Inhalation Exposure Core

The mission of the Inhalation Exposure Core is to provide a specialized scientific resource for the assessment of health impacts resulting from inhaled environmental constituents and evaluation of therapeutics for the mitigation of cardiorespiratory disease while serving as an educational resource for the technology comprising this service.  The Inhalation Exposure Core encompasses state-of-the-art facilities for the short- and long-term generation of precisely controlled atmospheres and delivery to both in vitro and in vivo laboratory animal models under the guidance of CNPRC Core and Affiliate Scientists. The Inhalation Exposure Core also supports the assessment of cardiorespiratory function and bronchoscopic collection of lung specimens for in vivo disease characterization, as well as response to clinical and preclinical therapeutics.

  • Inhalation Toxicology Expertise
  • Large In Vivo and In Vitro Exposure Capacity
  • Aerosol Generation and Characterization
  • Major Gaseous Pollutant Generation and Monitoring
  • Pulmonary Function Testing and Bronchoscopy Suite
  • GLP Study Capabilities
  • Project, Data, and Sample Management
  • Inhaled Therapeutic Trials
  • Adult Allergic Asthma
  • Adult Non-Allergic (Intrinsic) Asthma
  • Pediatric Allergic Asthma
  • Air Pollution (Ozone, PM, Wood Smoke) Inhalation
  • Tobacco Smoke and E-Cigarette Vaping
  • Endotoxin Inhalation
  • Adult and Pediatric Influenza

Beginning in 2000, under the leadership of Dr. Charles G. Plopper (UC Davis School of Veterinary Medicine, Emeritus), an important and major effort was initiated to study the development and exacerbation of asthma by oxidant air pollutants in nonhuman primates. The asthma studies necessitated the establishment of a pulmonary function laboratory with extensive capabilities for testing nonhuman primates under the direction of a pulmonary physiologist to assess function in animals undergoing exposure. Under the leadership of Dr. Dallas Hyde (UC Davis School of Veterinary Medicine, Emeritus), funding was obtained in 2010 from the US government – American Recovery and Regeneration Act – to build a Respiratory Disease Centerincluding a new inhalation exposure facility. It was recognized that the CNPRC is the only primate center with an inhalation exposure facility and respiratory diseases unit, enhancing research with nonhuman primate models of respiratory diseases.

Select Publications from IEC Activities

Royer C, Miller LA, Haczku A. A Novel Nonhuman Primate Model of Nonatopic Asthma. Methods Mol Biol. 2022;2506:83-94. doi:10.1007/978-1-0716-2364-0_6. PubMed PMID: 35771465; PMC in progress.

Bai H, Capitanio JP, Miller LA, Clougherty JE. Social status and susceptibility to wildfire smoke among outdoor-housed female rhesus monkeys: A natural experiment. Heliyon. 2021;7(11):e08333. Epub 20211109. doi: 10.1016/j.heliyon.2021.e08333. PubMed PMID: 34816037; PMCID: PMC8591456.

Cossette C, Miller LA, Ye Q, Chourey S, Reddy CN, Rokach J, Powell WS. Targeting the oxoeicosanoid (OXE) receptor with a selective antagonist inhibits allergen-induced pulmonary inflammation in non-human primates. Br J Pharmacol. 2021. Epub 20211112. doi: 10.1111/bph.15721. PubMed PMID: 34766334; PMCID: PMC8793878.

Enweasor C, Flayer CH, Haczku A. Ozone-Induced Oxidative Stress, Neutrophilic Airway Inflammation, and Glucocorticoid Resistance in Asthma. Frontiers in immunology. 2021;12:631092. Epub 20210226. doi: 10.3389/fimmu.2021.631092. PubMed PMID: 33717165; PMCID: PMC7952990.

Pabst R, Miller LA, Schelegle E, Hyde DM. Organized lymphatic tissue (BALT) in lungs of rhesus monkeys after air pollutant exposure. Anat Rec (Hoboken). 2020;303(11):2766-73. Epub 20200714. doi: 10.1002/ar.24456. PubMed PMID: 32445535; PMCID: PMC8793891.

