In a recent review published in Respirology entitled “Smoking-related idiopathic interstitial pneumonia: A review,” George Margaritopoulos from the Department of Thoracic Medicine and Laboratory of Molecular and Cellular Pneumonology at the University Hospital of Heraklion along with colleagues examined the current evidence regarding the association between cigarette smoking and the development of lung diseases, and found that although the exact mechanisms are not still well understood, the connection is clear.
Specifically, the researchers explored the mechanisms of smoking-related lung damage in pulmonary Langerhan’s cell histiocytosis, smoking-related interstitial fibrosis, combined pulmonary fibrosis, emphysema syndrome and idiopathic pulmonary fibrosis.
Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD) and lung cancer, and has also been implicated in the pathogenesis of diffuse interstitial lung diseases (DILD) including respiratory bronchiolitis (RB), RB-associated interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans cell histiocytosis (PLCH) and other types of interstitial lung disease (ILD) in the context of collagen tissue disorders, mainly in rheumatoid arthritis (RA).
Smoking may also play a key role in the development and progression of the most devastating form of DILD, namely idiopathic pulmonary fibrosis (IPF).
Smoking leads to exaggerated accumulation of inflammatory cells such as macrophages; neutrophils and Langerhan’s cells in small airways; distal air spaces and interstitium. Smoking also induces the production of transforming growth factor (TGF)-β1, a central mediator with crucial role in the development of lung fibrosis.
Nicotine is implicated in the development of fibrosis in various organs, as it promotes epithelial and endothelial cell damage, stimulates the production and release of TGF-β1, enhances the recruitment of inflammatory cells and the production of reactive oxygen species, and also stimulates the production of collagen, which is the major constituent of the extracellular cell matrix.
Two further hypotheses regarding the implication of smoking in the pathogenesis of smoking-related ILD have been proposed including abnormal telomere shortening and dysregulation of autophagy.
Smoking has been related to telomere shortening, a phenomenon observed in IPF and associated with its disease progression. Abnormally short telomeres have been documented in alveolar epithelial cells in IPF and impact on epithelium’s ability to regenerate. One of the main reasons of the abnormal shortening is mutations in the enzyme responsible for maintaining telomere length, namely telomerase, however, abnormal shortening has also been documented in the absence of telomerase mutations, suggesting that other factors such as cigarette smoking may be responsible for this phenomenon.
Autophagy is a homeostatic mechanism, with the main function of transporting damaged proteins and organelles such as mitochondria for degradation after fusion with lysosomes. Autophagy is enhanced in epithelial cells leading to apoptosis and development of emphysema, whereas it is defective in alveolar macrophages, which may allow for excess accumulation of particles in the setting of cigarette smoking and of various bacteria leading to increased oxidative stress, disease progression and acute exacerbations due to infections. In IPF lungs, autophagy has been found to be decreased, possibly mediated by increased levels of TGF-β1.
According to the researchers, studies looking at screening outcome rates for early identification of lung cancer using low-dose CT have determined that about 10% of smokers can present with interstitial lung abnormalities, which may progress if the patient continues to smoke. However, according to the researchers, whether these screening tests can identify smoking-related ILD, including IPF at an early stage, still needs further research.
In the review, the researchers indicate the vital aspect of smoking cessation and smoking prevention as prophylaxis for the development of lung diseases.