Newer Insights Into the Prevention of the Common Cold

Supported by an educational grant from Procter & Gamble.

FACULTY:

Amista L. Salcido, PharmD
Clinical Assistant Professor
Cooperative Pharmacy Program
University of Texas at El Paso/UT-Austin
El Paso, TX

FACULTY DISCLOSURE STATEMENTS:

Dr. Salcido has no actual or potential conflicts of interest in relation to this program.

U.S. Pharmacist does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacy
Postgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
Program No.: 430-000-07-026-H01-P; 430-000-07-026-H01-T
Credits: 2.0 hours (0.20 ceu)

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TARGET AUDIENCE:

This accredited program is targeted to pharmacists and pharmacy technicians.

DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL:

To educate pharmacists about the occurrence and transmission of the common cold and to provide accurate information to patients regarding methods of prevention.

OBJECTIVES:

After completing this program, participants will be able to:

1. Provide a basic overview of the epidemiology and economic impact of the common cold in the U.S.*
2. List the common symptom complex and potential complications associated with the common cold.*
3. Discuss the pathogenesis of the common cold.*
4. Describe the mechanisms for the transmission of the common cold.*
5. Identify preventative measures for the common cold, separating fact from fiction.*
6. List important counseling points for pharmacists to convey to their patients regarding prevention, symptom management, and physician referral in the setting of the common cold.

*Also applies to pharmacy technicians.

The common cold, also known as acute viral nasopharyngitis, is a mild, self-limiting infectious disease. Hippocrates first described the disease as early as the 5th century B.C.¹ The Egyptians even had a hieroglyph for a cold: a nose followed by a symbol representing something coming out.² The term "cold" was likely derived from ancient physicians who described "cold conditions" and "warm conditions" that were dependent on cold or warm environments. In modern times, the misnomer has persisted. The common cold is the most contracted infectious disease of humans and results in significant costs to the economy in lost workdays and school attendance. It is the leading cause of patient visits to health care providers and is the most prevalent entity of all respiratory infections.¹ It is also one of the most frequently reported maternal disorders during pregnancy.³ The common cold can be produced by over 200 viruses.⁴ Rhinoviruses, comprising more than 100 serotypes, are the most common pathogens, causing at least 50% of colds in adults.^1,5

Myth: Becoming cold or "chilled" leads to catching a cold.
Fact: Almost everybody becomes infected, whether they are "chilled" or not, if a cold virus is dropped into the nose.

EPIDEMIOLOGY

The common cold is so prevalent that its incidence is gauged in terms of number of colds per individual per year, as opposed to the usual epidemiologic measurement (e.g., incidence per 10,000 persons yearly).⁴ Colds are most prevalent among children, and seem to be related to their increased contact with other children in schools and day care centers, or their relative lack of resistance to infection. Children have about six to ten colds a year on average, but in families with children in school, the number of colds per child can be as high as 12 a year.⁶ Women, especially those aged 20 to 30 years, have more colds than men, possibly because of more close contact with children.⁶ Adults average about two to four colds per year,although the range varies widely.^6-8 On average, individuals older than 60 have fewer than one cold a year.⁶

Contrary to popular belief, being in a cold or wet environment does not increase susceptibility to the common cold. Breathing exceptionally dry air, however, can predispose the patient by limiting the capacity of mucokinesis to expel viral pathogens. Smokers are at an increased risk of contracting the common cold, and typically colds are more severe than those seen in nonsmokers. Low socioeconomic status also increases the risk of the common cold.⁴ In the United States, colds can occur at any time, but most commonly from late August through early April.

The economic impact of the common cold is enormous. The National Center for Health Statistics estimates that over 62 million cases of the common cold in the U.S. require medical attention or result in restricted activity annually.^6,9 Each year, the common cold causes workdays missed by employees suffering from a cold, the total economic impact of cold-related work loss exceeds $20 billion.¹⁰

The common cold leads to more than 100 million physician visits annually with a conservative cost estimate of $7.7 billion per year.¹ An additional $4 billion is spent each year for over-the-counter (OTC) medications to address common cold symptoms,^4,8 and another $400 million is spent on prescription medicines for symptomatic relief.^6,9,10 Additionally, more than $1.1 billion is spent annually on the estimated 41 million antibiotic prescriptions for cold sufferers, even though antibiotics have no effect on a viral illness.¹⁰ While these unnecessary costs are problematic, what is more concerning is how these treatment patterns contribute to the development of antibiotic resistance, a significant public health concern. ¹⁰

Myth: You can catch a cold from going outdoors in cold weather.
Fact: Colds are more common in the winter months because that is when viruses are more likely to spread. It has nothing to do with being outside in cold weather.

