ABCA3-related interstitial lung disease beyond infancy.

BACKGROUND: The majority of patients with childhood interstitial lung disease (chILD) caused by pathogenic variants in ATP binding cassette subfamily A member 3 (ABCA3) develop severe respiratory insufficiency within their first year of life and succumb to disease if not lung transplanted. This register-based cohort study reviews patients with ABCA3 lung disease who survived beyond the age of 1 year. METHOD: Over a 21-year period, patients diagnosed as chILD due to ABCA3 deficiency were identified from the Kids Lung Register database. 44 patients survived beyond the first year of life and their long-term clinical course, oxygen supplementation and pulmonary function were reviewed. Chest CT and histopathology were scored blindly. RESULTS: At the end of the observation period, median age was 6.3 years (IQR: 2.8-11.7) and 36/44 (82%) were still alive without transplantation. Patients who had never received supplemental oxygen therapy survived longer than those persistently required oxygen supplementation (9.7 (95% CI 6.7 to 27.7) vs 3.0 years (95% CI 1.5 to 5.0), p=0.0126). Interstitial lung disease was clearly progressive over time based on lung function (forced vital capacity % predicted absolute loss -1.1% /year) and on chest CT (increasing cystic lesions in those with repetitive imaging). Lung histology pattern were variable (chronic pneumonitis of infancy, non-specific interstitial pneumonia, and desquamative interstitial pneumonia). In 37/44 subjects, the ABCA3 sequence variants were missense variants, small insertions or deletions with in-silico tools predicting some residual ABCA3 transporter function. CONCLUSION: The natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.

Interstitial Lung Disease in Children With Selected Primary Immunodeficiency Disorders-A Multicenter Observational Study.

Primary immunodeficiencies (PIDs) are rare disorders of the immune system encompassing inborn errors of immunity. Primary antibody deficiencies constitute the largest group of PID with common variable immunodeficiency (CVID) being the most common symptomatic form. Combined immunodeficiencies (CID) accompanied by antibody deficiency can mimic CVID and these patients need the verification of the final diagnosis. Respiratory involvement, especially interstitial lung disease (ILD), poses a relevant cause of morbidity and mortality among patients with PID and in some cases is the first manifestation of immunodeficiency. In this study we present a retrospective analysis of a group of children with primary immunodeficiency and ILD - the clinical, radiological, histological characteristics, treatment strategies and outcomes. Eleven children with PID-related ILD were described. The majority of them presented CVID, in three patients CID was recognized. All patients underwent detailed pulmonary diagnostics. In eight of them histological analysis of lung biopsy was performed. We noted that in two out of 11 patients acute onset of ILD with respiratory failure was the first manifestation of the disease and preceded PID diagnosis. The most common histopathological diagnosis was GLILD. Among the analyzed patients three did not require any immunosuppressive therapy. All eight treated children received corticosteroids as initial treatment, but in some of them second-line therapy was introduced. The relevant side effects in some patients were observed. The study demonstrated that the response to corticosteroids is usually prompt. However, the resolution of pulmonary changes may be incomplete and second-line treatment may be necessary.

Analysis of hospital management of chronic respiratory diseases in light of the "Maps of Health Needs" project in Poland.

INTRODUCTION: The "Maps of Health Needs" project has been carried out in Poland since 2016 and its purpose is to implement quality-promoting and organisational solutions in the Polish healthcare system. This paper is the analysis of hospitalisations for chronic respiratory diseases recorded in Polish National Health Fund databases in 2014. MATERIAL AND METHODS: The study included 122,000 hospitalisations of adults and 22,000 hospitalisations of children. Epidemio-logical parameters (incidence and prevalence) and major hospitalisation parameters were determined through statistical analysis. RESULTS: The highest registered incidence was observed in asthma patients (548 per 100,000 inhabitants) followed by COPD patients (233 per 100,000 inhabitants). Asthma patients were also characterised by the highest prevalence, with lower values being observed in COPD patients. In the group of adults, patients aged 65 years or older and 80 years or older accounted for 44% and 14% of hospitalised adults respectively. The analysis also revealed that 66% of hospitalisations of adults included patients with asthma, COPD and respiratory failure. The development of respiratory failure prolongs hospitalisation and increases both in-hospital and post-discharge mortality. In children, 90% of the identified hospitalisations were for asthma, chronic inflammatory lung diseases and cystic fibrosis. CONCLUSIONS: The results of the study demonstrate that pulmonary obstructive diseases are associated with a considerable burden. Therefore, corrective actions within the Polish healthcare system are required to decrease the number of hospitalisations for these diseases.

