Angiotensin convertase activities in human alveolar macrophages: effects of cigarette smoking and sarcoidosis.

Angiotensin I convertase activity has been found in human alveolar macrophages from normal volunteers and patients with pulmonary sarcoidosis. This activity is higher in the alveolar macrophages from smokers than from nonsmokers, and is even more elevated in sarcoid patients. The activity can be detected with both angiotensin I and bradykinin analogs and appears to require protein synthesis, but the enzyme is not secreted by alveolar macrophages in culture.

Alveolar macrophage-derived chemotactic factor: kinetics of in vitro production and partial characterization.

Alveolar macrophages are the initial phagocytic cells that encounter foreign material and particulates deposited in the terminal airways. We have examined a mechanism by which these cells, after phagocytic challenge, may control or amplify the inflammatory response in lung parenchyma. Normal human alveolar macrophages (AM) were studied from eight subjects. With in vitro culture, AM produced and released two substances into culture media which have potent chemoattractant activity for blood polymorphonuclear granulocytes (PMN) and negligible activity for mononuclear cells. Release of these factors is maximally stimulated by aggregated human immunoglobulin (Ig)G or zymosan particles; however, simple adhesion of the macrophages to plastic surfaces is also sufficient to stimulate release of these chemotactic substances. The larger substance (10,000 daltons) is immunologically distinct from C5a and interacts with a different PMN membrane receptor than that known to exist for formyl-methionyl-leucyl-phenylalanine. Its chemotactic activity is sensitive to the enzymatic effect of trypsin. Although producing a single elution peak on gelfiltration chromatography, electrofocusing in polyacrylamide gels yielded five peaks of radioactivity. Chemotactic activity was localized to a fraction with a pI = 5.0. The smaller molecular weight substance has been less well characterized. Thus, the human AM can produce at least two factors which attract PMN and this capability may augment the local inflammatory response in the lung.

Cystic fibrosis pseudomonas opsonins. Inhibitory nature in an in vitro phagocytic assay.

Pseudomonas aeruginosa infection plays a primary pathogenetic role in the chronic respiratory tract disease of cystic fibrosis (CF) patients. Despite pronounced humoral immune responses, reflected by high levels of antibodies against Pseudomonas in serum and in sputum, the antibodies do not eliminate this bacterium. In the present study we have used affinity chromatography with a lipopolysaccharide substituted immunoadsorbent gel to isolate high titers (meanCF = 1:256) of immunotype specific Pseudomonas IgG antibodies from the sera of nine CF subjects, and have evaluated the functional ability of these antibodies to promote phagocytosis and intracellular killing of P. aeruginosa in an in vitro human alveolar macrophage culture system. The phagocytic and intracellular bactericidal kinetics revealed that CF IgG antibodies function in an inhibitory fashion. Both the rate of phagocytosis (rateCF = 204 cpm/unit time) and absolute bacterial uptakes maximal at 120 min (uptakeCF = 18 x 10(3) 14C cpm) were inhibited compared with appropriate positive controls (hyperimmune serum, HIS; [rateHIS = 399; uptakeHIS = 29 x 10(3), P less than 0.005]). The ability of such CF-derived opsonins to potentiate macrophage intracellular bactericidal processes was mildly impaired (bacterial survivalCF = 15 x 10(3) colony forming units (CFU)/min, survivalHIS = 9 x 10(3)). Further characterization of this defect, assessed with functional studies of the Fab and Fc portions of the immunoglobulin molecule, revealed an impairment in the attachment of these specific antibodies to the alveolar macrophage membrane Fc gamma receptors. Preliminary studies of the physical-chemical properties of these immunoglobulins were normal. The expression of this inhibitory activity in vivo may facilitate Pseudomonas colonization and the subsequent established infections in the respiratory tracts of CF subjects.

Intratumoral Bacillus Calmette-Guérin immunotherapy prior to surgery for carcinoma of the lung: results of a prospective randomized trial.

