Endurance training damages small airway epithelium in mice

Am J Respir Crit Care Med. 2007 Mar 1;175(5):442-9. doi: 10.1164/rccm.200608-1086OC. Epub 2006 Dec 21.


Rationale: In athletes, airway inflammatory cells were found to be increased in induced sputum or bronchial biopsies. Most data were obtained after exposure to cold and dry air at rest or during exercise. Whether training affects epithelial and inflammatory cells in small airways is unknown.

Objectives: To test whether endurance training under standard environmental conditions causes epithelial damage and inflammation in the small airways of mice.

Methods and measurements: Formalin-fixed, paraffin-embedded lung sections were obtained in sedentary (n = 14) and endurance-trained (n = 16) Swiss mice at baseline and after 15, 30, and 45 days of training. The following variables were assessed (morphometry and immunohistochemistry) in small airways (basement membrane length < 1 mm): (1) integrity, proliferation, and apoptosis of bronchiolar epithelium; and (2) infiltration, activation, and apoptosis of inflammatory cells.

Main results: Compared with sedentary mice, bronchiolar epithelium of trained mice showed progressive loss of ciliated cells, slightly increased thickness, unchanged goblet cell number and appearance, and increased apoptosis and proliferation (proliferating cell nuclear antigen) (p < 0.001 for all variables). Leukocytes (CD45(+) cells) infiltrated airway walls (p < 0.0001) and accumulated within the lumen (p < 0.001); however, apoptosis of CD45(+) cells did not differ between trained and sedentary mice. Nuclear factor-kappaB translocation and inhibitor-alpha of NF-kappaB (IkappaBalpha) phosphorylation were not increased in trained compared with sedentary mice.

Conclusions: Bronchiolar epithelium showed damage and repair associated with endurance training. Training increased inflammatory cells in small airways, but inflammatory activation was not increased. These changes may represent an adaptive response to increased ventilation during exercise.

MeSH terms

  • Animals
  • Apoptosis
  • Bronchitis / etiology
  • Bronchitis / metabolism
  • Bronchitis / pathology*
  • Cell Proliferation
  • Disease Models, Animal
  • Epithelium / metabolism
  • Epithelium / pathology*
  • Immunohistochemistry
  • Leukocyte Count
  • Leukocytes / pathology
  • Male
  • Mice
  • NF-kappa B / metabolism
  • Physical Conditioning, Animal / adverse effects*
  • Proliferating Cell Nuclear Antigen / metabolism


  • NF-kappa B
  • Proliferating Cell Nuclear Antigen