Breaking News from ERS 2014 - Munich Germany

In this news update from ERS 2014, I would like to focus on non-invasive approaches to diagnosing early lung disease. I comment on three abstracts on diagnosis of lung cancer, and further down there is one abstract on early cystic fibrosis lung disease:

There are two interesting studies studying the electronic nose (eNose) in context of lung cancer diagnosis, and one is looking at temperature in exhaled breath:

The eNose is a research tool that can be used to analyze the profile of volatile organic compounds (EVOCs) of exhaled breath. Sedda and colleagues from Milan, Italy used the eNose to compare the breath of 35 lung cancer patients and healthy controls. They found that the eNose could distinguish between lung cancer and healthy controls.

Similarly, Dent and colleagues from Brisbane, Australia report that eNose in their study was able to distinguish people with asymptomatic early stage lung cancer from healthy smokers, suggesting that the eNose could be useful in diagnosing lung cancer early.

A further promising non-invasive test in the diagnosis of lung cancer may be the simple measurement of temperature in the exhaled breath. Carpagnano and coworkers in their study of 82 subjects that underwent standard diagnostic and staging procedures for lung cancer, found exhaled breath temperature to raised in NSCLC and to correlated with number of packs/years and stage of lung cancer.
— CARE Respiratory Medicine Faculty – Dr. Hartmut Grasemann

ERS 2014. P348 Early diagnosis of lung cancer by the electronic nose: Preliminary results

G. Sedda, R. Gasparri, J. Guarize, D. Brambilla, A. Borri, M. Santonico, G. Pennazza, C. Di Natale, R. Paolesse, A. D'Amico, L. Spaggiari (Rome, Milan, Italy)

Introduction: Lung cancer is a major public health problem worldwide. During the years, several screening programs have been developed with the aim of detecting disease at a stage when cure and control are possible. Among the new available options for an early detection, analysis of exhaled air seems to be very promising thanks to its characteristics and stands out as a viable candidate for widespread screening.

Methods: Between 09/05/2013 and 30/01/2014, in the Division of Thoracic Surgery of the European Institute of Oncology in Milan, we prospectively investigated the breath of 70 subjects volunteers with signed consent. This work has been funded by the Italian Association for Cancer Research (AIRC) and approved by Ethic Commission. Population consisted of 35 patients with lung cancer and 35 healthy subjects, each one older than 50 years. Measurements were performed immediately after the collection. We analyzed the breath of the recruited subjects with an electronic nose (TEN NOSE) to validate the ability of the instrument to distinguish between healthy subjects and lung cancer patients. The data were analyzed by multivariate technical analysis.

Results: The statistical analysis found out a positive predictive value of 79% and a negative predictive value of 76%. Furthermore the sensitivity of the electronic nose was 74% and the specificity was 80%.

Conclusion: These preliminary results are satisfactory and define the electronic nose as a promising tool for early diagnosis. The novelty of these researches concerns the realization of a robust model to transfer the instrument in the clinical practice. Further studies are necessary to extend the analysis to evaluate larger groups of patients.


ERS 2014. P349 Electronic nose as a screening tool for early stage lung cancer

A. Dent, R. Bowman, P. Zimmerman, I. Yang, K. Fong (Brisbane, Australia)

Background: Computer tomography (CT), a gold standard screening tool for lung cancer in high risk symptomless subjects, has relatively high associated costs and risks with low incidence of cancer detection. There is a need for a tool to predict subjects with a higher probability of early stage lung cancer (ESLC - Staged I or II by 7th ed TNM system) prior to CT screening. We previously demonstrated that exhaled breath volatile organic compound (eVOC) profile differs between lung cancer and healthy smokers.

Aim: To determine if eVOC profile of subjects diagnosed with ESLC, without symptoms (ESLC-S) differs from that of those with symptoms (ESLC+S) and that of healthy smokers (HS).

Method: ESLC+S (n= 53), ESLC-S (n=29) and HS (n=188) subjects provided a breath sample after breathing filtered air for 5 mins for analysis on a 32 sensor Cyranose 320 (Sensigent). Sensor data were log transformed and reduced to principal components for canonical discriminant analysis to determine differences between groups. Accuracy (CVV) was calculated using SPSS V17.0 with leave one out cross validation. Sensitivity, specificity, PPV and NPV were calculated.

Results: The eVOC profile distinguished between ESLC-S and HS (p<0.0001), CVV 91%, sensitivity 38%, specificity 100%, PPV 100% and NPV 91 %. The difference in eVOC profile between ESLC+S and ESLC-S was not significant (P=0.08).

