History

Although the common cold undoubtedly has had an impact on the events of history, the specific symptom complex in ancient times was overshadowed by more severe contagious problems (influenza, plague, smallpox) and by septic diseases (otitis, sinusitis, mastoiditis, pneumonia) that were complications of upper respiratory tract viral infections. The name common cold most certainly arose from the fact that the onset of symptoms included the feeling of chilliness on exposure to cold. This association was perceived as a cause-and-effect relationship. More than 200 years ago, Benjamin Franklin pointed out that colds were caught from other people rather than by exposure to cold.

In 1914, Kruse showed that colds could be transmitted by the nasal instillation in healthy adults of Berkefeld-filtered nasal washings from ill individuals and that the causative agent was smaller than common bacteria. These findings were confirmed clearly in 1930 by Dochez and associates. The way was paved for more extensive study of respiratory viral infections in 1933, when Smith and colleagues reported the isolation and cultivation of an influenza A virus from a human.

The greatest contribution to the present understanding of the common cold has been the use of human volunteers under carefully controlled conditions. The Common Cold Research Unit at Salisbury, England, which was established in 1946, and volunteer studies at this institution and studies done in the United States *

* References .

Although studies of respiratory illness in children also have been extensive, controlled virus challenge trials have not been done. Pediatric studies have been most useful in delineating the spectrum of clinical manifestations by age group and seasonal prevalence rates of the respiratory viruses.

During the past decade the use of molecular methods has increased our understanding of the contributions of both newly discovered and established viruses in the etiology of the common cold and other respiratory illnesses.

Etiologic Agents

Initial investigations into the etiology of the common cold were based on the hypothesis that only one etiologic agent needed to be discovered. Subsequent studies revealed that many different groups of viruses were involved etiologically and that many types frequently existed within each group. Table 7.1 lists the agents associated with colds. Each of these agents is covered more fully in other chapters; this chapter presents an overview. As a group, rhinoviruses are the most common cause of colds in children and adults. Also of major importance in the etiology of colds are reinfections with parainfluenza viruses and respiratory syncytial virus (RSV). Although the quantitative contribution of coronaviruses to colds in children is less well known, they are significant contributors. More recent studies also indicate that human metapneumovirus and human bocavirus cause colds in children. *

* References .

Enteroviruses and adenoviruses have been implicated frequently in upper respiratory tract illnesses, but in most instances the illnesses do not conform to strictly defined colds. Reoviruses cause colds, but their contribution to the overall incidence is unknown. Mycoplasma pneumoniae, Chlamydophila (formerly Chlamydia ) pneumoniae, Streptococcus pneumoniae, and Haemophilus influenzae infections were identified serologically in one study involving young adults with colds, but, in most instances, concomitant viral infections also were noted. Other agents, such as Coccidioides immitis, Histoplasma capsulatum, Bordetella pertussis, B. parapertussis, B. bronchiseptica, B. holmesii, Chlamydophila psittaci, and Coxiella burnetii, also have been associated with illnesses with initial coldlike symptoms.

Epidemiology

The common cold is an exceedingly frequent illness in childhood. For rhinoviruses alone, more than 100 serologically different viral types can cause this illness. Nonetheless, a general predictability of incidence and seasonal occurrence exists for the common cold. In the past numerous epidemiologic studies were conducted on the occurrence of respiratory tract illnesses, but calculating a precise incidence of the common cold from these studies is difficult because criteria of disease classification were different. The findings in three carefully performed studies are presented in Table 7.2 . Two of these studies were done approximately 60 years ago, and the other was done more than 40 years ago. These studies involved a wide range of family life settings, and the average number of colds per year in children varied from three to eight. Adults had on average approximately half the number of colds as their children.

In more recent times and in the era of the common use of daycare facilities, studies of the scope and magnitude of those presented in Table 7.2 have not been done. In one study published in the 1980s, the incidence of acute respiratory tract infections in daycare attendees peaked at 10 per child-year during the second 6 months of life. A study by Wald and associates found that children in home care had 4.7 illnesses per year, whereas the illness rate was 7.1 per year in children in daycare. Of the illnesses, 89% in daycare attendees were respiratory tract infections.

