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.

Is the Pediatric Sleep Questionnaire sensitive for sleep-disordered breathing in children with complex chronic disease?

PURPOSE: Sleep-disordered breathing (SDB) is a disease defined by breathing or breathing irregularities while asleep. The current study examines the association between results of polysomnography (PSG) and the Pediatric Sleep Questionnaire (PSQ), and the specificity and sensitivity of the PSQ for obstructive sleep apnea (OSA) in patients with chronic illnesses. METHODS: Demographic and clinical attributes, in addition to PSQ and PSG outcomes were examined retrospectively among patients who underwent polysomnography (PSG) at our facility between 2012 and 2021. RESULTS: Of 745 patients included in the study, 462 (62%) were male. The median age was 81 months (34-151 months). 117 of the patients (15/8%) had chronic lung disease, and 80 (10.7%) had cerebral palsy. The most common indications for PSG were symptoms of OSA (n = 426; 57.1%). According to obstructive apnea-hypopnea index (AHI), 361 patients (48.5%) had normal PSG. The median PSQ score was 0.40 (0.22-0.57). The sensitivity and specificity of the PSQ were 71.8% and 40.4%, respectively, for individuals aged 2 to 18 years. Among the disease subgroups, the cerebral palsy group had the highest sensitivity of PSQ (88.8%) for diagnosis of OSA. CONCLUSION: Questionnaires for evaluating SDB are not sensitive or specific for identification of OSA in children with chronic conditions, and PSG remains the best method.

Changing clinical characteristics of non-cystic fibrosis bronchiectasis in children.

BACKGROUND: The prevalence of non-cystic fibrosis (CF) bronchiectasis is increasing in both developed and developing countries in recent years. Although the main features remain similar, etiologies seem to change. Our aim was to evaluate the clinical and laboratory characteristics of our recent non-CF bronchiectasis patients and to compare these with our historical cohort in 2001. METHODS: One hundred four children with non-CF bronchiectasis followed between 2002 and 2019 were enrolled. Age of diagnosis, underlying etiology and microorganisms in sputum culture were recorded. Clinical outcomes were evaluated in terms of lung function tests and annual pulmonary exacerbation rates at presentation and within the last 12 months. RESULTS: Mean FEV1 and FVC %predicted at presentation improved compared to historical cohort (76.6 ± 17.1 vs. 63.3 ± 22.1 and 76.6 ± 15.1 vs. 67.3 ± 23.1, respectively; p <  0.001). There was a significant decrease in pulmonary exacerbation rate from 6.05 ± 2.88 at presentation to 3.23 ± 2.08 during follow-up (p <  0.0001). In 80.8% of patients, an underlying etiology was identified. There was an increase in primary ciliary dyskinesia (PCD) (32.7% vs. 6.3%; p = 0.001), decrease in idiopathic cases (19.2% vs. 37.8%; p = 0.03) with no change in postinfectious and immunodeficiencies as underlying etiology. Sputum cultures were positive in 77.9% of patients which was 46.9% in the historical cohort (p = 0.001). CONCLUSION: Baseline pulmonary function tests were better and distribution of underlying etiology had changed with a remarkable increase in diagnosis of PCD in the recent cohort.

Assessment of patients' baseline cystic fibrosis knowledge levels following translation and adaptation of the CF R.I.S.E translation program into Turkish.

