Treatment of subacute and chronic cough in adults
- Steven E Weinberger, MD
Steven E Weinberger, MD
- Adjunct Professor of Medicine
- University of Pennsylvania School of Medicine
- Executive Vice President and CEO Emeritus
- American College of Physicians
- Ronald C Silvestri, MD
Ronald C Silvestri, MD
- Assistant Professor of Medicine
- Harvard Medical School
- Section Editors
- Peter J Barnes, DM, DSc, FRCP, FRS
Peter J Barnes, DM, DSc, FRCP, FRS
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Asthma
- Professor of Medicine
- National Heart and Lung Institute, Imperial College, London
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
Although an acute and self-limited cough often does not require therapy, prolonged cough can be a bothersome symptom that precipitates many outpatient visits to the clinician for treatment. Differing definitions for a chronic cough have been proposed that require symptoms for varying times from two weeks to three months [1,2]. Guidelines from the American College of Chest Physicians distinguish three categories of cough based upon duration :
●Acute cough, lasting less than three weeks
●Subacute cough, lasting between three and eight weeks
●Chronic cough, lasting more than eight weeks
The initial priorities for patients with cough lasting more than three weeks (subacute or chronic cough) are to identify a precipitant or etiology, and then to eliminate the precipitant or treat the underlying cause [3-6].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest 2006; 129:1S.
- Morice AH, Fontana GA, Sovijarvi AR, et al. The diagnosis and management of chronic cough. Eur Respir J 2004; 24:481.
- Irwin RS, Curley FJ. The treatment of cough. A comprehensive review. Chest 1991; 99:1477.
- Irwin RS, Madison JM. The diagnosis and treatment of cough. N Engl J Med 2000; 343:1715.
- Palombini BC, Villanova CA, Araújo E, et al. A pathogenic triad in chronic cough: asthma, postnasal drip syndrome, and gastroesophageal reflux disease. Chest 1999; 116:279.
- Iyer VN, Lim KG. Chronic cough: an update. Mayo Clin Proc 2013; 88:1115.
- Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy. Am Rev Respir Dis 1981; 123:413.
- Irwin RS, Curley FJ, French CL. Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis 1990; 141:640.
- Pratter MR, Bartter T, Akers S, DuBois J. An algorithmic approach to chronic cough. Ann Intern Med 1993; 119:977.
- Birring SS. Controversies in the evaluation and management of chronic cough. Am J Respir Crit Care Med 2011; 183:708.
- Woodcock A, Young EC, Smith JA. New insights in cough. Br Med Bull 2010; 96:61.
- Haque RA, Usmani OS, Barnes PJ. Chronic idiopathic cough: a discrete clinical entity? Chest 2005; 127:1710.
- Pratter MR. Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal drip syndrome): ACCP evidence-based clinical practice guidelines. Chest 2006; 129:63S.
- Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol 2008; 122:S1.
- Curley FJ, Irwin RS, Pratter MR, et al. Cough and the common cold. Am Rev Respir Dis 1988; 138:305.
- Grossman J, Banov C, Boggs P, et al. Use of ipratropium bromide nasal spray in chronic treatment of nonallergic perennial rhinitis, alone and in combination with other perennial rhinitis medications. J Allergy Clin Immunol 1995; 95:1123.
- Dicpinigaitis PV. Chronic cough due to asthma: ACCP evidence-based clinical practice guidelines. Chest 2006; 129:75S.
- Cheriyan S, Greenberger PA, Patterson R. Outcome of cough variant asthma treated with inhaled steroids. Ann Allergy 1994; 73:478.
- Spector SL, Tan RA. Effectiveness of montelukast in the treatment of cough variant asthma. Ann Allergy Asthma Immunol 2004; 93:232.
- Dicpinigaitis PV, Dobkin JB, Reichel J. Antitussive effect of the leukotriene receptor antagonist zafirlukast in subjects with cough-variant asthma. J Asthma 2002; 39:291.
- Hunter CJ, Brightling CE, Woltmann G, et al. A comparison of the validity of different diagnostic tests in adults with asthma. Chest 2002; 121:1051.
- Chatkin JM, Ansarin K, Silkoff PE, et al. Exhaled nitric oxide as a noninvasive assessment of chronic cough. Am J Respir Crit Care Med 1999; 159:1810.
- Song WJ, Kim HJ, Shim JS, et al. Diagnostic accuracy of fractional exhaled nitric oxide measurement in predicting cough-variant asthma and eosinophilic bronchitis in adults with chronic cough: A systematic review and meta-analysis. J Allergy Clin Immunol 2017; 140:701.
