Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. METHODS: This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. RESULTS: Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. CONCLUSION: The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

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.

Childhood sarcoidosis in the middle Anatolia of Turkey.

OBJECTIVE: This retrospective study aimed to describe the clinical and radiological features, diagnostic methods, laboratory findings, organ involvement, and treatment strategies of 22 patients who followed up with late-onset childhood sarcoidosis and compare them with the literature. MATERIAL AND METHOD: This retrospective multicenter study reviewed the medical records of 22 children with sarcoidosis who applied to the Pediatric pulmonology department of Erciyes University Faculty of Medicine and Necmettin Erbakan Faculty of Medicine in 2012 and 2022. RESULTS: The mean age of the patients at the time of diagnosis was 13.1/year (interquartile range [IQR]1:6.3-[IQR]3:15.7). The most common first presenting symptom was cough 40.9% (n = 9), weight loss 31.8% (n = 7), and dyspnea 22.7% (n = 5). There were elevated levels of C-reactive protein (CRP; 59%), angiotensin-converting enzyme (ACE; 54.5%), erythrocyte sedimentation rate (ESR; 54.5%), and immunoglobulin G (IgG; 54.5%). Twenty patients (90%) received systemic steroid treatment. Eighteen (81.8%) of these patients responded positively to treatment. Two patients had a recurrence. CONCLUSION: The incidence of sarcoidosis in children in Turkey is currently unknown. However, a regional average of 2.2 cases per year has been documented for the first time. Contrary to previous studies, a significant prevalence of consanguineous marriage was observed in our study. While constitutional symptoms were most common in other studies, the cough was the most common symptom in our study. To our knowledge, this is one of the Turkish studies with the highest number of sarcoidosis in children and one of the few European studies on sarcoidosis in children.

Patients with cystic fibrosis who could not receive the CFTR modulator treatment: What did they lose in 1 year?

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder caused by CF transmembrane conductance regulator (CFTR) genetic variants. CFTR modulators improve pulmonary function and reduce respiratory infections in CF. This study investigated the clinical and laboratory follow-up parameters over 1 year in patients with CF who could not receive this treatment. METHODS: This retrospective cohort study included 2018 and 2019 CF patient data from the CF registry of Turkey. Demographic and clinical characteristics of 294 patients were assessed, who had modulator treatment indications in 2018 but could not reach the treatment. RESULTS: In 2019, patients younger than 18 years had significantly lower BMI z-scores than in 2018. During the 1-year follow-up, forced expiratory volumes (FEV1) and FEV1 z-scores a trend toward a decrease. In 2019, chronic Staphylococcus aureus colonization, inhaled antipseudomonal antibiotic use for more than 3 months, oral nutritional supplement requirements, and oxygen support need increased. CONCLUSIONS: Patients who had indications for modulator treatments but were unable to obtain them worsened even after a year of follow-up. This study emphasized the importance of using modulator treatments for patients with CF in our country, as well as in many countries worldwide.

Clinical characteristics of patients requiring lung transplantation referral in national cystic fibrosis registry data.

BACKGROUND: We aimed to determine the number of cystic fibrosis (CF) patients recorded in the Cystic Fibrosis Registry of Türkiye (CFRT) who were in need of lung transplantation (LT) referral and examine clinical differences between patients who were LT candidates due to rapid forced expiratory volume in one second (FEV1) decline and LT candidates without rapid FEV1 decline in the last year to identify a preventable cause in patients with such rapid FEV1 decline. METHODS: All CF patients recorded in the CFRT in 2018 were evaluated in terms of LT. Patients were divided into those with FEV1 below 50% and in need of LT due to a decrease of 20% or more in the previous year (Group 1) and those who did not have FEV1 decline of more than 20% in the previous year but had other indications for LT (Group 2). Demographic and clinical features were compared between the two groups. RESULTS: Of 1488 patients registered in CFRT, 58 had a need for LT. Twenty patients were included in Group 1 and others in Group 2. Our findings did not reveal any significant variations in treatment, chronic infection status, or complications between the two groups. The average weight z-score was significantly higher in Group 1. Positive correlations were detected between weight z-score and FEV1 in 2017 in Group 1 and between FEV1 values in 2017 and 2018 in Group 2. CONCLUSIONS: There appears to be a relationship between the nutritional status and weight z-scores of CF patients and pulmonary function, which may indirectly affect the need for lung transplantation referral.

