Longitudinal Changes in Quantitative Interstitial Lung Disease on Computed Tomography after Immunosuppression in the Scleroderma Lung Study II

    loading  Checking for direct PDF access through Ovid

Abstract

Rationale:

The Scleroderma Lung Study II (SLS II) demonstrated significant improvements in pulmonary function and dyspnea at 24 months compared with baseline when patients with symptomatic scleroderma-related interstitial lung disease (SSc-ILD) were treated with either cyclophosphamide for 1 year (followed for another year on placebo) or mycophenolate mofetil for 2 years in a randomized, double-blind clinical trial. Physiologic and clinical outcomes of SLS II have been published previously.

Objectives:

The aim of the study was to assess changes from baseline in the extent of SSc-ILD on high-resolution computed tomography (HRCT) measured in the SLS II participants using quantitative image analysis after 2 years and to determine whether these HRCT changes were correlated with the changes in physiologic and clinical measures over the same time interval.

Methods:

Ninety-seven of the 142 randomized subjects (cyclophosphamide group, 47 subjects; mycophenolate mofetil group, 50 subjects) participating in SLS II underwent thoracic volumetric thin-section HRCT at both baseline and 24 months. Quantitative computer-aided diagnosis scores using volumetric HRCT scans were obtained using a previously developed computer-aided system. The scores were quantitative lung fibrosis, quantitative ground glass, quantitative honeycomb, and quantitative interstitial lung disease (QILD), the latter representing the sum of quantitative lung fibrosis, quantitative ground glass, and quantitative honeycomb. These scores were obtained both for the whole lung and for individual lobes. Paired t tests were used for the combined (pooled) cyclophosphamide and mycophenolate mofetil groups to compare 24-month changes from baseline in both the whole lung and the lobe of maximal involvement as determined at baseline (worst lobe).

Results:

At the end of the 24-month trial, QILD in the whole lung was significantly reduced by a mean of 2.51% in the pooled groups (adjusted 95% confidence interval, −4.00 to −1.03%; P = 0.001). There was no significant difference in the QILD score improvement between the cyclophosphamide (−2.66%) and mycophenolate (−2.38%) groups when assessed separately (P = 0.88). For the pooled group, the 24-month changes in QILD scores in the whole lung correlated significantly with other outcomes, including 24-month changes in forced vital capacity (ρ = −0.37), single-breath diffusing capacity of the lung for carbon monoxide (ρ = −0.22), and breathlessness as measured by the Transition Dyspnea Index (ρ = −0.26).

Conclusions:

Treatment of SSc-ILD with either cyclophosphamide for 1 year, followed by placebo for a second year, or mycophenolate for 2 years was associated with a significant reduction (improvement) in the extent of HRCT SSc-ILD assessed by computer-aided diagnosis scores, which correlated well with one or more other measures of treatment response. These findings demonstrate that actual changes in lung structure accompany improvements in physiologic and/or symptomatic measures in SSc-ILD.

Related Topics

    loading  Loading Related Articles