[45-year old patient with progressive shortness of breath and "crazy paving"]. / 45-jähriger Patient mit progredienter Dyspnoe und "crazy paving"

A 45-year-old man referred with progressive shortness of breath. Chest X-ray revealed a diffuse parenchymal process in the lungs, which was characterized as a "crazy paving" pattern in the thoracic CT. Pulmonary function test showed severe impairment of diffusion capacity and apparent respiratory insufficiency. Bronchoalveolar lavage and histological examinations of transbronchial lung biopsies revealed alveolar proteinosis. Because of the presence of anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies, a primary form of this disorder was diagnosed. Therapeutic whole-lung lavage was performed twice and resulted in a continuing remission.

[Intralobar pulmonary sequestration with aspergillosis in an asymptomatic 39-year-old man]. / Intralobulärer Lungensequester mit Aspergillose bei einem beschwerdefreien 39-jährigen Mann.

HISTORY AND CLINICAL FINDINGS: During a screening examination a pulmonary mass in the left lower lobe was detected in a 39-year-old man. The patient was asymptomatic and had hitherto been healthy. CT pulmonary angiography revealed an intralobar pulmonary sequestration with an afferent arterial branch from the thoracic aorta. DIAGNOSIS, TREATMENT AND COURSE: Thoracotomy with resection of the sequestration was performed. On the first postoperative day hemiparesis of the left side occurred because of an infarction of the arteria cerebri media. After aspiration of the thrombus and intraarterial thrombolysis the patient recovered completely. Histology of the sequestration showed invasive growth of aspergillus and severe inflammation, caused by invasive mycosis. Subsequently the patient received voriconazol for four weeks. CONCLUSION: Diagnosis of pulmonary sequestration in adults is rare. In asymptomatic patients there is still controversy about the treatment. Surgery, arterial embolisation and a "watch and wait" strategy can be taken into account. Because of the risk of infection an operative approach should be favoured.

Rheumatoid pneumoconiosis (Caplan's syndrome).

In 1953, Caplan described a characteristic radiographic pattern in coal miners with rheumatoid arthritis (RA) that was distinct from the typical progressive massive fibrosis pattern of coalworkers' pneumoconiosis. It consists of multiple well-defined rounded nodules on chest X-ray, from about 0.5 to about several centimetres in diameter, distributed throughout the lungs but predominantly at the lung periphery. Lesions appear often in crops, may coalesce and form a larger confluent nodule. Nodules often cavitate or calcify. They typically occur in the setting of pre-existing mild pneumoconiosis, but pneumoconiosis is not a prerequisite. The onset of the nodules is typically sudden, and their course varies thereafter, ranging from regression to progression. Histologically, the nodules have a characteristic appearance and are distinguishable from silicotic nodules or progressive massive fibrosis. Individual susceptibility is considered to play a role in the development of the disease. However, the pathogenetic link between exposure to silica, pneumoconiosis and RA has not been clarified conclusively. This review summarizes history, definition and current knowledge on epidemiology, pathology, pathophysiology, clinical presentation and treatment of Caplan's syndrome.

Pulmonary infiltrates in Costello Syndrome.

This paper reports on a patient with diffuse pulmonary infiltrates directly related to Costello Syndrome. This congenital disorder is characterised by multiple congenital abnormalities, such as psychomotor retardation, short stature, redundant skin, papillomata, curly hair, relative macroencephaly, distinctive face and various defects of internal organs. This study is the first to document the histopathological findings in the lungs. Most conspicuous was the depositing of abnormal collagen and elastic fibres and the development of endogenous lipid pneumonia.

Lysosomal cysteine proteases in the lung: role in protein processing and immunoregulation.

Lysosomal cysteine proteases are a family comprising > 10 enzymes. For many years it was believed that these enzymes catalyse protein breakdown unselectively, are highly redundant in their substrate specificity and are also expressed ubiquitously. This view has changed dramatically since a number of new lysosomal cysteine proteases with restricted expression and outstanding enzymatic activity have been described. In addition, knockout mice and selective protease inhibitors have been used to characterise specific functions of single proteases. In this review, some of these functions are discussed in relation to the lungs, especially the role of lysosomal cysteine proteases in matrix remodelling, immunoregulation and surfactant protein processing.