ETIOLOGY

The common cold can be caused by more than 200 different respiratory viruses; hence, the reason for the term "common cold syndrome."^3-5,11,12 The rhinovirus is the most commonly implicated virus; however, other pathogens include coronaviruses, influenza viruses, parainfluenza viruses, adenoviruses, echoviruses, respiratory syncytial viruses, and coxsackieviruses.^1,3-7,12 Identification of the specific virus does not impact management in the immune competent host; therefore, microbiological identification is infrequently pursued.

The human rhinovirus is the most common causative agent. Its name is derived from the Greek "rhin," meaning nose. It is a member of the of the Picornaviridae family, and has more than 110 distinct rhinovirus serotypes identified.^1,4-7,11,12 Because of the large number of subtypes and antigenic variation, immunization strategies have not been feasible. Rhinoviruses are estimated to cause 30% to 35% of all adult common colds, with most cases occurring in early fall, spring, and summer.

Rhinoviruses grow best at temperatures of 33°C (approximately 91°F), which is also the temperature of the human nasal mucosa.⁶ Rhinoviruses penetrate the mucous blanket of the nasal or bronchial mucociliary epithelium, and attach to the intercellular adhesion molecule-1 receptor. This results in damage to the ciliated cells and subsequent release of bradykinin, prostaglandin, histamine, and cytokines. These mediators facilitate the inflammatory response resulting in tissue inflammation in the nose, sloughing of ciliated cells, and destruction of the integrity of the epithelium. As a result, patients experience sneezing, rhinorrhea, and nasal stuffiness. These mediators are also responsible for sore throats.⁴

Coronaviruses primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. The most publicized human coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), which causes SARS, has a unique pathogenesis because it causes both upper and lower respiratory tract infections and can also cause gastroenteritis.

Coronaviruses are believed to cause a large percentage of all adult colds; however, the significance and economic impact of coronaviruses as causative agents of the common cold are difficult to assess because, unlike rhinoviruses, human coronaviruses are difficult to grow in the laboratory. Infections occur primarily in the winter and early spring. Of the more than 30 isolated strains, only five are known to infect humans.⁶

Other viruses are responsible for approximately 10% to 15% of adult common colds.⁶ These include adenoviruses, coxsackieviruses, echoviruses, orthomyxoviruses (including influenza A and B viruses), paramyxoviruses (including several parainfluenza viruses), respiratory syncytial viruses, and enteroviruses. ⁶ Common colds caused by these viruses may lead to more severe illnesses such as influenza or co-infection with a bacteria (usually group A beta-hemolytic streptococci).¹²

The causes of 30% to 50% of adult common colds are not identified.⁶ The same viruses that produce common colds in adults appear to cause common colds in children. The relative importance of various viruses in pediatric common colds, however, is unclear because of the difficulty in isolating the precise cause of symptoms in studies of children with common colds.⁶

SYMPTOMS AND RISK FACTORS

Symptoms associated with the common cold first occur 10 to 16 hours after virus entry into the nose, and peak on days 2 and 3 of infection, corresponding to highest levels of virus shedding.¹³ Symptoms associated with a common cold are usually first noticed as a slight soreness or scratchiness in the nasopharyngeal region or as nasal obstruction or discharge. This is followed by other symptoms such as rhinorrhea, sore throat, sneezing, cough, headache, muscular aches and pains, and a general feeling of malaise.^1,4,12,14 In infants and young children, fever can be present and climb to 102^oF.⁶

Common cold symptoms usually last seven days, but in 25% of patients may persist for up to two weeks.¹⁵If symptoms occur often or last much longer than two weeks, they may be the result of an allergy rather than a cold ( TABLE 1). The severity of symptoms varies with each viral agent. Some patients only experience a transient episode with minor symptoms lasting a few days. Others may experience extreme discomfort for a more sustained period of time. Frequent sinus involvement is caused by obstruction of normal sinus drainage. Eustachian tube dysfunction and middle ear pressure abnormalities are present when patients report earache or a feeling of pressure. Sleep is frequently disrupted due to symptoms.^4,12

Common colds occasionally can lead to secondary bacterial infections of the middle ear (otitis media) or sinuses, requiring treatment with antibiotics. High fever, swollen lymph glands in the neck, facial pain across the sinuses, and a cough that produces mucus may indicate a complication or more serious illness requiring evaluation by a physician.⁶

Myth: The greatest myth about the common cold is that susceptibility to colds requires a weakened immune system.
Fact: Healthy people with normal immune systems are highly susceptible to the common cold once the virus enters the nose. In volunteer studies, approximately 95% of normal adults became infected when virus was dropped into the nose.¹⁶

PATHOGENESIS

Viruses cause infection by overwhelming the body's natural defense system. One of the body's first lines of defense is the production of mucus by the membranes in the nose and throat. Mucus provides a barrier, trapping inhaled foreign material such as pollen, dust, bacteria, and viruses. When a virus penetrates the mucus and enters a cell, it redirects the cellular protein-making machinery to manufacture new viruses, which, in turn, attack surrounding cells.⁶

