Studies of acid aerosols in six cities and in a new multi-city investigation: design issues.

Techniques for measuring acid aerosols in the ambient environment have been developed only recently. As part of the on-going Harvard Study on the Health Effects of Sulfur Dioxide and Respirable Particulates, we have developed monitoring equipment for acidic particles that can be used in multiple field settings. Preliminary data suggest that these strong acid aerosol measurements may correlate with respiratory symptoms more closely than similar measurements of particulate matter less than 15 microns in size. These results have led to the beginning of a U.S.-Canadian cooperative study to assess the chronic effects of acid aerosols on the health of North American children. Communities are being selected on the basis of anticipated levels of H2SO4 in ambient air along with predicted levels of ozone and nitrates. Each community will undergo a 1-year period of every other day, 24-hr monitoring with newly developed monitoring equipment that will allow for quantification of H+ ion concentrations, as well as for specific measures of ozone and acid fractions. At the end of the 1-year period, while measurements are still being made, approximately 600 children aged 7 to 11 in each of up to 24 communities will be assessed with standardized questionnaires completed by parents, and pulmonary function will be measured in the children while in school. By estimating chronic exposure from the year-long measurement of acid aerosols and consideration of specific criteria for selecting communities to study, we hope to minimize potential confounding to allow us to assess the chronic impact of strong acid in the atmosphere on the respiratory health of these children

Lung Cancer in Railroad Workers Exposed to Diesel Exhaust

Diesel exhaust has been suspected to be a lung carcinogen. The assessment of this lung cancer risk has been limited by lack of studies of exposed workers followed for many years. In this study, we assessed lung cancer mortality in 54,973 U.S. railroad workers between 1959 and 1996 (38 years). By 1959, the U.S. railroad industry had largely converted from coal-fired to diesel-powered locomotives. We obtained work histories from the U.S. Railroad Retirement Board, and ascertained mortality using Railroad Retirement Board, Social Security, and Health Care Financing Administration records. Cause of death was obtained from the National Death Index and death certificates. There were 43,593 total deaths including 4,351 lung cancer deaths. Adjusting for a healthy worker survivor effect and age, railroad workers in jobs associated with operating trains had a relative risk of lung cancer mortality of 1.40 (95% confidence interval, 1.30–1.51). Lung cancer mortality did not increase with increasing years of work in these jobs. Lung cancer mortality was elevated in jobs associated with work on trains powered by diesel locomotives. Although a contribution from exposure to coal combustion products before 1959 cannot be excluded, these results suggest that exposure to diesel exhaust contributed to lung cancer mortality in this cohort

Reduction in Heart Rate Variability with Traffic and Air Pollution in Patients with Coronary Artery Disease

Introduction: Ambient particulate pollution and traffic have been linked to myocardial infarction and cardiac death risk. Possible mechanisms include autonomic cardiac dysfunction. Methods: In a repeated-measures study of 46 patients 43–75 years of age, we investigated associations of central-site ambient particulate pollution, including black carbon (BC) (a marker for regional and local traffic), and report of traffic exposure with changes in half-hourly averaged heart rate variability (HRV), a marker of autonomic function measured by 24-hr Holter electrocardiogram monitoring. Each patient was observed up to four times within 1 year after a percutaneous intervention for myocardial infarction, acute coronary syndrome without infarction, or stable coronary artery disease (4,955 half-hour observations). For each half-hour period, diary data defined whether the patient was home or not home, or in traffic. Results: A decrease in high frequency (HF; an HRV marker of vagal tone) of −16.4% [95% confidence interval (CI), −20.7 to −11.8%] was associated with an interquartile range of 0.3-μg/m3 increase in prior 5-day averaged ambient BC. Decreases in HF were independently associated both with the previous 2-hr averaged BC (−10.4%; 95% CI, −15.4 to −5.2%) and with being in traffic in the previous 2 hr (−38.5%; 95% CI, −57.4 to −11.1%). We also observed independent responses for particulate air matter with aerodynamic diameter ≤ 2.5 μm and for gases (ozone or nitrogen dioxide). Conclusion: After hospitalization for coronary artery disease, both particulate pollution and being in traffic, a marker of stress and pollution, were associated with decreased HRV

