Publications by authors named "Olivier Humblet"

18 Publications

  • Page 1 of 1

Effect of a mobile health, sensor-driven asthma management platform on asthma control.

Ann Allergy Asthma Immunol 2017 11;119(5):415-421.e1

Family Allergy and Asthma, Louisville, Kentucky.

Background: Asthma inflicts a significant health and economic burden in the United States. Self-management approaches to monitoring and treatment can be burdensome for patients.

Objective: To assess the effect of a digital health management program on asthma outcomes.

Methods: Residents of Louisville, Kentucky, with asthma were enrolled in a single-arm pilot study. Participants received electronic inhaler sensors that tracked the time, frequency, and location of short-acting β-agonist (SABA) use. After a 30-day baseline period during which reference medication use was recorded by the sensors, participants received access to a digital health intervention designed to enhance self-management. Changes in outcomes, including mean daily SABA use, symptom-free days, and asthma control status, were compared among the initial 30-day baseline period and all subsequent months of the intervention using mixed-model logistic regressions and χ tests.

Results: The mean number of SABA events per participant per day was 0.44 during the control period and 0.27 after the first month of the intervention, a 39% reduction. The percentage of symptom-free days was 77% during the baseline period and 86% after the first month, a 12% improvement. Improvement was observed throughout the study; each intervention month demonstrated significantly lower SABA use and higher symptom-free days than the baseline month (P < .001). Sixty-nine percent had well-controlled asthma during the baseline period, 67% during the first month of the intervention. Each intervention month demonstrated significantly higher percentages than the baseline month (P < .001), except for month 1 (P = .80).

Conclusion: A digital health asthma management intervention demonstrated significant reductions in SABA use, increased number of symptom-free days, and improvements in asthma control.

Trial Registration: Identifier: NCT02162576.
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November 2017

Use of a Remote Inhaler Monitoring Device to Measure Change in Inhaler Use with Chronic Obstructive Pulmonary Disease Exacerbations.

J Aerosol Med Pulm Drug Deliv 2018 06 16;31(3):191-198. Epub 2017 Oct 16.

3 Department of Health Services Research and Development, VA Puget Sound Health Care System , Seattle, Washington.

Background: Remote inhaler monitoring is an emerging technology that enables the healthcare team to monitor the time and location of a patient's inhaler use. We assessed the feasibility of remote inhaler monitoring for chronic obstructive pulmonary disease (COPD) patients and the pattern of albuterol inhaler use associated with COPD exacerbations.

Methods: Thirty-five participants with COPD used an electronic inhaler sensor for 12 weeks which recorded the date and time of each albuterol actuation. Self-reported COPD exacerbations and healthcare utilization were assessed monthly. We used generalized estimating equations with a logit link to compare the odds of an exacerbation day to a nonexacerbation day by the frequency of daily albuterol use.

Results: Average daily albuterol use on nonexacerbation days varied greatly between patients, ranging from 1.5 to 17.5 puffs. There were 48 exacerbation events observed in 29 participants during the study period, of which 16 were moderate-to-severe exacerbations. During the moderate-to-severe exacerbation days, the median value in average daily albuterol use increased by 14.1% (interquartile range: 2.7%-56.9%) compared to average nonexacerbation days. A 100% increase in inhaler use was associated with increased odds of a moderate-to severe exacerbation (odds ratio 1.54; 95% CI: 1.21-1.97). Approximately 74% of participants reported satisfaction with the sensor.

Conclusions: The electronic inhaler sensor was well received in older patients with COPD over a 12-week period. Increased albuterol use captured by the device was associated with self-reported episodes of moderate-to-severe exacerbations.
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June 2018

Feasibility of Deploying Inhaler Sensors to Identify the Impacts of Environmental Triggers and Built Environment Factors on Asthma Short-Acting Bronchodilator Use.

Environ Health Perspect 2017 02 24;125(2):254-261. Epub 2016 Jun 24.

Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, California, USA.

Background: Epidemiological asthma research has relied upon self-reported symptoms or healthcare utilization data, and used the residential address as the primary location for exposure. These data sources can be temporally limited, spatially aggregated, subjective, and burdensome for the patient to collect.

