Srihari Veeraraghavan

RATIONALE: In interstitial lung disease complicating systemic sclerosis (SSc-ILD), the optimal prognostic use of baseline pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) is uncertain. OBJECTIVES: To construct a readily applicable prognostic algorithm in SSc-ILD, integrating PFTs and HRCT. METHODS: The prognostic value of baseline PFT and HRCT variables was quantified in patients with SSc-ILD (n = 215) against survival and serial PFT data. MEASUREMENTS AND MAIN RESULTS: Increasingly extensive disease on HRCT was a powerful predictor of mortality (P < 0.0005), with an optimal extent threshold of 20%. In patients with HRCT extent of 10-30% (termed indeterminate disease), an FVC threshold of 70% was an adequate prognostic substitute. On the basis of these observations, SSc-ILD was staged as limited disease (minimal disease on HRCT or, in indeterminate cases, FVC >or= 70%) or extensive disease (severe disease on HRCT or, in indeterminate cases, FVC < 70%). This system (hazards ratio [HR], 3.46; 95% confidence interval [CI], 2.19-5.46; P < 0.0005) was more discriminatory than an HRCT threshold of 20% (HR, 2.48; 95% CI, 1.57-3.92; P < 0.0005) or an FVC threshold of 70% (HR, 2.11; 95% CI, 1.34-3.32; P = 0.001). The system was evaluated by four trainees and four practitioners, with minimal and severe disease on HRCT defined as clearly < 20% or clearly > 20%, respectively, and the use of an FVC threshold of 70% in indeterminate cases. The staging system was predictive of mortality for all scorers, with prognostic separation higher for practitioners (HR, 3.39-3.82) than trainees (HR, 1.87-2.60). CONCLUSIONS: An easily applicable limited/extensive staging system for SSc-ILD, based on combined evaluation with HRCT and PFTs, provides discriminatory prognostic information.

Survival is linked to the histopathologic distinction between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), the most commonly encountered fibrotic idiopathic interstitial pneumonia. We retrospectively compared the prognostic significance of histopathologic diagnoses, baseline pulmonary function indices, and serial trends in pulmonary function indices (diffusing capacity, FVC, FEV1, the recently defined composite physiologic index) at 6 and 12 months in 104 patients (UIP, n = 63; fibrotic NSIP, n = 41). Survival was lower in UIP than in fibrotic NSIP (p = 0.001) but not in patients with severe functional impairment; mortality during the first 2 years was linked solely to the severity of functional impairment at presentation. The composite physiologic index was the strongest determinant of outcome (p < 0.001). At 6 months, serial diffusing capacity levels (p = 0.003) and histopathologic diagnosis (p = 0.002) were prognostically equivalent. At 12 months, serial pulmonary function trends were the only major prognostic determinant (p < 0.0005 for all variables), with no independent significance associated with the distinction between UIP and fibrotic NSIP. We conclude that at 12 months, serial pulmonary function trends have considerable prognostic value in UIP and NSIP. Their histologic distinction provides no additional prognostic information when pulmonary function trends are clear cut or when functional impairment is severe.

PURPOSE: To evaluate computed tomographic (CT) patterns of lung disease in patients with systemic sclerosis (SSc) and compare them with CT appearance in patients with biopsy-proved idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (NSIP). MATERIALS AND METHODS: The CT features of consecutive patients with SSc (n = 225; male patients, 44; female patients, 181; median age, 47 years; age range, 16-78 years), IPF (n = 40; men, 26; women, 14; median age, 54.5 years; age range, 36-77 years) and NSIP (n = 27; men, 18; women, nine; median age, 53 years; age range, 32-68 years) were quantified separately by two observers. The extent of interstitial lung disease, ground-glass opacification, emphysema, and the coarseness of a reticular pattern were quantified. Group comparisons were made nonparametrically with the Wilcoxon rank sum test. Differences in CT features were identified with multiple logistic regression analysis. RESULTS: The coarseness of fibrosis was similar in patients with SSc and idiopathic NSIP but strikingly different between patients with SSc (median coarseness score, 5.5; range, 0.0-13.3) and IPF (median coarseness score, 8.8; range, 2.5-15.0) (P <.001). The proportion of ground-glass opacification at CT was similar in patients with SSc and idiopathic NSIP but differed significantly between patients with SSc (median proportion, 49.9%; range, 0.0%-100.0%) and IPF (median proportion, 23.5%; range, 0.0%-97.2%) (P <.001). At logistic regression analysis, there were no differences in the CT features between patients with SSc and those with NSIP after controlling for age, disease extent, and the percentage predicted forced vital capacity and carbon monoxide diffusing capacity. CONCLUSION: Interstitial lung disease in patients with SSc is less extensive, less coarse, and characterized by a greater proportion of ground-glass opacification than that in patients with IPF. The CT features of lung disease in patients with SSc closely resemble those in patients with idiopathic NSIP.

The aim of this study was to evaluate interstitial vascularity in cryptogenic fibrosing alveolitis (CFA) and in fibrosing alveolitis associated with systemic sclerosis (FASSc). Open lung biopsies from eight patients with CFA, nine patients with FASSc, and normal lung from 12 patients undergoing surgery for lung cancer were studied. Markers for endothelial cells (CD34) and cell proliferation (proliferating cell nuclear antigen) were localized by sequential immunohistochemistry and quantified using computer-assisted analysis. Vascular distribution was evaluated at increasing distances (up to 160 microm) from the airspaces. Vessel density was markedly reduced in both FASSc (3.9%) and in CFA (4.5%) compared with control samples (20.4%, p < 0.0001). The percentage of tissue occupied by vessels decreased with increasing distance from alveoli in control samples but not in CFA or FASSc samples. Endothelial cell proliferation indices were increased in FASSc but not in CFA, compared with control samples (p = 0.006). In conclusion, there is net vascular ablation and redistribution of blood vessels in areas of interstitial thickening in both CFA and FASSc, which may contribute to gas exchange impairment.

PURPOSE: To describe the appearance and frequency of a perilobular pattern at thin-section computed tomography (CT) in patients with organizing pneumonia. MATERIALS AND METHODS: Thin-section CT scans of 21 consecutive patients with cryptogenic organizing pneumonia were retrospectively reviewed. Two thoracic radiologists in consensus recorded the presence and distribution of the CT abnormalities (consolidation, ground-glass opacification, nodules, bandlike opacities, interlobular septal thickening, and findings of fibrosis), with a particular focus on the presence and predominant location of the perilobular pattern, that is, a poorly defined arcadelike or polygonal appearance. RESULTS: The perilobular pattern was present in 12 (57%) of 21 patients, 10 of whom had five or more perilobular opacities. Other CT features were consolidation (20 patients, 95%), which was predominantly a subpleural and/or peribronchial distribution in 17 patients, and ground-glass opacification (18 patients, 86%). Bandlike opacities and interlobular septal thickening were observed in four patients and one patient, respectively. The perilobular pattern abutted the pleural surface in 10 of 12 patients and was surrounded by aerated lung parenchyma in 11 of 12 patients. There was no obvious relationship between perilobular opacities and CT findings indicative of established fibrosis. CONCLUSION: A perilobular pattern was present in more than half of the patients, along with the expected thin-section CT features of organizing pneumonia.