Download An Evidence-Based Approach to Management of the Common Cold

CLINICAL REVIEW
An Evidence-Based Approach to Management of the
Common Cold
Sherif B. Mossad, MD
Introduction
he common cold is one of the most frequent illnesses
worldwide. Each year, the average adult develops
two to four colds and the average child develops four
to eight colds, resulting in a substantial amount of time lost
from work and school [1]. Most colds are caused by rhinovirus, but several other agents can be involved [2,3].
Patients usually exhaust several home remedies and overthe-counter medications before seeking help from their
physicians. The challenge of how to treat these patients
should be addressed with the best evidence-based information available. Although no cure for the common cold is
known, the medical literature describes a number of treatments. This article reviews the literature on treatments and
presents a practical approach to caring for patients suffering
with a common cold.
T
Methods
A MEDLINE search for articles published between 1966 and
1998 regarding management of common colds was done.
Well-designed studies, reviews, and other references selected from articles cited were reviewed.
Review of Treatment Modalities
Treatments for the common cold can be grouped into four
modalities: measures to relieve symptoms, pharmacologic
blockers, antiviral medications, and other agents whose
mechanism of activity has not yet been determined [4]. The
two models used most often to study cold treatments are the
virus-challenge model (ie, experimentally induced colds)
and the naturally occurring cold model. Both models have
advantages and disadvantages [5].
Symptomatic Measures
Antihistamines. The first-generation antihistamines doxylamine succinate, clemastine fumarate, and chlorpheniramine have been shown to alleviate rhinorrhea and sneezing but not other symptoms of the common cold [6–8].
However, attempts to confirm this subjective improvement
by objective measures, such as rhinomanometry and tympanometry, were not consistently successful [9]. A disadvantage of first-generation antihistamines is that they must be
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administered frequently because of their relatively short
half-life. Because these medications cause drowsiness, they
are especially beneficial to patients whose sleep is disturbed by cold symptoms. Second-generation, long-acting
antihistamines are less effective in relieving rhinorrhea
and sneezing, most likely because of their selective action
on histamine 1 receptors and lack of anticholinergic
activity.
Anticholinergics (parasympatholytics). Intranasal application of ipratropium bromide [10] or atropine methonitrate
[11] spray remarkably reduced sneezing and nasal drainage
in both naturally occurring and experimentally induced
common colds. Like first-generation antihistamines, anticholinergics are short-acting and require repeated application to maintain their therapeutic effect. Nasal dryness,
headache, and occasional epistaxis are the most common
side effects.
α-Adrenergic agonists (sympathomimetics). Oral and
intranasal phenylephrine [12] and oxymetazoline [13] are
potent decongestants that effectively relieve rhinorrhea associated with the common cold. It is important to note that
some generic formulations of these medications were not
found to be bioequivalent to the brand name products [14].
Prolonged or excessive use of α-adrenergic agonists results
in a rebound phenomenon—rhinitis medicamentosa—
after stopping the medication. In addition, patients receiving
antihypertensive medications must be warned of the potential drug interactions and possible worsening of hypertension.
Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs
have long been used to alleviate fever, malaise, and headache in a variety of illnesses. Their therapeutic effects are
attributed to the inhibition of prostaglandins involved in
the pathogenesis of inflammation and fever. Earlier studies
involving aspirin [15] and ibuprofen [16] warned about
Sherif B. Mossad, MD, Staff Physician, Department of Infectious
Diseases, Cleveland Clinic Foundation, Cleveland, Ohio.
JCOM January 1999 39
MANAGEMENT OF THE COMMON COLD
possible prolongation of viral shedding and decreased
serum-neutralizing antibody response with their use. More
recently, naproxen, a cyclooxygenase inhibitor, was found
not to cause these problems [17]. Aspirin and aspirincontaining products should be used with caution in children
because of the risk of Reye syndrome. Gastric irritation is the
most common side effect of NSAID use.
Steam inhalation. Breathing in steam from a bowl decreases
the local nasopharyngeal irritation that accompanies colds.
Studies to assess this maneuver under controlled circumstances have yielded conflicting results, thought to be due to
differences in the devices used, treatment schedules, and
placement of the heating nozzle [18,19]. However, it is clear
that viral shedding and antibody response are not altered by
raising the temperature inside the nasopharynx to 43°C [20].
The only possible adverse effect of steam inhalation is local
irritation. Given the degree of precision needed to achieve a
beneficial effect, this therapy may not be practical for the
pediatric age-group.
