Proinflammatory indicators and the relevance of echocardiography in children with cystic fibrosis.

As the life expectancy improves in cystic fibrosis, cardiac dysfunction is becoming an important risk factor for morbidity and mortality. Here, the association of cardiac dysfunction with proinflammatory markers and neurohormones between cystic fibrosis patients and healthy children was investigated. Echocardiographic measurements of right and left ventricular morphology and functions together with levels of proinflammatory markers and neurohormones (renin, angiotensin-II, and aldosterone) were obtained and analysed in a study group of 21 cystic fibrosis children aged 5-18 years and compared with age- and gender-matched healthy children. It was shown that patients had significantly higher interleukin-6, C-reactive protein, renin and aldosterone levels (p < 0.05), dilated right ventricles, decreased left ventricle sizes, as well as both right and left ventricular dysfunction. These echocardiographic changes correlated with hypoxia, interleukin-1 α, interleukin-6, C-reactive protein, and aldosterone (p < 0.05) levels. The current study revealed that hypoxia, proinflammatory markers, and neurohormones are major determinants of subclinical changes in ventricular morphology and function. While the right ventricle anatomy was affected by cardiac remodeling, the left ventricle changes were induced by right ventricle dilation and hypoxia. A significant but subclinical systolic and diastolic right ventricle dysfunction in our patients was associated with hypoxia and inflammatory markers. Systolic left ventricle function was affected by hypoxia and neurohormones. Echocardiography is a reliable and non-invasive method that is used safely in cystic fibrosis children for screening and detection of cardiac anatomical and functional changes. Extensive studies are needed to determine the time and frequency of screening and treatment suggestions for such changes.

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.

Rotational Thromboelastometry Profile in Children With Chronic Spontaneous Urticaria.

The pathogenesis of chronic spontaneous urticaria (CSU) is incompletely understood. There is a growing interest in the role of the coagulation cascade in chronic urticaria. Rotational thromboelastometry (ROTEM) assay enables the global assessment of coagulation status. In the present study, we aimed to test the coagulation profile in children with CSU using ROTEM and correlate these parameters with those of a healthy group. A total of 24 children with active CSU (11 girls and 13 boys) 8 to 17 years of age and age-matched and sex-matched 30 healthy control participants were enrolled in the study. ROTEM assays (intrinsic thromboelastometry and extrinsic thromboelastometry) were used to measure and analyze coagulation time, clot formation time, and maximum clot firmness. The CSU patients and controls did not differ in age, sex, erythrocyte, neutrophil, and platelet counts. Also, ROTEM parameters did not show any difference between the 2 groups. ROTEM is increasingly being used as a tool for monitoring coagulation status. In this study, ROTEM parameters did not show any difference between CSU patients and the healthy group. Further studies are needed to confirm our findings on a larger number of CSU patients.

Evaluation of contact sensitivity to food additives in children with atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory disease caused by the complex interaction of genetic, immune and environmental factors such as food and airborne allergens. The atopy patch test (APT) is a useful way to determine delayed-type hypersensitivity reactions to food and aeroallergens. Many studies have also suggested that food additives are associated with dermatologic adverse reactions and the aggravation of pre-existing atopic dermatitis symptoms. AIM: To elucidate the contact sensitivity to food additives in children suffering from AD by using standardized atopy patch testing. MATERIAL AND METHODS: A total of 45 children with AD and 20 healthy children have been enrolled. All the children have regularly consumed food containing additives, and were subjected to atopy patch tests. RESULTS: In total, 28 (62%) children with AD and 4 (20%) healthy children have had positive patch test reactions to ≥ 1 allergens. There has been a significant difference (p = 0.04) between the groups in terms of the positivity rate in the patch test and the most common allergen that elicited positive patch test results in the AD group was azorubine (n = 11, 24.4%, p = 0.014). CONCLUSIONS: In our study, contact sensitivity was detected more frequently in AD patients. Food additives may play a role in the development and exacerbation of AD. Atopy patch testing with food additives can be useful in the treatment and follow-up of children with AD.

