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.

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.

Evaluation of specificity and sensitivity of IRT/IRT protocol in the cystic fibrosis newborn screening program: 6-year experience of three tertiary centers.

We aimed to evaluate cutoff values of immunoreactive trypsinogen (IRT)/IRT and determine relationship between IRT values and clinical characteristics of children with cystic fibrosis (CF). This study is cross-sectional study. Data of children with positive newborn screening (NBS) between 2015 and 2021 were evaluated in three pediatric pulmonology centers. Age at admission, sex, gestational age, presence of history of meconium ileus, parental consanguinity, sibling with CF, and doll-like face appearance, first and second IRT values, sweat chloride test, fecal elastase, fecal fat, biochemistry results, and age at CF diagnosis were recorded. Sensitivity and specificity of IRT cutoff values were evaluated. Of 815 children with positive NBS, 58 (7.1%) children were diagnosed with CF. Median values of first and second IRT were 157.2 (103.7-247.6) and 113.0 (84.0-201.5) µg/L. IRT values used in current protocol, sensitivity was determined as 96.6%, specificity as 17.2% for first IRT, and 96.6% sensitivity, 20.5% specificity for second IRT. Positive predictive value (PPV) was determined as 7.1%. When cutoff value for first IRT was estimated as 116.7 µg/L, sensitivity was 69.0% and specificity was 69.6%, and when cutoff value was set to 88.7 µg/L for second IRT, sensitivity was 69.0% and specificity was 69.0%. Area under curve was 0.757 for first and 0.763 for second IRT (p < 0.001, p < 0.001, respectively). PPV was calculated as 4.3%.    Conclusion: Although sensitivity of CF NBS is high in our country, its PPV is significantly lower than expected from CF NBS programs. False-positive NBS results could have been overcome by revising NBS strategy. What is Known: • Although immunoreactive trypsinogen elevation is a sensitive test used in cystic fibrosis newborn screening, its specificity is low. • In countries although different algorithms are used, all strategies begin with the measurement of immunoreactive trypsinogen in dried blood spots. What is New: • In our study, it was shown that use of the IRT/IRT protocol for cystic fibrosis newborn screening is not sufficient for the cut-off values determined by the high number of patients. • Newborn screening strategy should be reviewed to reduce false positive newborn screening results.

Psychological status of mothers of children with cystic fibrosis and primary ciliary dyskinesia.

OBJECTIVES: We aimed to investigate depression, burnout, attitude, and burden of caregivers of children with cystic fibrosis (CF), and especially caregivers of children with primary ciliary dyskinesia (PCD) due to limited number of studies on this topic, and to compare them according to their children's clinical status. METHODS: Clinical features and demographic data of children and their families were asked from caregivers in four pediatric pulmonology centers. Beck Depression Inventory, Maslach Burnout Inventory, Zarit Caregiver Burden Scale, and Parental Attitude Research Instrument were administered to caregivers in both groups. Results were compared between the two groups. RESULTS: In total, 131 children with CF and 39 with PCD and their caregivers were involved in the study. All primary caregivers were mothers in both groups. Depression, burnout, and burden scores of mothers of children with CF were significantly higher than mothers of children with PCD (p = 0.017, p = 0.024, p = 0.038, respectively). Burnout was higher in both CF and PCD groups with low family income (p = 0.022, p = 0.034). Number of hospital visits in the previous 6 months was correlated with burnout in both CF and PCD groups (r = 0.207, p = 0.034; r = 0.352, p = 0.044). CONCLUSIONS: Although mothers with children with CF have higher levels of depression, burnout, burden, and negative attitudes toward children than mothers with children with PCD, these are also significantly high in mothers with children with PCD. Psychological problems of mothers of children with CF and PCD may increase with frequent hospital visits, hospitalizations, low family income, number of children, and chronic disease in another child.

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.

Thoracic Air Leak Syndrome, Pulmonary Aspergillosis, and COVID-19 Pneumonia After Allogeneic Stem Cell Transplantation in a Child With Myelodysplastic Syndrome.

Thoracic air leak syndromes (TALS) are very rare among the noninfectious pulmonary complications (PCs). They can either be idiopathic or have several risk factors such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), graft versus host disease and rarely pulmonary aspergillosis. We present a 14-year-old girl with hypoplastic myelodysplastic syndrome who developed graft versus host disease on day 60, TALS on day 150, bronchiolitis obliterans syndrome on day 300, pulmonary aspergillosis on day 400 and COVID-19 pneumonia on day 575 after allo-HSCT. This is the first report of a child who developed these subsequent PCs after allo-HSCT. Therefore, the manifestations of these unfamiliar PCs like TALS and COVID-19 pneumonia, and concomitant pulmonary aspergillosis with management options are discussed.

