Marco Santonico

An investigation on electronic nose diagnosis of lung cancer

The use of gas sensor arrays as medical diagnosis instruments has been proposed several years ago. Since then, the idea has been proven for a limited number of diseases. The case of lung cancer is particularly interesting because it is supported by studies that have shown the correlation between the composition of breath and the disease. However, it is known that many other diseases can alter the breath composition, so for lung cancer diagnosis it is necessary not only to detect generic alterations but those specifically consequent to cancer. In this paper an experiment, performed in the bronchoscopy unit of a large hospital, aimed at discriminating between lung cancer, diverse lung diseases and reference controls is illustrated. Results show not only a satisfactory identification rate of lung cancer subjects but also a non-negligible sensitivity to breath modification induced by other affections. Furthermore, the effects of some compounds frequently found in the breath of lung cancer subjects have also been studied. Results indicate that breath samples of control individuals drift towards the lung cancer group when added with either single or mixtures of these alleged cancer-related compounds.

Diagnostic Performance of an Electronic Nose, Fractional Exhaled Nitric Oxide, and Lung Function Testing in Asthma

BACKGROUND Analysis of exhaled breath by biosensors discriminates between patients with asthma and healthy subjects. An electronic nose consists of a chemical sensor array for the detection of volatile organic compounds (VOCs) and an algorithm for pattern recognition. We compared the diagnostic performance of a prototype of an electronic nose with lung function tests and fractional exhaled nitric oxide (FENO) in patients with atopic asthma. METHODS A cross-sectional study was undertaken in 27 patients with intermittent and persistent mild asthma and in 24 healthy subjects. Two procedures for collecting exhaled breath were followed to study the differences between total and alveolar air. Seven patients with asthma and seven healthy subjects participated in a study with mass spectrometry (MS) fingerprinting as an independent technique for assessing between group discrimination. Classification was based on principal component analysis and a feed-forward neural network. RESULTS The best results were obtained when the electronic nose analysis was performed on alveolar air. Diagnostic performance for electronic nose, FENO, and lung function testing was 87.5%, 79.2%, and 70.8%, respectively. The combination of electronic nose and FENO had the highest diagnostic performance for asthma (95.8%). MS fingerprints of VOCs could discriminate between patients with asthma and healthy subjects. CONCLUSIONS The electronic nose has a high diagnostic performance that can be increased when combined with FENO. Large studies are now required to definitively establish the diagnostic performance of the electronic nose. Whether this integrated noninvasive approach will translate into an early diagnosis of asthma has to be clarified. TRIAL REGISTRATION EUDRACT https://eudralink.emea.europa.eu; Identifier: 2007-000890-51; and clinicaltrials.gov; Identifier: NCT00819676.

Identification of melanoma with a gas sensor array.

Background/purpose: The relationship between diseases and alterations of the airborne chemicals emitted from the body has been found in many different pathologies and in particular for various forms of cancer. Metabolism of cancer cells is greatly altered during their lifetime; then, modification of chemicals is supposed to be large around cancer tissues. Positive hints in this direction were provided, as an example, on studying the breath composition of lung cancer‐affected subjects. Besides the conventional analytical approaches, in recent years sensor arrays were also applied to these researches considering the chemical composition changes as those occurring in other applications such as for instance, those dealing with food quality measurements.

A European Respiratory Society technical standard: exhaled biomarkers in lung disease

Breath tests cover the fraction of nitric oxide in expired gas (FENO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FENO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FENO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management. Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members. Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised. Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice. ERS technical standard: exhaled biomarkers in lung disease http://ow.ly/mAjr309DBOP

Differential detection of potentially hazardous Fusarium species in wheat grains by an electronic nose.

Fungal infestation on wheat is an increasingly grave nutritional problem in many countries worldwide. Fusarium species are especially harmful pathogens due to their toxic metabolites. In this work we studied volatile compounds released by F. cerealis, F. graminearum, F. culmorum and F. redolens using SPME-GC/MS. By using an electronic nose we were able to differentiate between infected and non-infected wheat grains in the post-harvest chain. Our electronic nose was capable of distinguishing between four wheat Fusaria species with an accuracy higher than 80%.

The lung cancer breath signature: a comparative analysis of exhaled breath and air sampled from inside the lungs

Results collected in more than 20 years of studies suggest a relationship between the volatile organic compounds exhaled in breath and lung cancer. However, the origin of these compounds is still not completely elucidated. In spite of the simplistic vision that cancerous tissues in lungs directly emit the volatile metabolites into the airways, some papers point out that metabolites are collected by the blood and then exchanged at the air-blood interface in the lung. To shed light on this subject we performed an experiment collecting both the breath and the air inside both the lungs with a modified bronchoscopic probe. The samples were measured with a gas chromatography-mass spectrometer (GC-MS) and an electronic nose. We found that the diagnostic capability of the electronic nose does not depend on the presence of cancer in the sampled lung, reaching in both cases an above 90% correct classification rate between cancer and non-cancer samples. On the other hand, multivariate analysis of GC-MS achieved a correct classification rate between the two lungs of only 76%. GC-MS analysis of breath and air sampled from the lungs demonstrates a substantial preservation of the VOCs pattern from inside the lung to the exhaled breath.