Objectives: First, we aimed to test the feasibility of collecting rescue inhaler use data in space-time using electronic sensors. Second, we aimed to evaluate whether these data have the potential to identify environmental triggers and built environment factors associated with rescue inhaler use and to determine whether these findings would be consistent with the existing literature.

Methods: We utilized zero-truncated negative binomial models to identify triggers associated with inhaler use, and implemented three sensitivity analyses to validate our findings.

Results: Electronic sensors fitted on metered dose inhalers tracked 5,660 rescue inhaler use events in space and time for 140 participants from 13 June 2012 to 28 February 2014. We found that the inhaler sensors were feasible in passively collecting objective rescue inhaler use data. We identified several environmental triggers with a positive and significant association with inhaler use, including: AQI, PM10, weed pollen, and mold. Conversely, the spatial distribution of tree cover demonstrated a negative and significant association with inhaler use.

Conclusions: Utilizing a sensor to capture the signal of rescue inhaler use in space-time offered a passive and objective signal of asthma activity. This approach enabled detailed analyses to identify environmental triggers and built environment factors that are associated with asthma symptoms beyond the residential address. The application of these new technologies has the potential to improve our surveillance and understanding of asthma. Citation: Su JG, Barrett MA, Henderson K, Humblet O, Smith T, Sublett JW, Nesbitt L, Hogg C, Van Sickle D, Sublett JL. 2017. Feasibility of deploying inhaler sensors to identify the impacts of environmental triggers and built environment factors on asthma short-acting bronchodilator use. Environ Health Perspect 125:254-261;
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February 2017

Perfluoroalkyl chemicals and asthma among children 12-19 years of age: NHANES (1999-2008).

Environ Health Perspect 2014 Oct 6;122(10):1129-33. Epub 2014 Jun 6.

Robert Wood Johnson Foundation Health and Society Scholars Program, Department of Psychiatry, University of California, San Francisco, San Francisco, California, USA.

Background: Perfluoroalkyl chemicals (PFCs) are a family of commonly used industrial chemicals whose persistence and ubiquity in human blood samples has led to concern about possible toxicity. Several animal studies and one recent human study have suggested a link between exposure to PFCs and asthma, although few epidemiologic studies have been conducted.

Objectives: We investigated children's PFC serum concentrations and their associations with asthma-related outcomes.

Methods: We evaluated the association between serum concentrations of eight PFCs, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), with self-reported lifetime asthma, recent wheezing, and current asthma using data from participants 12-19 years of age from the 1999-2000 and 2003-2008 National Health and Nutrition Examination Surveys.

Results: In multivariable-adjusted models, PFOA was associated with higher odds of ever having received a diagnosis of asthma [odds ratio (OR) = 1.18; 95% CI: 1.01, 1.39 for a doubling in PFOA], whereas for PFOS there were inverse relationships with both asthma and wheezing (OR = 0.88; 95% CI: 0.74, 1.04, and OR = 0.83; 95% CI: 0.67, 1.02, respectively). The associations were attenuated after accounting for sampling weights. No associations were seen between the other PFCs and any outcome.

Conclusions: This cross-sectional study provides some evidence for associations between exposure to PFCs and asthma-related outcomes in children. The evidence is inconsistent, however, and prospective studies are needed.
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October 2014

Big Data and Disease Prevention: From Quantified Self to Quantified Communities.

Big Data 2013 Sep 22;1(3):168-75. Epub 2013 Aug 22.

1 Center for Health and Community, University of California-San Francisco , San Francisco, California.

Big data is often discussed in the context of improving medical care, but it also has a less appreciated but equally important role to play in preventing disease. Big data can facilitate action on the modifiable risk factors that contribute to a large fraction of the chronic disease burden, such as physical activity, diet, tobacco use, and exposure to pollution. It can do so by facilitating the discovery of risk factors for disease at population, subpopulation, and individual levels, and by improving the effectiveness of interventions to help people achieve healthier behaviors in healthier environments. In this article, we describe new sources of big data in population health, explore their applications, and present two case studies illustrating how big data can be leveraged for prevention. We also discuss the many implementation obstacles that must be overcome before this vision can become a reality.
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September 2013

Genetic modification of the association between peripubertal dioxin exposure and pubertal onset in a cohort of Russian boys.

