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Cough Remedies for Children and Adolescents: Current and Future Perspectives

  • Therapy in Practice
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Abstract

Cough is a widespread symptom in children and adolescents. Despite advances in scientific knowledge about the neurophysiological mechanisms underlying the cough reflex, the best therapeutic approaches for children and adolescents who cough remain unclear, and many needs are still unmet. Many remedies for cough are self-prescribed, reflecting strong demand, but significant evidence of their efficacy and safety is missing in pediatric populations. Moreover, as most coughs are part of self-limited illnesses, treatment could be considered unnecessary in some patients. Drug therapy to relieve cough and other symptoms is an essential part of treating a child with cough. However, unfortunately, the number of studies in each category of cough medications is minimal, and dosing and treatment duration varies significantly among studies. Some treatments have been shown to be no more effective than placebo. Lack of clear indications for dosing and treatment duration, the number of available drugs, the numerous active ingredients in products, and multiple caregivers administering medication to children have been considered contributors to an increased risk of inappropriate prescribing, accidental overdosing, and adverse events. This review presents the most recent evidence on the safety and efficacy of available cough remedies, focusing on the pediatric age group, and includes H1 receptor antagonists, mucolytics and expectorants, drugs acting peripherally on the cough reflex, drugs acting centrally on the cough reflex, drugs acting both peripherally and centrally on the cough reflex, and other compounds, including menthol, glycerol, honey, and medical devices composed of complex natural substances. Future perspectives on new therapeutic targets are also discussed.

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References

  1. US Food and Drug Administration. FDA releases recommendations regarding use of the over-the-counter cough and cold products. 2008. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm. Accessed 22 July 2020.

  2. US Food and Drug Administration. OTC Cough and Cold Products: Not For Infants and Children Under 2 Years of Age; 2018. https://www.fda.gov/consumers/consumer-updates/otc-cough-and-cold-products-not-infants-and-children-under-2-years-age. Aaccessed 16 July 2020.

  3. Parisi GF, Leonardi S, Ciprandi G, Corsico A, Licari A, Miraglia Del Giudice M, et al. cetirizine uses in childhood: an update of a friendly 30-year drug. Clin Mol Allergy. 2020;18:2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Parisi GF, Licari A, Papale M, Manti S, Salpietro C, Marseglia GL, et al. Antihistamines: ABC for the pediatricians. Pediatr Allergy Immunol. 2020;31(Suppl 24):34–6.

    Article  PubMed  Google Scholar 

  5. Simons FER. Advances in H1-antihistamines. N Engl J Med. 2004;351:2203–17.

    Article  PubMed  CAS  Google Scholar 

  6. Chang AB, Peake J, McElrea MS. Anti-histamines for prolonged non-specific cough in children. Cochrane Database Syst Rev. 2008;2:CD005604.

    Google Scholar 

  7. Ciprandi G, Tosca M, Ricca V, Passalacqua G, Fregonese L, Fasce L, et al. Cetirizine treatment of allergic cough in children with pollen allergy. Allergy. 1997;52:752–4.

    Article  PubMed  CAS  Google Scholar 

  8. Ciprandi G, Tosca M, Ricca V, Passalacqua G, Riccio AM, Bagnasco M, et al. Cetirizine treatment of rhinitis in children with pollen allergy: evidence of its antiallergic activity. Clin Exp Allergy. 1997;27(10):1160–6.

    Article  PubMed  CAS  Google Scholar 

  9. Ciprandi G, Buscaglia S, Catrullo A, Marchesi E, Bianchi B, Canonica GW. Loratadine in the treatment of cough associated with allergic rhinoconjunctivitis. Ann Allergy Asthma Immunol. 1995;75:115–20.

