Author(s)

J. D. Maclay, D. A. McAllister, R. Rabinovich, I. Haq, S. Maxwell, S. Hartland, M. Connell, J. T. Murchison, E. J. R. van Beek, R. D. Gray, N. L. Mills, W. MacNee

ISBN

0040-6376

Publication year

2012

Periodical

Thorax

Periodical Number

7

Volume

67

Pages

606-612

Author Address

Maclay, JD Univ Edinburgh, Queens Med Res Inst, ELEGI Colt Lab, 47 Little France Crescent, Edinburgh EH16 4TJ, Midlothian, Scotland Univ Edinburgh, ELEGI Colt Labs, Ctr Inflammat Res, Edinburgh EH16 4TJ, Midlothian, Scotland Univ Cambridge, Cambridge Inst Med Res, Cambridge, England Royal Infirm Edinburgh NHS Trust, Dept Pathol, Edinburgh, Midlothian, Scotland Univ Edinburgh, Ctr Inflammat Res, Edinburgh EH16 4TJ, Midlothian, Scotland Royal Infirm Edinburgh NHS Trust, Dept Med Phys, Edinburgh, Midlothian, Scotland Univ Edinburgh, Clin Res Imaging Ctr, Edinburgh EH16 4TJ, Midlothian, Scotland Royal Infirm Edinburgh NHS Trust, Dept Radiol, Edinburgh, Midlothian, Scotland Univ Edinburgh, BHF Univ Ctr Cardiovasc Sci, Edinburgh EH16 4TJ, Midlothian, Scotland

Full version

Background Development of emphysema and vascular stiffness in chronic obstructive pulmonary disease (COPD) may be due to a common mechanism of susceptibility to pulmonary and systemic elastin degradation.
Objectives To investigate whether patients with COPD have evidence of systemic elastin degradation in the skin.
Methods The authors measured cutaneous elastin degradation using immunohistochemistry (percentage area of elastin fibres) in sun-exposed (exposed) and non-sun-exposed (non-exposed) skin biopsies in 16 men with COPD and 15 controls matched for age and cigarette smoke exposure. Quantitative PCR of matrix metalloproteinase (MMP)-2, -9, -12 and tissue inhibitor of metalloproteinase-1 mRNA and zymography for protein expression of MMP-2 and -9 were performed on homogenised skin. Arterial stiffness and emphysema severity were measured using carotid-femoral pulse wave velocity and quantitative CT scanning.
Results Skin elastin degradation was greater in exposed and non-exposed skin of patients with COPD compared with controls (exposed, mean (SD); 43.5 (12.1)% vs 26.3 (6.9)%, p<0.001; non-exposed 22.4 (5.2)% vs 18.1 (4.3)%, p = 0.02). Cutaneous expression of MMP-9 mRNA and proMMP-9 concentrations was increased in exposed skin of COPD patients (p = 0.004 and p = 0.02, respectively) and was also associated with increased skin elastin degradation (r = 0.62, p<0.001 and r = 0.47, p = 0.01, respectively). In the entire cohort of ex-smokers, cutaneous elastin degradation was associated with emphysema severity, FEV1 and pulse wave velocity. Conclusions Patients with COPD have increased skin elastin degradation compared with controls, which is related to emphysema severity and arterial stiffness. Systemic elastin degradation due to increased proteolytic activity may represent a novel shared mechanism for the pulmonary, vascular and cutaneous features of COPD.