Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers.

Bombesin-related peptides are growth factors for a variety of cells, including normal human bronchial epithelial cells. An ELISA for bombesin-like peptides (BLP) has been devised using the MAb BBC353, which is specific for the biologically active carboxy-terminal fragment shared by all known BLP. Using this ELISA, we measured bronchoalveolar lavage (BAL) fluid levels of BLP in normal cigarette smokers (n = 15) and normal nonsmokers (n = 18). Smokers' BAL fluid contained increased levels of BLP, whether expressed in terms of BAL fluid volume (P = 0.0001) or protein content (P less than 0.05). BLP levels did not correlate with any cellular constituent in the BAL fluid but immunostaining of lung tissue with BBC353 revealed an intense specific staining of neuroendocrine cells, implying these as a potential source. Two peaks of bombesin-like immunoreactivity were purified using sequential reverse phase and gel filtration HPLC. Both BLP have apparent molecular weights similar to gastrin-releasing peptide on gel filtration HPLC analysis. However, the amino acid composition of these BLP is different from that of gastrin-releasing peptide or neuromedin B, the only known mammalian forms of BLP, suggesting either incomplete purification or novel peptides. Sequence analysis could not be performed due to blocking groups at the amino terminus of these peptides. Our data demonstrate that cigarette smoking is associated with increased levels of pulmonary BLP and imply a potential role for these neuropeptides in the lung's response to tobacco smoke.

Right ventricular dysfunction and the exercise limitation of chronic obstructive pulmonary disease.

This study examined right ventricular function during exercise in patients with chronic obstructive pulmonary disease to answer the following questions: Is there a significant correlation between oxygen consumption at maximal exercise and exercise right ventricular ejection fraction? Does the right ventricular ejection fraction response to exercise correlate with exercise changes in pulmonary artery pressure, total pulmonary resistance or pulmonary vascular resistance? Which combinations of cardiac, ventilatory and blood gas variables are the best predictors of oxygen consumption at maximal exercise? Twenty-six patients with stable chronic obstructive pulmonary disease performed symptom-limited supine bicycle exercise with simultaneous hemodynamic and radionuclide ventriculographic measurements. The oxygen consumption at maximal exercise correlated with the exercise right ventricular ejection fraction (n = 21, r = 0.66; p less than 0.005), exercise stroke volume (r = 0.68; p less than 0.001), exercise cardiac output (r = 0.77; p less than 0.00005) and exercise ventilation (r = 0.85; p less than 0.00001). The change in right ventricular ejection fraction from rest to exercise correlated inversely with the change from rest to exercise in total pulmonary resistance (r = -0.51; p less than 0.05) but not with the change in mean pulmonary pressure (r = -0.37) or in pulmonary vascular resistance (r = 0.09). Multivariate analysis showed that the variables giving the highest combined correlation with oxygen consumption were ventilation and right ventricular ejection fraction (r = 0.95, adjusted r2 = 0.88). These results suggest that exercise oxygen consumption of patients with chronic obstructive pulmonary disease is related to right ventricular systolic function, exercise right ventricular dysfunction is related, in part, to abnormal exercise total pulmonary resistance, and exercise limitation in chronic obstructive pulmonary disease occurs as a result of the dynamic interaction between disordered right heart function and ventilation.

Massive pleural effusions from prostatic lymphangitic carcinomatosis: resolution with endocrine therapy.

Pleural effusions are a rare complication of metastatic adenocarcinoma of the prostate and have not been noted to resolve with endocrine therapy. In a patient with massive bilateral pleural effusions as the initial manifestation of underlying prostatic cancer, lung biopsy specimens documented the presence of lymphangitic carcinomatosis and pleural biopsy tissue was normal. The effusions cleared on two occasions after diethylstilbestrol diproprionate therapy was started. We conclude that massive pleural effusions occasionally complicate prostatic lymphangitic carcinomatosis and that they may resolve with endocrine therapy.

Tuberculosis of the skull.

Because tuberculosis of the skull is relatively unusual occurrence, it may not be immediately recognized. It responds readily to chemotherapy and should be suspected in disseminated tuberculosis or in any draining lesion of the skull that is sterile or fails to respond to conventional antibiotic therapy.

Acute nephritis and pulmonary alveolitis following pneumococcal pneumonia.

