative. OBJECTIVE: The aim of this study is to document the sustainability and safety of Bottle-PEP therapy as a home rehabilitation aid. METHODS: The study has been designed as a prospective case series. Patients with CF at the age of 6-18 years in acute exacerbation period were included in the study. Bottle-PEP training was given by a competent physiotherapist to those patients who did not use any method, and those who currently use another device were followed up with their existing devices. Thus, patients divided into two groups were followed up for 1 year. The patients were evaluated by phone every 2 weeks for exacerbation, regular and proper use of the device, and satisfaction during their follow-up. The patients were evaluated every 3 months with pulmonary function tests, 6-minute walking test (6MWT) and quality of life. RESULTS: Thirty-four patients were included in the study. The acute exacerbation score of the patients was 4.5 in the Bottle-PEP group and 6 in the other group, showing no significant difference (p = .1). Treatment compliance scores were compared, the median value of the Bottle-PEP group was 24 the other group was 27 and there was no significant difference (p = .6). During follow-up of, there were no significant differences in FEV1, 6MWT and quality of life data (p > .05). CONCLUSION: Bottle-PEP treatment is not different from other devices in terms of long-term usability and safety in patients diagnosed with cystic fibrosis.

Parent's report on oral health-related quality of life of children with cystic fibrosis.

BACKGROUND: Health-related quality of life (HRQoL) scales are now widely used in children with cystic fibrosis (cwCF) which reflects the course of the disease. In this cross-sectional study, our primary aim was to compare the Pediatric Oral Health-Related Quality of Life (POQL) and Oral Health Score (OHS) between cwCF and healthy group. Our secondary aim was to evaluate the association between Pseudomonas aeruginosa (PA) colonization, pulmonary function test, OHS and POQL in cwCF. METHODS: The study population (age ranging 6-14) included 55 cwCF followed at the Marmara University Division of Pediatric Pulmonology compared with 50 healthy peers. A survey consisted of general questions (age, sex, etc.) and the POQL instrument were filled by parents. The decayed, missing, and filled teeth for both primary (dft) and permanent dentition (DMFT) was detected according to WHO criteria. Data like current body mass index (BMI z score), colonization status with PA, predicted value for forced expiratory volume in 1 second (FEV1pp), and any hospitalizations during the previous year were obtained from their medical. Differences between the groups were evaluated using Chi-square and Mann-Whitney U test with a significance level set at 0.05. RESULTS: There was no significant difference between PA-colonized cwCF and healthy controls in DMFT (p = 0.916). For all domains of POQL (emotional function, social function, role function), scores of cwCF were significantly better than healthy controls (p < 0.05). There were no statistically significant differences between all domains of POQL scores in PA colonized and non-PA colonized cwCF' POQL scores (p > 0.05). CONCLUSION: Although POQL scores of cwCF were encouraging, dental caries prevention and regular follow-ups should be taken into consideration.

The utility of risk assessment tools for acute pulmonary embolism in children.

BACKGROUND AND AIM: Pulmonary embolism (PE) is a potentially life-threatening disease in children. The objective of the study is to evaluate the utility of adult-based pulmonary embolism rule-out criteria (PERC), Pediatric PE Model, and D-dimer in the diagnosis of PE in children. MATERIAL AND METHODS: The study consisted of patients under 18 years of age who were consulted to the Pediatric Pulmonology Clinic for the evaluation of PE. Patients were divided into two groups based on the confirmation of PE. The group with the presence of PE (n = 20) consisted of children who were diagnosed with PE. The group with the absence of PE (n = 28) consisted of children with clinically suspected PE but negative diagnostic imaging. Adult validated clinical decision PERC rule and Pediatric PE Model were retrospectively applied to the patients. RESULTS: In the study, PERC demonstrated a sensitivity of 60% and a specificity of 46% for the diagnosis of PE in children. When PE Model was evaluated for the children, it was found a 50% sensitivity and 75% specificity. Combining PE Model and PERC rule with D-dimer did not increase the specificity and sensitivity. Smoking was found to be relevant for PE in the childhood. Twenty-five percent of the patients had a genetic tendency for PE. All of the patients had an underlying disease as well. CONCLUSION: None of the current risk assessment tools (PE Model, PERC, D-dimer) were found to be accurate in predicting PE. Further larger population studies are still required to develop a better diagnostic approach.

Collaboration between two CF centers; one in USA and one in Turkey before and during CoV2 pandemic.

To address the discrepancy in the quality of care and outcomes between cystic fibrosis centers (CFCs) in high-income countries and limited resources countries (LRCs), a collaboration between our team at the University of Michigan CFC (UMCFC) and a CF center in Turkey (Marmara University CFC [MUCFC], Istanbul) was established. The collaboration included evaluation of all aspects of care and initiation of quality improvement (QI) measures. Teaching and implementing QI tools has led to start of improvement in MUCFC care. Close monitoring and sharing resources like UMCFC algorithms, protocols, and QI processes were done.

