Factors associated with pulmonary function decline of patients in the cystic fibrosis registry of Turkey: A retrospective cohort study.

BACKGROUND: The decline in pulmonary function is a predictor of disease progression in patients with cystic fibrosis (CF). This study aimed to determine the decline rate of percent predicted forced expiratory volume in 1 s (ppFEV1) based on the data of the CF Registry of Turkey. The secondary aim was to investigate the risk factors related to the decline in ppFEV1. METHODS: A retrospective cohort study of CF patients over 6 years old, with pulmonary function data over at least 2 years of follow-up was extracted from the national CF registry for years 2017-2019. Patients were classified according to disease severity and age groups. Multivariate analysis was used to predict the decline in ppFEV1 and to investigate the associated risk factors. RESULTS: A total of 1722 pulmonary function test results were available from 574 patients over the study period. Mean diagnostic age was older and weight for age, height for age, and body mass index z scores were significantly lower in the group of ppFEV1 < 40, while chronic Pseudomonas aeruginosa (p < .001) and mucoid P. aeruginosa colonization (p < .001) were significantly higher in this group (p < .001). Overall mean annual ppFEV1 decline was -0.97% (95% confidence interval [CI] = -0.02 to -1.92%). The mean change of ppFEV1 was significantly higher in the group with ppFEV1 ≥ 70 compared with the other (ppFEV1 < 40 and ppFEV1: 40-69) two groups (p = .004). Chronic P. aeruginosa colonization (odds ratio [OR] = 1.79 95% CI = 1.26-2.54; p = .01) and initial ppFEV1 ≥ 70 (OR = 2.98 95% CI = 1.06-8.36), p = .038) were associated with significant ppFEV1 decline in the whole cohort. CONCLUSIONS: This data analysis recommends close follow-up of patients with normal initial ppFEV1 levels at baseline; advocates for early interventions for P. aeruginosa; and underlines the importance of nutritional interventions to slow down lung disease progression.

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.

Antibiotic allergy in children with cystic fibrosis: A retrospective case-control study.

Antibiotic allergy is a big problem that may affect the treatment and life quality of patients with cystic fibrosis (CF). AIM: To evaluate predictive factors for confirmed antibiotic hypersensitivity in children with CF. METHODS: In this case-controlled study, we examined 15 patients with CF who had been confirmed with antibiotic allergy. Additionally, we included a control group of age- and gender-matched 45 CF patients with no antibiotic allergy. The diagnosis of antibiotic allergy was confirmed in the presence of a compatible history and a positive response in the drug skin test or provocation test. Multiple drug hypersensitivity was classified according to the temporal relationship of antibiotics: (i) distant, (ii) simultaneous, and (iii) sequential. The data were analyzed by conditional logistic regression. RESULTS: ß-lactam allergy was confirmed in eight patients (ceftazidime n = 5, piperacillin-tazobactam n = 3) and non-ß-lactam allergy was confirmed in two patients (ciprofloxacin n = 1, azithromycin n = 1). Additionally, multiple drug hypersensitivity in five patients (distant n = 4, sequential n = 1), among whom two patients showed hypersensitivity against ceftazidime/piperacillin-tazobactam+ ciprofloxacin/levofloxacin, two patients showed hypersensitivity against ceftazidime+ ciprofloxacin n = 2, and one patient showed hypersensitivity against piperacillin-tazobactam+ amikacin+ trimethoprim-sulfamethoxazole. All patients (n = 13) with confirmed ß-lactam allergy were meropenem tolerant. Multivariate analysis indicated that immediate reactions (, p < 0.001) and allergic evaluation in the first six months after the reaction (p = 0.036) were significant risk factors for the prediction of antibiotic hypersensitivity. CONCLUSION: Beta-lactam antibiotic allergy is the most commonly confirmed drug allergy in children with CF. However, unlike normal children, ceftazidime and piperacillin-tazobactam account for the majority.

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.

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.

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

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

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.

Acute obstructive respiratory tract diseases in a pediatric emergency unit: evidence-based evaluation.