Detection and identification of cancers by the electronic nose

INTRODUCTION The early determination of serious pathologies has so far been an important issue in both the medical and social fields. The search for an instrument able to detect cancers has led to the consideration of the usage of chemicals of the human body, which carry, through its volatile compounds, information coming from or related to defined pathologies. AREAS COVERED The electronic nose (EN) seems to represent a good solution for the detection of cancers of different types. Recent results showed the utility of an EN to smell chemicals related to lung, melanoma, prostatic, breast and pancreatic cancers. The results obtainable from ENs are chemical images and, as it will be shown in this paper, the probability of cancer recognition is rather high. Main results obtained at international level and by the authors of this paper will be commented upon. EXPERT OPINION A personal opinion is given trying to foresee future developments of the olfaction strategy. To this purpose, two main aspects are considered: looking for better overall stability of the EN and for a new use of ENs in detecting alterations between blood and pathology components.

Reproducibility and Respiratory Function Correlates of Exhaled Breath Fingerprint in Chronic Obstructive Pulmonary Disease

Background The electronic nose (e nose) provides distinctive breath fingerprints for selected respiratory diseases. Both reproducibility and respiratory function correlates of breath fingerprint are poorly known. Objectives To measure reproducibility of breath fingerprints and to assess their correlates among respiratory function indexes in elderly healthy and COPD subjects. Method 25 subjects (5 COPD patients for each GOLD stage and 5 healthy controls) over 65 years underwent e-nose study through a seven sensor system and respiratory function tests at times 0, 7, and 15 days. Reproducibility of the e nose pattern was computed. The correlation between volatile organic compound (VOC) pattern and respiratory function/clinical parameters was assessed by the Spearmans rho. Measurements and Main Results VOC patterns were highly reproducible within healthy and GOLD 4 COPD subjects, less among GOLD 1–3 patients.VOC patterns significantly correlated with expiratory flows (Spearmans rho ranging from 0.36 for MEF25% and sensor Co-Buti-TPP, to 0.81 for FEV1% and sensor Cu-Buti-TPP p<0.001)), but not with residual volume and total lung capacity. Conclusions VOC patterns strictly correlated with expiratory flows. Thus, e nose might conveniently be used to assess COPD severity and, likely, to study phenotypic variability. However, the suboptimal reproducibility within GOLD 1–3 patients should stimulate further research to identify more reproducible breath print patterns.

Chronic Obstructive Pulmonary Disease in the elderly.

The prevalence of Chronic Obstructive Pulmonary Disease (COPD) dramatically increases with age, and COPD complicated by chronic respiratory failure may be considered a geriatric condition. Unfortunately, most cases remain undiagnosed because of atypical clinical presentation and difficulty with current respiratory function diagnostic standards. Accordingly, the disease is under-recognized and undertreated. This is expected to impact noticeably the health status of unrecognized COPD patients because a timely therapy could mitigate the distinctive and important effects of COPD on the health status. Comorbidity also plays a pivotal role in conditioning both the health status and the therapy of COPD besides having major prognostic implication. Several problems affect the overall quality of the therapy for the elderly with COPD, and current guidelines as well as results from pharmacological trials only to some extent apply to this patient. Finally, physicians of different specialties care for the elderly COPD patient: physicians specialty largely determines the kind of approach. In conclusion, COPD, in itself a complex disease, becomes difficult to identify and to manage in the elderly. Interdisciplinary efforts are desirable to provide the practicing physician with a multidisciplinary guide to the identification and treatment of COPD.

Exhaled breath analysis by electronic nose in respiratory diseases.

Breath analysis via electronic nose is a technique oriented around volatile organic compound (VOC) profiling in exhaled breath for diagnostic and prognostic purposes. This approach, when supported by methodologies for VOC identification, has been often referred to as metabolomics or breathomics. Although breath analysis may have a substantial impact on clinical practice, as it may allow early diagnosis and large-scale screening strategies while being noninvasive and inexpensive, some technical and methodological limitations must be solved, together with crucial interpretative issues. By integrating a review of the currently available literature with more speculative arguments about the potential interpretation and application of VOC analysis, the authors aim to provide an overview of the main relevant aspects of this promising field of research.