Lower limit of normal based spirometric abnormalities associated with radiographic abnormality in an elderly cohort at low risk for exposure.

BACKGROUND: Although the relation between radiographic abnormalities and spirometric impairment in people with asbestosis has been studied extensively, the extent of spirometric impairment associated with milder radiographic abnormalities is not established. OBJECTIVE: To test associations between mild radiographic abnormalities and Lower Limit of Normal (LLN)-based spirometry interpretation. METHODS: Spirometry and CXRs were collected for 1,026 at low risk of exposure to pneumoconiotic agents participants in a medical screening program. RESULTS: Individuals with each type of isolated or combined International Labour Organization (ILO) abnormalities had up to over sixfold statistically significant increase in odds of LLN-based restrictive pattern physiology (OR = 1.96, 95%CI 1.03-3.73 for parenchymal to OR = 6.09, 95%CI 1.94-19.10 for parenchymal and pleural) compared to those with normal films. CONCLUSIONS: The findings from this study confirm the association of mild profusion abnormalities with clinically relevant, LLN-based lung function abnormalities.

The Effect of Receiving Treatment Within a Clinical Trial Setting on Survival and Quality of Care Perception in Advanced Stage Non-Small Cell Lung Cancer.

OBJECTIVES: Treatment outcomes of advanced stage (IIIB and IV) non-small cell lung cancer (NSCLC) are poor. In this study, we explore the survival outcomes and the perception of the quality of care delivered in stage IIIB and IV NSCLC patients treated within versus outside a clinical trial. MATERIALS AND METHODS: Data were obtained from the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS). Baseline characteristics according to clinical trial participation were determined. The association between clinical trial enrollment and survival was assessed using a Cox proportional hazard model after adjusting for age, income, primary data collection and research site, comorbidities, self-reported performance status, presence of brain metastasis, stage IIIB versus IV, and cancer histology. RESULTS: Of 815 stage IIIB and IV NSCLC patients, 56 (7%) were enrolled in clinical trials. Median survival for the patients treated within versus outside a clinical trial was 20.5 versus 16.7 months, respectively (P=0.21). Using a multivariate survival model, clinical trial enrollment did not correlate with longer survival (P=0.81). Comparing patients according to clinical trial enrollment, patients treated within a clinical trial setting perceived a better overall quality of care (P<0.01). CONCLUSIONS: Management of stage IIIB and IV NSCLC patients within a clinical trial setting conveyed a perception of superior care that did not translate into survival benefit. These findings suggest that providing cancer care within a clinical trial should not imply a survival benefit when counseling stage IIIB and IV NSCLC patients about entering clinical trials.

Enhancement of carboplatin-mediated lung cancer cell killing by simultaneous disruption of glutathione and thioredoxin metabolism.

PURPOSE: Cancer cells (relative to normal cells) show increased steady-state levels of hydroperoxides that are compensated by increased glucose and hydroperoxide metabolism. The current study determined whether inhibitors of glucose and hydroperoxide metabolism could induce chemoradiosensitization by enhancing oxidative stress in lung cancer cells. EXPERIMENTAL DESIGN: A549 and NCI-H292 human lung carcinoma cells were treated with 2-deoxy-d-glucose (2DG) combined with carboplatin + ionizing radiation (IR). Lung cancer cells were further sensitized with inhibitors of glutathione (GSH)- and thioredoxin (Trx)-dependent metabolism [buthionine sulfoximine (BSO) and auranofin, respectively] in vitro and in vivo. RESULTS: When 2DG was combined with carboplatin + IR, clonogenic cell killing was enhanced in A549 and NCI-H292 cells, and this combination was more effective than paclitaxel + carboplatin + IR. The thiol antioxidant (N-acetylcysteine, NAC) was capable of protecting cancer cells from 2DG + carboplatin -induced cell killing. Simultaneous treatment of cancer cells with BSO and auranofin, at doses that were not toxic as single agents, also enhanced lung cancer cell killing and sensitivity to 2DG + carboplatin. This treatment combination also increased oxidation of both GSH and Trx, which were inhibited by NAC. Mice treated with auranofin + BSO showed no alterations in circulating leukocytes or red blood cells. Xenograft lung tumor growth in mice was more effectively inhibited by treatment with auranofin + BSO + carboplatin than animals treated with carboplatin or auranofin + BSO alone. CONCLUSIONS: These results show in vitro and in vivo that simultaneous inhibition of GSH and Trx metabolism can effectively inhibit lung cancer cell growth and induce chemosensitization by a mechanism that involves thiol-mediated oxidative stress.