[Diagnosis of multiple myeloma by demonstrating plasma cells in bronchoalveolar lavage]. / Diagnose eines Multiplen Myeloms durch den Nachweis von Plasmazellen in der bronchoalveolären Lavage.

HISTORY AND CLINICAL FINDINGS: A 61-year-old man was transferred from a peripheral hospital with the diagnosis of interstitial lung disease and an unclear mediastinal tumour. At the time of admission the patient had congestive heart disease NYHA class IV. INVESTIGATIONS: The echocardiogram showed a small left ventricle with concentric hypertrophy and a left ventricular ejection fraction of 35 %. The myocardium was relatively echo-rich with solid structures inside. Chest X-ray showed a massive rightsided pleural effusion. The abdominal ultrasound demonstrated ascites and hepatomegaly. The bronchoalveolar lavage showed an increased part of CD3 negative and CD16/CD56 positive cells, which were identified as plasma cells by light and electron microscopy. Aspiration and investigation of the bone marrow verified the diagnosis of a IgG multiple myeloma, highly differentiated characterised by monoclonal expression of light-lambda chains. Additionally Bence-Jones-proteins were found in the urine and osteolysis in the x-ray of the skull and the humerus. DIAGNOSIS: Multiple myeloma, IgG-lambda, stage IIA. THERAPY AND CLINICAL COURSE: Chemotherapy with prednisolone and melphalan was initiated. His general condition increased after administration of the first cycle of chemotherapy. CONCLUSION: Cardiopulmonary involvement is seldom seen in multiple myeloma but should be excluded when clinical symptoms are present.

Expression of cathepsins B, H, K, L, and S during human fetal lung development.

Cathepsins are involved in lysosomal protein degradation, proenzyme activation, antigen processing, and hormone maturation. They are secreted by tumor cells and macrophages and catalyze the remodeling of extracellular matrix proteins. To gain insight into the expression pattern of cathepsins during fetal lung development, the expression of cathepsins B, H, K, L, and S at protein and mRNA levels were evaluated by using immunohistochemistry and in situ hybridization. Early expression of cathepsins B, H, and K was found in epithelial cells of the branching presumptive bronchi (<12th week of gestation). The most intense cathepsin K-specific immunoreactivity was found in developing airways with a lumen. Cathepsin K was found in epithelial cells only, whereas in contrast, cathepsins B and H were detected both in epithelial and interstitial cells. During fetal maturation, interstitial cells displayed cathepsin L immunoreactivity and, in the saccular phase (>26th week of gestation), both cathepsin L and S immunoreactivities. A continuous decline in the proportion of cathepsin H-positive interstitial CD68-positive cells was observed. These discrete temporal and spatial variations in cathepsin expression during organogenesis of the human lung indicate different physiological roles for the individual enzymes in different cell types and developmental stages.

Cathepsin K expression in human lung.

Tissue remodeling is crucial in different lung diseases, in the embryonal development as well as in bronchial carcinoma. Cathepsins were proposed to be involved in the degradation of matrix proteins. Cathepsin K is one of the most potent matrix-degrading cysteine proteinases known as yet. The elastinolytic and collagenolytic activity of this papain-like protease is comparable with that of neutrophil elastase. We have investigated the cathepsin K expression in normal adult lung tissues, in embryonal lung tissue and in bronchial carcinoma. With help of specific anti-cathepsin K antibodies it could be shown that cathepsin K was expressed in bronchial epithelial cells. These data could be confirmed at mRNA level using a quantitative RT-PCR as well as by visualisation of the specific enzymatic activity in epithelial cell lines. During the embryonal development cathepsin K was expressed in the epithelial cells of the developing bronchi. The expression seemed to be upregulated in parallel with the development of the bronchial and alveolar lumen. In the later phase of lung development the cathepsin K expression was restricted to bronchial epithelial cells. Furthermore, using quantitative RT-PCR it could be shown that cathepsin K-mRNA was upregulated in lung tumor tissues in comparison to normal tissues from the same patients. These data suggest that cathepsin K may play an important role in matrix remodeling of the lung under physiological and pathological conditions.