FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3136644480> ?p ?o ?g. }

• W3136644480 abstract "Vol. 129, No. 3 Research LetterOpen AccessExposure to Diesel Exhaust and Plasma Cortisol Response: A Randomized Double-Blind Crossover Study Errol M. Thomson, Alain Filiatreault, Andrew Williams, Christopher F. Rider, and Chris Carlsten Errol M. Thomson Address correspondence to Errol Thomson, Inhalation Toxicology Laboratory, Environmental Health Science and Research Bureau, Health Canada, 2203B Tunney’s Pasture, Ottawa, Ontario, K1A 0K9, Canada. Telephone: (613) 614-2994. Email: E-mail Address: [email protected] Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada Search for more papers by this author , Alain Filiatreault Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada Search for more papers by this author , Andrew Williams Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada Search for more papers by this author , Christopher F. Rider Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada Search for more papers by this author , and Chris Carlsten Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada Search for more papers by this author Published:26 March 2021CID: 037701https://doi.org/10.1289/EHP8923AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit IntroductionTraffic-related air pollution (TRAP) is associated with a variety of adverse health effects. Although a central role has been proposed for oxidative stress, elucidating underlying mechanisms remains an area of active investigation. Experimental work has demonstrated that glucocorticoid stress hormones are potential mediators of pulmonary and systemic pollutant effects of both particulate and gaseous pollutants (Thomson 2019), but direct evidence of TRAP-dependent stress axis activation is lacking. Moreover, although oxidative stress is a regulator of glucocorticoid signaling (Okamoto et al. 1999), involvement in pollutant-induced stress axis activation is unknown. In population studies, nitrogen dioxide was associated with a flattened salivary cortisol profile in adolescents (Wing et al. 2018) and higher awakening cortisol and flattened profile in 45 to 85-y-old adults (Hajat et al. 2019), suggesting potential TRAP-related impacts. The present study evaluated whether short-term exposure to diesel exhaust increases plasma cortisol levels and considered effect modification by sex, asthma status, antioxidant gene variants, and antioxidant treatment.MethodsThe study was approved by the University of British Columbia, Vancouver Coastal Health Research Institute, and Health Canada ethics review boards, and registered at clinicaltrials.gov (trial NCT01699204). Each participant provided written informed consent. Study details, including exclusion criteria, diet and medications, questionnaires, assessment of airway hyperresponsiveness, and genotyping, are provided elsewhere (Carlsten et al. 2014). In brief, study participants [n=19; mean age 28 (range 19–46), 14 with doctor-diagnosed asthma (7 females, 7 males), and 5 without (3 females, 2 males); all free from current use of inhaled corticosteroids or long-acting β2 agonists, from regular use of bronchodilators, and from vitamin A, C, or E supplementation] took N-acetylcysteine (NAC; 600mg) or placebo capsules three times daily for 6 d. On day 6, participants were exposed for 2 h to filtered air or diesel exhaust, producing three experimental conditions [filtered air with placebo (FAP), diesel exhaust with placebo (DEP), and diesel exhaust with NAC (DEN)], using a randomized, double-blind, crossover design that included a minimum 2-wk washout period between exposures. The protocol is nearly identical to another in which analysis of questionnaires demonstrated that participants were effectively blinded to exposures (Carlsten et al. 2013). Diesel exhaust was generated using a 6.0-kW diesel generator operated to simulate on-road emissions and diluted to maintain a nominal particulate concentration of 300 μg/m3 [fine particulate matter (PM) with aerodynamic diameter less than or equal to 2.5μm (PM2.5); mass median aerodynamic diameter of 102.5±14 nm)]. Blood was collected by venipuncture into EDTA tubes 18 h prior to exposure, immediately before exposure (0 h), and at 2, 6, and 30 h. Plasma was assessed in duplicate using Arbor Assays cortisol enzyme immunoassay kits (Cedarlane Laboratories Canada). Blood samples from each volunteer underwent polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis to measure the variant status of two