Wong EM, Tablin F, Schelegle ES. Comparison of nonparametric and parametric methods for time-frequency heart rate variability analysis in a rodent model of cardiovascular disease. PLoS One. 2020;15(11):e0242147. Epub 20201109. doi: 10.1371/journal.pone.0242147. PubMed PMID: 33166366; PMCID: PMC7652293.

Barrios J, Kho AT, Aven L, Mitchel JA, Park JA, Randell SH, Miller LA, Tantisira KG, Ai X. Pulmonary Neuroendocrine Cells Secrete γ-Aminobutyric Acid to Induce Goblet Cell Hyperplasia in Primate Models. Am J Respir Cell Mol Biol. 2019;60(6):687-94. doi: 10.1165/rcmb.2018-0179OC. PubMed PMID: 30571139; PMCID: PMC6543741.

Flayer CH, Ge MQ, Hwang JW, Kokalari B, Redai IG, Jiang Z, Haczku A. Ozone Inhalation Attenuated the Effects of Budesonide on. Frontiers in immunology. 2019;10:2173. Epub 20190913. doi: 10.3389/fimmu.2019.02173. PubMed PMID: 31572383; PMCID: PMC6753328.

Flayer CH, Larson ED, Joseph A, Kao S, Qu W, Van Haren A, Royer CM, Miller LA, Capitanio JP, Sielecki T, Christofidou-Solomidou M, Haczku A. Ozone-induced enhancement of airway hyperreactivity in rhesus macaques: Effects of antioxidant treatment. J Allergy Clin Immunol. 2020;145(1):312-23. Epub 2019/10/20. doi: 10.1016/j.jaci.2019.08.034. PubMed PMID: 31627909; PMCID: PMC6949398.

Miller LA, Cossette C, Chourey S, Ye Q, Reddy CN, Rokach J, Powell WS. Inhibition of allergen-induced dermal eosinophilia by an oxoeicosanoid receptor antagonist in non-human primates. Br J Pharmacol. 2020;177(2):360-71. Epub 20200117. doi: 10.1111/bph.14872. PubMed PMID: 31655023; PMCID: PMC6989951.

Smit-McBride Z, Nguyen J, Elliott GW, Wang Z, McBride RA, Nguyen AT, Oltjen SL, Yiu G, Thomasy SM, Pinkerton KE, Lee ES, Cunefare D, Farsiu S, Morse LS. Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the Rhesus macaque. Mol Vis. 2018;24:633-46. Epub 2018/10/09. PubMed PMID: 30294202; PMCID: PMC6161805.

Wong EM, Walby WF, Wilson DW, Tablin F, Schelegle ES. Ultrafine Particulate Matter Combined With Ozone Exacerbates Lung Injury in Mature Adult Rats With Cardiovascular Disease. Toxicol Sci. 2018;163(1):140-51. doi: 10.1093/toxsci/kfy018. PubMed PMID: 29394414; PMCID: PMC5920298.

Herring MJ, Putney LF, St George JA, Avdalovic MV, Schelegle ES, Miller LA, Hyde DM. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs. Toxicol Appl Pharmacol. 2015 Feb 15;283(1):35-41. doi: 10.1016/j.taap.2014.12.006. Epub 2014 Dec 27. PubMed PMID:25545987; PMCID: PMC5922427.

Davis BB, Zeki AA, Bratt JM, Wang L, Filosto S, Walby WF, Kenyon NJ, Goldkorn T, Schelegle ES, Pinkerton KE. Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy. European Respiratory Journal. 2014 Apr;43(4):1211-2. doi: 10.1183/09031936.00015314. PubMed PMID: 24687675; PMCID: PMC6018050.

