A real - life observational pilot study to evaluate the effects of two-week treatment with montelukast in patients with chronic cough

Roxana K Mincheva, Tanya Z Kralimarkova, Miroslava Rasheva, Zlatko Dimitrov, Denislava Nedeva, Maria Staevska, Vera Papochieva, Penka Perenovska, Karina Bacheva, Vasil D Dimitrov, Todor A Popov, Roxana K Mincheva, Tanya Z Kralimarkova, Miroslava Rasheva, Zlatko Dimitrov, Denislava Nedeva, Maria Staevska, Vera Papochieva, Penka Perenovska, Karina Bacheva, Vasil D Dimitrov, Todor A Popov

Abstract

Background: Different conditions make the proximal airways susceptible to tussigenic stimuli in the chronic cough (CC) syndrome. Leukotrienes can be implicated in the inflammatory mechanism at play in it. Montelukast is a selective cysteinyl-leukotriene receptor antagonist with proven effectiveness in patients with asthma. The aim of our real-life pilot study was to use montelukast to relieve cough symptoms in patients with CC allegedly due to the two frequent causes other than asthma - upper airway cough syndrome and gastroesophageal reflux (GER).

Methods: 14 consecutive patients with CC were evaluated before and after 2 weeks of treatment with montelukast 10 mg daily. Cough was assessed by validated cough questionnaire. Questionnaires regarding the presence of gastroesophageal reflux were also completed. Cough reflex sensitivity to incremental doubling concentrations of citric acid and capsaicin was measured. Lung function, airway hyperresponsiveness and exhaled breath temperature (EBT), a non-invasive marker of lower airway inflammation, were evaluated to exclude asthma as an underlying cause. Thorough upper-airway examination was also conducted. Cell counts, eosinophil cationic protein (ECP), lactoferrin, myeloperoxidase (MPO) were determined in blood to assess systemic inflammation.

Results: Discomfort due to cough was significantly reduced after treatment (P < 0.001). Cough threshold for capsaicin increased significantly (P = 0.001) but not for citric acid. The values of lactoferrin and ECP were significantly reduced, but those of MPO rose. EBT and pulmonary function were not significantly affected by the treatment.

Conclusion: Patients with CC due to upper airway cough syndrome or gastroesophageal reflux (GER) but not asthma reported significant relief of their symptoms after two weeks of treatment with montelukast. ECP, lactoferrin, MPO altered significantly, highlighting their role in the pathological mechanisms in CC. Clinical trial ID at Clinicaltrials.gov is NCT01754220.

Figures

Figure 1
Figure 1
Leicester cough Questionnaire (LCQ) scores before and after treatment.
Figure 2
Figure 2
Inverse correlation between LCQ and FSSG scores.
Figure 3
Figure 3
Cough indices for citric acid before and after treatment.
Figure 4
Figure 4
Cough indices for capsaicin before and after treatment.