Expectorants/antitussive agents. Cough suppressive agents
are rarely needed during the initial stages of common colds.
Expectorants, such as guaifenesin, may decrease sputum
thickness, particularly when the patient is well hydrated.
However, in controlled studies their effect was marginal
compared to placebo [21].
Summary: Antihistamines, anticholinergics, and
α -adrenergic agonists are effective in decreasing rhinorrhea. NSAIDs relieve headache and malaise accompanying colds. Steam inhalation may have a local soothing
effect.
Pharmacologic Blockers
Mast cell stabilizers. Widely used in the prevention of asthma attacks, mast cell stabilizers inhibit the release of histamine and other chemical mediators from mast cells in
response to infection and other triggers of inflammation.
They also down-regulate intracellular adhesion molecules
type 1 (ICAM-1), the receptors for rhinovirus attachment in
the respiratory epithelium. In preliminary studies, both
nedocromil sodium and sodium cromoglycate seemed to
reduce the severity of rhinovirus colds [22,23]. Neither,
however, affected the frequency of viral shedding or the
serologic response to infection. Mast cell stabilizers cause
minimal side effects, but larger studies to assess their effectiveness in treating the common cold are needed.
NSAIDs. As noted previously, these drugs are effective
inhibitors of the inflammatory mediators involved in
colds.
40 JCOM January 1999
Summary: Mast cell stabilizers are promising agents for
treating the common cold, but more studies are needed to
assess their effectiveness.
Antiviral Medications
Interferons. These nonspecific antiviral agents have been
studied widely in both natural cold and experimental cold
models. Interferon alfa-2b was prophylactic in both models
when given before symptoms developed, but its effect varied with the dosage, form, and frequency of administration
[24,25]. On the other hand, interferon-β was ineffective in
preventing the development of natural colds [26]. The main
adverse effects of interferon-β and interferon alfa-2b were
nasal irritation, dryness, and bleeding, which can be confused with the actual illness. Combining interferon with
other antiviral agents may help achieve synergy, prevent
emergence of resistance, and decrease some of these adverse
effects [27].
Specific antiviral agents. Specific antiviral agents inhibit
rhinovirus attachment or uncoating by binding to specific
hydrophobic pockets in the virion capsid [28]. In vitro studies with ribavirin were promising [29], but the clinical application and usefulness of this agent in the management
of colds are probably limited because of its side effects.
Other oral agents, such as dichloroflavan [30], and intranasal
agents, such as pirodavir [31], were not effective in preventing or treating colds in clinical trials, despite reducing viral
shedding. The main factors impeding the development of
effective antiviral agents for the common cold are the wide
array of causative viruses that need to be targeted, the development of mutant or resistant viral strains, and the accompanying toxicities in treating such a self-limiting illness.
Summary: At this time, interferon alfa-2b and specific
antiviral agents are not practical therapy for the management of the common cold.
Other Agents
Zinc salts. Four studies designed to assess zinc salts as treatment for the common cold showed them to have a therapeutic effect, whereas four similar studies showed them to
have no effect. A recent meta-analysis of the eight studies did
not find evidence to support the use of zinc lozenges in treating the common cold [32]; however, the results of this metaanalysis have been questioned [33]. Different causative
viruses and variations in the dosages given may explain the
discrepant results of these studies. The efficacy of zinc
lozenges in treating common colds is thought to depend on
the bioavailability of zinc ions [34].
The exact mechanism of action of zinc in the common
cold is not known, but it has been hypothesized that zinc
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CLINICAL REVIEW
blocks the binding of rhinovirus to the ICAM-1 receptors in
the respiratory epithelium, inhibits viral capsid protein
synthesis, has a membrane stabilizing effect, inhibits prostaglandin metabolites, or increases production of interferon. The main side effects of zinc lozenges are gastrointestinal upset, metallic taste, and potential copper deficiency.
Vitamin C. The controversy of whether to use vitamin C in
the treatment or prevention of common colds continues. In
1975, a meta-analysis by Chalmers [35] found no evidence to
support its use, given its minor questionable benefits and the
lack of data on long-term toxicity at that time. More recently,
Hemila [36] reanalyzed Chalmers’s review, pointed out several errors, and concluded that vitamin C significantly and
safely reduces the severity and duration of common colds.
The most appropriate dose has not been determined, but
doses greater than 1 g per day are thought to provide the
maximal benefit. The beneficial effects of vitamin C on common cold symptoms are thought to be due to the vitamin’s
antioxidant properties.
