Adam Silberman, ND
Bronner Handwerger, ND
Naturopathic Perspective
A persistent, lingering, non-productive cough following a viral upper respiratory tract infection (URTI) is not uncommon, and can persist for 2-8 weeks after the acute infection resolves.1 Although non-life-threatening, post-viral coughs can be painful, irritating, and annoying for the patient, invoking additional stress to the airway and associated structures, and potentially exposing the area to prolonged inflammatory and degenerative processes.
Several possibly interrelated mechanisms may be responsible for a prolonged cough after a viral URTI. Secretions from a lingering post-nasal drip can stimulate receptors in the upper respiratory tract, causing irritation that stimulates cough.2 Enhanced sensitivity of airway nerves due to viral-induced epithelial damage and inflammation may induce upregulation of the neurologically driven cough reflex arc, resulting in airway hyper-responsiveness and constriction, thereby inducing cough.3-5
The use of nebulized glutathione/N-acetylcysteine (NAC) solution, alongside key demulcent, antitussive, broncho-relaxant, and antimicrobial herbs, may be effective in combination at reducing severity and duration of post-viral cough by impacting the above mechanisms. Unfortunately, high-quality clinical outcome studies on integrative approaches for post-viral cough do not exist. That being said, clinically we have seen the severity and duration of post-viral cough reduced significantly when the therapeutics outlined below are implemented. We have also seen the prevalence of lingering post-viral cough reduced in our patients when these therapeutics have been employed at the first sign of a viral URTI.
Initiating therapy early can go a long way toward reducing the incidence of post-viral cough syndrome. For patients fortunate enough to be under our care, this annoying situation has been reduced or mitigated completely. The use of nebulized glutathione early on in an URI can significantly reduce the duration of the respiratory distress.
As always, a lingering cough refractive to intervention can be indicative of persistent pathology, and thus should be fully evaluated before a diagnosis of post-viral cough syndrome is made. Although any bacterial or viral URTI can result in a post-viral cough, the frequency of post-viral cough is increased in cases of Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis,6 with the recognition that pertussis in adolescents and adults has increased over the past decade.7 GERD and bronchial tumors must also be excluded, as well as exposure to inhaled irritants.1
Nebulized Glutathione & N-Acetylcysteine
Glutathione can be found in the epithelial lining fluid of the respiratory tract and is considered part of our host defense against infection and oxidative damage in this area. Administration of nebulized glutathione has been shown to increase levels of reduced glutathione in the epithelial lining fluid, decrease oxidant-induced damage in the area post-infection, locally reduce rhinorrhea, reduce post-nasal drip, increase oxygen saturation, and increase pulmonary function (FVC and FEV1).8 The ability of nebulized glutathione to positively impact post-viral cough syndrome could therefore be due to an increase in the antioxidant potential of the epithelial lining fluid via direct supplementation to the area, thereby aiding in the repair of any remaining epithelial induced damage post-URTI. In doing so, afferent nerve fibers previously exposed from epithelial lining damage post-URTI are no longer exposed, the cough reflex arc is interrupted, and airway hyper-responsiveness subsequently improves. Increased antioxidant potential of the epithelial lining fluid as a result of direct supplementation could also support ongoing host immune response to any lingering infection in the area, and reduce any post-nasal drip that may be contributing to elicitation of the cough response.
Although nebulized dosing can range from 600 mg to as high as 1.3 g daily, given in single or divided doses, we find maximum patient compliance and successful clinical outcomes in reducing post-viral coughs when administering 2-3 mL of a compounded 10% glutathione/10% NAC solution via nebulizer BID-QID alongside key herbal treatments discussed below. Other known formulas include a mixture of glutathione, licorice and NAC compounded together for nebulization, as well as 1 mL glutathione (200 mg/mL) mixed with 1 mL NAC and mixed into filtered water and nebulized.
Care may need to be taken when giving nebulized glutathione to asthmatic patients, due to the possibility of inducing bronchoconstriction, particularly if the patient has a sulfite sensitivity.9 In practice, this rarely occurs, but a dilute test dose should be administered if there is concern; most derive tremendous benefit from this treatment.
Herbal Considerations
The use of demulcent, antitussive, antimicrobial, and bronchial relaxants can help soothe the respiratory lining, targeting airway hyper-responsiveness and addressing any possible persistent infection in the area. Demulcent herbs contain mucilage and thus tend to soothe dry, irritated tissues that come along with post-viral cough. Key demulcent herbs to consider include Althaea officinalis (marshmallow root) and Ulmus rubra (slippery elm bark).10,11 Antitussive agents can reduce respiratory spasm and bronchoconstriction. Key antitussive herbs to consider include Prunus serotina (wild black cherry bark) and Glycyrrhiza glabra (licorice root), which also has antimicrobial effects.12,13 Bronchial relaxants to consider include Asclepias tuberosa (pleurisy root) and Pulmonaria officinalis (lungwort).14 Antimicrobial agents, including Usnea spp (old man’s beard), Ligusticum porteri (osha), Hydrastis canadensis (goldenseal rhizome), and Mahonia aquifolium (Oregon grape root), can combat lingering microbial insult in the area, particularly due to their berberine content.15-18 Soothing expectorants can also help relieve bronchial membrane irritation, and include Verbascum thapsus (mullein), and Inula helenium (elecampane).14,19
In combination with the nebulized solution listed above, we have found clinical success incorporating concentrated berberine supplementation (1 g TID) to address any lingering viral infection that could be contributing to post-viral cough. When taking this dose of berberine, patients are instructed to take it with food due to the hypoglycemic nature of berberine.