- Brightling CE. Chronic cough due to nonasthmatic eosinophilic bronchitis: ACCP evidence-based clinical practice guidelines. Chest 2006; 129:116S.
- Brightling CE, Ward R, Wardlaw AJ, Pavord ID. Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis. Eur Respir J 2000; 15:682.
- Irwin RS, French CL, Curley FJ, et al. Chronic cough due to gastroesophageal reflux. Clinical, diagnostic, and pathogenetic aspects. Chest 1993; 104:1511.
- Poe RH, Kallay MC. Chronic cough and gastroesophageal reflux disease: experience with specific therapy for diagnosis and treatment. Chest 2003; 123:679.
- Kahrilas PJ, Altman KW, Chang AB, et al. Chronic Cough Due to Gastroesophageal Reflux in Adults: CHEST Guideline and Expert Panel Report. Chest 2016; 150:1341.
- Chang AB, Lasserson TJ, Gaffney J, et al. Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev 2011; :CD004823.
- Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease. Gastroenterology 2008; 135:1383.
- Allen CJ, Anvari M. Gastro-oesophageal reflux related cough and its response to laparoscopic fundoplication. Thorax 1998; 53:963.
- Hoppo T, Komatsu Y, Jobe BA. Antireflux surgery in patients with chronic cough and abnormal proximal exposure as measured by hypopharyngeal multichannel intraluminal impedance. JAMA Surg 2013; 148:608.
- Iqbal M, Batch AJ, Spychal RT, Cooper BT. Outcome of surgical fundoplication for extraesophageal (atypical) manifestations of gastroesophageal reflux disease in adults: a systematic review. J Laparoendosc Adv Surg Tech A 2008; 18:789.
- Pratter MR. Cough and the common cold: ACCP evidence-based clinical practice guidelines. Chest 2006; 129:72S.
- Berkowitz RB, Tinkelman DG. Evaluation of oral terfenadine for treatment of the common cold. Ann Allergy 1991; 67:593.
- Berkowitz RB, Connell JT, Dietz AJ, et al. The effectiveness of the nonsedating antihistamine loratadine plus pseudoephedrine in the symptomatic management of the common cold. Ann Allergy 1989; 63:336.
- Braman SS. Postinfectious cough: ACCP evidence-based clinical practice guidelines. Chest 2006; 129:138S.
- Holmes PW, Barter CE, Pierce RJ. Chronic persistent cough: use of ipratropium bromide in undiagnosed cases following upper respiratory tract infection. Respir Med 1992; 86:425.
- Senzilet LD, Halperin SA, Spika JS, et al. Pertussis is a frequent cause of prolonged cough illness in adults and adolescents. Clin Infect Dis 2001; 32:1691.
- Cazzola M, Matera MG, Liccardi G, et al. Theophylline in the inhibition of angiotensin-converting enzyme inhibitor-induced cough. Respiration 1993; 60:212.
- Hargreaves MR, Benson MK. Inhaled sodium cromoglycate in angiotensin-converting enzyme inhibitor cough. Lancet 1995; 345:13.
- Malini PL, Strocchi E, Zanardi M, et al. Thromboxane antagonism and cough induced by angiotensin-converting-enzyme inhibitor. Lancet 1997; 350:15.
- Dicpinigaitis PV. Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines. Chest 2006; 129:169S.
- Lacourcière Y, Brunner H, Irwin R, et al. Effects of modulators of the renin-angiotensin-aldosterone system on cough. Losartan Cough Study Group. J Hypertens 1994; 12:1387.
- Tanaka H, Teramoto S, Oashi K, et al. Effects of candesartan on cough and bronchial hyperresponsiveness in mildly to moderately hypertensive patients with symptomatic asthma. Circulation 2001; 104:281.
- Morice AH. The cough hypersensitivity syndrome: a novel paradigm for understanding cough. Lung 2010; 188 Suppl 1:S87.
- Mitchell JE, Campbell AP, New NE, et al. Expression and characterization of the intracellular vanilloid receptor (TRPV1) in bronchi from patients with chronic cough. Exp Lung Res 2005; 31:295.
- Adcock JJ. TRPV1 receptors in sensitisation of cough and pain reflexes. Pulm Pharmacol Ther 2009; 22:65.
- Grace MS, Belvisi MG. TRPA1 receptors in cough. Pulm Pharmacol Ther 2011; 24:286.
- Belvisi MG, Geppetti P. Cough. 7: Current and future drugs for the treatment of chronic cough. Thorax 2004; 59:438.
- Irwin RS, Curley FJ, Bennett FM. Appropriate use of antitussives and protussives. A practical review. Drugs 1993; 46:80.
- Bolser DC. Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines. Chest 2006; 129:238S.
