Cough as a Red Flag

NOVEMBER 22, 2010
Guido R. Zanni, PhD
Serious medical conditions, as well as more common ailments, may be the underlying reason for some coughs.

Cough—an involuntary or deliberate explosive expiratory action intended to clear the airways—is a crucial adaptive behavior. Among healthy adults, cough is uncommon during the day and even less common at night, so it is usually devoid of clinical significance.1 When coughing becomes bothersome, however, or patients believe their coughing might signal something serious, they seek medical help—making cough the most frequent symptom for which patients seek relief.2,3 Indeed, a cough can be a red flag for a more serious condition. The economic cost of cough approximates $40 billion, including billions spent on OTC remedies.4 Negatively impacting quality of life, cough also has physical, psychological, and social burdens.1,5

The cough reflex is initiated by afferent receptors located on airway sensory nerves. Receiving this information, the brain stem’s vagus nerve stimulates efferent receptors, signaling respiratory musculature and laryngeal structures to execute the cough. Also, the cerebral cortex appears to be involved with voluntary control over coughing, including sensations associated with the need or urge to cough.3

Cough begins with the inspiratory phase (air is inhaled); then it has a compressive phase (pressure against a closed glottis); and then it ends with the audible expulsive phase (glottis opens followed by a forceful expiratory effort).3

Practitioners categorize cough as acute—duration of 3 weeks or less, or as chronic—duration greater than 3 weeks. Some practitioners define chronic cough as lasting longer than 8 weeks and refer to coughs lasting 3 to 8 weeks as subacute. Coughs may be productive (wet cough expelling secretions from the respiratory tract that are clear, colored, or malodorous) or nonproductive (dry hacking cough without a useful physiological purpose). Overall characteristics such as timing and sound are not useful indicators of cause.1 For example, green or yellow thick phlegm may suggest infection, but doesn’t distinguish bacterial from viral or fungal infections.6

Acute Cough Conditions
Six conditions generally cause acute cough:
• Upper respiratory tract infections (URTIs) including pneumonia
• Viral infections associated with the common cold or influenza
• Chronic obstructive pulmonary disease (COPD) exacerbations
• Postnasal drip
• Environmental irritants and pollution (females have a lower cough threshold to irritants than males)
• Allergies3,5-7

Chronic Cough Conditions
Up to 20% of coughs become chronic.7 Chronic coughs should not be ignored. In most instances, there is a serious and possibly life-threatening pathology. Along with the aforementioned acute conditions that may become chronic, other conditions include:
• Tobacco use—The most common cause of chronic cough; nicotine withdrawal increases coughing and the urge to cough. Most smokers lose their cough within a year of quitting.
• Asthma—Many asthma patients experience both wheezing and coughing, but cough may be asthma’s only symptom.
• Gastroesophageal reflux disease (GERD)—While many GERD pa– tients experience heartburn, in some in– stances cough is GERD’s only symptom.
• Sinus problems.
• Bacterial infection including pneumonia and bronchitis.
• Heart failure and disease—Cough is one of the earliest symptoms.
• Medications (especially angiotensinconverting enzyme inhibitors)3,8-10

Postnasal drip, tobacco use, asthma, and GERD are the most common conditions associated with chronic cough.1 Smoker’s cough should not be summarily dismissed as throat irritation. Coughs accompanied by involuntary weight loss suggest lung cancer, especially when blood-stained phlegm and shortness of breath are present.10 Table 1 highlights 10 serious conditions that have “red flag” coughs.

Idiopathic Cough
Up to 15% of coughs have no identifiable cause and are labeled idiopathic. Patients with idiopathic cough are a well-defined population, with 80% female prevalence, mostly postmenopausal women.11 Additionally, a URTI often precedes idiopathic cough.3 While a potential relationship between hormones and idiopathic cough is intriguing, the possibility exists that the observed prevalence in women may merely reflect gender differences in health-seeking behaviors.11

Until recently, researchers and practitioners agreed that idiopathic coughs resulted from cough reflex hypersensitivity. 7 This prevailing view, however, has come under fire from critics, who have postulated that idiopathic cough is not a separate clinical entity, but rather represents a failure to diagnose the cough’s underlying cause.11 Research findings tend to confirm these assertions.