Virus-infected cells in the nose send out signals that recruit specialized white blood cells to the site of the infection. In turn, these cells emit a range of immune system chemicals such as kinins. These chemicals cause swelling and inflammation of the nasal membranes, leakage of proteins and fluid from capillaries and lymph vessels, and increased production of mucus. Thus, symptoms associated with the common cold are the result of the body's immune response to the viral invasion.⁶

IDENTIFYING PATIENTS AT RISK FOR COMPLICATIONS

Most people do not develop complications from the common cold. However, complications associated with the common cold may be severe and at times life threatening. Complications may include sinusitis, otitis media, bronchitis, bacterial pneumonia, and exacerbation of asthma or chronic obstructive pulmonary disease.¹²Patients with asthma, cystic fibrosis, or chronic bronchitis; immune-compromised patients; infants; the elderly; and smokers with lower-respiratory track illnesses are at increased risk for developing complications.¹

Myth: Having symptoms associated with the common cold is a good thing because experiencing symptoms helps one to get over a cold sooner.
Fact: Approximately 25% of people who get the common cold are asymptomatic and yet they get over the common cold as well as people who experience symptoms.¹⁶ Sneezing and nasal secretions are useful in removing dust and pollen from the nose but do not eliminate common cold viruses, since the viruses multiply inside the nasal cells. Blowing one's nose propels nasal secretions into the sinus cavity. Nasal secretions contain viruses, bacteria, and inflammatory mediators, all of which are able to produce inflammation in the sinus cavity. This may lead to secondary bacterial infection. Thus, nose blowing, sneezing, and coughing will "benefit" viruses by helping to spread them to other people.

Table 1
Is it a Cold, Flu, or Allergies?1,4,12-14
Symptom/Factor	Cold	Flu	Allergies
Onset of Illness	Slow	Sudden; within hours	Sudden or slow
Duration	3-14 days	3-10 days	Many weeks
Fever	Rare, low grade	Usual: high (100-102°F) Lasts 3-4 days	Never
Headache	Rare, mild	Common, severe	Common
General aches, pains	Slight	Usual; often severe	Never
Fatigue, weakness	Mild, if any	Usual; can last up to 2-3 weeks	Sometimes
Extreme exhaustion	Never	Usual; at beginning of illness	Never
Stuffy nose	Common	Sometimes	Common
Runny nose	Common	Rare	Common
Sneezing	Usual	Sometimes	Usual
Sore throat	Common (scratchy)	Sometimes	Sometimes
Chest discomfort	Mild-moderate	Common; can become severe	Never
Cough	Severe or hacking cough	Dry	Sometimes
Appetite	Normal	Decreased	Normal
Itchy eyes	Rare or never	Rare or never	Common
Season	Year around; peaks winter	Between November and February	Peaks spring and fall
Treatment	Antihistamines, decongestants, NSAIDs	Antiviral medicines; refer to physician
Prevention	Wash hands often; avoid close contact with anyone with a cold	Annual vaccination, antiviral medicines; refer to physician	Avoid allergens (e.g., pollen, dust mites, mold, pet dander)
Complications	Sinus congestion, middle ear infection, asthma	Bronchitis, pneumonia; can be life threatening	Sinus infection, asthma

TRANSMISSION

Although many people are convinced that the common cold results from exposure to cold weather, "getting wet hair," "not wrapping up warm in the winter," or from getting chilled or overheated, researchers have found that these conditions have little or no effect on the development or severity of a cold. ¹⁷ People catch colds as often in the Southern Hemisphere as in the Northern Hemisphere, even at times when temperatures are significantly greater.

Research results suggest that environmental conditions such as crowding and damp low temperatures, as well as poor nutrition, psychological stress, allergic disorders affecting the nasal passages or pharynx, and menstrual cycles may have an impact on a person's susceptibility to virus infection by compromising the immune system. ^6,18,19 These factors, however, do not actually cause the infection or the symptoms.^6,20 Virus particles usually enter the respiratory system through the nostrils or the tear ducts and are then transported through the nasal cavity in the mucociliary flow to the nasopharynx. In the case of rhinoviruses, they adhere to molecule receptors on host epithelial cells. ¹³ The infective dose of rhinoviruses could possibly be as low as 30 virus particles.²¹

To produce an infection, the virus must enter the host epithelial cell, replicate, be released into the extra-cellular environment, and then re-infect new cells. Subsequent viral replication triggers the release of inflammatory mediators and activation of neurogenic pathways, which lead to symptoms. The virus is shed throughout the cold, but tends to peak at two to three days.¹⁷

