Common Cold

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[edit] Common Cold

Thomas A. O'Bryan

Nirmal Joshi

The term common cold generally refers to self-limited viral illnesses causing acute inflammation in the nasopharynx, resulting in typical symptoms of rhinorrhea, sore throat, coughing, and sneezing. In the United States the common cold is the leading cause of physician visits and a major reason for work and school absenteeism. Treatment of colds is often frustrating to both patient and physician. Almost $2 billion is spent each year for over-the-counter products to remedy cold symptoms. Use of home-based and alternative therapy may be increasing. Primary care physicians frequently feel pressure from patient expectations to inappropriately prescribe antibiotics. Health care providers should be prepared to provide education to patients with cold symptoms to dispel common misconceptions, provide realistic expectations, and discuss publicized treatment claims. This chapter reviews current concepts in epidemiology, pathogenesis, clinical characteristics, and evidence-based treatment of this all-too-familiar malady.

[edit] EPIDEMIOLOGY

[edit] Prevalence and Environmental Factors

The common cold is not a single clinical entity but rather a group of diseases with overlapping symptoms caused mainly by several families of viruses (Box 33-1). Rhinovirus is the most common pathogen associated with the common cold, accounting for 30% to 40% of colds in most population studies. Coronavirus is another important etiologic agent, causing an estimated 10% of common colds. Less is known about this organism due to lack of culture and diagnostic techniques. About 25% to 40% of colds are presumably caused by undiscovered viruses. In addition to many viral pathogens, multiple distinct immunotypes of specific viruses exist, such as the more than 100 known antigenic types of rhinovirus. Furthermore, reinfection, particularly with coronavirus, is known to occur. For these reasons the “cure for the common cold” remains unrealistic.

Colds occur worldwide. In temperate climates, illnesses from respiratory viruses are present throughout the year but peak in the cooler months. The seasonal nature may be related to increased indoor crowding and low relative humidity favored by some viruses. Certain viruses follow a seasonal pattern. Rhinovirus infections peak in the early fall and late spring, whereas coronavirus infections are more common during the winter months. Psychologic stress has been implicated as predisposing to cold symptoms. Cold temperature, damp environments, and presence or absence of tonsils do not appear to be independent risk factors in the development of colds (Box 33-2).^{[1][2][3][4][5][6][7][8][9]}

Colds are most common in early childhood but occur throughout life. One study reported a frequency of six acute respiratory illnesses per year in children under age 3, with boys having a higher rate than girls.^[10] Infection rates generally fell with increasing age, but increased somewhat in young adult females, most likely because of exposure to young children. Adults experienced a mean of two to three respiratory illnesses per year, declining to about 1.3 per year after age 60.

Young children are the main reservoir for respiratory viruses. Among adults, colds occur more frequently in those with children in the home. Colds are most often transmitted in the home, school, or day care. Studies suggest children in day-care facilities have a higher rate of respiratory illnesses during ages up to 36 months.^[9] The incidence may be lower in later years for children who remain in day care from infancy through the preschool years.

[edit] Transmission

Our understanding of the transmission of the common cold is incomplete. Most knowledge of spread is based on experimental data of rhinovirus. The extent to which this information is applicable to the natural environment or to other etiologic agents of the common cold is unclear.

Rhinovirus appears to require close contact for transmission. In a study of married childless couples in whom one partner was experimentally infected with rhinovirus, transmission occurred in 38% of susceptible spouses.^[3] Volunteer studies have demonstrated a linear relationship between transmission rate to susceptible individuals and donor-hours of exposure (number of infected donors times hours of confinement). Of recipients, 44% were infected after 150 donor-hours of exposure. None of five recipients was infected after 45 donor-hours of exposure. Similarly, brief contact (3 to 36 hours) with infected persons resulted in a transmission rate of less than 10%.^[2][11]

Experimental data suggest that direct contact with infectious secretions is the likely means of transmission in most rhinovirus infections. Viral transfer occurred in a majority of exposures after 10 seconds of hand contact with infected individuals.^[7] Rhinovirus has been recovered on 40% of hands but less than 10% of cough or sneeze samples from persons with colds. Virus has been shown to survive on hands and environmental surfaces for several hours. Experimental infections have been acquired by hand contact with contaminated objects such as coffee cup handles and plastic tiles.^[12] Furthermore, cold transmission in the home setting was significantly reduced when individuals with natural colds treated their hands with a virucidal solution, implying the importance of hand contact in the spread of natural colds.^[13]

The risk of infection clearly depends on the site of inoculation. The amount of viral inoculum needed for a 50% infection rate is about 8000-fold less by the nasal mucosa route than by the oral route. Prolonged kissing has been shown to be an inefficient means of rhinoviral spread, with a transmission rate of 8% in one study.^[2] Most symptomatic subjects do not have detectable virus in their saliva. Inoculation into the conjunctiva, however, results in transmission rates similar to the nasal mucosa.^[13] Rather than infecting conjunctival tissue, the virus presumably passes down the tear duct into the nasal mucosa.

