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Open Access 01-12-2018 | Research

Modelling the asthma phenotype: impact of cigarette smoke exposure

Authors: Maria G. Belvisi, Katie Baker, Nicole Malloy, Kristof Raemdonck, Bilel Dekkak, Michael Pieper, Anthony T. Nials, Mark A. Birrell

Published in: Respiratory Research | Issue 1/2018

Abstract

Background

Asthmatics that are exposed to inhaled pollutants such as cigarette smoke (CS) have increased symptom severity. Approximately 25% of adult asthmatics are thought to be active smokers and many sufferers, especially in the third world, are exposed to high levels of inhaled pollutants. The mechanism by which CS or other airborne pollutants alter the disease phenotype and the effectiveness of treatment in asthma is not known. The aim of this study was to determine the impact of CS exposure on the phenotype and treatment sensitivity of rodent models of allergic asthma.

Methods

Models of allergic asthma were configured that mimicked aspects of the asthma phenotype and the effect of CS exposure investigated. In some experiments, treatment with gold standard asthma therapies was investigated and end-points such as airway cellular burden, late asthmatic response (LAR) and airway hyper-Reactivity (AHR) assessed.

Results

CS co-exposure caused an increase in the LAR but interestingly attenuated the AHR. The effectiveness of LABA, LAMA and glucocorticoid treatment on LAR appeared to be retained in the CS-exposed model system. The eosinophilia or lymphocyte burden was not altered by CS co-exposure, nor did CS appear to alter the effectiveness of glucocorticoid treatment. Steroids, however failed to reduce the neutrophilic inflammation in sensitized mice exposed to CS.

Conclusions

These model data have certain parallels with clinical findings in asthmatics, where CS exposure did not impact the anti-inflammatory efficacy of steroids but attenuated AHR and enhanced symptoms such as the bronchospasm associated with the LAR. These model systems may be utilised to investigate how CS and other airborne pollutants impact the asthma phenotype; providing the opportunity to identify novel targets.

Zmirou D, Gauvin S, Pin I, et al. Traffic related air pollution and incidence of childhood asthma: results of the Vesta case-control study. J Epidemiol Community Health. 2004;58:18–23.CrossRefPubMedPubMedCentral

McConnell R, Berhane K, Yao L, et al. Traffic, susceptibility, and childhood asthma. Environ Health Perspect. 2006;114:766–72.CrossRefPubMedPubMedCentral

Salam MT, Islam T, Gilliland FD. Recent evidence for adverse effects of residential proximity to traffic sources on asthma. Curr Opin Pulm Med. 2008;14:3–8. https://doi.org/10.1097/MCP.0b013e3282f1987a.CrossRefPubMed

Patel MM, Quinn JW, Jung KH, et al. Traffic density and stationary sources of air pollution associated with wheeze, asthma, and immunoglobulin E from birth to age 5 years among new York City children. Environ Res. 2011;111:1222–9. https://doi.org/10.1016/j.envres.2011.08.004.CrossRefPubMedPubMedCentral

Clark NA, Demers PA, Karr CJ, et al. Effect of early life exposure to air pollution on development of childhood asthma. Environ Health Perspect. 2010;118:284–90. https://doi.org/10.1289/ehp.0900916.CrossRefPubMed

Gowers AM, Cullinan P, Ayres JG, et al. Does outdoor air pollution induce new cases of asthma? Biological plausibility and evidence; a review. Respirology. 2012;17:887–98. https://doi.org/10.1111/j.1440-1843.2012.02195.x.CrossRefPubMed

Chung KF, Zhang J, Zhong N. Outdoor air pollution and respiratory health in Asia. Respirology. 2011;16:1023–6. https://doi.org/10.1111/j.1440-1843.2011.02034.x.CrossRefPubMed

Apostol GG, Jacobs DRJ, Tsai AW, et al. Early life factors contribute to the decrease in lung function between ages 18 and 40: the coronary artery risk development in young adults study. Am J Respir Crit Care Med. 2002;166:166–72.CrossRefPubMed

Eisner MD, Iribarren C. The influence of cigarette smoking on adult asthma outcomes. Nicotine Tob Res. 2007;9:53–6. https://doi.org/10.1080/14622200601078293.CrossRefPubMed

10.

Jang A-S, Park J-S, Lee J-H, et al. The impact of smoking on clinical and therapeutic effects in asthmatics. J Korean Med Sci. 2009;24:209–14. https://doi.org/10.3346/jkms.2009.24.2.209.CrossRefPubMedPubMedCentral

11.