FARSA mutations mimic phenylalanyl-tRNA synthetase deficiency caused by FARSB defects.

Pathogenic variants in genes encoding aminoacyl-tRNA synthetases cause numerous disorders characterized by involvement of neurons, muscles, lungs and liver. Recently, biallelic FARSB defects have been shown to cause severe growth restriction with combined brain, liver and lung involvement (Rajab interstitial lung disease [ILD] with brain calcifications). Herein, for the first time, we present a patient with similar condition associated with biallelic mutations in FARSA (NM_004461.3: c.766T>C:p.Phe256Leu and c.1230C>A:p.Asn410Lys). Both detected FARSA variants are ultrarare and predicted to be damaging by in silico programs. Furthermore, they are both located in the active site of phenylalanyl-tRNA synthetase (PheRS) with Asn410Lys directly affecting a residue forming the wall of the phenylalanine-binding pocket. Clinical features shared between our patient and the FARSB syndrome include ILD with cholesterol pneumonitis, growth delay, hypotonia, brain calcifications with cysts and liver dysfunction. Our findings indicate that a disease similar to a syndrome associated with FARSB defects can also be caused by biallelic FARSA mutations. These findings are consistent with molecular structure of PheRS which is a tetramer including both FARSA and FARSB proteins.

Fluticasone or montelukast in preschool wheeze: a randomized controlled trial.

INTRODUCTION: Approximately 30% of children younger than 3 years experience at least 1 episode of wheezing. Antiasthmatic medication is routinely prescribed, but its effectiveness remains unclear. Our study was aimed to evaluate the effect of anti-inflammatory treatment on frequency and severity of preschool wheeze episodes (PWEs). METHODS: Children aged 6 to 36 months with the first up to the third PWE were randomly assigned to receive montelukast, fluticasone, or no treatment for 12 weeks. The outcome measures were the number of PWEs, the number of hospitalizations due to PWE, and the severity of respiratory symptoms. results: There were no significant differences in outcome measures between the groups. However, tobacco-exposed children treated with fluticasone had significantly fewer PWEs (P = .01). CONCLUSION: Neither montelukast nor fluticasone has proven effective in the prevention of PWE recurrence. Children of smoking parents may benefit from fluticasone treatment after PWE. This observation requires confirmation in larger studies.

[Coexistence of pulmonary sequestration and congenital cystic adenomatoid malformation. Case report and review of literature]. / Wspólistnienie sekwestracji pluca i wrodzonej torbielowatosci gruczolakowatej pluc. Prezentacja przypadku klinicznego i przeglad pismiennictwa.

This paper presents a case report of an infant, with a prenatally diagnosed congenital lung malformation, which proved to be pulmonary sequestration and congenital cystic adenomatoid malformation. The authors discuss current knowledge on diagnosis, clinical course and suggestions of ante- and postnatal management of patients with pulmonary sequestration or/and congenital cystic lung malformation.

Low prevalence of pulmonary involvement in children with inflammatory bowel disease.

