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Experimental Methods for Evaluating Pharmacodynamic Effects of Drugs for the Pulmonary System

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Drug Discovery and Evaluation: Methods in Clinical Pharmacology

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Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are distinct respiratory diseases with unmet medical needs affecting hundreds of millions of patients worldwide. While asthma and COPD do share a number of common features as they are chronic inflammatory conditions of the lung, they are clearly different diseases with unique characteristics and causes. However, treatment of both these diseases remains primarily the same. There is clearly a need for different drug classes to be developed for the treatment of these conditions. The use of animal models in investigating potential new drugs for asthma has tried to replicate both the early and late asthmatic response to allergen challenge, bronchial hyperresponsiveness, and airway remodelling. Historically, the guinea pig was the species of choice with its many advantages. However, more recently mice have been more widely used in preclinical research although they lack many features of the human condition. The primary characteristic of COPD that is replicated in animal models is non-allergic inflammation. The main challenge with this is that COPD often develops over a significant period of time which is difficult to accurately replicate in an animal model. Once again, different species have been used to best investigate the various aspects of this inflammation. In addition, cough is also an important feature of chronic lung conditions for which no treatment has been approved. Establishing improved animal models that exhibit a hypertussive response would be essential in the development of antitussive drugs. Overall, there is a clear need for the development of improved animal models to aid in the discovery and development of new treatments in both asthma and COPD.

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References and Further Reading

  • Adcock JJ, Douglas GJ, Garabette M, Gascoigne M, Beatch G, Walker M, Page CP (2003) RSD931, a novel anti-tussive agent acting on airway sensory nerves. Br J Pharmacol 138(3):407–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adner M, Canning BJ, Meurs H, Ford W, Ramos Ramirez P, van den Berg MPM, Birrell MA, Stoffels E, Lundblad LKA, Nilsson GP, Olsson HK, Belvisi MG, Dahlen SE (2020) Back to the future: re-establishing guinea pig in vivo asthma models. Clin Sci (Lond) 134(11):1219–1242

    Article  CAS  Google Scholar 

  • Anderson SD (2010) Indirect challenge tests: airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest 138(2 Suppl):25S–30S

    Article  CAS  PubMed  Google Scholar 

  • Anderson SD, Brannan JD (2010) Bronchial provocation testing and collection of sputum with inhaled mannitol. Clin Exp Allergy 40(2):193–196

    Article  CAS  PubMed  Google Scholar 

  • Aun MV, Bonamichi-Santos R, Arantes-Costa FM, Kalil J, Giavina-Bianchi P (2017) Animal models of asthma: utility and limitations. J Asthma Allergy 10:293–301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barnes PJ (1998) Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci (Lond) 94(6):557–572

    Article  CAS  Google Scholar 

  • Barnes PJ (2007a) Prevention of death in COPD. N Engl J Med 356(21):2211, author reply 2213–4

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ (2007b) Scientific rationale for using a single inhaler for asthma control. Eur Respir J 29(3):587–595

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ (2014) Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin Chest Med 35(1):71–86

    Article  PubMed  Google Scholar 

  • Belvisi MG, Birrell MA, Wortley MA, Maher SA, Satia I, Badri H, Holt K, Round P, McGarvey L, Ford J, Smith JA (2017) XEN-D0501, a novel transient receptor potential vanilloid 1 antagonist, does not reduce cough in patients with refractory cough. Am J Respir Crit Care Med 196(10):1255–1263

    Article  CAS  PubMed  Google Scholar 

  • Berry B, Wright JL (1991) Long-term pulmonary hypertension produced by cigarette smoking is associated with subendocardial fibrosis and inflammation of the right ventricle: a morphometric analysis in the guinea pig model. Exp Pathol 43(3–4):163–172

    Article  CAS  PubMed  Google Scholar 

  • Birring SS, Wijsenbeek MS, Agrawal S, van den Berg JWK, Stone H, Maher TM, Tutuncu A, Morice AH (2017) A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial. Lancet Respir Med 5(10):806–815