Mechanisms of Transmission

Depending on the virus type, any or all of the following routes of transmission may occur: 1) touching infectious respiratory secretions on skin and on environmental surfaces and then touching the eyes or nose, 2) inhaling relatively large particles of respiratory secretions transported briefly in the air, and 3) inhaling droplet nuclei (smaller infectious particles suspended in the air) for long periods of time. ⁶ The route of transmission can be direct transfer from hands to the nares or by inhalation of airborne droplets.²²

Decades of research have shown that person-to-person transmission of bacterial and viral agents is facilitated by the hands. In fact, it has been shown that the transmission of the common cold virus is more a function of hand transmission than airborne droplets emitted from the sneeze of an infected individual.^23,24 Much of the research on the transmission of the common cold has been done with rhinoviruses, which are shed in the highest concentration in nasal secretions. Studies suggest a person is most likely to transmit rhinoviruses in the second to fourth day of infection, when the amount of virus in nasal secretions is highest.^6,12 Spread by direct contact implies that infected individuals contaminate themselves and/or the environment with rhinoviruses that can be transferred to a susceptible recipient by casual contact. Viruses can be recovered from the hands of approximately 40% of adults with rhinovirus-related common colds.²⁵ The quantity recovered from the hands is greater than that recovered in coughs and sneezes and can readily be transferred to the hands of a recipient by direct contact.²⁵

PREVENTION

Prevention via Virucidal Topical Agents

The inactivation of rhinoviruses by acids is well known and has been used for many years to distinguish the rhinovirus from other picornaviruses. Effective prevention of rhinovirus infection appears to require complete eradication of the virus from the hands. Simple handwashing or the use of a variety of virucidal agents removes infectious virus from the hands. Viruses have been reported to remain on skin and inanimate objects for as long as three to four hours.^4,26 Thus, the practical use of a virucidal agent for prevention of common colds will require an agent that has virucidal activity that persists for an extended period of time after application.²⁶ Glutaric acid, a virucidal agent that was studied in the 1980s, reduced viral titer but did not reliably eradicate virus from the hands over extended periods of time and was ineffective for prevention of infection.^25,27

Other agents, such as 62% ethanol, were also deemed ineffective for complete removal of rhinoviruses from the hands and have not demonstrated persistent virucidal activity.²⁵ Iodine demonstrated the feasibility of the interruption of rhinovirus transmission for the prevention of colds; however, it is not an acceptable virucidal agent for general use.²⁶ People may be at a higher risk of developing thyroid dysfunction due to the excessive intake of iodine by using these products on a regular basis. Those at high risk, including pregnant or breast-feeding mothers, should avoid these products.

In more recent studies, a number of different organic acids were tested for residual antirhinoviral activity. Salicylic acid and pyroglutamic acid are two compounds whose antiviral efficacy persisted for at least three hours.²⁶ The immediate and residual antiviral activity demonstrated by commonly used OTC skin care and cosmetic products has substantial virucidal activity against rhinoviruses that persists for two to three hours after application. Persistent acidification of the skin surface appears to be the mechanism for the virucidal activity of these organic acids.²⁷ The amount of acid applied to the hands correlates directly with the prevention of infection. ²⁶

A presentation at the September 2007 meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy assessed the immediate and persistent antibacterial and antiviral efficacy of a reduced alcohol hand sanitizer containing triclosan in clinical studies.^28,29 In these studies, Escherichia coli ATCC 11229 and Rhinovirus 39 ATCC VR-340 served as markers. The clinical results demonstrated the immediate and persistent antibacterial and antiviral potency of this hand sanitizers. TABLE 2 lists some commonly used hand sanitizers.

Myth: Central heating dries the mucus membranes of the nose and makes a person more susceptible to catching the common cold.
Fact: A common cold virus does not need the help of dry mucus membranes to initiate an infection once it enters the nose. The nasal mucus membrane is very resistant to the effects of low humidity. Low humidity makes the nose feel dry, but the mucus membrane still continues to work normally. The cold season in the U.S. typically begins in late August and early September, a time when temperatures are still moderate and central heating is not being used.

Table 2
Commonly Used Hand Sanitizers
Product CleanHands Hand Sanitizer Germ-X Hand Sanitizer Handclens Foaming       Sanitizer & Lotion Body Clear       Body Wash Purell Instant Hand Sanitizer Various cosmetic products Vicks Early Defense       Foaming Hand Sanitizer	Active Ingredient SAB* Ethyl alcohol Benzalkonium chloride Salicylic acid Ethyl alcohol Pyroglutamic acid Triclosan
*Surfactants, allantoin, and benzalkonium chloride formulation. Source: www.drugstore.com, www.vicks.com, ww.woodwardlabs.com.

