Publications by authors named "Diane R Gold"

303 Publications

The Role of Childhood Asthma in Obesity Development: A Nationwide U.S. Multi-cohort Study.

Epidemiology 2021 Sep 20. Epub 2021 Sep 20.

Department of Preventive Medicine, University of Southern California, Los Angeles, CA Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Department of Civil and Environmental Engineering, Northeastern University, Boston, MA Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston MA Department of Pediatrics, Hackensack Meridian School of Medicine, Nutley NJ and the Albert Einstein College of Medicine, Bronx, NY Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN Departments of Pediatrics and Medicine, The University of Chicago, Chicago, IL University of Colorado, Anschutz Medical Campus, Aurora, CO Nell Hodgson Woodruff School of Nursing and Department of Family & Preventive Medicine, Emory University, Atlanta, GA Avera Research Institute, Sioux Falls, SD Kaiser Permanente Northern California Division of Research Department of Psychology The George Washington University, Washington, DC Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA University of California, Davis, School of Medicine, CA Geisel School of Medicine, Dartmouth College, Hanover, NH Department of Pediatrics & Environmental and Occupational Health Sciences, University of Washington, WA Department of Psychiatry and Human Behavior and Department of Pediatrics, Brown Alpert Medical School and Women and Infants Hospital, Providence, RI. Department of Education, University of Oregon, Eugene, OR Division of Pediatric Pulmonary Medicine, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY Department of Pediatrics, Oregon Health and Science University, Portland, OR Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY Departments of Psychiatry, Psychology, Neuroscience and Obstetrics and Gynecology, University of Rochester, NY Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT Division of Allergy, Immunology, and Pulmonary Medicine, Department of PediatricsSt. Louis Children's Hospital, Washington University School of Medicine St. Louis, MO Departments of Pediatrics, Environmental Medicine and Population Health, New York University School of Medicine, NY Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY Department of Internal Medicine, University of Utah, Salt Lake City, UT Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY.

Rationale: Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset.

Objectives: To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association.

Methods: We studied 8716 children between ages 6-18.5 years who were non-obese at study entry participating in 18 U.S. cohorts of the Environmental influences on Child Health Outcomes program (among 7299 children with complete covariate data mean [SD] study entry age=7.2 [1.6] years and follow-up=5.3 [3.1] years).

Measurements And Main Results: We defined asthma based on caregiver report of provider diagnosis. Incident obesity was defined as the first documented body mass index ≥95th percentile for age and sex following asthma status ascertainment. Over the study period, 26% of children had an asthma diagnosis and 11% developed obesity. Cox proportional hazards models with sex-specific baseline hazards were fitted to assess the association of asthma diagnosis with obesity incidence. Children with asthma had a 23% (95%CI: 4%, 44%) higher risk for subsequently developing obesity compared to those without asthma. A novel mediation analysis was also conducted to decompose the total asthma effect on obesity into pathways mediated and not mediated by asthma medication use. Use of asthma medication attenuated the total estimated effect of asthma on obesity by 64% (excess HR:-0.64 [95%CI:-1.05,-0.23]).

Conclusions: This nationwide study supports the hypothesis that childhood asthma is associated with later risk of obesity. Asthma medication may reduce this association and merits further investigation as a potential strategy for obesity prevention among children with asthma.
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http://dx.doi.org/10.1097/EDE.0000000000001421DOI Listing
September 2021

Effect of School Integrated Pest Management or Classroom Air Filter Purifiers on Asthma Symptoms in Students With Active Asthma: A Randomized Clinical Trial.

JAMA 2021 09;326(9):839-850

Harvard University Medical School, Boston, Massachusetts.

Importance: School and classroom allergens and particles are associated with asthma morbidity, but the benefit of environmental remediation is not known.

Objective: To determine whether use of a school-wide integrated pest management (IPM) program or high-efficiency particulate air (HEPA) filter purifiers in the classrooms improve asthma symptoms in students with active asthma.

Design, Setting, And Participants: Factorial randomized clinical trial of a school-wide IPM program and HEPA filter purifiers in the classrooms was conducted from 2015 to 2020 (School Inner-City Asthma Intervention Study). There were 236 students with active asthma attending 41 participating urban elementary schools located in the Northeastern US who were randomized to IPM by school and HEPA filter purifiers by classroom. The date of final follow-up was June 20, 2020.

Interventions: The school-wide IPM program consisted of application of rodenticide, sealing entry points, trap placement, targeted cleaning, and brief educational handouts for school staff. Infestation was assessed every 3 months, with additional treatments as needed. Control schools received no IPM, cleaning, or education. Classroom portable HEPA filter purifiers were deployed and the filters were changed every 3 months. Control classrooms received sham HEPA filters that looked and sounded like active HEPA filter purifiers. Randomization was done independently (split-plot design), with matching by the number of enrolled students to ensure a nearly exact 1:1 student ratio for each intervention with 118 students randomized to each group. Participants, investigators, and those assessing outcomes were blinded to the interventions.

Main Outcomes And Measures: The primary outcome was the number of symptom-days with asthma during a 2-week period. Symptom-days were assessed every 2 months during the 10 months after randomization.

Results: Among the 236 students who were randomized (mean age, 8.1 [SD, 2.0] years; 113 [48%] female), all completed the trial. At baseline, the 2-week mean was 2.2 (SD, 3.9) symptom-days with asthma and 98% of the classrooms had detectable levels of mouse allergen. The results were pooled because there was no statistically significant difference between the 2 interventions (P = .18 for interaction). During a 2-week period, the mean was 1.5 symptom-days with asthma after use of the school-wide IPM program vs 1.9 symptom-days after no IPM across the school year (incidence rate ratio, 0.71 [95% CI, 0.38-1.33]), which was not statistically significantly different. During a 2-week period, the mean was 1.6 symptom-days with asthma after use of HEPA filter purifiers in the classrooms vs 1.8 symptom-days after use of sham HEPA filter purifiers across the school year (incidence rate ratio, 1.47 [95% CI, 0.79-2.75]), which was not statistically significantly different. There were no intervention-related adverse events.

Conclusions And Relevance: Among children with active asthma, use of a school-wide IPM program or classroom HEPA filter purifiers did not significantly reduce symptom-days with asthma. However, interpretation of the study findings may need to consider allergen levels, particle exposures, and asthma symptoms at baseline.