The associations between the clinical course of children with tracheostomy and their mothers' depression, burnout, burden, and self-esteem.

AIMS AND OBJECTIVES: The aim of this study was to evaluate the clinical features of children with tracheostomy and the predictors of psychological status of their primary caregivers in order to determine the associations between the children's clinical course with their caregivers' psychological status. BACKGROUND: The caregivers of children with tracheostomy are responsible for providing basic tracheostomy care at home. All these responsibilities may be associated with significant changes in family members' lifestyles, daily routines and family dynamics. DESIGN: This study is a cross sectional study. METHODS: Data of the family's socioeconomic status and clinical status of children with tracheostomy were noted in four paediatric pulmonology centers. The Beck Depression Inventory, Maslach Burnout Inventory, Zarit Caregiver Burden Scale, and Rosenberg Self-esteem Scale were used for psychological measurements of the caregivers. The STROBE checklist was used for this study. RESULTS: Eighty-five children and their primary caregivers were enrolled in the study. The children's median age was 4.1 years. Thirty-eight of them were dependent on home ventilators. Twenty-one had bacterial colonisation. All children's primary caregivers were their mothers. Beck Depression Inventory scores of mothers of children with colonisation were higher. Number of hospitalizations in previous 6 months was related to mothers' emotional exhaustion and depersonalization scores. Duration of children's hospitalizations in previous 6 months was positively correlated to mothers' emotional exhaustion, depersonalization, and Beck Depression Inventory scores. CONCLUSIONS: Mothers of children with tracheostomy may experience psychological conditions, such as high levels of depression, burnout, burden and low levels of self-esteem. Frequent and long-term hospitalizations of children correlated with mother's depression and burnout. Therefore, primary caregivers should be evaluated and supported psychologically. RELEVANCE TO CLINICAL PRACTICE: Preventing mothers of children with tracheostomy from experiencing psychological conditions such as depression, burnout, burden and low self-esteem can also increase the quality of care for children.

Evaluation of specificity and sensitivity of IRT/IRT protocol in the cystic fibrosis newborn screening program: 6-year experience of three tertiary centers.

We aimed to evaluate cutoff values of immunoreactive trypsinogen (IRT)/IRT and determine relationship between IRT values and clinical characteristics of children with cystic fibrosis (CF). This study is cross-sectional study. Data of children with positive newborn screening (NBS) between 2015 and 2021 were evaluated in three pediatric pulmonology centers. Age at admission, sex, gestational age, presence of history of meconium ileus, parental consanguinity, sibling with CF, and doll-like face appearance, first and second IRT values, sweat chloride test, fecal elastase, fecal fat, biochemistry results, and age at CF diagnosis were recorded. Sensitivity and specificity of IRT cutoff values were evaluated. Of 815 children with positive NBS, 58 (7.1%) children were diagnosed with CF. Median values of first and second IRT were 157.2 (103.7-247.6) and 113.0 (84.0-201.5) µg/L. IRT values used in current protocol, sensitivity was determined as 96.6%, specificity as 17.2% for first IRT, and 96.6% sensitivity, 20.5% specificity for second IRT. Positive predictive value (PPV) was determined as 7.1%. When cutoff value for first IRT was estimated as 116.7 µg/L, sensitivity was 69.0% and specificity was 69.6%, and when cutoff value was set to 88.7 µg/L for second IRT, sensitivity was 69.0% and specificity was 69.0%. Area under curve was 0.757 for first and 0.763 for second IRT (p < 0.001, p < 0.001, respectively). PPV was calculated as 4.3%.    Conclusion: Although sensitivity of CF NBS is high in our country, its PPV is significantly lower than expected from CF NBS programs. False-positive NBS results could have been overcome by revising NBS strategy. What is Known: • Although immunoreactive trypsinogen elevation is a sensitive test used in cystic fibrosis newborn screening, its specificity is low. • In countries although different algorithms are used, all strategies begin with the measurement of immunoreactive trypsinogen in dried blood spots. What is New: • In our study, it was shown that use of the IRT/IRT protocol for cystic fibrosis newborn screening is not sufficient for the cut-off values determined by the high number of patients. • Newborn screening strategy should be reviewed to reduce false positive newborn screening results.