present/null alleles (GSTM1, GSTT1; coded as 0 or 1 for null), and three single-nucleotide polymorphisms [SNPs; (GSTP1 rs1695; NFκB1 rs28362491; NQO1 rs1800566; coded as 0, 1, or 2 for homozygous risk variant)]. Genetic risk scores were generated using unweighted summation of null and risk alleles. Data were divided into high (4–6) and low (0–3) risk scores based on the median value. A generalized estimating equation approach was used to analyze the data using geepack library (version 1.3-1) in the R software (R Development Core Team) environment (Højsgaard et al. 2005). Cortisol levels were logarithmically transformed and analyzed, assuming a normal distribution and an exchangeable correlation structure. Results were back-transformed, and the delta method was used to approximate the standard error for the estimates, with Holm-Sidak adjustment to control the familywise error rate.Results and DiscussionShort-term exposure to diesel exhaust rapidly and transiently increased plasma cortisol levels (Exposure×Time interaction; p<0.0001; DEP vs. FAP at 2 h; p=0.04; Figure 1). The relative increase in cortisol during exposure to diesel exhaust compared with filtered air was similar in males and females and was observed primarily in those diagnosed with asthma or with gene deletions or polymorphisms in antioxidant genes (Figure 2).Figure 1. Time course of plasma cortisol response to exposure. Participants (n=19) took the antioxidant NAC or placebo capsules three times daily for 6 d, followed by a 2-h inhalation exposure, leading to the following three experimental conditions: FAP, DEP, and DEN. Plasma cortisol was repeatedly measured pre- and post exposure at the times indicated. Data were assessed using a generalized estimating equation and adjusted according to the Holm-Sidak approach. Results are presented with 95% confidence intervals. Statistical significance is displayed for comparisons of treatments within a given time point. Note: DEN, diesel exhaust with NAC; DEP, diesel exhaust with placebo; FAP, filtered air with placebo; NAC, N-acetylcysteine.Figure 2. Cortisol response to exposure according to sex, asthma diagnosis, GSTM1 status (present or null) and GS (high or low). The change (delta) in log cortisol levels from 0 to 2-h time points for DEP or DEN exposures was compared to the delta over that same period for the FAP exposure. Analyses were conducted using the generalized estimating equation approach and adjusted according to the Holm-Sidak multiple comparison procedure. Results are presented with 95% confidence intervals. Statistical significance is indicated relative to the FAP exposure. DEN vs. DEP comparisons were all nonsignificant and for simplicity are not shown here. Note: DEN, diesel exhaust with NAC; DEP, diesel exhaust with placebo; FAP, filtered air with placebo; GS, genetic risk score; NAC, N-acetylcysteine.The data show that exposure to diesel exhaust affects levels of an important stress hormone with wide-ranging systemic effects, substantiating a role for cortisol as a potential mediator of TRAP-dependent health effects and providing support under controlled conditions for epidemiological associations between TRAP and cortisol. The variation in cortisol response to diesel exhaust across participants was in line with known variation in response to acute stressors within the population according to factors including age, genetic variability, disease, and chronic stress (Rohleder et al. 2003). Although genetic variability in antioxidant genes was associated with the magnitude of cortisol response, treatment with the antioxidant NAC tended to reduce, but did not eliminate, the diesel exhaust-dependent increase. It is unclear whether this reflects insufficient antioxidant supplementation to block effects, lack of involvement of oxidative stress in the response, or inadequate power to detect effect modification. Although contrasting with the hyporesponsiveness to psychosocial stressors of individuals with asthma, the heightened cortisol response to diesel exhaust in participants with asthma is similar to the greater cortisol response to inhaled allergen challenge produced in people with asthma (Peebles et al. 2000). Notwithstanding the association of asthma diagnosis with increased cortisol response, degree of airway hyperresponsiveness was not significantly associated with differential cortisol response to diesel exhaust (r=−0.083; p=0.77). The variability in cortisol responses to diesel exhaust seen here in relation to individual characteristics