We describe the characteristic clinical and pathologic findings of three cases of constrictive bronchiolitis. All three patients were middle-aged women with chronic respiratory illness characterized by chronic cough, dyspnea, mild to severe obstructive pulmonary dysfunction, relatively normal chest radiographs with occasional peribronchial infiltration, and lack of response to bronchodilators or prednisolone. The patients also had medical diseases such as non-Hodgkin's lymphoma and hyperprolactinemia in case 1 and 3, respectively. None of the patients smoked cigarettes and had clinical evidence of recent viral lower respiratory tract infection. Histologic study by open lung biopsy revealed a spectrum of changes ranging from active cellular bronchiolitis to obliterative peribronchiolar fibrosis. The intervening interstitial and alveolar areas showed no remarkable lesion. Immunohistochemically, the bronchiolar or peribronchiolar inflammatory infiltrates mainly comprised of mixed T- and B-lymphocytes. It may be possible that the active form of constrictive bronchiolitis is initiated by attendant lymphocytic inflammation of the airways, which is followed by fibrous obliteration of bronchioles.
Adult ; Biopsy ; Bronchiolitis/immunology/*pathology ; Bronchoconstriction/*immunology ; Female ; Human ; Middle Age ; Pulmonary Fibrosis/immunology/pathology ; T-Lymphocytes/immunology

OBJECTIVETo investigate the roles of different cells in the pulmonary lesions in the severe acute respiratory syndrome (SARS) patients.

METHODSThe monoclonal antibodies of CD8, CD20, CD34, LCA, CD56, CD68, and AE1/AE3 are used to demonstrate the different cells in the lung specimens of SARS patients in order to study the patterns of cell responses in this new disease. Meanwhile the HE stained slides were also carefully studied to compare with the results of immunohistochemical staining.

RESULTSThe number of capillaries increased and the capillaries clearly outlined the contour of alveolar wall from beginning to early stage of organization, the number of lymphocytes decreased sharply while the number of macrophage remarkably increased, together with proliferation of type II pneumocytes. The numbers of blood vessels decreased in the fibrotic and consolidated lung tissue, and the vessel cavities enlarged, losing the normal contour of alveolar septa.

CONCLUSIONSThe lesions in the lung from SARS patients are consisted of the tissue reaction to the inflammatory injury, including extensive exudation, capillary proliferation, fibrosis, and obvious infiltration of macrophages which may play a key role in the pathogenesis of pulmonary lesions of SARS.

Adult ; Antigens, CD ; immunology ; Antigens, CD20 ; immunology ; Antigens, CD34 ; immunology ; Antigens, Differentiation, Myelomonocytic ; immunology ; Capillaries ; pathology ; Edema ; pathology ; Female ; Fibrosis ; pathology ; Humans ; Immunohistochemistry ; Lung ; blood supply ; pathology ; Macrophages, Alveolar ; pathology ; Male ; Middle Aged ; Pulmonary Alveoli ; pathology ; Severe Acute Respiratory Syndrome ; pathology

OBJECTIVETo study the pulmonary pathology in patients died of fatal human influenza A(H1N1) infection.

METHODSEight cases of fatal human influenza A (H1N1) infection, including 2 autopsy cases and 6 paramortem needle puncture biopsies, were enrolled into the study. Histologic examination, immunohistochemitry, flow cytometry and Western blotting were carried out.

RESULTSThe major pathologic changes included necrotizing bronchiolitis with surrounding inflammation, diffuse alveolar damage and pulmonary hemorrhage. Influenza viral antigen expression was detected in the lung tissue by Western blotting. Immunohistochemical study demonstrated the presence of nuclear protein and hemagglutinin virus antigens in parts of trachea, bronchial epithelium and glands, alveolar epithelium, macrophages and endothelium. Flow cytometry showed that the apoptotic rate of type II pneumocytes (32.15%, 78.15%) was significantly higher than that of the controls (1.93%, 3.77%).

CONCLUSIONNecrotizing bronchiolitis, diffuse alveolar damage and pulmonary hemorrhage followed by pulmonary fibrosis in late stage are the major pathologic changes in fatal human influenza A (H1N1) infection.

Adolescent ; Adult ; Aged ; Alveolar Epithelial Cells ; pathology ; Antigens, Viral ; metabolism ; Apoptosis ; Autopsy ; Biopsy, Needle ; Bronchiolitis, Viral ; pathology ; Child ; Child, Preschool ; Female ; Hemagglutinin Glycoproteins, Influenza Virus ; metabolism ; Humans ; Influenza A Virus, H1N1 Subtype ; immunology ; Influenza, Human ; metabolism ; mortality ; pathology ; virology ; Lung ; immunology ; metabolism ; pathology ; Male ; Middle Aged ; Nuclear Proteins ; metabolism ; Pulmonary Alveoli ; pathology ; Pulmonary Fibrosis ; pathology ; Young Adult

OBJECTIVESevere acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in November 2002. The SARS-associated coronavirus (SARS-CoV) has been identified as the causal agent, but the pathology and pathogenesis are still not quite clear.