High Respiratory Tract Infection Rate in Patients With Familial Mediterranean Fever.

Background Familial Mediterranean fever (FMF) is a systemic autoinflammatory disease genetically transmitted with the autosomal recessive trait. Although the pathogenesis is not certain, it is known that there is a deficiency in the regulation of the natural immune system. In this study, we aimed to search whether patients with FMF are predisposed to respiratory tract infections and whether mannose-binding lectin (MBL), as a natural immune system member, contributes to it. Methods Fifty FMF patients and 20 control groups were enrolled in the study. First, the frequencies of upper respiratory tract infection (URTI) within the previous year of both patient and control groups were evaluated retrospectively. Then, both groups were followed up for URTI for one year after starting the study. The patient's immunoglobulin A (IgA), IgM, IgG, C-reactive protein (CRP), hemogram parameters, and mannose-binding lectin were evaluated. Results The median frequency of annual URTI with a retrospective evaluation of patients was higher than that of the control group. Also, the median frequency of URTI with the prospective evaluation of patients with FMF was higher than the control group. The rate of patients with low serum IgG levels was higher in the patient group than in the control group. However, serum IgG levels of FMF patients with frequent URTI were not different from those without. The median MBL levels of both groups were similar (1312 vs. 1534 ng/ml for the patient and control group, respectively). The rate of patients having low serum MBL levels was also similar between the groups. Conclusions In the present study, we found that patients with FMF had more URTI than healthy controls. However, the underlying cause is not fully explained. There is a need for further studies with a higher number of patients evaluating URTI in patients with FMF.

Pulmonary Embolism in Childhood: A Multicenter Experience from Turkey

Background: Pulmonary embolism is a clinical condition caused by the obstruction of the pulmonary artery and its branches with endogenous, exogenous embolism, or local thrombus formation. It is a rare but potentially life-threatening event in the pediatric population. Pediatric pulmonary embolism has many unknown characteristics. Aims: To evaluate clinical features, genetic and acquired risk factors, diagnostic imaging, and treatment strategies with long-term results in children with pulmonary embolism. Study Design: A retrospective multicenter clinical trial. Methods: Patients aged 0-18 years who were diagnosed with pulmonary embolism with computed tomography pulmonary angiography (CTPA) findings (intraluminal filling defect in the lobar or main pulmonary artery) in 3 university hospitals between 2006 and 2021 were included in the study. A form was created for data standardization, and variables were collected retrospectively through medical record review. In addition to the features given above, we also evaluated in situ pulmonary artery thrombosis (ISPAT) and patients' Wells scores. Follow-up CTPA results were evaluated for patient response to treatment. Complete recovery means that there were no lesions, incomplete recovery if there was still embolism, and no response if there was no change. Results: Twenty-four patients (female:13, male:11) were included in the study. The mean age was 13.5 years. All patients but one had at least one or more genetic or acquired risk factors. Factor V Leiden mutation (16.6%) was the most common genetic risk factor. Six of 16 patients with Doppler ultrasonography were diagnosed with ISPAT because there was no sign of thromboembolic thrombosis. Nine (41.6%) patients had a Wells score of >4 (pulmonary embolism clinically strong), and 15 (58.4%) patients scored <4 (pulmonary embolism clinically likely weak), indicating that an alternative diagnosis was more likely than pulmonary embolism (sensitivity %37.5). The mean follow-up period was 23 (±17) months. Complete and incomplete recovery was observed in 15 (62.5%) and 7 (29.1%) patients, respectively, among the patients who underwent follow-up evaluation. No response was obtained in 2 patients (8.3%) who died. Conclusion: The Wells scoring system seems insufficient to diagnose pulmonary embolism in children and should be improved by adding new parameters. ISPAT may be more common in children with congenital heart disease and systemic disease.