Environ Health Perspect 2013 Jan 10;121(1):111-7. Epub 2012 Oct 10.

Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Background: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins.

Objectives: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset.

Methods: In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8-9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations.

Results: After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-α (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene-environment tests or only to those with marginal genetic associations.

Conclusions: Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-α genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings.
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January 2013

Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children.

Clin Epigenetics 2012 Sep 25;4(1):17. Epub 2012 Sep 25.

Department of Pediatric Allergy and Immunology, Stanford University, 269 Campus Drive, Stanford, CA, 94305, USA.

Background: Secondhand smoke (SHS) and ambient air pollution (AAP) exposures have been associated with increased prevalence and severity of asthma and DNA modifications of immune cells. In the current study, we examined the association between SHS and AAP with DNA methylation and expression of interferon-gamma (IFN-γ) and forkhead box protein 3 (Foxp3) in T cell populations.

Methods: Subjects 7-18 years old were recruited from Fresno (high AAP; n = 62) and Stanford, CA (low AAP; n = 40) and divided into SHS-exposed (Fresno: n = 31, Stanford: n = 6) and non-SHS-exposed (nSHS; Fresno: n = 31, Stanford: n = 34) groups. T cells purified from peripheral blood were assessed for levels of DNA methylation and expression of IFN-γ (in effector T cells) or Foxp3 (in regulatory T cells).

Results: Analysis showed a significant increase in mean % CpG methylation of IFN-γ and Foxp3 associated with SHS exposure (IFN-γ: FSHS 62.10%, FnSHS 41.29%, p < 0.05; SSHS 46.67%, SnSHS 24.85%, p < 0.05; Foxp3: FSHS 74.60%, FnSHS 54.44%, p < 0.05; SSHS 62.40%, SnSHS 18.41%, p < 0.05) and a significant decrease in mean transcription levels of both genes (IFN-γ: FSHS 0.75, FnSHS 1.52, p < 0.05; SHS 2.25, nSHS 3.53, p < 0.05; Foxp3: FSHS 0.75, FnSHS 3.29, p < 0.05; SSHS 4.8, SnSHS 7.2, p < 0.05). AAP was also associated with hypermethylation (IFN-γ: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05) and decreased transcription of both genes (IFN-γ: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05). Average methylation between AAP- and SHS-only exposures was not significantly different (IFN-γ: p = 0.15; Foxp3: p = 0.27), nor was Foxp3 expression (p = 0.08); IFN-γ expression was significantly decreased in AAP-only subjects (p < 0.05).

Conclusions: Exposures to SHS and AAP are associated with significant hypermethylation and decreased expression of IFN-γ in Teffs and Foxp3 in Tregs. Relative contributions of each exposure to DNA modification and asthma pathogenesis warrant further investigation.
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September 2012

Serum concentrations of organochlorine pesticides and growth among Russian boys.

Environ Health Perspect 2012 Feb 7;120(2):303-8. Epub 2011 Oct 7.

Environmental and Occupational Medicine and Epidemiology Program, 665 Huntington Ave., Building I, Room 1404E, Boston, MA 02115 USA.

Background: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth.

Objective: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels.

Methods: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders.

Results: Among the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), β-hexachlorocyclohexane (βHCH), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, βHCH, and p,p´-DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p´-DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile.

Conclusions: Serum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.
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February 2012

Dioxin and polychlorinated biphenyl concentrations in mother's serum and the timing of pubertal onset in sons.

Epidemiology 2011 Nov;22(6):827-35

Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.

Background: Animal studies have demonstrated that timing of pubertal onset can be altered by prenatal exposure to dioxins or polychlorinated biphenyls (PCBs), but studies of human populations have been quite limited.