Prevention via Lifestyle Modification

Prevention of the common cold consists of denying invasion of the body by viral particles and reducing the possibility that viruses will be successful in invading tissues. There are several methods by which prevention may be accomplished.⁴

Handwashing: Since the primary method of viral transfer is touching one's mucous membranes with contaminated hands, patients should be cautioned to wash their hands frequently. Handwashing is the simplest and most effective way to keep from getting rhinovirus-related common colds. The Centers for Disease Control and Prevention recommend regularly scrubbing the hands for 15 seconds with warm, soapy water.^6,12 Unfortunately, handwashing is not always available when exposure occurs. Using a topical product containing triclosan, for example, is a good option, as persistent efficacy has been demonstrated.²⁸

Hand contact: Not touching the nose or eyes is another preventive measure. It is wise to avoid rubbing the eyes with the fingers and placing the fingers in the nose or mouth. Individuals with common colds should always sneeze or cough into a facial tissue and promptly throw it away.

Close exposure: If possible, one should avoid close, prolonged exposure to persons who have colds. If this is impractical, one should at least avoid touching objects persons with a cold have contacted and consider declining a handshake.

Cleanliness: Because rhinoviruses can survive up to three hours outside the nasal passages on inanimate objects and skin,^6,25-27 cleaning environmental surfaces with a virus-killing disinfectant might help to prevent the spread of infection. Contaminated surfaces should be cleaned with a virucidal disinfectant or a homemade solution of one part bleach to ten parts water.

Sleep: Sufficient sleep and exercise help the immune system to function optimally. ⁶

Smoking: Smoking interferes with mucokinesis and predisposes one to common colds; persons should avoid smoking and exposure to second-hand smoke.

Prevention via Pharmacological Interventions

The most efficient way to control or prevent the spread of the common cold would be to vaccinate everyone against it. This approach has worked for many conditions caused by bacteria or viruses. However, the development of a vaccine that could prevent the common cold has become beyond the realm of possibilities due to the discovery of numerous strains of viruses that cause the common cold. Each virus carries its own specific antigens. Until ways are found to combine many viral antigens into one vaccine, or take advantage of the antigenic cross-relationships that exist, prospects for a vaccine are dim. Evidence that changes exist in common cold virus antigens further complicates development of a vaccine. Such changes occur in some influenza virus antigens, which make it necessary to alter the influenza vaccine each year.⁴

Myth: You should feed a cold (and starve a fever).
Fact: This is definitely not a good idea in either case. You need more fluids than usual when you have the flu or a cold. Drink plenty of water and juice, eat enough food to satisfy your appetite, and drink hot fluids to ease your cough and sore throat.

TREATMENT STRATEGIES

For years, the only available intervention for the common cold was to treat its symptoms. This may include bed rest, adequate fluid intake, gargling with warm salt water, a nutritious diet as tolerated, humidified air with cool mist vaporizers or steamy showers, and petroleum jelly for a sore nose. Saline nasal sprays may be utilized to soothe irritated mucosal membranes and loosen encrusted mucus. Foods such as tea with lemon and honey, chicken soup, and hot broths are soothing and increase fluid intake. Limited evidence suggests that chicken soup could have anti-inflammatory activity.¹²

Nonprescription Therapies

Nonprescription cold remedies may relieve some cold symptoms but will not prevent, cure, or even shorten the duration of illness. Most have potential side effects, such as drowsiness, dizziness, insomnia, or upset stomach, and should be taken with care.^4,12 Furthermore, not all patients should self-treat their cold (TABLE 3). These patients should consult with their pharmacist or primary care provider first.

Single-entity products are preferred by most patients, even if their symptoms warrant multiple ingredients during a common cold episode. The pharmacist should explain what each product is used for and the potential for duplication in therapy and adverse reactions with combination products.

Patients may view the use of multiple single-entity products as cumbersome and prefer to use a combination product. Single-entity products may have different dosing intervals (TABLE 4) and may be more expensive than one combination product.

Nonprescription, sedating (first-generation) antihistamines may have some effect in relieving inflammatory responses such as runny nose and watery eyes that are commonly associated with the common cold.^4,8,12 They prevent the histamine-receptor interaction and subsequent mediator release. The pharmacologic effects associated with newer antihistamines (second and third generations) may not reflect those of the older agents when treating the common cold. This is due to the fact that they inhibit the release of mast cell mediators and may decrease cellular recruitment but have no anticholinergic activity and therefore no activity against rhinorrhea or sneezing.¹² Even if a slight clinical benefit exists, there are risks and adverse effects associated with the first-generation antihistamines. Main points to consider are adverse effects such as anxiety, drying of mucous membranes, blurred vision, urinary retention, and tachycardia. This poses potential contraindications with the following disease states: narrow-angle glaucoma, prostatic hypertrophy, acute asthma exacerbations, peptic ulcers, and concomitant use of MAOIs.^4,12

Myth: Chicken soup and hot toddies are effective treatments for colds.
Fact: A bowl of chicken soup is a popular home remedy. Although hot liquids may soothe a scratchy throat or cough, chicken soup has no special power to cure a cold. As for hot toddies, another folk remedy, any beverage containing alcohol should be avoided when you are sick.

