Carbon monoxide's potential comeback as a key air pollutant
Authors: Gerard Hoek
Journal: The Lancet Planetary Health (2021)

In The Lancet Planetary Health, Kai Chen and colleagues present an impressive study on the potential effects of short-term exposure to carbon monoxide (CO) on mortality.1Chen K Breitner S Wolf K et al.Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities.Lancet Planet Health. 2021; 5: e191-e199Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar Health effects of very high CO concentrations have been well documented,2WHO 2010WHO guidelines for indoor air quality: selected pollutants. WHO Regional Office for Europe, Copenhagen2010Google Scholar but it is less clear whether mortality effects still occur at the current, much lower outdoor pollution levels. Chen and colleagues collected daily data on all-cause mortality and air pollution from 337 cities around the world within the Multi-Country Multi-City Collaborative Research Network. Using advanced statistical methods, associations between CO and mortality were investigated, adjusting for major time-varying confounders including temperature and seasonality. The study found that a 1 mg/m3 increase in the CO concentration of the previous day was associated with a significant 0·91% (95% CI 0·32–1·50) increase in daily mortality, an effect size comparable to those found in time series studies of fine particles, nitrogen dioxide (NO2), and ozone.3Orellano P Reynoso J Quaranta N Bardach A Ciapponi A Short-term exposure to particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), and ozone (O3) and all-cause and cause-specific mortality: systematic review and meta-analysis.Environ Int. 2020; 142105876Crossref PubMed Scopus (58) Google Scholar Associations with CO exposures of the same day and 2 days before were also positive, although not significant. These associations were found at concentrations below 1 mg/m3, much lower than the current WHO 24-h average guideline for indoor air of 7 mg/m3 and the equivalent legally binding limit values for outdoor air in the EU and USA for a maximum 8-h average of 10 mg/m3. A key strength of the study is its multicity design. Multicity designs have proven very powerful in time series studies of outdoor air pollution,4Samoli E Touloumi G Schwartz J et al.Short-term effects of carbon monoxide on mortality: an analysis within the APHEA project.Environ Health Perspect. 2007; 115: 1578-1583Crossref PubMed Scopus (63) Google Scholar, 5Samet JM Dominici F Curriero FC Coursac I Zeger SL Fine particulate air pollution and mortality in 20 US cities, 1987–1994.N Engl J Med. 2000; 343: 1742-1749Crossref PubMed Scopus (1966) Google Scholar as they address concerns regarding potential publication bias and (lag) reporting bias and therefore are important in evidence synthesis.3Orellano P Reynoso J Quaranta N Bardach A Ciapponi A Short-term exposure to particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), and ozone (O3) and all-cause and cause-specific mortality: systematic review and meta-analysis.Environ Int. 2020; 142105876Crossref PubMed Scopus (58) Google Scholar The same group of researchers have also reported significant mortality associations with other major pollutants, including fine particulate matter6Liu C Chen R Sera F et al.Ambient particulate air pollution and daily mortality in 652 cities.N Engl J Med. 2019; 381: 705-715Crossref PubMed Scopus (450) Google Scholar and ozone,7Vicedo-Cabrera AM Sera F Liu C et al.Short term association between ozone and mortality: global two stage time series study in 406 locations in 20 countries.BMJ. 2020; 368: m108Crossref PubMed Scopus (41) Google Scholar raising the question of whether the association between CO and mortality is at least partly explained by co-pollutants. The daily variation of outdoor air pollution is primarily driven by variability in weather circumstances, including the stability of the atmosphere and temperature. Therefore, multiple pollutants can exhibit increased concentrations on the same days, implying that confounding by co-pollutants is possible. Chen and colleagues carefully evaluated the impact of other pollutants by including two-pollutant models.1Chen K Breitner S Wolf K et al.Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities.Lancet Planet Health. 2021; 5: e191-e199Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar They found that adjustment for PM10 reduced the estimated effect size for CO, and adjustment for NO2 in particular reduced the estimated effect to essentially null. Interpretation of multipollutant models is by no means straightforward. If the correlation between two pollutants is high, the coefficients from two-pollutant models can be unstable.8Dominici F Peng RD Barr CD Bell ML Protecting human health from air pollution: shifting from a single-pollutant to a multipollutant approach.Epidemiology. 2010; 21: 187-194Crossref PubMed Scopus (255) Google Scholar In Chen and colleagues' work,1Chen K Breitner S Wolf K et al.Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities.Lancet Planet Health. 2021; 5: e191-e199Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar the correlation between CO and NO2 was moderately high and, based on the similar width of the 95% CIs of the single-pollutant and two-pollutant models, the two-pollutant models provided interpretable results. Another interpretation issue arises when two pollutants derive from the same source, which in this case applies especially to CO and NO2, for which combustion and motorised road traffic are dominant sources. Indeed, there is a fundamental question in multipollutant modelling: do we want to isolate the effect of a single pollutant from the other components of a mixture or do we want to characterise the effects of the mixture?8Dominici F Peng RD Barr CD Bell ML Protecting human health from air pollution: shifting from a single-pollutant to a multipollutant approach.Epidemiology. 2010; 21: 187-194Crossref PubMed Scopus (255) Google Scholar, 9Hamra GB Buckley JP Environmental exposure mixtures: questions and methods to address them.Curr Epidemiol Rep. 2018; 5: 160-165Crossref PubMed Google Scholar Should we interpret Chen and colleagues' findings as an effect of the CO molecule or an effect of a mixture of related pollutants with the same source? The mixture interpretation seems attractive, but is difficult to address.8Dominici F Peng RD Barr CD Bell ML Protecting human health from air pollution: shifting from a single-pollutant to a multipollutant approach.Epidemiology. 2010; 21: 187-194Crossref PubMed Scopus (255) Google Scholar, 9Hamra GB Buckley JP Environmental exposure mixtures: questions and methods to address them.Curr Epidemiol Rep. 2018; 5: 160-165Crossref PubMed Google Scholar The same question has been raised in the interpretation of studies on NO2, black carbon, and ultrafine particles, all pollutants emitted by combustion sources. Given this background, what are the implications of this study for air quality policy? The authors note cautiously that air quality standards for CO need to be revisited.1Chen K Breitner S Wolf K et al.Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities.Lancet Planet Health. 2021; 5: e191-e199Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar This interpretation is valid within the current regulatory approach of regulating single pollutants. However, depending on how much value is placed on single-pollutant versus two-pollutant model estimates, it could be argued that there is little value in tightening a CO standard in the presence of an existing NO2 standard. The United States Environmental Protection Agency considers robustness after adjustment for co-pollutants as a criterium in its integrated science assessment.10United States Environmental Protection AgencyIntegrated science assessment (ISA) for nitrogen dioxide—health criteria. United States Environmental Protection Agency, Research Triangle Park, NC2016Google Scholar This argument might, however, be counterproductive in a single-pollutant regulatory approach, as all related components could fail the requirement of robustness against co-pollutant adjustment. In conclusion, the evidence presented by Chen and colleagues does not convincingly show that emission reduction policies specifically targeting CO are called for; however, their findings of adverse health effects at low levels suggest that policies further reducing emissions from combustion sources involving multiple pollutants are likely to improve public health. Hence, general policies encouraging active transport and electrification of motorised transport are supported by this large, multicity study. I declare no competing interests. Ambient carbon monoxide and daily mortality: a global time-series study in 337 citiesThis international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants. Full-Text PDF Open Access