    Article  CAS  PubMed  Google Scholar 

  • Bonvini SJ, Birrell MA, Smith JA, Belvisi MG (2015) Targeting TRP channels for chronic cough: from bench to bedside. Naunyn Schmiedeberg’s Arch Pharmacol 388(4):401–420

    Article  CAS  Google Scholar 

  • Boura AL, Green AF, Saunders IA (1970) An antitussive test using guinea-pigs. Br J Pharmacol 39(1):225P

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bousquet J, Clark TJ, Hurd S, Khaltaev N, Lenfant C, O'Byrne P, Sheffer A (2007) GINA guidelines on asthma and beyond. Allergy 62(2):102–112

    Article  CAS  PubMed  Google Scholar 

  • Brown RA, Clarke GW, Ledbetter CL, Hurle MJ, Denyer JC, Simcock DE, Coote JE, Savage TJ, Murdoch RD, Page CP, Spina D, O’Connor BJ (2008) Elevated expression of adenosine A1 receptor in bronchial biopsy specimens from asthmatic subjects. Eur Respir J 31(2):311–319

    Article  CAS  PubMed  Google Scholar 

  • Brusasco V, Crimi E, Pellegrino R (1998) Airway hyperresponsiveness in asthma: not just a matter of airway inflammation. Thorax 53(11):992–998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buday T, Gavliakova S, Mokry J, Medvedova I, Kavalcikova-Bogdanova N, Plevkova J (2016) The Guinea pig sensitized by house dust mite: a model of experimental cough studies. Adv Exp Med Biol 905:87–95

    Article  CAS  PubMed  Google Scholar 

  • Buels KS, Fryer AD (2012) Muscarinic receptor antagonists: effects on pulmonary function. Handb Exp Pharmacol 208:317–341

    Article  CAS  Google Scholar 

  • Busse WW (2012) What is the best pulmonary diagnostic approach for wheezing patients with normal spirometry? Respir Care 57(1):39–46, discussion 47–9

    Article  PubMed  Google Scholar 

  • Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ, M and groups, M. s. (2009) Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 374(9691):685–694

    Article  CAS  PubMed  Google Scholar 

  • Canning BJ (2003) Modeling asthma and COPD in animals: a pointless exercise? Curr Opin Pharmacol 3(3):244–250

    Article  CAS  PubMed  Google Scholar 

  • Carrington R, Jordan S, Pitchford SC, Page CP (2018) Use of animal models in IPF research. Pulm Pharmacol Ther 51:73–78

    Article  CAS  PubMed  Google Scholar 

  • Cazzola M, Rogliani P, Calzetta L, Lauro D, Page C, Matera MG (2017) Targeting mechanisms linking COPD to type 2 diabetes mellitus. Trends Pharmacol Sci 38(10):940–951

    Article  CAS  PubMed  Google Scholar 

  • Chapman DG, Tully JE, Nolin JD, Janssen-Heininger YM, Irvin CG (2014) Animal models of allergic airways disease: where are we and where to next? J Cell Biochem 115(12):2055–2064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chung KF (2013) New treatments for severe treatment-resistant asthma: targeting the right patient. Lancet Respir Med 1(8):639–652

    Article  CAS  PubMed  Google Scholar 

  • Chung HS, Kang M, Cho C, Parvez S, Park CH, Kim D, Oh J, Kim H, Shin M, Hong M, Kim Y, Bae H (2007) Inhibition of nitric oxide and tumor necrosis factor-alpha by moutan cortex in activated mouse peritoneal macrophages. Biol Pharm Bull 30(5):912–916

    Article  CAS  PubMed  Google Scholar 

  • Churg A, Cosio M, Wright JL (2008) Mechanisms of cigarette smoke-induced COPD: insights from animal models. Am J Physiol Lung Cell Mol Physiol 294(4):L612–L631

    Article  CAS  PubMed  Google Scholar 

  • Cisneros-Lira J, Gaxiola M, Ramos C, Selman M, Pardo A (2003) Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in guinea pigs. Am J Physiol Lung Cell Mol Physiol 285(4):L949–L956

