Health-related quality scores in childhood interstitial lung disease: Good agreement between patient and caregiver reports.

INTRODUCTION: Childhood interstitial lung disease (chILD) is a heterogeneous group of mostly chronic respiratory disorders. Assessment of health-related quality of life (HrQoL) in chILD has become increasingly important in clinical care and research. The aim of this study was to assess differences between patient-reported (self) and caregiver-reported (proxy) HrQoL scores. METHODS: This study used data obtained from the chILD-EU Register. After inclusion (baseline), the patient's health status was followed up at predefined study visits. At each study visit, caregivers and patients were handed validated, age-specific HrQoL questionnaires. HrQoL data entered at baseline were used to compare self- and proxy-reported HrQoL scores. For the longitudinal analysis, we compared HrQoL scores between the baseline and the next follow-up visit. RESULTS: No differences between patient- and caregiver-reported HrQoL scores were found for school functioning, chILD-specific questionnaire score, and physical health summary score. Self-reported HrQoL scores were higher for the subscales emotional functioning (77.4 vs. 70.7; p < .001), social functioning (81.9 vs. 76.2; p < .001), as well as psycho-social summary score (76.5 vs. 71.8; p < .001) and total score (74.7 vs. 70.8; <.001). The longitudinal analysis showed that a significant change in a patient-reported HrQoL score resulted in a significant change in a caregiver-reported HrQoL score after a mean time of 11.0 months (SD 9.4). CONCLUSIONS: We found a good agreement between children- and caregiver-related HrQoL scores. In chILD, caregivers are able to sense changes in children's HrQoL scores over time and may be used as a proxy for children unable to complete HrQoL questionnaires.

Whole lung lavage and GM-CSF use for pulmonary alveolar proteinosis in an infant with lysinuric protein intolerance: a case report.

BACKGROUND: Lysinuric protein intolerance (LPI) is a multi-organ metabolic disorder characterized by the imbalance in absorption and excretion of cationic amino acids like lysine, ornithine and arginine. Infants with LPI typically present with recurrent vomiting, poor growth, interstitial lung disease or renal impairment. The early onset of pulmonary alveolar proteinosis (PAP) has been reported to be associated with a severe form of LPI. Treatment of PAP most commonly consists of whole-lung lavage (WLL) and in autoimmune PAP, granulocyte-macrophage colony stimulating factor (GM-CSF) administration. Nevertheless, GM-CSF therapy in LPI-associated PAP has not been scientifically justified. CASE PRESENTATION: We describe the case of an 8-month-old infant presenting with respiratory failure due to LPI associated with PAP, who was twice treated with WLL; firstly, while on veno-venous ECMO assistance and then by the use of a selective bronchial blocker. After the two treatments with WLL, she was weaned from daytime respiratory support while on initially subcutaneous, then on inhaled GM-CSF therapy. CONCLUSIONS: This case supports the notion that GM-CSF therapy might be of benefit in patients with LPI-associated PAP. Further studies are needed to clarify the exact mechanism of GM-CSF in patients with LPI-associated PAP.

Healthcare resource utilisation and medical costs for children with interstitial lung diseases (chILD) in Europe.

BACKGROUND: No data on healthcare utilisation and associated costs for the many rare entities of children's interstitial lung diseases (chILD) exist. This paper portrays healthcare utilisation structures among individuals with chILD, provides a pan-European estimate of a 3-month interval per-capita costs and delineates crucial cost drivers. METHODS: Based on longitudinal healthcare resource utilisation pattern of 445 children included in the Kids Lung Register diagnosed with chILD across 10 European countries, we delineated direct medical and non-medical costs of care per 3-month interval. Country-specific utilisation patterns were assessed with a children-tailored modification of the validated FIMA questionnaire and valued by German unit costs. Costs of care and their drivers were subsequently identified via gamma-distributed generalised linear regression models. RESULTS: During the 3 months prior to inclusion into the registry (baseline), the rate of hospital admissions and inpatient days was high. Unadjusted direct medical per capita costs (€19 818) exceeded indirect (€1 907) and direct non-medical costs (€1 125) by far. Country-specific total costs ranged from €8 713 in Italy to €28 788 in Poland. Highest expenses were caused by the disease categories 'diffuse parenchymal lung disease (DPLD)-diffuse developmental disorders' (€45 536) and 'DPLD-unclear in the non-neonate' (€47 011). During a follow-up time of up to 5 years, direct medical costs dropped, whereas indirect costs and non-medical costs remained stable. CONCLUSIONS: This is the first prospective, longitudinal study analysing healthcare resource utilisation and costs for chILD across different European countries. Our results indicate that chILD is associated with high utilisation of healthcare services, placing a substantial economic burden on health systems.

[Solid organ transplantation in childhood]. / Szervtranszplantáció gyermekkorban.

