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.

Evaluation of the psychological status of mothers of children with cystic fibrosis and the relationship between children's clinical status.

AIM: In this study, we aimed to determine the psychosocial status of primary care givers of children with cystic fibrosis (CF) and its relationship with the clinical scores of children with CF. METHODS: Thirty-six patients with CF and their primary care givers were assessed. A personal information form, as well as the Parent Attitude Research Instrument, Maslach Burnout Inventory, Beck Depression Scale and modified Shwachman-Kulczycki Score, were used for data collection. RESULTS: All the CF children's primary care givers were their mothers. The mothers' occupation and educational level affected their child-rearing attitudes (P < 0.05). Furthermore, the frequency of hospital visits and hospitalizations was associated with increased emotional exhaustion, depression and negative attitudes towards child-rearing (P < 0.05). Higher levels of emotional exhaustion in mothers were associated with increased depersonalization and depression, while personal accomplishment was associated with lower levels of depression (P < 0.05). Depression was present in 69.4% of mothers, and its severity was correlated with their children having a poor clinical status. Moreover, increased depression was associated with increased negative attitudes towards child-rearing (P < 0.05). CONCLUSION: The rate of depression is high in mothers of children with CF. These mothers displayed a negative attitude towards child-rearing, along with the disease, which was more severe in their children. These mothers should undergo routine psychosocial screening, and support should be given to those in need.

Lung disease caused by ABCA3 mutations.

BACKGROUND: Knowledge about the clinical spectrum of lung disease caused by variations in the ATP binding cassette subfamily A member 3 (ABCA3) gene is limited. Here we describe genotype-phenotype correlations in a European cohort. METHODS: We retrospectively analysed baseline and outcome characteristics of 40 patients with two disease-causing ABCA3 mutations collected between 2001 and 2015. RESULTS: Of 22 homozygous (15 male) and 18 compound heterozygous patients (3 male), 37 presented with neonatal respiratory distress syndrome as term babies. At follow-up, two major phenotypes are documented: patients with (1) early lethal mutations subdivided into (1a) dying within the first 6 months or (1b) before the age of 5 years, and (2) patients with prolonged survival into childhood, adolescence or adulthood. Patients with null/null mutations predicting complete ABCA3 deficiency died within the 1st weeks to months of life, while those with null/other or other/other mutations had a more variable presentation and outcome. Treatment with exogenous surfactant, systemic steroids, hydroxychloroquine and whole lung lavages had apparent but many times transient effects in individual subjects. CONCLUSIONS: Overall long-term (>5 years) survival of subjects with two disease-causing ABCA3 mutations was <20%. Response to therapies needs to be ascertained in randomised controlled trials.

Is Hyperuricemia Overlooked when Treating Pediatric Tuberculosis Patients with Pyrazinamide?

The treatment of tuberculosis (TB) requires long-term multiple drug use. Hyperuricemia is frequently reported in adults, but there are few data for the pediatric population. This study aimed to review drug-related side effects in pediatric patients that received treatment for TB. Patients with active TB undergoing treatment were followed for drug-related side effects. During the 7 year period, 23 patients with a mean age of 7.9 ± 4.66 years were treated. Drug-related side effects were observed in 14 patients. Hyperuricemia occurred in 12 of the 14 patients, vs. hepatotoxicity in 2. In all, eight of the patients with hyperuricemia had ≥2 episodes during pyrazinamide (PZA) therapy. Based on these findings, we devised an algorithm that could be used for the management of hyperuricemia in patients receiving PZA because of TB, and recommend that hyperuricemia be closely monitored during PZA therapy.

Cyclosporine A in children with ABCA3 deficiency.

