Strategies for preventing the common cold: The current evidence

ABSTRACT:Although the common cold is usually benign, it can lead to exacerbations of asthma and chronic obstructive pulmonary disease, and it is a leading cause of missed school and work. Strategies for prevention have been directed at interruption of viral transmission between persons, as with the use of virucidal agents or disinfectants, and prevention of infection after acquisition of the pathogen. Hand washing continues to be recommended, but there is no proof that hand sanitizers or virucidal tissues are effective in preventing colds. Prophylactic therapies that have been considered include vitamin C, vitamin E, zinc, Echinacea, ginseng, and probiotics. Although some evidence may suggest possible benefits with zinc and probiotics, for example, overall, the data are insufficient to recommend any of these as prophylaxis for the common cold. (J Respir Dis. 2009;30)

The common cold is a ubiquitous clinical syndrome caused by a variety of viral pathogens. While most common colds are of little medical significance, these illnesses can have important consequences for some patient populations. Infections caused by rhinoviruses, the most common cause of viral upper respiratory tract illness, are associated with 60% to 70% of asthma exacerbations in school-aged children and are an important contributor to exacerbations of chronic obstructive pulmonary disease. Otitis media and rhinosinusitis frequently occur as complications of common colds.

Another important consequence of the common cold is the inappropriate use of antibiotics. In the United States in 1998, there were an estimated 25 million primary care office visits for the common cold, and 30% of these visits resulted in a prescription for antibiotics.¹ This unnecessary use of antibiotics contributes to the problem of increasing antibiotic resistance of pathogenic respiratory bacteria.

Although the medical consequences of the common cold are generally modest, the social and economic effects are substantial. The common cold is a leading cause of missed school and work and is the second most common diagnosis at physician office visits. One study estimated that the total economic impact of non-influenza–related viral respiratory infections approaches $40 billion annually in the United States.²

Treatment of the common cold is limited to symptomatic therapies that have modest efficacy and have no impact on the development of significant complications. Effective prevention would clearly have important medical and socioeconomic benefits. The development of effective prophylaxis, however, presents some unique challenges. Although from a societal perspective, these illnesses have a significant impact, for the individual patient, the common cold is generally benign, relatively short in duration, and self-limited. Thus, useful interventions must be convenient, cheap, and safe. These requirements pose a formidable barrier to the development of effective approaches to prophylaxis.

In this review, we will summarize the evidence for the efficacy of various interventions used to prevent the common cold.

EPIDEMIOLOGY AND PATHOGENESIS
Rhinoviruses represent the most frequent cause of the common cold, but other respiratory viruses-including coronavirus, parainfluenza virus, metapneumovirus, respiratory syncytial virus, and influenza virus-are associated with this syndrome. Colds occur most commonly in young children, with an average incidence of about 6 illnesses per year.³ The incidence decreases with age and by adulthood, the incidence is 2 to 3 per year.

Common colds occur year-round, but the incidence is greatest from the early fall until the late spring, reflecting the seasonal prevalence of the viral pathogens. The risk of acquiring a common cold is primarily determined by exposure to other infected persons. In the general population, household or occupational exposure to young children is the most important determinant of risk.

The route of transmission of viral pathogens has obvious implications for interventions to prevent infection. In general, the viruses that cause the common cold are spread by 3 mechanisms: small particle aerosols, large particle aerosols, and direct contact. Small particle aerosols form droplet nuclei that do not settle and can be transmitted over relatively long distances by airflow and may be deposited in the lower airway. Large particle aerosols are droplets generated from the airway that settle rapidly are transmitted only over relatively short distances. These particles are generally filtered by the upper respiratory tract and are not deposited in the lower respiratory tract.

Direct contact refers to contact with contaminated fomites as well as direct person-to-person contact. The different pathogens may presumably be spread by all of these mechanisms, but some routes of transmission appear to be more efficient for particular pathogens (Table).

