Chronic inflammation, chronic obstructive pulmonary disease, and lung cancer.
OBJECTIVE
Smoking is a major risk factor for lung cancer, which is the leading cause of cancer-related deaths both in the USA and worldwide. Chronic obstructive pulmonary disease and emphysema are comorbid conditions often found in lung cancer patients. The inflammatory pathways that link chronic obstructive pulmonary disease, emphysema, and lung cancer likely involve genetic and epigenetic modulations due to chronic tissue injury and abnormal tumor immunity in susceptible hosts.


RESULTS
Chronic airway inflammation contributes to alterations in the bronchial epithelium and lung microenvironment, provoking a milieu conducive to pulmonary carcinogenesis. For example, inflammation-inducible cyclooxygenase-2 is upregulated in nonsmall cell lung cancer and also plays an important role in promoting epithelial-to-mesenchymal transition. Genetic changes in the airway epithelium of smokers may help predict or identify individuals at risk for lung cancer. Finally, radiographic findings of emphysema have been established as independent risk factors for lung cancer.


CONCLUSIONS
The relationships between inflammation, airflow obstruction, and lung cancer are complex. Deregulated inflammation is complicit in the pathogenesis of chronic obstructive pulmonary disease and lung cancer, but the overlap of signaling events is not yet fully understood. Tobacco exposure is an important risk factor that confers long-term risk of lung disease. Diagnostic sensitivity of detecting lung cancer may improve with the utilization of genetic profiling in combination with pathologic evaluation of airway epithelium. Additional research is required to understand the role of epithelial-to-mesenchymal transition in chronic inflammatory lung diseases and lung carcinogenesis.
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Gina
G
Lee
Tonya C
TC
Walser
Steven M
SM
Dubinett
D002908:Chronic Disease; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D011014:Pneumonia / Q000150:complications*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects