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Respiratory Research
Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Research

Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children

Authors: Kyung Hwa Jung, David Torrone, Stephanie Lovinsky-Desir, Matthew Perzanowski, Joshua Bautista, Jacqueline R. Jezioro, Lori Hoepner, Jamie Ross, Frederica P. Perera, Steven N. Chillrud, Rachel L. Miller

Published in: Respiratory Research | Issue 1/2017

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Abstract

Background

Both short and long-term exposure to traffic-related air pollutants have been associated with asthma and reduced lung function. We hypothesized that short-term indoor exposure to fine particulate matter <2.5 μm (PM2.5) and vanadium (V) would be associated with altered buccal cell DNA methylation of targeted asthma genes and decreased lung function among urban children in a nested subcohort of African American and Dominican children.

Methods

Six day integrated levels of air pollutants were measured from children’s homes (age 9–14; n = 163), repeated 6 months later (n = 98). Buccal samples were collected repeatedly during visits. CpG promoter loci of asthma genes (i.e., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A), arginase 2 (ARG2)) were pyrosequenced and lung function was assessed.

Results

Exposure to V, but not PM2.5, was associated with lower DNA methylation of IL4 and IFNγ. In exploratory analyses, V levels were associated with lower methylation of the proinflammatory NOS2A-CpG+5099 among asthmatic overweight or obese children but not nonasthmatics. Short-term exposure to PM2.5, but not V, appeared associated with lower lung function (i.e., reduced z-scores for forced expiratory volume in one second (FEV1, FEV1/ forced vital capacity [FEV1/FVC] and forced expiratory flow at 25–75% of FVC [FEF25–75]).

Conclusions

Exposure to V was associated with altered DNA methylation of allergic and proinflammatory asthma genes implicated in air pollution related asthma. However, short-term exposure to PM2.5, but not V, appeared associated with decrements in lung function among urban children.
Appendix
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Literature
1.
Pope III C, Dockery D. Health effects of fine particulate air pollution: lines that connect. J Air Waste Manage Assoc. 2006;56:709–42.CrossRef
2.
Jung KH, Hsu SI, Yan B, Moors K, Chillrud SN, Ross J, Wang S, Perzanowski MS, Kinney PL, Whyatt RM. Childhood exposure to fine particulate matter and black carbon and the development of new wheeze between ages 5 and 7 in an urban prospective cohort. Environ Int. 2012;45:44–50.CrossRefPubMedPubMedCentral
3.
Gehring U, Gruzieva O, Agius RM, Beelen R, Custovic A, Cyrys J, Eeftens M, Flexeder C, Fuertes E, Heinrich J. Air pollution exposure and lung function in children: the ESCAPE project. Environmental Health Perspectives (Online). 2013;121:1357.
4.
Rice MB, Ljungman PL, Wilker EH, Gold DR, Schwartz JD, Koutrakis P, Washko GR, O’Connor GT, Mittleman MA. Short-term exposure to air pollution and lung function in the Framingham Heart Study. Am J Respir Crit Care Med. 2013;188:1351–7.CrossRefPubMedPubMedCentral
5.
Götschi T, Heinrich J, Sunyer J, Künzli N. Long-term effects of ambient air pollution on lung function: a review. Epidemiology. 2008;19:690–701.CrossRefPubMed
6.
Peltier RE, Lippmann M. Residual oil combustion: 2. Distributions of airborne nickel and vanadium within New York City. J Expo Sci Environ Epidemiol. 2010;20:342–50.CrossRefPubMed
7.
Lough GC, Schauer JJ, Park J-S, Shafer MM, DeMinter JT, Weinstein JP. Emissions of metals associated with motor vehicle roadways. Environ Sci Technol. 2005;39:826–36.CrossRefPubMed
8.
9.
Maciejczyk P, Chen LC. Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice: VIII. Source-related daily variations in in vitro responses to CAPs. Inhal Toxicol. 2005;17:243–53.CrossRefPubMed
10.
Bell ML, Ebisu K, Peng RD, Samet JM, Dominici F. Hospital Admissions and Chemical Composition of Fine Particle Air Pollution. Am J Respir Crit Care Med. 2009;179:1115.CrossRefPubMedPubMedCentral
11.
Dominici F, Peng RD, Ebisu K, Zeger SL, Samet JM, Bell ML. Does the effect of PM10 on mortality depend on PM nickel and vanadium content? A reanalysis of the NMMAPS data. Environ Health Perspect. 2007;1701–1703.
12.
Patel M, Hoepner L, Garfinkel R, Chillrud S, Reyes A, Quinn J, Perera F, Miller R. Ambient Metals, Elemental Carbon, and Wheeze and Cough in New York City Children through Age 24 Months. Am J Respir Crit Care Med. 2009;180:1107–13.CrossRefPubMedPubMedCentral
13.
Habre R, Fruin S, Gauderman J, Lurmann F, Gilliland F, McConnell R, Urman R. Exposure To Transition Metals In Particulate Matter Air Pollution And Children’s Lung Function In The Southern California Children’s Health Study. In B15 HEALTH EFFECTS OF INDOOR/OUTDOOR POLLUTION IN CHILDHOOD. Am Thoracic Soc; 2016: A2873-A2873
14.
Alexeeff SE, Litonjua AA, Suh H, Sparrow D, Vokonas PS, Schwartz J. Ozone exposure and lung function: effect modified by obesity and airways hyperresponsiveness in the VA normative aging study. CHEST Journal. 2007;132:1890–7.CrossRef
15.
Dubowsky SD, Suh H, Schwartz J, Coull BA, Gold DR. Diabetes, obesity, and hypertension may enhance associations between air pollution and markers of systemic inflammation. Environ Health Perspect. 2006;992–998.
16.
Lu KD, Breysse PN, Diette GB, Curtin-Brosnan J, Aloe C, Williams D, Peng RD, McCormack MC, Matsui EC. Being overweight increases susceptibility to indoor pollutants among urban children with asthma. J Allergy Clin Immunol. 2013;131:1017–23.CrossRefPubMedPubMedCentral
17.
