Tobacco smoke-induced lung fibrosis and emphysema

Annu Rev Physiol. 2014:76:493-513. doi: 10.1146/annurev-physiol-021113-170411. Epub 2013 Nov 18.


Despite public health campaigns discouraging smoking, 1,000 American children every day become smokers, ensuring that tobacco-related health complications will be with us for decades to come. Smoking is the greatest risk factor for both chronic obstructive lung disease and interstitial lung disease. The facts that not every smoker develops chronic lung disease and that lung pathology differs markedly among smokers indicate that individual susceptibility must be a central determinant of lung injury responses to cigarette smoke. Comparative examination of pathogenic mechanisms of smoke-induced lung disease can shed light on the homeostatic pathways critical to maintaining lung health. In this review, we explore common and divergent biological forces tilting the lung homeostatic balance away from health and toward emphysema or pulmonary fibrosis. We emphasize recent insights that highlight the greatest contrasts or similarities in the pathogenesis of these two chronic lung disease phenotypes.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging / physiology
  • Animals
  • Autophagy / drug effects
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Chronic Disease
  • DNA Damage
  • Humans
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Emphysema / etiology*
  • Pulmonary Emphysema / genetics
  • Pulmonary Emphysema / pathology
  • Pulmonary Fibrosis / etiology*
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / pathology
  • Smoke / adverse effects*
  • Smoking / adverse effects*
  • Telomere / drug effects
  • Telomere / pathology
  • Tobacco Smoke Pollution / adverse effects*


  • Carrier Proteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Smoke
  • Tobacco Smoke Pollution