Mind the gap

Abstract

Background: Recent analysis has demonstrated a remarkably consistent, nonlinear relationship between estimated inhaled dose of combustion particles measured as PM(2.5) (particulate matter with aerodynamic diameter ≤ 2.5 µm) and cardiovascular disease mortality over several orders of magnitude of dose--from cigarette smoking, environmental tobacco smoke (ETS) exposure, and ambient air pollution exposure.

Objectives: Here we discuss the implications of this relationship and point out the gaps in our knowledge that it reveals.

Discussion: The nonlinear exposure-response relationship that is revealed-much steeper at lower than at higher doses-explains the seemingly inconsistent risks observed from ambient air pollution and cigarette smoking but also raises important questions about the relative benefits of control at different points along the curve. This analysis also reveals a gap in the evidence base along the dose-response curve between ETS and active smoking, which is the dose range experienced by half the world's population from indoor biomass and coal burning for cooking and heating.

Conclusions: The shape of the exposure-response relationship implies much larger public health benefits of reductions at the lower end of the dose spectrum (e.g., from reductions in outdoor air pollution) than from reducing the rate of active smoking, which seems counterintuitive and deserving of further study because of its importance for control policies. In addition, given the potential risks and consequent global disease burden, epidemiologic studies are urgently needed to quantify the cardiovascular risks of particulate matter exposures from indoor biomass burning in developing countries, which lie in the dose gap of current evidence.

Figure 1

Adjusted relative risks (95% confidence intervals) of cardiovascular and cardiopulmonary mortality and estimated dose of PM_2.5 across studies of outdoor air pollution, ETS, and active cigarette smoking (adapted with permission from Pope et al. 2009, their Figure 2). Data on active smoking are from Pope et al. (2009); on ETS are from the 2006 Surgeon General’s Report (U.S. Department of Health and Human Services 2006) and INTERHEART study (Teo et al. 2006); on air pollution are from the Women’s Health Initiative cohort (Miller et al. 2007), the American Cancer Society cohort (Pope et al. 1995, 2002, 2004), and the Harvard Six Cities cohort (Dockery et al. 1993; Laden et al. 2006). Exposure was measured as daily inhaled dose of PM_2.5 (plotted on a log scale), calculated assuming 18 m³/day breathing rate. Active cigarette smoking was quantified as ≤ 3, 4–7, 8–12, 13–17, 18–22, and ≥ 23 cigarettes/day (relative to never-smokers). Also shown is the equivalent dose for the World Health Organization (WHO) (2006) Air Quality Guidelines (AQG) for PM_2.5 (10 μg/m³ annual average).

Figure 2

CVD deaths averted by shifting dose categories for inhalation of PM_2.5, as measured in estimated dose (mg/day). The calculations start with a population of heavy smokers that experiences 1 million CVD deaths per year and are based on the population-attributable fraction at each dose level using the relative risks from Figure 1. As dose decreases, the expected number of CVD deaths decreases as well. For example, at equilibrium, the number of annual CVD deaths in this population if shifted to light smokers would be 60,000 fewer (940,000 vs. 1 million if heavy smokers) compared with annual deaths if they remain heavy smokers.