Trial Registration: ClinicalTrials.gov Identifier: NCT02291302.
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http://dx.doi.org/10.1001/jama.2021.11559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424475PMC
September 2021

Regional and sociodemographic differences in average BMI among US children in the ECHO program.

Obesity (Silver Spring) 2021 Aug 31. Epub 2021 Aug 31.

Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.

Objective: The aim of this study was to describe the association of individual-level characteristics (sex, race/ethnicity, birth weight, maternal education) with child BMI within each US Census region and variation in child BMI by region.

Methods: This study used pooled data from 25 prospective cohort studies. Region of residence (Northeast, Midwest, South, West) was based on residential zip codes. Age- and sex-specific BMI z scores were the outcome.

Results: The final sample included 14,313 children with 85,428 BMI measurements, 49% female and 51% non-Hispanic White. Males had a lower average BMI z score compared with females in the Midwest (β = -0.12, 95% CI: -0.19 to -0.05) and West (β = -0.12, 95% CI: -0.20 to -0.04). Compared with non-Hispanic White children, BMI z score was generally higher among children who were Hispanic and Black but not across all regions. Compared with the Northeast, average BMI z score was significantly higher in the Midwest (β = 0.09, 95% CI: 0.05-0.14) and lower in the South (β = -0.12, 95% CI: -0.16 to -0.08) and West (β = -0.14, 95% CI: -0.19 to -0.09) after adjustment for age, sex, race/ethnicity, and birth weight.

Conclusions: Region of residence was associated with child BMI z scores, even after adjustment for sociodemographic characteristics. Understanding regional influences can inform targeted efforts to mitigate BMI-related disparities among children.
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http://dx.doi.org/10.1002/oby.23235DOI Listing
August 2021

Temporal trends of concentrations of per- and polyfluoroalkyl substances among adults with overweight and obesity in the United States: Results from the Diabetes Prevention Program and NHANES.

Environ Int 2021 12 29;157:106789. Epub 2021 Jul 29.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. Electronic address:

Background: Understanding the temporal trends and change of concentrations of per- and polyfluoroalkyl substances (PFAS) is important to evaluate the health impact of PFAS at both the individual- and population-level, however, limited information is available for pre-diabetic adults in the U.S.

Objectives: Determine trends and rate of change of plasma PFAS concentrations in overweight or obese U.S. adults and evaluate variation by sex, race/ethnicity, and age.

Methods: We described temporal trends of plasma PFAS concentrations using samples collected in 1996-1998, 1999-2001, and 2011-2012 from 957 pre-diabetic adults enrolled in the Diabetes Prevention Program (DPP) trial and Outcomes Study (DPPOS) and compared to serum concentrations from the National Health and Nutrition Examination Survey (NHANES 1999-2000, 2003-2016, adults with BMI ≥ 24 kg/m). We examined associations between participants' characteristics and PFAS concentrations and estimated the rate of change using repeated measures in DPP/DPPOS assuming a first-order elimination model.

Results: Longitudinal measures of PFAS concentrations in DPP/DPPOS individuals were comparable to NHANES cross-sectional populational means. Plasma concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid, perfluorohexanesulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), and N-methylperfluorooctane sulfonamido acetic acid (MeFOSAA) started to decline after the year 2000 and concentrations of perfluorononanoic acid (PFNA) increased after 2000 and, for NHANES, decreased after 2012. We consistently observed higher PFOS, PFHxS and PFNA among male, compared to female, and higher PFOS and PFNA among Black, compared to white, participants. The estimated time for concentrations to decrease by half ranged from 3.39 years for EtFOSAA to 17.56 years for PFHxS.

Discussion: We observed a downward temporal trend in plasma PFOS concentrations that was consistent with the timing for U.S. manufacturers' phaseout. Male and Black participants consistently showed higher PFOS and PFNA than female and white participants, likely due to differences in exposure patterns, metabolism or elimination kinetics.
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http://dx.doi.org/10.1016/j.envint.2021.106789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490287PMC
December 2021

Air pollution and lung function in children.

J Allergy Clin Immunol 2021 07;148(1):1-14

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Mass; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.

In this narrative review, we summarize the literature and provide updates on recent studies of air pollution exposures and child lung function and lung function growth. We include exposures to outdoor air pollutants that are monitored and regulated through air quality standards, and air pollutants that are not routinely monitored or directly regulated, including wildfires, indoor biomass and coal burning, gas and wood stove use, and volatile organic compounds. Included is a more systematic review of the recent literature on long-term air pollution and child lung function because this is an indicator of future adult respiratory health and exposure assessment tools have improved dramatically in recent years. We present "summary observations" and "knowledge gaps." We end by discussing what is known about what can be done at the individual/household, local/regional, and national levels to overcome structural impediments, reduce air pollution exposures, and improve child lung function. We found a large literature on adverse air pollution effects on children's lung function level and growth; however, many questions remain. Important areas needing further research include whether early-life effects are fixed or reversible; and what are windows of increased susceptibility, long-term effects of repeated wildfire events, and effects of air quality interventions.
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http://dx.doi.org/10.1016/j.jaci.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274324PMC
July 2021

Early pregnancy exposure to metal mixture and birth outcomes - A prospective study in Project Viva.

Environ Int 2021 11 17;156:106714. Epub 2021 Jun 17.

Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. Electronic address:

Background: Prenatal exposure to metals has been individually associated with birth outcomes. However, little is known about the effect of metal mixture, particularly at low exposure levels.

Objectives: To estimate individual and joint effects of metal mixture components on birth outcomes.

Methods: We used data from 1,391 mother-infant pairs in Project Viva (1999-2002). We measured 11 metals in maternal 1st trimester erythrocyte; abstracted birth weight from medical records; calculated gestational age from last menstrual period or ultrasound; and obtained birth length (n = 729) and head circumference (n = 791) from research measurements. We estimated individual and joint effects of metals using multivariable linear and Bayesian kernel machine regressions.

