1,25(OH)2D2 production by T lymphocytes and alveolar macrophages recovered by lavage from normocalcemic patients with tuberculosis.

To compare extra-renal 1,25(OH)2D3 production in different types of granulomatous disease, and to identify the cell types responsible, we have evaluated the conversion of 25(OH)D3 in 1,25(OH)2D3 by uncultured cells recovered by bronchoalveolar lavage and blood mononuclear cells from normocalcemic patients with sarcoidosis and tuberculosis. 1,25(OH)2D3 was produced both by lavage cells (12/12 tuberculosis patients, 2/6 sarcoidosis patients) and blood mononuclear cells (3/5 tuberculosis patients, 0/3 sarcoidosis patients) from patients but not controls, but significantly greater amounts were produced by lavage cells from tuberculosis patients than those of sarcoidosis patients (P less than 0.001). 1,25(OH)2D3 production by lavage cells from tuberculosis patients correlated with the number of CD8+ T lymphocytes present but not other cell types. T lymphocytes appeared to be an important source of 1,25(OH)2D3 production, since purified T lymphocytes from all patients with tuberculosis produced 1,25(OH)2D3, and 1,25(OH)2D3 production by these cells correlated closely with that produced by unseparated lavage cells. Because 1,25(OH)2D3 can improve the capacity of macrophages to kill mycobacteria, our results support the conclusion that macrophage-lymphocyte interactions, mediated at least in part by 1,25(OH)2D3, may be an important component of a successful antituberculous immune response.

Evidence for a cytotoxic T-lymphocyte alveolitis in human immunodeficiency virus-infected patients.

A T8 lymphocyte alveolitis occurs in HIV-positive patients, even in the absence of any lung infections or tumors. Using the monoclonal antibody (MAb) D44, the CD8+ T cells can be further subdivided into two functional subsets of cytotoxic T lymphocytes (CTL; CD8+, D44+) and suppressor T cells (CD8+, D44-). A dual fluorescence analysis of alveolar and peripheral lymphocytes has been used in HIV-positive patients without lung infections or tumors to reveal a dramatic increase in alveolar T8 lymphocytes (83%), compared to peripheral values (52%), which was mainly composed (89%) of CD8+ D44+ CTLs. Functional studies confirmed the cytolytic activity of these phenotypically defined alveolar CTLs on autologous alveolar macrophages used as target cells, excluding a natural killer-like activity. An immuno-enzyme analysis concomitantly revealed the co-expression of the p18 HIV antigen and the CD4 molecule on the autologous alveolar macrophages. These data suggest that CTL alveolitis occurs during HIV infection and is directed against HIV-infected alveolar macrophages which are presumably the targets of the locally recruited lung CTLs.

Extensive T8-positive lymphocytic visceral infiltration in a homosexual man.

Lymphocytic visceral infiltration has recently been noted in association with lymphadenopathy-associated virus infection. A homosexual man, who had clinical and immunologic features of the acquired immune deficiency syndrome (AIDS)-related complex, is described. The patient presented not only with peripheral blood lymphocytosis but also with extensive lymphocytic infiltration involving lungs, lymph nodes, nerves, muscles, and esophagus. Lymphocyte subset immunostaining analysis showed that the lymphocytes were T8-positive. Thirty months after the clinical onset of the disease, no evidence of progression to AIDS was seen. Moreover, clinical improvement was observed, even though the patient did not receive long-term treatment. The clinical history of this patient suggests that lung T8-positive lymphocytic infiltration is associated with an increased risk of infectious episodes such as pneumonia and bronchitis.

Technetium-99m-DTPA aerosol and gallium-67 scanning in pulmonary complications of human immunodeficiency virus infection.

