Pathogenic triad in COPD: oxidative stress, protease-antiprotease imbalance, and inflammation

Int J Chron Obstruct Pulmon Dis. 2011;6:413-21. doi: 10.2147/COPD.S10770. Epub 2011 Aug 5.


Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction. COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma. Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression. Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology. Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease-antiprotease imbalance, and oxidative stress. Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients. For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status.

Keywords: apoptosis; bronchitis; chronic obstructive pulmonary disease; emphysema; senescence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / metabolism
  • Aging / pathology
  • Biomarkers
  • Gene-Environment Interaction*
  • Genome-Wide Association Study
  • Humans
  • Immunohistochemistry
  • Inflammation* / complications
  • Inflammation* / genetics
  • Oxidative Stress / genetics*
  • Protease Inhibitors / metabolism*
  • Pulmonary Disease, Chronic Obstructive* / etiology
  • Pulmonary Disease, Chronic Obstructive* / metabolism
  • Pulmonary Disease, Chronic Obstructive* / physiopathology
  • Reactive Oxygen Species / metabolism
  • Respiratory Function Tests
  • Respiratory System / metabolism
  • Respiratory System / pathology
  • Respiratory System / physiopathology
  • Risk Factors
  • Smoking / metabolism
  • Smoking / physiopathology


  • Biomarkers
  • Protease Inhibitors
  • Reactive Oxygen Species