Pulmonary hypertension (PHT) is an important complication of systemic sclerosis (SSc). Echocardiography can be used to detect PHT and, with Doppler echocardiography, the pulmonary arterial systolic pressure (PASP) can often be estimated. We have undertaken a study to compare echocardiographic assessment with right heart catheterization (RHC) in 33 SSc patients in whom clinical assessment [including ECG, chest X-ray, lung function tests and high-resolution computed tomography (HRCT) had raised strong suspicion of PHT. The mean (S.D.) interval between echocardiography and RHC was 1.8 (2.3) months. Twenty-one patients (64%) had PHT (PASP > or = 30 mmHg) on RHC, and echocardiography correctly identified 19 of these (sensitivity 90%). Of the 12 patients without PHT on RHC, nine were correctly identified by echocardiography (specificity 75%). The five incorrectly classified patients all had PASP in the borderline normal/abnormal range. The presence of tricuspid regurgitation allowed Doppler measurement of PASP in 20 patients (61%) and this correlated significantly with RHC values (r = 0.83, P < 0.001). We conclude that echocardiography is a reliable method for detecting PHT and it may be particularly useful for the early detection and monitoring of this potentially fatal complication in SSc.

Abstractjunction with fibrosing alveolitis. In SSc comBackground -Systemic sclerosis (SSc) plicated by PHT the pulmonary vasculature may be complicated by pulmonary hyper-responsiveness to vasodilator medications is tension (PHT), which can occur both in often altered.2 When PHT complicates SSc the the setting of fibrosing alveolitis or as lone prognosis for survival is poor, and pulmonary pulmonary vascular disease. Nitric oxide disease complicated by PHT is the most com-(NO) is a powerful vasodilator and is pro-mon cause of death in these patients. duced by various cells in the respiratoryThe mechanism underlying the development tract including pulmonary vascular endo-of PHT in SSc is unknown. In other interstitial thelial cells and can be measured in ex-lung diseases PHT normally occurs as a late pired air. A study was undertaken to test complication of severe fibrosis or may occur in the hypothesis that exhaled NO levels the presence or absence of parenchymal lung would be decreased in patients with SSc disease or in conjunction with fibrosing alwith PHT and to assess the utility of this veolitis. In SSc, however, PHT may occur with measurement in discriminating between minor or no parenchymal fibrosis, suggesting patients with and without PHT, regardless that different mechanisms may be involved in of concurrent fibrosing alveolitis.the development of pulmonary vascular disMethods -Exhaled NO was measured with ease. Systemic sclerosis is characterised by a chemiluminescence analyser in 23 widespread vascular disease which can be manpatients with SSc (six with PHT, 17 sub-ifested in many organs. Endothelial morjects without) and in 67 normal in-phological 4-6 and functional 7 changes have been dividuals. Doppler echocardiography was found in patients with early SSc, suggesting used to assess pulmonary artery pressure that such abnormalities may be important in in subjects with SSc, and lung function the genesis of vascular disease in this condition. tests were performed at the same visit as The importance of endothelium and endo-NO measurements. Thin section CT scans thelium derived factors in controlling the pulwere analysed for the presence of ab-monary vasculature has been increasingly normality consistent with fibrosing al-recognised. veolitis.Once PHT has developed it is easily diagResults -Patients with SSc with PHT had nosed by Doppler echocardiography, but to a greater reduction in arterial oxygen identify patients at risk of developing PHT is tension (PaO 2 ) and carbon monoxide gas more difficult. A reduction in carbon monoxide transfer (TLCO) than patients with SSc transfer factor (T), particularly to less than without PHT. Exhaled NO was sig-50% of the predicted value, is recognised as a nificantly higher in patients with SSc with-risk factor for PHT. The specificity of this test out PHT than in normal individuals, and is low, however, and there remains the need was significantly decreased in patients for a test to identify reliably those patients with with SSc with PHT (mean (SD) 20 (6) ppb)...

Lone cryptogenic fibrosing alveolitis (CFA) is histologically identical to fibrosing alveolitis associated with systemic sclerosis (FASSc), but it has a much worse prognosis after matching for disease severity at presentation. Thin-section CT scanning (CT) provides a reproducible method of quantifying the morphologic extent of fibrosing alveolitis. The aim of this study was to gain insights into contrasting pathophysiologic mechanisms in the two diseases by comparing patterns of functional impairment after matching for extent of disease on CT, demographic factors, smoking history, and concurrent treatment. Patients with emphysema on CT (n = 16) and patients with FASSc with overt pulmonary hypertension (n = 5) were excluded; 111 patients were studied (CFA, n = 54; FASSc, n = 57). Patients with CFA were distinguished by more severe functional impairment and more extensive disease on CT (40.1 versus 22.1%, p < 0.00005). On multivariate analysis, patients with CFA had greater reduction in arterial P(O2) (p < 0.0005), wider AaP(O2) (p < 0.0005), greater oxygen desaturation on maximal exercise (p < 0.03), and higher dyspnea scores (p < 0.02) than did patients with FASSc after controlling for extent of disease on CT and other covariates. Measures of lung volume and gas transfer did not differ independently between CFA and FASSc. These findings persisted in subanalyses of patients with limited disease, extensive disease, histologic confirmation of fibrosing alveolitis, and with the reinclusion of patients with emphysema and pulmonary hypertension. The patterns of functional impairment were indicative of more severe ventilation-perfusion mismatch or anatomic shunting in CFA after adjustment for disease extent; we speculate that perfusion of poorly ventilated lung parenchyma in CFA occurs through new vessels formed in areas of intense inflammation. This mechanism may contribute to the greater mortality of patients with CFA than of patients with FASSc because of the deleterious effects of hypoxia on concurrent cardiac disease.

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Fibrosing alveolitis complicating systemic sclerosis (FASSc) carries a better prognosis than lone cryptogenic fibrosing alveolitis (CFA). We wanted to determine whether this improved prognosis is associated with differential neutrophil migration and activation in the lower respiratory tract.We therefore compared bronchoalveolar lavage (BAL) neutrophil numbers and levels of neutrophil-derived enzymes in FASSc, CFA and normal individuals. Bronchoalveolar lavage was performed on 45 subjects (FASSc n=20; CFA n=15; normals n=10); cell counts and levels of neutrophil-derived enzymes, myeloperoxidase, elastase (total elastase and elastase/α 1 -antitrypsin complexes), collagenase and lactoferrin were measured. Lung function testing was performed in subjects with fibrosing alveolitis.Significant differences in the levels of collagenase, myeloperoxidase and elastase/ α 1 -antitrypsin complexes were present in the BAL fluid from the three groups. Patients with CFA had significantly higher neutrophil percentages and levels of collagenase and myeloperoxidase than those with FASSc. Disease extent, as judged by lung volumes and gas transfer, was comparable in the CFA and FASSc groups. Forced vital capacity (% predicted) was significantly lower in patients with evidence of increased neutrophil enzyme release than those without.We conclude that: 1) increased neutrophil migration to the lung is accompanied by release both of primary and secondary granule enzymes in cryptogenic fibrosing alveolitis; and 2) the lower amounts of neutrophil products in fibrosing alveolitis complicating systemic sclerosis may account for the improved prognosis, even when disease is as extensive as in cryptogenic fibrosing alveolitis. Eur Respir J., 1996, 9, 992-999.