American journal of epidemiology
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Misclassification of exposure and surrogate endpoints of disease can obscure causal relations. Using data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS, 1997-2001), the authors explored the impact of exposure (human papillomavirus (HPV) detection) and endpoint (histologic cervical precancer) classification on their mutual association. Women referred into this study with an atypical squamous cells of undetermined significance Papanicolaou test with satisfactory results for all 4 HPV tests were included in this analysis (n = 3,215; 92.2%). ⋯ The overall accuracy of each HPV test, as measured by odds ratios, was greatest for consensus CIN-3 diagnoses, from 2- to 4-fold greater than for a less stringent precancer definition of any diagnosis of CIN 2 or more severe. In summary, there was convergence of greater certainty of carcinogenic HPV with greater certainty of a precancerous diagnosis, such that all 4 HPV tests almost always tested positive in women most likely to have cervical precancer. Finding increasingly strong associations when both test and diagnostic misclassification are reduced is a useful sign of "true association" in molecular epidemiology.
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Multicenter Study
Association of environmental tobacco smoke exposure in childhood with early emphysema in adulthood among nonsmokers: the MESA-lung study.
Mechanical stress to alveolar walls may cause progressive damage after an early-life insult such as exposure to environmental tobacco smoke (ETS). This hypothesis was examined by using data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort aged 45-84 years, free of clinical cardiovascular disease, recruited from 6 US sites in 2000-2002. The MESA-Lung Study assessed a fractal, structural measure of early emphysema ("alpha," lower values indicate more emphysema) and a standard quantitative measure ("percent emphysema") from cardiac computed tomography scans. ⋯ Analyses included 1,781 nonsmokers (<100 cigarettes, 20 cigars, or 20 pipefulls in their lifetime and urinary cotinine levels <100 ng/mL); mean age was 61 years (standard deviation, 10), and 65% were women. Childhood ETS exposure from 2 or more smokers (17%) compared with none (52%) was associated with 0.05 lower alpha and 2.8 higher percent emphysema (P for trend = 0.04 and 0.01, respectively) after adjustment for demographic, anthropometric, parental, and participant characteristics, as well as adult exposures (e.g., cumulative residential air pollution exposure, exposure to ETS as an adult). Childhood ETS exposure was associated with detectable differences on computed tomography scans of adult lungs of nonsmokers.