Acute glomerulonephritis developed in a man with pneumococcal pneumonia. Serum complement studies revealed decreased levels of C4, properdin, and C3. Renal immunofluorescence studies demonstrated pneumococcal antigen, C1q, C4, C3 proactivator, properdin, C3, IgG, and IgM. Circulating cryoglobulin contained pneumococcal antigen and antibody, C3, and immunoglobulins. Serial pneumococcal antigen and antibody levels did not display patterns that were characteristic of classical immune elimination, but the patterns may have been influenced by the reentry of antigen. A diffuse, pulmonary alveolitis also developed in the patient. Lung immunofluorescence studies revealed pneumococcal antigen, IgG, and C3 in alveolar walls and capillary basement membranes. The glomerulonephritis and alveolitis resolved after a prolonged course. These findings provide presumptive evidence for pneumococcal, immune complex glomerulonephritis with complement activation via both classical and alternative pathways and suggest an immunologic pathogenesis for the pulmonary alveolitis.

Diffuse alveolar hemorrhage and systemic lupus erythematosus. Clinical presentation, histology, survival, and outcome.

Diffuse alveolar hemorrhage (DAH) complicating systemic lupus erythematosus (SLE) remains a devastating pulmonary complication of this systemic disease. We conducted this study to review the clinicopathologic presentation and the effects of prior treatment, presence of infection, and current treatment on the survival and outcome of patients with DAH and SLE. We reviewed the records of 15 SLE patients who experienced 19 episodes of DAH over a 10-year period in a single tertiary care hospital. These patients were compared with 57 previously reported cases. The 19 episodes of DAH represented 3.7% of the 510 admissions occasioned by various complications of SLE. As previously reported, the majority (66%) were women with a median age of 27 years. The onset was often abrupt: < 3 days in 12 of the episodes. In 3 patients (20%), DAH was the initial manifestation of SLE, compared with 11% in the literature series. In the other patients in the present series, DAH appeared a median of 31 months following the diagnosis of SLE, versus 35 months in the literature series. In only 42% of the episodes in the present series, compared with 66% in the literature series, was hemoptysis present at the time of admission. However, hemoptysis eventually appeared in all 19 episodes. Temperature elevation (> 38 degrees C) was another inconsistent finding, found in only 5 episodes (26%) in the present series. The most constant concurrent systemic finding was lupus nephritis (14/15 patients). This represents a significant increase when compared with the literature series (29/48 patients). In 8 of 10 patients in whom lung tissue was available, pulmonary capillaritis accompanied the DAH. This represents a marked difference in the underlying histologic pattern when compared with the literature series. In those patients, 72% (31/43 patients) had bland pulmonary hemorrhage, and capillaritis was described in only 6 patients. The overall patient mortality rate was 53% in the current series and 50% in the literature series. Factors associated with an increased mortality in the present series include the following: mechanical ventilation (62%) versus no mechanical ventilation (0%); infection (78%) versus no infection (20%); and cyclophosphamide therapy for the acute DAH episode (70%) versus no cyclophosphamide therapy (20%). The incidence of infection in DAH and SLE (9/19 episodes) is far greater than previously reported (7/ 57 episodes). One possible explanation for this difference is the increased use of outpatient immunosuppressive therapy with monthly intravenous cyclophosphamide therapy for lupus nephritis. Eighteen DAH episodes in the present series were treated with intravenous methylprednisolone. When one combines both the current and literature series experience (16 episodes), the use of plasmapheresis does not improve survival. Of the 7 patients in the present series who survived all episodes of DAH, 6 remain alive a median of 50 months post episode and without recurrence of DAH. Diffuse alveolar hemorrhage is an uncommon but lethal complication of SLE. The survival rate remains unchanged from previous reports. The absence of hemoptysis should not exclude this diagnosis, particularly in those patients who experience an acute pulmonary syndrome with new radiographic infiltrates accompanied by falling hematocrit and the presence of a hemorrhagic bronchoalveolar lavage. Evidence for lupus nephritis is present in the great majority of cases. Most cases demonstrate the histologic pattern of pulmonary capillaritis. The mortality is adversely affected by the need for mechanical ventilation, either the presence of infection at the time of admission or the development of infection in the hospital, and the use of cyclophosphamide for treatment of the acute event.

