Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.

Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia.

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.

Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP).

BACKGROUND/AIMS: The pathogenesis of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), a chronic and incurable human respiratory disease, is not well established. This study was designed to investigate whether the apoptosis of type II pneumocytes could be the precipitating factor in the pathogenesis of IPF. METHODS: Nineteen specimens obtained by retrospective review of the medical and pathological records of 55 patients with IPF, four normal subjects, and 10 disease control lungs were analysed. The selected specimens had normal alveoli with intervening patchy scarring of the lung parenchyma, fulfilling the pathological criteria for UIP. To identify individual cells undergoing apoptosis in the normal alveoli, electron microscopy and in situ end labelling of fragmented DNA were performed on paraffin was embedded sections using digoxigenin-11-dUTP and the enzyme terminal deoxynucleotidyl transferase. RESULTS: Apoptosis was detected in the normal alveoli of 17 of the 19 patients with IPF/UIP and was absent in the controls. Electron microscopy demonstrated apoptotic changes in type II pneumocytes. These results indicate that apoptotic type II pneumocyte death occurs in normal alveoli of IPF/UIP and could be the principal cause of several events that account for the histological, clinical, and functional alterations seen in IPF/UIP. CONCLUSIONS: In conclusion, numerous type II pneumocytes from the normal alveoli of most patients with IPF/UIP actively undergo programmed cell death. This finding may shed new light on the pathogenesis of this disease, with implications mainly for the treatment of affected patients.

Primary malignant fibrous histiocytoma of the lung. Report of a case with bronchial brushing cytologic features.

BACKGROUND: Malignant fibrous histiocytoma (MFH) arising primarily in the lungs is rare, and a preoperative diagnosis, as well as a surgical planning, is very important because of the tumor's propensity for vascular invasion and its low incidence of lymph node metastasis. The correct preoperative diagnosis of thoracic MFH is not easy to establish because the small fragments from needle and transbronchial biopsies are often inadequate for a conclusive histologic analysis. A preoperative bronchial brushing cytology suggestion of the diagnosis of primary MFH of the lungs may be helpful in such cases. CASE: A 37-year-old male presented with a large, irregular mass in the inferior and middle lobes on chest roentgenography as well as on computed tomography. Two bronchoscopies were performed, with the diagnosis of undifferentiated large cell carcinoma. After surgical resection a more sophisticated pathologic analysis, including immunohistochemical and ultrastructural studies, revealed a primary MFH of the lungs. Revision of the bronchial brushing cytology disclosed many spindle-shaped cells with a "comet" configuration, strongly suggestive of MFH. CONCLUSION: The bronchial brushing cytology features of spindle-shaped and bizarre, multinucleated giant cells with a comet appearance may be the key to the cytomorphologic diagnosis of MFH.

Interstitial lung disease in primary Sjögren's syndrome. Clinical-pathological evaluation and response to treatment.

Interstitial disease is a recognized form of lung involvement in primary Sjögren's syndrome in which frequency and severity have not yet been established. We studied 20 patients 61.2 +/- 36.4 mo after the first symptoms of the syndrome that fulfilled criteria for both xerostomia and xerophtalmia. Eighteen patients exhibited pulmonary symptoms; nine presented a restrictive functional pattern. The chest roentgenogram disclosed interstitial involvement in nine patients. Gallium-67 lung scan presented hypercaptation in 15 of 19 patients studied. Thirteen patients who submitted to bronchoalveolar lavage presented higher cell counts with increases of lymphocytes and/or polymorphonuclear cells. All patients had abnormal results in at least one of the above. Lung biopsy, undertaken in 12 patients, showed a whole spectrum of interstitial disease, from a follicular bronchiolitis to a lymphoid interstitial pneumonia and finally fibrosis with honeycombing. One patient presented with associated sarcoid granulomas. We treated 11 patients with an azathioprine-based regimen and found a significant improvement in the forced vital capacity (p < 0.05) after at least 6 mo when compared with nontreated patients. We conclude that the frequency of interstitial lung disease is high in Sjögren's syndrome and that an azathioprine-based treatment can favorably change the outcome in this population.