A prospective randomized trial of preoperative intratumoral therapy with Bacillus Calmette-Guérin (BCG) was conducted in non-small cell lung cancer patients. Eighty-eight patients (48 BCG-treated and 40 control subjects) were entered into the study; three control subjects were removed from data analysis because histology revealed pathology other than non-small cell lung cancer. There were no differences between BCG-treated and control patients in sex, age, cigarettes smoked per day, pack-years of cigarette smoking, white blood cell count, or number of peripheral blood lymphocytes. Toxicity of BCG was limited to transient malaise and fever (average peak temperature, 38.7 degrees C). There was no significant difference in outcome (recurrence or survival) between BCG-treated and control groups with Stage I or Stage III tumors; there were too few Stage II tumors for separate statistical analysis. Outcome was not affected within or between the two treatment groups by tuberculin skin test status. Combining both treatment groups, Stage III patients had a worse outcome than did Stage I-II patients, non-squamous cell tumor patients (large cell and adenocarcinoma) had worse outcomes than did squamous cell tumor patients, and men had a worse outcome than women. We conclude that, although preoperative intratumoral BCG therapy is safe, it does not lengthen disease-free interval or prolong survival in patients with non-small cell lung cancer.

Timing of oral anticoagulation therapy in the treatment of angiographically proven acute pulmonary embolism.

The optimal time to begin oral anticoagulation therapy with warfarin sodium in the treatment of acute pulmonary embolism has not been defined. To evaluate the relative cost, efficacy, and safety of early initiation of warfarin therapy, we reviewed the medical records of 38 patients with angiographically proven pulmonary embolism. Patients were divided into two groups: those who received warfarin early (less than or equal to 3 days after initial heparin sodium bolus, n = 17) and those who were treated late (greater than 3 days after initial heparin bolus, n = 21). After three months of follow-up, there was a similar incidence of mortality, recurrent pulmonary embolism, and bleeding complications in both treatment groups. Length of hospitalization was substantially less in the early group (9.6 +/- 2.0 vs 11.8 +/- 2.1 days). Early warfarin therapy in the treatment of acute pulmonary embolism appears to be both cost-effective and safe. A prospective multicenter controlled trial should be performed.

Pulmonary manifestations of systemic lupus erythematosus: review of twelve cases of acute lupus pneumonitis.

Acute lupus pneumonitis was the presenting manifestation of systemic lupus erythematosus in six of 12 cases in this series. The clinical picture was characterized by severe dyspnea, tachypnea, fever and arterial hypoxemia. Radiographic findings included an acinar filling pattern which was invariably found in the lower lobes and was bilateral in 10 of the cases. Studies failed to reveal evidence of infection as a cause of the acute pulmonary infiltrates. All patients were treated with oxygen and corticosteroids; seven received azathioprine. Six patients survived and are clinically well 14 months to four years following their acute illness. Three of these patients have residual interstitial infiltrates with persistent pulmonary function test abnormalities indicating progression to chronic interstitial pneumonitis. Histologic sections of the lungs available from four patients revealed hyaline membranes and interstitial edema (four cases), acute alveolitis (two cases), arteriolar thrombosis (one case) and a prominent lymphocytic interstitial pneumonitis with organizing bronchiolitis (one case).

Interstitial lung disease in polymyositis and dermatomyositis: analysis of six cases and review of the literature.

Interstitial pneumonitis may be the presenting manifestation of polymyositis-dermatomyositis, or may occur later in the evolution of the disease. The clinical picture is characterized by non-productive cough, dyspnea and hypoxemia. The chest radiograph demonstrates interstitial infiltrates with predilection for the lung bases, often with an alveolar pattern in addition. The histopathologic features are those of organizing and interstitial pneumonitis and pleuritis, with variable fibrosis. In the present series, the patients with mixed alveolar and interstitial infiltrates on chest radiograph and organizing pneumonia and bronchiolitis obliterans in addition to interstitial pneumonitis. In one patient evolution from pulmonary inflammation to interstitial fibrosis was demonstrated. The etiology of primary lung disease in PM-DM is not known, but cell-mediated autoimmunity to an unidentified component of lung tissue is suggested. Including the present series, 50 percent of patients have responded favorably to corticosteroids with decreased dyspnea, clearing of the chest radiograph and improved pulmonary function tests.

Cytotoxic drug-induced lung disease.

