Integration of electronic nose technology with spirometry: validation of a new approach for exhaled breath analysis

Abstract

New 'omics'-technologies have the potential to better define airway disease in terms of pathophysiological and clinical phenotyping. The integration of electronic nose (eNose) technology with existing diagnostic tests, such as routine spirometry, can bring this technology to 'point-of-care'. We aimed to determine and optimize the technical performance and diagnostic accuracy of exhaled breath analysis linked to routine spirometry. Exhaled breath was collected in triplicate in healthy subjects by an eNose (SpiroNose) based on five identical metal oxide semiconductor sensor arrays (three arrays monitoring exhaled breath and two reference arrays monitoring ambient air) at the rear end of a pneumotachograph. First, the influence of flow, volume, humidity, temperature, environment, etc, was assessed. Secondly, a two-centre case-control study was performed using diagnostic and monitoring visits in day-to-day clinical care in patients with a (differential) diagnosis of asthma, chronic obstructive pulmonary disease (COPD) or lung cancer. Breathprint analysis involved signal processing, environment correction based on alveolar gradients and statistics based on principal component (PC) analysis, followed by discriminant analysis (Matlab2014/SPSS20). Expiratory flow showed a significant linear correlation with raw sensor deflections (R(2) = 0.84) in 60 healthy subjects (age 43 ± 11 years). No correlation was found between sensor readings and exhaled volume, humidity and temperature. Exhaled data after environment correction were highly reproducible for each sensor array (Cohen's Kappa 0.81-0.94). Thirty-seven asthmatics (41 ± 14.2 years), 31 COPD patients (66 ± 8.4 years), 31 lung cancer patients (63 ± 10.8 years) and 45 healthy controls (41 ± 12.5 years) entered the cross-sectional study. SpiroNose could adequately distinguish between controls, asthma, COPD and lung cancer patients with cross-validation values ranging between 78-88%. We have developed a standardized way to integrate eNose technology with spirometry. Signal processing techniques and environmental background correction ensured that the multiple sensor arrays within the SpiroNose provided repeatable and interchangeable results. SpiroNose discriminated controls and patients with asthma, COPD and lung cancer with promising accuracy, paving the route towards point-of-care exhaled breath diagnostics.

Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma

“…In conclusion, metabolomics of exhaled breath enables discrimination between stable periods and periods of loss of control during longitudinal follow‐up of patients with asthma, which is partly associated with sputum eosinophils. The present proof of principle supports bringing eNose technology to point of care for broad clinical validation in the monitoring and management of asthma.…”

“…It needs to be emphasized that although the breath analysis methods used in this study have been validated in earlier studies, the methods are not directly suitable for use in clinical day‐to‐day practice. Whereas GC/MS requires a laboratory for the handling of the samples, electronic nose technology is currently being modified for use at the doctor's office . Finally, the choice of the statistics may have affected our outcomes.…”

Breathomics from exhaled volatile organic compounds in pediatric asthma

“…Another possibility is to correct for compounds in ambient air but how to correct for this is still under debate. Correcting exhaled concentrations by subtracting inspiratory from expiratory concentrations, called alveolar gradients, is one possibility . However, this procedure does not take into account the complexity of gas exchange processes in the lung .…”

“…Other factors that generate variability in exhaled breath samples are exhalation flow, breath hold prior to exhalation and the number of exhalations (single or multiple exhalations) in one sample . In most studies, a single expiratory vital capacity maneuver is performed during single‐breath sampling .…”

Adding biological markers to COPD categorisation schemes: a way towards more personalised care?

“…Invasive airway sampling using bronchoscopy is obviously inadequate for routine clinical use. Sputum and exhaled air (which can be assessed using electronic nose technology) [28] can provide useful samples for research, but remain to be validated for routine use. Blood measurements could represent simple and relatively inexpensive tools, but so far only few data are available on their potential to add value to current categorisation processes, when added to usual clinical characteristics of patients assessed at steady state.…”