Cough suppressants have not been shown to reduce the frequency or severity of cough in children or adults, and some may suggest recommending against the use of these medications. ^6,12 Despite these conclusions, dextromethorphan provides a modest clinical benefit. Centrally-acting cough suppressants are not recommended in the American College of Chest Physicians guidelines due to the risk of secondary upper respiratory tract infections.⁷

Decongestants are the most common medications used to treat symptoms associated with the common cold, as virtually all viruses cause nasal symptoms. Available topical decongestants are sympathomimetic amines that stimulate adrenergic receptors of blood vessels, resulting in constriction of dilated nasal blood vessels (i.e., oxymetazoline and naphazoline).⁴ These topical products may cause temporary discomfort such as burning, stinging, sneezing, or an increase in nasal discharge. These products should not be used for more than three days, since more frequent or prolonged use may cause rebound nasal congestion or worsening of symptoms.^4,12 Use of topical decongestants is not recommended in patients with heart disease, hypertension, thyroid disease, diabetes, or trouble urinating due to an enlarged prostate gland, unless patients are directed by a physician to use such products.

Oxymetazoline is available as a gelling polymer nasal spray.²⁹ This new formula is heat-activated and targets the source of cold congestion, which helps to keep the product in the nose.

Oral decongestants are sympathomimetics that activate alpha-adrenergic receptors in nasal blood vessels to cause contraction of the smooth muscle of the nasal blood vessels. Pseudoephedrine also has beta-adrenergic stimulant properties. Therefore, with these agents, systemic effects such as anorexia, insomnia, excitation, headache, and irritability may occur.^4,12

Local anesthetics such as lozenges, troches, mouthwashes, and sprays are available for temporary relief of sore throats. These products may be used every three to four hours. Some products also contain local antiseptics, such as cetylpyridinium chloride, hexylresorcinol, menthol, and camphor. Local antiseptics have not been shown to be effective for viral infections;⁶ however, they may bring some temporary relief. Pharmacists should counsel patients with a history of allergic reactions to anesthetics to avoid products containing benzocaine.¹²

Systemic analgesics such as aspirin, ibuprofen, naproxen, ketoprofen, and acetaminophen may be used in adults only when headache or fever is present. Some research suggests that aspirin and acetaminophen suppress certain immune responses and increase nasal stuffiness in adults.^4,12

The use of aspirin has been linked to the development of Reye's syndrome in children recovering from influenza or chickenpox. Reye's syndrome is a rare but serious illness that usually occurs in children between the ages of three and 12 years. It can affect all organs of the body, but most often injures the brain and liver. While most children who survive an episode of Reye's syndrome do not suffer any lasting consequences, the illness can lead to permanent brain damage or death. The American Academy of Pediatrics recommends children and teenagers not be given aspirin or any medications containing aspirin when they have any viral illness, particularly chickenpox or influenza.^6,12

It should be noted that the FDA held a public health advisory meeting in October 2007 to discuss concerns surrounding reports of serious adverse events associated with the use of OTC cough and cold products in children. The reports were related to giving children more than the recommended amount of medication, giving the medication too often, or using more than one medication containing the same active ingredient. As a result of this concern, in October 2007 all oral cough and cold medicines labeled for infants or for use in children younger than two years of age were voluntarily withdrawn from the U.S. market.³⁰