    Article  CAS  PubMed  Google Scholar 

  • Clay E, Patacchini R, Trevisani M, Preti D, Brana MP, Spina D, Page C (2016) Ozone-induced Hypertussive responses in rabbits and guinea pigs. J Pharmacol Exp Ther 357(1):73–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cockcroft DW (2010) Direct challenge tests: airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest 138(2 Suppl):18S–24S

    Article  CAS  PubMed  Google Scholar 

  • Cockcroft DW, Killian DN, Mellon JJ, Hargreave FE (1977) Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy 7(3):235–243

    Article  CAS  PubMed  Google Scholar 

  • Dahlen SE (2006) Treatment of asthma with antileukotrienes: first line or last resort therapy? Eur J Pharmacol 533(1–3):40–56

    Article  CAS  PubMed  Google Scholar 

  • Dal Negro RW, Wedzicha JA, Iversen M, Fontana G, Page C, Cicero AF, Pozzi E, Calverley PMA, RESTORE group, RESTORE study (2017) Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study. Eur Respir J 50(4):1700711

    Google Scholar 

  • Dalen H (1983) An ultrastructural study of the tracheal epithelium of the guinea-pig with special reference to the ciliary structure. J Anat 136(Pt 1):47–67

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dekhuijzen R, Lavorini F, Usmani OS, van Boven JFM (2018) Addressing the impact and unmet needs of nonadherence in asthma and chronic obstructive pulmonary disease: where do we go from here? J Allergy Clin Immunol Pract 6(3):785–793

    Article  PubMed  Google Scholar 

  • Dell SD, Bola SS, Foty RG, Marshall LC, Nelligan KA, Coates AL (2015) Provocative dose of methacholine causing a 20% drop in FEV1 should be used to interpret methacholine challenge tests with modern nebulizers. Ann Am Thorac Soc 12(3):357–363

    Article  PubMed  Google Scholar 

  • Demoly P, Paggiaro P, Plaza V, Bolge SC, Kannan H, Sohier B, Adamek L (2009) Prevalence of asthma control among adults in France, Germany, Italy, Spain and the UK. Eur Respir Rev 18(112):105–112

    Article  CAS  PubMed  Google Scholar 

  • Dicpinigaitis PV, Morice AH, Birring SS, McGarvey L, Smith JA, Canning BJ, Page CP (2014) Antitussive drugs – past, present, and future. Pharmacol Rev 66(2):468–512

    Article  CAS  PubMed  Google Scholar 

  • Drake MG, Scott GD, Blum ED, Lebold KM, Nie Z, Lee JJ, Fryer AD, Costello RW, Jacoby DB (2018) Eosinophils increase airway sensory nerve density in mice and in human asthma. Sci Transl Med 10(457):eaar8477

    Google Scholar 

  • Dunnill MS (1971) The pathology of asthma. Ciba Found Study Group 38:35–46

    CAS  PubMed  Google Scholar 

  • el-Hashim A, D’Agostino B, Matera MG, Page C (1996) Characterization of adenosine receptors involved in adenosine-induced bronchoconstriction in allergic rabbits. Br J Pharmacol 119(6):1262–1268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernandez-Blanco JA, Aguilera M, Domenech A, Tarrason G, Prats N, Miralpeix M, De Alba J (2015) Enhanced cough reflex in a model of bleomycin-induced lung fibrosis in guinea pigs. Clin Sci (Lond) 129(12):1001–1010

    Article  CAS  Google Scholar 

  • Finney L, Berry M, Singanayagam A, Elkin SL, Johnston SL, Mallia P (2014) Inhaled corticosteroids and pneumonia in chronic obstructive pulmonary disease. Lancet Respir Med 2(11):919–932

    Article  CAS  PubMed  Google Scholar 

  • Fowdar K, Chen H, He Z, Zhang J, Zhong X, Zhang J, Li M, Bai J (2017) The effect of N-acetylcysteine on exacerbations of chronic obstructive pulmonary disease: a meta-analysis and systematic review. Heart Lung 46(2):120–128

    Article  PubMed  Google Scholar 

  • Fowler SJ, Dempsey OJ, Sims EJ, Lipworth BJ (2000) Screening for bronchial hyperresponsiveness using methacholine and adenosine monophosphate. Relationship to asthma severity and beta(2)-receptor genotype. Am J Respir Crit Care Med 162(4 Pt 1):1318–1322

