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. The work-flow of the pediatric DPLD categorization system included (i) the generation of a final working diagnosis, decision on the presence or absence of (ii) DPLD and (iii) a systemic or lung only condition, and (iv) the allocation to a category and subcategory. The validity and inter-observer dependency of this workflow was re-tested using a systematic sample of 100 cases. Results Two blinded raters allocated more than 80 % of the re-categorized cases identically. Non-identical allocation was due to lack of appreciation of all available details, insufficient knowledge of the classification rules by the raters, incomplete patient data, and shortcomings of the classification system itself. Conclusions This study provides a suitable workflow and hand-on rules for the categorization of pediatric DPLD. Potential pitfalls were identified and a foundation was laid for the development of consensus-based, international categorization guidelines

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Case presentation</p> <p>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. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child.</p> <p>Conclusions</p> <p>The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.</p

Lung alveolar proteomics of bronchoalveolar lavage from a pulmonary alveolar proteinosis patient using high-resolution FTICR mass spectrometry

High-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometry was developed and applied to the proteome analysis of bronchoalveolar lavage fluid (BALF) from a patient with pulmonary alveolar proteinosis. With use of 1-D and 2-D gel electrophoresis, surfactant protein A (SP-A) and other surfactant-related lung alveolar proteins were efficiently separated and identified by matrix-assisted laser desorption/ionization FTICR mass spectrometry . Low molecular mass BALF proteins were separated using a gradient 2-D gel. An efficient extraction/precipitation system was developed and used for the enrichment of surfactant proteins. The result of the BALF proteome analysis show the presence of several isoforms of SP-A, in which an N-non-glycosylierte form and several proline hydroxylations were identified. Furthermore, a number of protein spots were found to contain a mixture of proteins unresolved by 2-D gel electrophoresis, illustrating the feasibility of high-resolution mass spectrometry to provide identifications of proteins that remain unseparated in 2-D gels even upon extended pH gradients

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. The work-flow of the pediatric DPLD categorization system included (i) the generation of a final working diagnosis, decision on the presence or absence of (ii) DPLD and (iii) a systemic or lung only condition, and (iv) the allocation to a category and subcategory. The validity and inter-observer dependency of this workflow was re-tested using a systematic sample of 100 cases. Results Two blinded raters allocated more than 80 % of the re-categorized cases identically. Non-identical allocation was due to lack of appreciation of all available details, insufficient knowledge of the classification rules by the raters, incomplete patient data, and shortcomings of the classification system itself. Conclusions This study provides a suitable workflow and hand-on rules for the categorization of pediatric DPLD. Potential pitfalls were identified and a foundation was laid for the development of consensus-based, international categorization guidelines

Additional file 4: Table S3. of Categorizing diffuse parenchymal lung disease in children

Summary of reasons for incorrect categorization. (DOCX 15 kb

Additional file 6: Table S5. of Categorizing diffuse parenchymal lung disease in children

Centers and physicians contributing cases to the kids-lung-register. (DOCX 34 kb

Additional file 2: Figure S1. of Categorizing diffuse parenchymal lung disease in children

Routine work-flow used in the Kids lung register (KLR) to obtain a final working diagnosis and to categorize and subcategorize cases with suspected DPLD (black and red). The work-flow used for re-rating is depicted in red. *reference pathologist was Frank Brasch, **genetical diagnosis was made by Peter Lohse and ***lavage report on surfactant protein analysis, as well as the establishment of the final working diagnosis during routine KLR workflow were done by Matthias Griese. (PDF 176 kb

Additional file 3: Table S2. of Categorizing diffuse parenchymal lung disease in children

Blinded and independent re-rating of a random sample of 100 DPLD cases from the kids-lung register. Only differences to the original categorization are indicated; empty cells indicate correct categorization. (DOCX 35 kb