We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance measurements with those of fiberoptic bronchoscopy in 88 patients infected with the human immunodeficiency virus. Of 100 investigations, a pulmonary infection was diagnosed in 39, mainly Pneumocystis carinii pneumonia and a noninfectious disorder was found in 42, mainly Kaposi's sarcoma and lymphocytic alveolitis. Gallium scans and DTPA clearance were abnormal respectively in 74% and 92% of infectious complications, and in 12% and 60% of noninfectious disorders. In 10 cases, DTPA clearance was accelerated, while chest x-ray, arterial blood gases and even gallium scanning were normal. A value of DTPA clearance greater than 4.5%.min-1 was both sensitive and specific for the diagnosis of Pneumocystis carinii pneumonia. The gallium scan was always normal in bronchopulmonary Kaposi's sarcoma. We conclude that in symptomatic patients: (1) DTPA clearance measurements are useful for detecting lung disease when chest x-ray and/or PaO2 are normal and (2) a gallium scan is indicated to distinguish progressive Kaposi's sarcoma from a superimposed second process when radiological abnormalities of pulmonary Kaposi's sarcoma are present.

Late pleuropulmonary metastases of a cerebral ependymoma.

A patient with a 12-year history of occipital ependymoma was found to have late pleuropulmonary metastases without recurrence of the primary tumor. The pleural metastases were diagnosed by histologic, ultrastructural features and finally by glial fibrillary acidic protein (GFAP) labeling positive reaction. This case is unique because of the long interval between occurrence of the initial tumor and the metastases, and because of the apparent quiescence of the cerebral lesion when the pleuropulmonary metastases were discovered.

Leukocyte migration inhibition in amiodarone-associated pneumonitis.

Amiodarone-associated pneumonitis is now a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In four patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LIF), by peripheral blood lymphocytes after incubation with amiodarone in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving amiodarone but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. This production of LIF suggests that pneumonitis associated with amiodarone therapy is also associated with a specific cellular immune response to the drug.

Leukocyte migration inhibition in methotrexate-induced pneumonitis. Evidence for an immunologic cell-mediated mechanism.

Methotrexate-induced pneumonitis is a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In three patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LIF), by peripheral blood lymphocytes after incubation with methotrexate (MTX) in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving methotrexate but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. Along with these results, we obtained bronchoalveolar lavage (BAL) cell data displaying high grade lymphocyte alveolitis with a lymphocyte subset inverted ratio. This production of LIF suggests that pneumonitis associated with methotrexate therapy is also associated with a specific cellular immune response to the drug.

Pleural T-lymphocyte subsets in amiodarone-associated pleuropneumonitis.

Two male patients presented with lung disorders with all the characteristics of amiodarone-related pneumonitis. Bilateral exudative pleural effusions were associated with pneumonitis. High lymphocytosis was present in the pleural fluid with a ratio of T-lymphocyte subsets close to that found in peripheral blood; in the blood T-lymphocyte subset ratio was nearly normal. By contrast, and as is usual in similar cases, lymphocytic alveolitis with T-lymphocyte subset imbalance was found in bronchoalveolar lavage fluid. These findings, never published so far to our knowledge, would favor a compartmentalization of the immune response inside the lung.

Serum neuron-specific enolase. A marker for disease extent and response to therapy for small-cell lung cancer.

Serum neuron-specific enolase (S-NSE) levels in 43 newly diagnosed untreated patients with small-cell lung cancer (SCLC) were compared with levels in 35 adult controls, 14 patients with non-small cell lung cancer (N-SCLC), and nine patients with noncancerous lung disease (N-CLD). The S-NSE level was raised (greater than or equal to 16 ng/ml) in 28 of 43 patients with SCLC, six of 16 patients with limited stage SCLC, and 22 of 27 of those with extensive stage SCLC. Extensive stage patients with SCLC had a significantly higher mean S-NSE level (50 ng/ml) than did limited stage patients with SCLC (16 ng/ml). Mean S-NSE levels in patients with N-SCLC and in patients with N-CLD were respectively 11 and 7 ng/ml. Serial measurements performed on 19 patients between the three-day-courses of chemotherapy showed an excellent correlation between S-NSE and clinical evolution. In addition, S-NSE was measured during the first three-day course of chemotherapy in 13 other patients; among them, seven had S-NSE levels greater than or equal to 100 ng/ml (mean: 490 ng/ml); these seven patients were responders; the remaining six had S-NSE levels less than 100 ng/ml (mean 28 ng/ml): among them, only two were responders. Such S-NSE measurements during the first cytostatic course seem to reflect the importance of tumor burden and may be valuable as early indicators of the response rate to chemotherapy.