Presence of a single nucleotide polymorphism (RS3758581) in a boy with DRESS syndrome.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, potentially life-threatening, drug-induced hypersensitivity reaction that includes rash, hematologic abnormalities, lymphadenopathy, and internal organ involvement. The pathogenesis of DRESS syndrome is partially understood. Various medications have been described as the cause of DRESS syndrome. Phenytoin and allopurinol are the most commonly reported culprit drugs, although more than 50 drugs can induce DRESS syndrome. Members of the cytochrome P450 (CYP) superfamily are the most commonly involved enzymes in metabolism of drugs such as phenytoin. This case report addresses the influence of CYP2C9 genetic polymorphism (a single nucleotide polymorphism) on phenytoin drug metabolism, thereby causing DRESS syndrome.

The Addition of Inhaled Budesonide to Standard Therapy Shortens the Length of Stay in Hospital for Asthmatic Preschool Children: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Asthma exacerbations lead to frequent emergency visits and hospitalizations, and are associated with high morbidity and occasionally mortality. New therapeutic strategies are needed. We sought to investigate whether the addition of high-dose inhaled budesonide to standard therapy would shorten the length of stay (LOS) in hospital of children admitted for asthma exacerbations. METHODS: The study was designed as a single-center, double-blind, placebo-controlled and parallel-group trial. Children aged 7-72 months and admitted with an asthma exacerbation clinical asthma score (CAS) of between 3 and 9 were allocated to either the budesonide (n = 50) or the placebo (n = 50) group. Hospital LOS was compared between children who received 2 mg/day of budesonide versus placebo in addition to standard management of asthma exacerbation involving oxygen inhalation and ß2-agonist, anticholinergic and oral corticosteroid therapy. All patients were assessed every 4 h. Children with a CAS <3, a peripheral oxygen saturation >95% and normal pulmonary function, and those with a symptom-free period of at least 4 h after salbutamol treatment were discharged. RESULTS: Total hospital LOS was significantly shorter in the budesonide group than in the placebo group (median: 44 vs. 80 h, respectively; p = 0.01). When compared with placebo, the number of inpatients was significantly less in the budesonide group at all the assessed end points (Kaplan-Meier; p = 0.022). Additionally, nebulized budesonide was found to reduce the overall cost of treatment. CONCLUSION: We demonstrated that, for children hospitalized for asthma exacerbations, an additional 2 mg/day of nebulized budesonide significantly reduced hospital LOS as well as the overall cost of treatment.

Potential predictors of relapse after treatment of asthma exacerbations in children.

BACKGROUND: Knowledge of factors that affect relapse will allow close monitoring of patients at risk, resulting in a decreased rate of readmission to the emergency department. OBJECTIVE: To determine risk factors associated with relapse within 7 days after treatment of asthma exacerbations in children. METHODS: This was a multicenter, prospective study of children with asthma attacks. Patients between the ages of 6 months and 17 years who met the criteria between June 2009 and September 2012 were considered. RESULTS: The study included 1177 patients (775 males [65.8%]) with a mean (SD) age of 70.72 (48.24) months. Of them, 199 (16.9%) had a relapse within 1 week after being discharged from the hospital. Factors independently associated with relapse identified by a logistic regression model for the 1,177 study visits were having taken a short-acting inhaled ß2-agonist within 6 hours before admission (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.728-3.426; P = .001), presence of retraction on physical examination (OR, 1.76; 95% CI, 1.123-2.774; P = .01), no prescription for high-dose inhaled steroids on release (OR, 2.02; 95% CI, 1.370-3.002; P < .001), and not being given a written instructional plan (OR, 1.55; 95% CI, 1.080-2.226; P = .02). CONCLUSION: Whereas having taken short-acting ß2-agonists within 6 hours before admission and the presence of retractions on physical examination increased the risk of relapse after treatment of the acute attack, being given high-dose inhaled steroids and a written instructional plan when being sent home reduced the risk.

A Case Report and Pediatric Literature Review: Povidone as a Rare Cause of Anaphylaxis in Children.