Chan JK, Charrier JG, Kodani SD, Vogel CF, Kado SY, Anderson DS, Anastasio C, Van Winkle LS. Combustion-derived flame generated ultrafine soot generates reactive oxygen species and activates Nrf2 antioxidants differently in neonatal and adult rat lungs. Particle and Fibre Toxicology 10:34, 2013. doi: 10.1186/1743-8977-10-34. PubMed PMID: 23902943; PMCID: PMC3735485.

Chun K, Miller LA, Schelegle ES, Hyde DM, Capitanio JP. Behavioral inhibition in rhesus monkeys (Macaca mulatta) is related to the airways response, but not immune measures, commonly associated with asthma. PLoS One 8(8):71575, 2013. doi:10.1371/annotation/aade3c83-f488-446e-8b02-bca381d2fe60. PubMed PMID: 23951195; PMCID: PMC3739724.

Murphy SR, Schelegle ES, Miller LA, Hyde DM, Van Winkle LS. Ozone exposure alters serotonin and serotonin receptor expression in the developing lung. Toxicological Sciences 34(1):168-179, 2013. doi: 10.1093/toxsci/kft090. PubMed PMID: 23570994; PMCID: PMC3693130.

Chan JK, Vogel CF, Baek J, Kodani SD, Uppal RS, Bein KJ, Anderson DS, Van Winkle LS. Combustion derived ultrafine particles induce cytochrome P-450 expression in specific lung compartments in the developing neonatal and adult rat. American Journal of Physiology – Lung Cellular and Molecular Physiology 304(10):665-677, 2013. doi: 10.1152/ajplung.00370.2012. PubMed PMID: 23502512; PMCID: PMC3652057.

Chan JK, Kodani SD, Charrier JG, Morin D, Edwards PC, Anderson DS, Anastasio C, Van Winkle LS. Age-specific effects on rat lung glutathione and antioxidant enzymes after inhaling ultrafine soot. American Journal of Respiratory Cell and Molecular Biology 48(1):114-124, 2013. Epub 20121011. doi: 10.1165/rcmb.2012-0108OC. PubMed PMID: 23065132; PMCID: PMC3547088.

Murphy SR, Schelegle ES, Edwards PC, Miller LA, Hyde DM, Van Winkle LS. Postnatal exposure history and airways: oxidant stress responses in airway explants. American Journal of Respiratory Cell and Molecular Biology 47(6):815-823, 2012. Epub 20120906. doi: 10.1165/rcmb.2012-0110OC. PubMed PMID: 22962062; PMCID: PMC3547096.

Asgharian B, Price O, McClellan G, Corley R, Einstein DR, Jacob RE, Harkema J, Carey SA, Schelegle ES, Hyde D, Kimbell JS, Miller FJ. Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans. Inhalation Toxicology 24(13):869-899, 2012. doi: 10.3109/08958378.2012.725782. PubMed PMID: 23121298; PMCID: PMC5119470.

Avdalovic MV, Tyler NK, Putney L, Nishio SJ, Quesenberry S, Singh PJ, Miller LA, Schelegle ES, Plopper CG, Vu T, Hyde DM. Ozone exposure during the early postnatal period alters the timing and pattern of alveolar growth and development in nonhuman primates. Anatomical Record 295(10):1707-1716, 2012. Epub 20120813. doi: 10.1002/ar.22545. PubMed PMID: 22887719; PMCID: PMC5462601.

Mitchell VL, Van Winkle LS, Gershwin LJ. Environmental tobacco smoke and progesterone alter lung inflammation and mucous metaplasia in a mouse model of allergic airway disease. Clinical Reviews in Allergy & Immunology 43(1-2):57-68, 2012. doi: 10.1007/s12016-011-8280-0. PubMed PMID: 21837398.

McDonnell WF, Stewart PW, Smith MV, Kim CS, Schelegle ES. Prediction of lung function response for populations exposed to a wide range of ozone conditions. Inhalation Toxicology 24(10):619-633, 2012. doi: 10.3109/08958378.2012.705919. PubMed PMID: 22906168.