    PubMed  CAS  Google Scholar 

  10. Wei H, Li W, Jiang Z, Xi X, Qi G. Clinical efficacy of montelukast sodium combined with budesonide or combined with loratadine in treating children with cough variant asthma and influence on inflammatory factors in the serum. Exp Ther Med. 2019;18(1):411–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  11. Paul IM, Yoder KE, Crowell KR, Shaffer ML, McMillan HS, Carlson LC, et al. Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents. Pediatrics. 2004;114:e85–e90.

    Article  PubMed  Google Scholar 

  12. Yoder KE, Shaffer ML, La Tournous SJ, Paul IM. Child assessment of dextromethorphan, diphenhydramine, and placebo for nocturnal cough due to upper respiratory infection. Clin Pediatr (Phila). 2006;45:633–40.

    Article  Google Scholar 

  13. Shadkam MN, Mozaffari-Khosravi H, Mozayan MR. A comparison of the effect of honey, dextromethorphan, and diphenhydramine on nightly cough and sleep quality in children and their parents. J Altern Complement Med. 2010;16:787–93.

    Article  PubMed  Google Scholar 

  14. Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database Syst Rev. 2014;2014(11):CD001831.

    PubMed Central  Google Scholar 

  15. Clemens CJ, Taylor JA, Almquist JR, Quinn HC, Mehta A, Naylor GS. Is an antihistamine-decongestant combination effective in temporarily relieving symptoms of the common cold in preschool children? J Pediatr. 1997;130:463–6.

    Article  PubMed  CAS  Google Scholar 

  16. Hutton N, Wilson MH, Mellits ED, et al. Effectiveness of an antihistamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial. J Pediatr. 1991;118:125–30.

    Article  PubMed  CAS  Google Scholar 

  17. Unuvar E, Yildiz I, Kilic A, Toprak S, Selvi Aslan S, Aydin S, et al. Is acetaminophen as effective as an antihistamine-decongestant-acetaminophen combination in relieving symptoms of acute nasopharyngitis in children? A randomized, controlled trial. Int J Pediatr Otorhinolaryngol. 2007;71(8):1277–85.

    Article  PubMed  Google Scholar 

  18. Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Brightling CE, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest. 2006;129:1S–23S.

    Article  PubMed  Google Scholar 

  19. Morice A, Kardos P. Comprehensive evidence-based review on European antitussives. BMJ Open Resp Res. 2016;3:e000137.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Palmer RB, Reynolds KM, Banner W, Bond GR, Kauffman RE, Paul IM, et al. Adverse events associated with diphenhydramine in children, 2008–2015. Clin Toxicol (Phila). 2020;58(2):99–106.

    Article  CAS  Google Scholar 

  21. Olasińska-Wiśniewska A, Olasiński J, Grajek S. Cardiovascular safety of antihistamines. Postepy Dermatol Alergol. 2014;31(3):182–6.

    Article  PubMed  PubMed Central  Google Scholar 

  22. https://webarchive.nationalarchives.gov.uk/20141206123425/http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con041374.pdf. Accessed 20 July 2020.

  23. Australian Government. Department of Health and aging therapeutic goods administration. Review of cough and cold medicines in children. 2009. https://www.tga.gov.au/sites/default/files/consult-labelling-cough-cold-091022-review.pdf. Accessed 11 May 2020.

  24. Sidhu G, Akhondi H. Loratadine. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2020.

    Google Scholar 

  25. Curran MP, Scott LJ, Perry CM. Cetirizine: a review of its use in allergic disorders. Drugs. 2004;64(5):523–61.

    Article  PubMed  CAS  Google Scholar 

  26. Dicpinigaitis PV, Morice AH, Birring SS, McGarvey L, Smith JA, Canning BJ, et al. Antitussive drugs–past, present, and future. Pharmacol Rev. 2014;66:468–512.

    Article  PubMed  CAS  Google Scholar 

  27. Hosoe H, Kaise T, Ohmori K, Isohama Y, Kai H, Takahama K, et al. Mucolytic and antitussive effects of erdosteine. J Pharm Pharmacol. 1999;51:959–66.