Thus the accumulated data support the hypothesis that most common colds under natural conditions spread from hand-to-hand contact, followed by autoinoculation into the nasal mucosa or eye. Observational studies suggest that children and adults place themselves at risk for autoinoculation into their eyes or nose from their fingers several times a day.^[8]

Experimental rhinoviral transmission by aerosols has been demonstrated^[4] but appears to be a less efficient means of transmission.^[4] The extent to which this occurs in the natural setting is not known. Finally, viral pathogens other than rhinovirus may behave differently. For example, influenza and adenovirus seem to spread by small-particle aerosols.

[edit] PATHOGENESIS

As with our knowledge of transmission of common colds, most information on the pathogenesis comes from experimental studies of rhinovirus infection in volunteers. After intranasal inoculation, the rhinovirus gains entry into host cells by binding to intercellular adhesion molecule 1 (ICAM-1). Infection appears to begin in the posterior nasopharynx, progressing anteriorly to the turbinates 1 or 2 days later. Predominantly cilial epithelial cells are infected, although nonciliated cells may also be involved. Interestingly, biopsies of the nasal mucosa during experimental infection reveal focal infection of relatively few cells. Examination of specimens of the nasal epithelium by light or electron microscopy reveals no consistent lesions.^[14] Thus cytotoxicity does not appear to be a major component of rhinovirus upper respiratory infection.

Recent evidence suggests that chemical mediators play an important role in the pathogenesis of the common cold. The interleukins IL-1, IL-6, and IL-8 have been demonstrated in the nasal secretions of symptomatic subjects within 24 hours of experimental rhinovirus inoculation.^[15][16][17] The concentrations of these proteins appear to correlate with severity and duration of symptoms. Polymorphonuclear neutrophil leukocytes (PMNs), kinins, and albumin are also found in nasal lavage specimens of subjects with rhinovirus infections. As with interleukins, their concentrations seem to match the time course and degree of symptoms. The interrelationships among these mediators and their role in the disease process are unclear. The interleukins are potent chemoattractants for PMNs. IL-1 may increase the responsiveness of some cells to bradykinin and may increase vascular permeability, resulting in a transudate of increased albumin and kinin in the nasal passage. Intranasal challenges with bradykinin, IL-8, and certain prostaglandins have each produced rhinorrhea in normal volunteers. Corticosteroids, pentoxyfylline, and a bradykinin antagonist have failed to alleviate common cold symptoms. Further understanding of the role of mediators will require the availability of specific inhibitors.

Neutralizing antibody in serum is present 2 to 3 weeks after infection, although nonspecific immunoglobulins may be found in nasal secretions within a few days. Symptomatic individuals with experimental rhinovirus infection have demonstrated peripheral increases in PMNs and decreases in T lymphocytes. Increased PMN and T-lymphocyte concentrations are seen in the nasal mucosa and nasal secretions.^[18][19] These leukocyte migrations likely reflect the release of cytokines and suggest that the cellular immune response plays a role in rhinoviral pathogenesis. Other observations imply that the host's neurologic response, particularly cholinergic and α-adrenergic pathways, may also play a role in the development of rhinorrhea during rhinovirus colds.

[edit] CLINICAL MANIFESTATIONS

The typical clinical manifestations of the common cold are well known and are most frequently associated with infections from rhinoviruses and coronaviruses. Most individuals infected with rhinovirus become symptomatic. Rhinovirus infections typically present after an incubation period of 1 to 4 days. Symptoms usually begin with rhinorrhea and sneezing accompanied by nasal congestion. Sore throat is often present and may be the initial complaint. Significant systemic symptoms, such as headache and malaise, are relatively mild, and fever is usually absent. In most patients the illness resolves spontaneously without significant adverse consequences in 5 to 9 days (mean 7.4 days). In about 25% of patients, symptoms may last up to 2 weeks. Children may develop lower respiratory infection. Persistent cough has been noted, particularly in smokers. Also, rhinovirus infection may acutely exacerbate respiratory symptoms in patients with chronic obstructive lung disease.

The clinical manifestations of coronavirus infection are similar, with the exception of a slightly longer incubation period and a slightly shorter duration of illness (mean 6 to 7 days). In some studies the amount of nasal discharge in patients with common colds from coronaviruses is greater than in those from rhinoviruses. The prevalence of coronavirus infection is particularly high in late fall, winter, and early spring, when rhinovirus infections are somewhat less common.

Symptoms caused by other viruses may overlap those from the common cold but usually have clinically distinguishing features. Influenza virus, for example, is typically associated with marked constitutional symptoms, such as headache, myalgias, fever, and malaise. Infections from respiratory syncytial virus and parainfluenza virus are particularly prevalent in children and tend to cause lower respiratory tract illness.

