Abnormalities of Pulmonary Vascular Dynamics and Inflammation In Early Progressive Systemic Sclerosis

Abstract

Abnormalities of pulmonary function were studied in 10 patients with progressive systemic sclerosis (PSS) and 3 control subjects. All underwent *'M krypton lung scanning and total body gallium scanning. Immune complexes were measured by Raji cell radioimmunoassay and polyethylene glycol (PEG) assay. Perfusion scans were abnormal in 7 of 9 patients, and 5 of 9 showed a decrease in pulmonary perfusion after cold challenge. Increased gallium uptake was noted in the lungs of 6 of 9 patients. Krypton scans were normal in the control group. Elevated immune complexes were noted in 8 of 10 patients by the Raji assay and in 5 of 10 with the PEG assay. Efforts to separate patients with PSS into subgroups may lead to a better understanding of and advances in therapy for PSS.Although pulmonary changes in progressive systemic sclerosis (PSS) are common, little is known about the changes that occur in early PSS lung disease. A recent review of pulmonary involvement in PSS reemphasized the fibrotic, cystic, and vascular changes found in the lungs of most patients. Vascular changes that included intimal proliferation, medial hypertrophy, and myxomatous changes in arterioles were present in 26-100% of a pathologic series. Larger arteries were sometimes affected (1). The discordance of fibrotic and vascular changes was also noted.In a search for the etiology of the arteriolar changes in PSS, Alpert and Warner could not demonstrate the deposition of lgG, lgM, or complement on vessels in 1 subject and found neither PIC nor gamma globulin in other autopsy material ( 2 ) . However, circulating immune complexes (CIC), pulmonary histopathology, and immunofluorescence correlated in idiopathic pulmonary fibrosis (3). Since Crystal et al (4) stated that physiologic and histologic features of idiopathic pulmonary fibrosis were noted in patients with PSS, it appeared that a similar pathogenesis for PSS lung disease might still be possible, particularly since most reports of PSS lung pathology relate to long established disease in which inflammatory changes might no longer be prominent. CIC, pulmonary histopathology, and immunofluorescence also correlated in idiopathic interstitial pneumonia, a disease in which the pulmonary histology is similar to PSS (3,4). The vascular changes noted above in PSS have been postulated to be pathogenetically related to Raynaud's phenomenon since vascular reactivity to cold has been found in renal vessels, and the same might occur in the pulmonary vascular tree ( I ) . The latter hypothesis, although attractive, has never been demonstrated.This report investigates the etiology of the pulmonary changes in early PSS lung disease, using "gallium lung scans, measurement of CIC, and "M krypton perfusion lung scans. MATERIALS AND METHODSPatients. 'fen patients with PSS or 2.1 2 1.2 (SD) years duration from onset of their first symptoms were studied. These fully informed, voluntarily enrolled patients were part of ongoing prospective studies at UCLA that

Anticardiolipin Antibodies Are Associated with Pulmonary Hypertension in Patients with Mixed Connective Tissue Disease or Systemic Lupus Erythematosus

“…Both prostacycline and protein C play a crucial role in the anticoagulative activity of vessels. Furst et al [23] suggested that vasospasms may play some role in the development of PH in patients with Raynaud's phenomenon. Therefore aCL might affect the anticoagulant function of these substances in the pulmo nary artery, and also the vasodilative function of prostacy cline.…”

Pulmonary Vasospasm in Systemic Sclerosis: Noninvasive Techniques for Detection

“…Lampert 17 reported a reduction in DLCO in similar patients, although this was associated with a reduction in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) at RHC, suggesting that vasodilatation and intrapulmonary blood redistribution may be the un- nor Wise 13 detected change in DLCO in SSc patients after provocation testing. Other measurement techniques, including krypton perfusion lung scan (demonstrating reduced pulmonary perfusion) 20 and RHC (demonstrating an increase in mPAP and PVR in a subgroup of patients), 21 have provided support for the notion of pulmonary vasospasm, in at least a subgroup of patients. More recently, in SSc patients with established pulmonary hypertension, Coghlan and colleagues 22 found no change in right heart catheter parameters or circulating markers of endothelial cell activation after cold-pressor testing.…”

“…13 Various measurement techniques (including right heart catheterization [RHC], radioisotope lung perfusion scans, and diffusing capacity of the lung for carbon monoxide [DLCO]) have been evaluated for the detection of pulmonary vasospasm, with varying results. [14][15][16][17][18][19][20][21][22] Technological advances now allow for the assessment of pulmonary blood flow (PBF) with several noninvasive techniques, including inertgas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA).…”

High resolution computed tomography in systemic sclerosis. Real diagnostic utilities in the assessment of pulmonary involvement and comparison with other modalities of lung investigation

“…Systemic sclerosis is a chronic disease that affects all the lung compartments (16)(17)(18)(19). The severity of lung involvement in many cases plays a fundamental role in the prognosis of the disease, and may account for significant morbidity and mortality.…”