US Pharm. 2019;(1):8-12.

Cough is considered an important protective reflex mechanism, helping to clear the airways from excessive secretions and preventing foreign particles from entering the body, but when it compromises the respiratory system, a cough can become excessive, nonproductive, and potentially harmful.^1,2 Cough is a common complaint for which many patients will seek medical care. It is responsible for up to 30 million primary care visits annually and is among the leading reasons for office and emergency department visits.^3-5 Cough is classified based on duration; an acute cough is defined as lasting less than 3 weeks, a subacute cough is defined as having a duration between 3 and 8 weeks, and a chronic cough is one that is more than 8 weeks.⁶ Most acute coughs are due to upper respiratory tract infections, are self-limiting, and rarely require significant medical intervention.⁷ Noninfectious causes of acute cough include asthma and chronic obstructive pulmonary disease (COPD) exacerbations, allergic rhinitis, and exposure to environmental pollutants.^1,8 Common etiologies contributing to chronic cough are upper airway cough syndrome, gastroesophageal reflux disease, tobacco use, and angiotensin-converting enzyme inhibitor use.

Despite the nature of cough, it can be challenging to manage, causing the patient difficulties in performing daily activities and having a significant impact on a patient’s quality of life.^2,9 In a recent survey, 52% of respondents indicated that cough/cold impacted their daily life a fair amount to a lot, and almost 60% reported cough or nasal congestion as the symptoms making it most difficult to sleep.² Patients may also experience a reduced sense of well-being owing to feelings of self-consciousness, anxiety, musculoskeletal pain, and urinary incontinence.⁸ Many patients suffering from cough will seek out self-care options; more than $8 billion was spent in 2017 on cough and cold products.¹⁰ This places the pharmacist in a pivotal position to help identify patients who may need further evaluation and help in selecting the most appropriate product.

Assessment of Cough

When evaluating a cough, adults need to be assessed and treated differently than children. The American College of Chest Physicians’ clinical guidelines recommend that patients presenting with cough be divided into children (those younger than 15 years of age) and adults.¹¹ Although there are many similarities with regard to cough in both of these populations, there are also clinical and physiological differences between children and adults, such as adult definitions (e.g., chronic bronchitis and COPD) not recognized as pediatric diagnostic entities in children and differing responses to some medications.¹¹ In addition, patients with underlying and chronic diseases or those who are immunocompromised should be further evaluated.³ Patients who present with other identified factors (Table 1) should be referred for further evaluation; the presence of these alarm symptoms could be indicative of a more serious condition associated with cough, such as pulmonary embolism, pulmonary edema, foreign body inhalation, or status asthmaticus.^7,12

Treatment

There are a variety of products for cough available OTC. Most OTC products fall into two basic categories: cough suppressants (antitussives) and expectorants (Table 2). The availability of these products without a prescription promotes the perception that they are safe and efficacious. However, there is little evidence for or against the effectiveness of such products.¹³ The most recent guidelines for the management of acute cough do not recommend the use of OTC cough and cold products until they have been shown to make cough less severe or resolve sooner.¹⁴

H₁ Receptor Antagonists: First-generation H₁ receptor antagonist antihistamines have historically been used in the management of acute cough. The proposed action for their antitussive effect is the peripheral indirect mechanism involving cholinergic activity; many of the antihistamines have anticholinergic actions.¹⁵ Unlike the first-generation agents, the newer generation of H₁ antihistamines have not demonstrated usefulness in the treatment of cough.¹⁴ There are few trials that have demonstrated possible efficacy for the use of antihistamines as an antitussive.^16-20 In addition, a systematic review demonstrated that the combination of antihistamines with a decongestant provided inconsistent results, making it difficult to form any conclusion regarding their effectiveness.²¹ Similarly, the combination of antihistamines with an analgesic failed to show any effect on cough when compared with placebo or acetaminophen.²¹ Studies of the antitussive effect of antihistamines are lacking in the pediatric population; a Cochrane review concluded, based on the available data, that H₁ antihistamines should not be recommended for the treatment of cough in children.²² Overall, the common use of antihistamines for the resolution of cough is not supported by clinical evidence.

