Early-stage asymptomatic lung cancer in patients with chronic obstructive pulmonary disease (COPD) may be identified using molecular profiling of exhaled breath using an electronic technology called “eNose,” according study findings published in Chest.
Given the heightened risk of developing lung cancer in patients with COPD, investigators in the Netherlands sought to assess whether eNose technology could prospectively and accurately diagnose early-stage asymptomatic lung cancer in patients with COPD. The noninvasive eNose technology, which analyzes volatile organic compounds (VOCs) in exhaled breath, uses a metal oxide semiconductor and employs advanced pattern recognition algorithms for molecular profiling.
Investigators used data from the prospective, observational, multicenter BreathCloud study to evaluate the diagnostic accuracy of eNose technology for identifying cancer in patients with COPD. The current study included 2 groups of patients: 682 patients diagnosed with COPD and 211 patients with lung cancer. Participants were enrolled between May 2017 and November 2018 and followed for 2 years. eNose technology was used at baseline and over the 2-year study period to collect duplicate breath profiles of those obtained in day-to-day real-world clinical care. Patients with COPD received standard clinical care while being monitored for incidence of lung cancer.
Researchers divided patients into a training cohort (n=455 COPD, n=141 lung cancer) and validation cohort (n=227 COPD, n=70 lung cancer), analyzing data from both cohorts using receiver operating characteristic analysis (ROC-AUC), linear discriminant analysis, and principal component (PC) analysis.
Exhaled breath analysis by eNose identified COPD patients in whom lung cancer became clinically manifest within 2 years after inclusion. These results show eNose assessment may detect early stages of lung cancer in patients with COPD.
Data analysis showed that patients with COPD and lung cancer in both the training and validation cohorts showed significant differences with respect to principal components 1, 2 and 3, with ROC-AUCs of 0.89 (CI, 0.83-0.95) and 0.86 (CI:0.81-0.89).
During the 2-year study period, 37 patients (5.4%) with COPD developed clinically manifest lung cancer. Of those, 33 (89%) were identified by eNose at baseline as having lung cancer. Notably, principal components 1, 2, and 3 showed significant differences (P <.01) at baseline between the COPD patients who did and did not ultimately develop lung cancer during the 2-year study period (cross-validation value, 87%; ROC-AUC of 0.90; CI, 0.84-0.95).
In comparing characteristics of patients with COPD vs those with lung cancer in the training cohort, the researchers noted significant differences in pack years and forced expiratory volume in 1 second between the 2 cohorts (P <.05). However, no significant between-group differences were found in the validation set. Other than COPD staging and lung cancer pathology, patients in the training and validation sets had similar baseline characteristics.
The study authors did not identify the clinical characteristics associated with principal components 1, 2, and 3 that may have contributed to the manifestation of lung cancer. According to study authors, although “pack years [but not smoking status] was significantly driving the prediction of PC2,” there were no significant differences in pack years or smoking status among patients with COPD who were and were not diagnosed with lung cancer during the study period. Similarly, although “age, BMI, ethnicity, lung cancer staging, and lung cancer pathology also added significantly to the prediction of 1 or 2 [principal components],” participants with COPD and lung cancer in both cohorts were similar at baseline with respect to all of these clinical characteristics except for lung cancer pathology.
Study limitations include lack of CT baseline scans leaving unclear prior presence of tumors.
Researchers said that their analysis suggests cancer-related cellular and metabolic processes were already present in patients at the time of exhaled breath measurement, despite the absence of any symptoms signifying lung cancer. “Exhaled breath analysis by eNose identified COPD patients in whom lung cancer became clinically manifest within 2 years after inclusion,” researchers concluded. They added, “These results show eNose assessment may detect early stages of lung cancer in patients with COPD.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.