Loss of skin elasticity is associated with pulmonary emphysema, biomarkers of inflammation, and matrix metalloproteinase activity in smokers

Michael E O’Brien,Chad M Karoleski,Carl R Fuhrman,Robert C Wilson,Zsolt Urban,Divay Chandra,Frank C Sciurba,Jessica Bon,Joseph K Leader,Alison Morris,Jiantao Pu,Seyed Nouraie,Yingze Zhang

doi:10.1186/s12931-019-1098-7

Abstract

BackgroundElastin breakdown and the resultant loss of lung elastic recoil is a hallmark of pulmonary emphysema in susceptible individuals as a consequence of tobacco smoke exposure. Systemic alterations to the synthesis and degradation of elastin may be important to our understanding of disease phenotypes in chronic obstructive pulmonary disease. We investigated the association of skin elasticity with pulmonary emphysema, obstructive lung disease, and blood biomarkers of inflammation and tissue protease activity in tobacco-exposed individuals.MethodsTwo hundred and thirty-six Caucasian individuals were recruited into a sub-study of the University of Pittsburgh Specialized Center for Clinically Orientated Research in chronic obstructive pulmonary disease, a prospective cohort study of current and former smokers. The skin viscoelastic modulus (VE), a determinant of skin elasticity, was recorded from the volar forearm and facial wrinkling severity was determined using the Daniell scoring system.ResultsIn a multiple regression analysis, reduced VE was significantly associated with cross-sectional measurement of airflow obstruction (FEV1/FVC) and emphysema quantified from computed tomography (CT) images, β = 0.26, p = 0.001 and β = 0.24, p = 0.001 respectively. In emphysema-susceptible individuals, elasticity-determined skin age was increased (median 4.6 years) compared to the chronological age of subjects without emphysema. Plasma biomarkers of inflammation (TNFR1, TNFR2, CRP, PTX3, and SAA) and matrix metalloproteinase activity (MMP1, TIMP1, TIMP2, and TIMP4) were inversely associated with skin elasticity.ConclusionsWe report that an objective non-invasive determinant of skin elasticity is independently associated with measures of lung function, pulmonary emphysema, and biomarkers of inflammation and tissue proteolysis in tobacco-exposed individuals. Loss of skin elasticity is a novel observation that may link the common pathological processes that drive tissue elastolysis in the extracellular matrix of the skin and lung in emphysema-susceptible individuals.

Highlights

Elastin breakdown and the resultant loss of lung elastic recoil is a hallmark of pulmonary emphysema in susceptible individuals as a consequence of tobacco smoke exposure
One hundred and thirteen (47.9%) subjects had chronic obstructive pulmonary disease (COPD) based on spirometry (FEV1/forced vital capacity in s (FVC) < 0.70) with severity being nearly distributed between Global initiative for obstructive lung disease (GOLD) Stage I to IV COPD
Skin elasticity correlates with Daniell facial wrinkling score Bland-Altman analysis of facial wrinkling scores found excellent agreement between the two observers with a mean difference of − 0.063 (95% limits of agreement: − 1.25 to 1.12), intraclass correlation coefficient (ICC) of average for one-way random effects: 0.94 (95% confidence interval 0.93–0.96)

Summary

Introduction

Elastin breakdown and the resultant loss of lung elastic recoil is a hallmark of pulmonary emphysema in susceptible individuals as a consequence of tobacco smoke exposure. We investigated the association of skin elasticity with pulmonary emphysema, obstructive lung disease, and blood biomarkers of inflammation and tissue protease activity in tobacco-exposed individuals. More recent reports indicate that an independent association exists between facial wrinkling and airflow obstruction, which suggests that the lung and skin share common susceptibility to the deleterious effects of tobacco smoke exposure [13]. In smokers with COPD, elastin degradation in the skin is associated with emphysema severity and carotid pulse wave velocity, indicating that systemic elastin breakdown may be increased in susceptible individuals and not confined to the lung alone [19]. Alterations in skin elasticity may represent a novel non-invasive measure of the systemic effects that alter the extracellular matrix (ECM) in response to tobacco smoke in COPD

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