Psychological status of mothers of children with cystic fibrosis and primary ciliary dyskinesia.

OBJECTIVES: We aimed to investigate depression, burnout, attitude, and burden of caregivers of children with cystic fibrosis (CF), and especially caregivers of children with primary ciliary dyskinesia (PCD) due to limited number of studies on this topic, and to compare them according to their children's clinical status. METHODS: Clinical features and demographic data of children and their families were asked from caregivers in four pediatric pulmonology centers. Beck Depression Inventory, Maslach Burnout Inventory, Zarit Caregiver Burden Scale, and Parental Attitude Research Instrument were administered to caregivers in both groups. Results were compared between the two groups. RESULTS: In total, 131 children with CF and 39 with PCD and their caregivers were involved in the study. All primary caregivers were mothers in both groups. Depression, burnout, and burden scores of mothers of children with CF were significantly higher than mothers of children with PCD (p = 0.017, p = 0.024, p = 0.038, respectively). Burnout was higher in both CF and PCD groups with low family income (p = 0.022, p = 0.034). Number of hospital visits in the previous 6 months was correlated with burnout in both CF and PCD groups (r = 0.207, p = 0.034; r = 0.352, p = 0.044). CONCLUSIONS: Although mothers with children with CF have higher levels of depression, burnout, burden, and negative attitudes toward children than mothers with children with PCD, these are also significantly high in mothers with children with PCD. Psychological problems of mothers of children with CF and PCD may increase with frequent hospital visits, hospitalizations, low family income, number of children, and chronic disease in another child.

Caspase-1 and interleukin-18 in children with post infectious bronchiolitis obliterans: a case-control study.

The exact immunological mechanisms of post infectious bronchiolitis obliterans (PIBO) in childhood are not fully known. It has been shown that the inflammasome and IL-18 pathway play important roles in the pathogenesis of lung fibrosis. We aimed to investigate the role of caspase-1, IL-18, and IL-18 components in PIBO. From January to May 2020, children with PIBO, children with history of influenza infection without PIBO, and healthy children were asked to participate in the study in three pediatric pulmonology centers. Serum caspase-1, IL-18, IL-18BP, IL-18R, and INF-γ levels were measured by ELISA and compared between the 3 groups. There were 21 children in the PIBO group, 16 children in the influenza group, and 39 children in the healthy control group. No differences in terms of age and gender between the 3 groups were found. IL-18 and IL-18BP levels were higher in the healthy control group (p = 0.018, p = 0.005, respectively). IL-18R was higher in the PIBO group (p = 0.001) and caspase-1 was higher in the PIBO and influenza group than the healthy control group (p = 0.002). IFN-γ levels did not differ between the 3 groups. IL-18BP/IL-18 was higher in the influenza group than the PIBO group and the healthy control group (p = 0.003). CONCLUSIONS: Caspase-1 level was increased in patients with PIBO which suggests that inflammasome activation may have a role in fibrosis; however, IL-18 level was found to be low. Mediators other than IL-18 may be involved in the inflammatory pathway in PIBO. Further immunological studies investigating inflammasome pathway are needed for PIBO with chronic inflammation. WHAT IS KNOWN: • Post infectious bronchiolitis obliterans (PIBO) is a rare, severe chronic lung disease during childhood which is associated with inflammation and fibrosis which lead to partial or complete luminal obstruction especially in small airways. • The exact immunological mechanisms of PIBO in childhood are not fully known. WHAT IS NEW: • Inflammasome activation persists even years after acute infection and may play a role in fibrosis in PIBO. • Mediators other than IL-18 may be involved in these inflammatory pathway.

