Upper Respiratory Tract Infection-Associated Acute Cough and the Urge to Cough: New Insights for Clinical Practice
Publication: Pediatric Allergy, Immunology, and Pulmonology
Volume 33, Issue Number 1
Abstract
Upper respiratory tract infection (URTI)-associated acute cough is the most common symptom both in children and adults worldwide and causes economic and social problems with significant implications for the patient, the patient's family, and the health care system. New pathogenic mechanisms in acute cough, including the urge to cough (UTC) mechanisms, have been recently identified. The brainstem neural network, pharyngeal sensory innervation, airway mechanical stimulation, inflammatory mediators, and postnasal drip actively participate in the onset and maintenance of acute cough and the urge to cough phenomenon. However, there is still no effective pharmacological treatment capable of interfering with the pathophysiologic mechanisms involved in URTI-associated acute cough. Moreover, severe adverse events frequently occur in administering such cough medications, mainly in children. New evidence has been provided concerning polysaccharides, resins, and honey as potential cough relievers with high antitussive efficiency, effect on the UTC, and minimal side effects.
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Disclaimer
The authors declare that the article was written in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.
References
1. Shields MD, Bush A, Everard ML, et al. Recommendations for the assessment and management of cough in children. Thorax 2008; 63(Suppl III):1–15.
2. Gibson PG, Simpson JL, Ryan NM, et al. Mechanisms of cough. Curr Opin Allergy Clin Immunol 2014; 14:55–61.
3. Munyard P, Bush A. How much coughing is normal? Arch Dis Child 1996; 74:531–534.
4. Chang AB, Glomb WB. Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. Chest 2006; 129:260S–283S.
5. Galway NC, Shields MD. The child with an incessantr dry cough. Paediatr Respir Rev 2019; 30:58–64.
6. Gilchrist FJ. An approach to the child with a wet cough. Paediatr Respir Rev 2019; 31:75–81.
7. Morice A, Kardos P. Comprehensive evidence-based review on European antitussives. BMJ Open Resp Res 2016; 3:e000137.
8. Marseglia GL, Pagella F, Klersy C, et al. The 10-day mark is a good way to diagnose not only acute rhinosinusitis but also adenoiditis, as confirmed by endoscopy. Int J Pediatr Otorhinolaryngol 2007; 71:581–583.
9. Cohen HA, Rozen J, Kristal H, et al. Effect of honey on nocturnal cough and sleep quality: a double-blind, randomized, placebo-controlled study. Pediatrics 2012; 130:465–471.
10. Morice AH, McGarvey L, Pavord I, et al. Recommendations for the management of cough in adults. Thorax 2006; 61(Suppl):1–24.
11. Chang AB, Harrhy VA, Simpson J, et al. Cough, airway inflammation and mild asthma exacerbation. Arch Dis Child 2002; 86:270–275.
12. Hay AD, Wilson A, Fahey T, et al. The duration of acute cough in pre-school children presenting to primary care: a prospective cohort study. Fam Pract 2003; 20:6.
13. Thompson M, Vodicka TA, Blair PS, et al. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ 2013; 347:f7027.
14. De Blasio F, Dicpinigaitis PV, Rubin BK, et al. An onservational study on cough in children: epidemiology, impact on quality of sleep and treatment outcome. Cough 2012; 8:1.
15. National Institute for Health and Care Excellence. Cough (acute): antimicrobial prescribing. NICE guideline. London: NICE National Institute for Health and Care Excellence, 2019.
16. Dicpinigaitis PV. Effect of viral upper respiratory tract infection on cough reflex sensitivity. J Thorac Dis 2014; 6(Suppl 7):S708–S711.
17. Pappas DE, Hendley JO, Hayden FG, et al. Symptom profile of common colds in school-aged children. Pediatr Infect Dis J 2008; 271:8–11.
18. Brodlie M, Graham C, McKean MC. Childhood cough. BMJ 2012; 344:e1177.
19. Hay AD, Wilson AD. The natural history of acute cough in children aged 0 to 4 years in primary care: a systematic review. Br J Gen Pract 2002; 52:401–409.
