Role of lung maintenance program in the heterogeneity of lung destruction in emphysema

Rubin M. Tuder, Toshinori Yoshida, Iwona Fijalkowka, Shyam Biswal, Irina Petrache

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


Centrilobular emphysema caused by chronic cigarette smoking is a heterogeneous disease with a predominance of upper lobe involvement. It is presumed that this heterogeneity indicates a particular susceptibility to cigarette smoke or the fact that the inhaled smoke distributes preferentially to upper lung zones. The less involved areas might therefore retain the capacity for lung regeneration and gain of pulmonary function in terminally ill patients. We propose that the interplay between molecular and cellular switches involved in the lung response to environmental injuries determines the heterogeneous pattern of emphysema due to cigarette smoke. Regional activation of alveolar destruction by apoptosis and oxidative stress coupled with regional failure of defense mechanisms may account for the irregular pattern of lung destruction in cigarette smoke-induced emphysema. Protection afforded by the key antioxidant transcription factor Nrf-2 and the antiproteolytic and antiapoptotic actions of α1-antitrypsin is central to maintain lung homeostasis and lung structure. As the lung is injured by environmental pollutants, including cigarette smoke, molecular sensors of cellular stress, such as the mTOR/protein translation regulator RTP-801, may engage both inflammation and alveolar cell apoptosis. As injury prevails during the course of this chronic disease, it leads to a more homogeneous pattern of lung disease.

Original languageEnglish (US)
Pages (from-to)673-679
Number of pages7
JournalProceedings of the American Thoracic Society
Issue number8
StatePublished - Nov 2006
Externally publishedYes


  • Aging
  • Apoptosis
  • Emphysema
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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