Colds
The term “common cold” describes a self-limited catarrhal illness caused by a variety of respiratory viruses. It is indeed a common problem, with adults averaging two to four colds per year and almost 7 days lost from work per person per year. Although most patients treat their symptoms at home, physicians are still frequently consulted for upper respiratory infections. The primary task for the physician is to distinguish the common cold from bacterial infections, allergic conditions, and epidemic diseases such as influenza. Once the common cold is diagnosed, reassurance about the self-limited nature of the disease and patient education about its predominantly viral cause is the next step. However, upper respiratory tract infections continue to be a great source of inappropriate use of antibiotics. A recent survey demonstrated that physicians prescribe antibiotics to half of patients labeled with “colds.” Instead, physicians should be knowledgeable about symptomatic therapies, including over-the-counter remedies. A targeted treatment plan aimed at the predominant symptoms is not only more effective but also more responsible.
The oropharynx and nasopharynx are lined by a stratified squamous epithelium and are normally teeming with a varied microbial flora. In addition, many potentially pathogenic bacteria can temporarily reside on these epithelial surfaces as “colonizers” without causing true infection. With a few exceptions, such as herpes simplex virus and the Epstein-Barr virus, viruses are not usually long-term members of the normal flora of the respiratory tract.
Numerous host defenses protect the upper airway from infection. The first of these defenses are mechanical; particulate matter is expelled by the cough and sneeze reflexes, entrapped by viscous mucous secretions, and propelled outward by ciliary action. In addition, local immunologic defenses attempt to deal with organisms that have breached the mechanical barriers. These defenses include lymphoid tissue, respiratory secretions that contain immunoglobulin A antibodies, and a rich vasculature capable of rapidly delivering phagocytic leukocytes. Once in the nasal cavity, viruses gain access to the upper airway by binding to ICAM-1 (an intercellular adhesion molecule). Experimental trials are being conducted in which soluble ICAM-1 is used to block this step in the initiation of infection.
Mechanisms of transmission include airborne transmission of virus-laden respiratory secretions via small aerosolized particles that remain suspended or large particles that travel only a few feet. However, the most efficient means of transmission is direct mucous membrane contact with virus, usually on contaminated hands. Self-inoculation of viruses surviving on the hands is accomplished by touching one’s nose or eyes. Children remain an important reservoir of these viruses. The timeless motherly warning that “you’ll catch cold if you get wet or damp” has not been borne out by experimental studies, which have demonstrated equal susceptibility in chilled and nonchilled hosts. However, evidence from prospective controlled studies suggests that psychological stress, especially chronic life stresses and poor social supports, can increase the risk for infection.
The common cold is caused by viral agents, mostly from five major families of viruses. Rhinoviruses are the most common viral agent associated with upper respiratory tract illness. Because there are more than 110 antigenic serotypes, cross-immunity does not exist, and reinfection with another serotype right after a recent cold is common. Coronavirus, parainfluenza virus, coxsackievirus, and respiratory syncytial virus account for the rest of the etiologic agents. Influenza A and influenza B produce a more severe syndrome that overlaps with the common cold. Influenza infection typically occurs in the winter months (December to March) in the northern hemisphere. The clinical syndrome consists of fever and diffuse myalgia, often accompanied by a nonproductive cough and headache. Lack of fever significantly decreases the probability of influenza. Patients with underlying cardiopulmonary disease and the elderly are at higher risk for development of a secondary bacterial pneumonia following influenza infection.
Incubation periods for viral upper respiratory infections range from 1 to 5 days; virus shedding lasts up to 3 weeks. Typical symptoms include coryza, pharyngitis, laryngitis, headache, malaise, and fever, in various combinations. Experimental evidence suggests that these symptoms are more the results of the body’s response to the infection (through mediators like bradykinin, prostaglandin, interleukin, and histamine) than the actual viral infection itself. Ear and sinus discomfort also are often present, frequently caused by mucosal edema that impairs drainage.
