Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors

Abstract

Previous finding shown that the composition of the breath of patients with lung cancer contains information that could be used to detect the disease. These volatiles are mainly alkanes and aromatic compounds. Sensor arrays technology (electronic nose) proved to be useful to screen samples characterised by different headspace composition. Here we investigated the possibility of using an electronic nose to check whether volatile compounds present in expired air may diagnose lung cancer. Breath samples were collected and immediately analysed by an electronic nose. A total of 60 individuals were involved in the experiment. 35 of them were affected by lung cancer, 18 individuals were measured as reference and nine were measured after the surgical therapy. Two individuals were measured twice, before and after the surgical therapy, for a total of 62 measurements. An electronic nose, composed by eight quartz microbalance (QMB) gas sensors, coated with different metalloporphyrins, was used. These sensors show a good sensitivity towards those compounds previously indicated as possible lung cancer markers in breath. The application of a ‘partial least squares-discriminant analysis’ (PLS-DA) found out a 100% of classification of lung cancer affected patients, 94% of reference was correctly classified. The class of post-surgery patients were correctly individuated in 44% of the cases, while the other samples were classified as healthy references. The alteration of breath composition induced by the presence of lung cancer was enough to allow a complete identification of the sample of diseased individuals. Extended studies are necessary to evaluate the resolution of the method, namely the stage at which the disease may be identified in order to use this instrument for early diagnosis.

Introduction

The volatile organic compounds present in expired breath may give information about general metabolic conditions and, in particular, those of lung. Expired air contains a number of volatile organic constituents that are in quasi-equilibrium with several lung compartments, and may arise from either endogenous or exogenous volatile substances present in the blood. In addiction, certain substances in lung air may be in equilibrium with alveolar fluid or lining material.

In the past, many studies on breath analysis by combined gas chromatography–mass spectroscopy (GC–MS) have been published where the presence of several hundreds of different compounds in human breath was reported (Pauling et al., 1971). They associated the presence of some volatile compounds to certain diseases. For instance mercaptans and aliphatic acids were found in the breath of patients with liver cirrhosis (Kaji et al., 1978) while dimethyl- and trimethylamine were found in the breath of uremic patients (Simenhoff et al., 1977).

The expired air from lung cancer patients was also examined. Evidence that different volatile patterns occur in affected individuals has been claimed and that the presence of some of them may be correlated to the lung cancer was found. These compounds are mostly some alkanes (hexane and methylpentane among the others) and benzene derivatives such as o-toluidine and aniline (O'Neil et al., 1988). The correlation between breath composition and lung cancer has been recently confirmed in a cross-sectional study involving 108 individuals (Philips et al., 1999). Nonetheless, these studies still did not lead to a diagnostic method due to the overwhelming complexity of analysis carried out by GC–MS.

In the last two decades the introduction of chemical sensors lent the opportunity to reconsider these seminal studies in order to check whether novel diagnostic tools based on the chemical information contained in the exhaled volatile may be set out.

In the 80s the absence of selectivity, one of the major drawbacks of chemical sensors, was taken into consideration as the basis for a novel instrument able to provide global information about samples. This is somewhat resembling to the functioning of the human olfaction do with odorants (Persaud and Dodds, 1982).

These instruments are basically arrays on non-selective sensors. In fact, the sensors response is not univocally correlated with the concentration of a single compound (as in the classical analytical chemistry) but rather it is a sort of combination of all the chemical information contained in each sample. This is obtained through a broad selectivity, like a sort of chemical filtration.

Since then, these arrays, now widely known as electronic noses, have been applied to many different fields (Kress-Rogers, 1996). Food analysis was the most exploited field for many practical reasons, basically for the importance of human senses in food acceptance. This allowed interesting and successful comparisons between electronic noses and human olfaction (Sinesio et al., 2000).

Recently, medical field was also taken into consideration and the application of electronic nose to detect diseases was proposed. In this context some researchers have shown the ability of these devices to identify bacteria (Gardner et al., 1998, Holmberg et al., 1988, Pavolu et al., 2000). These researches were looking for the utilisation of electronic noses in the diagnosis of infections, such as pneumonia by the analysis of patient breath. The analysis of breath has also been supposed to be a useful indicator for the diagnosis of diabetes (Ping et al., 1997). In the tradition of olfactive medicine the application of electronic noses to fast detection of blood cells in urine has been reported (Di Natale et al., 1999).

Another possible application has been demonstrated in a recent paper in which the ability of chemical sensors to detect compounds secreted by the human body in the human sweat has been demonstrated (Di Natale et al., 2000).

In this study, the application of an electronic nose to the analysis of breath from patients affected by lung cancer is described.