O’Byrne PM, Lamm CJ, Busse WW, et al. The effects of inhaled budesonide on lung function in smokers and nonsmokers with mild persistent asthma. Chest. 2009;136:1514–20. https://doi.org/10.1378/chest.09-1049.CrossRefPubMed

12.

Siroux V, Pin I, Oryszczyn M, et al. Relationships of active smoking to asthma and asthma severity in the EGEA study. Epidemiological study on the genetics and environment of asthma. Eur Respir J. 2000;15:470–7.CrossRefPubMed

13.

Thomson NC, Chaudhuri R, Livingston E. Asthma and cigarette smoking. Eur Respir J. 2004;24:822–33. https://doi.org/10.1183/09031936.04.00039004.CrossRefPubMed

14.

Thomson NC, Chaudhuri R, Heaney LG, et al. Clinical outcomes and inflammatory biomarkers in current smokers and exsmokers with severe asthma. J Allergy Clin Immunol Published Online First: February 2013. https://doi.org/10.1016/j.jaci.2012.12.1574.

15.

Polosa R, Russo C, Caponnetto P, et al. Greater severity of new onset asthma in allergic subjects who smoke: a 10-year longitudinal study. Respir Res. 2011;12:16. https://doi.org/10.1186/1465-9921-12-16.CrossRefPubMedPubMedCentral

16.

Eisner MD, Klein J, Hammond SK, et al. Directly measured second hand smoke exposure and asthma health outcomes. Thorax. 2005;60:814–21. https://doi.org/10.1136/thx.2004.037283.CrossRefPubMedPubMedCentral

17.

Eisner MD, Yelin EH, Henke J, et al. Environmental tobacco smoke and adult asthma. The impact of changing exposure status on health outcomes. Am J Respir Crit Care Med. 1998;158:170–5. https://doi.org/10.1164/ajrccm.158.1.9801028.CrossRefPubMed

18.

Stankus RP, Menon PK, Rando RJ, et al. Cigarette smoke-sensitive asthma: challenge studies. J Allergy Clin Immunol. 1988;82:331–8.CrossRefPubMed

19.

Althuis MD, Sexton M, Prybylski D. Cigarette smoking and asthma symptom severity among adult asthmatics. J Asthma. 1999;36:257–64.CrossRefPubMed

20.

Gallefoss F, Bakke PS. Does smoking affect the outcome of patient education and self-management in asthmatics? Patient Educ Couns. 2003;49:91–7.CrossRefPubMed

21.

Dahms TE, Bolin JF, Slavin RG. Passive smoking. Effects on bronchial asthma. Chest. 1981;80:530–4.CrossRefPubMed

22.

Menon PK, Stankus RP, Rando RJ, et al. Asthmatic responses to passive cigarette smoke: persistence of reactivity and effect of medications. J Allergy Clin Immunol. 1991;88:861–9.CrossRefPubMed

23.

Menon P, Rando RJ, Stankus RP, et al. Passive cigarette smoke-challenge studies: increase in bronchial hyperreactivity. J Allergy Clin Immunol. 1992;89:560–6.CrossRefPubMed

24.

Chalmers GW, Macleod KJ, Little SA, et al. Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma. Thorax. 2002;57:226–30.CrossRefPubMedPubMedCentral

25.

Chaudhuri R, Livingston E, McMahon AD, et al. Cigarette smoking impairs the therapeutic response to oral corticosteroids in chronic asthma. Am J Respir Crit Care Med. 2003;168:1308–11. https://doi.org/10.1164/rccm.200304-503OC.CrossRefPubMed

26.

Laforest L, Van Ganse E, Devouassoux G, et al. Influence of patients’ characteristics and disease management on asthma control. J Allergy Clin Immunol. 2006;117:1404–10. https://doi.org/10.1016/j.jaci.2006.03.007.CrossRefPubMed

27.

Chaudhuri R, Livingston E, McMahon AD, et al. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am J Respir Crit Care Med. 2006;174:127–33. https://doi.org/10.1164/rccm.200510-1589OC.CrossRefPubMed

28.

Clatworthy J, Price D, Ryan D, et al. The value of self-report assessment of adherence, rhinitis and smoking in relation to asthma control. Prim Care Respir J. 2009;18:300–5. https://doi.org/10.4104/pcrj.2009.00037.CrossRefPubMed

29.

Lazarus SC, Chinchilli VM, Rollings NJ, et al. Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma. Am J Respir Crit Care Med. 2007;175:783–90. https://doi.org/10.1164/rccm.200511-1746OC.CrossRefPubMedPubMedCentral

30.