In 2008, Grüber and associates reported the history of respiratory infections in a cohort of German children. The children in this cohort were seen at ages 3, 6, 12, 18, and 24 months and then annually until age 12 years. The common cold illness rates per year were 3.1 in infancy, 3.2 at year 2, 2.1 at year 3, 2.3 at year 4, 1.8 at year 5, 1.3 at year 6, 1.1 at years 7 to 9, and 1.0 at years 10 to 12. The reason for these overall decreased rates in contrast to previous studies is not apparent, but less complete data ascertainment seems likely. In addition, smaller family size and less use of daycare could be factors.

In a study in Arizona, researchers found that 52% of 2-year-old children who attended large daycare centers had six to nine colds per year. The conventional spread of colds has its initial focus in the school. School-aged children become infected and introduce secondary infections into the home. Under these conditions, the secondary attack rate was highest in other school-aged and preschool-aged children. Generally, the secondary attack rate in adult family members was approximately half that of the children. The introduction of infection into the family by adults is unusual. In crowded settings, such as a university, infection is common and can be associated with substantial morbidity. In a cohort study of more than 3000 college students, colds and influenza-like illness were common findings and were associated with missed classes, poor performance on class assignments, missed extracurricular activities, and increases in use of medical care.

As noted previously, the present trend toward the use of daycare centers and preschool programs has increased the number of primary infections in younger children and has made them the source from which secondary family infections frequently occur. In a study that involved 606 children who received care at home or in a daycare program during the first 3 years of life, researchers found that children who attended a large daycare facility (six or more unrelated children) had more frequent colds at year 2 and less frequent colds at years 6 through 11 than did the children with home care only.

In a national telephone survey in Australia in 2008–09 acute respiratory infections (ARI) were noted in 19.8% of families during the 4-week period prior to the telephone call. Having a family member attending daycare was a significant risk factor for ARI in the family. In a daycare hand hygiene intervention study in the Netherlands, the yearly incidence of the common cold was 7.4 per child-year.

Close personal contact between children is necessary for the transmission of viruses that cause colds. In the typical pediatric practice office setting, no increased risk for the acquisition of respiratory tract illnesses by well infants has been shown. Among children, boys tend to have more colds than do girls. In the conventional family setting, mothers tend to have at least one more cold per year than their spouses have. The usual incubation period of colds is 1 to 5 days.

In all nonisolated populations, colds occur more frequently during the winter months than during the summer. This seasonal discrepancy in incidence is as apparent in areas of high wintertime mean temperatures as it is in locations with extremely low temperatures. In the tropics, colds are more prevalent during the rainy season. Colds occur throughout the world. In isolated populations in which the number of people is few (e.g., members of Antarctic exploration teams and isolated island communities), colds do not occur unless introduced by a visiting person.

Although colds can be produced regularly in volunteers, the method of transmission of viruses that results in colds under natural circumstances is unclear. *

* References .

The route of acquisition of virus is by the nose and possibly the conjunctiva. With these facts in mind, one can easily see that a susceptible individual can become infected by inhalation of virus in droplet nuclei (small particles) resulting from a sneeze, by the direct nasal hit of virus containing large droplets from a sneeze, by nose blowing, or by the inoculation of virus (usually by the fingers of the recipient) from nasal secretions from disseminators that have been transmitted directly or indirectly. In children, most likely the spread either involves close contact with large droplets of nasal secretions containing virus that are applied to the nose from the hands of the future host or occurs by close-range airborne acquisition.

Considerable folklore is related to the catching of a cold. However, all available evidence to date indicates that cold weather per se, chilling, wet feet, and drafts neither cause nor increase the susceptibility of individuals to colds caused by viral infections. A study of 180 adult subjects showed that acute cooling of the feet was associated with the onset of common cold symptoms. On day 4, after the cooling of the feet or the control procedure, significantly more subjects in the chilled group thought they were suffering from a cold (14.4%) compared with the control group (5.6%). The subjects who thought they were suffering from a cold had a history of more colds each year in contrast to subjects who did not develop cold symptoms. In this study, no virologic studies were done, so no evidence exists that the cold symptoms observed were caused by viral infections.

