Traffic-related air pollution induces non-allergic eosinophilic airway inflammation and cough hypersensitivity in guinea-pigs
Zhangfu Fang
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorChuqin Huang
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorJunfeng (Jim) Zhang
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Global Health Institute, Nicholas School of the Environment, Duke University, Durham, North Carolina
Search for more papers by this authorJiaxing Xie
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorShouhui Dai
Equipment Public Service Center, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China
Search for more papers by this authorErjia Ge
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Search for more papers by this authorJuan Xiang
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorHongmei Yao
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorRongquan Huang
Department of Pathology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorXinhui Bi
State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, China
Search for more papers by this authorBoguang Wang
Institute for Environmental and Climate Research, Jinan University, Guangzhou, China
Search for more papers by this authorNanshan Zhong
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorCorresponding Author
Kefang Lai
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Correspondence
Kefang Lai, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Email: [email protected]
Search for more papers by this authorZhangfu Fang
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorChuqin Huang
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorJunfeng (Jim) Zhang
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Global Health Institute, Nicholas School of the Environment, Duke University, Durham, North Carolina
Search for more papers by this authorJiaxing Xie
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorShouhui Dai
Equipment Public Service Center, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China
Search for more papers by this authorErjia Ge
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Search for more papers by this authorJuan Xiang
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorHongmei Yao
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorRongquan Huang
Department of Pathology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorXinhui Bi
State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, China
Search for more papers by this authorBoguang Wang
Institute for Environmental and Climate Research, Jinan University, Guangzhou, China
Search for more papers by this authorNanshan Zhong
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorCorresponding Author
Kefang Lai
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Correspondence
Kefang Lai, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Email: [email protected]
Search for more papers by this authorAbstract
Background
The pathogenesis and pathophysiology of eosinophilia-related chronic cough such as non-asthmatic eosinophilic bronchitis and cough variant asthma are still not clear.
Objective
This study is to examine the potential role of traffic-related air pollution (TRAP) in eosinophilic inflammation and cough responses.
Methods
Non-sensitized guinea-pigs were exposed to TRAP in an urban traffic tunnel or kept in a filtered air environment for 7 or 14 days. Reflexive cough was measured using citric acid and allyl isothiocyanate (AITC) challenges, respectively. Spontaneous cough counting was determined using audio recording and a waveform analysis. Airway inflammation was evaluated using differential cells in bronchoalveolar lavage fluid (BALF) and lung histopathology. To further elucidate the relationship between airway inflammation and cough hypersensitivity, a subgroup of those exposed for 14 days received a dexamethasone treatment.
Results
Compared to reflexive cough count (mean (95% confidence interval) in 10 minutes) provoked by the AITC challenge for the unexposed animals (3.1 (1.7-4.5)), those were increased significantly following both the 7-day (12.0 (6.8-17.2), P < 0.01) and the 14-day (12.0 (6.4-17.6), P < 0.01) TRAP exposure. The effect provoked by the citric acid challenge was more profound following the 14-day exposure (26.0 (19.5-32.5) vs 3.8 (1.5-6.0) for the control, P < 0.001). TRAP exposures enhanced spontaneous cough events, caused a significant increase of eosinophils and neutrophils in BALF and resulted in a dramatic eosinophilic infiltration in submucosal layer of trachea and bronchus, which can be inhibited significantly by dexamethasone treatment.
Conclusions & Clinical Relevance
TRAP exposures induced cough hypersensitivity and non-allergic eosinophilic inflammation of airways in guinea-pigs. This study highlights the potential mechanisms of eosinophilia-related chronic cough that can be induced by traffic-related air pollution.
CONFLICT OF INTEREST
The authors declare no conflict of interests.
Supporting Information
| Filename | Description |
|---|---|
| cea13308-sup-0001-FigS1-S4.pptxapplication/mspowerpoint, 212.9 KB | |
| cea13308-sup-0002-AppendixS1.docxWord document, 19.8 KB | |
| cea13308-sup-0003-Supinfo.docxWord document, 19.8 KB |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Guan W, Zheng X, Chung KF, Zhong N. Impact of air pollution on the burden of chronic respiratory diseases in china: time for urgent action. Lancet. 2016; 388: 1939-1951.
- 2Huang RJ, Zhang Y, Bozzetti C, et al. High secondary aerosol contribution to particulate pollution during haze events in china. Nature. 2014; 514: 218-222.
- 3Chung KF, Pavord I. Prevalence, pathogenesis, and causes of chronic cough. Lancet. 2008; 371: 1364-1374.
- 4Gehring U, Cyrys J, Sedlmeir G, et al. Traffic-related air pollution and respiratory health during the first 2 yrs of life. Eur Respir J. 2002; 19: 690-698.