    Article  PubMed  CAS  Google Scholar 

  28. Dal Negro RW, Visconti M, Micheletto C, Tognella S. Changes in blood ROS, e-NO, and some pro-inflammatory mediators in bronchial secretions following erdosteine or placebo: a controlled study in current smokers with mild COPD. Pulm Pharmacol Ther. 2008;21:304–8.

    Article  CAS  Google Scholar 

  29. Dal Negro RW, Visconti M, Trevisan F, et al. Erdosteine 600 mg, but not placebo and NAC 1200mg, restore airway response to inhaled salbutamol 200 mcg in COPD. In: Poster presented at the ERS Annual Meeting, Stockholm, 15–19 September 2007.

  30. Bolser DC. Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):238S–49S.

    Article  PubMed  CAS  Google Scholar 

  31. Shimura S, Okubo T, Maeda S, Aoki T, Tomioka M, Shindo Y, et al. Effect of expectorants on relaxation behavior of sputum viscoelasticity in vivo. Biorheology. 1983;20:677–83.

    Article  PubMed  CAS  Google Scholar 

  32. European Medicines Agency. Science Medicines. Health. Ambroxol and bromhexine containing medicinal products. September 10, 2015, EMA/PRAC/800767/201. https://www.ema.europa.eu/en/documents/referral/ambroxol-bromhexine-article-31-referral-prac-assessment-report_en.pdf. Accessed 15 May 2020.

  33. Balli F, Bergamini B, Calistru P, Ciofu EP, Domenici R, Doros G, et al. Clinical effects of erdosteine in the treatment of acute respiratory tract diseases in children. Int J Clin Pharmacol Ther. 2007;45:16–22.

    Article  PubMed  CAS  Google Scholar 

  34. Thomson ML, Pavia D, Jones CJ, McQuiston TA. No demonstrable effect of S-carboxymethyl cysteine on the clearance of secretions from the human lung. Thorax. 1975;30:669–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Edwards GF, Steel AE, Scott JK, Jordan JW. S-carboxymethyl cysteine in the fluidification of sputum and treatment of chronic airway obstruction. Chest. 1976;70:506–13.

    Article  PubMed  CAS  Google Scholar 

  36. Bolser DC, Poliacek I, Jakus J, Fuller DD, Davenport PW. Neurogenesis of cough, other airway defensive behaviors, and breathing: a hierarchical system? Respir Physiol Neurobiol. 2006;152:255–65.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Lavezzo A, Melillo G, Clavenna G, Omini C. Peripheral site of action of levodropropizine in experimental-induced cough: role of sensory neuropeptides. Pulm Pharmacol. 1992;5:143–7.

    Article  PubMed  CAS  Google Scholar 

  38. Mannini C, Lavorini F, Zanasi A, Saibene F, Lanata L, Fontana G. A randomized clinical trial comparing the effects of antitussive agents on respiratory center output in patients with chronic cough. Chest. 2017;151(6):1288–94.

    Article  PubMed  Google Scholar 

  39. Zanasi A, Lanata L, Fontana G, Saibene F, Dicpinigaitis P, De Blasio F. Levodropropizine for treating cough in adults and children: a meta-analysis of published studies. Multidiscip Respir Med. 2015;10:19.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Fiocchi R, Arancio P, Murgo G, Banderali G. Levodropropizine effectiveness on nocturnal cough in asthmatic children. Eur Respir J. 1991;4:594.

    Google Scholar 

  41. Banderali G, Riva E, Fiocchi A, Cordaro CI, Giovannini M. Efficacy and tolerability of levodropropizine and dropropizine in children with non-productive cough. J Int Med Res. 1995;23:175–83.

