Restrictive effects of thalassemia on respiratory functions: One center experience.

OBJECTIVE: Respiratory functions in thalassemia major (TM) patients concerning poor chelation are a frequently researched issue. Our study aims to evaluate the lung functions of our patients with TM in the chronic transfusion program and to correlate them with their age, ferritin levels, and pre-transfusion hemoglobin values. METHODS: Height, weight, pulmonary function test (PFT) results, pre-transfusion hemoglobin levels, and ferritin levels of 97 patients (55 boys and 42 girls) without any underlying cardiac or chronic respiratory disease were recorded. PFT is consisted of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), the ratio of FEV1/FVC to peak expiratory flow (PEF), and forced mid-exhaled flow between 25% and 75% of mid-expiratory flow (MEF25-75). Data were analyzed with IBM SPSS V25. RESULTS: Low FVC was observed in 58 patients (60%), and low FEV1 was observed in 26 patients (27.6%). Low PEF was observed in 62 patients (64.5%), and low MEF25-75 was observed in 8 (8.3%). PFT was affected in 75 patients (78.1%). The pattern of involvement was restrictive. Age, height, and ferritin values significantly affected the MEF25-75 (p<0.05). Age and pre-transfusion hemoglobin values had a significant effect on the FVC test (p<0.05). There was a weak negative correlation between ferritin values and MEF25-75 (r=-0.221) and a weak positive correlation between pre-transfusion hemoglobin and FVC (r=0.222). CONCLUSION: Age and height are the main risk factors affecting FEV1, MEF25-75, and PEF. Serum ferritin has only an effect on MEF25-75 in our study. The respiratory functions of TM patients were affected in a restrictive pattern.

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.

First Documented Case of Pulmonary Alveolar Proteinosis with Atopy Presenting Secondary to CSFR2B Mutation.

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. It is essential to gain a better understanding of the signs to clinically diagnose PAP and include PAP among the differential diagnoses of interstitial pulmonary diseases or other diseases with similar manifestations. We describe a 2.5-year patient with atopy who presented with pulmonary infiltration, recurrent wheezing, and cough despite steroid and salbutamol administration via inhalation. High-resolution computed tomography revealed crazy-paving patterns in both lungs, suggesting PAP. An open lung biopsy revealed intra-alveolar granular amphophilic material, which was strongly positive on periodic acid-Schiff staining. The results of pulmonary-associated surfactant protein B and C gene analyses were normal. However, granulocyte-macrophage colony-stimulating factor receptor beta-protein was not detected in leucocytes, and a novel mutation was identified in the CSF2RB gene. The patient was diagnosed with PAP and treated with whole-lung lavage. Key Words: Pulmonary alveolar proteinosis, Child, Atopy, Wheezing.

Clinical features of anaphylaxis in children.

Background: Despite the considerable increase in anaphylaxis frequency, there are limited studies on clinical features of anaphylaxis in children in developing countries. Objective: We aimed to analyze the demographic and clinical features of anaphylaxis in children in Turkey by comparing different age groups and triggers. Methods: Medical records of 147 children, ages 0-18 years, diagnosed with anaphylaxis between 2010 and 2019 were retrospectively analyzed. Results: The mean ± standard deviation age at first anaphylaxis episode was 5.9 ± 5.2 years, with a male predominance (63.9%); 25.2% were infants and 52.4% were < 6 years of age at their first anaphylaxis episode; 78.2% were atopic, with the highest frequency in children with food-induced anaphylaxis (FIA). The home (51.7%) was the most frequent setting. The overall leading cause of anaphylaxis was food (44.2%), which was more frequent at < 6 years of age, followed by drugs (28.6%) and bee venom (22.4%), both were more frequent among older children (>6 years). The patients with venom allergy had the highest rate of rapid onset of symptoms (p < 0.001). Gastrointestinal symptoms were observed significantly more in infants (48.6%) and in children with FIA (38.5%); cardiovascular symptoms were more frequently observed in children > 6 years of age (48.6%) and in children with drug-induced anaphylaxis (64.3%). Although recurrent anaphylaxis was reported for 23.1% of the patients, it was highest in the patients with FIA (35.9%). Overall, only 47.6% of the patients received epinephrine in the emergency department (ED) and 27.3% were referred to an allergy specialist, with the patients with FIA having the lowest rate for both, 32.3% and 10.8%, respectively. Children with drug-induced anaphylaxis had the highest rate of severe anaphylaxis (57.1%). Conclusion: There is a need to improve anaphylaxis recognition and management in all children regardless of age and trigger. Inadequate treatment was most evident in infants and patients with FIA.

Experience of Autoimmune and autoinflammatory diseases in a Turkish pediatric cohort with primary immunodeficiencies.