Codeine: Codeine is a naturally occurring alkaloid found in poppy extracts. It is a prodrug that is converted to morphine in the liver.²³ Codeine is a centrally acting cough suppressant and has long been considered the “gold standard” cough suppressant; however, there is little evidence to support this claim.²⁴ In one study investigating cough due to an upper respiratory tract infection (URTI), codeine 30 mg as a single dose or in a total daily dose of 120 mg demonstrated no greater efficacy than placebo in controlling cough.²⁵ In another study, codeine 50 mg was compared with placebo to determine the antitussive efficacy of codeine in cough associated with URTI. Again, no effect greater than that of placebo was observed.²⁶ The use of codeine is also associated with sedation, nausea, constipation, and potential physical dependency. Although codeine is one of the most widely used and prescribed antitussives, controlled studies have not supported its use as an effective antitussive.

Dextromethorphan: Dextromethorphan (DXM) is found in many cough and cold products. It was first used in 1953 as a treatment for cough without the undesirable effects of codeine, such as nausea, constipation, and dependency.²⁷ The exact mechanism by which DXM suppresses cough is not completely understood, but similar to codeine, it is a centrally acting cough suppressant.²⁴ It is the only agent that has been able to demonstrate significant suppression of acute cough using objective measures such as cough count, cough effort, and cough bouts.²⁸ However, it has been more difficult to demonstrate any clinically significant effects on cough, especially with URTI-related coughs; this is due to the lack of adequately powered, well-designed studies evaluating DXM’s effect both objectively and subjectively in the management of cough.

One concern with DXM use is its potential to be misused and abused, which is a continuing problem. High doses of DXM can produce a sensation of euphoria, relaxation, and intoxication.²⁹ Although recent data have shown a decrease in intentional DXM abuse among adolescents, more young adults are using DXM recreationally.³⁰

Menthol: Menthol’s antitussive effect was first commercialized in the 1890s with the development of a topical rub and has since become a stock ingredient in many OTC preparations.³¹ Its antitussive activity appears to be through the activation of nasal sensory afferents, modulating the cough response, rather than the lungs.³² Although menthol is widely used, there is little clinical evidence to support its antitussive effect. In two small studies, menthol vapor produced a short-lasting decrease in capsaicin-induced and citric acid–induced coughs.^33,34 Despite its widespread use, there are no published clinical trials supporting menthol’s antitussive effect in patients with either acute or chronic cough.

Guaifenesin: Guaifenesin is the only FDA-approved expectorant.³⁵ It is an ingredient found in many OTC  cough and cold products and is commonly used for the management of chest congestion and cough related to URTIs. Although the exact mechanism of action is not fully understood, guaifenesin has demonstrated multiple effects on mucus, including increasing the volume of bronchial secretions and decreasing mucus viscosity, resulting in an enhanced clearance of airway secretions.³⁶ It may also have direct effects on respiratory tract epithelial cells. In addition, guaifenesin may also have some effect inhibiting the cough-reflex sensitivity.³⁶

Despite its availability in multiple OTC preparations, the efficacy of guaifenesin as an expectorant in cold and flu preparations continues to be questioned. A 2014 Cochrane review of cough and cold products failed to find any evidence supporting the clinical efficacy of the drug either alone or in combination.¹³ Despite the lack of trials to demonstrate clinical benefit, guaifenesin continues to be promoted as an effective expectorant in OTC products. The drug is considered relatively safe and is not associated with any clinically significant drug interactions. When used at recommended doses, it is relatively well tolerated; at high doses, dizziness, headache, and gastrointestinal disturbances were cited as the most common side effects.³⁶