Whether known as the common cold, nasopharyngitis, or upper respiratory infection, these problems generally resolve spontaneously. Common viral upper respiratory infections rarely progress to pneumonia; most colds resolve spontaneously within 1 week, although symptoms may linger up to 2 weeks in one fourth of patients.
The diagnosis of the “common cold” remains a clinical one, based on the typical presentation. Patients should be examined for localized bacterial infection, such as otitis media, sinusitis, or streptococcal pharyngitis. If the patient presents with symptoms typical of influenza, further diagnostic testing can be considered with rapid testing, in which antibodies to common influenza antigens are usually used. The sensitivity of these tests appears to be high, and is even higher if nasopharyngeal washings rather than a swab are sent. Although not widely in use at present, these tests may become more important as new treatments for influenza become available (see below). On the other hand, identification of the specific virus causing the “common cold” is neither practical nor important.
The best things one can do to avoid “catching” a cold are to avoid aerosol exposure, wash hands, and keep hands away from mucous membranes (conjunctivae, nasal and oral mucosae). Gargling with “antiseptic” mouthwash is of no benefit. Initial studies on the use of inhaled a2-interferon have shown promising results for the prevention of rhinovirus infection, but such approaches remain experimental. The enthusiasm surrounding the use of high-dose vitamin C (ascorbic acid) for prophylaxis has waned as controlled studies have failed to demonstrate efficacy. Similarly, zinc lozenges have proved no better than placebo in controlled trials.
Therapeutic efforts are directed toward relieving nasal congestion, sneezing, rhinorrhea, headache, and grippelike symptoms and preventing complications such as otitis, sinusitis, and lower respiratory tract infection. Targeted therapy aimed at the most bothersome symptoms is preferred to all-inclusive cold remedies, which often contain irrational mixtures or subtherapeutic doses of active ingredients. Sympathomimetics remain the mainstay of decongestant therapy. Data suggesting a cholinergic pathophysiology for rhinorrhea and sneezing have stimulated interest in new forms of anticholinergic therapy.
Decongestants can be helpful, not only for providing symptomatic relief but also for preventing sinus and eustachian tube obstruction that can result in sinusitis and otitis media, respectively.
a-Adrenergic Agents are the most commonly used decongestants. They work by causing generalized vasoconstriction, thereby reducing the formation of secretions. Because they produce systemic vasoconstriction, sympathomimetics may raise blood pressure when used in doses sufficient to alleviate nasal congestion. No oral adrenergic agent provides selective local vasoconstriction; sympathomimetic nasal sprays (e.g., Afrin) are more effective for this purpose but may be associated with rebound congestion after as little as 3 days of continuous use, leading to difficulty discontinuing use and an increased risk of chronic abuse. According to most authorities, sympathomimetic nasal sprays are good for very short-term therapy, whereas oral preparations are better when treatment is to continue for longer than 3 to 4 days.
Anticholinergic Agents have been used for years in the treatment of the common cold, mostly in the form of over-the-counter sedating first-generation antihistamines, which exert an atropine-like drying effect. It is this effect, not antihistaminic activity, that probably accounts for the symptomatic usefulness of anticholinergics in patients bothered by profuse rhinorrhea and excessive sneezing. However, their marked drying effect can exacerbate symptoms of congestion and cause upper airway obstruction by impairing the flow of mucus. In addition, they cause drowsiness, a side effect that may impair daytime functioning, although it can provide some nighttime rest. These agents can also worsen symptomatic benign prostatic hypertrophy and glaucoma and should be avoided by patients with these conditions. Use of a prescription second-generation, nonsedating antihistamine is irrational and has no place in management of the common cold because these agents have little anticholinergic activity and cold symptoms have no allergic pathophysiology. Nonetheless, antihistamines continue to be widely consumed for use in colds, both in prescription form (which is extremely expensive and wasteful) and in over-the-counter preparations, usually in combination with a sympathomimetic and other substances (see below).
