CMAJ
February 18, 2014
vol. 186
no. 3
- Review
Prevention and treatment of the common cold: making sense of the evidence
- G. Michael Allan, MD⇑,
- Bruce Arroll, MB ChB PhD
- Evidence-Based Medicine, Department of Family Medicine (Allan), University of Alberta, Edmonton, Alta.; Department of General Practice and Primary Health Care (Arroll), University of Auckland, Auckland, New Zealand.
- Correspondence to: G. Michael Allan, michael.allan{at}ualberta.ca
The common cold is an acute, self-limiting
viral infection of the upper respiratory tract involving the nose,
sinuses, pharynx
and larynx. The virus is spread by hand contact with
secretions from an infected person (direct or indirect) or aerosol of
the secretions and virus.1 The incubation period varies but is just under two days for rhinovirus.2
Symptoms, which generally relate to the infected mucosa, typically peak
at 1–3 days and last 7–10 days, although they occasionally
persist for three weeks.1,3–5 They include sore throat, rhinitis, rhinorrhea, cough and malaise.1,4 The severity and type of symptoms will vary among individuals and with different infective agents. For example, fever is
common in children but rare and mild in adults.1 The incidence of the common cold declines with age.5–7 Children under two years have about six infections a year, adults two to three and older people about one per year.5–9 Stress10 and poor sleep11 may increase the risk of the common cold among adults, whereas attendance at a daycare centre12 increases the risk among preschool children.
Rhinovirus accounts for 24%–52% of clinical cases or 52%–76% of infections with an identified pathogen.6–8,13 No pathogen is identified in 31%–57% of upper respiratory tract infections,8,13 likely because of a host of reasons, including poor collection technique, low pathogen count due to sampling late in the
illness, or previously unidentified agents.1 Only about 5% of clinically diagnosed cases were found to have bacterial infection (with or without viral co-infection).13
Although self-limiting, the common cold is
highly prevalent and may be debilitating. It causes declines in function
and productivity
at work14,15 and may affect other activities such as driving.16 Its impact on society and health care is large. Of individuals with an upper respiratory tract infection, 7%–17% of adults17,18 and 33% of children17 visit a physician. Upper respiratory tract infections result in an estimated increase of 12.5% in patient visits per month
during cold and flu season.19 In the United States, direct medical costs related to the common cold (physician visits, secondary infections and medications)
were an estimated $17 billion a year in 1997.17 Indirect costs owing to missed work because of illness or caring for an ill child were an estimated $25 billion a year.17
We review the evidence underpinning
preventive and treatment interventions for the common cold. We do not
explore the proposed
biologic mechanisms for the different products,
because most are not substantiated and generally represent more
supposition
than science. The quality of the evidence was
frequently poor, with a moderate to high risk of bias. Although
preventive interventions
have somewhat discrete outcomes (presence of an upper
respiratory tract infection), interpretation of the evidence for
treatment
of the common cold is challenged by the complexity of
outcome reporting. The evidence used in this review is described in
Box 1.
Box 1:
Summary of literature review
In July and August 2012, a literature search was performed by one of us (G.M.A.) of PubMed, the Cochrane Database of Systematic
Reviews, ACP Journal Club and Evidence-Based Medicine.
Search terms included “common cold” and “upper respiratory tract
infection.” In PubMed, the search was restricted to randomized
controlled trials (RCTs), reviews, systematic
reviews and meta-analyses. Individual treatments were also searched
(e.g., “vitamin
C”). A similar search was performed in early 2012
by B.A. for a related project. We conducted a manual search of the
bibliographies
of included articles. Further details of the
literature search are available from the authors upon request.
We selected the highest level of evidence
available for each intervention, focusing on systematic reviews (with or
without
a meta-analysis) and RCTs. We rated the quality of
evidence for each intervention as high, moderate or low risk of bias.
For
systematic reviews, we considered the authors’
assessment of methodologic quality (e.g., blinding) of included trials
but
also examined the quality of the systematic review
itself (e.g., thoroughness of the literature search). For RCTs, we
considered
traditional validity criteria (e.g., allocation
concealment) as well other limitations (e.g., funding or restricted
populations).
Lastly, we considered the overall volume (size and
number of RCTs) and the consistency of the evidence. We used lower
levels
of evidence for general information such as
epidemiology.
How can the common cold be distinguished from other conditions?
The symptoms and signs of the common cold
overlap with those of other conditions. Allergic rhinitis presents
similarly, but
it may have a seasonal component or clear allergic
aggravation and is unlikely to have an accompanying sore throat. When
sore
throat is the primary complaint, streptococcal
pharyngitis should be considered. Centor criteria20 are helpful in delineating the need for throat swabs and antibiotics.