OBJECTIVES: The objective of this study was to determine the evidence-based performance of the pediatric emergency unit in the diagnosis of and treatment approach to the patients with asthma, bronchiolitis, and croup. METHODS: In this study conducted in a retrospective cross-sectional way, emergency cards and computer data have been used. In the performance evaluation, the National Hospital Ambulatory Medical Care Survey criteria were considered. In the evaluation of performance in diagnosis, the rates of chest x-ray studies and use of corticosteroids and antibiotics were examined. Use of antibiotics in the cases not having a fever or any symptoms of bacterial infection and failure in prescribing steroids to the cases with moderate-to-severe symptoms were considered as bad performance criteria. χ(2) test was used for the data, which can be classified; Mann-Whitney U and Student t tests were used for the data with normal distribution and for the continuous variables. RESULTS: Study groups were composed of 2795 patients (1742 cases with asthma, 115 cases with croup, 938 cases with bronchiolitis) aged between 3 and 140 months (mean [SD], 41.2 [31] months). Chest x-ray study was requested significantly more often in the cases of bronchiolitis and croup with severe symptoms. In asthma cases, chest x-ray study was requested in those with severe clinical symptoms. In all 3 groups, a significant difference between the severity levels of the cases, from whom hemogram was requested, was determined. Biochemical tests were requested more often in those with severe bronchiolitis or asthma. Antibiotics were prescribed to none of the mild bronchiolitis cases. However, steroids were recommended more often to patients with moderate and severe bronchiolitis. They were administered to all patients with croup. Systemic steroids were prescribed more often to those with moderate or severe asthma. CONCLUSIONS: In our unit, both antibiotics administration and chest x-ray studies requested in patients with bronchiolitis, croup, and asthma were in low rates. Steroids in asthma attacks were found to be high in severe cases and in croup cases as well.

[Evaluation of serological status of children following hepatitis B vaccination during infancy]. / Süt Çocuklugunda Hepatit B Asisi Uygulanan Çocuklarda Serolojik Durumun Degerlendirilmesi.

The aims of this study were to determine anti-HBs positivity in children who had received three doses of hepatitis B vaccine during infancy and to evaluate the factors that may affect the serological status. Local ethics committee approval was obtained at the beginning of the study. The study was carried out between December 2005 and October 2007 among children attending the outpatient clinics of medical school hospital. The study encompassed 912 children (393 female, 519 male; aged 1-5 years old) who had been immunized with three doses of intramuscular recombinant hepatitis B vaccine during infancy. All of the children were born to HBsAg negative mothers and did not have any known immune system problems. Sociodemographic characteristics and passive smoking status were gathered by a questionnaire. Anthropometric measurements were taken, and a detailed physical examination was carried out for each child. Blood samples were obtained to check serum HBsAg, anti-HBs and anti-HBc levels by commercial micro-ELISA (Sanofi Diagnostics Pasteur, Sydney) method. Levels of anti-HBs ≥ 10 mIU/ml were defined as seropositivity. In seronegative children, anti-HBs levels were re-checked 4 weeks after receiving one booster dose of hepatitis B vaccine. Of the children 877 (96.2%) were found anti-HBs positive, while all of them were negative for anti-HBc or HBsAg. Of children 34.8% were 12-23 months; 28.7% were 24-36 months; and 36.5% were 37-60 months-old, and anti-HBs negativity rate was higher in the older age group with a statistically significant difference (1.4%, 3.9% and 4.2%, respectively; p= 0.003). Anti-HBs antibodies were found negative in 2.8% of children who were born by vaginal route and in 5.8% of children who were born by cesarean section, the difference being statistically significant (p= 0.016). There were no significant differences between anti-HBs seropositivity and gender, working/ educational status of the mothers and the presence of smoking parents in the family (p> 0.05). Logistic regression analysis indicated that the factors that affect antibody levels in vaccinated children were the duration of breastfeeding only (4.77 ± 1.53 months in anti-HBs positives and 3.69 ± 2.13 months in negatives; p= 0.008), birth weight (3328.18 ± 318 g in anti-HBs positives and 3135.27 ± 488 g in negatives; p= 0.037) and pregnancy parity (anti-HBs was negative in 3.4% of children born from mothers who had < 2 parities, and 8.2% of children born from mothers who had < 3 parities; p= 0.037). The remaining 35 (3.8%) children with undetectable antibody levels became seropositive after one dose of hepatitis B vaccination, with the antibody levels of ≥ 100 mIU/ml. This response underlined the presence of immune memory in vaccinated children. The results of this study indicated that almost all 1-5 years old children who had received three doses of hepatitis B vaccine during infancy were protected from hepatitis B virus infection. It was concluded that similar studies should be carried out in different settings.