Plopper CG, Joad JP, Miller LA, Schelegle ES, Fanucchi MV, Van Winkle LS, Tyler NK, Avdalovic MV, Evans MJ, Lasley WL, Buckpitt AR, Pinkerton KE, Tarkington BK, Davis S, Nishio SJ, Gershwin LJ, Wu R, Hyde DM. Lung effects of inhaled corticosteroids in a rhesus monkey model of childhood asthma. Clinical & Experimental Allergy 42(7):1104-1118, 2012. doi: 10.1111/j.1365-2222.2012.04005.x. PubMed PMID: 22702509; PMCID: PMC3913647.

Schelegle ES, Adams WC, Walby WF, Marion MS. Modelling of individual subject ozone exposure response kinetics. Inhalation Toxicology 24(7):401-415, 2012. doi: 10.3109/08958378.2012.683891. PubMed PMID: 22642289.

Schelegle ES, Walby WF. Vagal afferents contribute to exacerbated airway responses following ozone and allergen challenge. Respiratory Physiology & Neurobiology 181(3):277-285, 2012. Epub 20120412. doi: 10.1016/j.resp.2012.04.003. PubMed PMID: 22525484; PMCID: PMC3366056.

Moore BD, Hyde D, Miller L, Wong E, Frelinger J, Schelegle ES. Allergen and ozone exacerbate serotonin-induced increases in airway smooth muscle contraction in a model of childhood asthma. Respiration 83(6):529-542, 2012. Epub 20120413. doi: 10.1159/000336835. PubMed PMID: 22507883; PMCID: PMC7068792.

Chou DL, Gerriets JE, Schelegle ES, Hyde DM, Miller LA. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa. Toxicology and Applied Pharmacology 257(3):309-318, 2011. Epub 20110912. doi: 10.1016/j.taap.2011.09.001. PubMed PMID: 21945493; PMCID: PMC3226879.

Chan JK, Fanucchi MV, Anderson DS, Abid AD, Wallis DA, Kumfer BM, Kennedy IM, Van Winkle LS. Susceptibility to inhaled flame-generated ultrafine soot in neonatal and adult rat lungs. Toxicological Sciences 124(2):472-486, 2011. Epub 20110913. doi: 10.1093/toxsci/kfr233. PubMed PMID: 21914721; PMCID: PMC3216412.

Abbas AR, Jackman JK, Bullens SL, Davis SM, Choy DF, Fedorowicz G, Tan M, Truong BT, Meng Gloria Y, Diehl L, Miller LA, Schelegle ES, Hyde DM, Clark HF, Modrusan Z, Arron JR, Wu LC. Lung gene expression in a rhesus allergic asthma model correlates with physiologic parameters of disease and exhibits common and distinct pathways with human asthma and a mouse asthma model. American Journal of Pathology 179(4):1667-1680, 2011. Epub 20110803. doi: 10.1016/j.ajpath.2011.06.009. PubMed PMID: 21819959; PMCID: PMC3181391.

Lee D, Wallis C, Van Winkle LS, Wexler AS. Disruption of tracheobronchial airway growth following postnatal exposure to ozone and ultrafine particles. Inhalation Toxicology 23(9):520-531, 2011. Epub 20110722. doi: 10.3109/08958378.2011.591447. PubMed PMID: 21780864.

Bremer AA, Stanhope KL, Graham JL, Cummings BP, Wang W, Saville BR, Havel PJ. Fructose-fed rhesus monkeys: a nonhuman primate model of insulin resistance, metabolic syndrome, and type 2 diabetes. Clinical and Translational Science 4(4):243-252, 2011. doi: 10.1111/j.1752-8062.2011.00298.x. Pubmed PMID: 21884510; PMCID: PMC3170136.

Capitanio JP, Miller LA, Schelegle ES, Mendoza SP, Mason WA, Hyde DM. Behavioral inhibition is associated with airway hyperresponsiveness but not atopy in a monkey model of asthma. Psychosomatic Medicine 73(4):288-294, 2011. Epub 20110502. doi: 10.1097/PSY.0b013e3182155c83. PubMed PMID: 21536834 PMCID: PMC3090450.