Results: In both single metal and metal mixture analyses, exposure to higher concentrations of arsenic was associated with lower birth weight in males, zinc with higher head circumference in females, and manganese with higher birth length in sex-combined analysis. We also observed sex-specific metal interactions with birth outcomes. Arsenic and manganese showed a synergistic association with birth weight in males, in whom an interquartile range (IQR) increase in arsenic was associated with 25.3 g (95% CI: -79.9, 29.3), 47.9 g (95% CI: -98.0, 2.1), and 72.2 g (95% CI: -129.8, -14.7) lower birth weight when manganese concentrations were at 25th, 50th, and 75th percentiles, respectively. Lead and zinc showed an antagonistic association with head circumference in males, where an IQR increase in lead was associated with 0.18 cm (95% CI: -0.35, -0.02), 0.10 cm (95% CI: -0.25, 0.04), 0.03 cm (95% CI: -0.2, 0.14) smaller head circumference when zinc concentrations were at 25th, 50th, and 75th percentiles, respectively. Exposure to higher concentrations of arsenic was also associated with lower gestational age in males when concentrations of manganese and lead were higher.

Discussion: Maternal erythrocyte concentrations of arsenic, manganese, lead, and zinc were individually and interactively associated with birth outcomes. The associations varied by infant sex and exposure level of other mixture components.
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http://dx.doi.org/10.1016/j.envint.2021.106714DOI Listing
November 2021

Associations of Snoring and Asthma Morbidity in the School Inner-City Asthma Study.

J Allergy Clin Immunol Pract 2021 Oct 6;9(10):3679-3685.e1. Epub 2021 Jun 6.

Harvard Medical School, Boston, Mass; Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass. Electronic address:

Background: Inner-city children are disproportionately affected by asthma and sleep-disordered breathing (SDB). However, little is known about the association of SDB symptoms with asthma morbidity in this vulnerable population.

Objective: Assess the relationship between snoring frequency and asthma morbidity.

Methods: This study was part of the School Inner-City Asthma Study, a longitudinal prospective cohort study of children with persistent asthma who attended schools in the Northeast United States from 2008 to 2013. Participants had baseline assessments of asthma symptoms, snoring, and allergy status. Caregivers completed quarterly surveys for 12 months on symptoms of asthma, snoring, and health care outcomes. Snoring frequency (non-, rare-, sometimes-, habitual-snoring) and its relationship with asthma symptoms and asthma morbidity were assessed by mixed-effects models.

Results: There were 1186 observations from 339 subjects. Mean age was 7.9 years; roughly half were male, and most were of minority race. Half were overweight or obese, and 65.5% had atopy. At initial snoring assessment, 24.8% reported habitual snoring, but report of snoring frequency varied over the study period. Multivariate analyses revealed increased odds of maximum asthma symptom days for habitual snoring compared with nonsnoring (1.58; 95% CI, 1.19-2.10; P < .002) and all other snoring categories. Habitual snoring was associated with greater odds of health care utilization (incidence rate ratio, 1.72; 95% CI, 1.10-2.69; P = .02) and worse asthma control (odds ratio, 1.49; 95% CI, 1.05-2.11; P = .03) compared with nonsnoring.

Conclusions: Snoring is common among inner-city school-age children with asthma, and habitual snoring is associated with increased asthma symptom burden and health care utilization.
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http://dx.doi.org/10.1016/j.jaip.2021.05.022DOI Listing
October 2021

An Overview of the Relevance of IgG4 Antibodies in Allergic Disease with a Focus on Food Allergens.

Children (Basel) 2021 May 20;8(5). Epub 2021 May 20.

Division of Allergy and Immunology, Nationwide Children's Hospital, Columbus, OH 43205, USA.

Antibodies of the IgG4 isotype are strongly associated with allergic disease but have several properties such as not precipitating with allergens, not activating complement and poor binding to Fcγ receptors that argue against a pro-inflammatory role. In keeping with that, IgG4 antibodies are a striking feature of the response to immunotherapy. In two naturally occurring situations IgG4 antibodies are common with low or absent IgE antibodies. The first example is children raised in a house with a cat and the second is eosinophilic esophagitis (EoE). In many population-based cohorts, the ownership of a cat in early childhood is associated with a decreased prevalence of a cat allergy at age 10. The second example (i.e., EoE) is a novel form of food allergy that is not mediated by IgE and is related to consuming cow's milk or wheat. In EoE, patients have IgG4 to milk proteins in high > 10 µg/mL or very high > 100 µg/mL titers. Enigmatically these patients are found to have deposits of IgG4 in the wall of their inflamed esophagus. The factors that have given rise to EoE remain unclear; however, changes in food processing over the past 50 years, particularly ultra-heat treatment and the high pressure homogenization of milk, represent a logical hypothesis.
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http://dx.doi.org/10.3390/children8050418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160978PMC
May 2021

Air Pollution, Neonatal Immune Responses, and Potential Joint Effects of Maternal Depression.

Int J Environ Res Public Health 2021 05 11;18(10). Epub 2021 May 11.

Department of Social and Behavioral Sciences, The Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

Prenatal maternal exposure to air pollution may cause adverse health effects in offspring, potentially through altered immune responses. Maternal psychosocial distress can also alter immune function and may increase gestational vulnerability to air pollution exposure. We investigated whether prenatal exposure to air pollution is associated with altered immune responses in cord blood mononuclear cells (CBMCs) and potential modification by maternal depression in 463 women recruited in early pregnancy (1999-2001) into the Project Viva longitudinal cohort. We estimated black carbon (BC), fine particulate matter (PM), residential proximity to major roadways, and near-residence traffic density, averaged over pregnancy. Women reported depressive symptoms in mid-pregnancy (Edinburgh Postnatal Depression Scale) and depression history by questionnaire. Immune responses were assayed by concentrations of three cytokines (IL-6, IL-10, and TNF-α), in unstimulated or stimulated (phytohemagglutinin (PHA), cockroach extract (Bla g 2), house dust mite extract (Der f 1)) CBMCs. Using multivariable linear or Tobit regression analyses, we found that CBMCs production of IL-6, TNF-a, and IL-10 were all lower in mothers exposed to higher levels of PM during pregnancy. A suggestive but not statistically significant pattern of lower cord blood cytokine concentrations from ever (versus never) depressed women exposed to PM, BC, or traffic was also observed and warrants further study.
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http://dx.doi.org/10.3390/ijerph18105062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150899PMC
May 2021

A distributed geospatial approach to describe community characteristics for multisite studies.

J Clin Transl Sci 2021 Feb 5;5(1):e86. Epub 2021 Feb 5.

Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
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http://dx.doi.org/10.1017/cts.2021.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111696PMC
February 2021

Pediatric Asthma Incidence Rates in the United States from 1980 to 2017.