BACKGROUND: Since extraintestinal sites of inflammation have been demonstrated in patients with Crohn's disease (CD) and ulcerative colitis (UC), both entities are regarded as systemic disorders. There are only scarce data on the prevalence of inflammatory bowel disease (IBD)-associated lung involvement in children. OBJECTIVES: The aim of our study was to investigate pulmonary involvement in pediatric patients with IBD. MATERIAL AND METHODS: Fifty children with IBD (25 UC and 25 CD, mean age 14.2 ± 3.2 yrs) and 39 age-matched, healthy, control subjects were included in the study. Pulmonary function testing, methacholine bronchial challenge, fractional exhaled nitric oxide (FeNO) and high resolution computed tomography (HRCT) were used to detect functional and/or structural pulmonary involvement. RESULTS: There were no differences in spirometric parameters, lung volumes or lung diffusion capacity for carbon monoxide between IBD patients and control subjects. Highly significant differences were found in FeNO between CD, UC and control patients (mean 9.3 ± 3.3, 27.7 ± 14.8 and 16.6 ± 9.28, respectively; p = 0.000). Bronchial hyperresponsiveness was diagnosed in six IBD cases (14.6%). HRCT (performed in 32 patients from the study group) revealed mild bilateral bronchiectasis in one patient. CONCLUSIONS: The prevalence of pulmonary involvement in children with IBD is low. Screening for pulmonary involvement in children and young adults with IBD may enable early detection of IBD-related pulmonary diseases which, seems to be notably more common in adult patients. Elevated FeNO could probably be regarded as a marker of airway involvement in non-smoking UC pediatric patients. This requires further studies.

Local treatment of empyema in children: a systematic review of randomized controlled trials.

UNLABELLED: The aim of the study is to systematically evaluate data from randomized controlled trials (RCTs) on the efficacy of using intrapleural fibrinolytic agents in the treatment of complicated parapneumonic effusions or empyema in children. The Cochrane Library, MEDLINE and EMBASE databases were searched in July 2009. Four RCTs, involving 194 children, were included. In two RCTs, intrapleural fibrinolytic treatment was compared with normal saline. One of these RCTs showed a significantly reduced hospital stay in those treated with urokinase compared with those treated with normal saline. Otherwise, no fibrinolytic agent had an effect on any other outcome. Two RCTs that compared fibrinolytic treatment with video-assisted thoracoscopic surgery (VATS) revealed no benefit of VATS. CONCLUSION: There is little evidence that intrapleural fibrinolysis is more effective than normal saline in the local treatment of complicated parapneumonic effusions or empyema in children. There is no evidence that VATS is more effective than fibrinolytic treatment. Only a limited number of trials were available for analysis, so some caution must be exercised in interpreting the strength of the evidence presented.

[Does the residual mediastinal mass have prognostic significance in children with Hodgkin's disease (HD)?]. / Czy obecnosc przetrwalej zmiany w sródpiersiu ma znaczenie prognostyczne w chorobie Hodgkina (HD) u dzieci?

Prognostic significance of residual mediastinal tumor mass in children treated for HD as well as the choice of the optimal management of these cases still remains unknown. In years 1994-2001 in 10 PPLLSG participating centers 480 children (age 2-19.7 years) were treated for HD (stages I-IV). In 338 cases initial mediastinal/lung hilus involvement was present. All patients with initial mediastinal/lung hilus involvement were treated with multidrug chemotherapy combined with involved field radiotherapy. In five cases remission was not achieved. Complete remission (CR) was achieved in 226 patients and uncertain complete remission (UCR) in 107 patients, in whom after completion of planned treatment residual changes in mediastinum/lung hilus were identified in radiological examinations. Twenty four children with persistent mediastinal tumor underwent thoracoscopy or thoracotomy. In only one case histopathological examination revealed the presence of neoplastic cells in mediastinal mass tissue, in 2 another cases cystic changes in mediastinum were present, in one case thymic tissue was identified, necrotic tissue was present in 20 cases. Among 107 children with residual mediastinal tumor and 226 patients with CR achieved, relapses occurred in 6 and 18 patients respectively. Over 5-year relapse-free survival was 92.4% and 91.3% respectively. Patients with the presence of mediastinal/lung hilus tumor after the completion of the treatment do not have an increased risk of relapse, but before the completion of therapy they require careful, clear-sighted and repeated examinations including computed tomography (CT), magnetic resonance imaging (MRI) and especially positron emission tomography (PET) to evaluate the nature of persistent lesions. Only in clinically and radiologically doubtful cases tumor biopsy with subsequent histopatological examination should be performed.

Fatal course of pulmonary Absidia sp. infection in a 4-year-old girl undergoing treatment for acute lymphoblastic leukemia.

