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.

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.

Successful desensitization protocol for pyridostigmine in a 12 year old patient with myasthenia gravis.

BACKGROUND: Myasthenia gravis is a chronic, autoimmune disease with muscle weakness. Acetylcholinesterase inhibitors are used in the symptomatic treatment of the disease. Allergic reaction to pyridostigmine bromide is rare. In the literature, no allergic reaction to pyridostigmine bromide has been reported in the pediatric population. CASE: A 12-year-old female patient diagnosed with myasthenia gravis consulted our clinic with the complaint of urticaria due to pyridostigmine bromide. The oral challenge test performed with pyridostigmine bromide was positive. As the patient was required to be continue pyridostigmine bromide with no suitable alternatives, it was decided that the patient had to be desensitized to pyridostigmine. During and after the desensitization protocol, no reaction was observed. CONCLUSIONS: In this report, a successful desensitization protocol for pyridostigmine bromide in a child with myasthenia gravis is discussed.

Experiences and attitudes of parents of children with cow's milk and other food-allergy.

INTRODUCTION AND OBJECTIVE: The attitude and behaviors of parents are important in the management of children with food allergy (FA). The aim of this study is to evaluate the experiences and attitudes of parents of children with allergy to cow's milk and other FA. MATERIALS AND METHODS: The parents of children with FA were asked to complete an 18-item questionnaire to evaluate the FA history and experiences during diagnosis, treatment, and follow up. RESULTS: The data from 558 (91.2%) survey questionnaire that were filled completely were analyzed. The mean age of the parents was 33.4+4.9. It was found that most common food allergen was cow's milk (85.3%). The mean time to diagnosis from the onset of symptoms was 10.9±18.4 months. Around 229 parents (41.6%) admitted to at least four different physicians and 68 (12.3%) parents admitted to at least five different physicians before diagnosis. The median time to diagnosis from the onset of symptoms was five (1-108) months in the patients admitted to four or more physicians, but it was one (1-48) month in the patients that admitted to less physicians (p˂0.001). The most common symptoms were dermatitis and mucus-bloody stool, the least common ones were cardiovascular symptoms. Only 21.1% of the patients were able to use hypoallergenic formulas (HAF) in accordance with the recommendation of the physician. CONCLUSIONS: Delayed diagnosis of FA is a major concern, and during this period the patients admit many physicians. A majority of the patients with CMPA experience difficulties while using HAFs, and only one-fifth of them is able to use formula regularly.

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 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.

The Effect of Serum Vitamin D Level on Allergic Rhinitis Symptoms in Children.

Background: Allergic rhinitis (AR) is a chronic disease that is becoming increasingly common worldwide and has a negative impact on school performance, work performance, and quality of life. The aim of this study was to investigate the effect of vitamin D on the symptoms of AR in children. Methods: Serum vitamin D levels of children with AR and age-matched healthy controls were compared using the high-pressure liquid chromatography method. The relationship between serum vitamin D levels and symptoms and severity of AR was then examined. Results: The study included 137 patients diagnosed with AR (76 males, 61 females; median age: 11 years). Serum vitamin D levels were lower in the patient group than in the control group (P = 0.001), lower in all aeroallergen groups (mites, pollen, and multiple inhalants) than in the healthy control group (P = 0.001), and lower in both the perennial AR group and the seasonal AR group than in the control group (P = 0.001). Spearman correlation analysis showed that there was no correlation between symptom score and vitamin D level (rs = -0.099; P = 0.25). Conclusions: We found no correlation between serum vitamin D level and symptoms and severity of AR. Serum vitamin D levels were lower in children with AR than in healthy children.

Food-induced anaphylaxis in early childhood and factors associated with its severity.

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6-18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.

Acute generalized exanthematous pustulosis due to Epstein-Barr virus infection in a neonate.

Acute generalized exanthematous pustulosis (AGEP) is an uncommon inflammatory subcorneal pustular dermatosis typically caused by exposure to a medication. Several viral infections have also been implicated in its development. We describe herein a rare case of AGEP associated with acute Epstein-Barr virus (EBV) infection in a neonate.

Healthcare workers` knowledge level regarding anaphylaxis and usage of epinephrine auto-injectors.

BACKGROUND: Inadequate practices in diagnosis and management of anaphylaxis in parallel with an increase in its prevalence may cause serious public health problems today. This is the first study aiming to assess the theoretical knowledge of professional and non-professional healthcare workers from different lines of the healthcare service chain about anaphylaxis management, and their practice approaches for epinephrine autoinjectors (EAIs) together. METHODS: The study included 697 participants comprising physicians, dentists, pharmacists, and school staff. In face-to-face interviews, each participant was asked to fill out the questionnaire forms prepared for assessing their demographic characteristics, experience with a case of anaphylaxis and EAI and theoretical knowledge about the diagnosis and treatment of anaphylaxis, and to demonstrate how to use EAI in practice with trainer device. RESULTS: The rates of 391 physicians, 98 dentists, 102 pharmacists and 105 school staff of knowing the diagnosis criteria of anaphylaxis were 47.6%, 31.6%, 31.1%, 19%, and knowing the first and life-saving treatment of anaphylaxis were 87.2%, 79.6%, 47.6%, 15.2%, respectively. Predictors that affected physicians in knowing the first and life-saving treatment of anaphylaxis were having experience with EAIs [OR:5.5, (%95CI:1.330-23.351, p=0.015)] and a case of anaphylaxis [OR:2.4, (%95CI:1.442-4.020, p=0.001)], and knowing the administration route of epinephrine correctly [OR:1.9, (%95CI:1.191-3.314, p=0.008)]. 31.1% of the participants demonstrated the EAI usage correctly. The EAI usage steps with the most errors were `Place the appropriate injection tip into outer thigh/Press the trigger so it `clicks`` and `Turn the trigger to arrow direction` (60.3% and 34.9%, respectively). CONCLUSIONS: Healthcare workers` knowledge level regarding anaphylaxis management and ability to use EAIs correctly are not adequate. That most errors were made in the same steps of EAI usage indicates that the industry should continue to strive for developing the ideal life-saving device.