BACKGROUND: Biallelic ATP-binding cassette subfamily A member 3 (ABCA3) variants can cause interstitial lung disease in children and adults, for which no proven treatments exist. Recent in vitro evidence suggested that cyclosporine A (CsA) could correct some ABCA3 variants, however for other variants this is unknown and no data in patients exist. METHODS: We retrieved the clinical data of two children aged 2 and 4 years carrying homozygous ABCA3 variants (G210C and Q1045R, respectively) and empiric CsA treatment from the Kids Lung Register database. In vitro experiments functionally characterized the two variants and explored the effects of CsA alone or combined with hydroxychloroquine (HCQ) in a human alveolar epithelial cell line (A549) derived from adenocarcinoma cells. RESULTS: Six weeks following the introduction of CsA, both children required a reduced O2 flow supply, which then remained stable on CsA. Later, when CsA was discontinued, the clinical status of the children remained unchanged. Of note, the children simultaneously received prednisolone, azithromycin, and HCQ. In vitro, both ABCA3 variants demonstrated defective lysosomal colocalization and impaired ABCA3+ vesicle size, with proteolytic cleavage impairment only in Q1045R. CsA alone corrected the trafficking impairment and ABCA3+ vesicle size of both variants with a variant-specific effect on phosphatidylcholine recycling in G210C. CsA combined with HCQ were additive for improving trafficking of ABCA3 in G210C, but not in Q1045R. CONCLUSIONS: CsA treatment might be helpful for certain patients with ABCA3 deficiency, however, currently strong clinical supporting evidence is lacking. Appropriate trials are necessary to overcome this unmet need.

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.

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.

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.

Persistent tachypnea of infancy: Follow up at school age.

BACKGROUND: Persistent tachypnea of infancy (PTI) is a rare pediatric lung disease of unknown origin. The diagnosis can be made by clinical presentation and chest high resolution computed tomography after exclusion of other causes. Clinical courses beyond infancy have rarely been assessed. METHODS: Patients included in the Kids Lung Register diagnosed with PTI as infants and now older than 5 years were identified. Initial presentation, extrapulmonary comorbidities, spirometry and clinical outcome were analyzed. RESULTS: Thirty-five children older than 5 years with PTI diagnosed as infants were analyzed. At the age of 5 years, 74% of the patients were reported as asymptomatic and did not develope new symptoms during the observational period at school-age (mean, 3.9 years; range, 0.3-6.3). At the age of about 10 years, none of the symptomatic children had abnormal oxygen saturation during sleep or exercise anymore. Lung function tests and breathing frequency were within normal values throughout the entire observational period. CONCLUSIONS: PTI is a pulmonary disease that can lead to respiratory insufficiency in infancy. As at school age most of the previously chronically affected children became asymptomatic and did not develop new symptoms. We conclude that the overall clinical course is favorable.

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.

Macrophage activation syndrome due to Nocardia spp in a pediatric patient with cystic fibrosis.

Nocardia spp is a gram-positive aerobic filamentous bacteria that causes pulmonary and systemic infections, especially in patients with immunosuppression or chronic lung diseases. It is rarely reported in children with cystic fibrosis. Macrophage activation syndrome is a life-threatening disease with an excessive inflammatory response usually triggered by infections. There are few reports in cystic fibrosis related to macrophage activation syndrome. Herein we report a child with cystic fibrosis who had macrophage activation syndrome due to Nocardia infection.

Successful embolization in childhood hemoptysis due to abnormal systemic arterial bleeding of the lung and review of the literature.

BACKGROUND AND AIMS: Hemoptysis in children is a rare but potentially life-threatening symptom of an underlying respiratory tract abnormality. Hemoptysis, when massive and untreated, has a mortality rate of more than 50%. With interventional radiological procedures and surgery, this rate has dropped to 7%-18%. The experience with bronchial arterial embolization in childhood is very limited; only a few case reports with short-term follow-up have been reported. METHODS: We report herein two patients with massive hemoptysis due to abnormal systemic arterial bleeding of the lung; neither patient had any lung or systemic disease. In both cases, the bleeding was controlled with endovascular embolization. The first case had bronchopulmonary arterial anastomosis and represents the first reported case with this anomaly. The second case had recurrent massive hemoptysis due to bronchial artery bleeding, and repeat embolization was performed. RESULTS: Both of these children had rare vascular anomalies without parenchymal lung disease and were treated successfully with bronchial arterial embolization. CONCLUSION: Massive hemoptysis due to abnormal systemic bleeding of the lung in the absence of parenchymal disease is an uncommon and severe symptom in childhood. Embolization can be a treatment option in children with abnormal vasculature bleeding and can be repeated safely when needed.