Once a person has come into contact with a common cold pathogen, the next step in pathogenesis is the initiation of infection. The production of symptoms requires infection of the upper respiratory tract mucosa. Inactivation of the virus in the respiratory secretions or prevention of attachment to the respiratory epithelium are potential targets for the prevention of colds, but these approaches have had limited success and no commercially available interventions use this approach.^4,5

The most important host factor for preventing infection after exposure to virus is the presence or absence of specific antibody to the pathogen as a result of either natural infection or immunization. There has been some suggestion that mannose-binding lectin deficiency is another host characteristic that may be associated with an increased incidence of common cold illnesses in young children.⁶ The data are not conclusive, however, and the importance of polymorphisms in this component of the innate immune system remains to be determined.

A number of putative interventions for preventing the common cold are claimed to act by enhancing or supporting immune function. Despite these claims, there is no evidence that nonspecific depression of immune function plays any role in the risk of infection.

There have been a number of studies of the effect of personality and stress on infection and illness associated with upper respiratory tract pathogens. These studies suggest that stress is not a factor in the acquisition of infection, but that chronic stress in particular is associated with the development of more severe symptoms.⁷ Personality type may also influence symptom severity. Introverted persons are reported to have more severe illness.⁸ In contrast, a positive emotional style, characterized by a general attitude of vigor and well being, is associated with less severe symptoms.⁹

APPROACHES TO PREVENTION
Strategies for prevention may be directed at interruption of viral transmission between persons or prevention of infection after acquisition of the pathogen. Prevention of viral transmission has relied on virucidal agents or disinfectants. There have been attempts to develop specific antivirals for prophylactic use but, with the exception of the neuraminidase inhibitors for influenza, these attempts have been unsuccessful.

A number of homeopathic treatments, vitamins, minerals, herbs, and lifestyle changes have been proposed to “boost immune function.” These functional claims are permitted by the FDA regulations, but there is no evidence that depressed immune function is important in the pathogenesis of colds or that these products produce meaningful effects on immune function. Specific claims that these agents prevent colds are not permitted in the absence of specific data.

Virucidal agents
Viral contamination of hands and subsequent person-to-person contact is an important mechanism for transmission of rhinovirus. Virus is recovered from the skin of the hands of approximately 40% of persons with natural rhinovirus colds and from 6% to 15% of objects in their environment.^10,11

A proof-of-concept study was conducted using 2% aqueous iodine as a virucidal treatment for the hands.¹⁰ Mothers who were exposed to a child with a fresh cold in the home applied iodine to their fingers. This treatment reduced colds by 67% compared with placebo. None of 11 mothers who were using iodine became infected with the same rhinovirus as the contact, compared with 31% of mothers who were using placebo. Unfortunately, virucidal products with activity equivalent to that of iodine are not commercially available.

Hand washing with soap and water removes rhinovirus from hands and would be expected to reduce transmission of common cold viruses. Despite the scientific basis for this approach, it has been difficult to demonstrate an effect of hand washing on the incidence of common colds in the natural setting. Similarly, alcohol hand sanitizers remove virus from the hands, but when used in the home setting have no effect on the incidence of respiratory infection.¹²

The reason for the failure of these interventions is not clear. Effective prevention of rhinovirus infection appears to require complete eradication of the virus from the hands, a formidable challenge to routine hand washing or the use of hand sanitizers. Furthermore, currently available hand sanitizers do nothing to prevent re-acquisition of the pathogen. The development of virucidal products that provide persistent activity in addition to immediate inactivation of virus might be more effective. Recent studies have demonstrated that virucidal products containing organic acids provide persistent antiviral activity, but the usefulness of these agents for preventing the common cold in the natural setting remains to be demonstrated.¹³

• Conclusion: Hand washing is clearly desirable for personal hygiene, but no definitive evidence supports the effectiveness of this approach for the prevention of colds.