[Kidney failure as a complication of the treatment of pulmonary paracoccidioidomycosis]. / Insuficiência renal como complicação do tratamento da paracoccidioidomicose pulmonar.

Sulfadiazine is one of the drugs of choice in the treatment of paracoccidioidomycosis. Side effects are uncommon. Cutaneous and gastrointestinal reactions and rarely leucopenia and jaundice may occur. A patient on sulfadiazine 6 g daily exhibiting a good response is reported. On the 12th day, he presented an intense abdominal pain and reduced urinary output. An ultrasonography revealed diffuse calculosis in urinary tract. Peritoneal dialysis, urinary alkalinization and rehydration were instituted with complete restoration of renal function. This case illustrates the importance of an adequate hydratation of patients receiving sulfadiazine, a simple measure in the prevention of this uncommon complication which carries a high morbidity.

[Transport of electrolytes in the respiratory epithelium in patients with cystic fibrosis]. / Transporte de eletrólitos no epitélio respiratório dos portadores de fibrose cística.

In the conducting airway, the epithelial electrolyte transport processes play an important role in determining the composition of the respiratory tract fluid. Apical membrane Cl- and Na+ channels control the secretion and absorption of epithelial cells. Defective regulation of these channels is a prominent characteristic of cystic fibrosis.

The relationship between pleural fluid findings and the development of pleural thickening in patients with pleural tuberculosis.

The objective of the study was to determine if residual pleural thickening after treatment for pleural tuberculosis could be predicted from the pleural fluid findings at the time of the initial thoracentesis. Forty-four patients initially diagnosed as having pleural tuberculosis between January 1986 and January 1988 were separated into two groups: the 23 patients in group 1 had residual pleural disease, while the 21 patients in group 2 had no residual pleural disease after treatment for their pleural tuberculosis was completed. The clinical characteristics of the two different groups did not differ significantly, but the patients in group 1 tended to be a little sicker in that the duration of their symptoms was longer, their hemoglobin values were lower, and weight loss and cough were more frequent. There were no significant differences in the pleural fluid findings in the two different groups. The mean pleural fluid protein level was 5.40 +/- 0.58 g/dl for group 1 and 5.17 +/- 0.80 g/dl for group 2, while the mean pleural fluid glucose level was 78.6 +/- 19.5 mg/dl for group 1 and 79.5 +/- 20.1 mg/dl for group 2. The mean pleural fluid lactate dehydrogenase (LDH) level in group 1 was 593 +/- 498 IU/L, while the mean level for group 2 was 491 +/- 198 IU/L. The presence of residual pleural thickening was not related to the chemotherapeutic regimen or the performance of a therapeutic thoracentesis. From this study we conclude that approximately 50 percent of patients with pleural tuberculosis will have residual pleural thickening when their therapy is completed, but that one cannot predict which patients will have residual pleural thickening from either their clinical characteristics or their pleural fluid findings.

[Primary lung neoplasm in a patient with breast cancer: report of a case]. / Neoplasia primária de pulmão em paciente com câncer de mama: relato de um caso.

A pulmonary nodule in a patient with a previous or concomitant diagnosis of extrathoracic malignancy is not always a synonym of metastasis. When dealing with breast cancer this is very important since the pulmonary lesion is usually not related to the primary tumor. We present a white, 69 years old patient, submitted to mastectomy four years earlier, in which a solitary pulmonary nodule was found, and after resection, the histopathologic examination disclosed a intravascular bronchoalveolar tumor. This is a rare lesion, here represented in an unusual way.

[Response to the administration of corticosteroids in patients with chronic obstructive lung disease and asthma]. / Resposta à administração de corticosteróide em pacientes portadores de doença pulmonar obstrutiva crônica e asma.