Pulmonary cavitation following pulmonary infarction.

Cavitation following bland pulmonary infarction is not commonly considered in the differential diagnosis of cavitary lung disease. In a 4-year period we have found 10 cases of cavitating pulmonary infarction (CPI) by reviewing serial chest radiographs from autopsies with pulmonary infarction and in all cases with positive ventilation-perfusion lung scans. We have compared these cases to 31 previously reported cases in the English literature that met our criteria for CPI. In our 10 patients, there were 12 radiographic cavities; 5 in the upper lobes, 5 in the lower lobes and 2 in the middle lobe. This distribution was consistent with a relative upper-lobe predominance in the literature review. In nine patients the cavitation appeared rapidly (mean, 5 days) and was associated with fever, purulent sputum, and leukocytosis. Sputum cultures were obtained in eight patients, revealing Pseudomonas aeruginosa and Escherichia coli in three each and Proteus species in two. In four patients, pulmonary infarction was not considered and the diagnosis was made at autopsy, a situation also common in previously reported cases. We have seen a high incidence of CPI in a retrospective review of patients with pulmonary infarction, and we believe that it is important to consider this diagnosis when evaluating cavitary lesions.

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.

Acute interstitial pneumonitis. Case series and review of the literature.

Acute interstitial pneumonitis (AIP) is an acute, idiopathic interstitial lung disease characterized by rapidly progressive diffuse pulmonary infiltrates and hypoxemia requiring hospitalization. The case-fatality ratio is high. Previous reports suggested that survivors of the acute event have a favorable outcome. We undertook this study to examine the natural history of survivors. We had observed several patients who experienced recurrent episodes of AIP and chronic progressive interstitial lung disease. We sought to determine longitudinal survival in these patients and to compare our experience with that in the medical literature. Overall, we identified 13 biopsy-proven cases of AIP. The mean patient age was 54 years in our review, which is identical to previous reports. Twelve patients were hospitalized and all 12 required mechanical ventilation. Overall hospital survival was 67%. All patients demonstrated abnormalities in gas exchange at presentation. Radiographs typically demonstrated bilateral patchy densities that progressed to a diffuse alveolar filling pattern in nearly all cases. All biopsy specimens showed organizing diffuse alveolar damage. Longitudinal data were available for 7 patients. Two died of AIP recurrences. A third died of complications of heart failure shortly after hospital discharge. One patient progressed to end-stage lung disease and required lung transplantation. Two patients experienced persistent pulmonary symptoms, accompanied in 1 by progressive lung fibrosis. One patient had nearly complete recovery of lung function 2 years following AIP. (Follow-up information was unavailable for 2 survivors.) In our literature review, 5 of 7 patients reported experienced some recovery of lung function. One case of progressive interstitial lung disease requiring lung transplantation was reported. The reported mortality was much higher than in our experience (74% versus 33%). The mean time from symptom onset to death was 26 days, compared with 34 days in our experience. The use of corticosteroids did not appear to influence survival, although this has not been tested in a rigorous manner. The better survival in our series may be related in part to a survivor selection bias. In contrast to previous reports, we found that survivors of AIP may experience recurrences and chronic, progressive interstitial lung disease. We did not identify any clinical or pathologic features that predict mortality in these patients. Likewise, there were no features that predicted the longitudinal course in survivors. Further study to identify causal factors is required in the hope of preventing morbidity and mortality related to this disease.

The use of fluorescent labeled antigen to follow the fate of instilled immune complexes in the rabbit lung.

To follow the fate of exogenously introduced immune complexes in the rabbit lung, a direct labeling method was devised. Bovine serum albumin was incubated with fluorescein isothiocyanate, washed and then bound at equivalence with antibovine serum albumin. Immune complexes thus prepared are injected into a rabbit airway and the animal was sacrificed. Using chilled alcohol fixative and paraffin embedding 4 micrometer sections were prepared for light and fluorescent microscopy. This technique readily verifies that labeled antigen is taken up by alveolar macrophages. Electron microscopy using ferritin-antiferritin complexes corroborate these light findings.

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.

Gas exchange at a given degree of volume restriction is different in sarcoidosis and idiopathic pulmonary fibrosis.