BACKGROUND: Cystic fibrosis (CF) patients have a limited life expectancy, but significant medical advances now highlight the need for successful transition programs from pediatric to adult care. The goal of this project was to introduce the transition program CF R.I.S.E (Responsibility. Independence. Self-care. Education.) to a CF center with limited resources at Marmara University (MU). METHODS: The program was adapted and translated into Turkish with the CF Foundation's permission. A team of experts collaborated to develop educational materials for patients and families. After translation and implementation of the CF S.O.B.E program, 11 Knowledge Assessment Questionnaire (KQA) tests were administered online to the patients aged between 16 and 25 years to assess the lack of patient knowledge. RESULTS: The CF R.I.S.E program was successfully implemented within 6 months. A pilot study showed positive feedback from randomly selected patients, indicating the program's effectiveness and understandability. The mean age of the patients was 19.4 ± 2.9 years, and 42 (52%) were female. The mean forced expiratory volume (FEV1pp) was 76.3 ± 23.2. Fourteen (17.3%) and 4 (4.9%) of the patients colonized with Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA), respectively. Fifteen (18.5%) were on modulator therapy. Eleven Knowledge Assessment Questionnaires (KAQ) surveys were administered to 81 patients. The percentage of correct responses to the KAQs ranged from 47.9% to 68.3%. CONCLUSION: MU CF Center in Turkey implemented the CF S.O.B.E (Responsibility, Self-care, Independence, and Education in Turkish) program. The center aims to make the program a regular practice and expand collaboration with adult clinics. Future studies will assess its long-term impact and applicability in different health settings. The final goal is to disseminate the program's resources and promote structured transition practices across the country.

Effects of caffeine therapy for apnea of prematurity on sleep and neurodevelopment of preterm infants at 6 months of corrected age.

STUDY OBJECTIVES: To determine the differences in sleep patterns between preterm infants who received caffeine and those who did not and to evaluate the effects of caffeine therapy on early neurodevelopment. Secondarily, actigraphy and polysomnography were compared to evaluate the sleep of preterm infants. METHODS: Twenty-eight preterm infants ages 28-34 weeks admitted to a single-center Level III neonatal intensive care unit between May 2020 and May 2021 were included. Sleep was assessed by actigraphy for 72 hours with Respironics Mini-Mitter® Actiwatch-2 and Brief Infant Sleep Questionnaire at 6 months corrected age. On the first day of actigraphy, infants underwent polysomnography between 10:00 am and 3:00 pm. Neurodevelopment was evaluated by the Bayley Scales of Infant and Toddler Development-III, the Ages & Stages Questionnaire, and the Hammersmith Infant Neurological Examination. RESULTS: There were no significant differences in sleep parameters measured by actigraphy, the Brief Infant Sleep Questionnaire, and polysomnography between infants in the caffeine group (n = 12) and no-caffeine group (n = 16). Sensitivity (91.07%) and agreement rate (77.21%) for the actigraphy against polysomnography were highest at the automatic threshold. No significant differences were observed in the neurodevelopment of infants in the caffeine group compared to the no-caffeine group. CONCLUSIONS: Sleep parameters and neurodevelopmental outcomes were not different in infants at 6 months of corrected age with regard to caffeine therapy. Actigraphy at the automatic threshold can be used in infants for sleep pattern assessment. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Influence of Caffeine Therapy in Preterm Infants; URL: https://www.clinicaltrials.gov/ct2/show/NCT04376749; Identifier: NCT04376749. CITATION: Atalah YEY, Baris HE, Akdere SK, et al. Effects of caffeine therapy for apnea of prematurity on sleep and neurodevelopment of preterm infants at 6 months of corrected age. J Clin Sleep Med. 2023;19(12):2075-2085.

Improvements in body mass index of children with cystic fibrosis following implementation of a standardized nutritional algorithm: A quality improvement project.

