Lung cancer is the leading cause of death from cancer in the US and the world. The high mortality rate (80-85% within 5 years) results, in part, from a lack of effective tools to diagnose the disease at an early stage. Given that cigarette smoke creates a field of injury throughout the airway, we sought to determine if gene expression in histologically normal large-airway epithelial cells obtained at bronchoscopy from smokers with suspicion of lung cancer could be used as a lung cancer biomarker. Using a training set (n = 77) and gene-expression profiles from Affymetrix HG-U133A microarrays, we identified an 80-gene biomarker that distinguishes smokers with and without lung cancer. We tested the biomarker on an independent test set (n = 52), with an accuracy of 83% (80% sensitive, 84% specific), and on an additional validation set independently obtained from five medical centers (n = 35). Our biomarker had approximately 90% sensitivity for stage 1 cancer across all subjects. Combining cytopathology of lower airway cells obtained at bronchoscopy with the biomarker yielded 95% sensitivity and a 95% negative predictive value. These findings indicate that gene expression in cytologically normal large-airway epithelial cells can serve as a lung cancer biomarker, potentially owing to a cancer-specific airway-wide response to cigarette smoke.
In clinical practice, men presenting with symptoms of sexual dysfunction often have concomitant sleep disorders requiring treatment. There is now evidence to suggest that treating SDB may be an effective treatment for ED. It is the authors' opinion that patients with erectile dysfunction would benefit from a sleep evaluation.
(1) A moderate morphine dose produced substantial relief of laboratory dyspnea, with a smaller reduction of ventilation. (2) In contrast to an earlier laboratory model of breathing effort, this laboratory model of air hunger established a highly significant treatment effect consistent in magnitude with clinical studies of opioids. Laboratory studies require fewer subjects and enable physiological measurements that are difficult to make in a clinical setting. Within-subject comparison of the response to carefully controlled laboratory stimuli can be an efficient means to optimize treatments before clinical trials.
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