Amiodarone-induced hypersensitivity pneumonitis. Evidence of an immunological cell-mediated mechanism.

Interstitial pneumonitis developed in a patient who had received a cumulative dose of 985 g of amiodarone in nine years. No other cause for pneumonitis was found. The following findings favor an immunologic mechanism of hypersensitivity due to amiodarone: positive skin and basophil degranulation tests with amiodarone; lymphocytosis and inverted ratio of helper/suppressor T lymphocytes in bronchoalveolar lavage fluid; secretion of leukocyte inhibitory factor, as shown by the inhibition of migration of peripheral blood leukocytes; and positive lymphoblastic transformation in the presence of amiodarone.

Pulmonary Hodgkin's disease in HIV-infected patient. Diagnosis by bronchoalveolar lavage.

We report herein the pulmonary recurrence of Hodgkin's disease coincidental with a marked decrease in the peripheral blood CD4 lymphocyte count in an HIV-seropositive patient with alveolar consolidation on chest roentgenogram. The diagnosis of lung parenchyma involvement was made by bronchoalveolar lavage cell analysis and illustrates the reliability of Reed-Sternberg cell identification in bronchoalveolar lavage for the diagnosis of pulmonary localization of Hodgkin's disease.

Provocation test coupled with bronchoalveolar lavage in diagnosis of drug (nilutamide)-induced hypersensitivity pneumonitis.

A 79-year-old man was given a cumulative dose of 16.5 g of nilutamide for treatment of prostate cancer. He then presented with a respiratory illness having clinical, radiologic and functional characteristics of interstitial pneumonitis. No other cause of pneumonitis was found. Bronchoalveolar lavage showed a lymphocytic alveolitis with an inverted lymphocyte subset ratio. After an 11-week period of drug withdrawal, clinical, radiologic and functional improvement was observed along with a normal alveolar lymphocytosis. Nilutamide therapy was then resumed for five weeks and induced the recurrence of clinical, functional and alveolar abnormalities. Nilutamide treatment was finally stopped and two months later, clinical and functional abnormalities resolved. This observation seems to exemplify the possible diagnostic value of coupling provocation test with BAL cell data in hypersensitivity pneumonitis induced by drugs. In addition, these data support the role of a cell-mediated immunologic mechanism in the pathogenesis of nilutamide-induced pneumonitis.

Leukocyte migration inhibition in propranolol-induced pneumonitis. Evidence for an immunologic cell-mediated mechanism.

About 20 cases of beta blocker-associated pneumonitis have been published in the mid-70s, and a case of interstitial pneumonitis has been attributed to propranolol. The pathogenesis of these cases of pneumonitis with or without pleural effusion is not clear. A 59-year-old man developed pneumonitis which showed all the characteristics of a drug-associated pneumonitis due to propranolol: BAL demonstrated a lymphocytosis, the variations of which closely correlated with a provocation test. The LIF appeared to be released by the patient's peripheral blood lymphocytes when cultured with optimal doses of propranolol. Production of LIF by the patients' lymphocytes suggests the existence of a drug-specific cellular immune response in propranolol-associated pneumonitis.

Bronchoalveolar lavage cell data in amiodarone-associated pneumonitis. Evaluation in 22 patients.

