[Kids Lung Registry and Child-EU Project - Progress in Rare and Interstitial Lung Diseases in Childhood Through Collaboration].

Background: Progress in rare and interstitial lung disease in childhood can most usefully be achieved through systematic, registry-based collection.

Question And Methods: What are the practicalities and benefits of participating in the pediatric lung registry/chILD-EU project? We report our clinical experiences.

Results: Pediatricians and pediatric pulmonologists identify children with rare lung diseases.

Mechanosensitive channel MscS is critical for termination of the bacterial hypoosmotic permeability response.

Free-living microorganisms are subjected to drastic changes in osmolarity. To avoid lysis under sudden osmotic down-shock, bacteria quickly expel small metabolites through the tension-activated channels MscL, MscS, and MscK. We examined five chromosomal knockout strains, ∆mscL, ∆mscS, a double knockout ∆mscS ∆mscK, and a triple knockout ∆mscL ∆mscS ∆mscK, in comparison to the wild-type parental strain.

Mechanosensitive channel MscS is critical for termination of the bacterial hypoosmotic permeability response.

Unlabelled: Free-living microorganisms are subjected to drastic changes in osmolarity. To avoid lysis under sudden osmotic down-shock, bacteria quickly expel small metabolites through the tension-activated channels MscL, MscS, and MscK. We examined five chromosomal knockout strains, Δ , Δ , a double knockout Δ Δ , and a triple knockout Δ Δ Δ in comparison to the wild-type parental strain.

COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study.

https://bit.ly/3M0wKnZ.

Pulmonary interstitial glycogenosis - A systematic analysis of new cases.

Background: Pulmonary interstitial glycogenosis (PIG) is a rare paediatric interstitial lung disease of unknown cause. The diagnosis can only be made by lung biopsy. Less than 100 cases have been reported.

International management platform for children's interstitial lung disease (chILD-EU).

Background: Children's interstitial lung diseases (chILD) cover many rare entities, frequently not diagnosed or studied in detail. There is a great need for specialised advice and for internationally agreed subclassification of entities collected in a register.Our objective was to implement an international management platform with independent multidisciplinary review of cases at presentation for long-term follow-up and to test if this would allow for more accurate diagnosis.

Tension-activated channels in the mechanism of osmotic fitness in .

(PA) is an opportunistic pathogen with an exceptional ability to adapt to a range of environments. Part of its adaptive potential is the ability to survive drastic osmolarity changes. Upon a sudden dilution of external medium, such as during exposure to rain, bacteria evade mechanical rupture by engaging tension-activated channels that act as osmolyte release valves.

Increased Risk of Interstitial Lung Disease in Children with a Single R288K Variant of ABCA3.

The gene encodes a lipid transporter in type II pneumocytes critical for survival and normal respiratory function. The frequent ABCA3 variant R288K increases the risk for neonatal respiratory distress syndrome among term and late preterm neonates, but its role in children's interstitial lung disease has not been studied in detail. In a retrospective cohort study of 228 children with interstitial lung disease related to the alveolar surfactant system, the frequency of R288K was assessed and the phenotype of patients carrying a single R288K variant further characterized by clinical course, lung histology, computed tomography and bronchoalveolar lavage phosphatidylcholine PC 32:0.

Cardiovascular risk in pulmonary alveolar proteinosis.

We hypothesized that cardiovascular events and/or indices of cardiac dysfunction may be increased in pulmonary alveolar proteinosis (PAP). Systemic and pulmonary arterial hypertension, arrhythmias, pulmonary embolism, stroke and ischemic heart attack were reported. Patients underwent serum anti-GM-CSF antibodies, disease severity score (DSS), Doppler transthoracic echocardiograph, glucose, thyroid hormones, lipids, troponin and pro-Brain natriuretic peptide (BNP) examination.

Persistent Tachypnea of Infancy. Usual and Aberrant.

Rationale: Persistent tachypnea of infancy (PTI) is a specific clinical entity of undefined etiology comprising the two diseases neuroendocrine cell hyperplasia of infancy (NEHI) and pulmonary interstitial glycogenosis. The outcome of typical NEHI is favorable. The outcome may be different for patients without a typical NEHI presentation, and thus a lung biopsy to differentiate the diseases is indicated.

Categorizing diffuse parenchymal lung disease in children.

Background: Aim of this study was to verify a systematic and practical categorization system that allows dynamic classification of pediatric DPLD irrespective of completeness of patient data.

Methods: The study was based on 2322 children submitted to the kids-lung-register between 1997 and 2012. Of these children 791 were assigned to 12 DPLD categories, more than 2/3 belonged to categories manifesting primarily in infancy.

Surfactant proteins in pediatric interstitial lung disease.

Background: Children's interstitial lung diseases (chILD) comprise a broad spectrum of diseases. Besides the genetically defined surfactant dysfunction disorders, most entities pathologically involve the alveolar surfactant region, possibly affecting the surfactant proteins SP-B and SP-C. Therefore, our objective was to determine the value of quantitation of SP-B and SP-C levels in bronchoalveolar lavage fluid (BALF) for the diagnosis of chILD.

GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders.