The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care.

BACKGROUND: Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow-up, clinical, growth, treatment, and complications of people with this disease. METHODS: Age at diagnosis, current age, sex, z-scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow-up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data. RESULTS: There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z-scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in 1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo-Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively). CONCLUSIONS: The z-scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow-up. The widespread use of national CF registry system across the country may be beneficial for the follow-up of people with CF.

Circulating fibrocyte level in children with cystic fibrosis.

BACKGROUND: This study aimed to evaluate circulating fibrocyte levels in cystic fibrosis (CF) patients during stable and exacerbation periods of the condition. METHODS: The study group consisted of 39 patients diagnosed with CF and 20 healthy controls. Individuals included in the study were divided into three groups: CF, CF exacerbated, and a healthy control group. Their circulating fibrocyte levels were compared. Findings from a pulmonary function test and high-resolution computed tomography of the lung were evaluated and compared. RESULTS: The circulating fibrocyte count was found to be significantly higher in patients with CF compared with the exacerbated and control groups. No correlation was found between the forced expiratory volume in 1 s and forced vital capacity values in the pulmonary function test and the circulating fibrocyte count. The circulating fibrocyte count in patients (in the CF group) with positive findings in the high-resolution computed tomography was statistically significantly lower. CONCLUSIONS: The circulating fibrocyte level in the peripheral blood of the patients with CF was increased.

The Genetic Analysis of Cystic Fibrosis Patients With Seven Novel Mutations in the CFTR Gene in the Central Anatolian Region of Turkey.

BACKGROUND: Cystic fibrosis, a pulmonary disease which is an autosomal recessive, inherited, multisystemic genetic disease commonly seen in the Caucasian race, is the most frequent cause of mortality and morbidity. So far, more than 2000 disease-causing gene variants have been found and this number has been increasing with the studies conducted. Although there is not yet enough data that include the Turkish population, the recent increase of studies is noteworthy. AIMS: To discover the genetic variation in patients diagnosed with cystic fibrosis in the Central Anatolian region. STUDY DESIGN: Cross-sectional study. METHODS: The study was carried out in the Central Anatolian region in 3 pediatric pulmonology departments (Kayseri, Konya, and Ankara) in Turkey between July 2014 and December 2017. The Sanger and Next Generation Sequence analyses were used for exon and exon-intron boundaries in the cystic fibrosis transmembrane conductance regulatory (CFTR) gene, and in selected patients, mutation analysis was performed using the Multiplex Ligation-dependent Probe Amplification technique for large deletions and duplications. RESULTS: CFTR gene analysis was performed for 316 patients and 215 of them were genetically diagnosed with cystic fibrosis. Sixtythree different variants were defined in these patients and 7 of these were large deletions/duplications detected with the MLPA method. The most frequent variants were F508del (29.6%), G85E (8.2%), N1303K (8.2%), Y515* (7.5%), and G542* (3.4%). CONCLUSION: Using sequencing and Multiplex Ligation-dependent Probe Amplification methods, the identification of seven new mutations that were not previously reported in the literature contributes to a better understanding of the heterogeneous nature of CFTR mutations in the Turkish population. When no mutations are detected (pathogenic/probably pathogenic) in clinically compatible cases, Multiplex Ligationdependent Probe Amplification analysis contributes significantly to the diagnosis.

Geographical barriers to timely diagnosis of cystic fibrosis and anxiety level of parents during newborn screening in Turkey.