- Yancy WS Jr, McCrory DC, Coeytaux RR, et al. Efficacy and tolerability of treatments for chronic cough: a systematic review and meta-analysis. Chest 2013; 144:1827.
- Matthys H, Bleicher B, Bleicher U. Dextromethorphan and codeine: objective assessment of antitussive activity in patients with chronic cough. J Int Med Res 1983; 11:92.
- Aylward M, Maddock J, Davies DE, et al. Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects. Eur J Respir Dis 1984; 65:283.
- Smith J, Owen E, Earis J, Woodcock A. Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease. J Allergy Clin Immunol 2006; 117:831.
- Woodcock A, McLeod RL, Sadeh J, Smith JA. The efficacy of a NOP1 agonist (SCH486757) in subacute cough. Lung 2010; 188 Suppl 1:S47.
- Chung KF. Currently available cough suppressants for chronic cough. Lung 2008; 186 Suppl 1:S82.
- Morice AH, Menon MS, Mulrennan SA, et al. Opiate therapy in chronic cough. Am J Respir Crit Care Med 2007; 175:312.
- Ryan NM. A review on the efficacy and safety of gabapentin in the treatment of chronic cough. Expert Opin Pharmacother 2015; 16:135.
- Gibson PG, Vertigan AE. Management of chronic refractory cough. BMJ 2015; 351:h5590.
- Gibson P, Wang G, McGarvey L, et al. Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report. Chest 2016; 149:27.
- Ryan NM, Birring SS, Gibson PG. Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial. Lancet 2012; 380:1583.
- Vertigan AE, Kapela SL, Ryan NM, et al. Pregabalin and Speech Pathology Combination Therapy for Refractory Chronic Cough: A Randomized Controlled Trial. Chest 2016; 149:639.
- Dicpinigaitis PV, Gayle YE, Solomon G, Gilbert RD. Inhibition of cough-reflex sensitivity by benzonatate and guaifenesin in acute viral cough. Respir Med 2009; 103:902.
- Doona M, Walsh D. Benzonatate for opioid-resistant cough in advanced cancer. Palliat Med 1998; 12:55.
- McLawhorn MW, Goulding MR, Gill RK, Michele TM. Analysis of benzonatate overdoses among adults and children from 1969-2010 by the United States Food and Drug Administration. Pharmacotherapy 2013; 33:38.
- Horton MR, Santopietro V, Mathew L, et al. Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial. Ann Intern Med 2012; 157:398.
- Lim KG, Rank MA, Hahn PY, et al. Long-term safety of nebulized lidocaine for adults with difficult-to-control chronic cough: a case series. Chest 2013; 143:1060.
- Boulet LP, Milot J, Boutet M, et al. Airway inflammation in nonasthmatic subjects with chronic cough. Am J Respir Crit Care Med 1994; 149:482.
- Evald T, Munch EP, Kok-Jensen A. Chronic non-asthmatic cough is not affected by inhaled beclomethasone dipropionate. A controlled double blind clinical trial. Allergy 1989; 44:510.
- Hodgson D, Anderson J, Reynolds C, et al. The Effects of Azithromycin in Treatment-Resistant Cough: A Randomized, Double-Blind, Placebo-Controlled Trial. Chest 2016; 149:1052.
- Yousaf N, Monteiro W, Parker D, et al. Long-term low-dose erythromycin in patients with unexplained chronic cough: a double-blind placebo controlled trial. Thorax 2010; 65:1107.
- Gibson PG, Vertigan AE. Speech pathology for chronic cough: a new approach. Pulm Pharmacol Ther 2009; 22:159.
- Chamberlain S, Birring SS, Garrod R. Nonpharmacological interventions for refractory chronic cough patients: systematic review. Lung 2014; 192:75.
- Abdulqawi R, Dockry R, Holt K, et al. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet 2015; 385:1198.
- SPECIFIC TREATMENT
- Upper airway cough syndrome
- Cough variant asthma
- Nonasthmatic eosinophilic bronchitis
- Gastroesophageal reflux
- - Lifestyle modifications
- - Acid-suppression medication
- - Other therapies
- Following an upper respiratory tract infection
- Angiotensin converting enzyme inhibitors and receptor blockers
- NONSPECIFIC TREATMENT
- Centrally acting antitussive agents
- - Dextromethorphan
- - Codeine
- - Morphine
- - Gabapentin and pregabalin
- Peripherally acting antitussive agents
- Inhaled glucocorticoids
- Ipratropium bromide
- Macrolide antibiotics
- Non-pharmacologic interventions
- FUTURE DIRECTIONS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS
- Specific therapy
- Nonspecific therapy