Methods: We assessed the association between maternal serum concentrations of dioxins and PCBs and the sons' age of pubertal onset in a prospective cohort of 489 mother-son pairs from Chapaevsk, Russia, a town contaminated with these chemicals during past industrial activity. The boys were recruited at ages 8 to 9 years, and 4 years of annual follow-up data were included in the analysis. Serum samples were collected at enrollment from both mothers and sons for measurement of dioxin and PCB concentrations using high-resolution mass spectrometry. The sons' pubertal onset--defined as pubertal stage 2 or higher for genitalia (G) or pubic hair (P), or testicular volume >3 mL--was assessed annually by the same physician.

Results: In multivariate Cox models, elevated maternal serum PCBs were associated with earlier pubertal onset defined by stage G2 or higher (4th quartile hazard ratio = 1.7 [95% confidence interval = 1.1- 2.5]), but not for stage P2 or higher or for testicular volume >3 mL. Maternal serum concentrations of dioxin toxic equivalents were not consistently associated with the sons' pubertal onset, although a dose-related delay in pubertal onset (only for G2 or higher) was seen among boys who breast-fed for 6 months or more.

Conclusions: Maternal PCB serum concentrations measured 8 or 9 years after sons' births--which may reflect sons' prenatal and early-life exposures--were associated with acceleration in some, but not all, measures of pubertal onset.
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November 2011

Temporal trends in serum concentrations of polychlorinated dioxins, furans, and PCBs among adult women living in Chapaevsk, Russia: a longitudinal study from 2000 to 2009.

Environ Health 2011 Jun 22;10:62. Epub 2011 Jun 22.

Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.

Background: The present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity.

Methods: Two serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry.

Results: The average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women, and the sum of PCBs decreased for six of eight women. During this nine year period, larger decreases in serum TEQs and PCBs were found in women with greater increases in body mass index.

Conclusions: This study provides suggestive evidence that average serum concentrations of dioxins, furans, and PCBs are decreasing over time among residents of this town.
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June 2011

Use of Specific IgE and Skin Prick Test to Determine Clinical Reaction Severity.

Br J Med Med Res 2011 ;1(4):410-429

2351 Clay Street, Suite 380, San Francisco, CA 94115, Department of Internal Medicine, California Pacific Medical Center, California, United States.

AIMS: To determine whether specific IgE and skin prick test correlate better in predicting reaction severity during a double-blinded placebo controlled food challenge (DBPCFC) for egg, milk, and multiple tree nut allergens. STUDY DESIGN: Prospective study. PLACE AND DURATION OF STUDY: Department of Pediatrics, Stanford University School of Medicine, August 2009 and ongoing. METHODOLOGY: We examined the reaction severity of twenty-four subjects to nine possible food allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut. Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were classified into mild (1), moderate (2), or severe (3) reactions using a modified Bock's criteria. RESULTS: Twenty four subjects underwent a total of 80 DBPCFC. Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%, were classified as mild. No reactions occurred with a SPT of zero mm while three reactions occurred with a negative specific IgE. All reactions were reversible with medication. CONCLUSION: These data suggest that SPT and specific IgE levels are not associated with reaction severity (p<0.64 and 0.27, respectively). We also found that combining specific IgE and SPT improved specificity but did not help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7 resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis 70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2).
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January 2011

Serum dioxins and polychlorinated biphenyls are associated with growth among Russian boys.

Pediatrics 2011 Jan 27;127(1):e59-68. Epub 2010 Dec 27.

Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave, Building I, Room 1404E, Boston, MA 02115, USA.

Objective: We evaluated the associations of serum dioxins and polychlorinated biphenyls (PCBs) with longitudinally assessed growth measurements among peripubertal Russian boys.

Methods: A total of 499 boys from Chapaevsk, Russia, aged 8 to 9 years were enrolled in the study from 2003 to 2005 and were followed prospectively for 3 years. Blood samples were collected and physical examinations were conducted at entry and repeated at annual study visits. Multivariate mixed-effects regression models for repeated measures were used to examine the associations of serum dioxins and PCBs with longitudinal measurements of BMI, height, and height velocity.