A spirometric study was performed in order to evaluate the response to the administration of 200 mg of salbutamol, just before and after the daily administration of 8 mg of triamcinolone, for an average period of 2 weeks, in 21 patients with chronic obstructive pulmonary disease or asthma. Eleven patients responded with a significant increase of FVC or FEV1 or FEF25-75%, after administration of corticoid. Ten patients did not respond. In average there was a significant increase of the FVC and VEF1 (p < 0.01) and of FEF25-75% (p < 0.05) after the administration of corticoid. There was no significant difference between the responders and not responders when the age, initial FVC, FEV1 and FEF25-75% were taken in consideration. A significantly greater number of responders to corticoid responded also to the bronchodilator with an increase of FEF25-75%. There was a significant negative correlation between the intensity of the response to corticoid versus bronchodilator measured with delta FEF25-75%. The administration of corticoid did not change the response to bronchodilator.

[Response of airflow to the administration of bronchodilator agents in patients with chronic obstructive lung disease or asthma]. / A resposta do fluxo aéreo à administração de broncodilatadores em pacientes portadores de doença pulmonar obstrutiva crônica ou asma.

Spirometric tests of 30 patients with chronic obstructive pulmonary disease (COPD) or asthma were evaluated just before and 15 minutes after the administration of 200 mg of salbutamol by inhalation. All patients had a significant increase os their airflow after the bronchodilator administration. In 15 patients the increase of FEV1 was greater than 13% (Group I) and in other 15 patients the increase of FEF25-75% was greater than 23% (Group II). The two groups showed differences with respect to the initial FEV1, and FEF25-75% (% of predicted), with values significantly lower (p 0.01) in Group I. There was no significant difference between the two Groups concerning the age, sex and the initial FVC (% for predicted).

[Lymph node tuberculosis in adults]. / Tuberculose ganglionar em adultos.

Tuberculous lymphadenitis is a form of extrapulmonary tuberculosis that was observed in 8.4% of all cases with tuberculosis in our series. In all instances the organism isolated was M. tuberculosis. There was a high rate of PPD positiveness. The chemotherapy yielded good results. The evolution was satisfactory in 75% of the patients treated for six months.

[Tuberculous pleural effusion: clinical and laboratory evaluation]. / Derrame pleural, tuberculoso: avaliação clínca e laboratorial.

Clinical data concerning 44 patients with pleural tuberculosis are presented. The average age was 35 years. The main symptoms were fever (41/44), chest pain (41/44) and weight loss (34/44). In all but one case the pleural effusion was unilateral without preference for one or other hemithorax. In ten patients (23%) parenchymal lesions could be recognized on chest roentgenograms. Three patients had coexisting active pulmonary disease with positive sputum culture. Forty-nine pleural biopsies were performed in 44 patients. The culture of pleural tissue was positive in 75%, and culture of pleural fluid in 22.5%. The pleural fluid was exudative with fluid-to-serum ratios of protein and LDH exceeding 0.5 and 0.6 respectively. The cellular characterization of pleural fluid has demonstrated predominance of lymphocytes and scarcity of mesothelial cells. The patients received adequate treatment with excellent results, exhibiting an increased weight, increased hemoglobin and decreased ESR. The development of residual pleural thickening occurred in 23 out of 44 cases.

[Bronchial stenosis of tuberculous etiology: pathogenesis and treatment]. / Estenose brônquica de etiologia tuberculosa: patogenia e tratamento.

Four cases of bronchial stenosis as an unusual complication of tuberculosis are described. In the first case, a 18-year-old woman, the bronchial stenosis resulted from cicatrization of a primary focus. The X-ray examination showed no pulmonary lesion and she did not receive any specific treatment for tuberculosis. In other three patients the bronchial stenosis was due to active disease, and there were acid-fast bacilli in the sputum. They received treatment for tuberculosis which resulted in resolution of stenosis in one of them while in the other two the fibrotic bronchial stenosis persisted.

[Alveolar proteinosis: report of 4 cases]. / Proteinose alveolar: apresentação de quatro casos.

