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.

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.

Analysis of predictive factors in children with high suspicion of pulmonary embolism.

BACKGROUND AND AIM: Since there is a limited number of predictive models designed for pediatric patients with pulmonary embolism (PE), healthcare providers have resorted to utilizing the Wells criteria and PE Rule-out Criteria (PERC) that have been validated for use in adults. The objective of the study is to identify the predictive factors for PE and assess the effectiveness of the PERC, Wells, and pediatric-specific PE (PPE) criteria. METHODS: The study included individuals between the ages of 0-18 years who underwent pulmonary CT angiography and/or ventilation-perfusion scintigraphy with suspicion of PE. Demographic characteristics, symptoms, physical examination findings, risk factors, and laboratory and imaging results were retrospectively analyzed, and PERC, Wells, and PPE criteria were applied to the study population. RESULTS: Of the 110 patients included in the study, 27 (24.5%) had PE. Saturation, albumin, cough, calf swelling, central catheter, and malignancy were found to significantly contribute to the model. The total weighted risk score, which represents the sum of all predictive scores, ranged from 0 to 16 with a mean of 5.41 ± 4.02. When the cut-off >6.5, the model had good discrimination power for positive PE (AUC 0.79, 77% sensitivity, and 70% specificity). In our study, the Wells criteria showed a sensitivity of 96% and a specificity of 24%. The PERC exhibited a sensitivity of 96% and a specificity of 21%, while the PPE demonstrated a sensitivity of 74% and a specificity of 30%. CONCLUSION: While the sensitivity of Wells, PERC, and PPE models was higher than our developed model, their specificities were considerably lower than our model.

A rare phenomenon, primary pulmonary smooth muscle tumor and its management.

Smooth muscle tumors of uncertain malignant potential, the borderline tumors arising from the smooth muscle cells, usually grow slowly and do not fulfill the diagnostic criteria of leiomyosarcoma and its variants, but may behave in a malignant manner. A 15-year-old female patient with an endobronchial mass in the left main bronchus on thoracic computed tomography underwent thoracotomy and tracheobronchoplasty with a wide and safe margin. Histopathological evaluation revealed a smooth muscle tumor of uncertain malignant potential. There were no complications related to the operation during the hospital stay. At six months of surgery, there were no symptoms or signs suggesting any recurrence in her follow-up. In conclusion, In conclusion, pulmonary leiomyomas may rarely present as an endobronchial mass and may mimic asthma by causing respiratory symptoms developing as attacks due to displacement of the mass within the lumen.

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.

Factors affecting formula compliance of infants with IgE mediated cow's milk protein allergy during the pandemic.

Introduction: Cow's milk protein allergy (CMPA) is the most commonly encountered food allergy in the world, usually seen in infants under the age of 2 years. This study aims to determine the factors including COVID-19 affecting formula compliance of CMPA patients. Methods: This study is a prospective, observational study based on 10 different Paediatric Allergy-Immunology clinics in Turkey. Patients aged between 6 months and 2 years, who were followed up with IgE-mediated CMPA treatment or newly diagnosed and using breast milk and/or formula were included in the study. The sociodemographic characteristics of the patients, their symptoms, the treatments they received, and the effects of the COVID-19 pandemic on adherence to formula were evaluated with a questionnaire administered to the parents. Results: The compliance rate for formula-based treatment was 30.8% (IQR: 28.3, SD: 21.86). The number of patients with a single and multiple food allergy was 127 (51.6%) and 71 (28.9%), respectively. Breastfeeding duration, daily amount of prescribed formula and addition of sweetener to the formula were found to reduce compliance (p = 0.010, p = 0.003, and p = 0.004, respectively). However, it was determined that the patient's height, weight, age at diagnosis, and age of formula onset did not have a significant effect on compliance. Conclusion: It was found that the duration of breastfeeding, the increase in the daily amount of formula requirement, and the addition of sweeteners had adverse effects on formula compliance. There was no significant correlation between the formula adherence of CMPA patients and the pandemic.

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.

Incidental pulmonary nodules in children: characteristic features and clinical course.