J Allergy Clin Immunol 2021 May 6. Epub 2021 May 6.

Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.

Background: Few studies have examined longitudinal asthma incidence rates (IRs) from a public health surveillance perspective.

Objective: Our aim was to calculate descriptive asthma IRs in children over time with consideration for demographics and parental asthma history.

Methods: Data from 9 US birth cohorts were pooled into 1 population covering the period from 1980 to 2017. The outcome was earliest parental report of a doctor diagnosis of asthma. IRs per 1,000 person-years were calculated.

Results: The racial/ethnic backgrounds of the 6,283 children studied were as follows: 55% European American (EA), 25.5% African American (AA), 9.5% Mexican-Hispanic American (MA) and 8.5% Caribbean-Hispanic American (CA). The average follow-up was 10.4 years (SD = 8.5 years; median = 8.4 years), totaling 65,291 person-years, with 1789 asthma diagnoses yielding a crude IR of 27.5 per 1,000 person-years (95% CI = 26.3-28.8). Age-specific rates were highest among children aged 0 to 4 years, notably from 1995 to 1999, with a decline in EA and MA children in 2000 to 2004 followed by a decline in AA and CA children in 2010 to 2014. Parental asthma history was associated with statistically significantly increased rates. IRs were similar and higher in AA and CA children versus lower but similar in EA and MA children. The differential rates by sex from birth through adolescence principally resulted from a decline in rates among males but relatively stable rates among females.

Conclusions: US childhood asthma IRs varied dramatically by age, sex, parental asthma history, race/ethnicity, and calendar year. Higher rates in the 0- to 4-year-olds group, particularly among AA/CA males with a parental history of asthma, as well as changes in rates over time and by demographic factors, suggest that asthma is driven by complex interactions between genetic susceptibility and variation in time-dependent environmental and social factors.
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http://dx.doi.org/10.1016/j.jaci.2021.04.027DOI Listing
May 2021

Contributions of asthma, rhinitis and IgE to exhaled nitric oxide in adolescents.

ERJ Open Res 2021 Apr 19;7(2). Epub 2021 Apr 19.

Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Exhaled nitric oxide fraction ( ) is an indicator of allergic airway inflammation. However, it is unknown how asthma, allergic rhinitis (AR) and allergic sensitisation relate to , particularly among adolescents and in overlapping conditions. We sought to determine the associations between asthma, AR, and aeroallergen immunoglobulin (Ig)E and in adolescents. We measured among 929 adolescents (aged 11-16 years) in Project Viva, an unselected prebirth cohort in Massachusetts, USA. We defined asthma as ever asthma physician diagnosis plus wheezing in the past year or taking asthma medications in the past month, AR as a physician diagnosis of hay fever or AR, and aeroallergen IgE as any IgE >0.35 IU·mL among 592 participants who provided blood samples. We examined associations of asthma, AR and IgE with percent difference in in linear regression models adjusted for sex, race/ethnicity, age and height, maternal education and smoking during pregnancy, and household/neighbourhood demographics. Asthma (14%) was associated with 97% higher (95% CI 70-128%), AR (21%) with 45% higher (95% CI 28-65%), and aeroallergen IgE (58%) with 102% higher (95% CI 80-126%) compared to those without each condition, respectively. In the absence of asthma or AR, aeroallergen IgE was associated with 75% higher (95% CI 52-101), while asthma and AR were not associated with in the absence of IgE. The link between asthma and AR with is limited to those with IgE-mediated phenotypes. may be elevated in those with allergic sensitisation alone, even in the absence of asthma or AR.
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http://dx.doi.org/10.1183/23120541.00945-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053905PMC
April 2021

Residential PM exposure and the nasal methylome in children.

Environ Int 2021 08 16;153:106505. Epub 2021 Apr 16.

Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Rationale: PMinduced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known.

Objectives: We aimed to study associations of fine particulate matter PM exposure with DNA methylation in nasal cells.

Methods: We conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina MethylationEPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA).

Results: In adjusted analyses, we found 362 CpGs associated with 1-year PM (FDR < 0.05), 20 CpGs passing Bonferroni correction (P < 7.0x10) and 10 Differentially Methylated Regions (DMRs). In 445 PIAMA participants (mean age 16.3 years) 11 of 203 available CpGs replicated at P < 0.05. We observed differential DNAm at/near genes implicated in cell cycle, immune and inflammatory responses. There were no CpGs or regions associated with PM levels at 1-day, 1-week, or 1-month prior to sample collection, although 2 CpGs were associated with past 3-month PM.

Conclusion: We observed wide-spread DNAm variability associated with average past year PM exposure but we did not detect associations with shorter-term exposure. Our results suggest that nasal DNAm marks reflect chronic air pollution exposure.
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http://dx.doi.org/10.1016/j.envint.2021.106505DOI Listing
August 2021

Ambient air pollution exposure and radiographic pulmonary vascular volumes.

Environ Epidemiol 2021 Apr 18;5(2):e143. Epub 2021 Mar 18.

Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Exposure to higher levels of ambient air pollution is a known risk factor for cardiovascular disease but long-term effects of pollution exposure on the pulmonary vessels are unknown.

Methods: Among 2428 Framingham Heart Study participants who underwent chest computed tomography (CT) between 2008 and 2011, pulmonary vascular volumes were calculated by image analysis, including the total vascular volume and small vessel volume (cross-sectional area <5 mm; BV5 defined as small vessel volume). Using spatiotemporal models and participant home address, we assigned 1-year (2008) and 5-year (2004-2008) average concentrations of fine particulate matter (PM), elemental carbon (EC), and ground-level ozone (O), and distance to major roadway. We examined associations of 1- and 5-year exposures, and distance to road, with CT vascular volumes using multivariable linear regression models.

Results: There was a consistent negative association of higher O with lower small vessel volumes, which persisted after adjustment for distance to road. Per interquartile range (IQR) of 2008 O, BV5 was 0.34 mL lower (95% confidence intervals [CI], -0.61 to -0.06; = 0.02), with similar results for 5-year exposure. One-year EC exposure and closer proximity to road were weakly associated with small vessel volumes; BV5 was 0.18 mL higher per IQR of 2008 EC (95% CI, -0.05 to 0.42; = 0.13) and 0.40 mL higher per IQR closer proximity to road (95% CI: -0.10 to 0.89; = 0.12). PM was not associated with small vascular volumes; BV5 was 0.26 mL lower per IQR of 2008 PM (95% CI: -0.68 to 0.16; = 0.22).

