Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study

doi:10.1016/S0140-6736(98)07552-7

The Lancet

Volume 353, Issue 9168, 5 June 1999, Pages 1930-1933

https://doi.org/10.1016/S0140-6736(98)07552-7 Get rights and content

Summary

Background

Many volatile organic compounds (VOCs), principally alkanes and benzene derivatives, have been identified in breath from patients with lung cancer. We investigated whether a combination of VOCs could identify such patients.

Methods

We collected breath samples from 108 patients with an abnormal chest radiograph who were scheduled for bronchoscopy. The samples were collected with a portable apparatus, then assayed by gas chromatography and mass spectroscopy. The alveolar gradient of each breath VOC, the difference between the amount in breath and in air, was calculated. Forward stepwise discriminant analysis was used to identify VOCs that discriminated between patients with and without lung cancer.

Findings

Lung cancer was confirmed histologically in 60 patients. A combination of 22 breath VOCs, predominantly alkanes, alkane derivatives, and benzene derivatives, discriminated between patients with and without lung cancer, regardless of stage (all p<0·0003). For stage 1 lung cancer, the 22 VOCs had 100% sensitivity and 81·3% specificity. Cross-validation of the combination correctly predicted the diagnosis in 71·7% patients with lung cancer and 66·7% of those without lung cancer.

Interpretation

In patients with an abnormal chest radiograph, a combination of 22 VOCs in breath samples distinguished between patients with and without lung cancer. Prospective studies are needed to confirm the usefulness of breath VOCs for detecting lung cancer in the general population.

Introduction

Every year, in the USA, 99 000 men and 78 000 women develop lung cancer. 5 years after diagnosis, only 14% of these people are alive. If, however, the lung cancer is localised at the time of diagnosis and treated promptly, 5-year survival increases to 48%.¹ This fact has stimulated the search for screening tests to detect lung cancer at an early stage when it is probably localised.

Breath may contain clinically useful markers of lung cancer.² In 1971, Pauling and co-workers³ reported that normal human breath contains a complex mixture of several hundred volatile organic compounds (VOCs). Since most VOCs are exhaled in picomolar concentrations, special methods are needed to collect and concentrate VOCs before assay. O'Neill and colleagues4, 5 identified 28 breath VOCs as candidate markers of lung cancer—principally alkanes such as hexane and methylpentane, and benzene derivatives. o-toluidine, aniline, and altered lipid-peroxidation activity have also been found in the breath of patients with lung cancer.6, 7

In this study, we studied VOCs in the breath of patients with and without lung cancer.

Section snippets

Methods

In a cross-sectional study, eligible patients were those scheduled for bronchoscopy to investigate a localised chest-radiograph abnormality. Other inclusion criteria were: aged 18 or older, comprehension of the breath-collection procedure, and signed informed consent. Patients with known neoplasms of any kind were excluded. The study was approved by the institutional review boards of Penn State Medical Center, Hammersmith Hospital, and St Vincent's Medical Center.

Bronchoscopy was done by

Results

Between August, 1995, and October, 1996, 108 eligible patients agreed to participate. The collection of breath samples was not associated with any adverse effects. Lung cancer was confirmed histologically in 60 patients (34 men) and excluded in 48 patients (29 men). The mean (SD) age of patients was 66·9 years (12·5) in patients with lung cancer and 61 years (13·4) in patients without. Five patients with lung cancer had never smoked compared with 12 in the group without lung cancer. The

Discussion

The 22 breath VOCs that discriminated between the patients with and without lung cancer were similar to those reported by O'Neill and co-workers⁴ to be markers of lung cancer. There were some minor differences in chemical structure which might be due to the use of different libraries of mass spectra. Structurally similar breath VOCs were observed in patients with and without lung cancer, but there were significant quantitative differences between the two groups.

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Early ReportVolatile organic compounds in breath as markers of lung cancer: a cross-sectional study

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

J Chromatogr

Anal Biochem

Eur J Cancer

Lancet

Chest

Arch Biochem Biophys

J Chromatogr

Chest

Neoplasms of the lung

Breath tests in medicine

Sci Am

Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography

Proc Nat Acad Sci USA

A computerized classification technique for screening for the presence of breath biomarkers in lung cancer

Clin Chem

Volatile organic compounds in exhaled air from patients with lung cancer

Clin Chem

Diagnostic value of investigating exhaled air condensate in lung cancer (in Russian)

Vopr Onkol

Optimal bronchoscopy

J Bronchology

Early Report
Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study