20. Hay AD, Schroeder K, Fahey T. Acute cough in children. 10-minute consultation. BMJ 2004; 328:1062.
21. Chang AB, Landau LI, Van Asperen PP, et al. Cough in children: definitions and clinical evaluation. Med J Aust 2006; 184:398–403.
22. Monto AS. Studies of the community and family: acute respiratory illness and infection. Epidemiol Rev 1994; 16:351–373.
23. Chang AB. Cough: are children really different to adults? Cough 2005; 1:7.
24. Urkin J, Ishay Y, Bilenko N, et al. Night-time cough in children with acute wheezing and with upper respiratory tract infection. Prim Care Respir J 2008; 17:217–221.
25. Keller JA, McGovern AE, Mazzone SB. Translating cough mechanisms into better cough suppressants. Chest 2017; 152:833–841.
26. Eccles R, Mallefet P. Soothing properties of glycerol in cough syrups for acute cough due to common cold. Pharmacy (Basel) 2017; 5:1.
27. Freestone C, Eccles R. Assessment of the antitussive efficacy of codeine in cough associated with common cold. J Pharm Pharmacol 1997; 49:1045–1049.
28. Wheeler-Hegland K, Pitts T, Davenport PW. Cortical gating of oropharyngeal sensory stimuli. Front Physiol 2010; 1:167.
29. Eccles R, Morris S, Jawad M. Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection. J Clin Pharm Ther 1992; 17:175–180.
30. Eccles R, Dicpinigaitis P, Turner RB, et al. Characterization of urge to cough and cough symptoms associated with the common cold: results of a US internet survey. Postgrad Med 2016; 128:485–491.
31. Steele CM, Miller AJ. Sensory input pathways and mechanisms in swallowing: a review. Dysphagia 2010,25:323–333.
32. Eccles in Redington AE, Morice H. Acute and chronic cough. London: Taylor and Francis, 2005, pp. 215–236.
33. Mu L, Sanders I. Sensory nerve supply of the human oro- and laryngopharynx: a preliminary study. Anat Rec 2000; 258:406–420.
34. Hegland KW, Pitts T, Bolser DC, et al. Urge to cough with voluntary suppression following mechanical pharyngeal stimulation. Bratisl Lek Listy 2011; 112:109–114.
35. Canning BJ, Chang AB, Bolser DC, et al. Anatomy and neurophysiology of cough. Chest 2014; 146:1633–1648.
36. Dicpinigaitis PV, Bhat R, Rhoton WA, et al. Effect of viral upper respiratory tract infection on the urge-to-cough sensation. Respir Med 2011; 105:615–618.
37. Mazzone SB. An overview of the sensory receptors regulating cough. Cough 2005; 1:2.
38. Chung KF. Chronic ‘cough hypersensitivity syndrome’: a more precise label for chronic cough. Pulm Pharmacol Ther 2011; 24:267–271.
39. Yoder KE, Shaffer ML, La Tournous SJ, et al. Child assessment of dextromethorphan, diphenhydramine, and placebo for nocturnal cough due to upper respiratory infection. Clin Pediatr (Phila) 2006; 45:633–640.
40. Anderson-James S, Marchant JM, Acworth JP, et al. Inhaled corticosteroids for subacute cough in children. Cochrane Database Syst Rev 2013; CT008888.
41. Smith SM, Schroeder K, Fahley T. Over-the-counter (OTC) medications for acute cough in children and adults in community setting (Review) Cochrane Database Syst Rev 2014; CD001831.
42. Goldman RD. Codeine for acute cough in children. Can Fam Phys 2010; 56:1293–1294.
43. Speich B, Thomer A, Aghlmandi S, et al. Treatments for subacute cough in primary care: systematic review and meta-analyses of randomised clinical trials. Br J Gen Pract 2018; 68:e694–e702.