Glucocorticoids. Two studies found that neither systemic
nor intranasal steroids prevented or relieved colds caused by
rhinovirus [37,38]. Nasal inflammation and kinin levels in
nasal washes were reduced, but the mean viral titers were
actually increased with prednisone. The side effects of
steroids are myriad, further justifying the avoidance of
glucocorticoids in the treatment of the common cold.
Aqueous iodine (2%). One small study [39] found that applying aqueous iodine to the hands of volunteers prevented
transmission of rhinovirus. The use of iodine is probably cosmetically impractical, but other less visible substances may
help prevent transmission among family members.
Echinacea. Echinacea is a native American plant that has
been used in traditional medicine for several decades. It promotes wound healing and enhances the immune response
by stimulating the phagocytic activity of polymorphonuclear neutrophilic granulocytes [40]. In addition, it was
found to be effective for prophylaxis and treatment of cold
and influenza symptoms [41,42]. Echinacea produces no
known side effects, but it becomes immunosuppressive
with continuous use for more than 6 weeks. However, the
U.S. Food and Drug Administration does not regulate the
dose and purity of such natural preparations, and standardization of the compound remains a concern [43].
Ginsana G. Ginsana G, a ginseng extract, was found to
decrease the frequency of influenza and the common cold by
potentiating the antibody response to influenza vaccine [44].
Its principal side effect is insomnia.
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Antibiotics. Despite the lack of utility of antibiotics in the
treatment of common colds, physicians continue to prescribe
them to 51% of adults and 45% of children with colds,
accounting for 10% and 12% of all antibiotic prescriptions,
respectively [45,46]. The abuse of antibiotics is additionally
attributable to patients’ misconceptions. One survey found
that 32% of parents believed that antibiotics are indicated for
treatment of their children’s colds and 18% actually had
given their children antibiotics before consulting a physician
[47]. Widespread antimicrobial resistance and the potential
adverse effects of all antibiotics are good reasons to change
such practices.
Summary: Controversy surrounding the use of zinc
salts and vitamin C in the treatment of colds persists.
The use of glucocorticoids or antibiotics for treating the
common cold should be discouraged.
A Practical Approach to Care
The majority of common colds are benign and self-limited,
but occasionally cases are associated with serious illness
[48,49]. Differentiating common cold from other upper respiratory tract illnesses remains difficult. Allergic rhinitis is
usually accompanied by nasal and eye itching with excessive
lacrimation, usually occurring in children who have a family
history of atopy. The rhinitis may be seasonal, perennial, hormonal, vasomotor, or gustatory [50,51]. Patients with streptococcal pharyngitis usually have fever, exudate on the posterior pharyngeal wall, and tender anterior cervical nodes [52].
Sinusitis is accompanied by headache and purulent nasal discharge. Patients with influenza are likely to have the systemic
symptoms of myalgia, arthralgia, and malaise.
A major obstacle to effective management of colds is the
inadequate education patients receive from their health
care providers about appropriate treatment [53]. Physicians
should be aware that patients’ satisfaction does not hinge
on receiving prescription or nonprescription medicines
[54]. Patients with colds should be advised to rest, to stay
home during the initial period of the illness to prevent the
spread of infection, and to drink plenty of fluids to avoid
dehydration. Agents aimed specifically at alleviating rhinorrhea (eg, antihistamines, anticholinergics, α-adrenergic
agonists) are usually helpful during the initial phase of
the illness. NSAIDs can be given to alleviate malaise,
headache, and fever. Vitamin C in doses exceeding 1 g per
day and zinc lozenges when given during the first 24 hours
of the illness may be effective in decreasing the symptoms
of colds. Only a small subset of patients who harbor pathogenic bacteria in their nasopharyngeal secretions may
benefit from antibiotics [55]. Prescribing antibiotics for the
management of uncomplicated colds is clearly not indicated. Physicians should advise patients to call or return in a
JCOM January 1999 41
MANAGEMENT OF THE COMMON COLD
few days for reassessment if their symptoms do not improve.
Finally, physicians should help patients avoid unnecessary and potentially harmful medications. Patients should
be cautioned about the large number of over-the-counter
combinations advertised as effective treatments for colds
[56]. It is alarming that two-thirds of families keep several
over-the-counter medications in their homes that are potentially toxic to children [57]. In 1996, 6.2% of all toxic pediatric
exposures were from cough and cold preparations [58].
12.
13.
14
This article is based on research reported in Mossad SB. Treatment of
the common cold. BMJ 1998;317:33–6.
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