Conclusion: These data indicate the ability of exhaled breath VOC profiles to distinguish people with asymptomatic early stage lung cancer from healthy smokers, and therefore support its potential as a non-invasive screening tool for early detection of lung cancer. Supported by The Prince Charles Hospital Foundation and Private Practice Trust Fund.


ERS 2014. Abstract 1928.  Exhaled breath temperature in NSCLC: Could be a new non invasive marker?

G. E. Carpagnano, G. Scioscia, D. Lacedonia, A. Spanevello, D. Martinelli, V. Saliani, C. Ruggieri, M.P. Foschino-Barbaro (Foggia, Italy)

Background and aim: The exhaled breath temperature (EBT) has been proven to be the expression of airways inflammation as well as of the increased vascularity. Although both these conditions characterize lung cancer pathogenesis, this is the first study where the exhaled breath temperature has been analysed in patients affected by non-small cell lung cancer. The aim of this study was to verify whether and how the lung cancer being examined influences the exhaled breath temperature for possible future clinical implications.

Material and Methods: 82 consecutive subjects with a radiological suspicion of lung cancer were enrolled and underwent standard diagnostic and staging procedures for cancer. EBT was measured in all the subjects at the enrollement with the X-Halo device.

Results: 40 patients resulted as affected by lung cancer while 42 as false positive (controls). We found a higher exhaled breath temperature in NSCLC patients compared to healthy subjects. The EBT was correlated with number of packs/years and associated with the stage of lung cancer. We identified a cut-off value for the EBT that is able to screen patients with lung cancer with a high sensitivity and specificity.

Conclusions: Our results suggest that lung cancer causes an increase of the exhaled breath temperature which, whether confirmed and validated, could become a new non-invasive clinical tool in the screening and monitoring of this disease.

It is now widely accepted that significant lung disease can occur in patients with cystic fibrosis (CF) before it becomes clinically evident. Recent studies have demonstrated early abnormalities using chest computed tomography (CT) imaging but this technique has the disadvantage of radiation exposure. Marshall et al from the UK compared the sensitivity of different techniques to detect early-stage lung disease in children with CF. They found that magnetic resonance imaging (MRI) with 3Helium was more sensitive to early ventilation changes in CF than lung clearance index (LCI), 1H MRI or pulmonary function tests. Both 3Helium MRI and CT detected lung abnormalities in CF children with sub-clinical disease. These data imply that imaging screening for early CF lung disease could be done by polarized gas MRI, thus avoiding the radiation exposure associated with CT scanning.
— CARE Respiratory Medicine Faculty – Dr. Hartmut Grasemann

ERS 2014. Abstract 3448 Detection of early-stage lung disease in cystic fibrosis; comparing the sensitivity of 3He and 1H MRI, CT and LCI

H. Marshall, D. Hughes, A. Horsley, F. Horn, L. Smith, J. Parra-Robles, S. Cunningham, L. Armstrong, I. Aldag, C. Taylor, J. Wild (Sheffield, Edinburgh, United Kingdom)

Introduction: Detection of early-stage lung disease in cystic fibrosis (CF) is critical to guide clinical treatment to prolong the onset of irreversible lung disease.

Objective: To investigate the relative sensitivity of imaging; 3He and 1H MRI, CT and lung clearance index (LCI) for detection of early stage lung disease in children with mild CF.

Methods: 11 CF patients (7-16yrs) and 5 controls (7-14yrs) were assessed with 3He and 1H MRI, sitting and supine multi-breath washout (MBW), low-dose CT (patients only) and pulmonary function tests. All participants had spirometry within normal range. Quantitative 3He MRI measures were calculated. Images were read by a paediatric. chest radiologist.

Results: The 3He MRI measures of un-ventilated volume percentage (UVP) and ventilation heterogeneity (coefficient of variation standard deviation (CV)) were significantly higher in patients than controls (UVP 4.3 vs 2.1 and CV 10.9 vs 9.8, p<0.05). LCI was elevated in patients compared to controls, but not significantly so. Abnormalities were detected in the 3He MRI of 10 patients, the CT of 9 patients and the 1H MRI of 4 patients (fig 1). Sitting LCI was abnormal (>7.4) in 5 patients. All controls had normal MRI and LCI.

Conclusion: 3He MRI is more sensitive to early ventilation changes in CF than LCI, 1H MRI or pulmonary function tests. 3He MRI and CT detected lung abnormalities in CF children with sub-clinical disease.