BACKGROUND: Primary immunodeficiency diseases (PID) are the diseases characterized by a dysfunction of the immune system. Affected patients share a different phenotype such as chronic infections, allergy, autoimmunity, and autoinflammation. METHODS: In all, 433 children with PID were enrolled in this study. Clinical, laboratory, and demographic data of patients were reviewed retrospectively to investigate autoimmune and autoinflammatory complications. Autoinflammation in all patients with inflammation was confirmed by genetic analysis after excluding infectious etiology. RESULTS: Clinical features of 433 PID patients were evaluated retrospectively with long-term follow-up. Autoimmune disorders were identified in 69 (15.9%) patients with PID; 31 (45%) patients had a history of autoimmune disease before diagnosis of PID. The frequency of autoimmunity in immune dysregulation subgroup (76.6%) was higher than other forms of PID. The most common autoimmune manifestations were reported to be Addison's disease, hypoparathyroidism, and autoimmune hemolytic anemia. Autoinflammation were identified in 22 of the 433 (5.1%) patients with PID, including hyper immunoglobulin D syndrome (n = 9), Aicardi-Goutieres syndrome 1 (n = 6), adenosine deaminase 2 deficiency (n = 3), Blau syndrome (n = 2), tumor necrosis factor (TNF) receptor-associated periodic syndrome (n = 1), and auto-inflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation syndrome (n = 1). CONCLUSIONS: It is important to recognize association between autoimmunity, autoinflammation, and PID, which in the future could be useful for increased awareness and early diagnosis for these diseases.

Asthma and risk factors in the first 6 years of life in a population-based cohort.

BACKGROUND: The frequency of asthma increases in childhood and asthma is associated with risk factors varying across age groups. The aim of our study was to assess the prevalence of asthma and its associated risk factors in the first six years of life. METHODS: Within the scope of the Adana Pediatric Allergy and Risk Factor (ADAPAR) birth cohort study, 203 infants that had experienced at least one wheezing attack during the first year of life were followed for asthma development until the age of six years. Additionally, 223 infants that were followed within the scope of the same study and had no wheezing attacks in the first year of life were assigned to the control group. RESULTS: At the end of the sixth year, 46 (22.7%) infants were diagnosed with asthma and the use of antibiotics of the mother during pregnancy (OR: 2.98), the presence of allergic diseases in the mother (OR: 4.70) and sibling (OR:2.11), the presence of atopy (OR:4.76), and recurrence of wheezing in the first age (OR:17.35) were identified as risk factors for asthma. CONCLUSIONS: The prevalence of asthma at six years of age was higher than that of other studies. Prevention of infections at an early age and during pregnancy can reduce the prevalence of asthma.

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 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.

Evaluation of high resolution computed tomography findings of cystic fibrosis.

BACKGROUND/AIMS: Morphological changes due to lung disease in patients with cystic fibrosis (CF) were evaluated using high resolution computed tomography (HRCT), and the HRCT scores obtained using the Bhalla scoring system were correlated with those obtained using clinical and laboratory indicators. METHODS: Medical records of 28 children with CF who underwent chest CT in Department of Pediatric Allergy and Immunology, Cukurova University Balcali Hospital between March 2011 and January 2016 were retrospectively reviewed. Demographic data and physical examination, respiratory cultures, pulmonary function tests, and chest HRCT findings were evaluated. Patients were divided into the following two groups according to their forced expiratory volume in the first second (FEV1) values: normal FEV1 (≥ 80% of predicted values) and low FEV1 (< 80% of predicted values). Deep throat or sputum cultures were evaluated for the presence of Pseudomonas aeruginosa (PsA) and other bacteria. HRCT scans were scored using the Bhalla scoring system. RESULTS: No significant correlation was found between the Bhalla scores and sex, age group, or height percentiles. Significant relationships were found between the Bhalla score and weight (p = 0.036) and body mass index (BMI) (p = 0.032) percentiles below the third percentile, bacterial growth in the sputum/ deep throat cultures (p = 0.009), and presence of PsA (p = 0.004). Moreover, a significant correlation was found between the Bhalla score and FEV1 (r = -0.315, p = 0.0272), forced vital capacity (FVC; r = -0.381, p = 0.0178), forced expiratory flow between 25% and 75% of FVC (r = -0.229, p = 0.0431), and BMI (r = -3.368, p = 0.050). CONCLUSION: Chest HRCT is an important diagnostic tool for the pulmonary evaluation of children with CF.

Two years of newborn screening for cystic fibrosis in Turkey: Çukurova experience.

Sasihüseyinoglu AS, Altintas DU, Bisgin A, Dogruel D, Yilmaz M, Serbes M. Two years of newborn screening for cystic fibrosis in Turkey: Çukurova experience. Turk J Pediatr 2019; 61: 505-512. The severity of cystic fibrosis (CF) depends on the type of cystic fibrosis transmembrane conductance regulator (CFTR) mutation. The primary goal of newborn screening (NBS) is to decrease morbidity, mortality and associated disabilities. The National NBS for CF programme was initiated in Turkey since 01.01.2015. The aim of this study was to present two years of experience of our CF center which is located in the south of Turkey. The study population comprised of infants who were born in Adana between 1 January 2015 - 31 December 2016, referred to our CF center as part of NBS for CF and performed CFTR gene analysis. The infants were divided into three groups according to laboratory tests and symptoms as CF, CRMS (cystic fibrosis transmembrane conductance regulator-related metabolic syndrome) and false positive NBS. Between January 1, 2015 and December 31, 2016, NBS was performed in 77,437 newborns in Adana. Two hundred seven (0.26%) newborns screened were positive for CF. A total of 184 infants were included to the study. We reported 12 babies as CF with an incidence of 1:6,452. The babies diagnosed as CF constituted 6.5% of positive CF NBS. Rest of study group diagnosed with CRMS/CFSPID (54/184, 29.5%) and false positive (118/184, 64%). Positive predictive value (PPV) of NBS was 6.5%. The most common CFTR mutations were 508del, p.F1052L and p.L997 F. The implementation of CF-NBS program has been successful in Turkey. But it is too early to determine the specificity and sensitivity of the program.