Absidia sp. is a rare etiologic agent responsible for infectious complications in immunosuppressed patients. The authors describe a 4-year-old girl with acute lymphoblastic leukemia complicated with pleuropneumonia caused by an Absidia infection during the induction of remission. A review of the published reports in current literature is included for comparison. To the authors' knowledge only six cases of primary pulmonary absidiomycosis have been published. Despite its uncommon pulmonary presentation, mucormycosis should be considered in patients with an immunosuppressing illness and positive risk factors and when a pulmonary lesion is not responding to appropriate antibiotic therapy.

[Influence of age on treatment results in children and adolescents with Hodgkin's disease]. / Wplyw wieku na wyniki leczenia dzieci i mlodziezy z choroba Hodgkina.

Over the last few years, treatment failures (progression, relapse) in Hodgkin's disease (HD) occurred mainly in elder children treated in the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) participating centers. That is why analysis of the influence of age on the treatment outcome in children and adolescents treated with the protocol introduced in 1997 was performed. In years 1997-2001, in 10 centers of PPLLSG, 280 patients (age 2.3-18.8 years) were treated for HD. In all patients MVPP and B-DOPA chemotherapy with or without radiotherapy was introduced. Among 280 treated children the first remission was achieved in 275 patients (98.2%). Relapses occurred in 11 patients (4%). The 5-year probability of overall survival, relapse-free survival (RFS) and event-free survival (EFS) was 99%, 93% and 90%, respectively. All children with relapse were over 10 years old at the time of diagnosis (range: 10.6-17.1, median 14.6 years); mediastinal tumor mass was present in all of them. The logistic regression analysis did not reveal the border value for increasing the probability of relapse or event, thus age of 10 years (age of the youngest child with relapse) was identified as the border value. The probability of 5-year EFS and RFS for children over and under the 10th year of age was 98%, 92% and 100%, 92%, respectively. The differences were not statistically significant. Among children over the 10th year of age some features of the disease occurred more frequently: female sex, shorter history of the disease, presence of mediastinal tumor, greater stage of the disease, NS histopathological type of the disease, presence of general signs and ESR over 50 mm, greater tumor burden and higher number of involved lymphatic regions. Among the patients over the 10th year of age, the presence of the general signs and mediastinal tumor influenced the occurrence of relapses substantially. The aim of the further treatment modifications ought to comprise the need of better treatment outcome, especially in patients over the 10th years of age in which unfavorable prognostic factors are identified. child with relapse) was identified as the border value. The probability of 5-year EFS and RFS for children over and under the 10th year of age was 98%, 92% and 100%, 92%, respectively. The differences were not statistically significant. Among children over the 10th year of age some features of the disease occurred more frequently: female sex, shorter history of the disease, presence of mediastinal tumor, greater stage of the disease, NS histopathological type of the disease, presence of general signs and ESR over 50 mm, greater tumor burden and higher number of involved lymphatic regions. Among the patients over the 10th year of age, the presence of the general signs and mediastinal tumor influenced the occurrence of relapses substantially. The aim of the further treatment modifications ought to comprise the need of better treatment outcome, especially in patients over the 10th years of age in which unfavorable prognostic factors are identified.

[Evaluation of systolic and diastolic function of the left ventricle in children with acute lymphoblastic leukaemia before treatment]. / Ocena czynnosci skurczowej i rozkurczowej lewej komory serca u dzieci z ostra bialaczka limfoblastyczna przed rozpoczeciem leczenia.

Between 1995 and 2001 echo-cardiography was performed in 244 children (128 boys, 116 girls) with acute lymphoblastic leukaemia (ALL) before the beginning of therapy with anthracyclines (medium 5.4 days after the diagnosis). The mean age at diagnosis was 5.4 years (range 9 months to 17.7 years). 189 children (97 boys and 92 girls) were included into the standard and medium risk groups and 55 (31 boys and 24 girls) into the high risk group. 29% of ALL children had disturbances in ECG. Changes in the thickness of the intraventricular septum (%IVSTh) and left ventricular posterior wall (%LVPWTh) were statistically lower, especially in children under 7 years of age. Some children showed lowering of shortening fraction (%FS - 8.6%), ejection fraction (%EF - 10.2%) and corrected velocity of fibber-shortening (Vcfc - 25.8%). Children with decreased shortening fraction (%FS) had left ventricular posterior wall thickness (%LVPWTh) impairment. Changes in diastolic function indicate impaired relaxation and compliance of the left ventricle. Decreased peak early filling velocity (E) was found. There were also longer deceleration time (EDecT) and decreased deceleration from peak E velocity (E/Dec) and longer isovolumetric relaxation time in children in standard and medium risk groups. Shorter acceleration time (EAccT) was seen in the high risk group. Evaluation of cardiac function before anthracycline chemotherapy will allow to select patients with pre-existing cardiac impairment for whom cardioprotective treatment is absolutely necessary.