Pulmonary alveolar proteinosis is a rare disease characterized by the filling of the alveolar spaces of the lung by a PAS-positive lipoproteinaceous material. Despite the clear characterization of this material, the etiopathogenesis of the disease remains obscure. We present four patients who were admitted in our Department over the last seven years. The diagnosis was confirmed by lung biopsy in all cases. Three patients improved after bronchoalveolar lavage. Spontaneous remission was observed in one case.

[Septic pulmonary embolism with primary focus in the middle ear]. / Embolia séptica pulmonar com foco primário em ouvido médio.

A case of septic pulmonary embolism is presented in which the primary site of infection was the middle ear. The implicated bacteria were aerobics both Gram positive and Gram negative and anaerobics. There were 8 different agents isolated from blood cultures. The cultures of urine and sputum were also positive. The patient received a broad spectrum antibiotic therapy and a surgical exploration of the initial site of infection was performed. A favorable response was observed after 40 days of treatment with antibiotics.

[Foreign-body aspiration in adults]. / Aspiração de corpo estranho em adulto.

Proximal airway obstruction and acute life-threatening asphyxia is the most important complication of foreign body aspiration. Small foreign bodies that transverse the larynx may be initially asymptomatic appearing serious respiratory disturbances only later. Three patients with different clinical evolutions are reported and the diagnostic and therapeutic approaches, discussed.

Glucocorticoid receptor in active pulmonary sarcoidosis.

Glucorticoid receptor (GR) content of open-chest lung biopsies of 8 patients with active non treated pulmonary sarcoidosis was compared to 10 normal lungs. Results showed a higher GR level in sarcoid lungs (86.0 +/- 8.0 fMol/mg protein) than in control ones (8.2 +/- 3.1 fMol/mg protein). Our findings suggest that this increase is due to the accumulation of active cells in the sarcoid granuloma, possibly lymphocytes and or macrophages that may express cytosolic GR. The high level of this receptor in sarcoidosis may represent an indicator of the responsiveness of this disease to corticoids.

Respiratory failure caused by adiaspiromycosis.

Adiaspiromycosis is a rare pulmonary disorder caused by the fungus Emmonsia crescens (or Chrysosporium parvum var crescens). According to the amount of inhaled conidia, man may develop symptomatic disease. After reaching the alveoli, the adiaconidia do not multiply or disseminate, but will induce a granulomatous inflammatory reaction that may lead to fatal respiratory failure. Up to now, only five cases of disseminated pulmonary infection have been documented. This work describes the occurrence, in Brazil, of two further cases of symptomatic disease with diffuse interstitial infiltrates and severe functional impairment. Possible massive infestation during activities in closed and stuffy environments is suggested. The specific diagnosis was troublesome and could not be made by cultures, skin tests or bronchoalveolar lavage. Both patients were successfully treated, but a spontaneous resolution of the process is seriously considered.

[Septic pulmonary embolism and endocarditis caused by Staphylococcus aureus in the tricuspid valve after infectious abortion. Report of 2 cases]. / Embolia pulmonar séptica e endocardite por Staphylococcus aureus na valva tricúspide após abortamento infectado. Relato de dois casos.

We report the cases of two patients with septic pulmonary embolism and respiratory failure after septic abortion. Hysterectomy was performed in both patients after unsuccessful uterine curettage and antibiotic therapy for treatment of the infection. The first patient (27 years-old) remained feverish. The blood cultures yielded Staphylococcus aureus. Tricuspid valve endocarditis was identified as the reason for persistent infection. Antibiotic treatment properly planned was administered and the patient was discharged. The second patient (23 years-old) apparently recovered after hysterectomy. Nevertheless, one month later, infection and septic pulmonary embolism recurred. The diagnosis of Staphylococcus aureus tricuspid valve endocarditis was made. Persistent infection unresponsive to medical treatment led to surgical treatment. The patient died after valve replacement. Thus the persistence or recurrence of infection and septic abortion may be due to tricuspid valve endocarditis.