Evaluation of neural reflex activation as a potential mode of action for respiratory and cardiovascular effects of fine particulate matter

Abstract

Objectives

Mortality from respiratory and cardiovascular health conditions contributes largely to the total mortality that has been associated with exposure to PM_2.5 in epidemiology studies. A mode of action (MoA) for these underlying morbidities has not been established, but it has been proposed that some effects of PM_2.5 occur through activation of neural reflexes.

Materials and Methods

We critically reviewed the experimental studies of PM_2.5 (including ambient PM_2.5, diesel exhaust particles, concentrated ambient particles, diesel exhaust, and cigarette smoke) and neural reflex activation, and applied the principles of the International Programme on Chemical Safety (IPCS) MoA/human relevance framework to assess whether they support a biologically plausible and human-relevant MoA by which PM_2.5 could contribute to cardiovascular and respiratory causes of death. We also considered whether the evidence from these studies supports a non-threshold MoA that operates at low, human-relevant PM_2.5 exposure concentrations.

Results and Discussion

We found that the proposed MoA of neural reflex activation is biologically plausible for PM_2.5-induced respiratory effects at high exposure levels used in experimental studies, but further studies are needed to fill important data gaps regarding the relevance of this MoA to humans at lower PM_2.5 exposure levels. A role for the proposed MoA in PM_2.5-induced cardiovascular effects is plausible for some effects but not others.

Conclusions

Further studies are needed to determine whether neural reflex activation is the MoA by which PM_2.5 could cause either respiratory or cardiovascular morbidities in humans, particularly at the ambient concentrations associated with total mortality in epidemiology studies.

Keywords:

• Particulate matter
• cardiovascular morbidity
• respiratory morbidity
• mode of action
• neural reflex
• mortality

Disclosure statement

All of the authors are employed by Gradient, an independent environmental risk science consulting firm. The work reported in this paper was conducted during the normal course of employment, with financial support from the American Petroleum Institute (API) and was reviewed by members of API while in preparation. This paper is the professional work product of the authors, and the opinions and conclusions within are not necessarily those of their employers or the financial sponsor of the work.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.