Polymorphic repeat in AIB1 does not alter breast cancer risk

INTRODUCTION: A causal association between endogenous and exogenous estrogens and breast cancer has been established. Steroid hormones regulate the expression of proteins that are involved in breast cell proliferation and development after binding to their respective steroid hormone receptors. Coactivator and corepressor proteins have recently been identified that interact with steroid hormone receptors and modulate transcriptional activation [1]. AIB1 (amplified in breast 1) is a member of the steroid receptor coactivator (SRC) family that interacts with estrogen receptor (ER)α in a ligand-dependent manner, and increases estrogen-dependent transcription [2]. Amplification and overexpression of AIB1 has been observed in breast and ovarian cancer cell lines and in breast tumors [2,3]. A polymorphic stretch of glutamine amino acids, with unknown biologic function, has recently been described in the carboxyl-terminal region of AIB1 [4]. Among women with germline BRCA1 mutations, significant positive associations were observed between AIB1 alleles with 26 or fewer glutamine repeats and breast cancer risk [5] AIM: To establish whether AIB1 repeat alleles are associated with breast cancer risk and specific tumor characteristics among Caucasian women. PATIENTS AND METHODS: We evaluated associations prospectively between AIB1 alleles and breast cancer risk in the Nurses' Health Study using a nested case-control design. The Nurses' Health Study was initiated in 1976, when 121 700 US-registered nurses between the ages of 30 and 55 years returned an initial questionnaire reporting medical histories and baseline health-related exposures. Between 1989 and 1990 blood samples were collected from 32 826 women. Eligible cases in this study consisted of women with pathologically confirmed incident breast cancer from the subcohort who gave a blood specimen. Cases with a diagnosis anytime after blood collection up to June 1, 1994, with no previously diagnosed cancer except for nonmelanoma skin cancer were included. Controls were randomly selected participants who gave a blood sample and were free of diagnosed cancer (except nonmelanoma skin cancer) up to and including the interval in which the cases were diagnosed, and were matched to cases on year of birth, menopausal status, postmenopausal hormone use, and time of day, month and fasting status at blood sampling. The nested case-control study consisted of 464 incident breast cancer cases and 624 matched controls. The protocol was approved by the Committee on Human Subjects, Brigham and Womens' Hospital, Boston, Massachusetts USA. Information regarding breast cancer risk factors was obtained from the 1976 baseline questionnaire, subsequent biennial questionnaires, and a questionnaire that was completed at the time of blood sampling. Histopathologic characteristics, such as stage, tumor size and ER and progesterone receptor (PR) status, were ascertained from medical records when available and used in case subgroup analyses. AIB1 repeat alleles were determined by automated fluorescence-based fragment detection from polymerase chain reaction (PCR)-amplified DNA extracted from peripheral blood lymphocytes. Fluorescent 5' -labeled primers were utilized for PCR amplification, and glutamine repeat number discrimination was performed using the ABI Prism 377 DNA Sequencer (Perkin-Elmer, Foster City, CA, USA). Genotyping was performed by laboratory personnel who were blinded to case-control status, and blinded quality control samples were inserted to validate genotyping identification procedures (n = 110); concordance for the blinded samples was 100%. Methods regarding plasma hormone assays have previously been reported [6]. Conditional and unconditional logistic regression models, including terms for the matching variables and other potential confounders, were used to assess the association of AIB1 alleles and breast cancer characterized by histologic subtype, stage of disease, and ER and PR status. We also evaluated whether breast cancer risk associated with AIB1 genotype differed within strata of established breast cancer risk factors, and whether repeat length in AIB1 indirectly influenced plasma hormone levels. RESULTS: The case-control comparisons of established breast cancer risk factors among these women have previously been reported [7], and are generally consistent with expectation. The mean age of the women was 58.3 (standard deviation [SD] 7.1) years, ranging from 43 to 69 years at blood sampling. There were 188 premenopausal and 810 postmenopausal women, with mean ages of 48.1 (SD 2.8) years and 61.4 (SD 5.0) years, respectively, at blood sampling. Women in this study were primarily white; Asians, African-Americans and Hispanics comprised less than 1% of cases or controls. The distribution of AIB1 glutamine repeat alleles and AIB1 genotypes for cases and controls are presented in Table 1. Women with AIB1 alleles of 26 glutamine repeats or fewer were not at increased risk for breast cancer (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.75-1.36; Table 2). Results were also similar by menopausal status and in analyses additionally adjusting for established breast cancer risk factors. Among premenopausal women, the OR for women with at least one allele with 26 glutamine repeats or fewer was 0.82 (95% Cl 0.37-1.81), and among postmenopausal women the OR was 1.09 (95% Cl 0.78-1.52; Table 2). We did not observe evidence of a positive association between shorter repeat length and advanced breast cancer, defined as women with breast cancer having one or more involved nodes (OR 1.07, 95% Cl 0.64-1.78), or with cancers with a hormone-dependent phenotype (ER-positive: OR 1.16, 95% Cl 0.81-1.65; Table 3). No associations were observed among women who had one or more alleles with 26 glutamine repeats or fewer, with or without a family history of breast cancer (family history: OR 1.09; 95% Cl 0.46-2.58; no family history: OR 0.94; 95% Cl 0.68-1.31; test for interaction P = 0.65). We also did not observe associations with breast cancer risk to be modified by other established breast cancer risk factors. Among postmenopausal controls not using postmenopausal hormones, geometric least-squared mean plasma levels of estrone sulfate and estrone were similar among carriers and noncarriers of AIB1 alleles with 26 glutamine repeats or fewer (both differences: ≤ +3.5%; P >0.50). Mean levels of estradiol were slightly, but nonsignificantly elevated among carriers of alleles with 26 glutamine repeats or fewer (+11.6%; P = 0.08). DISCUSSION: In this population-based nested case-control study, women with at most 26 repeating glutamine codons (CAG/CAA) within the carboxyl terminus of AIB1 were not at increased risk for breast cancer. We did not observe shorter repeat alleles to be positively associated with breast cancer grouped by histologic subtype, stage of disease, or by ER and PR status. These data suggest that AIB1 repeat length is not a strong independent risk factor for postmenopausal breast cancer, and does not modify the clinical presentation of the tumor among Caucasian women in the general population