Jung KH, Perzanowski M, Rundle A, Moors K, Yan B, Chillrud SN, Whyatt R, Camann D, Perera FP, Miller RL. Polycyclic aromatic hydrocarbon exposure, obesity and childhood asthma in an urban cohort. Environ Res. 2014;128:35–41.CrossRefPubMed
18.
19.
Rossnerova A, Tulupova E, Tabashidze N, Schmuczerova J, Dostal M, Rossner Jr P, Gmuender H, Sram RJ. Factors affecting the 27 K DNA methylation pattern in asthmatic and healthy children from locations with various environments. Mutat Res Fundam Mol Mech Mutagen. 2013;741:18–26.CrossRef
20.
Salam MT, Byun H-M, Lurmann F, Breton CV, Wang X, Eckel SP, Gilliland FD. Genetic and epigenetic variations in inducible nitric oxide synthase promoter, particulate pollution, and exhaled nitric oxide levels in children. J Allergy Clin Immunol. 2012;129:232–9. e237.CrossRefPubMed
21.
Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J, Tager I. Ambient air pollution impairs regulatory T-cell function in asthma. J Allergy Clin Immunol. 2010;126:845–52. e810.CrossRefPubMed
22.
Magari SR, Schwartz J, Williams PL, Hauser R, Smith TJ, Christiani DC. The association of particulate air metal concentrations with heart rate variability. Environ Health Perspect. 2002;110:875.CrossRefPubMedPubMedCentral
23.
Fan T, Fang SC, Cavallari JM, Barnett IJ, Wang Z, Su L, Byun H-M, Lin X, Baccarelli AA, Christiani DC. Heart rate variability and DNA methylation levels are altered after short-term metal fume exposure among occupational welders: a repeated-measures panel study. BMC Public Health. 2014;14:1.CrossRef
24.
Liu J, Ballaney M, Al-alem U, Quan C, Jin X, Perera F, Chen L-C, Miller RL. Combined inhaled diesel exhaust particles and allergen exposure alter methylation of T helper genes and IgE production in vivo. Toxicol Sci. 2008;102:76–81.CrossRefPubMed
25.
Breton CV, Byun H-M, Wang X, Salam MT, Siegmund K, Gilliland FD. DNA methylation in the arginase–nitric oxide synthase pathway is associated with exhaled nitric oxide in children with asthma. Am J Respir Crit Care Med. 2011;184:191–7.CrossRefPubMedPubMedCentral
26.
Yang IV, Pedersen BS, Liu A, O’connor GT, Teach SJ, Kattan M, Misiak RT, Gruchalla R, Steinbach SF, Szefler SJ. DNA methylation and childhood asthma in the inner city. J Allergy Clin Immunol. 2015;136:69–80.CrossRefPubMedPubMedCentral
27.
Tarantini L, Bonzini M, Apostoli P, Pegoraro V, Bollati V, Marinelli B, Cantone L, Rizzo G, Hou L, Schwartz J. Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation. Environ Health Perspect. 2009;117:217.CrossRefPubMed
28.
Bhutani M, Pathak AK, Fan Y-H, Liu DD, Lee JJ, Tang H, Kurie JM, Morice RC, Kim ES, Hong WK. Oral epithelium as a surrogate tissue for assessing smoking-induced molecular alterations in the lungs. Cancer Prev Res. 2008;1:39–44.CrossRef
29.
Richmond R, Simpkin A, Woodward G, Gaunt T, Lyttleton O, McArdle W, Ring S, Smith A, Timpson N, Tilling K, et al. Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC). Hum Mol Genet. 2015;24:8.CrossRef
30.
Murphy S, Adigun A, Huang Z, Overcash F, Wang F, Jirtle R, Schildkraut J, Murtha A, Iversen E, Hoyo C. Gender-specific methylation differences in relation to prenatal exposure to cigarette smoke. Gene. 2012;494:36–43.CrossRefPubMed
31.
Michel S, Busato F, Genuneit J, Pekkanen J, Dalphin J, Riedler J, Mazaleyrat N, Weber J, Karvonen A, Hirvonen M, et al. Farm exposure and time trends in early childhood may influence DNA methylation in genes related to asthma and allergy. Allergy. 2013;68:355–64.CrossRefPubMed
32.
Clifford RL, Jones MJ, MacIsaac JL, McEwen LM, Goodman SJ, Mostafavi S, Kobor MS, Carlsten C. Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation. J Allergy Clin Immunol. 2017;139:112–21.CrossRefPubMed
33.
Perera FP, Illman SM, Kinney PL, Whyatt RM, Kelvin EA, Shepard P, Evans D, Fullilove M, Ford J, Miller RL, et al. The challenge of preventing environmentally related disease in young children: community-based research in New York City. Environ Health Perspect. 2002;110:197–204.CrossRefPubMedPubMedCentral