To assess the value of bronchoalveolar lavage (BAL) for diagnosis, understanding, and treatment of amiodarone-associated pneumonitis, we examined the results of BAL total and differential cell counts and phenotyping of lymphocytes in 22 patients with this lung disorder and in 33 normal subjects. Overall, the total cell count was found to be almost the same as that seen in control subjects; the macrophage population was significantly reduced, and the lymphocyte, neutrophil, and eosinophil populations were increased in absolute number and percentage. When results were analyzed individually, BAL data appeared to be distributed according to two patterns. In the first pattern, there was no abnormal lymphocytosis. In the second pattern a lymphocyte alveolitis was found in percentage and in absolute number. This lymphocyte alveolitis was present either alone or associated with neutrophil alveolitis or with eosinophil alveolitis. In the first pattern, despite the normal level of the lymphocyte population, the percentage of CD4 T-lymphocytes and the CD4:CD8 T-lymphocyte ratio were significantly lowered. In the second pattern the CD8 T-lymphocyte count was increased in absolute number and percentage, with a low CD4:CD8 ratio. In six patients relavaged two to four months after amiodarone withdrawal, there was a significant fall in alveolar lymphocytosis, but the progressive increase in the neutrophil population over time seemed to be associated with the seriousness and progression of the disease. Finally, these findings closely resembled those obtained in patients with hypersensitivity pneumonitis due to inhalation of organic dust and suggest that an underlying immunologic cell-mediated mechanism may play a role in this iatrogenic pulmonary disease.

Bronchoalveolar lavage cell data in 19 patients with drug-associated pneumonitis (except amiodarone)

We examined bronchoalveolar lavage (BAL) cell data from 19 patients with a lung disorder presenting clinical, radiologic, functional, and course characteristics of drug-associated interstitial pneumonitis. In each of them, one of 13 different drugs was incriminated and no other cause was found. In one case due to bleomycin, a neutrophil and eosinophil alveolitis was present. In the other 18, the common denominator was a lymphocyte alveolitis, either pure (n = 6) or associated with neutrophilia (n = 5), eosinophilia (n = 3), or neutrophilia and eosinophilia (n = 4). In addition, in all patients, an inverted CD4/CD8 lymphocyte ratio was observed. In eight patients who underwent another BAL, lymphocyte alveolitis decreased but was persistent in two of them two to four months after cessation of treatment with the drug incriminated, whereas interstitial pneumonitis had resolved clinically. In five patients, after resolution of pneumonitis and after an almost normal BAL cell profile was obtained, resumption of treatment with the suspected drug for two to four weeks induced a rise in lymphocyte population in a third BAL. In conclusion, apart from one case of bleomycin lung, the most striking feature of drug-associated alveolitis in this series was expansion of lymphocyte population and imbalance in lymphocyte subsets. When a provocation test was performed, variations in alveolar lymphocyte levels paralleled withdrawal and readministration of the drug responsible for alveolitis. These data could be of value in diagnosing and understanding drug-induced lung disorders.

Assessment of bone marrow involvement by magnetic resonance imaging in small cell lung cancer. No significant change of staging.

STUDY OBJECTIVE: This prospective study was performed in an attempt to evaluate (1) the rate of magnetic resonance imaging (MRI) demonstrating bone marrow (BM) abnormalities, (2) the correlation of these abnormalities with a pathologic malignant BM involvement, and (3) the possible modification of patients' usual disease staging in the light of these abnormalities. METHODS: After extensive staging investigations, patients' diseases were classified as limited or extensive. Dorsal and lumbar spine MRI was performed for second staging. RESULTS: Thirty-two patients were eligible for this study. In ten patients (31.2 percent), MRI showed abnormalities; in four of them, the BM sample from the posterior iliac crest was free from malignancy. Three of these four patients had extensive disease. The last patient, because he had limited disease, had biopsy at the site of MRI abnormalities; the biopsy specimen revealed a malignant involvement and therefore this patient, initially classified as having limited disease, was classified in the extensive disease group. In only 1 of 32 patients, BM-MRI data modified initial staging. CONCLUSIONS: The metastases disclosure yield of the MRI in the detection of medullar involvement is higher than BM biopsy but especially in patients with extensive disease. Therefore, MRI should not be considered in routine practice, in particular in patients with extensive disease.