Conclusions: Among community-dwelling adults living in the northeastern United States, higher exposure to O was associated with lower small pulmonary vessel volumes on CT.
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http://dx.doi.org/10.1097/EE9.0000000000000143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043731PMC
April 2021

Sources of indoor PM gross α and β activities measured in 340 homes.

Environ Res 2021 06 2;197:111114. Epub 2021 Apr 2.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Particle radioactivity (PR) exposure has been linked to adverse health effects. PR refers to the presence of α- and β-emitting radioisotopes attached to fine particulate matter (PM). This study investigated sources contributing to indoor PM gross α- and β-radioactivity levels. We measured activity from long-lived radon progeny radionuclides from archived PM samples collected in 340 homes in Massachusetts during the period 2006-2010. We analyzed the data using linear mixed effects models and positive matrix factorization (PMF) analysis. Indoor PM gross α-activity levels were correlated with sulfur (S), iron (Fe), bromine (Br), vanadium (V), sodium (Na), lead (Pb), potassium (K), calcium (Ca), silicon (Si), zinc (Zn), arsenic (As), titanium (Ti), radon (Rn) and black carbon (BC) concentrations (p <0.05). Indoor PM β-activity was correlated with S, As, antimony (Sb), Pb, Br and BC. We identified four indoor PM sources: outdoor air pollution (62%), salt aerosol source (14%), fireworks and environmental tobacco smoke (7%) and indoor mixed dust (17%). Outdoor air pollution was the most significant contributor to indoor PM α- and β-activity levels. The contributions of this source were during the summer months and when windows were open. Indoor mixed dust was also found to contribute to PM α-activity. PM α-activity was further associated with radon during winter months, showing radon's important role as an indoor source of ionizing radiation.
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http://dx.doi.org/10.1016/j.envres.2021.111114DOI Listing
June 2021

DNA methylation architecture of the ACE2 gene in nasal cells of children.

Sci Rep 2021 03 29;11(1):7107. Epub 2021 Mar 29.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 enters cells via angiotensin-Converting Enzyme 2 (ACE2) receptors, highly expressed in nasal epithelium with parallel high infectivity. The nasal epigenome is in direct contact with the environment and could explain COVID-19 disparities by reflecting social and environmental influences on ACE2 regulation. We collected nasal swabs from anterior nares of 547 children, measured DNA methylation (DNAm), and tested differences at 15 ACE2 CpGs by sex, age, race/ethnicity and epigenetic age. ACE2 CpGs were differentially methylated by sex with 12 sites having lower DNAm (mean = 12.71%) and 3 sites greater DNAm (mean = 1.45%) among females relative to males. We observed differential DNAm at 5 CpGs for Hispanic females (mean absolute difference = 3.22%) and lower DNAm at 8 CpGs for Black males (mean absolute difference = 1.33%), relative to white participants. Longer DNAm telomere length was associated with greater ACE2 DNAm at 11 and 13 CpGs among males (mean absolute difference = 7.86%) and females (mean absolute difference = 8.21%), respectively. Nasal ACE2 DNAm differences could contribute to our understanding COVID-19 severity and disparities reflecting upstream environmental and social influences. Findings need to be confirmed among adults and patients with risk factors for COVID-19 severity.
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http://dx.doi.org/10.1038/s41598-021-86494-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007733PMC
March 2021

Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children.

Pediatr Pulmonol 2021 07 22;56(7):1896-1905. Epub 2021 Mar 22.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: Exposure to violence (ETV) or chronic stress may influence asthma through unclear mechanisms.

Methods: Epigenome-wide association study (EWAS) of ETV or chronic stress measures and DNA methylation in nasal epithelium from 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed four measures of ETV and chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by p value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).

Results: Three CpGs (in SNN, PTPRN2, and LINC01164) were associated with maternal perceived stress or gun violence (p = 1.28-3.36 × 10 ), but not with atopic asthma, in EVA-PR. In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA-PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4, and ANAPC13) were associated with atopic asthma at FDR-p < .05.

Conclusions: Pending confirmation in longitudinal studies, our findings suggest that nasal epithelial methylation markers associated with measures of ETV and chronic stress may be linked to atopic asthma in children and adolescents.
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http://dx.doi.org/10.1002/ppul.25372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217314PMC
July 2021

Childhood patterns of overweight and wheeze and subsequent risk of current asthma and obesity in adolescence.

Paediatr Perinat Epidemiol 2021 Sep 22;35(5):569-577. Epub 2021 Mar 22.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Background: Obesity and asthma in childhood often co-occur. Few studies have examined this relationship using repeated measures of body mass index (BMI) or asthma symptoms (such as wheeze).

Objective: We compared two analytic approaches for repeated measures data to investigate this relationship.

Methods: Our baseline sample consisted of 1277 children enrolled in a Boston-area cohort with BMI or wheeze at age 1 year and no missing covariates. We used latent class growth models (LCGM) and inverse probability weighting (IPW) of marginal structural models to examine the extent to which presence of overweight across childhood was associated with early adolescent current asthma, and conversely of repeated measures of wheeze across childhood with early adolescent obesity.

Results: Using LCGM, a "persistent" childhood overweight class (vs "never") was associated with higher risk of asthma in early adolescence (RR 1.9; 95% CI 1.1, 3.0), while "persistent" childhood wheeze (vs "never") was associated with higher risk of obesity in early adolescence (RR 2.7; 95% CI 1.0, 6.4) after adjusting for baseline covariates. An IPW analysis treating childhood overweight and wheeze as time-varying exposures and adjusting for baseline and time-varying covariates resulted in weaker and less precise associations of "persistent" (vs "never") overweight with adolescent asthma (RR 1.3; 95% CI 0.3, 3.0), and of "persistent" (vs "never") wheeze with adolescent obesity (RR 2.3; 95% CI 0.4, 5.3).

Conclusion: Our point estimates from both approaches suggest an association between "persistent" childhood overweight and adolescent asthma, and between "persistent" childhood wheeze and adolescent obesity. LCGM results were stronger and more precise, whereas IPW results were less conclusive with wider 95% confidence intervals containing the null. The precision gained from LCGM may be at the expense of bias, and the use of both approaches helps to shed some light on this tradeoff.
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http://dx.doi.org/10.1111/ppe.12760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380670PMC
September 2021

E-Cigarettes and Cardiopulmonary Health.