Background: Povidone, a synthetic polymer commonly used in various products such as antiseptics, cosmetics, and medications, has been associated with allergic reactions, including anaphylaxis. Despite its widespread use, cases of povidone-induced anaphylaxis, especially in children, are under-recognized. This case report aims to highlight the importance of considering povidone allergy in pediatric patients presenting with anaphylaxis. Case Presentation: We describe a 3-year-old boy who experienced anaphylaxis following the application of povidone-iodine antiseptic solution to a leg wound. He presented with generalized urticaria, angioedema, dyspnea, and cough. Prompt diagnosis and management were initiated in the emergency department. He experienced the second anaphylaxis with povidone-containing eye drops prescribed during an ophthalmology visit. Conclusions: Povidone allergy should be considered in pediatric patients presenting with anaphylaxis, especially those with idiopathic reactions or multiple drug allergies. Clinicians should emphasize patient education on label reading and the provision of adrenaline autoinjectors to prevent life-threatening reactions associated with povidone exposure.

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.

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.

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.

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.

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.

Training of trainers on epinephrine autoinjector use.

The majority of physicians do not know how to use epinephrine autoinjectors. This displays that current education of physicians on anaphylaxis is inadequate for a thorough practice. We hypothesize that a theoretical lecture together with a practical session on epinephrine autoinjector use will improve its proper use by physicians. Residents, specialists, and consultants from General Pediatrics excluding allergists and allergy fellows were included in this study. All physicians were given an eight-item questionnaire followed by a practical session scoring and timing ability to use epinephrine autoinjector trainer. This ensued with one-to-one hands-on training on correct autoinjector use. Finally, a joint theoretical lecture on anaphylaxis including re-demonstration of epinephrine autoinjector use was given. All physicians were scored a second time on use of epinephrine autoinjector 6 months later. One hundred fifty-one of 196 participants completed all steps of the study in four tertiary hospitals. Correct use of epinephrine autoinjector improved from 23.3% to 74.2%, mean score from 3.49 ± 1.14 to 4.66 ± 0.65, need for prospectus from 91.4% to 29.1%, and mean time to administer autoinjector from 28.01 ± 6.22 s to 19.62 ± 5.01 s (p < 0.001 for each). The rate of most common mistakes during autoinjector use decreased but the ranking did not change. An integrated theoretical and practical education increased correct of epinephrine autoinjector use by physicians. Ongoing mistakes despite this education may be related with its design.

Common behavioral problems among children with asthma: is there a role of asthma treatment?

BACKGROUND: An increased prevalence of behavioral problems has been described among children with asthma. OBJECTIVE: To investigate those associations between common behavioral problems and asthma, with an emphasis on the roles of medications used for asthma. METHOD: We studied 409 children who had been followed-up in pediatric allergy clinics and 157 age-matched healthy controls. A diagnostic and statistical manual disorder-referenced symptom inventory was used to assess "attention deficit-hyperactivity disorder" (ADHD), "attention deficit" (AD), "hyperactivity and impulsivity" (HI), and "oppositional defiant disorder" (ODD) behavioral problems. RESULTS: The study group consisted of 409 patients (male: 251, female: 158), with a mean age of 9.0 ± 2.67 years, and the control group consisted of 157 children (male: 75, female: 82), with a mean age of 9.0 ± 2.86 years. Prevalences of AD, hyperactivity, ADHD, and ODD were not significantly different between the study and control groups. Among those patients receiving leukotriene antagonist (LA) drugs adjunctive to inhaled corticosteroids (ICS), duration of treatment was correlated with total scores calculated for hyperactivity (P = .035, r = 0.432), AD (P = .044, r = 0.414), ADHD (P = .042, r = 0.418), and ODD (P = .032, r = 0.439). Among patients with asthma, children with ODD had a significantly longer duration of LA+ICS use (P = .024) compared with those with no ODD. Patients with hyperactivity had a longer duration of ICS+LA use compared with those with no hyperactivity (P = .009). Patients with asthma receiving LA+ICS treatment had a higher risk for oppositional behavior (4.282 times compared with the control group [P = .042, confidence interval (CI): 1.542-15.949]) and 8.3 times compared with patients with asthma not using any drug (P = .021, CI: 1.419-48.543). CONCLUSION: Rather than asthma itself, adjunctive use of ICS+LA therapy appears to be related with symptoms of common behavioral problems, including hyperactivity, AD, ADHD, and ODD and to increase the risk of ODD.

The immunostimulant OM-85 BV prevents wheezing attacks in preschool children.