34.
Donohue KM, Miller RL, Perzanowski MS, Just AC, Hoepner LA, Arunajadai S, Canfield S, Resnick D, Calafat AM, Perera FP. Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children. J Allergy Clin Immunol. 2013;131:736–42. e736.CrossRefPubMedPubMedCentral
35.
CfDCa P. A SAS Program for the CDC Growth Charts. Atlanta, GA: Centers for Disease Control and Prevention; 2004.
36.
Jelena J, Baltic Z, Milica G, Jelena I, Marija B, Milka P, Mirjana L. Relationship between Body Mass Index and Body Fat Percentage among Adolescents from Serbian Republic. Journal of Childhood Obesity. 2016.
37.
Spolidoro JV, Pitrez Filho ML, Vargas LT, Santana JC, Pitrez E, Hauschild JA, Bruscato NM, Moriguchi EH, Medeiros AK, Piva JP. Waist circumference in children and adolescents correlate with metabolic syndrome and fat deposits in young adults. Clin Nutr. 2013;32:93–7.CrossRefPubMed
38.
Blanchard CL, Tanenbaum S, Lawson DR. Differences between weekday and weekend air pollutant levels in Atlanta; Baltimore; Chicago; Dallas–Fort Worth; Denver; Houston; New York; Phoenix; Washington, DC; and surrounding areas. J Air Waste Manage Assoc. 2008;58:1598–615.CrossRef
39.
Kinney PL, Chillrud SN, Ramstrom S, Ross J, Spengler JD. Exposures to multiple air toxics in New York City. Environ Health Perspect. 2002;110 Suppl 4:539–46.CrossRefPubMedPubMedCentral
40.
Suresh V, Mih JD, George SC. Measurement of IL-13–Induced iNOS-Derived Gas Phase Nitric Oxide in Human Bronchial Epithelial Cells. Am J Respir Cell Mol Biol. 2007;37:97–104.CrossRefPubMedPubMedCentral
41.
Cornell AG, Chillrud SN, Mellins RB, Acosta LM, Miller RL, Quinn JW, Yan B, Divjan A, Olmedo OE, Lopez-Pintado S. Domestic airborne black carbon and exhaled nitric oxide in children in NYC. J Expo Sci Environ Epidemiol. 2012;22:258–66.CrossRefPubMedPubMedCentral
42.
Stafoggia M, Schwartz J, Forastiere F, Perucci C. Does temperature modify the association between air pollution and mortality? A multicity case-crossover analysis in Italy. Am J Epidemiol. 2008;167:1476–85.CrossRefPubMed
43.
Nawrot T, Torfs R, Fierens F, De Henauw S, Hoet P, Van Kersschaever G, De Backer G, Nemery B. Stronger associations between daily mortality and fine particulate air pollution in summer than in winter: evidence from a heavily polluted region in western Europe. J Epidemiol Community Health. 2007;61:146–9.CrossRefPubMedPubMedCentral
44.
Vidal AC, Semenova V, Darrah T, Vengosh A, Huang Z, King K, Nye MD, Fry R, Skaar D, Maguire R. Maternal cadmium, iron and zinc levels. DNA methylation and birth weight BMC Pharmacology and Toxicology. 2015;16:1.
45.
Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159:702–6.CrossRefPubMed
46.
Rastogi D, Suzuki M, Greally JM. Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma. Sci Rep. 2013;3.
47.
Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MS, Zheng J. Multi-ethnic reference values for spirometry for the 3–95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012;2012(40):1324–43.CrossRef
48.
Strachan P, Medarov BI. Seasonal variation in lung function. CHEST Journal. 2005;128:173S-a-173S.
49.
Lovinsky-Desir S, Ridder R, Torrone D, Maher C, Narula S, Scheuerman M, Merle D, Kattan M, DiMango E, Miller RL. DNA methylation of the allergy regulatory gene interferon gamma varies by age, sex, and tissue type in asthmatics. Clin Epigenetics. 2014;6:1.CrossRef
50.
Torrone DZ, Kuriakose JS, Moors K, Jiang H, Niedzwiecki M, Perera F, Miller RL. Reproducibility and intraindividual variation over days in buccal cell DNA methylation of two asthma genes, interferon γ (IFNγ) and inducible nitric oxide synthase (iNOS). Clin Epigenetics. 2012;4:1.CrossRef
51.
Chen R, Qiao L, Li H, Zhao Y, Zhang Y, Xu W, Wang C, Wang H, Zhao Z, Xu X. Fine particulate matter constituents, nitric oxide synthase DNA methylation and exhaled nitric oxide. Environ Sci Technol. 2015;49:11859–65.CrossRefPubMed