Based on a small number of studies conducted in eastern Europe, an extract of Pelargonium sidoides (also known as EPs 7630) has been shown to reduce acute bronchitis symptom duration and intensity. Studies have demonstrated similar beneficial effects in children, adolescents, and adults.20-24
There are a few studies suggesting that ivy extract may reduce coughing fits and overall cough in patients with acute bronchitis.25,26
Cineole (eucalyptol), the main component of eucalyptus oil, has been observed to increase mucociliary beat rates and has broncho-dilating effects. One randomized placebo-controlled trial found that it improved bronchitis symptom scores, owing to a decrease in cough.27 Similar results were obtained in another randomized controlled trial of a preparation containing cineole, in which patients had a reduction in several cough-related symptoms, including night cough, coughing fits, and overall impairment.28
Conventional Treatments
From an allopathic approach, albuterol can be used for wheezing in patients with persistent symptoms. Its use is associated with reductions in cough frequency at 1 week and overall symptom improvement at 1 week.29,30 However, this potential benefit is not well supported by the available data and must be weighed against the adverse effects associated with its use.31,32 Combining albuterol with an antibiotic has shown no additional benefit over albuterol alone, although outcomes at >1 week have not been studied.29 The treatment benefits must be balanced by the adverse effects of nervousness and tremor, which may be more disruptive to the patient than the underlying cough. Inhaled corticosteroids have not been shown to be effective in post-viral cough in adults with subacute (3-8 weeks) or chronic (>8 weeks) cough, adolescents with a history of asthma but without recent asthma activity, or children with a history of episodic viral wheezing without asthma.33
Closing Comments
Although not life-threatening, post-viral cough syndrome can be irritating and annoying to patients, negatively impacting quality of life and potentially exposing the area to prolonged inflammatory and degenerative processes. By targeting the underlying pathologic mechanisms associated with the cough reflex arc through integrative approaches, we can actively reduce the severity and duration of patients’ symptoms, improve quality of life, and ultimately reduce prolonged exposure to degenerative airway inflammatory processes.
References
- Chung KF. Pathophysiology and therapy of chronic cough. Minerva Med. 2005;96(1):29-40.
- Iwata T, Ito I, Niimi A, et al. Mechanical Stimulation by Postnasal Drip Evokes Cough. PLoS One. 2015;10(11):e0141823.
- Canning BJ. Afferent nerves regulating the cough reflex: mechanisms and mediators of cough in disease. Otolaryngol Clin North Am. 2010;43(1):15-25, vii.
- Canning BJ. Functional implications of the multiple afferent pathways regulating cough. Pulm Pharmacol Ther. 2011;24(3):295-299.
- Dicpinigaitis PV. Effect of viral upper respiratory tract infection on cough reflex sensitivity. J Thorac Dis. 2014;6(Suppl 7):S708-S711.
- Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):1S-23S.
- Güriş D, Strebel PM, Bardenheier B, et al. Changing epidemiology of pertussis in the United States: increasing reported incidence among adolescents and adults, 1990-1996. Clin Infect Dis. 1999;28(6):1230-1237.
- Prousky J. The treatment of pulmonary diseases and respiratory-related conditions with inhaled (nebulized or aerosolized) glutathione. Evid Based Complement Alternat Med. 2008;5(1):27-35.
- Marrades RM, Roca J, Barberà JA, et al. Nebulized glutathione induces bronchoconstriction in patients with mild asthma. Am J Respir Crit Care Med. 1997;156(2 Pt 1):425-430.
- Sutovska M, Nosalova G, Franova S, Kardosova A. The antitussive activity of polysaccharides from Althaea officinalis l., var. Robusta, Arctium lappa L., var. Herkules, and Prunus persica L., Batsch. Bratisl Lek Listy. 2007;108(2):93-99.
- Gallagher R. Use of herbal preparations for intractable cough. J Pain Symptom Manage. 1997;14(1):1-2.
- Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res. 2008;22(6):709-724.
- Nosalova G, Fleskova D, Jurecek L, et al. Herbal polysaccharides and cough reflex. Respir Physiol Neurobiol. 2013;187(1):47-51.
- Fisher C, Painter G. Materia Medica of Western Herbs for the Southern Hemisphere. G Painter; 1996, p.29.