METHODSPost-mortem lung samples from six patients who died from SARS from April to July 2003 were studied by light and electron microscopy, Masson trichromal staining and immunohistochemistry. Evidence of infection with the SARS-CoV was determined by reverse-transcription PCR (RT-PCR) , serological examination and electron microscopy.

RESULTSFour of six patients had serological and RT-PCR evidence of recent infection of SARS-CoV. Morphologic changes are summarized as follows: (1) Diffuse and bilateral lung consolidation was seen in all patients (6/6) with increasing lung weight. (2) Diffuse alveolar damage was universal (6/6) with hyaline membrane formation (6/6), intra-alveolar edema/hemorrhage (6/6), fibrin deposition (6/6), pneumocyte desquamation (6/6). A marked disruption in the integrity of the alveolar epithelium was confirmed by immunostaining for the epithelial marker AE1/AE3 (6/6). (3) Type II pneumocytes, with mild hyperplasia, atypia, cytomegaly with granular amphophilic cytoplasm and intracytoplasmic lipid accumulation (5/6). (4) Giant cells in the alveoli were seen in five of 6 patients (5/6) , most of which were positive for the epithelial marker AE1/AE3 (5/6), but some cells were positive for the macrophage marker CD68(2/6). (5) A pronounced increase of macrophages were seen in the alveoli and the interstitium of the lung (6/6), which was confirmed by histological study and immunohistochemistry. (6) Haemophagocytosis was present in five of the 6 patients(5/6). (7) Lung fibrosis was seen in five patients(5/6), with alveolar septa and interstitium thickening(5/6), intraalveolar organizing exudates (6/6) and pleura thickening (4/6). Proliferation of collagen was confirmed by Masson trichromal staining, most of which was type III collagen by immunostaining. The formation of distinctive fibroblast/myofibroblast foci was seen in five patients (5/6) by light microscopy and immunochemistry. (8) Squamous metaplasia of bronchial mucosa was seen in five patients(5/6). (9) Thrombi was seen in all patients(6/6). (10) Accompanying infection was present in two patients, one was bacteria, the other was fungus. In addition, electron microscopy revealed viral particles in the cytoplasm of alveolar epithelial cells and endothelial cells corresponding to coronavirus.

CONCLUSIONDirect injury of SARS-CoV on alveolar epithelium, prominent macrophage infiltration and distinctive fibroblast/myofibroblast proliferation may play major roles in the pathogenesis of SARS.

Adult ; Antibodies, Monoclonal ; metabolism ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Epithelium ; pathology ; Female ; Humans ; Keratins ; immunology ; Lung ; pathology ; ultrastructure ; virology ; Male ; Middle Aged ; Pulmonary Alveoli ; pathology ; Pulmonary Fibrosis ; etiology ; pathology ; SARS Virus ; isolation & purification ; Severe Acute Respiratory Syndrome ; complications ; metabolism ; pathology ; virology

PURPOSE: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of pulmonary fibrosis. To understand the role of MMP-2 and MMP-9 in pulmonary fibrosis, we evaluated the sequential dynamic change and different cellular sources of the 2 MMPs along the time course and their differential expression in the bronchoalveolar lavage (BAL) fluid and in the lung parenchyma of the bleomycin-induced pulmonary fibrosis models in rats. MATERIALS AND METHODS: The level of MMPs in BAL fluid of 54 bleomycin-treated rats was assessed by zymography from 1 to 28 days after intratracheal bleomycin instillation. The level of MMPs in lung parenchyma was evaluated by immunohistochemistry. RESULTS: MMP-2 and MMP-9 were markedly increased in both the BAL fluid and in the lung parenchyma of the bleomycin-treated rats, especially in the early phase with the peak on the 4th day. The levels of both MMPs in the BAL fluid correlated generally well to those in lung parenchyma, although the level of MMP-9 in BAL fluid was higher than MMP-2. In the lung parenchyma, the 2 MMPs, in early stage, were predominantly expressed in the inflammatory cells. In late stage, type II pneumocytes and alveolar epithelial cells at the periphery of the fibrotic foci retained MMP expression, which was more prominent in the cells showing features of cellular injury and/or repair. CONCLUSION: In bleomycin-induced pulmonary fibrosis, MMP-2 and MMP-9 may play important roles, especially in the early phase. In the late stage, the MMP-2 and MMP-9 may play a role in the process of repair.
Animals ; Antibiotics, Antineoplastic/toxicity ; Bleomycin/toxicity ; Bronchioles/*enzymology/pathology ; Bronchoalveolar Lavage Fluid/cytology/immunology ; Disease Models, Animal ; Enzyme Activation ; Gelatin ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 2/*metabolism ; Matrix Metalloproteinase 9/*metabolism ; Neutrophils/pathology ; Pulmonary Fibrosis/chemically induced/*metabolism/*pathology ; Rats ; Rats, Sprague-Dawley