BACKGROUND: A collaboration between the University of Michigan (UM) Cystic Fibrosis Center (CFC) and Marmara University (MU) CFC was initiated in MU through conducting Quality Improvement projects (QIP). The global aim was to improve nutritional status of children with CF (cwCF), with a specific aim to increase the mean BMI percentile (BMIp) for cwCF by 10 percentile points in 12 months. METHODS: Body mass index (BMI) percentiles of cwCF were categorized as: nutritionally adequate (BMIp ≥ 50%); at risk (BMIp 25%-49%); urgently at risk (BMIp 10%-25%); critically at risk (BMIp < 10%). Appropriate interventions were made according to BMIp category every three months. Forced expiratory volume in one-second percent predicted (FEV1pp), and health-related quality of life (HRQoL) were evaluated. RESULTS: One hundred and eight-two cwCF with a mean age of 9.1 ± 4.3 years were included in the project. Baseline BMIp increased from 25.6 to 37.2 at the 12th month (p < 0.001). In the critically at-risk group BMIp increased from 3.6 to 20.5 (p < 0.001), in the urgently at risk group from 15.9 to 30.8 (p < 0.001), in the at risk group from 37.0 to 44.2 (p < 0.079) and in the nutritionally adequate group the increase was from 66.8 to 69.5 (p < 0.301). FEV1pp also improved significantly, from 81.3 ± 20.6 to 85.9 ± 20.8 (p < 0.001). Physical functioning, eating problems, and respiratory symptoms domains of the HRQoL evaluation improved (p < 0.05). CONCLUSION: This project has led to significant improvements in BMIp, FEV1pp and HRQoL of cwCF; similar projects could easily be implemented by centers in other developing countries.

Depression, anxiety, and sleep quality of caregivers of children with spinal muscular atrophy.

BACKGROUND: The aim of this study was to evaluate the prevalence of anxiety, depression, sleep, and associated factors in caregivers of children with spinal muscular atrophy (SMA). MATERIALS AND METHODS: Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory-State (STAI-S), the State-Trait Anxiety Inventory-Trait (STAI-T), and Pittsburgh Sleep Quality Index (PSQI) were used to assess the anxiety, depression, and sleep quality of the caregivers of children with SMA. Higher scores indicated worse outcome for all three questionnaires. RESULTS: Fifty-six caregivers of children with SMA were included in the study. Median age of children was 6 (3.2-10) years and mean age of the caregivers was 37.0 ± 6.5 years. Median scores of the BDI, STAI-S, STAI-T, and PSQI were 12 (7.2-17), 35.5 (31-44), 40.5 (35-48), and 7.0 (5.0-10.0), respectively. There was a positive correlation between BDI and PSQI scores (p < 0.05). There was a negative correlation between the age of the caregivers and PSQI, BDI, STAI-T scores (p = 0.01, r = -0.341; p = 0.006, r = -0.364; p = 0.003, r = -0.395, respectively). There was a negative correlation between the age of the patients and the PSQI scores of the caregivers (p = 0.01, r = -0.33). There was a negative correlation between BDI scores and household income (p = 0.01, r = -0.34). CONCLUSION: Caregivers of children with SMA had elevated depression and anxiety levels and they also had decreased sleep quality. Economic and social support resources are needed to help caregivers of those children.

Implementation of standardized cystic fibrosis care algorithm to improve the center data-quality improvement project international collaboration.

BACKGROUND: A collaboration between the University of Michigan (U of M) Cystic Fibrosis Center (CFC) and Marmara University (MU) CFC was initiated to improve the health status of people with cystic fibrosis (pwCF) at MU through implementing Quality Improvement (QI) initiatives. The main aim was to improve lung function in children with FEV1pp <80. The secondary aim was to assess the changes in health related quality of life. METHODS: Included in the project were pwCF who received cystic fibrosis (CF) care at the MU CFC and were 6-18 years of age with an FEV1pp <80. Flow charts were created and a standardized CF care algorithm was implemented. Weekly case review were done to develop individualized treatment plans. Appropriate intervention was applied and patient data were assessed at baseline, 3, 6, 9 and 12 months. The Cystic Fibrosis Revised Questionnaire (CFQ-R) was completed. RESULTS: 55 pwCF were included (mean age:11.8 ± 3.3 years). Mean FEV1pp (SD) at baseline, 6 and 12 month was 63.7 (14.6), 66.9 (16.6), 70.4 (19.2), respectively, with a relative increase of 5.0% in 6 months (p:0.002) and 10.5% in 12 months compared to baseline (p<0.001). Physical functioning, eating problems and respiratory symptoms domains of the CFQ-R questionnaire were improved at the end of the one year for 6-13 (p = 0.024, p = 0.009, p = 0.002) and 13-18 year olds (p = 0.013, p = 0.002, p = 0.038). CONCLUSION: There was significant improvement in pwCF with FEV1<80%pp after implementing this QI project. The processes and assessments used can be adopted by other low-middle income countries to improve similar measures.