    Article  PubMed  CAS  Google Scholar 

  42. Kim DS, Sohn MH, Jang GC. Levodropropizine in children with bronchitis. Diagn Treat. 2002;22:9.

    Google Scholar 

  43. De Blasio F, Dicpinigaitis PV, Rubin BK, De Danieli G, Lanata L, Zanasi A. An observational study on cough in children: epidemiology, impact on the quality of sleep and treatment outcome. Cough. 2012;8:1.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Zanasi A, Lanata L, Saibene F, Fontana G, Dicpinigaitis PV, Venier V, et al. Prospective study of the efficacy of antibiotics versus antitussive drugs for the management of URTI-related acute cough in children. Multidiscip Respir Med. 2016;11:29.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Choudry NB, Fuller RW, Anderson N, Karlsson JA. Separation of cough and reflex bronchoconstriction by inhaled local anesthetics. Eur Respir J. 1990;3(5):579–83.

    PubMed  CAS  Google Scholar 

  46. Belvisi MG, Geppetti P. Cough: current and future drugs for the treatment of chronic cough. Thorax. 2004;59:438–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Truesdale K, Jurdi A. Nebulized lidocaine in the treatment of intractable cough. Am J Hosp Palliat Care. 2013;30(6):587–9.

    Article  PubMed  Google Scholar 

  48. Tan W, Li S, Liu X, Gao X, Huang W, Guo J, Wang Z. Prophylactic intravenous lidocaine at different doses for fentanyl-induced cough (FIC): a meta-analysis. Sci Rep. 2018;8:9946.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Doona M, Walsh D. Benzonatate for opioid-resistant cough in advanced cancer. Palliat Med. 1998;12(1):55–8.

    Article  PubMed  CAS  Google Scholar 

  50. Korppi M, Laurikainen K, Pietikäinen M, Silvasti M. Antitussives in the treatment of acute transient cough in children. Acta Paediatr Scand. 1991;80:969–71.

    Article  PubMed  CAS  Google Scholar 

  51. Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM Jr. Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Arch Pediatr Adolesc Med. 2007;161(12):1140–6.

    Article  PubMed  Google Scholar 

  52. Chang AB, Glomb WB. Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 suppl):260S–83S.

    Article  PubMed  Google Scholar 

  53. Journey JD, Agrawal S, Stern E. Dextromethorphan Toxicity. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020. https://www.ncbi.nlm.nih.gov/books/NBK538502/. Accessed 6 July 2019.

  54. Chyka PA, Erdman AR, Manoguerra AS, Christianson G, Booze LL, Nelson LS, et al. Dextromethorphan poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007;45(6):662–77.

    Article  CAS  Google Scholar 

  55. Taylor JA, Novack AH, Almquist JR, Rogers JE. Efficacy of cough suppressants in children. J Paediatr. 1993;122:799–802.

    Article  CAS  Google Scholar 

  56. US Food and Drug Administration. Codeine cough-and-cold medicines in children: drug safety communication - FDA evaluating the potential risk of serious side effects, July 7, 2015. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm453379. Accessed 28 Apr 2020.

  57. Codeine containing medicinal products for the treatment of cough and/or cold in pediatric patients. Article 31 of Directive 2001/83/EC resulting from pharmacovigilance data. March 12 2015EMA/235820/2015. https://www.ema.europa.eu/en/documents/referral/codeine-article-31-referral-prac-assessment-report_en-0.

  58. Scotti L, Borzani M. Cloperastine fendizoate in the treatment of cough-producing diseases in pediatrics. Minerva Pediatr. 1988;40:283–6.

    PubMed  CAS  Google Scholar 

  59. Cicchetti M. Cloperastine syrup (Seki) in the treatment of cough in children. Aggiornamento Pediatrico. 1983;34:325–50.

    Google Scholar 

  60. Svitaylo OA. Efficacy and tolerability of cloperastine fendizoate in the treatment of children and adolescents with a cough caused by respiratory infections: effect on night-time cough and the quality of sleep of patients and parents. A randomized, double-blind, placebo-controlled study. Int J Drugs Ther. 2005;22:35–433.

