Skip Navigation LinksHome > March 2004 - Volume 15 - Issue 2 > Susceptible Subgroups: The Challenge of Studying Interaction...
Epidemiology:
doi: 10.1097/01.ede.0000112218.51486.bc
Commentary

Susceptible Subgroups: The Challenge of Studying Interactions

Peters, Annette

Free Access
Article Outline
Collapse Box

Author Information

Correspondence: Annette Peters, Institute of Epidemiology, GSF-National Research Center for Environment and Health, Ingolstaedter Landstr. 1, 85764 Nueherberg, Germany. E-mail: peters@gsf.de.

Environmental exposures can be nearly ubiquitous. Although large groups of people are often exposed (and, in the case of ambient air pollution, entire populations are exposed), the risks are usually very small. One might argue that the responsible agent is so innocuous that only very rarely is a case attributable to it. On the other hand, there may be susceptible subgroups within the population that carry the entire burden alone.

A paper by Bateson and Schwartz1 in this issue examines the effects of air pollution (PM10) in potentially susceptible subpopulations. These subpopulations included people with previous hospitalization for myocardial infarction, diabetes, congestive heart failure, chronic obstructive pulmonary disease, or conduction disorders. Patients with a history of myocardial infarction or diabetes had a 2- to 2.5-fold higher risk of mortality than people experiencing other heart or lung disease. This supports current hypotheses on the biologic mechanisms by which cardiovascular disease can be exacerbated by deposition of particles in the lung. However, the confidence limits around the risks for these subpopulations are wide and overlapping.

The effects on overall mortality in this study are considerably larger than in the National Morbidity, Mortality, and Air Pollution Study (NMMAPS). NMMAPS is based on the 88 largest U.S. metropolitan areas and can be used as a reference estimate for the United States. NMMAPS estimated that a 10-μg/m3 increase in PM10 increased mortality by 0.2%.2 The present study, based in Chicago, found a 1.1% increased mortality. However, the Chicago study was focused on patients with previous records of hospitalization for lung and heart disease and included only persons above age 65.1

The strength of the interaction seen within a disease subgroup depends in part on how well the subgroup has been defined. For example, recent research has shown that diabetes in patients with myocardial infarction was often not well managed a decade ago and received little medical attention. Furthermore, hospital admission for diabetes is most likely when the disease has been badly managed. Thus, the prevalence of diabetes is probably underestimated when relying (as this paper did) on hospital discharge diagnoses. To reduce potential misclassification, detailed individual-level data on exposure as well as on susceptibility should be available.

The study of susceptible groups is being extended beyond disease groups to include variations in physiological function defined by genetic polymorphisms. An elegant example can be found in this issue in which Lammer and his colleagues3 investigate the association between smoking and orofacial clefts. The presence of a certain detoxifying enzyme with slower metabolism apparently increased the risk of clefting with mother's smoking. Are genes the answer to the problem of carefully defining susceptible subgroups? Most likely not. This line of research may deepen our understanding of biologic mechanisms, but it also opens a Pandora's box. Genotype is not equal to phenotype. Of course, defining genes does not solve the problems of specifying exposure.

“There may be susceptible subgroups within the population that carry the entire burden alone.”

So, are small effects from environmental exposures really large effects among small groups? Have Bateson and Schwartz1 identified crucial subgroups that carry the entire burden of air pollution effects? We still do not know. The exposure and the disease conferring susceptibility have not been identified with enough precision. However, as difficult as such interaction studies are to conduct, the results are extremely important. The overall risk estimates from broad studies such as NMMAPS might provide poor estimates for risk assessment within susceptible subgroups. Although current studies are often merely suggestive, studies such as those by Bateson and Schwartz are important in that they test the current concepts of biologic plausibility, and lay the groundwork for more powerful and precise studies that may ultimately provide a sound basis for public health measures.

Back to Top | Article Outline

ABOUT THE AUTHOR

ANNETTE PETERS is leading the research unit on Air Pollution Epidemiology at the GSF-National Research Center for Environment and Health, Neuherberg near Munich, Germany. She has pioneered the study of systemic inflammatory effects of ambient air pollution in the general population. She is currently coordinating a study on gene–environment interactions assessing susceptibility to air pollution in myocardial infarction survivors.

Back to Top | Article Outline

REFERENCES

1. Bateson TF, Schwartz J. Who is sensitive to the effects of particulate air pollution on mortality? A case-crossover analysis of effect modifiers. Epidemiology. 2004;15:143–149.

2. Dominici F, McDermott A, Zeger SL, et al. Revised analyses of the National Morbidity, Mortality, and Air Pollution Study, Part II: Mortality among residents of 90 cities. Health Effects Institute Special Report. May 2003;9–24.

3. Lammer EJ, Shaw GM, Iovannisci DM, Van Waes J, Finnell RH. Maternal smoking and the risk of orofacial clefts: susceptibility with NAT1 and NAT2 polymorphisms. Epidemiology. 2004;15:150–156.

Cited By:

This article has been cited 3 time(s).

Occupational and Environmental Medicine
Long-term exposure to traffic-related air pollution and mortality in Shizuoka, Japan
Yorifuji, T; Kashima, S; Tsuda, T; Takao, S; Suzuki, E; Doi, H; Sugiyama, M; Ishikawa-Takata, K; Ohta, T
Occupational and Environmental Medicine, 67(2): 111-117.
10.1136/oem.2008.045542
CrossRef
American Journal of Epidemiology
Ambient air pollution and cardiovascular emergency department visits in potentially sensitive groups
Peel, JL; Metzger, KB; Klein, M; Flanders, WD; Mulholland, JA; Tolbert, PE
American Journal of Epidemiology, 165(6): 625-633.
10.1093/aje/kwk051
CrossRef
Epidemiology
Particulate Matter and Daily Mortality: A Case-Crossover Analysis of Individual Effect Modifiers
on behalf of the SISTI Group, ; Mallone, S; Miglio, R; Pandolfi, P; Rognoni, M; Serinelli, M; Tessari, R; Vigotti, M; Perucci, CA; Forastiere, F; Stafoggia, M; Berti, G; Bisanti, L; Cernigliaro, A; Chiusolo, M
Epidemiology, 19(4): 571-580.
10.1097/EDE.0b013e3181761f8a
PDF (492) | CrossRef
Back to Top | Article Outline

© 2004 Lippincott Williams & Wilkins, Inc.

Twitter  Facebook

Login

Article Tools

Share