Table 4
Dosage Guidelines for OTC Products4,12
Drug	Adults >12 years	Children 6-12 years	Children 2-6 years*
Brompheniramine †	4 mg q4-6h	2 mg q4-6h	Not recommended
Chlorpheniramine †	4 mg q4-6h (max 24 mg/day)	2 mg q4-6h (max 12 mg/day)	1 mg q4-6h (max 6 mg/day)
Codeine	10-20 mg q4-6h	5-10 mg q4-6h	1 kg/mg/day in 4 doses
Dexbrompheniramine	2 mg q4-6h	1 mg q4-6h	0.5 mg q4-6h
Dextromethorphan	10-20 mg q4h or 30 mg q6-8h	5-10 mg q4h or 15 mg q6-8h	2.5-5 mg q4h or 7.5 mg q6-8h
Diphenhydramine HCl	25-50 mg q6-8h (max 300 mg/day)	12.5-25 mg q4-6h (max 150 mg/day)	6.25 mg q4-6h (max 37.5 mg/day)
Doxylamine succinate	7.5-12.5 mg q4-6h	3.75-6.25 mg q4-6h	1.9-3.125 mg q4-6h
Ephedrine	2-3 drops/sprays (max q4h)	1-2 drops/sprays (max q4h)	Not recommended
Guaifenesin	200-400 mg q4h (max 2.4 g/day)	100-200 mg q4h (max 1.2 g/day)	50-100 mg q4h (max 300 mg/day)
Loratadine	10 mg q24h	10 mg q24h	5 mg q24h
Naphazoline	1-2 drops/sprays (max q6h)	Not recommended	Not recommended
Oxymetazoline	2-3 drops/sprays (max q10-12h)	2-3 drops/sprays (max q10-12h)	Not recommended
Phenylephrine †	1-2 drops/sprays (max q4h) 10 mg q4h	Not recommended 5 mg q4h	Not recommended 2.5 mg q4h
Pseudoephedrine †	60 mg q4-6h (max 240 mg/day)	30 mg q4-6h (max 120 mg/day)	15 mg q4-6h (max 60 mg/day)
Pyrilamine maleate	25-50 mg q6-8h	12.5-25 mg q6-8h	6.25-12.5 mg q6-8h
Triprolidine HCl	2.5 mg q4-6h	1.25 mg q4-6h	Age 4-6 y: 0.938 mg q4-6h Age 2-4 y: 0.625 mg q4-6h
Xylometazoline	2-3 drops/sprays (max q8-10h)	Not recommended	Not recommended
*No recommended dosages exist for children under 2 years of age, except under the advice and supervision of a physician. Weight-based dosing for children is not always available. † Extended-release formulations available; swallow whole (do not crush or chew).

Prescription Therapies

Prescription medications have also had limited value in treating symptoms associated with the common cold or as preventative interventions. Antibiotics have not been proven to kill viruses and, thus, should be used only for bacterial complications, such as sinusitis or ear infections. The use of antibiotics "just in case" will not prevent secondary bacterial infections. ⁴

Interferon-alpha has been studied extensively for the treatment of the common cold. Investigators have shown interferon, given in daily doses by nasal spray, may prevent infection and illness. Interferon, however, causes unacceptable side effects such as nosebleeds, headaches, and fatigue and does not appear to be useful in treating established colds.

Vitamins, Minerals, and Herbal Supplements

Patients today use various vitamins, minerals, and herbal supplements as a means to prevent and treat the common cold. These interventions carry great implications for pharmacists and patients, since their use in preventing colds may not be clinically documented.

A common unfounded belief is that taking large quantities of vitamin C will prevent colds or relieve symptoms. To test this theory, several large-scale, controlled studies involving children and adults have been conducted. To date, no conclusive data have shown that large doses of vitamin C prevent colds. The vitamin may reduce the severity or duration of symptoms, but there is no definitive evidence. ^4,31 In addition, taking large amounts of vitamin C over long periods of time may be harmful. Too much vitamin C can cause severe diarrhea, a particular danger for elderly people and small children. In addition, too much vitamin C distorts results of tests commonly used to measure the amount of glucose in urine and blood. Combining oral anticoagulant drugs and excessive amounts of vitamin C can produce abnormal results in blood-clotting tests (e.g., lowering prothrombin time).⁴

Myth: Large doses of vitamin C can keep you from catching common colds, or will quickly cure them.
Fact: These claims have not been proven. Still, it is important for one's overall health to consume the minimum daily requirement of vitamin C (90 mg/day for men and 75 mg/day for women 18 years or older).³²

Vitamin E has also been studied for the prevention of the common cold. One study showed that people age 65 or older living in nursing homes receiving vitamin E (200 IU) daily for one year were 20% less likely to be affected by the common cold than those who did not consume vitamin E. However, supplementation had no effect on the incidence or duration of other respiratory tract infections measured.³³

Echinacea is one of the most popular herbal products in the U.S. As with most cold remedies, however, the therapeutic effectiveness of echinacea in the treatment and prevention of the common cold has been debated. A recent meta-analysis on echinacea concluded that the available literature suggests some efficacy in the treatment of the common cold, although this conclusion was not based on statistical analysis.³⁴ Some trials using experimentally induced common colds also failed to show any significant superiority over placebo. ^6,34

Evidence suggests that patients should not take echinacea for more than eight weeks at a time due to the potential of suppressing the immune system. It also should not be taken by women who are breast-feeding or pregnant or by children younger than two years. Echinacea is a member of the Asteraceae family, which is the second largest family of flowering plants, with over 20,000 species known. It is more commonly known as the aster, daisy, or sunflower; therefore, patients who are allergic to these should not take echinacea, as well as anyone with compromised immune systems (e.g., patients with rheumatoid arthritis, lupus, or multiple sclerosis) or taking immunosuppressant medications.¹²