Using a stepwise diagnostic protocol, researchers were able to determine a cough’s cause in 98% of patients; causes included variants of asthma, rhinosinusitis associated with postnasal drip, and GERD.12 Also, within the last decade, new etiologies underlying chronic cough have been discovered. One such cause is eosinophilic airway syndrome, characterized by pulmonary eosinophilia in distal airways, air spaces, and the interstitial compartment of the lung.13

Treatment is dictated by cough’s etiology. For mild coughs, symptomatic relief is possible using OTC agents containing guaifenesin and/or dextromethorphan, increasing fluid intake, inhaling steam, and using lozenges.8 For dry cough, systemic antitussives (codeine, dextromethorphan, diphenhydramine) are preferred, whereas guaifenesin is preferred for wet, productive coughs.

Based on an initial assessment, many clinicians begin empiric treatment for postnasal drip (eg, antihistamine, decongestants, nasal corticosteroid sprays) or GERD (proton pump inhibitors, H2 blockers). A positive response often precludes the need for additional testing.6 Agents used for managing coughs are highlighted in Table 2. A cough persisting for 4 weeks or longer should not be simply silenced with a cough suppressant or mucolytic agent. Coughing is an adaptive physiological response or symptom, and its suppression may worsen the underlying condition.1 Efforts must focus on the cough’s etiology.

Most acute coughs resolve within 2 weeks, but may take up to 4 weeks for a small minority of patients. Antibiotics are not recommended for simple acute coughs, which are usually viral.1 While codeine is the drug of choice as a cough suppressant, research demonstrates that it is no more effective than placebo for COPD sufferers complaining of cough.14

Table 2. Managing Coughs
Antitussives Dextromethorphan and codeine depress the medullary cough center; benzonate anesthetizes stretch receptors of vagal afferent fibers in bronchi and alveoli.
Topical treatments Cough drops, honey, demulcents, and glycerin are popular among patients; while soothing, their use is not supported by evidence.
Protussives Protussive therapy is indicated when coughing should be encouraged (eg, to clear the airways of mucus). Terbutaline, amiloride, and hypertonic saline aerosols are most successful. May not be useful in treating acute bronchitis.
Bronchodilators Albuterol, ipratropium, and inhaled corticosteroids are effective for an URTI cough and asthma.
URTI = upper respiratory tract infection.
Adapted from references 6, 8, 16, and 17.

Final Thought
Despite their sales, evidence is mixed on the effectiveness of OTC medications in adults and children for acute cough.15 Nevertheless, pharmacists can anticipate numerous questions on OTC products. One survey found that 72% of people selftreat with OTC products, with 40% readily admitting uncertainty whether the product they chose was appropriate for their symptoms.2 The pharmacist is uniquely positioned to counsel patients regarding cough and cough products, as well as guide them to the appropriate treatments and follow-ups with their physicians when necessary. PT

Dr. Zanni is a psychologist and health systems consultant based in Alexandria, Virginia.


1.  Irwin RS, Madison JM. Symptom research on chronic cough: a historical
perspective. Ann Intern Med. 2001;134:809-814.
2. [No author] New surveys show U.S. adults confused about symptoms, treatments for coughs due to cold or flu as season begins. PR Newswire. December 16, 2009.
3.  McGarvey L. Acute and chronic cough syndromes differential diagnosis: infections or not? Available at:
4.  Fendrick AM, Monto AS, Nightengale B, Sarnes M. The economic burden of
non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med. 2003;163:487-494.
5. Smith JA. Assessing efficacy of therapy for cough. Otolaryngol Clin North Am.
2010;43:157-166, xi.
6.  Lechtzin N. Cough in adults. Merck Manuals Online Library. Available at:
7.  [No author] Seven kinds of cough that can have you barking for years. Sunday Independent (South Africa). October 26, 2008.
8.  Cunha JP. Chronic cough. Available at:
9.  Bolser DC. A streetcar named urge-to-cough. J Appl Physiol. 2010;108:1030-1031.
10. Bardana E, Braman S, Johnson J. When a cough just won’t go away. Patient Care. 1992;26:64-76.
11.  McGarvey LP. Idiopathic chronic cough: a real disease or a failure of
diagnosis? Cough. 2005;1:9.
12.  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(4 part 1):413-417.
13.  O’Connor D. Recognizing eosinophilic lung syndromes. RespiratoryReviews.Com. Available at:
14. Smith J, Owen E, Earis J, Woodcock A. Effect of codeine on objective
measurement of cough in chronic obstructive pulmonary disease. J Allergy Clin
15. Smith SM, Schroeder K, Fahey T. Over-the-counter medications for acute cough
in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2008;(1):CD001831.
16.  Bolser DC. Pharmacologic management of cough. Otolaryngol Clin North Am. 2010;43(1):147-155, xi.
17.  Knutson D, Braun C. Diagnosis and management of acute bronchitis. Am Fam


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