Results: Serum dioxin (total 2005 toxic equivalency [TEQ] median: 21.1 pg/g lipid) and PCBs (median sum of PCBs: 250 ng/g lipid) were measured in 468 boys. At study entry and during 3 years of follow-up, >50% of the boys had age-adjusted BMI and height z scores within 1 SD of World Health Organization-standardized mean values for age. Boys in the highest exposure quintile of the sum of dioxin and PCB concentrations and total TEQs had a significant decrease in mean BMI z scores of 0.67 for dioxins and TEQs and 1.04 for PCBs, compared with boys in the lowest exposure quintile. Comparison of the highest versus the lowest quintile revealed that higher serum PCB concentrations were associated with significantly lower height z scores (mean z-score decrease: 0.41) and height velocity (mean decrease: 0.19 cm/year) after 3 years of follow-up.

Conclusions: Our findings suggest that exposures to dioxins and PCBs are associated with reduced growth during the peripubertal period and may compromise adult body mass, stature, and health.
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January 2011

Predictors of serum dioxin, furan, and PCB concentrations among women from Chapaevsk, Russia.

Environ Sci Technol 2010 Jul;44(14):5633-40

Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.

Dioxins, furans, and polychlorinated biphenyls (PCBs) are persistent and bioaccumulative toxic chemicals that are ubiquitous in the environment. We assessed predictors of their serum concentrations among women living in a Russian town contaminated by past industrial activity. Blood samples from 446 mothers aged 23-52 years were collected between 2003-2005 as part of the Russian Children's Study. Serum dioxin, furan, and PCB concentrations were quantified using high-resolution gas chromatography-mass spectrometry. Potential determinants of exposure were collected through interviews. Multivariate linear regression models were used to identify predictors of serum concentrations and toxic equivalencies (TEQs). The median total PCB concentrations and total TEQs were 260 ng/g lipid and 25 pg TEQ/g lipid, respectively. In multivariate analyses, both total PCB concentrations and total TEQs increased significantly with age, residential proximity to a local chemical plant, duration of local farming, and consumption of local beef. Both decreased with longer breastfeeding, recent increases in body mass index, and later blood draw date. These demographic and lifestyle predictors showed generally similar associations with the various measures of serum dioxins, furans, and PCBs.
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July 2010

Blood lead levels and delayed onset of puberty in a longitudinal study of Russian boys.

Pediatrics 2010 May 5;125(5):e1088-96. Epub 2010 Apr 5.

Harvard School of Public Health, Department of Biostatistics, Boston, MA 02115, USA.

Objective: We evaluated the association of blood lead levels (BLLs) with pubertal onset in a longitudinal cohort of Russian boys.

Methods: A total of 489 Russian boys were enrolled in 2003-2005, at 8 to 9 years of age, and were monitored annually through May 2008. Cox proportional-hazards models were used to evaluate the association of BLLs at enrollment with time to pubertal onset during follow-up monitoring.

Results: A total of 481 boys had BLLs, with a median of 3 microg/dL and 28% with values of > or =5 microg/dL. The proportion of pubertal boys increased with age, from 12% at age 8 to 83% at age 12 for testicular volume of >3 mL, from 22% to 90% for genitalia stage 2 or higher, and from 4% to 40% for pubic hair stage 2 or higher. After adjustment for potential confounders including BMI and height, boys with high BLLs (> or =5 microg/dL) had 24% to 31% reduced risk of pubertal onset, on the basis of testicular volume of >3 mL (hazard ratio [HR]: 0.73 [95% confidence interval [CI]: 0.55-0.97]; P = .03), genitalia staging (HR: 0.76 [95% CI: 0.59-0.98]; P = .04), and pubic hair staging (HR: 0.69 [95% CI: 0.44-1.07]; P = .10), compared with those with lower BLLs. Pubertal onset occurred 6 to 8 months later, on average, for boys with high BLLs, compared with those with BLLs of <5 microg/dL.

Conclusion: Higher BLLs were associated with later pubertal onset in this prospective study of peripubertal Russian boys.
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May 2010

Dioxins and cardiovascular disease mortality.

Environ Health Perspect 2008 Nov 22;116(11):1443-8. Epub 2008 Jul 22.

Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.

Objective: In this systematic review we evaluated the evidence on the association between dioxin exposure and cardiovascular disease (CVD) mortality in humans.

