Interstitial pulmonary fibrosis is a common manifestation of systemic sclerosis (SSc) and is a pathologic feature shared by a variety of other diseases. In these other disease processes, the glycoprotein fibronectin (FN) has been shown to be released by the alveolar macrophage, and is thus implicated in the development of fibrosis. We therefore studied the release of FN by alveolar macrophages obtained by bronchoalveolar lavage of 17 patients with SSc and 14 controls. We found that SSc alveolar macrophages released significantly more FN than did those of controls. Furthermore, the level of FN correlated positively with the level of inflammation determined by cellular analysis of lavage fluid and negatively with carbon monoxide diffusing capacity. FN may therefore play a role in the development of lung fibrosis in SSc and may be a marker of alveolitis.Systemic sclerosis (SSc; scleroderma) is a disease characterized by an abnormal increase in fibrous tissue in many organs. Pulmonary fibrosis is a common Submitted for publication September 21, 1988; accepted in revised form December 22, 1988. feature of scleroderma, reported in 70-100% of cases in autopsy studies (1,2), and its relative importance in the clinical course of patients with this illness is increasing. Since the advent of improved treatment for renovascular hypertension and heart disease, which involve the 2 organ systems previously associated with the highest mortality in SSc (3), pulmonary fibrosis is emerging as the major cause of morbidity and mortality among SSc patients.Interstitial pulmonary fibrosis is a pathologic feature seen in both SSc and idiopathic pulmonary fibrosis (IPF). Bronchoalveolar lavage (BAL) has become an accepted tool for investigating changes in the lower respiratory tract in patients with these, as well as other pulmonary diseases (4). Numerous investigators have used BAL to characterize the cellular composition of the alveolar lining in SSc, and most have found changes similar to those in IPF (5-13). Alveolar macrophages of patients with IPF have been found to release factors that may directly influence the development of fibrosis, through recruitment and proliferation of fibroblasts (14-16). One such factor is the glycoprotein fibronectin (FN). We therefore undertook an investigation of pulmonary involvement in SSc, using BAL in nonsmoking patients, to evaluate the cellular content of the lavage fluid and to measure FN release by the alveolar macrophage. Correlations between the level of FN in alveolar macrophage culture supernatants and BAL cellular composition were studied, as were correlations with clinical measures of lung function. PATIENTS AND METHODSPatients and controls. The 17 SSc patients (10 women and 7 men) had a mean age of 45.3 years (range 24.9-62.5).
Progressive systemic sclerosis (PSS), or scleroderma, is a disease of unknown etiology that involves many organ systems, including the lungs. The interstitial lung disease of systemic sclerosis is becoming an increasing cause of morbidity and mortality. This process has been previously evaluated with single-site bronchoalveolar lavage (BAL), gallium scanning, pulmonary function testing, and, occasionally, by open lung biopsy. As BAL has been shown to correlate well with open lung biopsy in systemic sclerosis, we sought to determine if single-site BAL accurately reflects alveolitis in a second site in the lung, and if BAL results correlate with other noninvasive tests of lung inflammation: gallium uptake, chest radiography, or arterial blood gas analysis. We performed 17 studies in 13 patients with scleroderma and found no significant lobar differences in lavage results or gallium scanning. By our criteria for normal versus active alveolitis, only two of 17 patient lavages would have been classified as normal by one side and abnormal by the other side. Although percent gallium uptake was equal bilaterally and supported the concept of alveolitis uniformity, gallium uptake intensity did not correlate with activity as measured by BAL. Furthermore, chest radiograph and arterial blood gas analysis did not correlate with BAL results or gallium scanning. We believe these data support the suitability of single-site lavage in the investigation of systemic-sclerosis-associated alveolitis and diminish the importance of gallium scanning in the investigation of systemic sclerosis pulmonary disease.
Traditional thinking suggests that pleural fluid develops on the basis of systemic venous hypertension or a primary pleural process. Recent investigations, however, indicate that both acute lung injury and pulmonary venous hypertension can be important in the pathogenesis of pleural effusions. To evaluate the role of acute lung injury in the formation of pleural effusions, we developed a model of acute, reversible lung injury in NZW rabbits. Intravenous ethchlorvynol (ECV), known to produce permeability edema in humans, was used to produce permeability pulmonary edema in rabbits. The injury was examined over 14 days with bronchoalveolar lavage, pleural fluid analysis, and morphologic analysis. Ethchlorvynol injection (40 mg/kg) produced a PMN-predominant, exudative alveolitis (2 h), alveolar hemorrhage (6 to 10 h), and pleural effusions by 2 h (peak, 10 h). Pathologic findings included a patchy, subpleural, hemorrhagic PMN inflammatory response, which peaked by 24 h, and an acute PMN vasculitis of small arterioles and capillaries; these changes resolved in 5 to 7 days. No parietal pleural abnormalities were observed. We conclude that ECV induces an acute, reversible parenchymal lung injury resulting in a capillary leak and that fluid moves from the interstitium of the lung into the pleural space along a pressure gradient through a relatively permeable mesothelium. The data support the concept that diffuse or localized lung injury can result in pleural effusions.
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