Rabe KF, Adachi M, Lai CKW, et al. Worldwide severity and control of asthma in children and adults: the global asthma insights and reality surveys. J Allergy Clin Immunol. 2004;114:40–7. https://doi.org/10.1016/j.jaci.2004.04.042.CrossRefPubMed

31.

Raemdonck K, de Alba J, Birrell M a, et al. A role for sensory nerves in the late asthmatic response. Thorax. 2012;67:19–25. https://doi.org/10.1136/thoraxjnl-2011-200365.

32.

Underwood S, Foster M, Raeburn D, et al. Time-course of antigen-induced airway inflammation in the Guinea-pig and its relationship to airway hyperresponsiveness. Eur Respir J. 1995;8:2104–13.CrossRefPubMed

33.

Belvisi MG, Birrell MA, Khalid S, Wortley MA, Dockry R, Coote J, Holt K, Dubuis E, Kelsall A, Maher SA, Bonvini S, Woodcock A, Smith JA. Neurophenotypes in Airway Diseases. Insights from Translational Cough Studies. Am J Respir Crit Care Med. 2016;193(12):1364–72. https://doi.org/10.1164/rccm.201508-1602OC

34.

Eltom S, Stevenson C, Birrell MA. Cigarette smoke exposure as a model of inflammation associated with COPD. Curr Protoc Pharmacol. 2013;5:5.64.

35.

Birrell MA, Hardaker E, Wong S, et al. Ikappa-B kinase-2 inhibitor blocks inflammation in human airway smooth muscle and a rat model of asthma. Am J Respir Crit Care Med. 2005;172:962–71. https://doi.org/10.1164/rccm.200412-1647OC.

36.

Birrell M a, Battram CH, Woodman P, et al. Dissociation by steroids of eosinophilic inflammation from airway hyperresponsiveness in murine airways. Respir Res. 2003;4:3.CrossRefPubMedPubMedCentral

37.

Raemdonck K, Baker K, Dale N, Dubuis E, Shala F, Belvisi MG, Birrell MA. CD4⁺ and CD8⁺ T cells play a central role in a HDM driven model of allergic asthma. Respir Res. 2016;17(1):45. https://doi.org/10.1186/s12931-016-0359-y

38.

Rastrick JMD, Stevenson CS, Eltom S, et al. Correction: cigarette smoke induced airway inflammation is independent of NF-κB Signalling. PLoS One. 2013;8 https://doi.org/10.1371/annotation/754d7b19-2dac-479b-a23c-db9fed0431be.

39.

Birrell MA, De Alba J, Catley MC, et al. Liver X receptor agonists increase airway reactivity in a model of asthma via increasing airway smooth muscle growth. J Immunol. 2008;181:4265–71.CrossRefPubMed

40.

Eltom S, Stevenson CS, Rastrick J, et al. P2X7 receptor and caspase 1 activation are central to airway inflammation observed after exposure to tobacco smoke. PLoS One. 2011;6:–e24097. https://doi.org/10.1371/journal.pone.0024097.

41.

Boulet L-P, Lemière C, Archambault F, et al. Smoking and asthma: clinical and radiologic features, lung function, and airway inflammation. Chest. 2006;129:661–8. https://doi.org/10.1378/chest.129.3.661.CrossRefPubMed

42.

St-Laurent J, Bergeron C, Pagé N, et al. Influence of smoking on airway inflammation and remodelling in asthma. Clin Exp Allergy. 2008;38:1582–9. https://doi.org/10.1111/j.1365-2222.2008.03032.x.CrossRefPubMed

43.

Meghji Z, Dua B, Watson RM, et al. Allergen inhalation challenge in smoking compared with non-smoking asthmatic subjects. Clin Exp Allergy. 2011;41:1084–90. https://doi.org/10.1111/j.1365-2222.2011.03782.x.CrossRefPubMed

44.

Broekema M, ten Hacken NHT, Volbeda F, et al. Airway epithelial changes in smokers but not in ex-smokers with asthma. Am J Respir Crit Care Med. 2009;180:1170–8. https://doi.org/10.1164/rccm.200906-0828OC.CrossRefPubMed

45.

Moerloose KB, Pauwels RA, Joos GF. Short-term cigarette smoke exposure enhances allergic airway inflammation in mice. Am J Respir Crit Care Med. 2005;172:168–72. https://doi.org/10.1164/rccm.200409-1174OC.CrossRefPubMed

46.