    Article  CAS  PubMed  Google Scholar 

  • Franciosi LG, Diamant Z, Banner KH, Zuiker R, Morelli N, Kamerling IM, de Kam ML, Burggraaf J, Cohen AF, Cazzola M, Calzetta L, Singh D, Spina D, Walker MJ, Page CP (2013) Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials. Lancet Respir Med 1(9):714–727

    Article  CAS  PubMed  Google Scholar 

  • Galli SJ, Tsai M (2012) IgE and mast cells in allergic disease. Nat Med 18(5):693–704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghorani V, Boskabady MH, Khazdair MR, Kianmeher M (2017) Experimental animal models for COPD: a methodological review. Tob Induc Dis 15:25

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • GINA (2020) Global strategy for asthma management and prevention. Available at: https://ginasthma.org/reports/

  • Global Burden of Disease Study (2017) Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390(10100):1211–1259

    Article  Google Scholar 

  • GOLD (2020) 2020 global strategy for prevention, diagnosis and management of COPD. Available at: https://goldcopd.org/gold-reports/

  • Green AF, Ward NB (1955) The action of analgesics and nalorphine on the cough reflex. Br J Pharmacol Chemother 10(4):418–423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grootendorst DC, Rabe KF (2004) Mechanisms of bronchial hyperreactivity in asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc 1(2):77–87

    Article  CAS  PubMed  Google Scholar 

  • Hammad H, Lambrecht BN (2015) Barrier epithelial cells and the control of type 2 immunity. Immunity 43(1):29–40

    Article  CAS  PubMed  Google Scholar 

  • Han B, Poppinga WJ, Zuo H, Zuidhof AB, Bos IS, Smit M, Vogelaar P, Krenning G, Henning RH, Maarsingh H, Halayko AJ, van Vliet B, Stienstra S, Graaf AC, Meurs H, Schmidt M (2016) The novel compound Sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary disease. Sci Rep 6:26928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hogg JC, Timens W (2009) The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol 4:435–459

    Article  CAS  PubMed  Google Scholar 

  • Holmes AM, Solari R, Holgate ST (2011) Animal models of asthma: value, limitations and opportunities for alternative approaches. Drug Discov Today 16(15–16):659–670

    Article  PubMed  Google Scholar 

  • Horton MR, Santopietro V, Mathew L, Horton KM, Polito AJ, Liu MC, Danoff SK, Lechtzin N (2012) Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial. Ann Intern Med 157(6):398–406

    Article  PubMed  Google Scholar 

  • Jack D (1991) The 1990 Lilly Prize Lecture. A way of looking at agonism and antagonism: lessons from salbutamol, salmeterol and other beta-adrenoceptor agonists. Br J Clin Pharmacol 31(5):501–514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones TR, Labelle M, Belley M, Champion E, Charette L, Evans J, Ford-Hutchinson AW, Gauthier JY, Lord A, Masson P et al (1995) Pharmacology of montelukast sodium (Singulair), a potent and selective leukotriene D4 receptor antagonist. Can J Physiol Pharmacol 73(2):191–201

    Article  CAS  PubMed  Google Scholar 

  • Karlsson JA, Hansson L, Wollmer P, Dahlback M (1991) Regional sensitivity of the respiratory tract to stimuli causing cough and reflex bronchoconstriction. Respir Med 85(Suppl A):47–50

    Article  PubMed  Google Scholar 

  • Keir S, Boswell-Smith V, Spina D, Page C (2006) Mechanism of adenosine-induced airways obstruction in allergic guinea pigs. Br J Pharmacol 147(7):720–728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keir SD, Spina D, Douglas G, Herd C, Page CP (2011) Airway responsiveness in an allergic rabbit model. J Pharmacol Toxicol Methods 64(2):187–195

    Article  CAS  PubMed  Google Scholar 

  • Keir SD, Spina D, Page CP (2015) Bradykinin and capsaicin induced airways obstruction in the guinea pig are platelet dependent. Pulm Pharmacol Ther 33:25–31