BACKGROUND: Despite the availability of cystic fibrosis (CF) screening countrywide, diagnostic delay is still a crucial issue. The objectives of this study were to explore the stages of the NBS process, determine the risk factors associated with diagnostic delay and evaluate parent anxiety and experience throughout the process. METHODS: This is a multicenter cross-sectional study. A questionnaire was completed by parents of newborns diagnosed with CF via NBS in 17 centers. Socio-demographic characteristics, parent knowledge and experiences related to NBS, sweat test availability in the region of residence, and time to the definitive CF diagnosis were assessed through this questionnaire. Parents' anxiety levels were evaluated through the State-Trait Anxiety Inventory scales 1 and 2. Delayed diagnosis (DD) was defined as a definite CF diagnosis beyond the 8th week of life. Predictors of delayed CF diagnosis were evaluated by univariate and multivariate analysis. RESULTS: A total of 220 CF patients diagnosed via NBS were enrolled; 82 (37.3%) babies had DD. Multivariable analysis indicated that residence in the Southeast Anatolia region of Turkey (OR = 10.79, 95% CI = 2.37-49.2) was associated with a higher incidence of DD compared with other regions in Turkey. Of the total, 216 (98.1%) of the caregivers regarded the NBS program as useful and 180 (82%) reported high anxiety levels. CONCLUSION: The organization of newborn screening should take into account regional and socio-cultural characteristics to improve the early diagnosis of CF and also reduce the anxiety level of parents.

Type 1 Plasminogen Deficiency With Pulmonary Involvement: Novel Treatment and Novel Mutation.

Type 1 plasminogen deficiency is a rare genetic disorder. Type 1 plasminogen deficiency is characterized by fibrin-rich pseudomembrane formation on mucosal surfaces, particularly the conjunctiva. Tracheobronchial tree involvement is a less common reported manifestation of type 1 plasminogen deficiency. Pseudomembranes in the tracheobronchial tree may result in respiratory compromise and ultimately fail if not recognized and treated. Currently, there is no specific replacement therapy approved for the treatment of congenital plasminogen deficiency. In the present paper, we report that type 1 plasminogen deficiency with novel frameshift mutation and pulmonary involvement was treated initially with systemic fresh frozen plasma followed by pulmonary lavage with fresh frozen plasma and tissue plasminogen activator.

The relationship between immature platelet fraction and severity of acute bronchiolitis.

BACKGROUND AND OBJECTIVES: Acute bronchiolitis is one of the most common reasons for hospitalization in infants. Although patients with acute bronchiolitis generally have a good prognosis, death can also occur. In this study, we evaluate the immature platelet fraction (IPF) as an indicator of the severity of acute bronchiolitis. METHODS: In our study, 179 patients diagnosed with acute bronchiolitis were divided into three groups as mild (n: 48; 26.8%), moderate (n: 104; 58.10%) and severe (n: 27; 15.1%) bronchiolitis. There were 80 healthy children in the control group. The diagnostic capacity of IPF and hematological parameters (platelet distribution width (PDW), mean platelet volume (MPV), white blood cell count (WBC), and platelet count (PLT)) values to predict severity of acute bronchiolitis was evaluated using receiver operating characteristic (ROC) curves and their respective areas under the curves (AUCs) calculated with 95% confidence intervals. RESULTS: The IPF value of patients with acute bronchiolitis was significantly higher than the healthy group (p < 0.001). In addition, a positive correlation was observed between clinical severity of bronchiolitis and IPF. The ROC curve analysis indicated that the IPF cut-off point for predicting severity of acute bronchiolitis was > 3.2% (Sensitivity of 84%, specificity of 97%). We found that the AUCs for IPF, MPV, PDW, WBC and PLT were statistically significant for bronchiolitis relative to the healthy control group. The parameter with the greatest AUC value was IPF. CONCLUSION: The IPF may present for diagnosing and evaluating the clinical severity of acute bronchiolitis in children.

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

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 FEV1 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.