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 Genetic Analysis of Cystic Fibrosis Patients With Seven Novel Mutations in the CFTR Gene in the Central Anatolian Region of Turkey.

BACKGROUND: Cystic fibrosis, a pulmonary disease which is an autosomal recessive, inherited, multisystemic genetic disease commonly seen in the Caucasian race, is the most frequent cause of mortality and morbidity. So far, more than 2000 disease-causing gene variants have been found and this number has been increasing with the studies conducted. Although there is not yet enough data that include the Turkish population, the recent increase of studies is noteworthy. AIMS: To discover the genetic variation in patients diagnosed with cystic fibrosis in the Central Anatolian region. STUDY DESIGN: Cross-sectional study. METHODS: The study was carried out in the Central Anatolian region in 3 pediatric pulmonology departments (Kayseri, Konya, and Ankara) in Turkey between July 2014 and December 2017. The Sanger and Next Generation Sequence analyses were used for exon and exon-intron boundaries in the cystic fibrosis transmembrane conductance regulatory (CFTR) gene, and in selected patients, mutation analysis was performed using the Multiplex Ligation-dependent Probe Amplification technique for large deletions and duplications. RESULTS: CFTR gene analysis was performed for 316 patients and 215 of them were genetically diagnosed with cystic fibrosis. Sixtythree different variants were defined in these patients and 7 of these were large deletions/duplications detected with the MLPA method. The most frequent variants were F508del (29.6%), G85E (8.2%), N1303K (8.2%), Y515* (7.5%), and G542* (3.4%). CONCLUSION: Using sequencing and Multiplex Ligation-dependent Probe Amplification methods, the identification of seven new mutations that were not previously reported in the literature contributes to a better understanding of the heterogeneous nature of CFTR mutations in the Turkish population. When no mutations are detected (pathogenic/probably pathogenic) in clinically compatible cases, Multiplex Ligationdependent Probe Amplification analysis contributes significantly to the diagnosis.

Níveis de Tiol Sérico e Homeostase Tiol/Dissulfeto em Pacientes com Doença Valvar Mitral Reumatismal e em Sujeitos Saudáveis / Serum Thiol Levels and Thiol/Disulfide Homeostasis in Patients with Rheumatic Mitral Valve Disease and Healthy Subjects

Resumo Fundamento A doença valvar mitral reumatismal (DVMR) é a apresentação mais comum das doenças cardíacas reumáticas (DCR). Os processos de inflamação e fibrose também têm papéis significativos em sua patogênese. Estudos recentes demonstram que os tióis e o tiol-dissulfeto são marcadores de stress oxidativo inéditos e promissores. Objetivos O objetivo deste estudo foi avaliar diferenças entre os níveis de tiol sérico e de tiol-dissulfeto em pacientes com DVMR e no grupo de controle. Métodos Noventa e dois pacientes com DVMR foram cadastrados no estudo. Cinquenta e quatro sujeitos saudáveis, e com correspondência de sexo e idade em relação ao grupo de estudo, também foram incluídos no estudo como um grupo de controle. Foram investigados os níveis de tiol nos pacientes com DVMR e o grupo de controle. Os p-valores menores que 0,05 foram considerados estatisticamente significativos. Resultados Os pacientes com DVMR apresentaram pressão sistólica da artéria pulmonar (PSAP) e níveis de diâmetro do átrio esquerdo (AE) mais altos que os do grupo de controle. Os níveis de tiol nativo (407±83 μmol/L vs. 297±65 μmol/L, p<0,001) e tiol total (442±82 μmol/L vs. 329±65 μmol/L, p<0,001) são mais altos no grupo de controle. Níveis de dissulfeto (16,7±4,9 μmol/L vs. 14,8±3,7 μmol/L, p=0,011) são mais altos no grupo de pacientes com DVMR. Foi identificada uma correlação positiva entre as razões dissulfeto/tiol nativo e dissulfeto/tiol total com PSAP, diâmetro de AE, e gravidade da EMi. A razão dissulfeto/tiol total é significativamente mais alta em pacientes com EMi grave que em pacientes com EMi leve a moderada. Conclusões Até onde se sabe, este é o único estudo que avaliou a homeostase tiol/dissulfeto como um preditor inédito, que está relacionado de forma mais próxima à DVMR e à gravidade da EMi.