may have relevance to individual risk of local and systemic health effects of air pollutants (Thomas et al. 2018; Thomson 2019).LimitationsAlthough the crossover design is statistically powerful, the study may nevertheless be underpowered to detect effect modification. Participants were predominantly young and had asthma; it is unknown whether effects would manifest similarly in other populations. Despite the washout period between exposures, participants will have been exposed to TRAP elsewhere, which could condition responses. Finally, although we assessed antioxidant genes, other genetic variation could also influence cortisol responses.AcknowledgmentsThis work was supported by Health Canada through the Clean Air Regulatory Agenda and the Addressing Air Pollution Horizontal Initiative. The work was also supported by AllerGen NCE, the British Columbia Lung Association, the Canada Research Chairs program, the Canadian Institutes of Health Research, Mitacs (through the Mitacs-Accelerate program), and the Michael Smith Foundation for Health Research. The authors thank G. Mallach and P. Blagden for helpful comments during presubmission review of the manuscript.ReferencesCarlsten C, MacNutt MJ, Zhang Z, Sava F, Pui MM. 2014. Anti-oxidant N-acetylcysteine diminishes diesel exhaust-induced increased airway responsiveness in person with airway hyper-reactivity. Toxicol Sci 139(2):479–487, PMID: 24814479, 10.1093/toxsci/kfu040. Crossref, Medline, Google ScholarCarlsten C, Oron AP, Curtiss H, Jarvis S, Daniell W, Kaufman JD. 2013. Symptoms in response to controlled diesel exhaust more closely reflect exposure perception than true exposure. PLoS One 8(12):e83573, PMID: 24358296, 10.1371/journal.pone.0083573. Crossref, Medline, Google ScholarHajat A, Hazlehurst MF, Golden SH, Merkin SS, Seeman T, Szpiro AA, et al.2019. The cross-sectional and longitudinal association between air pollution and salivary cortisol: evidence from the Multi-Ethnic Study of Atherosclerosis. Environ Int 131:105062, PMID: 31491811, 10.1016/j.envint.2019.105062. Crossref, Medline, Google ScholarHøjsgaard S, Halekoh U, Yan J. 2005. The R package geepack for generalized estimating equations. J Stat Soft 15(2):1–11, 10.18637/jss.v015.i02. Crossref, Google ScholarOkamoto K, Tanaka H, Ogawa H, Makino Y, Eguchi H, Hayashi S, et al.1999. Redox-dependent regulation of nuclear import of the glucocorticoid receptor. J Biol Chem 274(15):10363–10371, PMID: 10187825, 10.1074/jbc.274.15.10363. Crossref, Medline, Google ScholarPeebles RS, Togias A, Bickel CA, Diemer FB, Hubbard WC, Schleimer RP. 2000. Endogenous glucocorticoids and antigen-induced acute and late phase pulmonary responses. Clin Exp Allergy 30(9):1257–1265, PMID: 10971472, 10.1046/j.1365-2222.2000.00890.x. Crossref, Medline, Google ScholarRohleder N, Wolf JM, Kirschbaum C. 2003. Glucocorticoid sensitivity in humans-interindividual differences and acute stress effects. Stress 6(3):207–222, PMID: 13129814, 10.1080/1025389031000153658. Crossref, Medline, Google ScholarThomas J, Guénette J, Thomson EM. 2018. Stress axis variability is associated with differential ozone-induced lung inflammatory signaling and injury biomarker response. Environ Res 167:751–758, PMID: 30236519, 10.1016/j.envres.2018.09.007. Crossref, Medline, Google ScholarThomson EM. 2019. Air pollution, stress, and allostatic load: linking systemic and central nervous system impacts. J Alzheimers Dis 69(3):597–614, PMID: 31127781, 10.3233/JAD-190015. Crossref, Medline, Google ScholarWing SE, Bandoli G, Telesca D, Su JG, Ritz B. 2018. Chronic exposure to inhaled, traffic-related nitrogen dioxide and a blunted cortisol response in adolescents. Environ Res 163:201–207, PMID: 29454852, 10.1016/j.envres.2018.01.011. Crossref, Medline, Google ScholarThe authors declare they have no actual or potential competing financial interests.FiguresReferencesRelatedDetails Vol. 129, No. 3 March 2021Metrics About Article Metrics Publication History Manuscript received5 January 2021Manuscript revised19 February 2021Manuscript accepted10 March 2021Originally published26 March 2021 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days." @default.
• W3136644480 created "2021-03-29" @default.
• W3136644480 creator A5009909921 @default.
• W3136644480 creator A5013456973 @default.
• W3136644480 creator A5038066341 @default.
• W3136644480 creator A5044032784 @default.
• W3136644480 creator A5087671250 @default.
• W3136644480 date "2021-03-01" @default.
• W3136644480 modified "2023-09-25" @default.