[Over 30-year experience of Polish Pediatric Leukemia/Lymphoma Study Group for treatment of Hodgkin's disease in children and adolescents: improvement curability and decrease of serious complications]. / Ponad 30-letnie doswiadczenie Polskiej Grupy ds. Leczenia Bialaczek i Chloniaków w leczeniu choroby Hodgkina u dzieci i mlodziezy: poprawa wyleczalnosci i zmniejszenie powaznych powiklan.

Currently over 90% of children with HD can be cured thanks to use of chemotherapy (CT) combined with involved field radiotherapy (IF-RT). From 1971 to 2001, 1062 children and adolescents with HD (stage I to IV) were treated in 10 oncological centers PPLLSG. Majority of patients were treated with CT combined with IF-RT. Year by year the intensity of therapy (CT and RT) was gradually adjusted to the risk-factor groups, and invasive methods of staging were also gradually limited. Supportive care was improved at the same time. Along with the modified therapy protocol, five consecutive periods of time (I: 1971-82; II: 1983-87; IIII: 1988-93; IV: 1994-96; V: 1997-2001) were analyzed. In the first period the basic CT was MVPP (mechlorethamine, vinblastine, procarbazine, prednisone), while later B-DOPA (bleomycin, dacarbazine, vincristine, prednisone, doxorubicin) was gradually introduced alone or alternately with MVPP. In order to decrease the incidence of late complications, the dose of IF-RT from 45 Gy to 15-30 Gy was reduced in the next periods. In V period in 21 children with stage IA and IIA with favorable prognostic factors, CT alone was used. The probability of over 5-year: overall survival, relapse free survival and event free survival were in the I period: 92%, 83% and 77%, in the II period: 97%, 92% and 89%, in the III period: 97%, 93% and 91%, in the IV period: 95%, 91% and 90%, in the V period: 95%, 95% and 93%. Decreased rate of serious complications was also observed. Intensity of therapy should be tailored to the stage of disease, and to other significant prognostic factors. The current strategy of diagnosing and treatment of HD is aimed at balancing between the highest possible cure rates and risk of late complications.

[Efficacy of idarubicin in the treatment of childhood acute non-lymphoblastic leukemia: report of Polish Pediatric Leukemia/Lymphoma Study Group]. / Zastosowanie idarubicyny w leczeniu ostrej bialaczki nielimfoblastycznej u dzieci--Raport Polskiej Grupy Pediatrycznej ds Bialaczek i Chloniaków.

UNLABELLED: Results of treatment of childhood ANLL remained unsatisfactory for a long time, and introduction of a new drug seemed justified as the EFS achieved in this disease between 1993-97 was 42%. In 1998 a new protocol containing idarubicine in dose 12 mg/m2 (each dose regardless of treatment phase) was introduced. Between 1998 and 2001, 137 children with ANLL were referred to nine participating centers of PPLLSG. Thirty nine were uneligible, so 98 were evaluated. Among them 56 were qualified to standard risk group (SRG) and 35 to high risk group (HRG). In 7 children the risk group was not established due to early death. Remission rate was 79% in the whole group and 98% and 63% in SRG and HRG, respectively. The actuarial 3-year overall survival (OS), 3-year event-free survival (EFS) and 3-year event-free interval (EFI) are respectively: In the whole group 61%, 54% and 67%; in SRG 81%, 70% and 71%; in HRG 40%, 40%, and 53%. CONCLUSIONS: Due to introduction if idarubicine significant improvement of the results was achieved in SRG (better OS, EFS and EFI). Better new treatment methods are required in HRG.