- 5Hazenkamp-von Arx ME, Schindler C, Ragettli MS, Kunzli N, Braun-Fahrlander C, Liu LJ. Impacts of highway traffic exhaust in alpine valleys on the respiratory health in adults: a cross-sectional study. Environ Health. 2011; 10: 13.
- 6Morgenstern V, Zutavern A, Cyrys J, et al. Respiratory health and individual estimated exposure to traffic-related air pollutants in a cohort of young children. Occup Environ Med. 2007; 64: 8-16.
- 7Lai K, Chen R, Lin J, et al. A prospective, multicenter survey on causes of chronic cough in china. Chest. 2013; 143: 613-620.
- 8Bowatte G, Lodge C, Lowe AJ, et al. The influence of childhood traffic-related air pollution exposure on asthma, allergy and sensitization: a systematic review and a meta-analysis of birth cohort studies. Allergy. 2015; 70: 245-256.
- 9Hashimoto K, Ishii Y, Uchida Y, et al. Exposure to diesel exhaust exacerbates allergen-induced airway responses in guinea pigs. Am J Respir Crit Care Med. 2001; 164: 1957-1963.
- 10Brandt EB, Kovacic MB, Lee GB, et al. Diesel exhaust particle induction of IL-17a contributes to severe asthma. J Allergy Clin Immunol. 2013; 132: 1194-1204.
- 11Carlsten C, Blomberg A, Pui M, et al. Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study. Thorax. 2016; 71: 35-44.
- 12Chen L, Lai K, Lomask JM, Jiang B, Zhong N. Detection of mouse cough based on sound monitoring and respiratory airflow waveforms. PLoS ONE. 2013; 8: e59263.
- 13Dekkers BG, Bos IS, Gosens R, Halayko AJ, Zaagsma J, Meurs H. The integrin-blocking peptide rgds inhibits airway smooth muscle remodeling in a guinea pig model of allergic asthma. Am J Respir Crit Care Med. 2010; 181: 556-565.
- 14Bos I, De Boever P, Emmerechts J, et al. Changed gene expression in brains of mice exposed to traffic in a highway tunnel. Inhal Toxicol. 2012; 24: 676-686.
- 15McCreanor J, Cullinan P, Nieuwenhuijsen MJ, et al. Respiratory effects of exposure to diesel traffic in persons with asthma. N Engl J Med. 2007; 357: 2348-2358.
- 16Larsson BM, Sehlstedt M, Grunewald J, et al. Road tunnel air pollution induces bronchoalveolar inflammation in healthy subjects. Eur Respir J. 2007; 29: 699-705.
- 17 WHO air quality guidelines for particulate matter, ozone, nitrogen dioxide and sulfur dioxide: Global update 2005: Summary of risk assessment. http://www.who.int/phe/health_topics/outdoorair/outdoorair_aqg/en/. Accessed June 24, 2018.
- 18Morice AH, Fontana GA, Belvisi MG, et al. ERS guidelines on the assessment of cough. Eur Respir J. 2007; 29: 1256-1276.
- 19Kollarik M, Ru F, Undem BJ. Acid-sensitive vagal sensory pathways and cough. Pulm Pharmacol Ther. 2007; 20: 402-411.
- 20Jordt SE, Bautista DM, Chuang HH, et al. Mustard oils and cannabinoids excite sensory nerve fibres through the trp channel anktm1. Nature. 2004; 427: 260-265.
- 21Brozmanova M, Mazurova L, Ru F, Tatar M, Kollarik M. Comparison of TRPA1-versus TRPV1-mediated cough in guinea pigs. Eur J Pharmacol. 2012; 689: 211-218.
- 22Buday T, Kovacikova L, Ruzinak R, Plevkova J. TRPV4 antagonist gsk2193874 does not modulate cough response to osmotic stimuli. Respir Physiol Neurobiol. 2017; 236: 1-4.
- 23Ferrari S, Silva M, Guarino M, Aerts JM, Berckmans D. Cough sound analysis to identify respiratory infection in pigs. Comput Electron Agr. 2008; 64: 318-325.
- 24Lv H, Yue J, Chen Z, et al. Effect of transient receptor potential vanilloid-1 on cough hypersensitivity induced by particulate matter 2.5. Life Sci. 2016; 151: 157-166.
- 25Robinson RK, Birrell MA, Adcock JJ, et al. Mechanistic link between diesel exhaust particles and respiratory reflexes. J Allergy Clin Immunol. 2018; 141: 1074-1084.e1079.
- 26Keller JA, Mcgovern AE, Mazzone SB. Translating cough mechanisms into better cough suppressants. Chest. 2017; 152: 833-841.