Cytotoxic drugs, principally bleomycin, methotrexate and busulfan, have been associated with pulmonary toxicity. Cytotoxic drug-induced lung disease may be difficult to establish with certainty because other causes of pulmonary disease are frequently present. We discuss the clinical, roentgenographic and histologic effects of the administration of bleomycin, methotrexate, busulfan and other cytotoxic agents on the lungs and suggest that these agents may also cause pulmonary malignancies. We note the importance of careful patient monitoring and withdrawal of a demonstrated offending agent.

Bacteremic hemophilus influenzae pneumonia in adults. A report of 24 cases and a review of the literature.

Twenty-four cases of Hemophilus influenzae pneumonia diagnosed by positive blood or pleural fluid cultures are compared to 43 cases previously reported in the literatrue. Frequently associated illnesses in both series include alcoholism, chronic airways obstruction and preceding respiratory tract infection. Moderate temperature elevation and slight leukocytosis were common on admission in both groups. Chest roentgenograms in our series revealed both bronchopneumonia (75 per cent) and lobar consolidation (38 per cent). Pleural disease occurred frequently, with two empyemas noted on admission and nine additional effusions developing during therapy. Treatment of choice was ampicillin. All five patients who did not receive ampicillin died, whereas 16 to 19 who received this drug survived. High mortality (33 per cent) in our series may be attributed to the advanced age of the patients and the presence of associated illnesses. In addition, a 10 year review suggests a true increase in the incidence of H. influenzae pneumonia in adults.

Effect of positive end-expiratory pressure on right ventricular performance. Importance of baseline right ventricular function.

Thirty-six patients with diverse baseline right ventricular function were evaluated during incremental positive end-expiratory pressure (PEEP) application. Right heart pressures, cardiac output, right ventricular ejection fractions, and ventricular volumes were obtained at each PEEP level. Right ventricular peak systolic pressure-end-systolic volume relations were analyzed as an index of contractile function. Patients with severely depressed baseline right ventricular ejection fractions (30 percent or less) had an increase in end-diastolic (270 +/- 74 to 391 +/- 76 ml, 0 to 20 cm water (H2O) PEEP, p less than 0.05) and end-systolic volumes (210 +/- 70 to 321 +/- 70 ml, 0 to 20 cm H2O PEEP, p less than 0.05). These patients also had a decline in estimated right ventricular contractile function at 20 cm H2O PEEP as estimated by the slope of systolic pressure-volume relations (0.12 to 0.04 mm Hg/ml, 0 to 15 and 15 to 20 cm H2O PEEP, respectively, p less than 0.05). Patients with normal (40 percent or more) or moderately depressed (31 to 40 percent) baseline right ventricular ejection fractions had no change in right ventricular volumes or estimated contractile function. Therefore, the effect of PEEP on right ventricular function differs depending on the baseline right ventricular ejection fraction.

Noninvasive radiographic assessment of cardiovascular function in acute and chronic respiratory failure.

Noninvasive radiographic techniques have provided a means of studying the natural history and pathogenesis of cardiovascular performance in acute and chronic respiratory failure. Chest radiography, radionuclide angiocardiography and thallium-201 imaging, and M mode and cross-sectional echocardiography have been employed. Each of these techniques has specific uses, attributes and limitations. For example, measurement of descending pulmonary arterial diameters on the plain chest radiograph allows determination of the presence or absence of pulmonary arterial hypertension. Right and left ventricular performance can be evaluated at rest and during exercise using radionuclide angiocardiography. The biventricular response to exercise and to therapeutic interventions also can be assessed with this approach. Evaluation of the pulmonary valve echogram and echocardiographic right ventricular dimensions have been shown to reflect right ventricular hemodynamics and size. Each of these noninvasive techniques has been applied to the study of patients with respiratory failure and has provided important physiologic data.

Contrasting acute effects of vasodilators (nitroglycerin, nitroprusside, and hydralazine) on right ventricular performance in patients with chronic obstructive pulmonary disease and pulmonary hypertension: a combined radionuclide-hemodynamic study.