Ipratropium, a topically active anticholinergic agent now available in a nasal spray preparation, is being heavily promoted for relief of nasal symptoms of the common cold. In a placebo-controlled, double-blind, randomized trial, the nasal spray preparation provided a significant reduction in subjective and objective measures of rhinorrhea and sneezing in comparison with saline placebo spray and with no treatment. Of note, significant benefit was also found with use of the saline control spray in comparison with no treatment. Global ratings by patients for overall effectiveness followed a similar pattern. Observed side effects included increased nasal dryness and blood-tinged mucus in approximately 10% to 15% of subjects. No cases of sinusitis or marked nasal obstruction were reported, which suggests that short-term use of the spray (up to 5 days) might be reasonably well tolerated. The nasal spray is expensive.
Analgesics are useful for relief of the headache, fever, and achiness that often accompany a cold. Aspirin and acetaminophen have similar analgesic and antipyretic effects and are key ingredients in the combination cold remedies. However, both have been found capable of delaying the immune response to experimental rhinovirus infection, although neither prolongs viral shedding. Nonprescription doses of ibuprofen showed similar effects, but prescription doses of naproxen did not alter viral shedding or antibody response in one trial. All remain clinically useful for symptomatic relief of the headache, myalgias, and fever that may accompany a cold. Salicylate derivatives such as salicylamide are sometimes used, although they are much less effective than aspirin. Of all the analgesics, plain aspirin is by far the least costly; the other agents can be expensive.
Expectorants and Heated Humidification. Expectorants are included in many preparations in the belief that they stimulate the flow of mucus. There is no evidence to support this view, although these agents are widely prescribed and requested by patients. More important is adequate hydration, which helps loosen secretions and prevent upper airway obstruction and the complications that may ensue. Warm fluids (including tea and, yes, chicken soup) can increase the rate of mucous flow, providing some symptomatic relief, as can inhaled steam (another of grandmother’s remedies) or use of a dilute saline nasal spray.
Research suggesting that increasing the nasal mucosal temperature to 37°C could limit viral replication and decrease nasal congestion led to a renewed interest in the inhalation of warm, humidified air. A double-blinded study of steam inhalation through an active device showed no significant benefit over placebo therapy, although both were associated with considerable subjective improvement. An expensive heated nebulizer device (the Viralizer) has been heavily promoted as a means of promptly and completely relieving cold symptoms. Controlled study has failed to confirm such excessive claims.
Cough Suppressants, including narcotics such as codeine and non-narcotic agents such as dextromethorphan, are effective and useful symptomatically, especially in allowing the patient to sleep uninterrupted by cough. In many patients, a decongestant is even more effective in suppressing cough because postnasal drip accounts for much of the cough stimulus. These agents are commonly available in combination with expectorants, although they may be prescribed alone, which is more sensible therapy.
Zinc is thought to inhibit viral attachment and replication and improve cellular immune function. Such effects have stimulated interest in its use as a treatment for the common cold. The results of well-designed, controlled studies utilizing zinc gluconate lozenges have been equally divided between showing efficacy and showing no benefit. In the studies with positive findings, adequate blinding has been questioned because zinc lozenges have a distinct taste that may alert study subjects to their allotted treatment. The studies with negative findings have been criticized for subtherapeutic doses or ineffective preparations. One highly publicized study of 100 patients recruited from hospital employees demonstrated a significant reduction (nearly 40%) in the duration of illness, and also in the duration of coughing, nasal drainage and congestion, hoarseness, headache, and sore throat. The lozenges in this study contained 13.3 mg of zinc, and patients were instructed to take them every 2 hours while awake (average of six per day). Side effects included nausea and a bad taste in the mouth, experienced by most of the patients. Patients may be informed of the possible benefit of zinc lozenges but should be forewarned about the likely side effects.
Echinacea. Extracts from plants of the genus Echinacea have gained widespread acceptance in Germany as a treatment for the common cold. These plant products are postulated to have immunomodulator activity, such as macrophage activation and interleukin production. Although many randomized trials have suggested a benefit in the reduction of symptoms, the interpretation of results is complicated by the variety of species used (E. purpurea, E. pallida, and E. angustifolia) and the different plant parts (root or herb) and formulations (tablets, liquid extracts, capsules). Further studies based on standardized preparations and validated outcome measures will be needed before recommendations may be made for or against the use of Echinacea.
