Decreased nitric oxide in the exhaled air of patients with systemic sclerosis with pulmonary hypertension

Abstract

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)...

Severity of scleroderma lung disease is related to alveolar concentration of nitric oxide

“…The current results are consistent with those from a previous study showing increased eNO in a limited number of SSc patients with pulmonary arterial hypertension [8]. In contrast, by measuring FeNO in mixed expired air, KHARITONOV et al [15] found decreased eNO in SSc patients with pulmonary hypertension. It is, however, difficult to compare these results with data from the present study due to different methodological approaches used to measure eNO.…”

Effect of N-acetyl-l-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis

“…However, since no correlation among lung inflammatory parameters and iNOS expression has been found, the higher iNOS expression in SSc might be considered an early but aspecific pathological sign suggesting that previous lung inflammation (ground glass without increased cellularity) or current lung inflammation (ground glass with increased cellularity), priming macrophages for iNOS expression, may be an aspecific event secondary to the process of systemic inflammation. The up-regulation of iNOS in macrophages might contribute to the increased levels of exhaled NO [1,2]. Our data also demonstrate that alveolar macrophages are not functionally impaired since fMLP can increase both ONOO À and O À 2 anion production.…”

“…In systemic sclerosis (SSc) patients, NO is increased in exhaled air [1,2] while it is decreased in those patients with pulmonary hypertension [2,3]. Moreover, serum NO levels are enhanced [4], iNOS is highly expressed in mononuclear cells infiltrating the skin [4] and peripheral blood mononuclear cells produce increased NO levels when stimulated with IL-1 [5].…”

Pulmonary hypertension in chronic obstructive pulmonary disease

“…Changes in the NO concentration in expired air have been identified in different respiratory disorders and it has been suggested that expired NO may be a useful marker of disease activity in some conditions [90]. The presence of pulmonary hypertension has been associated with lower NO output both at rest [91] and during exercise [92]. In patients with heart failure and pulmonary hypertension, expired NO is negatively correlated with PVR [92].…”