Human Interindividual Variability in Susceptibility to Airborne Particles

Hattis, Dale; Russ, Abel; Goble, Robert; Banati, Prerna; Chu, Margaret

doi:10.1111/0272-4332.214137

Cited by 33 publications

(12 citation statements)

References 30 publications

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“…However, susceptibility information has a greater influence on the relative distribution of benefits than do other assumptions, many of which tend to affect all populations identically (e.g., the population-averaged concentration-response function). Furthermore, a broader view of areas of heterogeneity or susceptibility [e.g., assumptions regarding particle size and chemical composition, time-activity data, or physiologic factors (63)] could increase the importance of this evidence. Further analysis that considers the full array of uncertainties and evaluates which (if any) would be influential in policy decisions would be warranted.…”

Section: Discussionmentioning

confidence: 99%

The importance of population susceptibility for air pollution risk assessment: a case study of power plants near Washington, DC.

Levy

Greco

Spengler

2002

Environ Health Perspect

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In evaluating risks from air pollution, health impact assessments often focus on the magnitude of the impacts without explicitly considering the distribution of impacts across subpopulations. In this study, we constructed a model to estimate the magnitude and distribution of health benefits associated with emission controls at five older power plants in the Washington, DC, area. We used the CALPUFF atmospheric dispersion model to determine the primary and secondary fine-particulate-matter (< 2.5 micro m in aerodynamic diameter) concentration reductions associated with the hypothetical application of "Best Available Control Technology" to the selected power plants. We combined these concentration reductions with concentration-response functions for mortality and selected morbidity outcomes, using a conventional approach as well as considering susceptible subpopulations. Incorporating susceptibility had a minimal effect on total benefits, with central estimates of approximately 240 fewer premature deaths, 60 fewer cardiovascular hospital admissions (CHA), and 160 fewer pediatric asthma emergency room visits (ERV) per year. However, because individuals with lower education appear to have both higher background mortality rates and higher relative risks for air-pollution-related mortality, stratifying by educational attainment implies that 51% of the mortality benefits accrue among the 25% of the population with less than high school education. Similarly, diabetics and African Americans bear disproportionate shares of the CHA and ERV benefits, respectively. Although our ability to characterize subpopulations is constrained by the available information, our analysis demonstrates that incorporation of susceptibility information significantly affects demographic and geographic patterns of health benefits and enhances our understanding of individuals likely to benefit from emission controls.

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Section: Discussionmentioning

confidence: 99%

The importance of population susceptibility for air pollution risk assessment: a case study of power plants near Washington, DC.

Levy

Greco

Spengler

2002

Environ Health Perspect

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“…A recent study evaluating differences in human response to airborne particles found that the most sensitive members of a population respond to doses 150 to 450-fold lower than median (50th percentile) responders [15]. Factors that contribute to these differences include variations in breathing rates, deposition and elimination of air particles from the respiratory tract, and differences in lung response to the chemicals found in the air.…”

Section: Ictx 2004mentioning

confidence: 99%

Non-precautionary aspects of toxicology

Grandjean

2005

Toxicology and Applied Pharmacology

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Empirical studies in toxicology aim at deciphering complex causal relationships, especially in regard to human disease etiologies. Several scientific traditions limit the usefulness of documentation from current toxicological research, in regard to decision-making based on the precautionary principle. Among non-precautionary aspects of toxicology are the focus on simplified model systems and the effects of single hazards, one by one. Thus, less attention is paid to sources of variability and uncertainty, including individual susceptibility, impacts of mixed and variable exposures, susceptible life-stages, and vulnerable communities. In emphasizing the need for confirmatory evidence, toxicology tends to penalize false positives more than false negatives. An important source of uncertainty is measurement error that results in misclassification, especially in regard to exposure assessment. Standard statistical analysis assumes that the exposure is measured without error, and imprecisions will usually result in an underestimation of the dose-effect relationship. In testing whether an effect could be considered a possible result of natural variability, a 5% limit for "statistical significance" is usually applied, ICTX 2004Grandjean, Philippe even though it may rule out many findings of causal associations, simply because the study was too small (and thus lacked statistical power) or because some imprecision or limited sensitivity of the parameters precluded a more definitive observation. These limitations may be aggravated when toxicology is influenced by vested interests. Because current toxicology overlooks the important goal of achieving a better characterization of uncertainties and their implications, research approaches should be revised and strengthened to counteract the innate ideological biases, thereby supporting our confidence in using toxicology as a main source of documentation and in using the Precautionary Principle as a decision procedure in the public policy arena.

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“…The applicability of this theory was demonstrated by Hattis et al (2001), who created a database of quantitative observations of parameters likely to affect responses to particles. This study was based on epidemiological studies of methacholine, flour dust, and other agents that induce acute changes in lung function.…”

Section: Population Heterogeneitymentioning

confidence: 99%

Linear low-dose extrapolation for noncancer health effects is the exception, not the rule

Rhomberg

Goodman

Haber

et al. 2011

Critical Reviews in Toxicology

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The nature of the exposure-response relationship has a profound influence on risk analyses. Several arguments have been proffered as to why all exposure-response relationships for both cancer and noncarcinogenic end-points should be assumed to be linear at low doses. We focused on three arguments that have been put forth for noncarcinogens. First, the general “additivity-to-background” argument proposes that if an agent enhances an already existing disease-causing process, then even small exposures increase disease incidence in a linear manner. This only holds if it is related to a specific mode of action that has nonuniversal properties—properties that would not be expected for most noncancer effects. Second, the “heterogeneity in the population” argument states that variations in sensitivity among members ofthe target population tend to “flatten out and linearize” the exposure-response curve, but this actually only tends to broaden, not linearize, the dose-response relationship. Third, it has been argued that a review of epidemiological evidence shows linear or no-threshold effects at low exposures in humans, despite nonlinear exposure-response in the experimental dose range in animal testing for similar endpoints. It is more likely that this is attributable to exposure measurement error rather than a true non-threshold association. Assuming that every chemical is toxic at high exposures and linear at low exposures does not comport to modern-day scientific knowledge of biology. There is no compelling evidence-based justification for a general low-exposure linearity; rather, case-specific mechanistic arguments are needed.

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Human Interindividual Variability in Susceptibility to Airborne Particles

Cited by 33 publications

References 30 publications

The importance of population susceptibility for air pollution risk assessment: a case study of power plants near Washington, DC.

The importance of population susceptibility for air pollution risk assessment: a case study of power plants near Washington, DC.

Non-precautionary aspects of toxicology

Linear low-dose extrapolation for noncancer health effects is the exception, not the rule

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