[Kids Lung Registry and Child-EU Project - Progress in Rare and Interstitial Lung Diseases in Childhood Through Collaboration]. / Kinderlungenregister (chILD-EU) ­ Zusammenarbeit führt zu Fortschritten bei den seltenen und interstitiellen Lungenerkrankungen.

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. These are reported to the Kid's Lung Register after parental consent. Clinical data, imaging, and blood are sent to the registry. Genetic analysis can be arranged if desired. With completeness of the data, a peer-review process by pediatric radiology, possibly lung pathology, clinical and possibly genetic experts takes place in an interdisciplinary conference. A working diagnosis is established and communicated to the responsible physician via the registry and, if necessary, further discussed in case-related discussions. Assistance in entering the data is provided by the registry. Follow-ups are performed annually, and all registered physicians are invited to regular, web-based case discussions. Significant questions are answered in scientific projects and jointly published (>110 publications to date). CONCLUSIONS: Due to voluntary additional work of all participants beyond clinical routine, more than 1000 children with rare lung diseases have been included in the registry with biobank to date. A deeper understanding of the clinical courses of large cohorts of rare diseases and the initial description of new entities contributes to better care for these children.

Quantitative Lipidomics in Pulmonary Alveolar Proteinosis.

Rationale: Pulmonary alveolar proteinosis (PAP) is characterized by filling of the alveolar spaces by lipoprotein-rich material of ill-defined composition, and is caused by molecularly different and often rare diseases that occur from birth to old age.Objectives: To perform a quantitative lipidomic analysis of lipids and the surfactant proteins A, B, and C in lavage fluids from patients with proteinosis of different causes in comparison with healthy control subjects.Methods: During the last two decades, we have collected BAL samples from patients with PAP due to autoantibodies against granulocyte-macrophage colony-stimulating factor; genetic mutations in CSF2RA (colony-stimulating factor 2 receptor α-subunit), MARS (methionyl aminoacyl-tRNA synthetase), FARSB (phenylalanine-tRNA synthetase, ß-subunit), and NPC2 (Niemann-Pick disease type C2); and secondary to myeloid leukemia. Their lipid composition was quantified.Measurements and Main Results: Free cholesterol was largely increased by 60-fold and cholesteryl esters were increased by 24-fold. There was an excessive, more than 130-fold increase in ceramide and other sphingolipids. In particular, the long-chain ceramides d18:1/20:0 and d18:1/24:0 were elevated and likely contributed to the proapoptotic environment observed in PAP. Cellular debris lipids such as phosphatidylethanolamine and phosphatidylserine were only moderately increased, by four- to sevenfold. The surfactant lipid class phosphatidylcholine expanded 17-fold, lysophosphatidylcholine expanded 54-fold, and the surfactant proteins A, B, and C expanded 144-, 4-, and 17-fold, respectively. These changes did not differ among the various diseases that cause PAP.Conclusions: This insight into the alveolar lipidome may provide monitoring tools and lead to new therapeutic strategies for PAP.

Treating Allergic Bronchopulmonary Aspergillosis with Short-Term Prednisone and Itraconazole in Cystic Fibrosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus contributing to cystic fibrosis (CF) lung disease. OBJECTIVE: To evaluate the combination of oral prednisone for 18 days together with itraconazole therapy for at least 12 months in CF-related ABPA with regard to long-term pulmonary function and side effects. METHODS: Sixty-five patients with CF treated for ABPA and 127 patients with CF without ABPA serving as matched controls were retrospectively analyzed for a median period of 4.8 years. Serial lung functions were analyzed alongside clinical, microbiological, and laboratory data including itraconazole therapeutic drug monitoring. RESULTS: The used ABPA treatment regimen restored FEV1 values to pre-ABPA levels within 3 months (P < .0001). Long-term FEV1 courses of patients showed no difference when compared with those of ABPA-free controls. Glucocorticoid treatment was not associated with increased CF-related diabetes incidence, growth restriction, or Pseudomonas aeruginosa acquisition. Patients who experienced ABPA relapses displayed lower itraconazole trough levels during the first 3 months of treatment (P < .05). A decreased risk of ABPA recurrence was further associated with P aeruginosa colonization. CONCLUSIONS: The proposed treatment scheme for CF-related ABPA is effective in preserving lung function capacity over years in affected individuals without the known glucocorticoid-associated side effects. Itraconazole therapeutic drug monitoring seems useful to prevent disease flares, for which P aeruginosa-negative patients with CF might be particularly susceptible.