- Laxinamujila, Bao HY, Bau T. Advance in studies on chemical constituents and pharmacological activity of lichens in Usnea genus. Zhongguo Zhong Yao Za Zhi. 2013;38(4):539-545. [Article in Chinese]
- Sinclair S. Chinese herbs: a clinical review of Astragalus, Ligusticum, and Schizandrae. Altern Med Rev. 1998;3(5):338-344.
- Ettefagh KA, Burns JT, Junio HA, et al. Goldenseal (Hydrastis canadensis L.) extracts synergistically enhance the antibacterial activity of berberine via efflux pump inhibition. Planta Med. 2011;77(8):835-840.
- Slobodníková L, Kost’álová D, Labudová D, et al. Antimicrobial activity of Mahonia aquifolium crude extract and its major isolated alkaloids. Phytother Res. 2004;18(8):674-676.
- Turker AU, Gurel E. Common mullein (Verbascum thapsus L.): recent advances in research. Phytother Res. 2005;19(9):733-739.
- Timmer A, Günther J, Rücker G, et al. Pelargonium sidoides extract for acute respiratory tract infections. Cochrane Database Syst Rev. 2008;(3):CD006323.
- Agbabiaka TB, Guo R, Ernst E. Pelargonium sidoides for acute bronchitis: a systematic review and meta-analysis. Phytomedicine. 2008;15(5):378-385.
- Kamin W, Maydannik V, Malek FA, Kieser M. Efficacy and tolerability of EPs 7630 in children and adolescents with acute bronchitis – a randomized, double-blind, placebo-controlled multicenter trial with a herbal drug preparation from Pelargonium sidoides roots. Int J Clin Pharmacol Ther. 2010;48(3):184-191.
- Matthys H, Lizogub VG, Malek FA, Kieser M. Efficacy and tolerability of EPs 7630 tablets in patients with acute bronchitis: a randomised, double-blind, placebo-controlled dose-finding study with a herbal drug preparation from Pelargonium sidoides. Curr Med Res Opin. 2010;26(6):1413-1422.
- Kamin W, Maydannik VG, Malek FA, Kieser M. Efficacy and tolerability of EPs 7630 in patients (aged 6-18 years old) with acute bronchitis. Acta Paediatr. 2010;99(4):537-543.
- Kemmerich B, Eberhardt R, Stammer H. Efficacy and tolerability of a fluid extract combination of thyme herb and ivy leaves and matched placebo in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled clinical trial. Arzneimittelforschung. 2006;56(9):652-660.
- Cwientzek U, Ottillinger B, Arenberger P. Acute bronchitis therapy with ivy leaves extracts in a two-arm study. A double-blind, randomised study vs. an other ivy leaves extract. Phytomedicine. 2011;18(13):1105-1109.
- Fischer J, Dethlefsen U. Efficacy of cineole in patients suffering from acute bronchitis: a placebo-controlled double-blind trial. Cough. 2013;9(1):25.
- Gillissen A, Wittig T, Ehmen M, et al. A multi-centre, randomised, double-blind, placebo-controlled clinical trial on the efficacy and tolerability of GeloMyrtol® forte in acute bronchitis. Drug Res (Stuttg). 2013;63(1):19-27.
- Hueston WJ. Albuterol delivered by metered-dose inhaler to treat acute bronchitis. J Fam Pract. 1994;39(5):437-440.
- Hueston WJ. A comparison of albuterol and erythromycin for the treatment of acute bronchitis. J Fam Pract. 1991;33(5):476-480.
- Braman SS. Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):95S-103S.
- Becker LA, Hom J, Villasis-Keever M, et al. Beta2-agonists for acute cough or a clinical diagnosis of acute bronchitis. Cochrane Database Syst Rev. 2015;(9):CD001726.
- Insel K, Lyon C. Clinical inquiry: Are inhaled steroids effective for a postviral cough? J Fam Pract. 2015;64(3):189.
Adam Silberman, ND, provides integrative and preventative family medical services alongside regenerative orthopedic therapies at Integrative Health Solutions in La Jolla, California, with Dr Bronner Handwerger, ND. Dr Silberman dedicates time every week to serving the underserved and has a mission to bring integrative and preventative family medicine to the front line of primary care. His project, Blueprint Wellness, provides corporate programs for employees and their families. His blog, My Health Matters, provides information on maximizing health and vitality to the public. He shares his life’s passions with his lovely wife Serena and inspiring son Jaxon. Find Adam online at: www.blueprintwellness.org.
Bronner Handwerger, ND, treats many professional NFL and Olympic athletes along with Special Ops and Navy SEALs using state-of-the-art regenerative therapies. He has been successfully using regenerative modalities such as platelet-rich plasma, prolotherapy, and other techniques to treat and help heal patients’ injuries, both acute and chronic. He also focuses on endocrinology and family practice. Website: www.docbron.com