Review of the Air Quality Criteria Document for Particulate Matter

Chapter 9 - General CommentsThis chapter is offered with the general and needed purpose of providing an “integration of keyinformation”. Unfortunately, it falls far short on this purpose, reading more as a summary, withinterspersed comments and indications of research gaps. Even these comments, are notparticularly penetrating. See, for example, lines 22-30, page 9-36, which overviews some issuesin interpreting the epidemiological evidence. A higher level of analysis should be adhered to,particularly given the sophistication of the discussion since the last CD with regard tointerpretation of the epidemiological data.One approach that could be taken in this chapter would be to follow the NRC Committee’sframework and to provide an “across the box” linking of what is known. The framework couldalso be used to highlight what is known and the uncertainties, as well as systematically point toresearch needs. This might be an appropriate way to conclude the chapter.Follow-up CommentsThese comments are intended to supplement the peer-review comments submitted inadvance of the July 23-24, 2001, meeting of the Clean Air Scientific Advisory Committee(CASAC). These comments are based on my spoken remarks concerning interpretation of theepidemiological evidence in Chapter 6. Copies of transparencies used as the basis for theseremarks are attached.My remarks strongly urged rigorous and standardized use of epidemiologic terminologyand concepts throughout the Criteria Document, particularly in Chapter 6. The CriteriaDocument needs to define and then uniformly apply the concepts of confounding and effectmodification. As noted on the first transparency, confounding arises when a factor, associated inits own right with the outcome of interest, is also associated with the exposure underinvestigation. In this circumstance, a spurious association may arise between the exposure andoutcome because of the confounding factor. For a variable to be a “confounder” in a particulardata set, two conditions must be met: 1) the confounder needs to be associated with theoutcome factor independently (i.e., it is a risk factor for the outcome); and 2) the confoundingfactor is associated with the exposure of interest in the data under consideration. A distinctionshould be made between a confounding factor and a “potential” confounding factor, that is afactor which would be a confounder if these two conditions were met in a data set of concern.Frequently, critics of epidemiological findings raise the possibility of confounding, citingnumerous potential confounders, without attention as to whether these two conditions are, infact, met.Effect modification is distinct from confounding. It refers to circumstances in which theexposure/outcome relationship depends on the presence or absence (or level) of the modifyingfactor. In such circumstances, there are a series of risks for the outcome of interest associatedwith exposure, depending on level of the modifying factor.The next two transparencies concern the theoretical example of particulate matter (PM), nitrogendioxide (NO 2 ), and mortality. In many settings, PM and NO 2 , have common sources and there isa potential for either confounding or effect modification. Of course, for NO 2 to be a confounder,it would need to be a predictor of mortality, an association that has not been consistentlydemonstrated. Thus, on the basis of understanding of toxicology of NO 2 and the epidemiologicaldata available, it would not be a candidate to be a confounder.In the diagram labeled “causal”, I have indicated that particulate matter is associated withincreased risk for mortality. NO 2 and PM concentrations may be associated because of theircommon sources, but the diagram does not link NO 2 with increased mortality, reflectingunderstanding of its toxicity.Next on the page, the example is designated “causal pathway”. In this example, NO 2 is in thecausal pathway for the increased risk of mortality associated with PM. It contributes to theA - 76