COVID-19 disease characteristics in different pediatric age groups.

INTRODUCTION: Little is known about the COVID-19 disease characteristics and differences between different pediatric age groups. This study aimed to investigate the disease characteristics according to age groups. METHODOLOGY: We conducted a retrospective, single-center study of pediatric COVID-19 in a tertiary care hospital in Turkey. The patients were divided into three groups: 15 days-24 months old (Group 1), 25-144 months old (Group 2), and 145-210 months old (Group 3) according to age. RESULTS: A total of 139 pediatric patients with COVID-19 were examined. Twenty-nine patients (20.9%) were in Group 1, 52 (37.4%) were in Group 2, 58 (41.7%) were in Group 3. Thirty-nine patients (28.1%) were hospitalized. The most common symptoms were cough (55.4%) and fever (51.8%). The median chest X-ray (CXR) score of hospitalized patients was 1 (min 0-max 7), and the median CXR score of outpatients was 1 (min 0-max 6). Fever was significantly more frequent in Group 1, and chest pain was more frequent in Group 3. Group 1 had significantly higher WBC, lymphocyte, thrombocyte counts, AST, LDH, D-dimer, and Troponin T levels but lower hemoglobin, total protein, and albumin levels. The treatment included antibiotics, oseltamivir, hydroxychloroquine, and supportive therapy. Only one patient (0.7%) received non-invasive mechanical ventilatory support. CONCLUSIONS: As we know the clinical course of COVID-19 in children is less severe than in adults. We also found significant differences in both clinical and laboratory findings between different pediatric age groups which supports the theory that disease pathogenesis is highly variable according to age.

Successful treatment of allergic bronchopulmonary aspergillosis with posaconazole in a child with cystic fibrosis: Case report and review of the literature.

Allergic bronchopulmonary aspergillosis (ABPA) is recognized as a rare, progressive, allergic disorder in patients with cystic fibrosis (CF) and asthma. Treatment of ABPA mainly includes systemic corticosteroids (CSs) and antifungal agents. Here, we report posaconazole treatment in a 9-year-old male child with ABPA and also review the literature on antifungal management of ABPA. The child with CF was admitted to the emergency room with complaints of fever, productive cough, and acute dyspnea. Auscultation of the lungs revealed obvious bilateral fine crackles and bilateral rhonchus. He was started with intravenous meropenem and amikacin for acute exacerbation. The patient was diagnosed with ABPA because of his failure to respond to antibiotherapy, elevated serum immunoglobulin (Ig) E, specific IgE, to Aspergillus fumigatus levels and sputum growth of A. fumigatus. He was successfully treated with posaconazole with marked clinical and laboratory improvement and no adverse effects. CSs and antifungal agents are the mainstay of therapy in patients with ABPA based on observational studies in children. Posaconazole is a useful treatment option for patients with ABPA.

Novel mutations and deletions in cystic fibrosis in a tertiary cystic fibrosis center in Istanbul.

BACKGROUND: Cystic fibrosis (CF) genotyping has garnered increased attention since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 led to the identification of over 1700 mutations on chromosome 7. Yet, little is known about the genetic profile of CF patients in Turkey. This study sought to determine the mutation distribution among CF patients seeking care at Marmara University. METHODS: Two hundred fifty previously diagnosed CF patients were included in the study. CFTR gene exons 1 to 27 were amplified by a polymerase chain reaction and whole DNA sequencing was performed. Duplications and deletions were investigated by the multiplex ligation-dependent probe amplification (MLPA) technique in patients with one or two unidentified mutations in sequence analysis. RESULTS: CFTR mutation analysis revealed 80 mutations and five large deletions were present in our study population. The five most common mutations were (delta) F508 (c.1521-1523delCTT) (28.4%), 1677delTA (c.1545-1546delTA) (6.4%), 2789 + 5G- > A (c.2657 + 5G > A) (5.8%), N1303K (c.3909C > G) (2.4%), and c.2183AA- > G (c.2051-2052delAAinsG) (4.0%). Large deletions were found in 16 patients. Four novel mutations and two novel deletions were detected in this study. CONCLUSIONS: We have identified four novel mutations and two novel deletions using next-generation DNA sequencing and the MLPA technique and obtained an overall mutation detection rate of 91.4%. Detection of novel variants in CF patients will assist in genetic counseling and in determining appropriate patients for new therapies.