Fourteen patients with chronic obstructive pulmonary disease, mild to moderate pulmonary hypertension, and diminished right ventricular (RV) ejection fraction were studied acutely with use of a combined radionuclide-hemodynamic approach to assess and contrast the effects of 3 vasodilators on RV performance and central hemodynamic function. Nitroglycerin significantly decreased mean right atrial pressure, RV end-diastolic volume index, mean pulmonary artery pressure, cardiac index, and arterial oxygen tension, but did not affect pulmonary vascular resistance index and increased RV ejection fraction. Nitroprusside had similar effects on mean right atrial pressure, RV end-diastolic volume index, mean pulmonary artery pressure, cardiac index, and arterial oxygen tension, but also mildly decreased pulmonary vascular resistance index and did not alter RV ejection fraction. In contrast, hydralazine decreased pulmonary vascular resistance index and increased cardiac index and RV ejection fraction. The increase in ejection fraction correlated well with the decrease in pulmonary vascular resistance. These data suggest that in patients with mild to moderate secondary pulmonary hypertension, acute administration of hydralazine results in a substantial improvement in RV performance by virtue of decreasing pulmonary vascular resistance. In contrast, nitroglycerin and nitroprusside demonstrate predominant effects that reduce preload, cardiac index, and arterial oxygen tension. Based on these data, afterload reduction with vasodilators such as hydralazine may be potentially useful in selected patients with pulmonary disease and secondary pulmonary hypertension and appear preferable to agents that primarily reduce preload. Further long-term studies are necessary to establish therapeutic efficacy.

Noninvasive diagnosis of pulmonary arterial hypertension in chronic obstructive pulmonary disease: right ventricular ejection fraction at rest.

Because right ventricular ejection fraction (RVEF) depends on impedance to RV ejection, the hypothesis was tested that an abnormality in radionuclide-determined RVEF would be a useful noninvasive predictor of pulmonary artery (PA) hypertension in patients with chronic obstructive pulmonary disease (COPD). Simultaneous measurements of resting RVEF and PA pressure were made in 30 patients with COPD. All were stable and without clinical evidence of respiratory decompensation or congestive heart failure. Eleven patients had normal (less than 20 mm Hg) mean PA pressure and 19 patients had PA hypertension. The average RVEF was 41 +/- 7% (range 29 to 60%). Five patients had normal (greater than 45%) and 25 patients depressed RVEF. An inverse linear relation between mean PA pressure and RVEF was present (r = -0.74). In the group with normal PA pressure, RVEF averaged 48% (range 42 to 60%). In the group with PA hypertension, RVEF averaged 36% (range 29 to 44%). RVEF was significantly higher in the group with PA hypertension. Using RVEF less than 45% as an indicator of PA hypertension, the sensitivity was 100%, the specificity 55%, and the predictive accuracy of a positive result 79%. Using RVEF less than or equal to 40% as an indicator of PA hypertension, the sensitivity was 75%, the specificity 100%, and the predictive accuracy of a positive study 100%. Thus, radionuclide-determined RVEF using the first-pass technique and a multicrystal camera is a useful noninvasive test for diagnosing PA hypertension in patients with advanced COPD.

Assessment of cardiac performance with quantitative radionuclide angiocardiography: right ventricular ejection fraction with reference to findings in chronic obstructive pulmonary disease.

A reproducible noninvasive technique for measuring righ ventricular ejection fraction was developed using first pass quantitative radionuclide angiocardiography. Studies were obtained in the anterior position with a computerized multicrystal scintillation camera with high count rate capabilities. Right ventricular ejection fraction was calculated on a beat to beat basis from the high frequency components of the background-corrected right ventricular time-activity curve. In 50 normal adults, right ventricular ejection fraction averaged 55 percent (range of 45 to 65 percent). This radionuclide measure of right ventricular function was reproducible, with minimal inter- and intraobserver variability, and was sensitive to changes in inotropic state induced with isoproterenol. In 36 patients with chronic obstructive pulmonary disease, right ventricular ejection fraction ranged from 19 to 71 percent. All 10 patients with corpulmonale, as well as 9 additional patients, had an abnormal right ventricular ejection fraction. Arterial oxygen tension and forced expiratory volume were depressed significantly more in patients with abnormal right ventricular ejection fraction than in subjects with normal right ventricular function. There was no relation between abnormalities in right and left ventricular ejection fraction.

Differing responses in right and left ventricular filling, loading and volumes during positive end-expiratory pressure.