Abstract Background Rheumatic mitral valve disease (RMVD) is the most common presentation of rheumatic heart disease (RHD). Inflammation and fibrosis processes also play significant roles in its pathogenesis. Recent studies showed that thiols and thiol-disulfide are promising novel oxidative stress markers. Objectives The present study aimed to evaluate differences in the serum thiol and thiol-disulfide levels in patients with RMVD and the control group. Methods Ninety-two patients with RMVD were enrolled in the study. Fifty-four healthy subjects, age, and gender-matched with the study group, were also included in the study as a control group. This study investigated thiol levels in patients with RMVD and the control group. P-values lower than 0.05 were considered statistically significant. Results The patients with RMVD presented higher systolic pulmonary artery pressure (SPAP) and left atrial (LA) diameter levels than the control group. Native thiol (407±83 μmol/L vs. 297±65 μmol/L, p<0.001) and total thiol (442±82 μmol/L vs. 329±65 μmol/L, p<0.001) levels were higher in the control group. Disulfide (16.7±4.9 μmol/L vs. 14.8±3.7 μmol/L, p=0.011) levels were higher in the group of patients with RMVD. A positive correlation was found between disulfide/native and disulfide/total thiols ratio with SPAP, LA diameter, and MS severity. Disulfide/total thiols ratio was significantly higher in patients with severe MS than with mild to moderate MS patients. Conclusions To the best of our knowledge, this is the only study of its kind that has evaluated thiol/disulfide homeostasis as a novel predictor, which was more closely related to RMVD and the severity of MS.

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.

Pulmonary Mycobacterium abscessus Infection in an 11-Year-Old Child, Successfully Treated with Inhaled/Parenteral Amikacin: A Case Report and Review of Literature.

Mycobacterium abscessus appears to be increasing cause of pulmonary infection in children with underlying risk factors including cystic fibrosis, chronic lung disease and immunodeficiency syndromes. We present a case of pulmonary M. abscessus infection in a pediatric patient with primary ciliary dyskinesia and he was successfully treated with parenteral amikacin, linezolid and oral clarithromycin combined with inhaled amikacin. Clinical improvement was observed after adding inhaled amikacin to the treatment.

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

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

Effect of the COVID-19 pandemic on anxiety among children with cystic fibrosis and their mothers.

BACKGROUND: We aimed to evaluate anxiety among children with cystic fibrosis (CF) and their mothers related to the COVID-19 pandemic. METHODS: A total of 45 patients with CF and their mothers were enrolled in the study together with 90 age-matched healthy children and their mothers as a control group. The State and Trait Anxiety Inventory (STAI) was administered by teleconference with children aged 13 to 18 years old and their mothers. The STAI for children was administered with children aged 9 to 12 years. Results were compared with age-matched healthy children and their mothers. The relationship between anxiety scores of children with CF and their mothers was evaluated by comparing with clinical data of children with CF. At the conclusion of the teleconference, mothers were asked whether their anxiety had changed as a result of the interview. RESULTS: It was found that healthy children aged 13 to 18 years had higher state anxiety scores than age-matched children with CF. Mothers of children with CF had higher trait anxiety scores, especially those of children aged 0 to 12 years, than mothers of healthy children (P < .05). For mothers of children with CF, state anxiety scores were higher among those whose children had chronic Pseudomonas infection (P < .05). Most mothers of children with CF stated that their anxiety decreased following the interview. CONCLUSION: The COVID-19 pandemic may increase anxiety among mothers of children with CF as well those with healthy children. However, COVID-19 had no effect on the anxiety of children with CF. Informing parents of children with CF about COVID-19 by teleconference may decrease anxiety.

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.

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.

Postinfectious bronchiolitis obliterans masked by misdiagnosis as asthma.