Moerloose KB, Robays LJ, Maes T, et al. Cigarette smoke exposure facilitates allergic sensitization in mice. Respir Res. 2006;7:49. https://doi.org/10.1186/1465-9921-7-49.CrossRefPubMedPubMedCentral

47.

Van Hove CL, Moerloose K, Maes T, et al. Cigarette smoke enhances Th-2 driven airway inflammation and delays inhalational tolerance. Respir Res. 2008;9:42. https://doi.org/10.1186/1465-9921-9-42.CrossRefPubMedPubMedCentral

48.

Min MG, Song DJ, Miller M, et al. Coexposure to environmental tobacco smoke increases levels of allergen-induced airway remodeling in mice. J Immunol. 2007;178:5321–8.CrossRefPubMed

49.

Seymour BW, Pinkerton KE, Friebertshauser KE, et al. Second-hand smoke is an adjuvant for T helper-2 responses in a murine model of allergy. J Immunol (Baltimore, Md 1950). 1997;159:6169–75.

50.

Rumold R, Jyrala M, Diaz-Sanchez D. Secondhand smoke induces allergic sensitization in mice. J Immunol (Baltimore, Md 1950). 2001;167:4765–70.CrossRef

51.

Trimble NJ, Botelho FM, Bauer CMT, et al. Adjuvant and anti-inflammatory properties of cigarette smoke in murine allergic airway inflammation. Am J Respir Cell Mol Biol. 2009;40:38–46. https://doi.org/10.1165/rcmb.2008-0107OC.CrossRefPubMed

52.

Botelho FM, Llop-Guevara A, Trimble NJ, et al. Cigarette smoke differentially affects eosinophilia and remodeling in a model of house dust mite asthma. Am J Respir Cell Mol Biol. 2011;45:753–60. https://doi.org/10.1165/rcmb.2010-0404OC.CrossRefPubMed

53.

Melgert BN, Timens W, Kerstjens HA, et al. Effects of 4 months of smoking in mice with ovalbumin-induced airway inflammation. Clin Exp Allergy. 2007;37:1798–808. https://doi.org/10.1111/j.1365-2222.2007.02843.x.CrossRefPubMed

54.

Melgert BN, Postma DS, Geerlings M, et al. Short-term smoke exposure attenuates ovalbumin-induced airway inflammation in allergic mice. Am J Respir Cell Mol Biol. 2004;30:880–5. https://doi.org/10.1165/rcmb.2003-0178OC.CrossRefPubMed

55.

Robbins CS, Pouladi MA, Fattouh R, et al. Mainstream cigarette smoke exposure attenuates airway immune inflammatory responses to surrogate and common environmental allergens in mice, despite evidence of increased systemic sensitization. J Immunol. 2005;175:2834–42.CrossRefPubMed

56.

Thatcher TH, Benson RP, Phipps RP, et al. High-dose but not low-dose mainstream cigarette smoke suppresses allergic airway inflammation by inhibiting T cell function. Am J Physiol Lung Cell Mol Physiol. 2008;295:L412–21. https://doi.org/10.1152/ajplung.00392.2007.CrossRefPubMedPubMedCentral

57.

Lanckacker EA, Tournoy KG, Hammad H, et al. Short cigarette smoke exposure facilitates sensitization and asthma development in mice. Eur Respir J Published Online First: August 2012. https://doi.org/10.1183/09031936.00096612.

58.

Maes T, Provoost S, Lanckacker EA, et al. Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation. Respir Res. 2010;11:7. https://doi.org/10.1186/1465-9921-11-7.CrossRefPubMedPubMedCentral

59.

Song DJ, Min MG, Miller M, et al. Environmental tobacco smoke exposure does not prevent corticosteroids reducing inflammation, remodeling, and airway hyperreactivity in mice exposed to allergen. Am J Physiol Lung Cell Mol Physiol. 2009;297:L380–7. https://doi.org/10.1152/ajplung.90588.2008.CrossRefPubMedPubMedCentral

60.

Marwick JA, Kirkham PA, Stevenson CS, et al. Cigarette smoke alters chromatin remodeling and induces Proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol. 2004;31:633–42. https://doi.org/10.1165/rcmb.2004-0006OC.CrossRefPubMed

61.

Marwick JA, Caramori G, Stevenson CS, et al. Inhibition of PI3Kδ restores glucocorticoid function in smoking-induced airway inflammation in mice. Am J Respir Crit Care Med. 2009;179:542–8. https://doi.org/10.1164/rccm.200810-1570OC.CrossRefPubMed

62.

