David M. Hansell

Serum Interleukin 6 Is Predictive of Early Functional Decline and Mortality in Interstitial Lung Disease Associated with Systemic Sclerosis

Objective. Biomarkers of progression of interstitial lung disease (ILD) are needed to allow early therapeutic intervention in patients with scleroderma-associated disease (SSc-ILD). Methods. A panel of 8 serum cytokines [interleukin 6 (IL-6), IL-8, IL-10, CCL2, CXCL10, vascular endothelial growth factor, fibroblast growth factor 2, and CX3CL1] was assessed by Luminex bead technology in exploratory cohorts of 74 patients with SSc and 58 patients with idiopathic pulmonary fibrosis (IPF). Mortality and significant lung function decline [forced vital capacity (FVC) ≥ 10%; DLCO ≥ 15%] from date of serum collection were evaluated by proportional hazards analysis. Based on these findings, the prognostic value of serum IL-6, evaluated by ELISA, was assessed in a larger test cohort of 212 patients with SSc-ILD. Results. In the exploratory cohort, only serum IL-6 was an independent predictor of DLCO decline in both IPF and SSc-ILD. The IL-6 threshold level most predictive of DLCO decline within a year was 7.67 pg/ml. In the larger test cohort, serum IL-6 > 7.67 pg/ml was predictive of decline in FVC (HR 2.58 ± 0.98, p = 0.01) and in DLCO (HR 3.2 ± 1.7, p = 0.02) within the first year, and predictive of death within the first 30 months (HR 2.69 ± 0.96, p = 0.005). When stratified according to severity (FVC < 70%), serum IL-6 > 7.67 pg/ml was predictive of functional decline or death within the first year in patients with milder disease (OR 3.1, 95% CI 1.4–7.2, p = 0.007), but not in those with severe ILD. Conclusion. In SSc-ILD, serum IL-6 levels appear to be predictive of early disease progression in patients with mild ILD, and could be used to target treatment in this group, if confirmed by prospective studies.

Smoking-Related Small Airways and Interstitial Lung Disease

The consequences of airways and interstitial inflammation caused by cigarette smoking are many and varied. In addition to well-recognized smoking-related disorders, including chronic bronchitis and emphysema, there is increasing appreciation of the complex relationship between small airways and interstitial damage, typified by respiratory bronchiolitis interstitial lung disease. Individual diseases ascribable to cigarette smoking and their relationship to each other are described.

Automatic assessment of small airways disease with computed tomography

Bronchiolar obstruction is commonly manifested in computed tomographic (CT) images as areas of decreased attenuation relative to adjacent normal lung parenchyma. The certain identification of such areas is difficult in practice, particularly is such areas are poorly marginated. This paper presents a novel approach to the enhancement of feature differences between normal and diseased lung parenchyma so that reliable visual assessment can be made. The method relies on a hybrid structural filtering technique which removes pulmonary vessels appearing in the CT cross- sectional images without affecting intrinsic subtle intensity details of the lung parenchyma. In order to restore possible structural distortions introduced by the hybrid filter, a feature localization process based on wavelet reconstruction of feature extrema is used. After contrast enhancement the resultant images are used to delineate region borders of the diseased areas and quantification is made with regard to the extent of the disease. Clinically, the proposed technique is especially valuable for presymptomatic cases in which direct visual assessment of the unprocessed images by different observers often yields inconsistent results.