OBJECTIVES: Asthma and postinfectious bronchiolitis obliterans (PIBO) have similar clinical findings, and PIBO may be misdiagnosed with asthma. This study aimed to determine the clinical features of PIBO in children and the causes of delay in its diagnosis. METHODS: We retrospectively evaluated all patients diagnosed with PIBO in four pediatric pulmonology centers between 2007 and 2018. In total, 64 PIBO patients were retrospectively reviewed. We compared the clinical and laboratory differences between PIBO patients who had initially been misdiagnosed with asthma and correctly diagnosed with PIBO. RESULTS: Of the 64 patients, 22 (34.4%) had initially been misdiagnosed with asthma. Adenovirus was the most common infectious agent in children. The age upon diagnosis was older, and the symptom duration was significantly longer in patients misdiagnosed with asthma (P < .05). There were no statistical differences in terms of sex, history of prematurity, duration of hospitalization, treatment, history of oxygen or mechanical ventilation support, pulmonary function test (PFT) results and asthma-predisposing findings between the two groups (P > .05). CONCLUSIONS: Patients with PIBO who had initially been misdiagnosed with asthma were correctly diagnosed at older ages and had longer symptom duration. Asthma may mask PIBO diagnosis by the similarity of symptoms and the clinical response to inhaled ß2-agonist or steroid treatment. PFTs may not help clinicians because of the age of children. The delay in the diagnosis of PIBO is probably attributable to the fact that some clinicians fail to include PIBO in the differential diagnosis when there is no clinical response to asthma medication.

Respuesta de las citocinas a la combinación de simbióticos y lactoferrina en recién nacidos de muy bajo peso al nacer: ensayo controlado aleatorizado / Cytokine responses to symbiotic and lactoferrin combination in very low birth weight neonates: a randomized control trial

Introducción. Los probióticos y prebióticos presentan beneficios potenciales en la inflamacióncrónica de las mucosas, incluida la prevención de la enterocolitis necrosante. No obstante, los mecanismos y resultados de estos efectos inmunomoduladores son confusos. El objetivo fue investigar la respuesta de las citocinas a Lactobacillus y Bifidobacterium asociados con fructo- y galactooligosacáridos (simbióticos) y lactoferrina en recién nacidos de muy bajo peso al nacer.Población y métodos. Se asignó aleatoriamente a lactantes con ≤32 semanas de gestación y ≤1500 g de peso para recibir simbióticos o 1 ml de agua destilada como placebo desde la primera alimentación hasta el alta. Se obtuvieron muestras de sangre los días posnatales 0 ± 2, 14 ± 2 y 28 ± 2, y se midieron interferón-γ, interleucina (IL)-5, IL-10 e IL-17A.Resultados. En el grupo del estudio (n = 25), la concentración de IL-10 disminuyó a lo largo del estudio (p = 0,011), pero no cambió en el grupo de referencia. La concentración de IL-5 se mantuvo constante los primeros 14 días y luego disminuyó significativamente (p= 0,042) en el grupo del estudio, mientras que aumentó en los primeros 14 días (p = 0,019) y luego disminuyó en 28 días (p = 0,011) en el grupo de referencia (n = 25).La concentración de otras citocinas no cambió a lo largo del estudio.Conclusión. El uso combinado de probióticos con oligosacáridos y lactoferrina estuvo asociado con una disminución en la concentración de IL-10, pero no se observó un cambio en las otras citocinas.

Introduction. Probiotics and prebiotics, which are multifunctional agents, have potential benefits in chronic mucosal inflammation, including the prevention of necrotizing enterocolitis. However, the mechanisms and the results of these immunomodulatory effects are not clear. This study aimed to investigate the cytokine response to the combination of Lactobacillus and Bifidobacterium together with fructo- and galacto-oligosaccharides (symbiotic) and lactoferrin in very low birth weight neonates.Population and Methods. Infants ≤ 32 GWs and ≤ 1,500 g were randomly assigned to receive a symbiotic combination or 1 ml distilled water as placebo starting with the first feed until discharge. Blood samples were obtained at postnatal 0 ± 2, 14 ± 2, and 28 ± 2 days, and the serum levels of interferon-γ, interleukin (IL)-5, IL-10, and IL-17A were measured.Results. In the study group (n = 25), the IL-10 levels decreased throughout the study period (p = 0.011) but did not change in the control group. The IL-5 levels remained steady in the first 14 days and decreased significantly thereafter (p = 0.042) in the study group, whereas they increased in the first 14 days (p = 0.019), and then decreased in 28 days (p = 0.011) in the control group (n = 25). The levels of the other cytokines did not change throughout the study period.Conclusion.The combined use of probiotics with oligosaccharides and lactoferrin was associated with a decrease in IL-10 levels, but no change was observed in the other cytokines.

Cytokine responses to symbiotic and lactoferrin combination in very low birth weight neonates: a randomized control trial. / Respuesta de las citocinas a la combinación de simbióticos y lactoferrina en recién nacidos de muy bajo peso al nacer: ensayo controlado aleatorizado.