44. Bonvini SJ, Belvisi MG. Cough and airway disease: the role of ion channels. Pulm Pharmacol Ther 2017; 47:21–28.
45. Rimsza ME, Newberry S. Unexpected infant deaths associated with use of cough and cold medications. Pediatrics 2008; 122:e318–e322.
46. Agence française de sécurité sanitaire des produits de santé (Afssaps, 2010). Retrait des spécialités mucolytiques chez le nourrisson: dernière étape de l'opération de rappel. http://ansm.sante.fr/S-informer/Informations-de-securite-Retraits-de-lots-et-de produits (accessed January 22, 2020).
47. AIFA. Nota Informativa Dell'agenzia Italiana Del Farmaco. Ufficio di Farmacovigilanza. Rome: Agenzia Italiana del Farmaco, 2010.
48. Vernacchio L, Kelly JP, Kaufman DW, et al. Medication use among children <12 years of age in the United States: results from the Slone Survey. Pediatrics 2009; 124:446–454.
49. Dicpinigaitis PV. Cough: an unmet clinical need. Br J Pharmacol 2011; 163:116–124.
50. Dicpinigaitis PV, Morice AH, Birring SS, et al. Antitussive drugs-past, present, and future. Pharmacol Rev 2014; 66:468–512.
51. Bolser DC. Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines. Chest 2006; 129(Suppl 1):238S–249S.
52. Bolser DC. Pharmacologic management of cough. Otolaryngol Clin North Am 2010; 43:147–155.
53. Grace MS, Dubuis E, Birrell MA, et al. Pre-clinical studies in cough research: role of Transient Receptor Potential (TRP) channels. Pulm Pharmacol Ther 2013; 26:498–507.
54. Mazzone SB, McLennan L, McGovern AE, et al. Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging. Am J Respir Crit Care Med 2007; 176:327–332.
55. Eccles R. Mechanisms of the placebo effect of sweet cough syrups. Respir Physiol Neurobiol 2006; 152:340–348.
56. Leech J, Mazzone SB, Farrell M. Brain activity associated with placebo suppression of the urge-to-cough in humans. Am J Respir Crit Care Med 2013; 188:1069–1075.
57. Bolser DC. A streetcar named urge-to-cough. J Appl Physiol 2010; 108:1030–1031.
58. Smith JA, Badri H. Cough: new pharmacology. J Allergy Clin Immunol Pract 2019; 7:1731–1738.
59. Thirawong N, Nunthanid J, Puttipipatkhachorn S, et al. Mucoadhesive properties of various pectins on gastrointestinal mucosa: an in vitro evaluation using texture analyzer. Eur J Pharm Biopharm 2007; 67:132–140.
60. Bone K, Mills S. Principles and practices of phytotherapy modern herbal medicine, second ed. London: Churchill Livingstone-Elsevier, 2013, pp. 25–248.
61. Avachat AM, Dash RR, Shrotriya SN. Recent investigations of plant based natural gums, mucilages and resins in novel drug delivery systems. Indian J Pharm Educ Res 2011; 45:1.
62. Schmidgall J, Schnetz E, Hensel A. Evidence for bioadhesive effects of polysaccharides and polysaccharide-containing herbs in an ex vivo bioadhesion assay on buccal membranes. Planta Med 2000; 66:48–53.
63. ESCOP Monographs. Altheae radix. Second edition. New York: Thieme, 2003, pp. 32–35.
64. Galati EM, Monforte MT, Miceli N, et al. Opuntia ficus indica (L.) Mill. mucilages show cytoprotective effect on gastric mucosa in rat. Phytother Res 2007; 21:344–346.
65. Yang Q, Huang B, Li H, et al. Gastroprotective activities of a polysaccharide from the fruiting bodies of Pleurotus ostreatus in rats. Int J Biol Macromol 2012; 50:1224–1228.
66. Smart JD. The basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev 2005; 57:1556–1568.
67. Nosalova G, Fleskova D, Jurecek L, et al. Herbal polysaccharides and cough reflex. Respir Physiol Neurobiol 2013; 187:47–51.
