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.

Clinical findings of patients with cystic fibrosis according to newborn screening results.

BACKGROUND: Cystic fibrosis (CF) is a lethal recessive genetic disease caused by loss of function associated with mutations in the CF trans-membrane conductance regulator. It is highly prevalent (approximately 1 in 3,500) in Caucasians. The aim of this study was to compare demographic and clinical features, diagnostic tests, treatments, and complications of patients with CF whose newborn screening (NBS) with twice-repeated immune reactive trypsinogen testing was positive, normal, and not performed. METHODS: In this study, 359 of all 1,488 CF patients recorded in the CF Registry of Turkey in 2018, who had been born through the process of NBS, were evaluated. Demographic and clinical features were compared in patients diagnosed with positive NBS (Group 1), normal (Group 2), or without NBS (Group 3). RESULTS: In Group 1, there were 299 patients, in Group 2, there were 40 patients, and in Group 3, there were 20 patients. Among all patients, the median age at diagnosis was 0.17 years. The median age at diagnosis was higher in Groups 2 and 3 than in Group 1 (P = 0.001). Fecal elastase results were higher in Group 2 (P = 0.033). The weight z-score was lower and chronic Staphylococcus aureus infection was more common in Group 3 (P = 0.017, P = 0.004, respectively). CONCLUSIONS: Frequency of growth retardation and chronic S. aureus infection can be reduced with an early diagnosis using NBS. In the presence of clinical suspicion in patients with normal NBS, further analyses such as genetic testing should be performed, especially to prevent missing patients with severe mutations.

Sleep disturbances in children with cystic fibrosis, primary ciliary dyskinesia and typically developing children during COVID-19 pandemic.

AIM: We aimed to investigate sleep disturbances in children with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) and typically developing (TD) children during the COVID-19 pandemic. METHODS: Primary care givers of children with CF and PCD aged 3-16 years were asked to enrol in the study. Primary care givers of TD children were included as control group. The Sleep Disturbance Scale for Children (SDSC) was used, and questions related to sleep habits during the pandemic were asked. Results of the three groups were compared. RESULTS: Primary care givers of 33 children with CF, 16 children with PCD and 66 TD children were included in the study. There were no differences in terms of age and gender between the three groups. Changes in sleep patterns during the pandemic were more common among TD children and their families, with 75% of the children and 80% of their families sleeping later than before. The sleep initiation and maintenance disorder scores were higher in TD children (P = 0.001), whereas the sleep breathing disorder scores were higher in children with PCD (P = 0.001), and the sleep hyperhidrosis scores were higher in children with CF and PCD (P = 0.011). No relationships were found between sleep parameters and clinical findings of children with lung disease. CONCLUSIONS: Children's sleep habits have changed during the pandemic. Children with chronic lung diseases and even TD children may experience sleep disturbances during this period.

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.

Neutrophil lymphocyte ratio, mean platelet volume, and immunoreactive trypsinogen as early inflammatory biomarkers for cystic fibrosis in infancy: A retrospective cohort study.

BACKGROUND: Airway inflammation starts in early life in cystic fibrosis (CF) and limited, objective markers are available to help identify infants with increased inflammation. We aimed to investigate neutrophil, lymphocyte ratio (NLR), mean platelet volume (MPV) and immunoreactive trypsinogen (IRT) to be a possible inflammatory biomarker for CF in infancy. METHODS: This was a retrospective cohort study in three centers. Between January 2015 and December 2022, children with CF newborn screening (NBS) positivity and diagnosed as CF were included in the study. Correlation analysis were performed with NLR, MPV, IRT and follow-up parameters such as z-scores, modified Shwachman-Kulczycki score (mSKS) at the first, second, third and sixth ages and pulmonary function test (PFT) at the sixth age. RESULTS: A total of 92 children with CF included in the study and 47.8% of them were female. There were no correlations between NLR, MPV and weight and height z-scores for all ages (p > 0.05), a negative correlation was found between MPV and body mass indexes (BMI) z-score at the age of 6 (r = -0.443, p = 0.038). No correlation was found between NLR, MPV and PFT parameters and mSKS at all ages (p > 0.05). There was a negative correlation between first IRT and BMI z-score at 6 years of age (r = -0.381, p = 0.046) and negative correlations between second IRT and weight and BMI z-score at the age of 6 (r = -0.462, p = 0.010; r = -0.437, p = 0.016, respectively). CONCLUSION: Higher MPV and IRT levels during NBS period are associated with worse nutritional outcome which may reflect chronic inflammation. Children with higher MPV and IRT should be followed up closely in terms of chronic inflammation and nutritional status.