Using a combined hemodynamic and radionuclide technique, 20 patients with varied ventricular function were evaluated during positive end-expiratory pressure (PEEP) application. Left ventricular (LV) and right ventricular (RV) ejection fractions and cardiac output were measured, and ventricular volumes were derived. Seven patients (group 1) who had an increase in LV end-diastolic volume with PEEP and 13 patients (group 2) who had the more typical response, a decrease in LV end-diastolic volume with PEEP, were identified. Compared with group 2, group 1 patients had a higher incidence of coronary artery disease (5 of 7 vs 1 of 13, p less than 0.005) and lower cardiac output (3.9 +/- 1.6 vs 9.1 +/- 3.2 liters/min, p less than 0.005), LV ejection fraction (27 +/- 13 vs 51 +/- 21%, p less than 0.05), RV ejection fraction (15 +/- 6 vs 32 +/- 8%, p less than 0.005) and peak filling rate (1.32 +/- 0.43 vs 3.51 +/- 1.70 end-diastolic volumes/s, p less than 0.05). LV and RV volumes increased and peak filling rate decreased with PEEP in group 1, whereas in group 2 LV volume decreased and RV volume and peak filling rate remained unchanged. Using stepwise regression analysis, the change in LV volume with PEEP was related directly to baseline systemic vascular resistance and inversely to baseline blood pressure. Similarly, the change in peak filling rate with PEEP was inversely related to the change in RV end-diastolic volume. Thus, the hemodynamic response to PEEP is heterogeneous and may be related to LV ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

First-pass radionuclide assessment of right and left ventricular performance in patients with cardiac and pulmonary disease.

First-pass radionuclide angiocardiography allows noninvasive determination of right and left ventricular performance from a single study. Analysis is made from the high frequency components of the regional radionuclide time-activity curves. Both regional and global ventricular performance can be assessed at rest and during exercise. Sequential studies can be performed to evaluate therapeutic interventions. This technique has been applied in a broad spectrum of patients with cardiac and pulmonary disease and has been shown to have major clinical impact.

Favorable cardiovascular effects of theophylline in COPD.

Theophylline has been utilized widely as a bronchodilator. However, recent studies have shown the potential for administering this drug to enhance cardiovascular performance in patients with chronic obstructive pulmonary disease (COPD). Administered to COPD patients orally as a sustained-action preparation or intravenously as aminophylline, theophylline enhances both right and left heart systolic pump function and lowers both pulmonary artery pressure and pulmonary vascular resistance. These favorable cardiovascular actions suggest an additional use for theophylline in COPD beyond its effects as a bronchodilator.

Effects of theophylline on cardiovascular performance in chronic obstructive pulmonary disease.

Theophylline is a widely used bronchodilator, but only recently have its positive cardiovascular actions been recognized in patients with chronic obstructive pulmonary disease (COPD). Intravenous aminophylline acutely reduces pulmonary artery pressures and pulmonary vascular resistance and increases both right and left ventricular ejection fraction. Oral long-acting theophylline produces a similar and chronic improvement in biventricular performance. Postulated mechanisms by which theophylline enhances right and left ventricular systolic pump performance include reduction in ventricular afterload and positive effects of the drug on ventricular inotropy. Theophylline may be particularly valuable in patients with a combination of COPD, pulmonary artery hypertension, and right or left heart failure.

Enlarging, atypically located pericardial cyst. Recent experience and literature review.

Pericardial cysts frequently are recognized when they present in a cardiophrenic angle, but may not be suspected when they occur elsewhere in the chest. To highlight the unusual presentations of pericardial cysts, we present two patients with cysts in the upper mediastinum and review the reported experience with similar lesions. Our patients' cysts are particularly instructive because one cyst enlarged over 23 months and because the other did not appear cystic on a computerized tomographic scan. Because percutaneous aspiration may be an attractive alternative to surgical resection when a pericardial cyst is suspected, clinicians should include pericardial cyst in the differential diagnosis of upper mediastinal masses.

Cardiovascular-pulmonary monitoring in the intensive care unit (Part 2).

Proliferation of technology in the ICU likely will continue at a rapid pace. This presents a strong challenge to the clinician's task of "above all, do not harm." While invasive techniques carry obvious direct risks, both invasive and noninvasive monitoring present a more subtle threat. Pitfalls in the acquisition and interpretation of data must be recognized before appropriate therapeutic decisions can be made. Advanced monitoring devices and techniques must supplement and not supplant clinical assessment.