68. Najafian Y, Hamedi SS, Farshchi MK, et al. Plantago major in traditional persian medicine and modern phytotherapy: a narrative review. Electron Physician 2018; 10:6390–6399.
69. Meo SA, Al-Asiri SA, Mahesa AL, et al. Role of honey in modern medicine. Saudi J Biol Sci 2017; 24:975–978.
70. Pasupuleti VR, Sammugam L, Ramesh N, et al. Honey, propolis, and royal gelly: a comprehensive review of their biological actions and health benefits. Oxid Med Cell Longev 2017; 2017:1259510.
71. Ahmed S, Sulaiman SA, Baig AA, et al. Honey as a potential natural antioxidant medicine: an insight into its molecular mechanism of action. Oxid Med Cell Longev 2018; 2018:ID8367846.
72. Cianciosi D, Forbes-Hermandez TY, Afrin S, et al. Phenolic compounds in honey and their associated health benefits: a review. Molecules 2018; 23:2322.
73. Hills SP, Mitchell P, Wells C, et al. Honey supplementation and exercise: a systematic review. Nutrients 2019; 11:1586.
74. Ramli NZ, Chin KY, Zarkasi KA, et al. A review of the protective effects of honey against metabolic síndrome. Nutrients 2018; 10:1009.
75. Lan Nguyen HT, Panyoyai N, Kasapis S, et al. Honey and its role in relieving multiple facets of aterosclerosis. Nutrients 2019; 11:167.
76. Does a spoonful of honey make the medicine go down? Editorial. Lancet 2018; 392:712.
77. Barker SJ. Honey for acute cough in children. Pediatr Child Health 2016; 21:199–200.
78. Goldman RD. Honey for treatment of cough in children. Can Fam Physician 2014; 60:1107–1110.
79. WHO. Cough and cold remedies for the treatment of acute respiratory infections in young children 2001. Geneva, Switzerland: World Health Organization, 2001.
80. Ayazi P, Mahyar A, Yousef-Zanjani M, et al. Comparison of the effect of two kinds of iranian honey and diphenhydramine on nocturnal cough and the sleep quality in coughing children and their parents. PLoS One 2017; 12:e0170277.
81. Paul IM, Beiler J, McMonagle A, et al. Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Arch Pediatr Adolesc Med 2007; 161:1140–1146.
82. 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; 16:787–793.
83. Oduwole O, Udoh EE, Oyo-Ita A, et al. Honey for acute cough in children. Cochrane Database Syst Rev 2018; CD007094.
84. Nitsche MP, Carreño M. Is honey an effective treatment for acute cough in children? Medwave 2016; 16(Suppl 2):e6454.
85. Cox N, Hinkle R. Infant botulism. Am Fam Physician 2002; 65:1388–1392.
86. Canciani M, Murgia V, Caimmi D, et al. Efficacy of Grintuss® pediatric syrup in treating cough in children: a randomized, multicenter, double blind, placebo-controlled clinical trial. Ital J Pediatr 2014; 40:56.
87. Cohen HA, Hoshen M, Gur S, et al. 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.
Information & Authors
Information
Published In
Pediatric Allergy, Immunology, and Pulmonology
Volume 33 • Issue Number 1 • March 2020
Pages: 3 - 11
PubMed: 33406022
Copyright
Copyright 2020, Mary Ann Liebert, Inc., publishers.
History
Published online: 17 March 2020
Published in print: March 2020
Accepted: 5 February 2020
Received: 23 December 2019
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Author Contributions
All authors made a substantial contribution to the conception of the work. V.M., M.D.F., and S.M. reviewed the literature on the subject. V.M. and A.L. drafted the final version of the manuscript. G.C. edited the final version. A.L., G.C., and G.L.M. discussed and revised it critically for important intellectual content. All authors finally approved the version to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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No competing financial interests exist.
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No funding was received for this article.
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