Exhaled carbon monoxide: a non-invasive biomarker of short-term exposure to outdoor air pollution

Outdoor air pollution (OAP) especially from vehicular traffic is of growing importance since it occurs largely in urban areas expected to constitute 66% of the world population by 2050 [1]. According to the United Nations [1], much of the expected urban growth will take place in low and middle-income countries (LMICs), particularly Africa. The 68th United Nations World Health Assembly called for action to reduce the burden of OAP in LMICs [2]. Taking action to reduce exposure to OAP warrants the assessment of the exposure level through personal and environmental monitoring.

Several epidemiologic studies have found that ambient air pollution (from generators, vehicular emissions, agriculture and open burning, and household air pollution) is associated with risk of developing a broad range of diseases [3‐5]. Ambient air pollution, for example particulate matter [6], is classified by the International Agency for Research on Cancer (IARC) as a group 1 carcinogen to humans lungs [7]. Sulphur dioxide (SO2), Nitrous oxide (NOX), carbon monoxide (CO) and low molecular weight particulate matter (e.g. PM_2.5) from traffic-related air pollution (TRAP) are likely important contributors to OAP and have been extensively measured. Several potential biomarkers of OAP have been studied e.g., fraction of exhaled nitric oxide (FeNO), spirometry parameters, constituent cytokines, exhaled breath condensate, and induced sputum [8]; however, these measurements need technical expertise and may be expensive to carry out. In addition, they cannot be performed routinely in developing countries where the burden of OAP may be substantial and the majority of exposed urban citizens live.

Exhaled carbon monoxide (exhCO) has been used routinely and successfully for monitoring in the context of tobacco smoking cessation [9, 10]. Hence, it is conceivable that it could be used as an index of exposure to other air pollution sources other than tobacco smoking such as ambient air pollution which contains CO. CO rapidly combines with hemoglobin to form carboxyhemoglobin when inhaled; and its concentration in ambient air and duration of exposure are the most important determinants of carboxyhemoglobin saturation [11, 12]. The half-life of inhaled CO varies from 2 to 6 h depending on physiologic factors such as respiratory rate, making it a potential marker of recent exposure [13, 14]. Few studies have evaluated the correlation between exhCO with exposures from CO in solid fuels used in the households [15, 16], but none examined its relationships with OAP exposures. This study aimed to assess changes in exhCO over a shift of 8 h and its relationship with CO exposures following a short-term exposure to OAP in exposed males in Cotonou. Cotonou is the economical capital of Benin and has a quite elevated level of pollutants [17, 18]. We hypothesized that exhaled CO will increase over the shift and the post-shift exhaled CO will be associated with the mean value of CO measurement in ambient air of the last 2, 4 and 6 h of exposure.

We are not aware of other studies that have assessed the relationship between exhaled CO and short-term exposure to CO in ambient air from outdoor air pollution, especially traffic emissions. We have demonstrated that exhaled CO had a stronger association to 2-h ambient CO exposure (β = 0.34, p < 0.001) compared with the last 4 and 6 h of exposure. The weaker association of the exhaled CO to the average values of the last 4 and 6 h CO exposure may be due to the half-life of the inhaled CO. The half-life of CO is 2–6 h and it is thus understandable that exhCO might better reflect the most recent 2-h exposure. Moreover, we found a significant difference between the measurements of baseline exhCO and exhCO at the end of the 8-h shift. This difference was strongly associated with the average values of the 2 last hours of exposure to CO from outdoor air pollution. The baseline exhaled CO was 13.4 ± 7.6 ppm and this is higher than the cut-off value of 6 to 9 ppm commonly used to distinguish smokers from non-smokers [14, 20]. Although the baseline elevation in exhaled CO could be related to other causes, it is most likely related to the ambient exposure the study participants were exposed to before they arrived at our local laboratory in the morning hours. This high baseline exhCO compared to the cut-off value used in evaluating the success of smoking cessation, and the pre-post work shift difference supports the clinical relevance of air pollution exposure for commercial motorcycle riders and other groups who work on and/or live near roads with heavy traffic.

This study also showed that measurement of exhaled CO is feasible in a limited resource setting. The level of carboxyhemoglobin can be calculated from the Coburn-Forster-Kane Equation. We were able to measure the baseline exhaled CO and the exhaled CO after 8 h in individuals exposed to OAP. Indeed, study participants were asked to come into our local laboratory in Benin for the measurement. This can be done routinely in a health care center with a relatively inexpensive device and low-cost disposable mouthpieces. In a patient for whom the healthcare provider suspected that exposure to OAP is a risk factor, exhCO measurement can be done to confirm exposure or for assessing intervention effectiveness. A cost-effectiveness analysis is needed to confirm whether this simple and non-invasive biomarker of OAP exposure is indeed useful in patient care.

We assumed that all the exposures happened outdoors based on the participant’s declaration and the hours of measurements although we did not use a device like a GPS tracker to confirm it.

In non-smoking and non-cooking men exposed to OAP, exhCO can be used as a biomarker of short-term exposure to ambCO. Therefore, exhCO can be used to assess exposure to air pollution in less wealthy countries where this test is already routinely used in evaluating smoking cessation programs.