PURPOSE: It is likely that the relationship between lung volume changes and gas exchange in patients with idiopathic pulmonary fibrosis (IPF) and patients with sarcoidosis is different since the two conditions vary widely in histopathology and prognosis. Few studies, however, have examined this relationship. The goal of this investigation was to measure diffusing capacity and gas exchange in patients with IPF and sarcoidosis in whom the reduction of lung volume was equivalent. PATIENTS AND METHODS: In 21 patients with IPF and 20 patients with pulmonary sarcoidosis with comparable reductions in lung volume, the single breath diffusing capacity for carbon monoxide and gas exchange at rest and during exercise were compared. RESULTS: The relationship between lung volume and gas transfer differed in the two groups of patients. Resting and exercise gas exchange tended to be relatively normal and the diffusing capacity was higher in patients with sarcoidosis than in those with IPF. These differences could not be attributed to disparities in race, age, smoking habits, or the radiographic stage of sarcoidosis. CONCLUSION: The preservation of gas exchange in sarcoidosis as opposed to IPF, despite equivalent degrees of volume restriction, suggests that different pathophysiologic mechanism underlie the volume loss and gas exchange defects seen in these disorders. Furthermore, these findings suggest that diffusing capacity may not be a sensitive indicator of pulmonary pathology in sarcoidosis since lung volume can be altered independently of abnormalities in the diffusing capacity.

A new radiologic sign of subpulmonic effusion.

A new radiologic sign of subpulmonic effusion is described. That is obliteration of the intrapulmonary blood vessels which are seen below the level of the diaphragmatic dome. One hundred normal chest films are reviewed as well as nine patients with subpulmonic effusions. In three of the patients with subpulmonic effusions, this sign was the first evidence of pleural effusion.

Massive hemoptysis from a pulmonary artery aneurysm associated with an emphysematous bulla.

A 66-year-old man with a history of COPD and Aspergillus fumigatus infection developed massive hemoptysis. Pulmonary artery angiography revealed an aneurysm which was successfully treated with coil embolization. This is the first known report of a pulmonary artery aneurysm causing massive hemoptysis in a patient with bullous emphysema.

Unsuspected pulmonary alveolar proteinosis complicating acute myelogenous leukemia.

A patient with acute myelogenous leukemia developed pulmonary alveolar proteinosis in the terminal phase of the leukemia. The diagnosis of pulmonary alveolar proteinosis was unsuspected during life and was established only at autopsy. Other reported cases of the same association are reviewed. This report serves to stress the importance of considering the diagnosis of pulmonary alveolar proteinosis in malignant hematologic diseases and the need for hematologic evaluations in pulmonary alveolar proteinosis.

Acute eosinophilic pneumonia in AIDS.

A 39-year-old man with AIDS presented with acute respiratory distress and diffuse bilateral infiltrates seen on a chest radiograph. Acute eosinophilic pneumonia (AEP) was diagnosed by thoracoscopic lung biopsy. There was no evidence of an infectious etiology, and the patient rapidly improved with corticosteroid therapy. Several of the idiopathic interstitial pneumonias have been reported in adult patients with AIDS. To our knowledge, this case represents the first tissue-confirmed case of AEP associated with adult AIDS.

Gaucher's disease. An unusual cause of intrathoracic extramedullary hematopoiesis.

A thoracic paravertebral mass in an asymptomatic woman with type 1 Gaucher's disease proved to be due to extramedullary hematopoiesis. This is, to our knowledge, the first case of intrathoracic extramedullary hematopoiesis reported with Gaucher's disease.

Diffuse alveolar hemorrhage due to antibasement membrane antibody disease appearing with a polyglandular autoimmune syndrome.

We describe a patient with type 3-C polyglandular autoimmune syndrome who presented with diffuse alveolar hemorrhage and normal renal function. The diagnosis of antibasement membrane antibody disease was established by immunofluorescent staining of transbronchial biopsy specimens. We suggest the incorporation of antibasement membrane antibody disease into the spectrum of diseases that define the polyglandular autoimmune syndromes.

Hypoxemia explained 36 years later.

A 37-year-old man who had an atrial septal defect (ASD) corrected as an infant was found to be hypoxemic with a 22% shunt. An MRI scan revealed that the patient's inferior vena cava drained into his left rather than his right atrium, a previously undetected complication of his ASD repair 36 years before.