    Article  CAS  PubMed  Google Scholar 

  • Lambrecht BN, Hammad H (2012) The airway epithelium in asthma. Nat Med 18(5):684–692

    Article  CAS  PubMed  Google Scholar 

  • Lexmond AJ, Keir S, Terakosolphan W, Page CP, Forbes B (2018) A novel method for studying airway hyperresponsiveness in allergic guinea pigs in vivo using the PreciseInhale system for delivery of dry powder aerosols. Drug Deliv Transl Res 8(3):760–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Wilson JW (1997) Increased vascularity of the bronchial mucosa in mild asthma. Am J Respir Crit Care Med 156(1):229–233

    Article  CAS  PubMed  Google Scholar 

  • Li X, Cao X, Guo M, Xie M, Liu X (2020) Trends and risk factors of mortality and disability adjusted life years for chronic respiratory diseases from 1990 to 2017: systematic analysis for the Global Burden of Disease Study 2017. BMJ 368:m234

    Article  PubMed  PubMed Central  Google Scholar 

  • Lieutier-Colas F, Purohit A, Meyer P, Fabries JF, Kopferschmitt MC, Dessanges JF, Pauli G, de Blay F (2003) Bronchial challenge tests in patients with asthma sensitized to cats: the importance of large particles in the immediate response. Am J Respir Crit Care Med 167(8):1077–1082

    Article  PubMed  Google Scholar 

  • Lloyd CM, Gonzalo JA, Coyle AJ, Gutierrez-Ramos JC (2001) Mouse models of allergic airway disease. Adv Immunol 77:263–295

    Article  CAS  PubMed  Google Scholar 

  • Lundgren R, Soderberg M, Horstedt P, Stenling R (1988) Morphological studies of bronchial mucosal biopsies from asthmatics before and after ten years of treatment with inhaled steroids. Eur Respir J 1(10):883–889

    CAS  PubMed  Google Scholar 

  • Lungarella G, Barni-Comparini I, Fonzi L (1984) Pulmonary changes induced in rabbits by long-term exposure to n-hexane. Arch Toxicol 55(4):224–228

    Article  CAS  PubMed  Google Scholar 

  • Manzini S (1992) Bronchodilatation by tachykinins and capsaicin in the mouse main bronchus. Br J Pharmacol 105(4):968–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McDonough JE, Yuan R, Suzuki M, Seyednejad N, Elliott WM, Sanchez PG, Wright AC, Gefter WB, Litzky L, Coxson HO, Pare PD, Sin DD, Pierce RA, Woods JC, McWilliams AM, Mayo JR, Lam SC, Cooper JD, Hogg JC (2011) Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N Engl J Med 365(17):1567–1575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Menzella F, Galeone C, Bertolini F, Castagnetti C, Facciolongo N (2017) Innovative treatments for severe refractory asthma: how to choose the right option for the right patient? J Asthma Allergy 10:237–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meshi B, Vitalis TZ, Ionescu D, Elliott WM, Liu C, Wang XD, Hayashi S, Hogg JC (2002) Emphysematous lung destruction by cigarette smoke. The effects of latent adenoviral infection on the lung inflammatory response. Am J Respir Cell Mol Biol 26(1):52–57

    Article  CAS  PubMed  Google Scholar 

  • Miller I, Rogel-Gaillard C, Spina D, Fontanesi L, de Almeida AM (2014) The rabbit as an experimental and production animal: from genomics to proteomics. Curr Protein Pept Sci 15(2):134–145

    Article  CAS  PubMed  Google Scholar 

  • Minshall EM, Riccio MM, Herd CM, Douglas GJ, Seeds EA, McKenniff MG, Sasaki M, Spina D, Page CP (1993) A novel animal model for investigating persistent airway hyperresponsiveness. J Pharmacol Toxicol Methods 30(4):177–188

    Article  CAS  PubMed  Google Scholar 

  • Muccitelli RM, Tucker SS, Hay DW, Torphy TJ, Wasserman MA (1987) Is the guinea pig trachea a good in vitro model of human large and central airways? Comparison on leukotriene-, methacholine-, histamine- and antigen-induced contractions. J Pharmacol Exp Ther 243(2):467–473

