The nature of small-airway obstruction in chronic obstructive pulmonary disease

N Engl J Med. 2004 Jun 24;350(26):2645-53. doi: 10.1056/NEJMoa032158.


Background: Chronic obstructive pulmonary disease (COPD) is a major public health problem associated with long-term exposure to toxic gases and particles. We examined the evolution of the pathological effects of airway obstruction in patients with COPD.

Methods: The small airways were assessed in surgically resected lung tissue from 159 patients--39 with stage 0 (at risk), 39 with stage 1, 22 with stage 2, 16 with stage 3, and 43 with stage 4 (very severe) COPD, according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD).

Results: The progression of COPD was strongly associated with an increase in the volume of tissue in the wall (P<0.001) and the accumulation of inflammatory mucous exudates in the lumen (P<0.001) of the small airways. The percentage of the airways that contained polymorphonuclear neutrophils (P<0.001), macrophages (P<0.001), CD4 cells (P=0.02), CD8 cells (P=0.038), B cells (P<0.001), and lymphoid aggregates containing follicles (P=0.003) and the absolute volume of B cells (P=0.03) and CD8 cells (P=0.02) also increased as COPD progressed.

Conclusions: Progression of COPD is associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells that form lymphoid follicles. These changes are coupled to a repair or remodeling process that thickens the walls of these airways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Airway Obstruction / pathology*
  • Analysis of Variance
  • B-Lymphocytes
  • Bronchi / immunology
  • Bronchi / pathology*
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Disease Progression
  • Female
  • Forced Expiratory Volume
  • Humans
  • Inflammation
  • Inflammation Mediators / analysis*
  • Leukocyte Count
  • Macrophages
  • Male
  • Middle Aged
  • Neutrophils
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology


  • Inflammation Mediators