Sinusitis (acute or subacute) is a
clinical diagnosis without reliable clinical scoring criteria to help
differentiate it
from the common cold. Groups reviewing the evidence
for the antibiotic treatment of sinusitis recommend that symptoms be
present
for 7–10 days and not show signs of improvement
before antibiotics are considered.21,22
Ear pain and otitis media commonly
accompany or follow the common cold, particularly in children. Findings
on physical examination
can be helpful in diagnosing otitis media (e.g., a
bulging tympanic membrane has a likelihood ratio of 51),23 and there are simple rules for prescribing antibiotics or using watchful waiting in children with possible otitis media.24
People with influenza usually are sicker
than those with the common cold, the former having fever, chills,
headaches, myalgia
and malaise. Influenza can be serious in older
people and those who are immunocompromised. More serious illness should
prompt
consideration of meningococcal disease or
septicemia.
More details regarding primary conditions whose signs and symptoms overlap with those of the common cold are available in
guidelines and review articles on allergic rhinitis,25 sore throat,26 sinusitis,21 otitis media24 and influenza.27,28 In addition, the National Institute for Health and Care Excellence (NICE) has released a primary care guide for prescribing
antibiotics for upper respiratory tract infections.29
What interventions are effective for preventing the common cold?
View this table:
Table 1:
Interventions for the prevention of the common cold
Physical interventions
A Cochrane systematic review examined
the effectiveness of traditional physical public health interventions in
preventing
upper respiratory tract infections in 67 studies
of various types (randomized controlled trials [RCTs], cluster RCTs,
retrospective
and prospective cohort studies, case–control
studies and before–after studies).30
The type of interventions varied considerably — handwashing, use of
alcohol-based disinfectants, other disinfectants, hand-wipes,
gloves, masks, gowns and various combinations.
As a result, pooling of data was limited, and many of the studies had an
unclear
or high risk of bias. Nevertheless, the majority
of results suggested that physical preventive measures such as
handwashing
reduced the risk of getting or spreading upper
respiratory tract infections.
Zinc
Zinc appears to be effective in reducing the number of colds per year, at least in children. A Cochrane review31 of the prophylactic efficacy of orally administered zinc considered two RCTs that we also examined individually.32,33
These studies had methodologic concerns and included only children
given zinc sulfate 10 mg or 15 mg daily. The mean number
of colds was significantly lower in the zinc
group than in the placebo group both in the pooled analysis (Table 1) and in the individual studies (mean 1.2 v. 1.7 [p = 0.003] in one trial32 and 1.7 v. 3.1 [p < 0.001] in the other33). School absences were significantly lower in the zinc groups of each study, by an average of 0.4 days (p = 0.04)32 and 0.8 days (p < 0.001).33 Antibiotic use was also significantly lower in the zinc groups of each study (5 v. 18 [p = 0.009]32 and 20 v. 47 [p < 0.001]33 respectively). In one of the studies,32 the proportion of children with no colds during the study period was 33% in the zinc group versus 14% in the control group,
for a number needed to treat of six.
Although the evidence for cold prevention with zinc comes from studies involving only children, there is no biological reason
why zinc would work only in children and not adults.
Probiotics
Probiotics may be helpful in preventing upper respiratory tract infections, but the interventions and evidence are inconsistent.
A systematic review of 14 RCTs included 10 trials (n = 3451) that provided sufficient data for pooling.34
Pediatric and adult populations from a wide variety of countries were
included. Probiotic prophylaxis reduced the number
of participants who had one or more upper
respiratory tract infections (odds ratio [OR] 0.58, 95% confidence
interval [CI]
0.36 to 0.92) and the number of upper
respiratory tract infections per person-year (rate ratio 0.88, 95% CI
0.81 to 0.96).
Both outcomes had inconsistent results in the
individual studies, reflected in estimates of heterogeneity (I2
= 69% and 44%, respectively). However, use of probiotics reduced
antibiotic use (risk ratio 0.67, 95% CI 0.45 to 0.98). In
all but two studies, the probiotics varied in
types of organisms, combinations of organisms, formulations (e.g.,
pills, liquids)
and quantity (colony-forming units). These
inconsistencies limit the clinical application of the study findings.
We examined the two highest-quality studies included in the systematic review. In the first,35 638 children aged three to six years attending a community preschool or daycare were randomly assigned to receive either
a drink containing the probiotic strain Lactobacillus casei DN-114 001 (108 colony-forming units) or a matching placebo for 90 days. Use of the probiotic resulted in a reduction of 0.6 upper respiratory
tract infections per 100 person-days (p = 0.036). In the second RCT,36 742 children more than 12 months of age who were admitted to hospital were randomly assigned to drink 100 mL of a fermented
milk product containing either Lactobacillus rhamnosus strain GG (109
colony-forming units) or no probiotic for the duration of their
hospital stay. The incidence of upper respiratory tract infections
was reduced in the probiotic group (relative
risk 0.38, 95% CI 0.18 to 0.85), for a number needed to treat of 30.
