Airways oxidative stress, lung function and cognitive impairment in aging.

Abstract BACKGROUND: An altered balance of oxidants/antioxidants is one of the pathological mechanisms of many age-dependent disorders. We aimed to investigate the age-related airways oxidative stress, using non invasive, safe and repeatable techniques; to evaluate the correspondence between systemic and local oxidative stress in healthy subjects of different age ranges; to analyse the correlation between systemic and local oxidative stress with lung function and with cognitive impairment. METHODS: Thirty consecutive healthy high school graduated subjects (8 M, 22 F), divided in three ranges of age ( 60 years) were enrolled. All subjects underwent oxygen free radicals and exhaled nitric oxide measurement (by the diacron reactive oxygen metabolites test and by a rapid-response chemiluminescence nitric oxide analyzer), lung function tests, and cognitive impairment scales (Mini Mental State Examination and Geriatric Depression Scale). RESULTS: A significant increase of oxygen free radicals, exhaled nitric oxide, and Geriatric Depression Scale score and a significant decrease of forced expiratory volume in 1 second and forced expiratory vital capacity from younger to older subjects were identified. Moreover, the significant positive correlation between oxygen free radicals and exhaled nitric oxide, and between oxygen free radicals and exhaled nitric oxide with Geriatric Depression Scale score were found. The significant negative correlation between forced expiratory volume in 1 second and oxygen free radicals or exhaled nitric oxide was also demonstrated. CONCLUSIONS: Our data supports the role of progressive local oxidative stress in damaging the lung function and in inducing depression symptoms

New biomolecular methodologies in diagnosis of lung cancer

Lung cancer remains the most frequent tumour and cause of cancer death in worldwide. Unfortunately most of patients still discover their tumour in advanced stage. Lung cancer results from the occurrence of a number of genetic alterations in oncogenes and tumour suppressor genes that are potential markers either for screening procedures or for earlier detection in patients with non small-cell lung cancer (NSCLC). It was estimated that about 10 to 20 genetic events are required for lung tumorigenesis. These genetic changes are triggered by smoking and persist for many years after smoking cessation. Continuously, more sophisticated methods for the analysis of these genetic alterations involved in lung cancer become available. Several molecular alterations involved in lung cancer have been already identified in different biological samples (biopsy, BAL) that are collected with highly invasive techniques that make them poorly suitable for wider screening. Recently the DNA has been extracted from exhaled breath condensate, demonstrating the suitability of this sample for the study of genetic alterations and its potential role in screening programs of subjects at risk of lung cancer

Cigarette smoke and increased COX-2 and survivin levels in exhaled breath condensate of lung cancer patients: how hot is the link?

One of the most current intriguing hypotheses on lung cancerogenesis envisages a role for inflammation as a possible trigger of both epithelial-mesenchymal transition and cancer development. Cigarette smoke has been suggested to be the main factor underlying the inflammation of the airways described in lung cancer patients. Cycloxygenase and survivin, a COX-2 dependent factor of apoptosis resistance, seem to play a key role in this regard. PURPOSE: The aim of this study was to study COX-2 and survivin in the airways of lung cancer patients and in those of a group of smokers in a view to increasing our understanding of the link between smoking, airway inflammation and lung cancer. PATIENTS AND METHODS: 70 NSCLC patients (28 smokers, 26 ex-smokers and 16 non-smokers) and 30 healthy subjects (20 smokers and 10 non-smokers) were enrolled in the study. Both COX-2 and survivin concentrations were measured in the exhaled breath condensates of all the subjects under study using EIA kits. RESULTS: Higher levels of exhaled survivin and COX-2 were found in NSCLC patients compared to healthy smokers and non-smokers. These levels were observed to be significantly elevated in smokers (patients with lung cancer and healthy) and ex-smokers compared to non-smokers and exhibited a positive correlation with the number of cigarettes smoked expressed as pack/year. A correlation was also found between exhaled COX-2 and survivin and the progression of cancer. CONCLUSIONS: We support the hypothesis that cigarette smoke be strongly connected to the inflammation of the airways observed in lung cancer patients. On the basis of the results obtained the use of exhaled breath condensate COX-2 and survivin levels could be suggested as two potential markers within an early non-invasive screening of populations of smokers at risk of lung cancer

Exhaled ERCC-1 and ERCC-2 microsatellite alterations in NSCLC patients

Background: The excision repair cross-complementation (ERCC) enzyme plays a rate-limiting role in nucleotide excision repair pathway. Microsatellite alterations (MAs) at the long arm of chromosome 19, where are located the ERCC genes, have recently been associated with non-small cell lung cancer (NSCLC) pathogenesis and reduced survival.The aim of the present study was to explore MAs at 19q in DNA from exhaled breath condensate (EBC) of NSCLC patients investigating their possible correlation with the smoking habit, with the biological behaviour of the tumour and their predictive survival power. Methods: 34 NSCLC patients and 33 healthy controls (19 non-smokers and 14 smokers) were enrolled. All the subjects underwent 19q microsatellite analysis of their EBC. A total of 25 patients were either given a follow-up of at least 102 weeks, or were followed up until death. Results: No MAs were found in EBC or WB in the healthy non-smokers, while 16% of exhaled MAs were found in healthy smokers and 25% of exhaled MAs in NSCLC patients. The number of MAs resulted related with tobacco consumption and with NSCLC patients' survival. Conclusions: In conclusion, the study of MAs at 19q resulted feasible in EBC-DNA. These genetic alterations are specific for lung cancer and predictive of survival in NSCLC patients. Our results suggest interesting clinical perspectives for the analysis of exhaled MAs at 19q in NSCLC patients. © 2010 Elsevier Ireland Ltd