Function (Oxf) 2021 8;2(2):zqab004. Epub 2021 Feb 8.

Dorothy M. Davis Heart and Lung Research Institute, Colleges of Medicine and Nursing, The Ohio State University, Columbus, OH, USA.

E-cigarettes have surged in popularity over the last few years, particularly among youth and young adults. These battery-powered devices aerosolize e-liquids, comprised of propylene glycol and vegetable glycerin, typically with nicotine, flavors, and stabilizers/humectants. Although the use of combustible cigarettes is associated with several adverse health effects including multiple pulmonary and cardiovascular diseases, the effects of e-cigarettes on both short- and long-term health have only begun to be investigated. Given the recent increase in the popularity of e-cigarettes, there is an urgent need for studies to address their potential adverse health effects, particularly as many researchers have suggested that e-cigarettes may pose less of a health risk than traditional combustible cigarettes and should be used as nicotine replacements. This report is prepared for clinicians, researchers, and other health care providers to provide the current state of knowledge on how e-cigarette use might affect cardiopulmonary health, along with research gaps to be addressed in future studies.
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http://dx.doi.org/10.1093/function/zqab004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948134PMC
February 2021

Plasma Concentrations of Per- and Polyfluoroalkyl Substances and Body Composition From Mid-Childhood to Early Adolescence.

J Clin Endocrinol Metab 2021 Aug;106(9):e3760-e3770

Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, ME, USA.

Context: Per- and polyfluoroalkyl substances (PFAS) may alter body composition by lowering anabolic hormones and increasing inflammation, but data are limited, particularly in adolescence when body composition is rapidly changing.

Objective: To evaluate associations of PFAS plasma concentrations in childhood with change in body composition through early adolescence.

Methods: A total of 537 children in the Boston-area Project Viva cohort participated in this study. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) to examine associations of plasma concentrations of 6 PFAS, quantified by mass spectrometry, in mid-childhood (mean age, 7.9 years; 2007-2010) with change in body composition measured by dual-energy x-ray absorptiometry from mid-childhood to early adolescence (mean age, 13.1 years).

Results: In single-PFAS linear regression models, children with higher concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoate (PFDA), and perfluorohexane sulfonate (PFHxS) had less accrual of lean mass (eg, -0.33 [95% CI: -0.52, -0.13] kg/m2 per doubling of PFOA). Children with higher PFOS and PFHxS had less accrual of total and truncal fat mass (eg, -0.32 [95% CI: -0.54, -0.11] kg/m2 total fat mass per doubling of PFOS), particularly subcutaneous fat mass (eg, -17.26 [95% CI -32.25, -2.27] g/m2 per doubling of PFOS). Children with higher PFDA and perfluorononanoate (PFNA) had greater accrual of visceral fat mass (eg, 0.44 [95% CI: 0.13, 0.75] g/m2 per doubling of PFDA). Results from BKMR mixture models were consistent with linear regression analyses.

Conclusion: Early life exposure to some but not all PFAS may be associated with adverse changes in body composition.
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http://dx.doi.org/10.1210/clinem/dgab187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372642PMC
August 2021

Per- and polyfluoroalkyl substances and calcifications of the coronary and aortic arteries in adults with prediabetes: Results from the diabetes prevention program outcomes study.

Environ Int 2021 06 22;151:106446. Epub 2021 Feb 22.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Background: Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals that have been associated with cardiovascular risk factors including elevated body weight and hypercholesterolemia. Therefore, PFAS may contribute to the development of atherosclerosis and cardiovascular disease (CVD). However, no previous study has evaluated associations between PFAS exposure and arterial calcification.

Methods And Results: This study used data from 666 prediabetic adults enrolled in the Diabetes Prevention Program trial who had six PFAS quantified in plasma at baseline and two years after randomization, as well as measurements of coronary artery calcium (CAC) and ascending (AsAC) and descending (DAC) thoracic aortic calcification 13-14 years after baseline. We performed multinomial regression to test associations between PFAS and CAC categorized according to Agatston score [low (<10), moderate (11-400) and severe (>400)]. We used logistic regression to assess associations between PFAS and presence of AsAC and DAC. We adjusted models for baseline sex, age, BMI, race/ethnicity, cigarette smoking, education, treatment assignment (placebo or lifestyle intervention), and statin use. PFAS concentrations were similar to national means; 53.9% of participants had CAC > 11, 7.7% had AsAC, and 42.6% had DAC. Each doubling of the mean sum of plasma concentrations of linear and branched isomers of perfluorooctane sulfonic acid (PFOS) was associated with 1.49-fold greater odds (95% CI: 1.01, 2.21) of severe versus low CAC. This association was driven mainly by the linear (n-PFOS) isomer [1.54 (95% CI: 1.05, 2.25) greater odds of severe versus low CAC]. Each doubling of mean plasma N-ethyl-perfluorooctane sulfonamido acetic acid concentration was associated with greater odds of CAC in a dose-dependent manner [OR = 1.26 (95% CI:1.08, 1.47) for moderate CAC and OR = 1.37 (95% CI:1.07, 1.74) for severe CAC, compared to low CAC)]. Mean plasma PFOS and n-PFOS were also associated with greater odds of AsAC [OR = 1.67 (95% CI:1.10, 2.54) and OR = 1.70 (95% CI:1.13, 2.56), respectively], but not DAC. Other PFAS were not associated with outcomes.

Conclusions: Prediabetic adults with higher plasma concentrations of select PFAS had higher risk of coronary and thoracic aorta calcification. PFAS exposure may be a risk factor for adverse cardiovascular health among high-risk populations.
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http://dx.doi.org/10.1016/j.envint.2021.106446DOI Listing
June 2021

Associations between acute and long-term exposure to PM2.5 components and temperature with QT interval length in the VA Normative Aging Study.

Eur J Prev Cardiol 2021 Jan 20. Epub 2021 Jan 20.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue Building 1, Boston, Massachusetts 02115, USA.

Aims: Our study adds to the sparse literature on the effect of multiple fine particulate matter (PM2.5) components on QT interval length, an outcome with high clinical relevance in vulnerable populations. To our knowledge, this is the first study to examine the association between spatiotemporally resolved exposures to PM2.5 components and QT interval length.