- 27Eccles R. Central mechanisms IV: conscious control of cough and the placebo effect. Handb Exp Pharmacol. 2009; 181: 241-262.
10.1007/978-3-540-79842-2_12 Google Scholar
- 28Niimi A, Torrego A, Nicholson A, Cosio B, Oates T, Chung K. Nature of airway inflammation and remodeling in chronic cough. J Allergy Clin Immunol. 2005; 116: 565-570.
- 29Widdicombe JG. Neurophysiology of the cough reflex. Eur Respir J. 1995; 8: 1193-1202.
- 30Barnhart M, Chen S, Salley S, Puro H. Ultrastructure and morphometry of the alveolar lung of guinea pigs chronically exposed to diesel engine exhaust: six month's experience. J Appl Toxicol. 1981; 1: 88-103.
- 31Boland S, Baezasquiban A, Fournier T, et al. Diesel exhaust particles are taken up by human airway epithelial cells in vitro and alter cytokine production. Am J Physiol. 1999; 276: 604-613.
- 32Luo W, Lai K, Chen R, et al. Characteristics of airway inflammatory cells and mediators in eosinophilic bronchitis patients. Chin J Tuberc Respir Dis. 2005; 28: 626-629.
- 33Fujimura M, Ogawa H, Yasui M, Matsuda T. Eosinophilic tracheobronchitis and airway cough hypersensitivity in chronic non-productive cough. Clin Exp Allergy. 2000; 30: 41-47.
- 34De Grove KC, Provoost S, Brusselle GG, Joos GF, Maes T. Insights in particulate matter-induced allergic airway inflammation: focus on the epithelium. Clin Exp Allergy. 2018; 48: 773-786.
- 35Alexis NE, Carlsten C. Interplay of air pollution and asthma immunopathogenesis: a focused review of diesel exhaust and ozone. Int Immunopharmacol. 2014; 23: 347-355.
- 36Yu S, Kim HY, Chang YJ, DeKruyff RH, Umetsu DT. Innate lymphoid cells and asthma. J Allergy Clin Immunol. 2014; 133: 943-950.
- 37Yang Q, Ge MQ, Kokalari B, et al. Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol. 2016; 137: 571-578.
- 38Nishikawa M, Kakemizu N, Ito T, et al. Superoxide mediates cigarette smoke-induced infiltration of neutrophils into the airways through nuclear factor-kappaB activation and IL-8 mRNA expression in guinea pigs in vivo. Am J Respir Cell Mol Biol. 1999; 20: 189-198.
- 39Miyabara Y, Ichinose T, Takano H, Lim HB, Sagai M. Effects of diesel exhaust on allergic airway inflammation in mice. J Allergy Clin Immunol. 1998; 102: 805-812.
- 40Lee CC, Liao JW, Kang JJ. Motorcycle exhaust particles induce airway inflammation and airway hyperresponsiveness in balb/c mice. Toxicol Sci. 2004; 79: 326-334.
- 41Provoost S, Maes T, Pauwels NS, et al. NLRP3/caspase-1-independent IL-1 beta production mediates diesel exhaust particle-induced pulmonary inflammation. J Immunol. 2011; 187: 3331-3337.
- 42Inoue K, Takano H, Yanagisawa R, et al. The role of toll-like receptor 4 in airway inflammation induced by diesel exhaust particles. Arch Toxicol. 2006; 80: 275-279.
- 43Stiegel MA, Pleil JD, Sobus JR, Madden MC. Inflammatory cytokines and white blood cell counts response to environmental levels of diesel exhaust and ozone inhalation exposures. PLoS ONE. 2016; 11: e0152458.
- 44Gieseck RL 3rd, Wilson MS, Wynn TA. Type 2 immunity in tissue repair and fibrosis. Nat Rev Immunol. 2017; 18: 62-76.
- 45Fukakusa M, Bergeron C, Tulic MK, et al. Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-gamma-inducible protein 10 expression in asthmatic airway mucosa. J Allergy Clin Immunol. 2005; 115: 280-286.
- 46Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci. 1998; 94: 557-572.
- 47Lai K, Guo X, Wang C, Guo X, Qian G. Inhibition of glucocorticoids on human eosinophil survival: an in vitro study. Chin J Hematol. 2000; 21: 381-382.
- 48Brightling C, Ward R, Wardlaw A, Pavord I. Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis. Eur Respir J. 2000; 15: 682-686.
- 49Tobias A, Recio A, Diaz J, Linares C. Health impact assessment of traffic noise in Madrid (Spain). Environ Res. 2015; 137: 136-140.
- 50Pretolani M, Vargaftig B. From lung hypersensitivity to bronchial hyperreactivity. What can we learn from studies on animal models? Biochem Pharmacol. 1993; 45: 791-800.
Citing Literature