Gargling
Frequent gargling with water may help
reduce episodes of upper respiratory tract infection, but evidence is
limited to a single
study. The well-designed RCT involved 387 adults
randomly assigned to gargling with water, gargling with a diluted
povidone–iodine
solution or usual care (control).37 Gargling with the povidone–iodine solution had no effect, whereas gargling with water was effective in reducing the risk
of an upper respiratory tract infection (30.1% v. 40.8% in the control group; p
= 0.044), for a number needed to treat of 10. The degree of gargling
required was considerable (20 mL for 15 seconds repeated
three times, performed three times daily).
Confirmation from a second RCT would be helpful before recommending
gargling.
Ginseng
The role of ginseng in preventing colds is questionable. A familiar product in Canada is COLD-FX, a proprietary extract produced
from the roots of North American ginseng (Panax quinquefolius). A meta-analysis38 of five RCTs (four of COLD-FX and one of Asian ginseng [P. ginseng]) and one RCT39
of COLD-FX have provided inconsistent results. Some of the trials
showed a statistically significant reduction in laboratory-confirmed
colds and influenza, whereas others found small
changes in clinical, but not laboratory-confirmed, upper respiratory
tract
infections only.40
Trials of COLD-FX were found to have multiple problems, including
dropout rates above 10% before a single dose was taken,
post-hoc modification of analyses to achieve
statistical significance (per-protocol analysis, combination of trials
or selection
of certain time frames), multiple analyses, a
focus on laboratory (not clinical) outcomes and inconsistent results.40
Other interventions
A variety of other interventions have been studied for the prevention of the common cold. Studies of exercise,41 garlic42,43 and homeopathy44–46 showed unclear evidence of benefit, whereas those of vitamin D48,49 and echinacea50 showed no evidence of benefit. Vitamin C47 may provide some benefit in people under physical stress (e.g., marathon runners or soldiers in subarctic environments),
but no meaningful benefit has been shown for the average patient.
Summarized details of these interventions can be found in Table 1. See also Appendix 1 (available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.121442/-/DC1) for a more detailed discussion of each intervention.
What medications are effective for treating the common cold?
View this table:
Table 2:
Pharmacologic interventions for the treatment of the common cold
Vapour rub
Vapour rub containing camphor, menthol and eucalyptus oil is applied to the neck and chest. In the one RCT60 we found that assessed its efficacy, harms appeared to outweigh benefits. No effect was found on rhinorrhea. Scores for cough
frequency and severity were improved compared with no treatment (p = 0.006 or better) but not compared with petrolatum (placebo). Scores for child and parental sleep were both significantly
improved with vapour rub versus petrolatum (p = 0.008 or better). For the combination of all scales (range 6–42), vapour rub had an improved score of about 4 higher than
petrolatum (p = 0.03). However, significantly increased adverse events over placebo included burning sensation to the skin (28%), nose
(14%) and eyes (16%) (p < 0.001
each). Rash and redness of skin each occurred in 5% of patients using
vapour rub, compared with none using petrolatum.
Other interventions
Nonsteroidal anti-inflammatory drugs and acetaminophen appear to be effective in relieving pain and fever in people with upper
respiratory tract infection but not in relieving other symptoms.61–63 Ibuprofen has been shown to be superior to acetaminophen in fever control, whereas the safety of these drugs, at least in
pediatric populations, is equivalent.64,65 Antibiotics have no beneficial effect on the common cold but do increase adverse events.66
Because many symptoms of bacterial upper respiratory tract infections
overlap with cold symptoms, clinicians may be tempted
to prescribe antibiotics. Although prescribing
should be minimized, issuing a delayed prescription for an antibiotic at
times
of uncertainty has been shown to reduce
antibiotic use from 93% to 32%.70
Summarized details of these interventions can be found in Table 2. See also Appendix 1 for a more detailed discussion of each intervention.
What alternative and nonpharmacologic treatments of the common cold are effective?
Alternative and nonpharmacologic treatments of the common cold are summarized in Table 3.47,50,71–80
View this table:
Table 3:
Alternative and nonpharmacologic interventions for the treatment of the common cold
Honey
Consistent findings of three RCTs involving children suggest that a single night-time dose of honey can have a small effect
on cough and sleep in children over 12 months old.71–73
Multiple methodologic issues were present in one or more of the trials,
including inadequate description of randomization
and allocation, no blinding, exclusion of
patients who deviated from the protocol, substitution of clinician
ratings in place
of parent or child ratings, funding by the Honey
Board and uncertain clinical significance.68,71–73 There was no consistency in adverse events between the trials. Honey should not be given to children younger than 12 months.