Maniar-Hew K, Postlethwait EM, Fanucchi MV, Ballinger CA, Evans MJ, Harkema JR, Carey SA, McDonald R J, Bartolucci AA, and Miller LA. Postnatal episodic ozone results in persistent attenuation of pulmonary and peripheral blood responses to LPS challenge. American Journal of Physiology – Lung Cellular and Molecular Physiology 300(3):462-471, 2011. Epub 20101203. doi: 10.1152/ajplung.00254.2010. PubMed PMID: 21131396; PMCID: PMC3064293.

Carey SA, Ballinger CA, Plopper CG, McDonald RJ, Bartolucci AA, Postlethwait EM, Harkema JR. Persistent rhinitis and epithelial remodeling induced by cyclic ozone exposure in the nasal airways of infant monkeys. American Journal of Physiology – Lung Cellular and Molecular Physiology 300(2):242-254, 2011. Epub 20101203. doi: 10.1152/ajplung.00177.2010. PubMed PMID: 21131400; PMCID: PMC3043815.

Van Winkle LS, Chan JK, Anderson DS, Kumfer BM, Kennedy IM, Wexler AS, Wallis C, Abid AD, Sutherland KM, and Fanucchi MV. Age specific responses to acute inhalation of diffusion flame soot particles: cellular injury and the airway antioxidant response. Inhalation Toxicology 22 Suppl 2:70-83, 2010. Epub 20101021. doi: 10.3109/08958378.2010.513403. PubMed PMID: 20961279; PMCID: PMC3110018.

Lee DC, Wallis AS, Wexler ES, Schelegle LS, Van Winkle, Plopper CG, Fanucchi MV, Kumfer B, Kennedy IM, and Chan JK. Small particles disrupt postnatal airway development. Journal of Applied Physiology 109(4):1115-1124, 2010. Epub 20100715. doi: 10.1152/japplphysiol.00295.2010. PubMed PMID: 20634362; PMCID: PMC4182294.

Sekizawa S, Bechtold AG, Tham RC, Kott KS, Hyde DM, Joad JP, Bonham AC. House-dust mite allergen and ozone exposure decreases histamine H3 receptors in the brainstem respiratory nuclei. Toxicology and Applied Pharmacology 247(3):204-210, 2010. Epub 20100630. doi: 10.1016/j.taap.2010.06.014. PubMed PMID: 20600210.

Van Winkle LS, Baker GL, Chan JK, Schelegle ES, Plopper CG. Airway mast cells in a rhesus model of childhood allergic airways disease. Toxicological Sciences 116(1):313-322, 2010. Epub 20100419. doi: 10.1093/toxsci/kfq119. PubMed PMID: 20403968; PMCID: PMC2886865.

Evans MJ, Fanucchi MV, Plopper CG, Hyde DM. Postnatal development of the lamina reticularis in primate airways. Anatomical Record 293(6):947-954, 2010. doi: 10.1002/ar.20824. PubMed PMID: 20503389.

Evans MJ, Fanucchi MV, Miller, LA, Carlson MA, Nishio SJ, Hyde DM. Reduction of collagen VII anchoring fibrils in the airway basement membrane zone of infant rhesus monkeys exposed to house dust mite. American Journal of Physiology – Lung Cellular and Molecular Physiology 298(4):543-547, 2010. Epub 20100205. doi: 10.1152/ajplung.00337.2009. PubMed PMID: 20139177; PMCID: PMC2853345.

Sekizawa S, Joad JP, Pinkerton KE, Bonham AC. Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates. Toxicology and Applied Pharmacology 242(2):199-208, 2010. Epub 20091019. doi: 10.1016/j.taap.2009.10.009. PubMed PMID: 19850058.

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Q: Can I ask for customized services?

A: Yes!  If you do not see your desired service, please contact the Inhalation Exposure Facility directly and inquire about custom fabrication of exposure apparatus/systems.