A variation on the use of virucidal agents as a hand treatment is the incorporation of virucidal agents into nasal tissues. A combination of citric acid, malic acid, and sodium lauryl sulfate is virucidal for rhinoviruses and has been incorporated into a commercially available nasal tissue. Although these tissues prevent viral contamination of the hands during nose blowing, tissues without the virucidal agents are also effective barriers to hand contamination.¹⁴ Studies in the natural setting have failed to demonstrate a benefit of the virucidal impregnated tissues on infection rates compared with the use of normal tissues.¹⁵

• Conclusion: Virucidal tissues appear to afford no additional protection above standard nasal tissues in the prevention of common cold illness.

The viruses associated with the common cold can be routinely isolated from environmental surfaces. Various virucidal commercial cleansers, such as disinfectant sprays, domestic bleach, and ethanol-based products, can inactivate virus in the environment.¹⁶ However, the usefulness of these agents for the prevention of infection is not clear. Studies in experimental settings have failed to demonstrate transmission of infection from environmental surfaces even under conditions of very heavy virus contamination.¹⁷ In light of the apparently limited impact of environmental contamination on the incidence of common cold illness, it would be very difficult to demonstrate that eradicating virus from surfaces affects the frequency of infection.

• Conclusion: Environmental cleansers are effective virucidal agents, but an impact on prevention of the common cold has yet to be proved.

Vitamin C
The use of large doses of vitamin C for preventing and treating the common cold was popularized by the late Nobel Laureate Linus Pauling. This use of vitamin C was subsequently evaluated in a number of studies that have shown little or no benefit.

A systematic review and meta-analysis examined 33 studies involving 11,350 participants who were randomly assigned to take prophylactic vitamin C or placebo.¹⁸ The results showed no statistically significant benefit for vitamin C prophylaxis in the prevention of acute upper respiratory tract infection. However, a subgroup analysis of 6 studies showed a potential benefit of vitamin C in patients who participated in vigorous activity. Specifically, vitamin C decreased the incidence of colds by 50% in persons who experienced vigorous activity, such as marathon running or skiing, and in soldiers in sub-arctic conditions.¹⁸

A major limitation of studies of vitamin C has been the inability to effectively mask the taste of the treatment.¹⁹ Insufficient blinding is a serious problem in studies that generally rely on subjective symptom reporting as the primary outcome measure.

• Conclusion: We do not recommend vitamin C for prophylaxis of the common cold. Limited evidence suggests that vitamin C may provide modest benefit to persons who engage in intense physical activity or who are exposed to extremely cold environmental conditions.

Zinc
The use of zinc for treatment of the common cold has been the subject of many studies, but relatively few have evaluated it for prevention. Zinc treatment has its origin in early in vitro studies that identified zinc as an inhibitor of an enzyme important in rhinovirus replication. Subsequent studies revealed zinc to have little effect on rhinovirus replication at concentrations achievable in vivo.²⁰ Other mechanisms of action have been proposed but are unproven.

In studies of experimental colds, zinc products given either before or immediately after virus challenge and before onset of symptoms have had no effect on illness severity.^21,22 A study of prophylaxis of natural colds in children reported that zinc reduced the incidence from 1.7 to 1.2 colds per child over a 7-month period.²³ While this suggests a potential benefit of zinc prophylaxis, additional studies are needed in light of the previous negative data and the absence of a plausible mechanism of action for zinc.

• Conclusion: The data are insufficient to recommend zinc prophylaxis for the common cold.

Vitamin E
This potent anti-oxidant has been evaluated as an anti-inflammatory agent for cardiovascular protection. There is some evidence that virus-induced oxidant stress may play a role in the common cold, and it is plausible that an antioxidant might have a beneficial effect on symptoms.²⁴

The effect of vitamin E supplementation has been examined in several clinical studies. The results are inconclusive. All of the published literature is in elderly adults. Two studies, one published in 2002 and another published in 2007, found no significant effect of vitamin E supplementation on viral upper respiratory tract illness.^25,26 In fact, one of these studies suggested that supplementation may be associated with more severe illness.²⁵

In contrast, a trial conducted in 2004 reported that vitamin E may provide a protective effect against upper respiratory tract illness.²⁷ A study published in 2006 reported a beneficial effect in some subpopulations, but other groups actually had an increased severity of illness.²⁸

• Conclusion: In light of the inconsistent results and the apparent potential for harm, we advise against vitamin E supplementation for prevention of the common cold.

Echinacea
Echinacea is the most frequently used botanical in the United States and is most commonly used for prevention or treatment of the common cold and other upper respiratory tract infections. The efficacy of Echinacea for preventing or treating the common cold has been evaluated in many studies, although the quality of these studies has been questioned.²⁹

A Cochrane Database Review included 3 studies that were focused on the role of Echinacea for preventing colds.³⁰ None of these studies demonstrated prophylactic efficacy. In addition, 2 studies of prophylaxis in experimental rhinovirus colds failed to detect any effect of various Echinacea preparations on infection or illness.^31,32 A single well-designed trial of Echinacea with propolis and vitamin C suggested a beneficial effect for preventing respiratory infections in children.³³ Confirmation of these results has not been published.

A primary difficulty in assessing the efficacy of Echinacea in clinical studies continues to be the lack of standardization of the various preparations of Echinacea. The genus Echinacea contains 9 species, 3 of which are used for medicinal purposes (Echinacea angustifolia, Echinacea pallida, and Echinacea purpurea).

Furthermore, the phytochemical composition of Echinacea is affected by many factors related to climate, geography, and processing. This variation, together with the absence of accepted criteria for characterization of medicinal preparations, prevents a rigorous assessment of specific phytochemical compositions of Echinacea. Until such standards are available, it will be difficult to generalize the results of the findings in clinical studies to the use of Echinacea in the general population.

• Conclusion: Current data do not support the use of Echinacea preparations to prevent the common cold.

Ginseng
There are limited data on the use of ginseng for cold prevention. In a randomized, double-blind, placebo-controlled study, 323 persons received either North American ginseng or placebo for 4 months during influenza season.³⁴ Ginseng was associated with a modest but significant reduction in the incidence of viral respiratory illness. However, the criteria for participation in this study required very severe illnesses, which would be atypical for common colds.

There is no clear rationale for the use of ginseng for the treatment of colds. Additional studies of well-characterized and standardized preparations of ginseng in virologically proven infections or more typical common cold illnesses are needed.

• Conclusion: Current data are insufficient to recommend ginseng for protection from the common cold.

Exercise
The benefits of regular exercise for the promotion of overall cardiovascular health are indisputable. The specific impact of exercise on the incidence of viral respiratory infection has been examined in a limited number of studies, and the results are mixed. There is some evidence that intense exercise such as that experienced by elite athletes is associated with an increased incidence of upper respiratory tract illness.³⁵ In contrast, more moderate exercise has been reported to reduce the incidence of the common cold in postmenopausal women.³⁶

• Conclusion: The benefits of exercise on general health are well established, but there are insufficient data to support a recommendation of exercise specifically for preventing the common cold.

Probiotics
There has been a recent resurgence of interest in probiotics as immunomodulators that might affect the incidence or severity of illness. A preliminary evaluation of the ingestion of probiotic bacteria for the prevention of colds found that the incidence of colds was not affected, but that the severity of symptoms was reduced.³⁷

• Conclusion: There are insufficient data to support a recommendation of probiotics for the prevention of the common cold at this time.

CONCLUSIONS
Effective intervention to prevent common cold illnesses can be determined only by careful execution of well-designed clinical trials. Unfortunately, few of the interventions proposed for prevention of these illnesses have been subjected to such rigorous evaluation, and no clearly effective interventions have been identified. Hand washing and exercise have undeniable benefits for health in general and can be recommended despite the paucity of evidence specific to common cold prevention. Other interventions, while apparently safe, have no demonstrable benefit and simply contribute to the unnecessary health care expenditures related to the common cold.

References:

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