INTRODUCTION: Probiotics and prebiotics, which are multifunctional agents, have potential benefits in chronic mucosal inflammation, including the prevention of necrotizing enterocolitis. However, the mechanisms and the results of these immunomodulatory effects are not clear. This study aimed to investigate the cytokine response to the combination of Lactobacillus and Bifidobacterium together with fructo- and galacto-oligosaccharides (symbiotic) and lactoferrin in very low birth weight neonates. POPULATION AND METHODS: Infants ≤ 32 GWs and ≤ 1,500 g were randomly assigned to receive a symbiotic combination or 1 ml distilled water as placebo starting with the first feed until discharge. Blood samples were obtained at postnatal 0 ± 2, 14 ± 2, and 28 ± 2 days, and the serum levels of interferon-y, interleukin (IL)-5, IL-10, and IL-17A were measured. RESULTS: In the study group (n = 25), the IL-10 levels decreased throughout the study period (p = 0.011) but did not change in the control group. The IL-5 levels remained steady in the first 14 days and decreased significantly thereafter (p = 0.042) in the study group, whereas they increased in the first 14 days (p = 0.019), and then decreased in 28 days (p = 0.011) in the control group (n = 25). The levels of the other cytokines did not change throughout the study period. CONCLUSION: The combined use of probiotics with oligosaccharides and lactoferrin was associated with a decrease in IL-10 levels, but no change was observed in the other cytokines.

Introducción: Los probióticos y prebióticos presentan beneficios potenciales en la inflamación crónica de las mucosas, incluida la prevención de la enterocolitis necrosante. No obstante, los mecanismos y resultados de estos efectos inmunomoduladores son confusos. El objetivo fue investigar la respuesta de las citocinas a Lactobacillus y Bifidobacterium asociados con fructo- y galactooligosacáridos (simbióticos) y lactoferrina en recién nacidos de muy bajo peso al nacer. Población y métodos: Se asignó aleatoriamente a lactantes con ≤32 semanas de gestación y ≤1500 g de peso para recibir simbióticos o 1 ml de agua destilada como placebo desde la primera alimentación hasta el alta. Se obtuvieron muestras de sangre los días posnatales 0 ± 2, 14 ± 2 y 28 ± 2, y se midieron interferón-y, interleucina (IL)-5, IL-10 e IL-17A. Resultados: En el grupo del estudio (n = 25), la concentración de IL-10 disminuyó a lo largo del estudio (p = 0,011), pero no cambió en el grupo de referencia. La concentración de IL-5 se mantuvo constante los primeros 14 días y luego disminuyó significativamente (p = 0,042) en el grupo del estudio, mientras que aumentó en los primeros 14 días (p = 0,019) y luego disminuyó en 28 días (p = 0,011) en el grupo de referencia (n = 25).La concentración de otras citocinas no cambió a lo largo del estudio. Conclusión: El uso combinado de probióticos con oligosacáridos y lactoferrina estuvo asociado con una disminución en la concentración de IL-10, pero no se observó un cambio en las otras citocinas.

Cystic fibrosis in Turkey: First data from the national registry.

BACKGROUND: Cystic fibrosis (CF) care has been implemented in Turkey for a long time; however, there had been no patient registry. For this purpose, the Turkish National CF Registry was established. We present the first results of registry using data collected in 2017. METHODS: The data were collected using a data-entry software system, which was accessed from the internet. Demographic and annually recorded data consisted of 15 and 79 variables, respectively. RESULTS: There were 1170 patients registered from 23 centers; the estimated coverage rate was 30%. The median age at diagnosis was 1.7 years (median current age: 7.3 years); 51 (4.6%) patients were aged over 18 years. Among 293 patients who were under 3 years of age, 240 patients (81.9%) were diagnosed through newborn screening. Meconium ileus was detected in 65 (5.5%) patients. Genotyping was performed in 978 (87.4%) patients and 246 (25.2%) patients' mutations were unidentified. The most common mutation was deltaF508 with an allelic frequency of 28%, followed by N1303K (4.9%). The median FEV1% predicted was 86. Chronic colonization with Pseudomonas aeruginosa was seen in 245 patients. The most common complication was pseudo-Bartter syndrome in 120 patients. The median age of death was 13.5 years in a total of 15 patients. CONCLUSIONS: Low coverage rate, lack of genotyping, unidentified mutations, and missing data of lung functions are some of our greatest challenges. Including data of all centers and reducing missing data will provide more accurate data and help to improve the CF care in Turkey in the future.