Silicosis is a fibrotic lung disease caused by inhalation of free crystalline silicon dioxide or silica. Occupational exposure to respirable crystalline silica dust particles occurs in many industries. Phagocytosis of crystalline silica in the lung causes lysosomal damage, activating the NALP3 inflammasome and triggering the inflammatory cascade with subsequent fibrosis.

Impairment of lung function increases with disease progression, even after the patient is no longer exposed. Diagnosis of silicosis needs carefully documented records of occupational exposure and radiological features, with exclusion of other competing diagnoses. Mycobacterial diseases, airway obstruction, and lung cancer are associated with silica dust exposure. As yet, no curative treatment exists, but comprehensive management strategies help to improve quality of life and slow deterioration.

Further efforts are needed for recognition and control of silica hazards, especially in developing countries.

Matrix metalloprotease-1 (MMP1), a collagenase and activator of the G protein-coupled protease activated receptor-1 (PAR1), is an emerging new target implicated in oncogenesis and metastasis in diverse cancers. However, the functional mouse homologue of MMP1 in cancer models has not yet been clearly defined.

We report here that Mmp1a is a functional MMP1 homologue that promotes invasion and metastatic progression of mouse lung cancer and melanoma. Lewis lung carcinoma (LLC1), and primary mouse melanoma cells harboring active BRAF, express high levels of endogenous Mmp1a which is required for invasion through collagen. Silencing of either Mmp1a or PAR1 suppressed invasive stellate growth of lung cancer cells in 3-dimensional matrices. Conversely, ectopic expression of Mmp1a conferred an invasive phenotype in epithelial cells that do not express endogenous Mmp1a.

Consistent with Mmp1a acting as a PAR1 agonist in an autocrine loop, inhibition or silencing of PAR1 resulted in a loss of the Mmp1a-driven invasive phenotype. Knockdown of Mmp1a on tumor cells resulted in significantly decreased tumorigenesis, invasion, and metastasis in xenograft models.

Together, these data demonstrate that cancer cell-derived Mmp1a acts as a robust functional homologue of MMP1 by conferring pro-tumorigenic and metastatic behavior to cells.

Prior to evidence of efficacy, lung cancer screening was being ordered by many physicians. The National Lung Screening Trial (NLST), which demonstrated a 20 percent reduction in lung cancer mortality among those randomized to receive low-dose computed tomography (LDCT), will likely lead to increased screening use.

METHODS: We estimated the prevalence of chest x-ray and CT use in the United States using data from the 2010 National Health Interview Survey (NHIS). Subjects included 15,537 NHIS respondents aged ≥40 years without prior diagnosis of lung cancer. Estimates of the size of the U. S. population by age and smoking status were calculated. Multivariate logistic regression examined predictors of test use adjusting for potential confounders.

RESULTS: Twenty-three percent of adults reported chest x-ray in the previous year, and 2.5 percent reported chest x-ray specifically to check for lung cancer; corresponding numbers for chest CT were 7.5 and 1.3 percent. Older age, black race, male gender, smoking, respiratory disease, personal history of cancer, and having health insurance were associated with test use. Approximately 8.7 million adults in the United States would be eligible for LDCT screening according to NLST eligibility criteria.

Conclusions and Impact: Monitoring of trends in the use of lung screening tests will be vital to assess the impact of NLST and possible changes in lung cancer screening recommendations and insurance coverage in the future. Education of patients by their physicians, and of the general public, may help ensure that screening is used appropriately, in those most likely to benefit.