Safety Concerns of OTC Products in Children

In January 2008, the FDA advised against the use of all OTC cough and cold products in children under the age of 2 years because of the occurrence of serious and potentially life-threatening side effects.³⁷ In October 2008, the Consumer Healthcare Products Association (CHPA) announced that manufacturers were voluntarily changing the labels on pediatric OTC cough and cold products to read “do not use in children under the age of four years.”³⁸ There is very limited data regarding efficacy of cough and cold products in the pediatric population; most data have been extrapolated from adult studies. In addition, the studies that have been conducted in the pediatric population have shown that OTC cough and cold products demonstrate no significant difference when compared with placebo in the reduction of cough.³⁹ Most of these products often are unintentionally misused, leading to serious adverse effects and death.^40,41 More recently, in January 2018, the FDA announced that it will be requiring safety labeling changes to limit the use of opioid cough and cold medicines in children younger than age 18 years because the serious risks associated with the use of these medications outweigh the potential benefits in this patient population. These products will no longer be indicated in the treatment of cough in those younger than age 18 years.⁴² 

Role of the Pharmacist

Pharmacists are often consulted by patients regarding the selection of OTC products for the management of cough. Most acute coughs are caused by a viral respiratory infection and are usually self-limiting. In some cases, a cough may be indicative of a more serious complication, and pharmacists need to be aware of symptoms that warrant referral for further evaluation. Unfortunately, the majority of therapies available are currently recommended based on historical practice rather than on scientific evidence.

The 2017 updated American College of Chest Physician guidelines on the management of acute cough recommend against the use of OTC cough and cold medications until they have been shown to make cough less severe or resolve it sooner.¹⁴ However, if patients choose to use any of the OTC cough preparations, pharmacists need to educate consumers on the safe use of these products, especially parents or guardians of small children. Currently the FDA does not recommend the use of these products in children under the age of 2 years; CHPA supports the safe and effective use of pediatric cough products for children aged 4 years and older.

Instead, pharmacists can recommend alternative therapies such as a steamy bath or use of a cool mist vaporizer. Although no randomized, placebo-controlled trials exist examining these therapies, studies have indicated a placebo effect associated with the treatment of cough; almost 40% of patients reported improvement when treated with placebo.^25,43,44 There is also some evidence that honey may reduce the duration of cough, especially in children. A Cochrane review demonstrated that honey may relieve cough symptoms more than no treatment, diphenhydramine, and placebo, but it has not been shown to be better than DXM. Honey, however, should not be recommended in infants younger than age 12 months because of the high risk of botulism.⁴⁵

Acute cough is one of the most common symptoms to affect patients, especially after a URTI. Pharmacists are ideally positioned to educate patients about the occurrence of cough, its duration, and the efficacy of the current available treatments.

Patient Information

What causes a cough?

Cough is divided into three different categories based on how long a person is coughing. An acute cough is one that lasts for less than 3 weeks. This is most frequently caused by the common cold. The cough is usually worse the first few days but eventually goes away in about 2 weeks.

A cough that lasts between 3 to 8 weeks is a subacute cough. This cough usually stays after a cold or other infection but will eventually go away without treatment.

A cough that lasts more than 8 weeks is a chronic cough. This is most commonly due to other conditions such as allergies, asthma, and acid reflux disease; it also occurs in smokers. Some medicines can also cause chronic cough. Angiotensin-converting enzyme inhibitors are a common group of medicines that can cause cough. This class of medicine is used to treat high blood pressure.

When should you see your healthcare provider?

If you have a persistent cough that is not getting better, you should be examined by your primary care provider. If you have a cough and have other symptoms including shortness of breath, a fever, chest pain, bloody phlegm, or phlegm with pus, wheezing, or voice changes, you should reach out to your primary care provider immediately.

What can I take to help relieve my cough?

Treatment is going to depend on the cause. If another condition is causing your cough, treatment will be aimed at controlling the underlying cause.

For acute coughs due to the common cold or another upper respiratory infection, there are many OTC products available, but none of them have been proven effective in treating a cough. The FDA also recommends that these products not to be used in children under the age of 2 years because of serious and potentially life-threatening side effects. Most often these coughs will go away in a few weeks once the infection has gotten better. You should make sure you drink plenty of fluids. You can also try taking a steamy bath or using a cool-mist vaporizer to help relieve the cough.

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