52.
Kile ML, Fang S, Baccarelli AA, Tarantini L, Cavallari J, Christiani DC. A panel study of occupational exposure to fine particulate matter and changes in DNA methylation over a single workday and years worked in boilermaker welders. Environ Health. 2013;12:1.CrossRef
53.
Collison A, Siegle JS, Hansbro NG, Kwok C-T, Herbert C, Mattes J, Hitchins M, Foster PS, Kumar RK. Epigenetic changes associated with disease progression in a mouse model of childhood allergic asthma. Dis Model Mech. 2013;6:993–1000.CrossRefPubMedPubMedCentral
54.
55.
Zhang Y, Rohde C, Tierling S, Jurkowski TP, Bock C, Santacruz D, Ragozin S, Reinhardt R, Groth M, Walter J. DNA methylation analysis of chromosome 21 gene promoters at single base pair and single allele resolution. PLoS Genet. 2009;5:e1000438.CrossRefPubMedPubMedCentral
56.
Wills-Karp M, Ewart SL. The genetics of allergen-induced airway hyperresponsiveness in mice. Am J Respir Crit Care Med. 1997;156:S89–96.CrossRefPubMed
57.
Cui J, Pazdziorko S, Miyashiro JS, Thakker P, Pelker JW, DeClercq C, Jiao A, Gunn J, Mason L, Leonard JP. T H 1-mediated airway hyperresponsiveness independent of neutrophilic inflammation. J Allergy Clin Immunol. 2005;115:309–15.CrossRefPubMed
58.
Losana G, Bovolenta C, Rigamonti L, Borghi I, Altare F, Jouanguy E, Forni G, Casanova J-L, Sherry B, Mengozzi M. IFN-γ and IL-12 differentially regulate CC-chemokine secretion and CCR5 expression in human T lymphocytes. J Leukoc Biol. 2002;72:735–42.PubMed
59.
Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, Shuai K. Specific inhibition of Stat3 signal transduction by PIAS3. Science. 1997;278:1803–5.CrossRefPubMed
60.
Eljaafari A, Robert M, Chehimi M, Chanon S, Durand C, Vial G, Bendridi N, Madec A-M, Disse E, Laville M. Adipose tissue–derived stem cells from obese subjects contribute to inflammation and reduced insulin response in adipocytes through differential regulation of the Th1/Th17 balance and monocyte activation. Diabetes. 2015;64:2477–88.CrossRefPubMed
61.
Eeftens M, Hoek G, Gruzieva O, Mölter A, Agius R, Beelen R, Brunekreef B, Custovic A, Cyrys J, Fuertes E. Elemental composition of particulate matter and the association with lung function. Epidemiology. 2014;25:648–57.CrossRefPubMed
62.
Sormani G, Haerter JO, Lövkvist C, Sneppen K. Stabilization of epigenetic states of CpG islands by local cooperation. Mol Biosyst. 2016.
63.
Spivack SD, Hurteau GJ, Jain R, Kumar SV, Aldous KM, Gierthy JF, Kaminsky LS. Gene-environment interaction signatures by quantitative mRNA profiling in exfoliated buccal mucosal cells. Cancer Res. 2004;64:6805–13.CrossRefPubMed
64.
Kumar SV, Jain R, Mokhiber K, Venezia A, Sheehan A, Spivack SD. Exfoliated buccal and microdissected lung cell expression of antioxidant enzymes. Cancer Detect Prev. 2005;29:552–61.CrossRefPubMed
65.
Brody JG, Morello-Frosch R, Zota A, Brown P, Pérez C, Rudel RA. Linking exposure assessment science with policy objectives for environmental justice and breast cancer advocacy: The Northern California Household Exposure Study. Am J Public Health. 2009;99:S600–9.CrossRefPubMedPubMedCentral
66.
Jung KH, Patel MM, Moors K, Kinney PL, Chillrud SN, Whyatt R, Hoepner L, Garfinkel R, Yan B. Effects of heating season on residential indoor and outdoor polycyclic aromatic hydrocarbons, black carbon, and particulate matter in an urban birth cohort. Atmos Environ. 2010;44:4545–52.CrossRefPubMedCentral
Metadata
Title
Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children
Authors
Kyung Hwa Jung
David Torrone
Stephanie Lovinsky-Desir
Matthew Perzanowski
Joshua Bautista
Jacqueline R. Jezioro
Lori Hoepner
Jamie Ross
Frederica P. Perera
Steven N. Chillrud
Rachel L. Miller
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-017-0550-9

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