• W3136644480 title "Exposure to Diesel Exhaust and Plasma Cortisol Response: A Randomized Double-Blind Crossover Study" @default.
• W3136644480 cites W1950067960 @default.
• W3136644480 cites W2045557277 @default.
• W3136644480 cites W2055432096 @default.
• W3136644480 cites W2078592237 @default.
• W3136644480 cites W2137854065 @default.
• W3136644480 cites W2335228305 @default.
• W3136644480 cites W2791164660 @default.
• W3136644480 cites W2891411499 @default.
• W3136644480 cites W2945980358 @default.
• W3136644480 cites W2968910851 @default.
• W3136644480 doi "https://doi.org/10.1289/ehp8923" @default.
• W3136644480 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7997608" @default.
• W3136644480 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33769847" @default.
• W3136644480 hasPublicationYear "2021" @default.
• W3136644480 type Work @default.
• W3136644480 sameAs 3136644480 @default.
• W3136644480 citedByCount "7" @default.
• W3136644480 countsByYear W31366444802021 @default.
• W3136644480 countsByYear W31366444802022 @default.
• W3136644480 countsByYear W31366444802023 @default.
• W3136644480 crossrefType "journal-article" @default.
• W3136644480 hasAuthorship W3136644480A5009909921 @default.
• W3136644480 hasAuthorship W3136644480A5013456973 @default.
• W3136644480 hasAuthorship W3136644480A5038066341 @default.
• W3136644480 hasAuthorship W3136644480A5044032784 @default.
• W3136644480 hasAuthorship W3136644480A5087671250 @default.
• W3136644480 hasBestOaLocation W31366444801 @default.
• W3136644480 hasConcept C126322002 @default.
• W3136644480 hasConcept C134018914 @default.
• W3136644480 hasConcept C138171918 @default.
• W3136644480 hasConcept C142724271 @default.
• W3136644480 hasConcept C168563851 @default.
• W3136644480 hasConcept C178790620 @default.
• W3136644480 hasConcept C185592680 @default.
• W3136644480 hasConcept C204787440 @default.
• W3136644480 hasConcept C27081682 @default.
• W3136644480 hasConcept C3432839 @default.
• W3136644480 hasConcept C71924100 @default.
• W3136644480 hasConcept C87813604 @default.
• W3136644480 hasConceptScore W3136644480C126322002 @default.
• W3136644480 hasConceptScore W3136644480C134018914 @default.
• W3136644480 hasConceptScore W3136644480C138171918 @default.
• W3136644480 hasConceptScore W3136644480C142724271 @default.
• W3136644480 hasConceptScore W3136644480C168563851 @default.
• W3136644480 hasConceptScore W3136644480C178790620 @default.
• W3136644480 hasConceptScore W3136644480C185592680 @default.
• W3136644480 hasConceptScore W3136644480C204787440 @default.
• W3136644480 hasConceptScore W3136644480C27081682 @default.
• W3136644480 hasConceptScore W3136644480C3432839 @default.
• W3136644480 hasConceptScore W3136644480C71924100 @default.
• W3136644480 hasConceptScore W3136644480C87813604 @default.
• W3136644480 hasIssue "3" @default.
• W3136644480 hasLocation W31366444801 @default.
• W3136644480 hasLocation W31366444802 @default.
• W3136644480 hasOpenAccess W3136644480 @default.
• W3136644480 hasPrimaryLocation W31366444801 @default.
• W3136644480 hasRelatedWork W1966504330 @default.
• W3136644480 hasRelatedWork W1966775726 @default.
• W3136644480 hasRelatedWork W1979139803 @default.
• W3136644480 hasRelatedWork W1991560548 @default.
• W3136644480 hasRelatedWork W2030889776 @default.
• W3136644480 hasRelatedWork W2037631372 @default.
• W3136644480 hasRelatedWork W2040058909 @default.
• W3136644480 hasRelatedWork W2132898409 @default.
• W3136644480 hasRelatedWork W2748952813 @default.
• W3136644480 hasRelatedWork W4249176446 @default.
• W3136644480 hasVolume "129" @default.
• W3136644480 isParatext "false" @default.
• W3136644480 isRetracted "false" @default.
• W3136644480 magId "3136644480" @default.
• W3136644480 workType "article" @default.