BACKGROUND: There exists insufficient information about the natural course of incidental pulmonary nodules (IPN) determined on tomography in children. The aim was to determine the characteristic features and factors affecting the course of IPN. METHODS: This retrospective study included patients who presented at the Pediatric Pulmonology, Allergy & Immunology Section of Akdeniz University Hospital between January 2014-2020, and were determined with pulmonary nodules on high-resolution computed tomography (HRCT). The patients were separated into two groups as those with a nodule decreased in size or which had disappeared on the follow-up HRCT (Group 1) and those with a nodule which had remained at the same size (Group 2). These two groups were compared in respect to demographic data, nodule size and characteristics, and accompanying findings on HRCT. RESULTS: A total of 177 nodules were determined in the 66 patients included in the study. A follow-up HRCT was taken within mean 16.29±11.38 months in 27 patients. In these patients, 78 nodules were determined on the initial HRCT. On the follow-up, twelve of the nodules were seen to have shrunk or disappeared compared to the initial images, 66 had remained the same size, and none had grown. The mean age of the patients in Group 1 was statistically significantly lower than that of patients in Group 2 (p < 0.001). The rates of an accompanying mosaic attenuation pattern (p < 0.001) on HRCT and subsolid density (p=0.011) of the nodules in Group 1 were statistically significantly higher compared to Group 2 and the rate of calcification content was statistically significantly lower (p=0.002). No suspicious or confirmed malignancy was observed in any case throughout the mean follow-up period of 38.33±16.5 months after the initial HRCT. CONCLUSIONS: The young age of patients, subsolid structure of nodules, calcification content and the presence of an accompanying mosaic attenuation pattern on HRCT, could be useful factors in the estimation of size in the follow-up of nodules.

The Asthma Risk Is Increased in Children with Severe Allergic Rhinitis.

OBJECTIVE: The aim of the study was to evaluate the allergic rhinitis severity, to identify risk fac- tors associated with asthma, and to determine the frequency of comorbid conditions in allergic rhinitis patients with positive skin prick test. MATERIALS AND METHODS: Clinical characteristics of pediatric patients with allergic rhinitis were investigated. The frequency of comorbidities and risk factors for asthma development were investigated. RESULTS: A total of 120 patients with a mean age of 13.05 ± 3.20 years were included in the study. Dermatophagoides pteronyssinus was the most common source of allergic sensitization (n = 78, 61.0%), whereas mild-persistent disease was the most common type of allergic rhini- tis severity (n = 44, 36.6%). Sensitization to Dermatophagoides farinea, Dermatophagoides pteronyssinus, and Alternaria was more common in patients with a moderate-severe course of allergic rhinitis than in the mild group (P = .006, P = .008, and P = .005, respectively). The most frequent comorbidity in children with allergic rhinitis was allergic conjunctivitis (71.7%). The inci- dence of asthma in those with moderate-severe allergic rhinitis was found to be significantly higher compared to those with mild disease severity (P = .009). Also, the multivariate analysis disclosed moderate-severe allergic rhinitis severity and persistent allergic rhinitis symptoms (OR: 3.822; 95% CI: 1.587-9.200; P =0.003 and OR: 0.333; 95% CI: 0.150-0.737; P =.007, respec- tively) as risk factors for asthma development. CONCLUSION: Sensitization to Dermatophagoides farinea, Dermatophagoides pteronyssinus, and Alternaria was more frequent in patients with moderate-severe allergic rhinitis course. Also, having moderate-severe allergic rhinitis severity and persistent allergic rhinitis symptoms are associated with the development of asthma. Awareness of the risk factors could prevent the progression and complications of allergic rhinitis in children.

Specific Granule Deficiency Due To Novel Homozygote SMARCD2 Variant.