    CAS  PubMed  Google Scholar 

  • Nishi Y, Boswell V, Ansari T, Piprawala F, Satchi S, Page CP (2003) Elastase-induced changes in lung function: relationship to morphometry and effect of drugs. Pulm Pharmacol Ther 16(4):221–229

    Article  CAS  PubMed  Google Scholar 

  • O’Byrne PM, Inman MD (2003) Airway hyperresponsiveness. Chest 123(3 Suppl):411S–416S

    Article  PubMed  Google Scholar 

  • Page C, Black J (1994) Airways and vascular remodelling in asthma and cardiovascular disease: implications for therapeutic intervention: based on the Scientific Program, Silverado, Napa Valley, California, May 12th–14th, 1993. Academic, London

    Google Scholar 

  • Page C, O’Shaughnessy B, Barnes P (2017) Pathogenesis of COPD and asthma. Handb Exp Pharmacol 237:1–21

    CAS  PubMed  Google Scholar 

  • Palmqvist M, Cui ZH, Sjostrand M, Linden A, Lotvall J (2001) Reduced late asthmatic response by repeated low-dose allergen exposure. Eur Respir J 17(5):872–880

    Article  CAS  PubMed  Google Scholar 

  • Pare PD, McParland BE, Seow CY (2007) Structural basis for exaggerated airway narrowing. Can J Physiol Pharmacol 85(7):653–658

    Article  CAS  PubMed  Google Scholar 

  • Patel NR, Cunoosamy DM, Fageras M, Taib Z, Asimus S, Hegelund-Myrback T, Lundin S, Pardali K, Kurian N, Ersdal E, Kristensson C, Korsback K, Palmer R, Brown MN, Greenaway S, Siew L, Clarke GW, Rennard SI, Make BJ, Wise RA, Jansson P (2018) The development of AZD7624 for prevention of exacerbations in COPD: a randomized controlled trial. Int J Chron Obstruct Pulmon Dis 13:1009–1019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pauwels RA, Lofdahl CG, Laitinen LA, Schouten JP, Postma DS, Pride NB, Ohlsson SV (1999) Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med 340(25):1948–1953

    Article  CAS  PubMed  Google Scholar 

  • Persson CG, Erjefalt JS, Korsgren M, Sundler F (1997) The mouse trap. Trends Pharmacol Sci 18(12):465–467

    Article  CAS  PubMed  Google Scholar 

  • Phillipps GH (1990) Structure-activity relationships of topically active steroids: the selection of fluticasone propionate. Respir Med 84(Suppl A):19–23

    Article  PubMed  Google Scholar 

  • Piper PJ (1985) Leukotrienes: potent mediators of airway constriction. Int Arch Allergy Appl Immunol 76(Suppl 1):43–48

    Article  CAS  PubMed  Google Scholar 

  • Pitchford SC, Riffo-Vasquez Y, Sousa A, Momi S, Gresele P, Spina D, Page CP (2004) Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation. Blood 103(2):639–647

    Article  CAS  PubMed  Google Scholar 

  • Platts-Mills TA, Wheatley LM (1996) The role of allergy and atopy in asthma. Curr Opin Pulm Med 2(1):29–34

    CAS  PubMed  Google Scholar 

  • Poblete MT, Garces G, Figueroa CD, Bhoola KD (1993) Localization of immunoreactive tissue kallikrein in the seromucous glands of the human and guinea-pig respiratory tree. Histochem J 25(11):834–839

    Article  CAS  PubMed  Google Scholar 

  • Postma DS, Rabe KF (2015) The asthma-COPD overlap syndrome. N Engl J Med 373(13):1241–1249

