Pathophysiology of airflow limitation in chronic obstructive pulmonary disease

Lancet. 2004 Aug;364(9435):709-21. doi: 10.1016/S0140-6736(04)16900-6.


The airflow limitation that defines chronic obstructive pulmonary disease (COPD) is the result of a prolonged time constant for lung emptying, caused by increased resistance of the small conducting airways and increased compliance of the lung as a result of emphysematous destruction. These lesions are associated with a chronic innate and adaptive inflammatory immune response of the host to a lifetime exposure to inhaled toxic gases and particles. Processes contributing to obstruction in the small conducting airways include disruption of the epithelial barrier, interference with mucociliary clearance apparatus that results in accumulation of inflammatory mucous exudates in the small airway lumen, infiltration of the airway walls by inflammatory cells, and deposition of connective tissue in the airway wall. This remodelling and repair thickens the airway walls, reduces lumen calibre, and restricts the normal increase in calibre produced by lung inflation. Emphysematous lung destruction is associated with an infiltration of the same type of inflammatory cells found in the airways. The centrilobular pattern of emphysematous destruction is most closely associated with cigarette smoking, and although it is initially focused on respiratory bronchioles, separate lesions coalesce to destroy large volumes of lung tissue. The panacinar pattern of emphysema is characterised by a more even involvement of the acinus and is associated with alpha1 antitrypsin deficiency. The technology needed to diagnose and quantitate the individual small airway and emphysema phenotypes present in people with COPD is being developed, and should prove helpful in the assessment of therapeutic interventions designed to modify the progress of either phenotype.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Airway Resistance
  • Antigen Presentation
  • Bronchi / pathology
  • Bronchitis, Chronic / pathology
  • Cytokines / physiology
  • Humans
  • Inflammation
  • Leukocyte Count
  • Leukocytes / physiology
  • Lung / immunology
  • Lung / pathology
  • Lung / physiopathology
  • Lung Compliance
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Pulmonary Emphysema / pathology
  • Pulmonary Emphysema / physiopathology
  • Pulmonary Ventilation*
  • Smoking / adverse effects


  • Cytokines