    Google Scholar 

  61. Aliprandi P, Castelli C, Bernorio S, Dell'Abate E, Carrara M. Levocloperastine in the treatment of chronic non-productive cough: comparative efficacy versus standard antitussive agents. Drugs Exp Clin Res. 2004;30:133–41.

    PubMed  CAS  Google Scholar 

  62. Abelmann WH, Gaensler EA, Badger TL. Clinical evaluation of toryn, a new synthetic cough depressant. Dis Chest. 1954;25:532–41.

    Article  PubMed  CAS  Google Scholar 

  63. Glick J. Codeine vs. caramiphen in cough control. Del Med J. 1963;35:180.

    PubMed  CAS  Google Scholar 

  64. Bickerman HA, Itkin SE. Further studies on the evaluation of antitussive agents employing experimentally induced cough in human subjects. Clin Pharmacol Ther. 1960;1:180–91.

    Article  PubMed  CAS  Google Scholar 

  65. Oral prescription drugs offered for relief of symptoms of cough, cold, or allergy; drug efficacy study implementation; caramiphen edisylate; final actions on supplemental new drug applications. Federal Register. 2000;65:42017

  66. Kobayashi T, Ikeda K, Ichikawa T, Togashi S, Kumanishi T. Effects of sigma ligands on the cloned mu-, delta- and kappa-opioid receptors co-expressed with G-protein-activated K+ (GIRK) channel in Xenopus oocytes. Br J Pharmacol. 1996;119:73–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. https://www.federalregister.gov/documents/2014/07/02/2014-15371/additions-and-modifications-to-the-list-of-drug-products-that-have-been-withdrawn-or-removed-from. Accessed 20 July 2020.

  68. Kamatou GP, Vermaak I, Viljoen AM, Lawrence BM. Menthol: a simple monoterpene with remarkable biological properties. Phytochemistry. 2013;96:15–25.

    Article  PubMed  CAS  Google Scholar 

  69. Kenia P, Houghton T, Beardsmore C. Does inhaling menthol affect nasal patency or cough? Pediatr Pulmonol. 2008;43:532–7.

    Article  PubMed  Google Scholar 

  70. Paul IM, Beiler JS, King TS, Clapp ER, Vallati J, Berlin CM Jr. Vapor rub, petrolatum, and no treatment for children with nocturnal cough and cold symptoms. Pediatrics. 2010;126:1092–9.

    Article  PubMed  Google Scholar 

  71. Food and Drug Administration Proposed rules: external analgesic drug products for over-the-counter human use; tentative final monograph. Federal Register. 1983;48

  72. Cough and cold remedies for the treatment of acute respiratory infections in young children. WHO/FCH/CAH/01.02. World Health Organization; 2001.

  73. Cianciosi D, Forbes-Hernández TY, Afrin S, Gasparrini M, Reboredo-Rodriguez P, Manna PP, et al. Phenolic compounds in honey and their associated health benefits: a review. Molecules. 2018;23:2322.

    Article  PubMed Central  CAS  Google Scholar 

  74. Goldman RD. Honey for treatment of cough in children. Can Fam Physician. 2014;60(12):1107–8 (1110. PMID: 25642485; PMCID: PMC4264806).

    PubMed  PubMed Central  Google Scholar 

  75. Cohen HA, Rozen J, Kristal H, Laks Y, Berkovitch M, Uziel Y, et al. Effect of honey on nocturnal cough and sleep quality: a double-blind, randomized, placebo-controlled study. Pediatrics. 2012;130:465–71.

    Article  PubMed  Google Scholar 

  76. Oduwole O, Meremikwu MM, Oyo-Ita A, Udoh EE. Honey for acute cough in children. Cochrane Database Syst Rev. 2012(3):CD007094.