References

    1. Pratter MR. Overview of common causes of chronic cough: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):59S–62S.
    1. Palombini BC, Villanova CA, Araújo E, Gastal OL, Alt DC, Stolz DP, Palombini CO. A pathogenic triad in chronic cough: asthma, postnasal drip syndrome, and gastroesophageal reflux disease. Chest. 1999;116(2):279–84. doi: 10.1378/chest.116.2.279.
    1. Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet. 2008;371(9621):364–74.
    1. Chung KF. Chronic cough: future directions in chronic cough: mechanisms and antitussives. Chron Respir Dis. 2007;4(3):159–65. doi: 10.1177/1479972307077894.
    1. Chung KF, Widdicombe JG. Pharmacology and therapeutics of cough. Preface. Handb Exp Pharmacol. 2009;187:v–vi.
    1. Dicpinigaitis PV. Short- and long-term reproducibility of capsaicin cough challenge testing. Pulm Pharmacol Ther. 2003;16(1):61–5. doi: 10.1016/S1094-5539(02)00149-9.
    1. Irwin RS. Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):80S–94S.
    1. Decalmer S, Stovold R, Houghton LA, Pearson J, Ward C, Kelsall A, Jones H, McGuinness K, Woodcock A, Smith JA. Chronic cough: relationship between microaspiration, gastroesophageal reflux, and cough frequency. Chest. 2012;142(4):958–64.
    1. Kastelik JA, Redington AE, Aziz I, Buckton GK, Smith CM, Dakkak M, Morice AH. Abnormal oesophageal motility in patients with chronic cough. Thorax. 2003;58(8):699–702. doi: 10.1136/thorax.58.8.699.
    1. Peters-Golden M, Henderson WR. Leukotrienes. N Engl J Med. 2007;357(18):1841–54. doi: 10.1056/NEJMra071371.
    1. Kanaoka Y, Boyce AA. Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses. J Immunol. 2004;173(3):1503–1510.
    1. McAlexander MA, Myers AC, Undem BJ. Inhibition of 5-lipoxygenase diminishes neurally evoked tachykinergic contraction of guinea pig isolated airway. J Pharmacol Exp Ther. 1998;285(2):602–607.
    1. GINA Guidelines. 2014. [cited 2014 20 Jan]; Available from:
    1. Tintinger GR, Feldman C, Theron AJ, Anderson R. Montelukast: more than a Cysteinyl Leukotriene Receptor Antagonist? Sci World J. 2010;10:2403–13.
    1. Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, van Wijk RG, Ohta K, Zuberbier T. Schünemann HJ; Global Allergy and Asthma European Network; Grading of Recommendations Assessment, Development and Evaluation Working Grou Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 Revision. J Allergy Clin Immunol. 2010;126(3):466–476. doi: 10.1016/j.jaci.2010.06.047.
    1. Kita T, Fujimura M, Ogawa H, Nakatsumi Y, Nomura S, Ishiura Y, Myou S, Nakao S. Antitussive effects of the leukotriene receptor antagonist montelukast in patients with cough variant asthma and atopic cough. Allergol Int. 2010;59(2):185–92. doi: 10.2332/allergolint.09-OA-0112.
    1. Spector SL, Tan RA. Effectiveness of montelukast in the treatment of cough variant asthma. Ann Allergy Asthma Immunol. 2004;93(3):232–6. doi: 10.1016/S1081-1206(10)61493-7.
    1. Dicpinigaitis V, Dobkin JB, Reichel J. Antitussive effect of the leukotriene receptor antagonist zafirlukast in subjects with cough-variant asthma. J Asthma. 2002;39(4):291–7. doi: 10.1081/JAS-120002285.
    1. Birring SS, Prudon B, Carr AJ, Singh SJ, Morgan MD, Pavord ID. Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ) Thorax. 2003;58(4):339–43. doi: 10.1136/thorax.58.4.339.
    1. Kusano M, Shimoyama Y, Sugimoto S, Kawamura O, Maeda M, Minashi K, Kuribayashi S, Higuchi T, Zai H, Ino K, Horikoshi T, Sugiyama T, Toki M, Ohwada T, Mori M. Development and evaluation of FSSG: frequency scale for the symptoms of GERD. J Gastroenterol. 2004;39(9):888–91. doi: 10.1007/s00535-004-1417-7.
    1. Birring SS. Controversies in the evaluation and management of chronic cough. Am J Respir Crit Care Med. 2011;183(6):708–15. doi: 10.1164/rccm.201007-1017CI.
    1. Popov TA, Kralimarkova TZ, Dimitrov VD. Measurement of exhaled breath temperature in science and clinical practice. Breathe. 2012;8(3):187–92.
    1. Morice AH, Fontana GA, Belvisi MG, Birring SS, Chung KF, Dicpinigaitis PV, Kastelik JA, McGarvey LP, Smith JA, Tatar M, Widdicombe J. ERS guidelines on the assessment of cough. Eur Respir J. 2007;29(6):1256–76. doi: 10.1183/09031936.00101006.
    1. Morice AH, Higgins KS, Yeo WW. Adaptation of cough reflex with different types of stimulation. Eur Respir J. 1992;5(7):841–7.
    1. Irwin RS, Zawacki JK, Curley FJ, French CL, Hoffman PJ. Chronic Cough as the Sole Presenting Manifestation of Gastroesophageal Reflux. Am Rev Respir Dis. 1989;140(5):1294–1300. doi: 10.1164/ajrccm/140.5.1294.
    1. Gibson PG, Dolovich J, Denburg J, Ramsdale EH, Hargreave FE. Chronic Cough - Eosinophilic Bronchitis without Asthma. Lancet. 1989;1(8651):1346–1348.
    1. Takemura M, Niimi A, Matsumoto H, Ueda T, Matsuoka H, Yamaguchi M, Jinnai M, Chin K, Mishima M. Clinical, physiological and anti-inflammatory effect of montelukast in patients with cough variant asthma. Respiration. 2012;83(4):308–15. doi: 10.1159/000332835.
    1. Hay DW. Pharmacology of leukotriene receptor antagonists. More than inhibitors of bronchoconstriction. Chest. 1997;111(2 Suppl):35S–45S.
    1. Huber C, Marschallinger J, Tempfer H, Furtner T, Couillard-Despres S, Bauer HC, Rivera FJ, Aigner L. Inhibition of leukotriene receptors boosts neural progenitor proliferation. Cell Physiol Biochem. 2011;28(5):793–804. doi: 10.1159/000335793.
    1. Taylor MB, Zweiman B, Moskovitz AR, von Allmen C, Atkins PC. Platelet-activating factor- and leukotriene B4-induced release of lactoferrin from blood neutrophils of atopic and nonatopic individuals. J Allergy Clin Immunol. 1990;86(5):740–8. doi: 10.1016/S0091-6749(05)80178-2.
    1. Lee CW, Lewis RA, Tauber AI, Mehrotra M, Corey EJ, Austen KF. The myeloperoxidase-dependent metabolism of leukotrienes C4, D4, and E4 to 6-trans-leukotriene B4 diastereoisomers and the subclass-specific S-diastereoisomeric sulfoxides. J Biol Chem. 1983;258(24):15004–10.
    1. Kubala L, Schmelzer KR, Klinke A, Kolarova H, Baldus S, Hammock BD. Eiserich J Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation. Free Radic Biol Med. 2010;48(10):1311–20. doi: 10.1016/j.freeradbiomed.2010.02.010.
    1. Dicpinigaitis PV. Review: effect of drugs on human cough reflex sensitivity to inhaled capsaicin. Cough. 2012;8(1):10. doi: 10.1186/1745-9974-8-10.
    1. Roche N, Reddel H, Agusti A, Bateman ED, Krishnan JA, Martin RJ, Papi A, Postma D, Thomas M, Brusselle G, Israel E, Rand C, Chisholm A, Price D. Respiratory Effectiveness Group. Integrating real-life studies in the global therapeutic research framework. Lancet Respir Med. 2013;1(8):30–32.
    1. Schäper C, Noga O, Koch B, Ewert R, Felix SB, Gläser S, Kunkel G, Gustavus B. Anti-inflammatory properties of montelukast, a leukotriene receptor antagonist in patients with asthma and nasal polyposis. J Investig Allergol Clin Immunol. 2011;21(1):51–8.

Source: PubMed

3
Tilaa