Lung structure and function relation in systemic sclerosis: Application of lung densitometry

Highlights

• A quantitative CT parameter of lung parenchyma in systemic sclerosis is presented.

• We examine the optimal percentage threshold for the percentile density.

• The 85th percentile density threshold correlated significantly with lung function.

• A lung structure–function relation is confirmed.

• We report applicability of Perc85 in progression mapping of interstitial lung disease.

Abstract

Introduction

Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function.

Material and methods

We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis.

Results

Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R = −0.49, P = 0.001) and FVC %predicted (R = −0.64, P < 0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly.

Conclusions

We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure–function relation in SSc. This provides support for future studies to determine whether structural changes do precede lung function decline.

Introduction

Clinical risk assessment of organ manifestations in systemic sclerosis (SSc) has revealed that interstitial lung disease (ILD) is present in 53% of cases with diffuse cutaneous SSc (dcSSC) and in 35% of cases with limited cutaneous SSc (lcSSc) [1]. For evaluating the response to treatment of ILD, pulmonary function tests (PFTs) such as the diffusion capacity for carbon monoxide (DLCO) and forced vital capacity (FVC) are key outcome measures. However, these measures are affected by pulmonary vascular changes and chest wall skin stiffening, respectively [1]. Therefore, more specific measures of lung parenchymal involvement of ILD may provide additional structural information.

Currently, chest high-resolution computed tomography (HRCT) is considered the most accurate noninvasive imaging method for ILD assessment. Both severity and extent of ILD are usually estimated by semi-quantitative scoring of a limited number of cross-sectional slices through the lungs [2], [3]. However, visual scoring has limited reproducibility, because of its subjective nature, and is time-consuming, thereby constraining the number of slices that can be assessed. HRCT data provide a means to quantitatively analyze the structure of the whole lung, since inflammation, ground glass opacities and fibrosis can be quantified by lung densitometry. Therefore, objective quantitative techniques by CT densitometry may provide a more sensitive measurement, similar to what has been proven in assessing progression of pulmonary emphysema by the percentile density method [4]. Since these quantitative techniques are automated, it is feasible to quantify the entire lungs instead of only a limited number of slices, with a smaller chance of missing pathological changes.

Previously, Camiciotolli et al. [5] reported that lung density histogram parameters are more reproducible than visual assessment of HRCT and are more closely related to functional, exercise and quality-of-life impairment in SSc. In their evaluation of each patient, they calculated the average global density of the lung and included kurtosis and skewness of the density histogram of the whole lung. However, this analysis did not provide a single overall score for the structure of the lungs and, more importantly, lung density values were not corrected for lung volume. In a recent report, the same investigators clearly demonstrated the need for volume correction of density parameters [6]. By a so-called sponge model [7], in which the lungs are considered mass preserving (i.e. the total lung mass is constant during breathing), density values can be corrected in a relatively simple calculation. Volume-corrected lung density parameters calculated by specific software may be useful outcome measures in evaluating the progression of ILD and the response to treatment. Therefore, the aim of this study was to identify the optimal volume correction and percentage threshold for the percentile density method in SSc.