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.

Prevalence of atopic diseases in children with papular urticaria.

BACKGROUND: Papular urticaria is a hypersensitivity reaction characterized by chronic and recurrent papular erythema. It occurs as a result of the bites of mosquitoes, fleas, bed bugs, and other insects; and it is generally seen in children. This study examines the prevalence of atopic diseases in patients with papular urticaria. METHODS: The medical records of 130 pediatric patients with the diagnosis of papular urticaria between August 2017 and August 2019, whose disease progression was followed in two tertiary care centers, were reviewed retrospectively. The patients were divided into two groups: under 5 and above 5 years old. The prevalence of the atopic disease in children with papular urticaria was compared with those in age-matched controls without papular urticaria. RESULTS: The study included 130 patients who were diagnosed with papular urticaria (64 males, 66 females, median age: 60 months). The prevalences of atopic disease, recurrent wheezing, and atopic dermatitis were higher in the group under 5 years old with papular urticaria than in the same-age control group (p=0.001, 0.002, and 0.001, respectively). The prevalences of atopic disease, asthma, allergic rhinitis, and atopic dermatitis were higher in the group above 5 years old with papular urticaria than in the same-age control group (p=0.001, 0.001, 0.001, and 0.007, respectively). CONCLUSIONS: Many children with papular urticaria are atopic children. These patients should be assessed not only in terms of papular urticaria but also in terms of comorbid atopic diseases.

Proven Food-Induced Acute Urticaria and Predictive Factors for Definitive Diagnosis in Childhood.

BACKGROUND: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy. OBJECTIVE: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood. METHODS: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study. RESULTS: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow's milk, hen's eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow's milk-induced acute urticaria was 92% (95% CI: 81-96%). A history of cow's milk-induced and/or hen's egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen's kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002). CONCLUSION: Cow's milk, hen's eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria.

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.

The pharmacists' ability to use pressurized metered-dose inhalers with a spacer device and factors affecting it.

Objective: The aim of this study is to evaluate the pharmacists' ability to use pMDIs with a spacer device and the factors that affect this ability.Method: Face to face interviews were conducted with the pharmacists. A nine item questionnaire was completed and the checklist for how to use pMDIs with a spacer device was filled out.Results: A total of 307 pharmacists voluntarily participated in this study. Fifty-six (18.2%) of the pharmacists stated that they did not know how to use pMDIs with a spacer device. These pharmacists were excluded and remaining 251 pharmacists included in the study. Only 100 (39.8%) pharmacists demonstrated all of the inhaler spacer device usage steps correctly. The step in which pharmacists made the most mistakes was "take 5-6 deep and slow breaths, hold for 10 s and slow breaths." Those pharmacists who were more likely to correctly use pMDIs with a spacer device were younger (p = 0.023), had dispensed more asthma medications per day (p < 0.001), had dispensed more asthma medications per day for patients younger than six years of age (p = 0.016), and sold inhaler spacer devices at their pharmacy (p = 0.042).Conclusion: Approximately one third of the pharmacists in the current study were able to correctly demonstrate all of the steps for proper usage of pMDIs with a spacer device, which indicates that pharmacists should be included in the training program and be provided continuous training on the use of pMDIs with a spacer device.

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 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.

ILC3 deficiency and generalized ILC abnormalities in DOCK8-deficient patients.

BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) deficiency is the main cause of the autosomal recessive hyper-IgE syndrome (HIES). We previously reported the selective loss of group 3 innate lymphoid cell (ILC) number and function in a Dock8-deficient mouse model. In this study, we sought to test whether DOCK8 is required for the function and maintenance of ILC subsets in humans. METHODS: Peripheral blood ILC1-3 subsets of 16 DOCK8-deficient patients recruited at the pretransplant stage, and seven patients with autosomal dominant (AD) HIES due to STAT3 mutations, were compared with those of healthy controls or post-transplant DOCK8-deficient patients (n = 12) by flow cytometry and real-time qPCR. Sorted total ILCs from DOCK8- or STAT3-mutant patients and healthy controls were assayed for survival, apoptosis, proliferation, and activation by IL-7, IL-23, and IL-12 by cell culture, flow cytometry, and phospho-flow assays. RESULTS: DOCK8-deficient but not STAT3-mutant patients exhibited a profound depletion of ILC3s, and to a lesser extent ILC2s, in their peripheral blood. DOCK8-deficient ILC1-3 subsets had defective proliferation, expressed lower levels of IL-7R, responded less to IL-7, IL-12, or IL-23 cytokines, and were more prone to apoptosis compared with those of healthy controls. CONCLUSION: DOCK8 regulates human ILC3 expansion and survival, and more globally ILC cytokine signaling and proliferation. DOCK8 deficiency leads to loss of ILC3 from peripheral blood. ILC3 deficiency may contribute to the susceptibility of DOCK8-deficient patients to infections.