Performance of a new quantitative computed tomography index for interstitial lung disease assessment in systemic sclerosis

Marialuisa Bocchino,Nicola Sverzellati,Alessandro Sanduzzi,Dario Bruzzese,Emanuele Romeo,Paola Argiento,Barbara Russo,Annalisa Capaccio,Tullio Valente,Serena Vettori,Alessia Borgia,Gaetano Rea,Michele D’Alto

doi:10.1038/s41598-019-45990-7

Abstract

Quantitative high resolution computed tomography (HRCT) may objectively assess systemic sclerosis (SSc)-interstitial lung disease (ILD) extent, using three basic densitometric measures: mean lung attenuation (MLA), skewness, and kurtosis. This prospective study aimed to develop a composite index - computerized integrated index (CII) – that accounted for MLA, skewness, and kurtosis by means of Principal Component Analysis over HRCTs of 83 consecutive SSc subjects, thus eliminating redundancies. Correlations among CII, cardiopulmonary function and immune-inflammatory biomarkers (e.g. sIL-2Rα and CCL18 serum levels) were explored. ILD was detected in 47% of patients at visual HRCT assessment. These patients had worse CII values than patients without ILD. The CII correlated with lung function at both baseline and follow-up, and with sIL-2Rα and CCL18 serum levels. The best discriminating CII value for ILD was 0.1966 (AUC = 0.77; sensitivity = 0.81 [95%CI:0.68–0.92]; specificity = 0.66 [95%CI:0.52–0.80]). Thirty-four percent of patients without visual trace of ILD had a CII lower than 0.1966, and 67% of them had a diffusing lung capacity for CO <80% of predicted. We showed that this new composite CT index for SSc-ILD assessment correlates with both lung function and immune-inflammatory parameters and could be sufficiently sensitive for capturing early lung density changes in visually ILD-free patients.

Highlights

Interstitial lung disease (ILD) is a leading cause of disability and mortality in systemic sclerosis (SSc)[1,2], a chronic multiorgan disease characterized by autoimmune phenomena, microangiopathy, and fibrosis of the skin and internal organs[3,4,5]
The computerized integrated index (CII) was associated with the main lung function parameters suggestive of a restrictive ventilation pattern, as with the diffusing lung capacity for carbon oxide (DLCO) and subcategories of the 6-minute walking test (6-MWT) at baseline
These data are in line with previous studies that reported similar associations of lung function parameters in SSc with each of the lung density CT histograms that have been hereby used to elaborate the CII16–18

Summary

Introduction

Interstitial lung disease (ILD) is a leading cause of disability and mortality in systemic sclerosis (SSc)[1,2], a chronic multiorgan disease characterized by autoimmune phenomena, microangiopathy, and fibrosis of the skin and internal organs[3,4,5]. Basic density-based CT analysis, such as mean lung attenuation (MLA, average global attenuation value of lung parenchyma), skewness (degree of histogram asymmetry) and kurtosis (degree of histogram peakedness), is widely available and could replace the visual scoring for SSc-ILD assessment[14,15,16]. This method showed higher sensitivity as compared to the visual scoring[15]. In order to develop a single composite densitometric index for SSc-ILD quantification integrating MLA, skewness and kurtosis, we investigated a prospective series of SSc patients by low-dose thin section volumetric lung CT and searched for associations of this index with cardiopulmonary function parameters, and circulating markers of immune system activation (e.g. soluble interleukin-2 receptor alpha - sIL-2Rα - and chemokine CCL18) previously implicated in SSc and in SSc-ILD progression[19,20,21,22]

Methods

Results

Conclusion