BACKGROUND: No reagents have been shown to be effective in preventing wheezing attacks provoked by acute respiratory tract illnesses (ARTIs) in preschool children. New therapeutic agents and preventive strategies are needed. OBJECTIVES: We assessed the effect of OM-85 BV (Broncho-Vaxom; OM Pharma, Geneva, Switzerland) in preventing ARTI-provoked wheezing attacks in preschool children with recurrent wheezing. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was carried out between August 2007 and September 2008. The study included 75 children with recurrent wheezing who were 1 to 6 years old. Participants were randomly assigned to groups given either OM-85 BV or a placebo (1 capsule per day for 10 days each month for 3 consecutive months) at the start of the trial. Participants were followed for 12 months, which included the administration period of the test article. RESULTS: Subjects given OM-85 BV had a lower rate of wheezing attacks. The cumulative difference in wheezing attacks between the 2 groups was 2.18 wheezing attacks per patient in 12 months; there was a 37.9% reduction in the group given OM-85 BV compared with the group given placebo (P < .001). Stepwise multiple (linear) regression analysis showed that the main difference between the OM-85 BV and placebo groups was a reduction the number of ARTIs (R = -0.805, P < .001). The duration of each wheezing attack was 2 days shorter in the group given OM-85 BV than in the group given placebo (P = .001). CONCLUSION: Administration of OM-85 BV significantly reduced the rate and duration of wheezing attacks in preschool children with ARTIs.

Evaluation of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy.

Specific immunotherapy (SIT) is one of the treatment modalities recomended for the management of asthma and allergic rhinitis by international guidelines. A potential benefit of immunotherapy (IT) is to prevent the development of sensitisation to new allergens. There is stil no conclusion on this subject. One hundred twenty-two children 8-18 years old with intermittent asthma, with or without allergic rhinitis, all of whom were monosensitised to house dust mite (HDM) were selected. Sixty two of these children accepted to receive SIT with HDM extract for 4 years and the remaining 60 did not accept SIT and were treated with asthma medications only. This second group of children served as the control group. At the end of the 4-year study period, 36 of the 53 patients (67.9%) in the SIT group showed no new sensitizations, compared to 38 of 52 (73.0%) in the control group (p = 0.141). The most frequent new sensitizations at the end of the study were pollens, grasses and olive polen, followed by animal dander, alternaria and cockroach. In conclusion, SIT may not prevent the onset of new sensitizations in asthmatic children monosensitized to house dust mites. Further investigation is required to clarify the immunologic mechanisms and other factors by which SIT reduces or not the development of new sensitizations in monosensitized children.

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.

Clinical, Histochemical, and Molecular Study of Three Turkish Siblings Diagnosed with H Syndrome, and Literature Review.

BACKGROUND: The term "H syndrome" was coined to denote the major clinical findings, which include hyperpigmentation, hypertrichosis, hearing loss, hepatosplenomegaly, hyperglycaemia, hypogonadism, hallux flexion contractures, and short height. OBJECTIVE: To report the clinical, endocrinological, histochemical, and genetic findings of three siblings. METHODS: Skin and liver biopsies were taken to investigate the histochemical characteristics of hyperpigmented hypertrichotic skin lesions and massive hepatomegaly. The levels of basal serum thyroid hormones, oestradiol, total testosterone, follicle-stimulating hormone, luteinising hormone, and stimulated growth hormone (GH) were measured to investigate the endocrine aspects of the syndrome. Mutation analysis was carried out in all six exons and exon-intron boundaries of SLC29A3 by direct sequencing. RESULTS: Physical examination of the patients revealed common charac-teristic findings of H syndrome. Additional clinical findings were sectorial iris atrophy in the younger sister. Laboratory evaluation revealed microcytic anaemia, markedly increased erythrocyte sedimentation rate and C-reactive protein levels, and humoral immune deficiency in the younger siblings, who presented with recurrent fever and sinopulmonary infection. Two different GH stimulation tests revealed GH deficiency in the younger sister with short stature. Liver and skin biopsies revealed polyclonal lymphohistiocytic and plasma cell infiltration. Sequencing of SLC29A3 in the three siblings revealed a novel homozygous mutation in exon 6, which caused the transition of arginine to tryptophan. CONCLUSION: This study not only extended the clinical and mutation spectrum of SLC29A3 in H syndrome, but also showed that short children should be assessed according to the guidelines for short stature in children.