Extended Work Duration and the Risk of Self-Reported Percutaneous Injuries in Interns

Context: In their first year of postgraduate training, interns commonly work shifts that are longer than 24 hours. Extended-duration work shifts are associated with increased risks of automobile crash, particularly during a commute from work. Interns may be at risk for other occupation-related injuries. Objective: To assess the relationship between extended work duration and rates of percutaneous injuries in a diverse population of interns in the United States. Design, Setting, and Participants: National prospective cohort study of 2737 of the estimated 18 447 interns in US postgraduate residency programs from July 2002 through May 2003. Each month, comprehensive Web-based surveys that asked about work schedules and the occurrence of percutaneous injuries in the previous month were sent to all participants. Case-crossover within-subjects analyses were performed. Main Outcome Measures: Comparisons of rates of percutaneous injuries during day work (6:30 am to 5:30 pm) after working overnight (extended work) vs day work that was not preceded by working overnight (nonextended work). We also compared injuries during the nighttime (11:30 pm to 7:30 am) vs the daytime (7:30 am to 3:30 pm). Results: From a total of 17 003 monthly surveys, 498 percutaneous injuries were reported (0.029/intern-month). In 448 injuries, at least 1 contributing factor was reported. Lapse in concentration and fatigue were the 2 most commonly reported contributing factors (64% and 31% of injuries, respectively). Percutaneous injuries were more frequent during extended work compared with nonextended work (1.31/1000 opportunities vs 0.76/1000 opportunities, respectively; odds ratio [OR], 1.61; 95% confidence interval [CI], 1.46-1.78). Extended work injuries occurred after a mean of 29.1 consecutive work hours; nonextended work injuries occurred after a mean of 6.1 consecutive work hours. Injuries were more frequent during the nighttime than during the daytime (1.48/1000 opportunities vs 0.70/1000 opportunities, respectively; OR, 2.04; 95% CI, 1.98-2.11). Conclusion: Extended work duration and night work were associated with an increased risk of percutaneous injuries in this study population of physicians during their first year of clinical training