Methods And Results: Among 578 men living in Eastern Massachusetts between 2000 and 2011, we utilized time-varying linear mixed-effects regressions with a random intercept to examine associations between acute (0-3 days), intermediate (4-28 days), and long-term (1 year) exposure to PM2.5 components, temperature, and heart-rate corrected QT interval (QTc). Each of the PM2.5 components and temperature was geocoded to the participant's residential address using validated ensemble and hybrid exposure models and gridMET predictions. We also evaluated whether diabetic status modified the association between PM2.5 components and QTc interval. We found consistent results that higher sulfate levels and colder temperatures were associated with significant longer QTc across all moving averages except the day of exposure. The greatest effect of sulfate and temperature was detected for the 28-day moving average. In the multi-pollutant model, each 1.5 µg/m3 IQR increase in daily sulfate was associated with a 15.1 ms [95% confidence interval (CI): 10.2-20.0] increase in QTc interval and in the single-pollutant models a 15.3 ms (95% CI: 11.6-19.1) increase in QTc interval. Other secondary particles, such as nitrate and organic carbon, also prolonged QT interval, while elemental carbon decreased QT interval. We found that diabetic status did not modify the association between PM2.5 components and QTc interval.

Conclusion: Acute and long-term exposure to PM2.5 components and temperature are associated with changes in ventricular repolarization as measured by QT interval.
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http://dx.doi.org/10.1093/eurjpc/zwaa161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289946PMC
January 2021

Perinatal granulopoiesis and risk of pediatric asthma.

Elife 2021 Feb 10;10. Epub 2021 Feb 10.

Department of Microbiology and Immunology, University of Illinois, Chicago, United States.

There are perinatal characteristics, such as gestational age, reproducibly associated with the risk for pediatric asthma. Identification of biologic processes influenced by these characteristics could facilitate risk stratification or new therapeutic targets. We hypothesized that transcriptional changes associated with multiple epidemiologic risk factors would be mediators of pediatric asthma risk. Using publicly available transcriptomic data from cord blood mononuclear cells, transcription of genes involved in myeloid differentiation was observed to be inversely associated with a pediatric asthma risk stratification based on multiple perinatal risk factors. This gene signature was validated in an independent prospective cohort and was specifically associated with genes localizing to neutrophil-specific granules. Further validation demonstrated that umbilical cord blood serum concentration of PGLYRP-1, a specific granule protein, was inversely associated with mid-childhood current asthma and early-teen FEV/FVCx100. Thus, neutrophil-specific granule abundance at birth predicts risk for pediatric asthma and pulmonary function in adolescence.
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http://dx.doi.org/10.7554/eLife.63745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889076PMC
February 2021

Associations between PM metal components and QT interval length in the Normative Aging Study.

Environ Res 2021 04 4;195:110827. Epub 2021 Feb 4.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States.

Background: Several studies have found associations between increases in QT interval length, a marker of cardiac electrical instability, and short-term fine particulate matter (PM) exposures. To our knowledge, this is the first study to examine the association between specific PM metal components and QT interval length.

Methods: We measured heart-rate corrected QT interval (QTc) duration among 630 participants in the Normative Aging Study (NAS) based in Eastern Massachusetts between 2000 and 2011. We utilized time-varying linear mixed-effects regressions with a random intercept for each participant to analyze associations between QTc interval and moving averages (0-7 day moving averages) of 24-h mean concentrations of PM metal components (vanadium, nickel, copper, zinc and lead) measured at the Harvard Supersite monitoring station. Models were adjusted for daily PM mass estimated at a 1 km × 1 km grid cell from a previously validated prediction model and other covariates. Bayesian kernel machine regression (BKMR) was utilized to assess the overall joint effect of the PM metal components.

Results: We found consistent results with higher lead (Pb) associated with significant higher QTc intervals for both the multi-pollutant and the two pollutant (PM mass and a PM component) models across the moving averages. The greatest effect of lead on QTc interval was detected for the 4-day moving average lead exposure. In the multi-pollutant model, each 2.72 ng/m increase in daily lead levels for a 4-day moving average was associated with a 7.91 ms (95% CI: 3.63, 12.18) increase in QTc interval. In the two-pollutant models with PM mass and lead, each 2.72 ng/m increase in daily lead levels for a 4-day moving average was associated with an 8.50 ms (95% CI: 4.59, 12.41) increase in QTc interval. We found that 4-day moving average of copper has a negative association with QTc interval when compared to the other PM metal components. In the multi-pollutant model, each 1.81 ng/m increase in daily copper levels for a 4-day moving average was associated with an -3.89 ms (95% CI: -6.98, -0.79) increase in QTc interval. Copper's essential function inside the human body could mediate its cardiotoxicity on cardiac conductivity and explain why we found that copper in comparison to the other metals was less harmful for QTc interval.

Conclusions: Exposure to metals contained in PM are associated with acute changes in ventricular repolarization as indicated by QT interval characteristics.
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http://dx.doi.org/10.1016/j.envres.2021.110827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987821PMC
April 2021

Chromosome 17q12-21 Variants Are Associated with Multiple Wheezing Phenotypes in Childhood.

Am J Respir Crit Care Med 2021 04;203(7):864-870

Asthma and Airway Disease Research Center.

Birth cohort studies have identified several temporal patterns of wheezing, only some of which are associated with asthma. Whether 17q12-21 genetic variants, which are closely associated with asthma, are also associated with childhood wheezing phenotypes remains poorly explored. To determine whether wheezing phenotypes, defined by latent class analysis (LCA), are associated with nine 17q12-21 SNPs and if so, whether these relationships differ by race/ancestry. Data from seven U.S. birth cohorts ( = 3,786) from the CREW (Children's Respiratory Research and Environment Workgroup) were harmonized to represent whether subjects wheezed in each year of life from birth until age 11 years. LCA was then performed to identify wheeze phenotypes. Genetic associations between SNPs and wheeze phenotypes were assessed separately in European American (EA) ( = 1,308) and, for the first time, in African American (AA) ( = 620) children. The LCA best supported four latent classes of wheeze: infrequent, transient, late-onset, and persistent. Odds of belonging to any of the three wheezing classes (vs. infrequent) increased with the risk alleles for multiple SNPs in EA children. Only one SNP, rs2305480, showed increased odds of belonging to any wheezing class in both AA and EA children. These results indicate that 17q12-21 is a "wheezing locus," and this association may reflect an early life susceptibility to respiratory viruses common to all wheezing children. Which children will have their symptoms remit or reoccur during childhood may be independent of the influence of rs2305480.
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http://dx.doi.org/10.1164/rccm.202003-0820OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017591PMC
April 2021

Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial.