    Article  CAS  PubMed  Google Scholar 

  • Prior H, Baldrick P, Beken S, Booler H, Bower N, Brooker P, Brown P, Burlinson B, Burns-Naas LA, Casey W, Chapman M, Clarke D, de Haan L, Doehr O, Downes N, Flaherty M, Gellatly N, Moesgaard SG, Harris J, Holbrook M, Hui J, Jones D, Jones K, Kedar H, Mahl A, Manninen A, McGuire A, Mortimer-Cassen E, Peraza M, Pugsley MK, Richard J, Roberts R, Roosen W, Rothfuss A, Schoenmakers A, Sewell F, Weaver R, Weir L, Wolfreys A, Kimber I (2020) Opportunities for use of one species for longer-term toxicology testing during drug development: a cross-industry evaluation. Regul Toxicol Pharmacol 113:104624

    Article  CAS  PubMed  Google Scholar 

  • Reed CE (1986) New therapeutic approaches in asthma. J Allergy Clin Immunol 77(4):537–543

    Article  CAS  PubMed  Google Scholar 

  • Ressmeyer AR, Larsson AK, Vollmer E, Dahlen SE, Uhlig S, Martin C (2006) Characterisation of guinea pig precision-cut lung slices: comparison with human tissues. Eur Respir J 28(3):603–611

    Article  CAS  PubMed  Google Scholar 

  • Reynolds SM, Docherty R, Robbins J, Spina D, Page CP (2008) Adenosine induces a cholinergic tracheal reflex contraction in guinea pigs in vivo via an adenosine A1 receptor-dependent mechanism. J Appl Physiol (1985) 105(1):187–196

    Article  CAS  Google Scholar 

  • Rogliani P, Matera MG, Page C, Puxeddu E, Cazzola M, Calzetta L (2019) Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine. Respir Res 20(1):104

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sadarani BN, Majumdar AS (2015) Resveratrol potentiates the effect of dexamethasone in rat model of acute lung inflammation. Int Immunopharmacol 28(1):773–779

    Article  CAS  PubMed  Google Scholar 

  • Seemungal T, Harper-Owen R, Bhowmik A, Moric I, Sanderson G, Message S, Maccallum P, Meade TW, Jeffries DJ, Johnston SL, Wedzicha JA (2001) Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 164(9):1618–1623

    Article  CAS  PubMed  Google Scholar 

  • Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ (2011) Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ 342:d2549

    Article  PubMed  PubMed Central  Google Scholar 

  • Singh D, Beeh KM, Colgan B, Kornmann O, Leaker B, Watz H, Lucci G, Geraci S, Emirova A, Govoni M, Nandeuil MA (2019) Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD. Respir Res 20(1):180

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Smith JA, Badri H (2019) Cough: new pharmacology. J Allergy Clin Immunol Pract 7(6):1731–1738

    Article  PubMed  Google Scholar 

  • Sonnex K, Alleemudder H, Knaggs R (2020) Impact of smoking status on the efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review. BMJ Open 10(4):e037509

    Article  PubMed  PubMed Central  Google Scholar 

  • Spina D, Page CP (2002) Asthma – a need for a rethink? Trends Pharmacol Sci 23(7):311–315

    Article  CAS  PubMed  Google Scholar 

  • Sterk PJ, Bel EH (1989) Bronchial hyperresponsiveness: the need for a distinction between hypersensitivity and excessive airway narrowing. Eur Respir J 2(3):267–274

    CAS  PubMed  Google Scholar 

  • Tepper RS, Wise RS, Covar R, Irvin CG, Kercsmar CM, Kraft M, Liu MC, O’Connor GT, Peters SP, Sorkness R, Togias A (2012) Asthma outcomes: pulmonary physiology. J Allergy Clin Immunol 129(3 Suppl):S65–S87

    Article  PubMed  PubMed Central  Google Scholar 

  • Touvay C, Pfister A, Vilain B, Carre C, Page CP, Lellouch-Tubiana A, Pignol B, Mencia-Huerta JM, Braquet P (1991) Effect of long-term infusion of platelet-activating factor on pulmonary responsiveness and morphology in the guinea-pig. Pulm Pharmacol 4(1):43–51

    Article  CAS  PubMed  Google Scholar 

  • Traver GA, Cline MG, Burrows B (1979) Predictors of mortality in chronic obstructive pulmonary disease. A 15-year follow-up study. Am Rev Respir Dis 119(6):895–902