Polymorphic repeat in AIB1 does not alter breast cancer risk

We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor characteristics. These findings suggest that AIB1 repeat genotype does not influence postmenopausal breast cancer risk among Caucasian women in the general population

Oral contraceptive use and mortality after 36 years of follow-up in the Nurses\u27 Health Study: Prospective cohort study

Objective To determine whether use of oral contraceptives is associated with all cause and cause specific mortality. Design Prospective cohort study. Setting Nurses’ Health Study, data collected between 1976 and 2012. Population 121 701 participants were prospectively followed for 36 years; lifetime oral contraceptive use was recorded biennially from 1976 to 1982. Main outcome measures Overall and cause specific mortality, assessed throughout follow-up until 2012. Cox proportional hazards models were used to calculate the relative risks of all cause and cause specific mortality associated with use of oral contraceptives. Results In our population of 121 577 women with information on oral contraceptive use, 63 626 were never users (52%) and 57 951 were ever users (48%). After 3.6 million person years, we recorded 31 286 deaths. No association was observed between ever use of oral contraceptives and all cause mortality. However, violent or accidental deaths were more common among ever users (hazard ratio 1.20, 95% confidence interval 1.04 to 1.37). Longer duration of use was more strongly associated with certain causes of death, including premature mortality due to breast cancer (test for trend P<0.0001) and decreased mortality rates of ovarian cancer (P=0.002). Longer time since last use was also associated with certain outcomes, including a positive association with violent or accidental deaths (P=0.005). Conclusions All cause mortality did not differ significantly between women who had ever used oral contraceptives and never users. Oral contraceptive use was associated with certain causes of death, including increased rates of violent or accidental death and deaths due to breast cancer, whereas deaths due to ovarian cancer were less common among women who used oral contraceptives. These results pertain to earlier oral contraceptive formulations with higher hormone doses rather than the now more commonly used third and fourth generation formulations with lower estrogen doses

Chronic Fine and Coarse Particulate Exposure, Mortality, and Coronary Heart Disease in the Nurses’ Health Study

Background: The relationship of fine particulate matter &lt; 2.5 μm in diameter (PM2.5) air pollution with mortality and cardiovascular disease is well established, with more recent long-term studies reporting larger effect sizes than earlier long-term studies. Some studies have suggested the coarse fraction, particles between 2.5 and 10 μm (PM10–2.5), may also be important. With respect to mortality and cardiovascular events, questions remain regarding the relative strength of effect sizes for chronic exposure to fine and coarse particles. Objectives: We examined the relationship of chronic PM2.5 and PM10–2.5 exposures with all-cause mortality and fatal and nonfatal incident coronary heart disease (CHD), adjusting for time-varying covariates. Methods: The current study included women from the Nurses’ Health Study living in metropolitan areas of the northeastern and midwestern United States. Follow-up was from 1992 to 2002. We used geographic information systems–based spatial smoothing models to estimate monthly exposures at each participant’s residence. Results: We found increased risk of all-cause mortality [hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.02–1.54] and fatal CHD (HR = 2.02; 95% CI, 1.07–3.78) associated with each 10-μg/m3 increase in annual PM2.5 exposure. The association between fatal CHD and PM10–2.5 was weaker. Conclusions: Our findings contribute to growing evidence that chronic PM2.5 exposure is associated with risk of all-cause and cardiovascular mortality

Association Between Concussion Burden During Professional American-Style Football and Postcareer Hypertension

Previous work has demonstrated an association between American-style football (ASF) and the development of hypertension among collegiate athletes.1 In addition, hypertension prevalence has been shown to be higher among active professional ASF athletes compared with similarly aged members of the general population.2 Whereas causal factors including deliberate weight gain, repetitive isometric strength training, sleep apnea, and nonsteroidal anti-inflammatory drug use have been suggested, definitive mechanisms remain incompletely understood. Recent studies in general populations have shown associations between brain injury and subsequent hypertension.3 Given that ASF players are at particular risk for recurrent head injury, the relationship between concussion history and later life hypertension deserves focused exploration