Human immunodeficiency virus-related lymphocytic alveolitis.

We observed 276 HIV-infected patients to determine the frequency, degree, and clinical presentation of the lymphocytic alveolitis in different stages of HIV disease, and also to identify the lymphocyte subsets involved. In 154 patients with proved lung infections or tumors (group A), bronchoalveolar lavage fluid showed lymphocytosis in 78 percent of cases. In 122 subjects (31 AIDS and 91 HIV-infected non-AIDS patients) without evidence of lung tumor or infection (group B), lymphocytic alveolitis was seen in 72 percent of cases. In 61 of 88 (69 percent) group B lymphocytic patients, we observed respiratory symptoms or diffuse interstitial opacities; however, we also observed such alveolitis in 27 of 46 (59 percent) group B patients free of respiratory symptoms and abnormality of chest x-ray film. This alveolitis was seen not only in AIDS or ARC patients but also at earlier stages of HIV infection. T-lymphocyte analysis showed a large majority (40 to 93 percent) of CD8 positive lymphocytes in the 37 patients tested. A dual fluorescence analysis revealed, in 18 subjects, that those cells were phenotypically cytotoxic (CD8 + D44 +). These findings suggest that, regardless of HIV-infection stages and of opportunistic lung infections, a CD8-positive T-lymphocyte alveolitis may be present in HIV-infected patients and could be responsible for cough, dyspnea, interstitial pneumonitis, and abnormalities of pulmonary function tests.

[Pulmonary infections caused by Pneumocystis carinii]. / Les infections pulmonaires à Pneumocystis carinii.

The following topics are discussed: 1. Pneumocystis carnii: appearance, antigenic structure, pathogenicity...; 2. Human pneumocytosis: clinical, diagnostic, prognostic and therapeutic aspects; 3. Pneumocystis carnii and the pneumocystoses: coexistence, theoretical and practical consequences, difficulties in interpretation of bronchiolo-alveolar lavage.

[Radiologic aspects of acute invasive pulmonary aspergillosis in 18 immunodepressed patients]. / Aspects radiologiques de l'aspergillose pulmonaire aiguë invasive chez 18 malades immuno-déprimés.

A retrospective study of 18 immunodepressed patients with acute invasive pulmonary aspergillosis enabled the radiologic picture of this increasingly frequent opportunist affection to be described, and different manifestations of the disease as a function of underlying conditions to be determined. Two groups could be distinguished: the first of patients with malignant blood diseases (n = 10) when the "aplasia" factor was dominant; the second of patients without blood diseases (n = 8) when the immunodepression was usually induced by a recent increase in corticoid therapy. Neutropenia was not a finding in any of these patients. The most frequent radiologic finding was single or multiple round excavating foci, these corresponding to zones of bronchopneumonia containing aspergillus filaments with central tissue necrosis forming the "target" lesion. The aplasia was distinguished by the multiplicity of lesions and their excavation following aplasia in the shape of a crescent due to sequestrum formation. Prognosis was related to severity of subjacent lesions. In the 2nd group, lesions could be single and nodular; prognosis was improved by the possibility of reducing immunodepression factors.

[Interstitial pulmonary involvements in polymyositis and dermatopolymyositis. Apropos of 3 cases. Review of the literature]. / Atteintes pulmonaires interstitielles des polymyosites (PM) et dermatopolymyosites (DP). A propos de 3 observations. Revue de la littérature.

The authors report 3 cases of myositis associated with pulmonary lesions that preceded or succeeded the muscular disorder. In one of these cases, which was particularly difficult to diagnose, the patient's serum was positive for the anti-Jol antibody. These 3 cases have encouraged the authors to review the literature with particular attention to the diagnostic approach, the latest physiopathological data and the therapeutic basis of the "specific" pulmonary lesions associated with polymyositis and dermatomyositis.