The effect of coronavirus disease 2019 on anxiety levels of children with cystic fibrosis and healthy peers.

BACKGROUND: Cystic fibrosis (CF) is a chronic disease causing recurrent respiratory tract infections. Viral respiratory tract infections are more severe in CF. The first case of coronavirus disease 2019 (COVID-19) was seen in Turkey on March 11, 2020, and nationwide school closure and lockdown were implemented. School closure and home confinement might have adverse effects on children's physical and mental health. In this study, we aimed to compare the effect of the COVID-19 pandemic on psychological reactions of CF patients and healthy controls. METHODS: This is a controlled cross-sectional study including 7-18-year-old children with CF. The survey included questions regarding family environment and peer relations, self-care, and psychological reactions to the COVID-19 pandemic. The questionnaire was administered to children via telephone calls under parental supervision. RESULTS: We evaluated 132 CF patients and 135 of their healthy peers. Mean age was 11.5 ± 2.9 years in the CF group and 11.8 ± 3.2 years in the control group (P = 0.98). There were 55 girls (41.7%) in the CF group and 81 girls (60%) in the control group (P = 0.027). The socioeconomic status of their families was similar. The CF patients were found to be less anxious for family members at risk of COVID-19, less upset about school closure, and less anxious about the COVID-19 pandemic (P < 0.001, 0.02, 0.01, respectively). CONCLUSIONS: Cystic fibrosis patients seem to show more resilience in coping with the pandemic. Appropriate psychological support should be provided to them and resilience strategies in coping with the pandemic should be nurtured.

Comparison of intravenous and non-intravenous antibiotic regimens in eradication of P. aeruginosa and MRSA in cystic fibrosis.

BACKGROUND: Chronic pulmonary infection is the leading cause of mortality and morbidity in patients with cystic fibrosis (CF). The most common pathogens isolated in CF are Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Chronic infection of PA and methicillin-resistant S. aureus (MRSA) are associated with worse survival and antibiotic eradication treatment is recommended for both. This study compared the outcomes between intravenous (IV) and non-IV antibiotics in eradication of PA and MRSA. METHODS: This was a single-center retrospective study. All respiratory specimen cultures of 309 CF patients and eradication regimens between 2015 and 2019 were reviewed. Patients received eradication treatment in case of first ever isolation or new isolation after being infection-free ≥1 year. The primary analysis was the comparison of the percentage of successful eradication after receiving IV and non-IV eradication regimens. Demographic and clinical risk factors for eradication failure were also analyzed. RESULTS: One hundred and two patients with PA isolations and 48 patients with MRSA were analyzed. At 1 year, 21.6% in PA group and 35.4% in MRSA group were successfully eradicated. There was not any statistically significant difference between IV versus non-IV antibiotic regimens on eradication in either group. Additionally, none of the clinical risk factors was significantly associated with eradication failure in PA and MRSA groups. CONCLUSION: In the eradication of PA and MRSA, IV and non-IV treatment regimens did not show any superiority to one another. Non-parenteral eradication could be a better option considering the cost-effectiveness and the treatment burden of IV treatments due to hospitalization and the need for IV access.

Pediatric flexible bronchoscopy in the intensive care unit: A multicenter study.

INTRODUCTION: Flexible bronchoscopy (FB) is frequently used for assessment and treatment of patients with respiratory diseases. Our aim was to investigate the contribution of FB to diagnosis and therapy in children admitted to the intensive care units (ICU) and to evaluate the safety of FB in this vulnerable population. METHODS: Children less than 18 years of age who underwent FB in the five neonatal and pediatric ICUs in Istanbul between July 1st, 2015 and July 1st, 2020 were included to the study. Demographic and clinical data including bronchoscopy indications, findings, complications, and the contribution of bronchoscopy to the management were retrospectively reviewed. RESULTS: One hundred and ninety-six patients were included to the study. The median age was 5 months (range 0.3-205 months). The most common indication of FB was extubation failure (38.3%), followed by suspected airway disease. Bronchoscopic assessments revealed at least one abnormality in 90.8% patients. The most common findings were airway malacia and the presence of excessive airway secretions (47.4% and 35.7%, respectively). Positive contribution of FB was identified in 87.2% of the patients. FB had greater than 1 positive contribution in 138 patients and 80.6% of the patients received a new diagnosis. Medical therapy was modified after the procedure in 39.8% and surgical interventions were pursued in 40% of the patients. Therapeutic lavage was achieved in 18.9%. There were no major complications. CONCLUSION: Flexible bronchoscopy is a valuable diagnostic and therapeutic tool in neonatal and pediatric ICUs and is not associated with major complications.