  77. Malesker MA, Callahan-Lyon P, Ireland B, Irwin RS, CHEST Expert Cough Panel. Pharmacologic and nonpharmacologic treatment for acute cough associated with the common cold: CHEST EXPERT PANEL REPOrt. Chest. 2017;152:1021–37.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Miceli Sopo S, Greco M, Monaco S, Varrasi G, Di Lorenzo G, Simeone G, et al. Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review. Allergol Immunopathol (Madr). 2015;43:449–55.

    Article  CAS  Google Scholar 

  79. Cox N, Hinkle R. Infant botulism. Am Fam Physician. 2002;65:1388–92.

    PubMed  Google Scholar 

  80. Eccles R. The powerful placebo in cough studies. Pulm Pharmacol Ther. 2002;15:303–8.

    Article  PubMed  CAS  Google Scholar 

  81. Canciani M, Murgia V, Caimmi D, Anapurapu S, Licari A, Marseglia GL. Efficacy of Grintuss® pediatric syrup in treating cough in children: a randomized, multicenter, double-blind, placebo-controlled clinical trial. Ital J Pediatr. 2014;10(40):56.

    Article  CAS  Google Scholar 

  82. Cohen HA, Hoshen M, Gur S, Bahir A, Laks Y, Blau H. Efficacy and tolerability of a polysaccharide-resin-honey based cough syrup as compared to carbocysteine syrup for children with colds: a randomized, single-blinded, multicenter study. World J Pediatr. 2017;13:27–33.

    Article  PubMed  CAS  Google Scholar 

  83. Shrivastava R, Carrois F, Pisak M, Chabrillat T, Shrivastava R. Clinical efficacy of novel filmogen, antimicrobial, cleaning, fluidizing cough treatment. J Clin Trials. 2017;7:318.

    Article  Google Scholar 

  84. Eccles R, Mallefet P. Soothing properties of glycerol in cough syrups for acute cough due to common cold. Pharmacy (Basel). 2017;5:1.

    Google Scholar 

  85. Abdulqawi R, Dockry R, Holt K, Layton G, McCarthy BG, Ford AP, Smith JA. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomized, double-blind, placebo-controlled phase 2 study. Lancet. 2015;385(1198–20):35.

    Google Scholar 

  86. Smith J, Kitt M, Sher M, Butera P, Ford AP. A phase 2 dose-escalation study with AF-219, a P2X3 antagonist for the treatment of chronic cough. Am J Respir Crit Care Med. 2016;193:A6524.

    Article  Google Scholar 

  87. US Nation Library of Medicine. Phase 3 Study of Gefapixant (MK-7264) in Adult Participants with Chronic Cough (MK-7264-027). 2018. https://clinicaltrials.gov/ct2/show/NCT03449134. Accessed 28 Apr 2020.

  88. US National Library of Medicine. A Study of Gefapixant (MK-7264) in Adult Participants with Chronic Cough (MK-7264-030). 2018. https://clinicaltrials.gov/ct2/show/NCT03449147. Accessed 28 Apr 2020.

  89. Khalid S, Murdoch R, Newlands A, Smart K, Kelsall A, Holt K, et al. Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind, randomized controlled trial. J Allergy Clin Immunol. 2014;134:56–62.

    Article  PubMed  CAS  Google Scholar 

  90. Bonvini SJ, Birrell MA, Grace MS, Maher SA, Adcock JJ, Wortley MA, et al. Transient receptor potential cation channel, subfamily V, member four and airway sensory afferent activation: role of adenosine triphosphate. J Allergy Clin Immunol. 2016;138(249–261):e12.

    Google Scholar 

  91. Birrell MA, Belvisi MG, Grace M, Sadofsky L, Faruqi S, Hele DJ, et al. TRPA1 agonists evoke coughing in guinea pig and human volunteers. Am J Respir Crit Care Med. 2009;180:1042–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Belvisi MG, Birrell MA, Wortley MA, Maher SA, Satia I, Badri H, et al. XEN-D0501, a novel transient receptor potential vanilloid 1antagonist, does not reduce cough in patients with refractory cough. Am J Respir Crit Care Med. 2017;196:1255–63.