Pedersen B, Dahl R, Karlström R, et al. Eosinophil and neutrophil activity in asthma in a one-year trial with inhaled budesonide. The impact of smoking. Am J Respir Crit Care Med. 1996;153:1519–29.CrossRefPubMed

63.

Ameredes BT, Otterbein LE, Kohut LK, et al. Low-dose carbon monoxide reduces airway hyperresponsiveness in mice. Am J Physiol Lung Cell Mol Physiol. 2003;285:L1270–6. https://doi.org/10.1152/ajplung.00145.2003.CrossRefPubMed

64.

Chang WC, Lee YC, Liu CL, et al. Increased expression of iNOS and c-fos via regulation of protein tyrosine phosphorylation and MEK1/ERK2 proteins in terminal bronchiole lesions in the lungs of rats exposed to cigarette smoke. Arch Toxicol. 2001;75:28–35.CrossRefPubMed

65.

Foster PS, Hogan SP, Ramsay AJ, et al. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med. 1996;183:195–201.CrossRefPubMed

66.

Hamelmann E, Oshiba A, Loader J, et al. Antiinterleukin-5 antibody prevents airway hyperresponsiveness in a murine model of airway sensitization. Am J Respir Crit Care Med. 1997;155:819–25.CrossRefPubMed

67.

Hamelmann E, Takeda K, Schwarze J, et al. Development of eosinophilic airway inflammation and airway hyperresponsiveness requires interleukin-5 but not immunoglobulin E or B lymphocytes. Am J Respir Cell Mol Biol. 1999;21:480–9.CrossRefPubMed

68.

Grünig G, Warnock M, Wakil AE, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998;282:2261–3.CrossRefPubMedPubMedCentral

69.

Mattes J, Yang M, Siqueira A, et al. IL-13 induces airways hyperreactivity independently of the IL-4R alpha chain in the allergic lung. J Immunol (Baltimore, Md 1950). 2001;167:1683–92.CrossRef

70.

Barczyk A, Pierzchala W, Sozañska E. Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respir Med. 2003;97:726–33.CrossRefPubMed

71.

Barlow JL, Bellosi A, Hardman CS, et al. Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity. J Allergy Clin Immunol. 2012;129:191–8.4. https://doi.org/10.1016/j.jaci.2011.09.041.CrossRefPubMed

72.

Hansen G, McIntire JJ, Yeung VP, et al. CD4(+) T helper cells engineered to produce latent TGF-beta1 reverse allergen-induced airway hyperreactivity and inflammation. J Clin Invest. 2000;105:61–70. https://doi.org/10.1172/JCI7589.CrossRefPubMedPubMedCentral

73.

Schramm C, Herz U, Podlech J, et al. TGF-beta regulates airway responses via T cells. J Immunol (Baltimore, Md 1950). 2003;170:1313–9.CrossRef

74.

Kim DY, Kwon EY, Hong GU, et al. Cigarette smoke exacerbates mouse allergic asthma through Smad proteins expressed in mast cells. Respir Res. 2011;12:49. https://doi.org/10.1186/1465-9921-12-49.CrossRefPubMedPubMedCentral

75.

Birrell MA, Wong S, Catley MC, et al. Impact of tobacco-smoke on key signaling pathways in the innate immune response in lung macrophages. J Cell Physiol. 2008;214:27–37. https://doi.org/10.1002/jcp.21158.CrossRefPubMed

76.

Ma X, Cheng Z, Kong H, et al. Changes in biophysical and biochemical properties of single bronchial smooth muscle cells from asthmatic subjects. Am J Physiol Lung Cell Mol Physiol. 2002;283:L1181–9. https://doi.org/10.1152/ajplung.00389.2001.CrossRefPubMed

77.

Ebina M, Takahashi T, Chiba T, et al. Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma. A 3-D morphometric study. Am Rev Respir Dis. 1993;148:720–6.CrossRefPubMed

78.

Fang Q, Zhao M, Ren G. Effects of cigarette smoke extract on proliferation and ET-1 release of airway smooth muscle cells. Zhonghua Yi Xue Za Zhi. 1997;77:201–4.PubMed

79.

Lin J, Xu Y, Zhang Z, et al. Effect of cigarette smoke extract on the role of protein kinase C in the proliferation of passively sensitized human airway smooth muscle cells. J Huazhong Univ Sci Technolog Med Sci. 2005;25:269–73.CrossRefPubMed

80.