Paediatric organ transplantation today is considered and accepted and widely available therapy in children with end-stage organ failure. It is important to know that in childhood, diseases leading to end-stage organ failure differ from those in adults. Beside this, in children there are different surgical and paediatric challenges before and after transplantation (size differences of the patient and donor organ, special and paediatric infections, different pharmacokinetics and pharmacodynamics of immunosuppressive drugs, noncompliance). However, paediatric organ transplantation in the last decades became a success story of the Hungarian health care owing to several working groups in Hungary and outside the country. Orv Hetil. 2018; 159(46): 1948-1956.

Polymorphisms of the TNF-alpha gene and risk of celiac disease in T1DM children.

BACKGROUND: Type 1 diabetes mellitus (T1DM) and celiac disease (CD) frequently occur together. Previous reports suggested that the (-308)A variant of the tumor necrosis factor-alpha (TNF-alpha) gene is associated either with T1DM or with CD. The aim of our study was to determine whether (-308)A and (-238)A allelic variants of the TNF-alpha gene might have any impact on the risk of CD in T1DM children. METHODS: Three hundred and one T1DM children were enrolled to the study. The presence of CD was screened with IgA endomysial antibodies (EMA) test. Jejunal biopsy was performed to confirm CD. TNF-alpha-308 and -238 genetic variants were tested using the method of restriction fragment length polymorphism. RESULTS: The prevalence of CD in the enrolled diabetic children was 6.3% (19 out of 301 children). The frequency of the (-308)A TNF-alpha variant was similar in the CD and the non-CD groups, exceeding the Hungarian healthy reference value. The number of (-238)A allele carriers was higher in the CD (4/19) than in the non-CD group (17/277) (p < 0.05). CONCLUSIONS: Our study is limited by the small number of CD patients. On the basis of our findings, carriers of TNF (-308)A allele do not seem to have an increased risk for CD in T1DM. The association between TNF-alpha(-238)A allele carrier state and CD requires further investigation.

Association between interleukin-6 polymorphism and age-at-onset of type 1 diabetes. Epistatic influences of the tumor necrosis factor-alpha and interleukin-1beta polymorphisms.

Multiple immune mediators have been mentioned as playing a role in the pathomechanism of type1 DM. Interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha play a central role in the autoimmune destruction of pancreatic beta-cells, whereas IL-6 inhibits TNF-alpha secretion, and may have some protecting effects. In our study, we aimed to investigate the association between these three cytokines' single nucleotide polymorphisms (IL-6 gene G(-174)C, TNF-alpha gene G(-308)A and IL-1beta gene C(3954)T polymorphisms) and age-at-onset of type 1 diabetes mellitus (T1DM) in 165 diabetic children (median age: 17 years). Polymorphisms were determined using the PCR-RFLP method. We found that the age-at-onset of T1DM was significantly different in patients with a different IL-6 genotype (median age-at-onset of T1DM was: 8, 6 and 4.5 years in children with the (-174)GG, GC and CC genotypes, respectively; p < 0.01). Adjusted for TNF-alpha and IL-1beta polymorphisms, patients with a IL-6 (-174)CC genotype have a 3.0-fold (95% CI: 1.2-7.1) increased risk of developing diabetes before the age of 6 years than (-174)G allele carrier patients. However, we found this association to be present only in patients who carried the TNF-alpha (-308)A or IL-1beta (3954)T allele, i.e. in patients with high TNF-alpha and high IL-1beta producer genotypes. We suppose that in the case of high TNF-alpha and IL-1beta producer genotypes, elevated proinflammatory cytokine levels result in a higher production of IL-6 in (-174)G allele carrier patients. This elevated IL-6 level may have a protective effect against the development of T1DM and may delay the destruction of pancreatic beta-cells.

Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus.

OBJECTIVE: Recent data have indicated the significance of vitamin D receptor (VDR) polymorphisms in type 1 diabetes mellitus (T1DM). We have studied the association of five known restriction enzyme polymorphisms of the VDR gene in patients with T1DM. DESIGN AND METHODS: One hundred and seven children with T1DM (T1DM for 5 Years; age, 1-14 Years; boys/girls, 57/50; body mass index, 17.0+/-2.3 kg/m(2); haemoglobin A(Ic) (HbA(Ic)), 7.87+/-1.05) and 103 healthy subjects were enrolled. The VDR polymorphisms ApaI, BsmI, FokI, TaqI and Tru9I ("a", "b", "f", "t" and "u" alleles respectively) were investigated. RESULTS: The "t" and "T" alleles miss the Hardy-Weinberg equilibrium (P<0.01) in control and diabetic populations; we therefore excluded this polymorphism from further analysis. We did not find a difference in the allele prevalence in T1DM patients and controls of any of the five polymorphisms. However, when the "b", "a" and "u" alleles were simultaneously compared in girls, there was a significantly higher prevalence in patients with diabetes compared with controls ("b"+"a"+"u" present/absent: healthy, 0/53; diabetic, 13/37; P<0.005). In boys the prevalence of "b"+"a"+"u" genotype was similar in T1DM and controls. CONCLUSIONS: The impact of the "t" allele cannot be investigated in this study population. Not a single VDR polymorphism increases the susceptibility to T1DM. The common presence of the "b", "a" and "u" alleles greatly increases the probability of T1DM in girls.