Development of breath test for pneumoconiosis: a case-control study

Abstract

Background: Lipid peroxidation plays an important role in the pathogenesis of pneumoconiosis. Volatile organic compounds (VOCs) generated from lipid peroxidation might be used to detect pneumoconiosis. The objective of this study was to develop a breath test for pneumoconiosis.

Methods: A case-control study was designed. Breath and ambient air were analysed by gas chromatography/mass spectrometry. After blank correction to prevent contamination from ambient air, we used canonical discriminant analysis (CDA) to assess the discrimination accuracy and principal component analysis (PCA) to generate a prediction score. The prediction accuracy was calculated and validated using the International Classification of Radiographs of the Pneumoconiosis criteria combined with an abnormal pulmonary function test as a reference standard. We generated a receiver operator characteristic (ROC) curve and calculated the area under the ROC curve (AUC) to estimate the screening accuracy of the breath test.

Results: We enrolled 200 stone workers. After excluding 5 subjects with asthma and 16 subjects who took steroids or nonsteroidal anti-inflammatory drugs, a total of 179 subjects were used in the final analyses, which included 25 cases and 154 controls. By CDA, 88.8% of subjects were correctly discriminated by their exposure status and the presence of pneumoconiosis. After excluding the VOCs of automobile exhaust and cigarette smoking, pentane and C5-C7 methylated alkanes constituted the major VOCs in the breath of persons with pneumoconiosis. Using the prediction score generated from PCA, the ROC-AUC was 0.88 (95% CI = 0.80-0.95), and the mean ROC-AUC of 5-fold cross-validation was 0.90. The breath test had good accuracy for pneumoconiosis diagnosis.

Conclusion: The analysis of breath VOCs has potential in the screening of pneumoconiosis for its non-invasiveness and high accuracy. We suggest that a multi-centre study is warranted and that all procedures must be standardized before clinical application.

Keywords: Breath test; Breathomics; Lipid peroxidation; Pneumoconiosis; Volatile organic compounds.

Fig. 1

Classification of subjects by the exposure status and presence of pneumoconiosis. Legend: The subjects were classified into three groups. By canonical discriminant analysis and a forward stepwise method, 88.8% of the original grouped cases were correctly classified

Fig. 2

Receiver operating characteristic curves for pneumoconiosis using 5-fold cross-validation. Legend: The data were randomly divided into 5 groups. For each test, one group was removed from the set and was considered the test set, and the remaining four groups formed the training set. The model was built on the training set and was validated on the test set. The mean area under the curve (AUC) of the model is greater than 0.9, which suggests high diagnostic accuracy of the breath test