Environ Int 2021 03 19;148:106375. Epub 2021 Jan 19.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. Electronic address:

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996-2002) trial and Outcomes Study (DPPOS, 2002-2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40-64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999-2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m lower eGFR (95% CI: -4.12, -0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.
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http://dx.doi.org/10.1016/j.envint.2020.106375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929640PMC
March 2021

Ambient Particle Components and Newborn Blood Pressure in Project Viva.

J Am Heart Assoc 2021 01 29;10(1):e016935. Epub 2020 Dec 29.

Department of Environmental Health Harvard School of Public Health Boston MA.

Background Both elemental metals and particulate air pollution have been reported to influence adult blood pressure (BP). The aim of this study is to examine which elemental components of particle mass with diameter ≤2.5 μm (PM) are responsible for previously reported associations between PM and neonatal BP. Methods and Results We studied 1131 mother-infant pairs in Project Viva, a Boston-area prebirth cohort. We measured systolic BP (SBP) and diastolic BP (DBP) at a mean age of 30 hours. We calculated average exposures during the 2 to 7 days before birth for the PM components-aluminum, arsenic, bromine, sulfur, copper, iron, zinc, nickel, vanadium, titanium, magnesium, potassium, silicon, sodium, chlorine, calcium, and lead-measured at the Harvard supersite. Adjusting for covariates and PM, we applied regression models to examine associations between PM components and median SBP and DBP, and used variable selection methods to select which components were more strongly associated with each BP outcome. We found consistent results with higher nickel associated with significantly higher SBP and DBP, and higher zinc associated with lower SBP and DBP. For an interquartile range increase in the log Z score (1.4) of nickel, we found a 1.78 mm Hg (95% CI, 0.72-2.84) increase in SBP and a 1.30 (95% CI, 0.54-2.06) increase in DBP. Increased zinc (interquartile range log Z score 1.2) was associated with decreased SBP (-1.29 mm Hg; 95% CI, -2.09 to -0.50) and DBP (-0.85 mm Hg; 95% CI: -1.42 to -0.29). Conclusions Our findings suggest that prenatal exposures to particulate matter components, and particularly nickel, may increase newborn BP.
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http://dx.doi.org/10.1161/JAHA.120.016935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955476PMC
January 2021

Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children.

medRxiv 2020 Nov 4. Epub 2020 Nov 4.

Background: Exposure to violence (ETV) or stress may cause asthma through unclear mechanisms.

Methods: Epigenome-wide association study (EWAS) of DNA methylation in nasal epithelium and four ETV or chronic stress measures in 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed measures of ETV or chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by P-value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).

Results: In the EWAS of stress/violence in EVA-PR, gun violence was associated with methylation of cg18961589 in (β=0.03, =1.28×10 ), and maternal stress was associated with methylation of cg03402351 in (β=0.04, =1.69×10 ) and cg19064846 in (β=0.03, =3.36×10 ). In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence in EVA-PR, CpGs in and were associated with atopic asthma at FDR- < 0.05.

Conclusions: ETV and chronic stress may increase the risk of atopic asthma through DNA methylation in airway epithelium, though this needs confirmation in future longitudinal studies.
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http://dx.doi.org/10.1101/2020.11.03.20225250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654924PMC
November 2020

Asthma Prevalence and Mold Levels in US Northeastern Schools.

J Allergy Clin Immunol Pract 2021 03 19;9(3):1312-1318. Epub 2020 Oct 19.

Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address:

Background: Asthma is among the most common chronic diseases of children in the United States (US). Mold exposures have been linked to asthma development and exacerbation. In homes, mold exposures have been quantified using the Environmental Relative Moldiness Index (ERMI), and higher home ERMI values have been linked to occupant asthma.

Objective: In this analysis of the School Inner-City Asthma Study (SICAS), we aimed to evaluate the ERMI's applicability to measuring mold in schools compared with homes and to examine the prevalence of asthma in relationship to students' demographics and the physical characteristics of school buildings.

Methods: Northeastern US schools (n = 32) and homes (n = 33) were selected, and the 36 ERMI molds were quantified in a dust sample from each classroom (n = 114) or home. School building characteristics data were collected from SICAS. Asthma prevalence and student demographics data were obtained from government websites. Linear regression and mixed models were fit to assess the association of the current asthma prevalence and physical characteristics of the school, make-up of the student body, and the ERMI metric.

Results: Levels of outdoor group 2 molds were significantly (P < .01) greater in schools compared with homes. The presence of air-conditioning in school buildings correlated significantly (P = .02) with lower asthma prevalence.

Conclusion: The prevalence of asthma in student bodies is associated with many factors in schools and homes.
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http://dx.doi.org/10.1016/j.jaip.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946701PMC
March 2021

DNA Methylation Architecture of the ACE2 gene in Nasal Cells.

medRxiv 2020 Sep 16. Epub 2020 Sep 16.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 enters cells via angiotensin-Converting Enzyme 2 (ACE2) receptors, highly expressed in nasal epithelium with parallel high infectivity.1,2 The nasal epigenome is in direct contact with the environment and could explain COVID-19 disparities by reflecting social and environmental influences on ACE2 regulation. We collected nasal swabs from anterior nares of 547 children, measured DNA methylation (DNAm), and tested differences at 15 ACE2 CpGs by sex, age, race/ethnicity and epigenetic age. ACE2 CpGs were differentially methylated by sex with 12 sites having lower DNAm (mean=12.71%) and 3 sites greater DNAm (mean=1.45%) among females relative to males. We observed differential DNAm at 5 CpGs for Hispanic females (mean absolute difference=3.22%) and lower DNAm at 8 CpGs for Black males (mean absolute difference=1.33%), relative to white participants. Longer DNAm telomere length was associated with greater ACE2 DNAm at 11 and 13 CpGs among males (mean absolute difference=7.86%) and females (mean absolute difference=8.21%), respectively. Nasal ACE2 DNAm differences could contribute to our understanding COVID-19 severity and disparities reflecting upstream environmental and social influences.
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http://dx.doi.org/10.1101/2020.08.25.20182105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523147PMC
September 2020
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