Airborne is an OTC combination of vitamins and herbs (including echinacea and vitamins A and C) intended to prevent and shorten the duration of common illnesses such as colds and flu. It has become popular in a short period of time, to the extent that stores often have trouble keeping it on the shelves. Generic versions are now available with the same ingredients in different packaging. There is no warning on the Airborne packaging relating to minimum or maximum dosing. But if taken as the label states ("take at the first sign of a cold symptom or before entering crowded environments and repeat every three hours as necessary"), eight doses of Airborne would provide eight times the recommended daily allowance of vitamin A, and would be at least four times the amount to start causing liver damage.³⁵

Clinical trials have been inconsistent in their findings with regard to the effectiveness of zinc gluconate or acetate lozenges. Inconsistent results are likely attributable to reductions in the efficacy of zinc secondary to changes in formulation in efforts to mask the unpleasant properties of zinc.^6,36 Recent reports have demonstrated that treatment with zinc nasal gel is effective in reducing the duration and severity of common cold symptoms if taken within 24 hours of symptom onset.³⁶Patients should be counseled to begin zinc at the very first sign of cold symptoms, and should continue until symptoms resolve or until otherwise advised.

Isolated reports have alleged an association between the use of zinc nasal gel and the onset of anosmia, although no clinical trial has reported this loss of diminished smell. All of the cases reporting anosmia involve zinc gel applied intranasally from a squeeze bottle. The squirt was made forcefully, and almost all of the patients reported an immediate intense burning sensation for minutes to hours. Patients reported an awareness of anosmia within the next few days.^37,38 Thewidespread use of intranasal zinc gluconate could result in a significant number of cases of anosmia. It is impossible to estimate the incidence of the syndrome from data presently available. Therefore, the risk versus benefit ratio appears unfavorable for use of a product with potential for permanent anosmia.³⁸

Many other botanicals have been studied for the prevention and treatment of the common cold. Such items include high lactoferrin whey protein, devil's claw, elderberry, ephedra, garlic, Panax ginseng, goldenseal, horehound, larch arabinogalactans, licorice, olive leaf extract, astragalus, baptisia, wild cherry, isatis, and yerba santa. None of these products has scientific evidence supporting their safety and efficacy. Pharmacists should not recommend these products to their patients.

Myth: Herbal remedies are effective treatments for the common cold.
Fact: Echinacea and other herbs are receiving a great amount of publicity as cold remedies. Zinc lozenges are also said to cure colds quickly. However, the effectiveness and safety of these remedies have not been supported by large-scale clinical studies.

THE ROLE OF THE PHARMACIST

Education

Pharmacists field many questions regarding the common cold and its associated problems. Since each patient may experience one or more possible symptoms, pharmacists should first determine which symptoms are most troublesome. If questions about the patient's medical history or medication use do not reveal exclusions for self-treatment, pharmacists may recommend a product that targets the specific symptoms. The patient should also be asked about self-treatment of current and previous colds and the effectiveness of these treatments.

Counseling

The patient who suffers from the common cold may require dedicated counseling by pharmacists. In order to make the appropriate recommendations, pharmacists need to keep in mind the symptoms related to the common cold. Pharmacists must ask enough questions to ensure that the symptoms are not related to a more serious medical condition. If there is any doubt, referral to a physician is warranted. Nonpharmaceutical measures may be effective in relieving the discomfort associated with common cold symptoms. Pharmacists should explain the appropriate non-drug measures for the patient's particular symptoms.

If pharmaceutical measures are warranted, the purpose of each medication should be explained and the patient should be counseled how to safely administer the appropriate medication to optimize its effectiveness. Possible side effects, drug interactions, and precautions should be explained to the patient.¹² For nasal spray decongestants, it is important to review the proper technique of administering the product. Remember to stress the importance of only using these products for a maximum of three days to prevent rebound congestion.

Referral

If signs and symptoms worsen, then patients should be encouraged to consult with their physician. Referral to a primary care provider is required for patients who meet the exclusions for self-treatment (TABLE 5 ). Follow-up is usually not necessary for patients with uncomplicated colds.

SUMMARY

Since most colds are self-limiting, symptoms will usually resolve on their own in seven to ten days. For the majority of patients, treatment is symptomatic and targeted at the most bothersome symptoms. Specific non-prescription therapy may relieve cold symptoms but should be used with caution, especially in at-risk patient populations. Patients should monitor for worsening symptoms, and progression of complications. Medical referral is appropriate for patients with symptoms suggestive of nonallergic rhinitis, otitis media, sinusitis, or lower respiratory tract problems such as pneumonia, asthma, or bronchitis.

Prevention is the mainstay. Good hand hygiene, including frequent handwashing and the use of hand sanitizers, is still the most effective intervention to prevent the common cold. Commonly used organic acids have virucidal activity for rhinoviruses that persists for hours after application, which has important implications for the prevention of these infections. This simple and safe intervention seems to be the most logical tool we have at this time to prevent the common cold.

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