Perceived Need for Mental Health Services Among Healthcare Workers During the Coronavirus Disease-19 Pandemic in Turkey: A Multicenter Cross-sectional Study

Background: The coronavirus disease-2019 pandemic has contributed to work-related psychosocial risks in healthcare workers. Aims: To evaluate the perceived need for mental health services and related factors in Turkish healthcare workers practicing in pandemic hospitals. Study Design: Cross-sectional study. Methods: Data were collected from face-to-face interviews with healthcare workers at 19 pandemic hospitals in 13 provinces between September and November 2021. The study survey included the evaluation of the perceived need for and utilization of mental health services in the previous year, as well as sociodemographic, health-related, and work-related characteristics, the General Health Questionnaire-12, the World Health Organization Quality of Life-BREF (WHOQoL-BREF) questionnaire, and the Fear of coronavirus disease-2019 scale (FCV-19S). Results: Of 1,556 participants, 522 (33.5%) reported a perceived need for mental health services, but only 133 (8.5%) reported receiving these services. Multiple logistic regression analysis of the perceived need for mental health services revealed significant relationships with lower age, female sex, being a current smoker, having a chronic disease, having a mental disorder, coronavirus disease-2019 contact within the last three months in settings other than the home or workplace, a positive coronavirus disease-2019 vaccination history, being a physician, being a non-physician healthcare professional, and coronavirus disease-2019 contact within the last three months at work. After adjustment for these characteristics, higher General Health Questionnaire-12 and FCV-19S scores and lower WHOQoL-BREF domain scores were related to the perceived need for mental health services in logistic regression analyses. Conclusion: The findings indicate a substantial need for mental health services amongst Turkish healthcare workers during the pandemic and outline participants' characteristics regarding high-priority groups for the intervention. Future research may focus on developing actions and evaluating their efficiency.

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.

ERS International Virtual Congress 2021: Highlights from the Turkish Thoracic Society Early Career Members.

This review aimed to highlight some important points derived from the presentations of the European Respiratory Society 2021 Virtual International Congress by a committee formed by the Early Career Task Group of the Turkish Thoracic Society. We summarized a wide range of topics including current developments of respiratory diseases and provided an overview of important and striking topics of the congress. Our primary motivation was to give some up-to-date information and new developments discussed during congress especially for the pulmonologists who did not have a chance to follow the congress. This review also committed an opportunity to get an overview of the newest data in the diverse fields of respiratory medicine such as post-coronavirus disease 2019, some new interventional and technologic developments related to respiratory health, and new treatment strategies.

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.

Evaluation of age at diagnosis and clinical findings of children with primary ciliary dyskinesia.

OBJECTIVE: Patients with primary ciliary dyskinesia (PCD) may present with different clinical findings at different ages, and age at diagnosis may differ. We aimed to review clinical factors that affected age at diagnosis of patients with PCD. STUDY DESIGN: All 70 patients with PCD who were followed in our pediatric pulmonology department were included. Demographic features, clinical findings, PrImary CiliAry DyskinesiA Rule (PICADAR) scores and pulmonary function tests of patients were recorded and clinical factors that affected age at diagnosis were evaluated. RESULTS: The mean age at diagnosis was 8.3 ± 4.6 years. Most of patients (95.7%) had a persistent wet cough. The mean PICADAR score was 6.5 ± 3.2, and there was a negative correlation between PICADAR and age at diagnosis (r = -0.271, p = .023). The mean ages at diagnosis of patients with situs abnormality and recurrent wheezing were earlier than in patients without situs abnormality and recurrent wheezing (6.7 ± 4.3 and 6.8 ± 4.3, p = .002 vs. 9.8 ± 4.3 and 9.0 ± 4.6 years, p = .040, respectively). The mean age at diagnosis of patients with bronchiectasis was later than in patients without bronchiectasis (10.8 ± 3.9 and 6.9 ± 4.4 years, p = .001). Other clinical features were not statistically significant according to age at diagnosis (p > .05). There was no statistically significant relation between age at diagnosis and sex, sibling or relative with PCD and parental consanguinity (p > .05). CONCLUSION: Although most patients diagnosed with PCD had symptoms, the diagnosis may be delayed. High PICADAR score is a useful guide to evaluate PCD. Situs abnormality and recurrent wheezing could be clues for early diagnosis of PCD. Early diagnosis of PCD may prevent bronchiectasis.

Cigarette smoking in adolescents with type 1 diabetes mellitus and congenital adrenal hyperplasia.

Asfuroglu P, Arasli-Yilmaz A, Aycan Z. Cigarette smoking in adolescents with type 1 diabetes mellitus and congenital adrenal hyperplasia. Turk J Pediatr 2019; 61: 236-243. Adolescence is a long period involving many physical and psycho-social changes experienced during transition from childhood to adulthood. In this period, behaviors such as curiosity and risk-taking are common, and cigarette smoking initiation is one of those behaviors. In this study, it was aimed to find out whether chronic diseases are an effective factor or not in the cigarette smoking initiation of adolescents. One-hundred adolescents with Type 1 Diabetes Mellitus (T1DM) and 50 adolescents with Congenital Adrenal Hyperplasia (CAH) aged 12 and above under follow-up at the Pediatric Endocrinology Clinic and 100 healthy adolescents within the same age group who applied to the Adolescent Outpatient Clinic were included in the study. A survey was applied to all of these adolescents, which had been developed by researchers and contained questions about their socio-demographic features and cigarette smoking. Fourteen (5.6%) of the 250 adolescents were smokers. The rate of those who tried, but quitted cigarette smoking was found as approximately 20%. Cigarette smoking rate of those with T1DM was 1%, of those with CAH was 4%, and of the healthy adolescents was 11%. Cigarette smoking was significantly lower in those with a chronic disease (2%) than those who were healthy (11%). Adolescents` parents and friends had an effect on the cigarette smoking initiation, and adolescents smoked their first cigarette generally because of curiosity. It was seen in this study that the adolescents with a chronic disease less frequently smoked cigarettes than the healthy adolescents, the rate of cigarette smoking in parents of cigarette smoking adolescents was very high, and their parents and friends had an effect on cigarette smoking initiation of adolescents.