Data Sources And Extraction: We conducted a PubMed search in December 2007 and considered all English-language epidemiologic studies and their citations regarding dioxin exposure and CVD mortality. To focus on dioxins, we excluded cohorts that were either primarily exposed to polychlorinated biphenyls or from the leather and perfume industries, which include other cardiotoxic coexposures.

Data Synthesis: We included results from 12 cohorts in the review. Ten cohorts were occupationally exposed. We divided analyses according to two well-recognized criteria of epidemiologic study quality: the accuracy of the exposure assessment, and whether the exposed population was compared with an internal or an external (e.g., general population) reference group. Analyses using internal comparisons with accurate exposure assessments are the highest quality because they minimize both exposure misclassification and confounding due to workers being healthier than the general population ("healthy worker effect"). The studies in the highest-quality group found consistent and significant dose-related increases in ischemic heart disease (IHD) mortality and more modest associations with all-CVD mortality. Their primary limitation was a lack of adjustment for potential confounding by the major risk factors for CVD.

Conclusions: The results of this systematic review suggest that dioxin exposure is associated with mortality from both IHD and all CVD, although more strongly with the former. However, it is not possible to determine the potential bias, if any, from confounding by other risk factors for CVD.
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November 2008

Environmental pollutants and breast cancer: epidemiologic studies.

Cancer 2007 Jun;109(12 Suppl):2667-711

Silent Spring Institute, Newton, Massachusetts 02458, USA.

Laboratory research has shown that numerous environmental pollutants cause mammary gland tumors in animals; are hormonally active, specifically mimicking estrogen, which is a breast cancer risk factor; or affect susceptibility of the mammary gland to carcinogenesis. An assessment of epidemiologic research on these pollutants identified in toxicologic studies can guide future research and exposure reduction aimed at prevention. The PubMed database was searched for relevant literature and systematic critical reviews were entered in a database available at URL: and URL: (accessed April 10, 2007). Based on a relatively small number of studies, the evidence to date generally supports an association between breast cancer and polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in conjunction with certain genetic polymorphisms involved in carcinogen activation and steroid hormone metabolism. Evidence regarding dioxins and organic solvents is sparse and methodologically limited but suggestive of an association. Methodologic problems include inadequate exposure assessment, a lack of access to highly exposed and unexposed populations, and a lack of preclinical markers to identify associations that may be obscured by disease latency. Among chemicals identified in toxicologic research as relevant to breast cancer, many have not been investigated in humans. The development of better exposure assessment methods is needed to fill this gap. In the interim, weaknesses in the epidemiologic literature argue for greater reliance on toxicologic studies to develop national policies to reduce chemical exposures that may be associated with breast cancer. Substantial research progress in the last 5 years suggests that the investigation of environmental pollutants will lead to strategies to reduce breast cancer risk.
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June 2007

Core group evolution over time: high-risk sexual behavior in a birth cohort between sexual debut and age 26.

Sex Transm Dis 2003 Nov;30(11):818-24

AIDS Epidemiology Group, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

Background And Objective: Among the limitations of the concept of a sexually transmitted disease core is uncertainty about the stability of sexual behavior over time. The objective was to shed light on characteristics and stability of the core group by assessing sexual behavior longitudinally in a birth cohort.

Goals: The goals were to describe group size and characteristics of people who report 5 or more heterosexual partners per year (a surrogate for the core group) at ages 18, 21, and 26 years.

Study Design: We used a prospective cohort study with a computer-presented questionnaire on sexual behavior.

Results: Of the original cohort members, 991 (97.3% of those believed to be alive) responded at at least one age. A total of 14.7% of women and 26.0% of men were in the core group at either age 18 or 21 or 26, but only 0.5% and 0.9% of women and men, respectively, were in the core group at all ages. Those in the core group were significantly more likely to report concurrent partnerships and higher sexually transmitted disease (STD) rates. Early age at first sex was consistently associated with being in the core group, whereas those with less education were more likely to be in the core group at age 18 but not at later ages.

Conclusion: The high degree of variability in sexual behavior over time of individuals adds another degree of complexity to the identification of a core group for STD transmission.
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November 2003