[edit] DIAGNOSIS

The diagnosis of the common cold is made almost exclusively on clinical grounds. The typical constellation of symptoms, including rhinorrhea, sore throat, cough, and low-grade fever, in the absence of severe constitutional symptoms is usually sufficient. A more important issue to the physician may be to consider coexisting or complicating conditions that may require specific therapy, such as streptococcal pharyngitis or sinusitis. In the patient with pharyngeal exudate and fever, definitive diagnosis of a bacterial etiology is difficult on clinical grounds alone, and a throat culture or rapid antigen testing is usually required.

[edit] TREATMENT

Several medications have been used, primarily directed at symptoms of the common cold. Consistently effective therapy directed toward the causative organism is still lacking. Unfortunately, clinical studies on treatment are difficult to perform and interpret because of the highly subjective and variable reports of symptoms.

[edit] Antihistamines and Anticholinergic Agents

Luks and Anderson^[20] reviewed clinical studies on antihistamines for the common cold, including terfenadine, chlorpheniramine, astemizole, and clemastine. The outcome measures included total symptom scores and nasal symptoms (sneezing and nasal discharge). Although some studies showed a statistically significant improvement in specific nasal symptoms, no study was able to demonstrate a statistically significant (p < 0.05) improvement in total symptom scores. In addition, the authors noted several flaws in study design and also questioned the clinical significance of the modest improvement in symptoms. They concluded that little data supported the use of antihistamines in the treatment of the common cold. An earlier review, however, reported that the antihistamine chlorpheniramine and the anticholinergic agents atropine and ipratropium improved nasal symptoms in adults with common cold. More recently, the antihistamine clemastine was found to improve sneezing and rhinorrhea.^[21] Again, it is difficult to quantify the clinical significance of this finding. Also, sedation was noted in 14% of clemastine recipients.

Terfenadine (no longer commercially available), a second-generation, nonsedating, selective H₁-receptor antihistamine, is ineffective in the treatment of symptoms of common cold. Although loratadine inhibits histamine-induced expression of ICAM-1 in cultured respiratory epithelial cells in vitro, the results of clinical efficacy trials are currently not available. In one study, the anticholinergic nasal spray ipratropium bromide was used at a dose of two sprays three times daily in each nostril. Compared with controls, rhinorrhea and sneezing were reduced by 30% in the treatment group. Patient assessment of overall effectiveness of treatment was more favorable for ipratropium than for control spray. Nasal dryness was noted as a side effect in 12% of ipratropium recipients.^[22]

[edit] Decongestants

Through the sympathomimetic effect, decongestants result in vasoconstriction of the nasal mucosa, reducing discharge and blockage. Smith and Feldman^[23] reviewed studies using these agents. Oral pseudoephedrine resulted in a substantial decrease in nasal symptoms, including congestion and sneezing. Oxymetazoline and phenylpropanolamine improved nasal patency and symptom scores. At least one study, however, reported medication side effects in 30% of recipients, including tachycardia, palpitations, and elevated blood pressure. Smith and Feldman's review also reported the lack of efficacy of expectorants such as guaifenesin.

[edit] Antiinflammatory Agents

A placebo-controlled trial using sodium chromoglycate nasal spray for acute respiratory illness of undefined primary etiology showed improvement in cough and voice disturbances in the treatment group.^[24] A related compound, nedocromil sodium, reduced colds' severity and nasal mucous secretion in experimental rhinovirus infection.^[25] These agents, in addition to preventing the release of inflammatory mediators from mast cells, may also affect neurogenic reflexes, which may contribute to cold symptoms.

Oral corticosteroids have not been found to be beneficial in the treatment of the common cold. Since prostaglandins can induce some symptoms of common colds when administered intranasally to healthy subjects, nonsteroidal antiinflammatory drugs (NSAIDs) have been tried clinically. In experimental rhinovirus-induced colds, early treatment with naproxen was effective in reducing headache, malaise, myalgia, and cough.^[26] Aspirin and acetaminophen have been found to impair antibody response and increase symptoms of nasal congestion and discharge; no effect on viral shedding was noted.^[27]

[edit] Other Agents

The use of zinc in the form of lozenges has been extensively studied recently. Of 11 double-blind, placebo-controlled trials, five reported benefit and six did not, and several flaws were highlighted for each study.^[28] For studies reporting benefit, inadequate blinding remains a concern because of the distinctive taste of zinc lozenges. For those studies reporting no benefit, certain formulations may result in inactivation of zinc salts before absorption. A meta-analysis of available studies concluded that there is insufficient evidence of zinc's efficacy in reducing the duration of common colds.^[29] Clearly, better studies are needed to ensure adequate blinding and intake of adequate doses of bioavailable zinc and to make more definite clinical recommendations.

Encouraging initial results have been reported with specific antiviral therapy using interferon-α as prophylaxis against rhinovirus infection. Combination therapy using this agent with ipratropium and naproxen within 24 hours of experimental rhinovirus infection may be useful in reducing symptoms and viral shedding. Cost and potential toxicity will likely limit the use of such therapy.^[30]

[edit] REFERENCES