Other Agents and Combination Preparations. Americans spend nearly a billion dollars annually on over-the-counter cold remedies. Most contain a combination of ingredients, including first-generation sedating antihistamines, sympathomimetic amines, and analgesics. Some even contain more than one antihistamine or sympathomimetic. Antitussives, atropine, caffeine, vitamin C, belladonna alkaloids, and expectorants are other common additives. Antacids, laxatives, quinine, and papaverine are found occasionally. In general, these combination preparations should not be recommended as first-line therapy. As noted above, the vitamin C included has not been shown to have any significant effect, even when given in gram doses.
If the diagnosis of influenza is confirmed or highly suspected, several medications may be useful in decreasing the duration of symptoms if administered within the first 48 hours of the illness. Amantadine and rimantadine are oral antiviral drugs effective against influenza A only. Rimantadine is more expensive but has fewer side effects, notably less central nervous system effects. The dosage for both drugs is 100 mg twice daily except in the elderly, in whom decreased drug clearance allows for once-daily dosing. The drug should be discontinued after 3 to 5 days (or earlier if symptoms resolve) to decrease the opportunity for drug resistance, which may occur in up to one third of treated patients.
Neuraminidase inhibitors, zanamivir and oseltamivir, are newly approved agents for the treatment of influenza. These drugs are sialic acid analogues that inhibit the viral neuraminidase enzyme, essential to replication for both influenza A and influenza B. Early randomized trials of these agents show a decrease in the duration of illness of 1 to 1.5 days if the drug is administered within 48 hours of symptom onset, similar to the effect seen with the older agents. Zanamivir is administered by an inhaler twice daily; oseltamivir is given as a pill (75 mg) twice daily. The advantage of these newer agents is their activity against both influenza A and influenza B; they have not been in use long enough to determine whether viral resistance will be problematic. In addition, because the average cost of these agents is at least 10 times greater than that of influenza vaccine, vaccination is clearly the more cost-effective method to avoid flu symptoms.
Among the most frustrating experiences in primary care practice is the request by patients suffering from a cold for antibiotics. Explaining that antibiotics have no role in an uncomplicated viral upper respiratory infection can be time-consuming at best and has the potential to develop into a power struggle. A proactive approach is to send educational materials to patients at the beginning of the upper respiratory infection season. Pamphlets and other informational materials are much appreciated by patients and can help cut down on unnecessary visits and telephone calls. They should include helpful hints at self-care and the indications for seeking medical attention (e.g., high fever; marked pain or tenderness in an ear or sinus; increasingly purulent sputum, dyspnea, pleuritic chest pain). The role of antibiotics in the treatment of viral upper respiratory infection should also be reviewed (i.e., only for complications such as otitis and sinusitis), in addition to the risks of unnecessary antibiotic therapy (e.g., allergic reactions, alteration of bacterial flora, emergence of resistant strains). Unnecessary office visits and telephone calls have been reduced by as much as 30% to 40% through well-designed educational efforts.
Prevention is difficult, but hand washing, keeping fingers away from mucous membranes, and avoidance of droplet exposure may help. Relief from cold symptoms and avoidance of complications are facilitated by rest, adequate fluid intake, aspirin, and perhaps inhalation of steam. Taking a cough suppressant before bed (e.g., 15 mg of codeine sulfate) and using a sympathomimetic nasal decongestant spray for a few days (e.g., phenylephrine; may aid in symptomatic management and are superior to expensive combination agents. Symptoms of incapacitating rhinorrhea and sneezing not well controlled by first-generation antihistamines may be treated with a short course of ipratropium nasal spray (two sprays of a 0.06% solution in each nostril four times daily). Proactive patient education just before the beginning of the cold season may help reduce unnecessary office visits, telephone calls, and requests for antibiotics. Zinc and Echinacea remain popular among patients, but their efficacy has not been clearly demonstrated. Second-generation antihistamines and antibiotics are of no use in an uncomplicated viral upper respiratory infection.