Circulating adhesion molecules and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis

Abstract

Adhesion molecules may contribute to the development of interstitial lung disease (ILD) and have been proposed as prognostic biomarkers in idiopathic pulmonary fibrosis. Our objective was to determine whether the circulating adhesion molecules soluble intracellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1 and P-selectin are associated with subclinical ILD in community-dwelling adults.The Multi-Ethnic Study of Atherosclerosis enrolled males and females aged 45–84 years from six communities in the United States in 2000–2002. High attenuation areas were defined as the percentage of imaged lung volume with attenuation −600–−250 HU on cardiac computed tomography (CT). Interstitial lung abnormalities were visually assessed on full-lung CT. Spirometry was performed on a subset of individuals. ILD hospitalisations and deaths were adjudicated.In fully adjusted analyses, higher levels of sICAM-1, sVCAM-1 and P-selectin were associated with greater high attenuation areas (2.94%, 95% CI 1.80–4.07%; 1.24%, 95% CI 0.14–2.35%; and 1.58%, 95% CI 0.92–2.23%, respectively), and greater rate of ILD hospitalisations (HR 1.36, 95% CI 1.03–1.80; 1.40, 95% CI 1.07–1.85; and 2.03, 95% CI 1.16–3.5, respectively). sICAM-1 was associated with greater prevalence of interstitial lung abnormalities (OR 1.39, 95% CI 1.13–1.71). sICAM-1 and P-selectin were associated with lower forced vital capacity (44 mL, 95% CI 12–76 mL and 29 mL, 95% CI 8–49 mL, respectively). sVCAM-1 and P-selectin were associated with increased risk of ILD death (HR 2.15, 95% CI 1.26–3.64 and 3.61, 95% CI 1.54–8.46, respectively).Higher levels of circulating sICAM-1, sVCAM-1 and P-selectin are independently associated with CT and spirometric measures of subclinical ILD, and increased rate of adjudicated ILD events among community-dwelling adults.

Elevated VCAM-1, MCP-1 and ADMA serum levels related to pulmonary fibrosis of interstitial lung disease associated with rheumatoid arthritis

“…First, we found that VCAM-1 serum levels were increased in patients with RA-ILD + in relation to those with RA-ILDand IPF. In this context, it has been described that VCAM-1 is induced by both inflammatory cytokines and hypoxia (Peter et al, 1999;Dessein et al, 2005;Navarro-Hernández et al, 2009;Cook-Mills et al, 2011;Murdaca et al, 2012;Wang et al, Frontiers in Molecular Biosciences frontiersin.org 2015; Kong et al, 2018;McGroder et al, 2019), which may explain the increase of this protein observed in our RA-ILD + patients. Likewise, its ability to stimulate the fibroblast proliferation may be related to the fibrotic properties of this disease (Agassandian et al, 2015;McGroder et al, 2019).…”

Interstitial lung abnormalities – current knowledge and future directions

“…In addition, among familial interstitial pneumonia patients, those with ILA have been found to have shorter telomeres in peripheral blood than those without ILA [ 40 ]. Among other possible biomarkers, the adhesion molecule sICAM-1 has been associated with ILA [ 41 ] as well as pro-inflammatory molecule resistin [ 17 ]. Additionally, leptin and the metabolites phosphatidylcholine, phosphatidic acid, betaine aldehyde, phosphatidylethanolamine, and 1-acylglycerophosphocholine [ 42–44 ] have been linked with ILA and certain microRNAs, in particular miR-193a-5p and miR–502–5p, have been shown to be upregulated in ILA and suggested as ILA biomarkers [ 45 ].…”

Familial Interstitial Lung Disease

“…The MUC5B promoter variant has been associated with interstitial lung abnormalities (ILAs) in both families 132 and population-based cohorts. [133][134][135] Several peripheral blood biomarkers have been associated with early interstitial changes in families 131 or general populationbased cohorts [136][137][138][139] ; however, none of these biomarkers is currently approved or available for clinical use. The role of environmental exposures as a determinant of disease penetrance and phenotype has not been well studied; identifying modifiable risk factors could enable preventive strategies in high-risk individuals.…”