    CAS  PubMed  Google Scholar 

  • Van Den Berge M, Meijer RJ, Kerstjens HA, de Reus DM, Koeter GH, Kauffman HF, Postma DS (2001) PC(20) adenosine 5′-monophosphate is more closely associated with airway inflammation in asthma than PC(20) methacholine. Am J Respir Crit Care Med 163(7):1546–1550

    Article  Google Scholar 

  • Van Schoor J, Pauwels R, Joos G (2005) Indirect bronchial hyper-responsiveness: the coming of age of a specific group of bronchial challenges. Clin Exp Allergy 35(3):250–261

    Article  PubMed  Google Scholar 

  • Venkatasamy R, McKenzie A, Page CP, Walker MJ, Spina D (2010) Use of within-group designs to test anti-tussive drugs in conscious guinea-pigs. J Pharmacol Toxicol Methods 61(2):157–162

    Article  CAS  PubMed  Google Scholar 

  • Vestbo J, TORCH Study Group (2004) The TORCH (towards a revolution in COPD health) survival study protocol. Eur Respir J 24(2):206–210

    Article  CAS  PubMed  Google Scholar 

  • Ward AJ, McKenniff MG, Evans JM, Page CP, Costello JF (1994) Bronchial responsiveness is not always increased after allergen challenge. Respir Med 88(6):445–451

    Article  CAS  PubMed  Google Scholar 

  • Wedzicha JA, Seemungal TA (2007) COPD exacerbations: defining their cause and prevention. Lancet 370(9589):786–796

    Article  PubMed  PubMed Central  Google Scholar 

  • Wenzel SE (2012) Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 18(5):716–725

    Article  CAS  PubMed  Google Scholar 

  • Widdicombe JG (1980) Mechanism of cough and its regulation. Eur J Respir Dis Suppl 110:11–20

    CAS  PubMed  Google Scholar 

  • Winter CA, Flataker L (1954) Antitussive compounds: testing methods and results. J Pharmacol Exp Ther 112(1):99–108

    CAS  PubMed  Google Scholar 

  • Woisin FE, Herd CM, Douglas GJ, Raynor K, Spina D, Mitchell HW, Page CP (2001) Relationship of airway responsiveness with airway morphometry in normal and immunized rabbits. Pulm Pharmacol Ther 14(2):75–83

    Article  CAS  PubMed  Google Scholar 

  • Wright JL, Churg A (1990) Cigarette smoke causes physiologic and morphologic changes of emphysema in the guinea pig. Am Rev Respir Dis 142(6 Pt 1):1422–1428

    Article  CAS  PubMed  Google Scholar 

  • Wright JL, Churg A (1991) Effect of long-term cigarette smoke exposure on pulmonary vascular structure and function in the guinea pig. Exp Lung Res 17(6):997–1009

    Article  CAS  PubMed  Google Scholar 

  • Wright JL, Sun JP (1994) Effect of smoking cessation on pulmonary and cardiovascular function and structure: analysis of guinea pig model. J Appl Physiol (1985) 76(5):2163–2168

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Sackler Institute of Pulmonary Pharmacology, King’s College London, London, UK

    S. D. Keir-Rudman, Y. Riffo-Vasquez, C. L. Robaina Cabrera & C. P. Page

Authors
  1. S. D. Keir-Rudman
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  2. Y. Riffo-Vasquez
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  3. C. L. Robaina Cabrera
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  4. C. P. Page
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Correspondence to C. P. Page .

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Editors and Affiliations

  1. CorDynamics, Dieburg, Germany

    Franz J. Hock

  2. CorDynamics, Chicago, IL, USA

    Michael R. Gralinski

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Keir-Rudman, S.D., Riffo-Vasquez, Y., Robaina Cabrera, C.L., Page, C.P. (2020). Experimental Methods for Evaluating Pharmacodynamic Effects of Drugs for the Pulmonary System. In: Hock, F.J., Gralinski, M.R. (eds) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer, Cham. https://doi.org/10.1007/978-3-319-56637-5_73-1

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  • DOI: https://doi.org/10.1007/978-3-319-56637-5_73-1

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