Zinc, oral or intranasal
Inconsistent evidence from a meta-analysis suggests that orally administered zinc reduces the duration and severity of the
common cold in adults.74
A 23-mg zinc gluconate lozenge every two hours was the most commonly
studied regimen, although there was considerable variability
across studies in dose (4.5 to 23.7 mg),
frequency (twice daily to 10 times daily) and formulations (gluconate,
sulfate or
acetate).74 Zinc shortened the course of colds significantly (mean difference −1.65 d, 95% CI −2.5 to −0.8, compared with placebo),74 a finding similar to but somewhat better than the Cochrane review31
(standardized mean difference −0.97 d, 95% CI −1.56 to −0.38). However,
zinc was found to have no significant effect on the
duration of colds in children (mean difference
−0.26, 95% CI −0.78 to 0.25), but the effect was significant in adults
(mean
difference −2.63, 95% CI −3.69 to −1.58).74
Higher doses appeared to be more effective than lower doses. Zinc did
not significantly affect symptom severity in children
(standard mean difference −0.05, 95% CI −0.27 to
0.17) but did reduce severity in adults (standard mean difference
−0.64,
95% CI −1.05 to −0.24).74 Although the data were positive for adults, heterogeneity was consistently high in all results (I2 = 55% to 95%), which reflected a high level of inconsistency, even in subgroup testing.74 Use of oral zinc supplements was associated with an increased risk of adverse events such as bad taste and nausea (risk ratio
1.24, 95% CI 1.05 to 1.46).74 It is unclear why oral zinc treatment seems to benefit adults more than children.
The evidence to support intranasal use of zinc is weak, and important risks exist.79 We found only three RCTs of zinc used intranasally, 0.044 mg to 2.1 mg daily in four doses.79 There was no significant difference in any persisting symptoms at day 3 for all pooled studies, and again the heterogeneity
was very high (I2 = 99%). Adverse events such as nasal stinging and burning were more common with zinc used intranasally than with placebo.
In addition, anosmia was described in a case series,80 and a US manufacturer settled legal claims for anosmia.79
Other interventions
Although seven trials with more than 3000 patients examined vitamin C for the treatment of the common cold, no clear benefit
was shown.47 It is not possible to determine whether benefit exists for most other alternative therapies. Studies of nasal irrigation,75 humidified air,76 Chinese herbal medicines77 and echinacea50 all showed inconsistent results. A single clinical trial of ginseng did not report efficacy outcomes.78 We did not identify any high-level evidence for garlic or probiotics in the treatment of the common cold.
Summarized details of these interventions can be found in Table 3. See also Appendix 1 for a more detailed discussion of each intervention.
Unanswered questions
In 1931, the author of a CMAJ article on the common cold said, “The common cold is so common that we are apt to pass it by with a contemptuous gesture,
unless, of course, we are the sufferers ourselves.”81
Much more evidence now exists in this
area, but many uncertainties remain regarding interventions to prevent
and treat the
common cold. We focused on RCTs and systematic
reviews and meta-analyses of RCTs for therapy, but few of the studies
had a
low risk of bias. However, many of the results were
inconsistent and had small effects (e.g., vitamin C), which arouses
suspicion
that any noted benefit may represent bias rather
than a true effect.82
We encourage researchers to perform well-designed RCTs on promising
treatments or on preventive methods with limited evidence
(i.e., gargling or garlic). Further work to help
clinicians clearly distinguish the common cold from other upper
respiratory
tract infections would also be useful.
Key points-
Evidence for interventions aimed at preventing and treating the common cold is frequently of poor quality, and results are inconsistent.
-
The best evidence for the prevention of the common cold supports physical interventions (e.g., handwashing) and possibly the use of zinc supplements.
-
The best evidence for traditional treatments supports the use of acetaminophen and nonsteroidal anti-inflammatory drugs (for pain and fever) and possibly antihistamine–decongestant combinations and intranasal ipratropium. Ibuprofen appears to be superior to acetaminophen for the treatment of fever in children.
-
The best evidence for nontraditional treatments of the common cold supports the use of oral zinc supplements in adults and honey at bedtime for cough in children over one year.
Footnotes
-
Competing interests: Bruce Arroll organizes general lectures for the New Zealand government’s Pharmaceutical Management Agency. No competing interests declared by Michael Allan.
-
This article has been peer reviewed.
-
Contributors: Michael Allan and Bruce Arroll independently searched and reviewed the evidence. Michael Allan prepared the first evidence summary and draft of the article. Bruce Arroll confirmed the evidence summary and edited the draft critically for content. Both authors approved the final version submitted for publication.
References
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