Background: The majority of cases with severe pulmonary alveolar proteinosis (PAP) are caused by auto-antibodies against GM-CSF. A multitude of genetic and exogenous causes are responsible for few other cases. Goal of this study was to determine the prevalence of GATA2 deficiency in children and adults with PAP and hematologic disorders.

Genotype alone does not predict the clinical course of SFTPC deficiency in paediatric patients.

Patients with interstitial lung disease due to surfactant protein C (SFTPC) mutations are rare and not well characterised. We report on all subjects collected over a 15-year period in the kids-lung register with interstitial lung disease and a proven SFTPC mutation. We analysed clinical courses, interventions and outcomes, as well as histopathological and radiological interrelations.

Long-term follow-up and treatment of congenital alveolar proteinosis.

Background: Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP) due to mutations in the GM-CSF receptor are not well known.

Case Presentation: A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways.

Expression of therapeutic proteins after delivery of chemically modified mRNA in mice.

Current viral vectors for gene therapy are associated with serious safety concerns, including leukemogenesis, and nonviral vectors are limited by low gene transfer efficiency. Here we investigate the therapeutic utility of chemically modified mRNA as an alternative to DNA-based gene therapy. A combination of nucleotide modifications abrogates mRNA interaction with Toll-like receptor (TLR)3, TLR7, TLR8 and retinoid-inducible gene I (RIG-I), resulting in low immunogenicity and higher stability in mice.

Some ABCA3 mutations elevate ER stress and initiate apoptosis of lung epithelial cells.

Background: ABCA3 transporter (ATP-binding cassette transporter of the A subfamily) is localized to the limiting membrane of lamellar bodies, organelles for assembly and storage of pulmonary surfactant in alveolar epithelial type II cells (AECII). It transports surfactant phospholipids into lamellar bodies and absence of ABCA3 function disrupts lamellar body biogenesis. Mutations of the ABCA3 gene lead to fatal neonatal surfactant deficiency and chronic interstitial lung disease (ILD) of children.

Respiratory disease in Niemann-Pick type C2 is caused by pulmonary alveolar proteinosis.

Niemann-Pick diseases are hereditary neurovisceral lysosomal lipid storage disorders, of which the rare type C2 almost uniformly presents with respiratory distress in early infancy. In the patient presented here, the NPC2 exon 4 frameshift mutation c.408_409delAA caused reduced NPC2 protein levels in serum and lung lavage fluid and the synthesis of an aberrant, larger sized protein of around 28 kDa.

Inhalation of alpha(1)-protease inhibitor in cystic fibrosis does not affect surfactant convertase and surface activity.

The inhalation of alpha(1)-protease inhibitor (alpha(1)-PI) was assessed in a pilot study to restore the protease-antiprotease balance in the lungs of cystic fibrosis (CF) patients. In addition, the effect of this treatment on the surface active properties of lung surfactant and the metabolic conversion of aggregate forms was studied. Eight young adults with CF inhaled 100 mg of alpha(1)-PI twice daily over 8 weeks and bronchoalveolar lavages (BAL) were obtained before and 12 h after the last inhalation.

Health effects of sulfur-related environmental air pollution: the pulmonary surfactant system is not disturbed by exposure to acidic sulfate and neutral sulfite aerosols.

The goal of this study was to assess the impact of long-term exposure to environmental sulfur-related aerosols on the biochemical and biophysical properties of lung surfactant. Eight Beagle dogs were housed under clean air conditions for 450 days, followed by an exposure period of 400 days to 0.36 mg/m3 of sulfite (16.

Amphotericin B and pulmonary surfactant.

Targeted intrapulmonary delivery of drugs may reduce systemic toxicity, improve treatment efficacy, but inhaled drugs may also interfere with pulmonary surfactant function. We hypothesized that the lipophilic drug amphotericin B used to treat or prevent pulmonary infections with aspergillus species, might destroy surface activity of lung surfactant, as assessed in a pulsating bubble surfactometer. Pure amphotericin B had no effect on a natural surfactant preparation or on the lipid extracted surfactant SurvantaTM.

Tracheobronchial surface active material in cystic fibrosis.

Surface active material potentially present in the airway is difficult to analyse due to the tight binding of surfactant components to mucins. A surface active sol-fraction was obtained from sputum of patients with cystic fibrosis (CF), analysed and compared with the sol-fraction from sputum of tracheomized, non-CF patients. The release of phospholipids from CF sputum was relatively fast being completed within minutes, temperature dependent and averaged 5.

Clinical evaluation of heat-pressed glass-ceramic inlays in vivo: 2-year results.

In the present study, the 2-year clinical and scanning electron microscope (SEM) results for heat-pressed ceramic inlays are reported. In a selected patient population, 51 cavities were restored with all-ceramic inlays. All margins were located within the enamel.

Recombinant human DNase (rhDNase) influences phospholipid composition, surface activity, rheology and consecutively clearance indices of cystic fibrosis sputum.

Cystic fibrosis (CF) is caused by mutation in the gene for the CF transmembrane conductance regulator which leads to massive, abnormally viscous, purulent sputum, chronic destructive endobronchitis and early death. Purified recombinant human (rh) DNase can digest extracellular DNA and its inhalation in these patients significantly improves lung function. To evaluate the poorly understood mechanisms, saliva protected sputum from patients treated with and without rhDNase were evaluated.