Background: Specific granule deficiency (SGD) is a rare immunodeficiency associated with CCAT/enhancer-binding protein epsilon (CEBPE) gene variants. It can cause severe recurrent infections and is lethal without successful stem cell transplantation. Few cases with SGD of both type 1 and type 2 have been described in the literature. In this study, we present the first report of a case with a novel homozygous c.511 C > T (p.Gln171Ter) mutation in the SMARCD2 gene of SGD type 2, which was successfully treated with bone marrow transplantation. Case: A male infant presented to our neonatal intensive care unit on the second day of life with an icteric appearance and mild hypotonia. He was evaluated for immunodeficiency as the cause of delayed cord separation and refractory neutropenia. At 6 weeks of age, SGD type 2 with a new variant was diagnosed and successfully treated by bone marrow transplantation. Conclusion: SGD is an immunodeficiency disease that is quite rare. However, we believe that SGD diagnosis and associated new variants can be detected more frequently with the widespread use of all whole-exome sequencing techniques.

Novel Gene Variants Associated with Primary Ciliary Dyskinesia.

OBJECTIVES: To determine the demographic, clinical, and genetic profile of Turkish Caucasian PCD cases. METHODS: Targeted next-generation sequencing (t-NGS) of 46 nuclear genes was performed in 21 unrelated PCD cases. Sanger sequencing confirmed of potentially disease-related variations, and genotype-phenotype correlations were evaluated. RESULTS: Disease-related variations were identified in eight different genes (CCDC39, CCDC40, CCDC151, DNAAF2, DNAAF4, DNAH11, HYDIN, RSPH4A) in 52.4% (11/21) of the cases. The frequency of variations for CCDC151, DNAH11, and DNAAF2 genes which were highly mutated genes in the cohort was 18% in 11 patients. Each of the remaining gene variations was detected once (9%) in different patients. The variants, p.R482fs*12 in CCDC151, p.E216* in DNAAF2, p.I317* in DNAAF4, p.L318P and p.R1865* in DNAH11, and p.N1505D and p.L1167P in HYDIN gene were identified as novel variations. Interestingly, varying phenotypic findings were identified even in patients with the same mutation, which once again confirmed that PCD has a high phenotypic heterogeneity and shows individual differences. CONCLUSION: This t-NGS panel is potentially helpful for exact and rapid identification of reported/novel PCD-disease-causing variants to establish the molecular diagnosis of ciliary diseases.

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.

Psychological State of Parents of Children with Primary Immunodeficiencies During the COVID-19 Pandemic.

Background: COVID-19 has affected humanity not only physically but also mentally. It was expected to have impact on high-risk groups such as the immunocompromised patients and parents/caregivers of them. Our study was aimed to investigate the COVID-19 related anxiety, post-traumatic stress levels, and sleep-related parameters of the parents of children with primary immunodeficiency. Methods: Parents of children with primary immunodeficiency and age and gender-matched control group completed questionnaires. Results: Anxiety and post-traumatic stress levels of the study group were found to be significantly higher than the control group. Furthermore, sleep time of the study group was significantly lower than the control group. The subjective sleep quality of the study group was also lower in the study group, but the difference did not reach a significant level. Conclusions: In the ongoing and other possible pandemic processes, professional support for the parents of these children is of great importance.

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.

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.

Clinical phenotypes of childhood food allergies based on immune mechanisms: A multicenter study.

Background: Food allergies (FA) are an important public health concern that place a major burden on the lives of children and their families. The complex pathogenesis of FAs results in multisystemic and heterogenous clinical presentations. Objective: To evaluate, according to immune mechanisms, the characteristics and risk factors of childhood FA in Turkey. Methods: This descriptive multicenter study included 1248 children with FA, aged < 18 years,, who were evaluated by pediatric allergists in 26 different centers. Results: Immune mechanisms of FA were immunoglobulin E (IgE) mediated in 71.8%, non-IgE mediated in 15.5%, and mixed IgE/non-IgE mediated in 12.7% of the patients. An episode of anaphylaxis had occurred in 17.6% of IgE-mediated FA. The most common food allergens were classified into five categories (in order of decreasing frequency): cow's milk, egg, tree nuts and/or peanut, wheat, and seafood. Allergies to cow's milk and egg declined significantly with age, whereas tree nuts and/or peanut allergies increased with age. The 0-2 year age group accounted for 62.5% of the cases. The most frequent cause of FA and food anaphylaxis was cow's milk before age 13 years and tree nuts and/or peanut during adolescence (ages 13-18 years). Compared with other phenotypes, male sex (odds ratio [OR] 1.486; p = 0.032), sibling(s) (OR 1.581; p = 0.021), and maternal atopy (OR 1.531; p = 0.045) increased the likelihood of IgE-mediated FA, whereas high household income (OR 1.862; p = 0.026) increased the likelihood of non-IgE-mediated FA in multivariate regression analysis. Conclusion: This study showed that the clinical findings of FA were highly variable, depending on age and underlying immune mechanism. Knowing the population characteristics will enable better management of FA in children.

Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.

Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.

Association Between Cystic Fibrosis Severity Markers and CFTR Genotypes in Turkish Children.

OBJECTIVE: To compare class I/II cystic fibrosis transmembrane conductance regulator (CFTR) mutations to class III-V mutations with regards to cystic fibrosis disease severity markers in children. MATERIAL AND METHODS: This study was designed as a cross-sectional study in Antalya province, located on the south coast of Turkey. The study included 38 cystic fibrosis patients aged between 0.6 and 18 years. The CFTR genotype of the patients was categorized into 2 groups based on the presence or absence of class I or class II mutations in any of the alleles. Group I comprised 8 homozygous, 8 with unknown alleles, and 8 compound heterozygous patients, and group II comprised 11 homozygous and 3 compound heterozygous patients. The groups were analyzed in respect of cystic fibrosis disease severity markers, such as spirometry, ShwachmanKulczycki score, body mass index (BMI), sweat chloride concentration, chronic Pseudomonas aeruginosa infection, annual exacerbation frequency, and severe exacerbations requiring hospitalization during the previous year. RESULTS: In the comparison of group I and group II patients, a significant difference was observed in pancreas insufficiency (83.3% vs. 35.7%; P = .005), chronic P. aeruginosa infection (58.3% vs. 7.1%; P = .002), cough severity score (1.7 ± 1.1 vs. 0.9 ± 1.5; P = .029), number of severe exacerbations requiring hospitalization during the previous year (0.9 ± 1 vs. 0.3 ± 0.8; P = .03), and sweat chloride levels (76.7 ± 15.2 vs. 61 ± 22.3; P = .02). All these values were higher in group I patients. The mean BMI values (15.8 ± 2.2 vs. 17.6 ± 2.8; P = .03) were lower in group I patients. CONCLUSION: There seems to be a difference between class I/II CFTR mutations and class III-V mutations on the severity of the disease in cystic fibrosis patients.

Hematopoietic stem cell transplantation in CD40 ligand deficiency: A single-center experience.

Deficiency of the CD40L, expressed on the surface of T lymphocytes, is caused by mutations in the glycoprotein CD40L (CD154) gene. Resulting defective humoral and cellular responses cause a clinical presentation that includes recurrent sinopulmonary bacterial infections, opportunistic infections, sclerosing cholangitis, neutropenia, and autoimmune manifestations. HSCT represents the only curative treatment modality. However, the therapeutic decision to use HSCT proves challenging in many cases, mainly due to the lack of a phenotype-genotype correlation. We retrospectively reviewed patients with CD40L deficiency who were transplanted in Antalya and Göztepe MedicalPark Pediatric HSCT units from 2014 to 2019 and followed by Akdeniz University School of Medicine Department of Pediatric Immunology. The records of eight male cases, including one set of twins, were evaluated retrospectively. As two transplants each were performed on the twins, a total of ten transplants were evaluated. Conditioning regimens were predominantly based on myeloablative protocols, except for the twins, who received a non-myeloablative regimen for their first transplantation. Median neutrophil and platelet engraftment days were 13 (range 10-19) and 14 (range 10-42) days, respectively. In seven of ten transplants, a CMV reactivation was developed without morbidity. None of the patients developed GVHD, except for one mild case of acute GVHD. All patients survived, and the median follow-up was 852 days. Our data show that HSCT for patients with CD40 ligand deficiency is a potentially effective treatment for long-term disease control.

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.