Clinical and polysomnographic features of children evaluated with polysomnography in pediatric sleep laboratory.

AIM: Sleep disordered breathing is a common problem in childhood that encompasses a spectrum of disorders extending from primary snoring to obstructive sleep apnea. This study aims to investigate the results of children undergoing evaluation with polysomnography in the sleep laboratory of a tertiary care hospital. MATERIAL AND METHODS: Demographic and clinical features as well as sleep associated symptoms, scores of pediatric sleep questionnaire and Pittsburgh sleep quality index and polysomnography results are retrospectively evaluated. RESULTS: Totally 131 patients were evaluated, of which 47.3% (n=62) were females and 52.7% (n=69) were males. Mean age was 101.85±59.15 months at the time of the study. Fifty percent (n=59) of patients complained of snoring and 43.7% (n=52) of patients complained of apnea during sleep. Mean obstructive hypopnea-apnea index was 5.12±11.72. Mean obstructive hypopnea-apnea index of snorers (6.93±13.53) was significantly higher than the mean obstructive hypopnea-apnea index of nonsnorers (2.32±5.43) (p=0.011). Mean obstructive hypopnea-apnea index of patients experiencing apnea during sleep (7.52±14.25) was significantly higher than the mean obstructive hypopnea-apnea index of the children who do not experience apnea (2.61±5.84) (p=0.008). No significant correlation was observed between obstructive hypopnea-apnea index and scores of pediatric sleep questionnaire and Pittsburgh sleep quality index. The prevalence of obstructive sleep apnea was 33.6% (n=44). Forty nine patients (39.8%) were treated after polysomnography. Frequently suggested treatment options were noninvasive mechanical ventilation (n=23, 46.9%), intranasal steroid (n=15, 30.6%), montelukast (n=11, 22.4%) and adenotonsillectomy (n=9, 18.4%). CONCLUSIONS: Polysomnography is the gold standard in the diagnosis of sleep disordered breathing in children. Pediatricians should be able to recognize early signs and symptoms of sleep disordered breathing and refer the patients in risk to centers where evaluation with polysomnography is available.

Neurologic Adverse Events Associated with Voriconazole Therapy: Report of Two Pediatric Cases.

Although voriconazole, a triazole antifungal, is a safe drug, treatment with this agent is associated with certain adverse events such as hepatic, neurologic, and visual disturbances. The current report presents two cases, one a 9-year-old boy and the other a 17-year-old girl, who experienced neurologic side effects associated with voriconazole therapy. Our aim is to remind readers of the side effects of voriconazole therapy in order to prevent unnecessary investigations especially for psychological and ophthalmologic problems. The first case was a 9-year-old boy with cystic fibrosis and invasive aspergillosis that developed photophobia, altered color sensation, and fearful visual hallucination. The second case was a 17-year-old girl with cystic fibrosis and allergic bronchopulmonary aspergillosis, and she experienced photophobia, fatigue, impaired concentration, and insomnia, when the dose of voriconazole therapy was increased from 12 mg/kg/day to 16 mg/kg/day. The complaints of the two patients disappeared after discontinuation of voriconazole therapy. Our experience in these patients reminded us of the importance of being aware of the neurologic adverse events associated with voriconazole therapy in establishing early diagnosis and initiating prompt treatment. In addition, although serum voriconazole concentration was not measured in the present cases, therapeutic drug monitoring for voriconazole seems to be critically important in preventing neurologic side effects in pediatric patients.