Pera T, Gosens R, Lesterhuis AH, et al. Cigarette smoke and lipopolysaccharide induce a proliferative airway smooth muscle phenotype. Respir Res. 2010;11:48. https://doi.org/10.1186/1465-9921-11-48.CrossRefPubMedPubMedCentral

81.

Zhang X-Y, Xu Y-J, Liu X-S, et al. Cigarette smoke extract promotes proliferation of airway smooth muscle cells in asthmatic rats via regulating cyclin D1 expression. Chin Med J. 2010;123:1709–14.PubMed

82.

Xu G-N, Yang K, Xu Z-P, et al. Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility. Toxicol Appl Pharmacol. 2012;262:70–9. https://doi.org/10.1016/j.taap.2012.04.020.CrossRefPubMed

83.

Stavenow L, Falke P, Berglund A. Effects of different injurious stimuli on cell death, proliferation, and collagen secretion by rabbit aortic smooth muscle cells and human umbilical vein endothelial cells in culture. Med Biol. 1983;61:214–8.PubMed

84.

Yoon CH, Park H-J, Cho Y-W, et al. Cigarette smoke extract-induced reduction in migration and contraction in normal human bronchial smooth muscle cells. Korean J Physiol Pharmacol. 2011;15:397–403. https://doi.org/10.4196/kjpp.2011.15.6.397.CrossRefPubMedPubMedCentral

85.

Zhang W, Case S, Bowler RP, et al. Cigarette smoke modulates PGE2 and host defence against Moraxella catarrhalis infection in human airway epithelial cells. Respirology. 2011;16:508–16.CrossRefPubMed

86.

Sathish V, Vanoosten SK, Miller BS, et al. Brain-derived neurotrophic factor in cigarette smoke-induced airway hyperreactivity. Am J Respir Cell Mol Biol. 2013;48:431–8. https://doi.org/10.1165/rcmb.2012-0129OC.CrossRefPubMedPubMedCentral

87.

Cisneros-Lira J, Gaxiola M, Ramos C, et al. Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in Guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003;285:L949–56. https://doi.org/10.1152/ajplung.00074.2003.CrossRefPubMed

88.

Andrè E, Campi B. Cigarette smoke–induced neurogenic inflammation is mediated by α, β-unsaturated aldehydes and the TRPA1 receptor in rodents. J Clin Invest. 2008;118:2574–82. https://doi.org/10.1172/JCI34886.2574.PubMedPubMedCentral

89.

Simon SA, Liedtke W. How irritating: the role of TRPA1 in sensing cigarette smoke and aerogenic oxidants in the airways. J Clin Invest. 2008;118:2383–6.PubMedPubMedCentral

90.

Bautista DM. Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci. 2005;102:12248–52.CrossRefPubMedPubMedCentral

91.

Bessac BF, Sivula M, von Hehn CA, et al. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest. 2008;118:1899–910.CrossRefPubMedPubMedCentral

92.

Takahashi N, Kuwaki T, Kiyonaka S, et al. TRPA1 underlies a sensing mechanism for O2. Nat Chem Biol. 2011;7:701–11.CrossRefPubMed

93.

Sawada S, Suehisa H, Yamashita M. Inhalation of corticosteroid and β-agonist for persistent cough following pulmonary resection. Gen Thorac Cardiovasc Surg. 2012;60:285–8.CrossRefPubMed

94.

Andersson DA, Gentry C, Moss S, et al. Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci. 2008;28:2485–94. https://doi.org/10.1523/JNEUROSCI.5369-07.2008.CrossRefPubMedPubMedCentral

95.

Dubuis E, Wortley MA, Grace MS, et al. Theophylline inhibits the cough reflex through a novel mechanism of action⋆. J Allergy Clin Immunol. 2014:1–11. https://doi.org/10.1016/j.jaci.2013.11.017.

96.

Smit M, Zuidhof AB, Bos SIT, et al. Bronchoprotection by olodaterol is synergistically enhanced by tiotropium in a Guinea pig model of allergic asthma. J Pharmacol Exp Ther. 2014;348:303–10. https://doi.org/10.1124/jpet.113.208439.CrossRefPubMed

Title: Modelling the asthma phenotype: impact of cigarette smoke exposure
Authors: Maria G. Belvisi
Katie Baker
Nicole Malloy
Kristof Raemdonck
Bilel Dekkak
Michael Pieper
Anthony T. Nials
Mark A. Birrell
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Respiratory Research / Issue 1/2018
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-018-0799-7

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