    Article  PubMed  CAS  Google Scholar 

  93. US National Library of Medicine. A Study to Assess the Effectiveness and Side Effects of GSK2798745 in Participants with Chronic Cough. 2019. https://clinicaltrials.gov/ct2/show/NCT03372603. Accessed 28 Apr 2020.

  94. EU Clinical Trials Register. A Phase 2a, Multi-Centre, Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate Efficacy, Safety, and Tolerability of Inhaled GRC 17536, Administered for 4 Weeks, in Patients with Refractory Chronic Cough. 2013. https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-002728-17/GB. Accessed 28 Apr 2020.

  95. Boeckxstaens GE, Rydholm H, Lei A, Adler J, Ruth M. Effect of lesogaberan, a novel GABA(B)-receptor agonist, on transient lower oesophageal sphincter relaxations in male subjects. Aliment Pharmacol Ther. 2010;31:1208–17.

    Article  PubMed  CAS  Google Scholar 

  96. Birring SS, Wijsenbeek MS, Agrawal S, van den Berg JWK, Stone H, et al. A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomized, double-blind, proof-of-concept, phase 2 trial. Lancet Respir Med. 2017;5:806–15.

    Article  PubMed  CAS  Google Scholar 

  97. Harle ASM, Blackhall FH, Molassiotis A, Holt K, Dockry R, Russell P, et al. Neurokinin-1 receptor antagonism for the treatment of cough in lung cancer. Eur Respir J. 2016;48:PA3547.

    Google Scholar 

  98. Menlo Therapeutics Inc. Menlo Therapeutics Announces Results from a Phase 2 Clinical Trial of Serlopitant for the Treatment of Refractory Chronic Cough. 2018. https://ir.menlotherapeutics.com/index.php/press-releases. Accessed 28 Apr 2020.

  99. Lieberman JA, Dunbar G, Segreti AC, Girgis RR, Seoane F, Beaver JS, et al. A randomized exploratory trial of an alpha-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia. Neuropsychopharmacology. 2013;38:968–75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Walling D, Marder SR, Kane J, Fleischhacker WW, Keefe RS, Hosford DA, et al. Phase 2 trial of an alpha-7 nicotinic receptor agonist (TC-5619) in negative and cognitive symptoms of schizophrenia. Schizophr Bull. 2016;42:335–43.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Pediatric Respiratory Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

    Sara Manti

  2. Allergy Center, Istituto Giannina Gaslini, Genoa, Italy

    Maria Angela Tosca

  3. Pediatric Clinic, Pediatrics Department, Policlinico San Matteo, University of Pavia, Pavia, Italy

    Amelia Licari, Ilaria Brambilla, Thomas Foiadelli & Gian Luigi Marseglia

  4. Allergy Clinic, Casa di Cura Villa Montallegro, Via P. Boselli 5, 16146, Genoa, Italy

    Giorgio Ciprandi

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  1. Sara Manti
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Correspondence to Giorgio Ciprandi.

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The publication has been supported by the Italian Society of Pediatric Allergy and Immunology (SIAIP).

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Sara Manti, Mariangela Tosca, Amelia Licari, Giorgio Ciprandi, and Gian Luigi Marseglia have no conflict of interest directly relevant to the content of this article.

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All authors contributed to study conception and design. The first draft of the manuscript was written by SM and was critically revised by MAT, AL, GC, GLM. All authors read and approved the final manuscript.

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Manti, S., Tosca, M.A., Licari, A. et al. Cough Remedies for Children and Adolescents: Current and Future Perspectives. Pediatr Drugs 22, 617–634 (2020). https://doi.org/10.1007/s40272-020-00420-4

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  • DOI: https://doi.org/10.1007/s40272-020-00420-4

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