In a study of respiratory tract infections in Finnish military recruits, it was found that cold temperature and low humidity were associated with an increased occurrence of respiratory infections; a decrease in temperature and humidity preceded the onset of the infections. However no virologic data support the findings in this study.

In contrast, in controlled studies in which virologic studies were performed, no increased susceptibility to colds after exposure to chilling conditions was found. In adults, risk factors for increased susceptibility to colds include stress, smoking, high basal levels of catecholamines, infrequent exercise, low intake of vitamin C, low sleep efficiencies, and lack of diverse social networks. Physical stress, as opposed to mental stress, does not seem to be associated with increased susceptibility to colds. In a study of nine healthy men who were competitive cyclists who underwent intensive interval training, the men experienced enhanced performance but had no change in white blood cells, cytokine levels, or the frequency of upper respiratory tract infections.

A fascinating volunteer study in adults by Cohen and colleagues was reported in 2008. In this study the subjects were given rhinovirus 39 or influenza A/Texas/36/91 intranasally. It was found that subjects with increased subjective socioeconomic status were less susceptible to upper respiratory tract infections than subjects with decreased subjective socioeconomic status. In contrast, no relationship was found between objective socioeconomic status and susceptibility to the two challenge viruses.

Pathophysiology

The pathophysiology of human infections with viruses that cause colds is presented in the sections of this book covering the individual infectious agents. A general overview is presented here. Few studies on the pathophysiology of respiratory tract infections have been done in children; the material presented in this section has been derived mainly from studies in adults. *

* References .

Although the primary site of virus inoculation in some colds may be on the conjunctival surface, most result from inhalation or self-inoculation of virus onto the nasal mucosa. After acquisition of a virus has occurred, infection of the cells of the local respiratory epithelium develops. This infection varies in the degree of cytopathology on the basis of the viral agent. The infection spreads locally, resulting in an increase in nasal secretions with an increased protein content. Symptoms (nasal stuffiness and throat irritation followed by sneezing) begin on the second or third day and are caused by cellular damage and irritation. Virus shedding is at its maximum in 2 to 7 days, although some shedding may continue for another 2 weeks.

Hilding examined biopsy specimens, scrapings, and smears of nasal secretions and noted that submucosal edema occurred initially, followed by shedding of the ciliated epithelial cells. By the fifth day, the epithelial damage had reached its maximum, with regeneration occurring during the next 10 days. Winther and associates performed similar studies and noted the sloughing of epithelial cells, but they found that the epithelial lining remained continuous with normal cell borders. On the second day of disease, an increase in the number of neutrophils in the epithelium and lamina propria occurred. Epithelial mast cells were not involved in the inflammation. The nasal discharge during the second to the seventh day is mucopurulent owing to its content of desquamated epithelial cells and polymorphonuclear leukocytes.

In experimental rhinovirus colds in adults, little or no discernible damage to the nasal epithelium has been shown. Arruda and associates noted in adults infected with rhinovirus types 14 and 39 that virus replicates in ciliated and nonciliated cells in the nasopharynx and that only a very small proportion of the cells were infected.

Because damage to the nasal epithelium is not noted in rhinovirus colds, apparently cell death is not the cause of symptoms. Naclerio and colleagues and Proud and associates found that kinins are generated locally, and their concentrations correlate with the severity of symptoms. The cause-and-effect relationship between kinins and symptoms is questionable, however, because treatment with a bradykinin antagonist failed to lessen symptoms. In addition, steroid therapy was found to reduce the concentration of kinins in nasal wash fluid, but it did not affect clinical symptoms.

In 1994, researchers noted that interleukin-1 (IL-1) may contribute to the pathogenesis of rhinovirus infections. Ongoing molecular and biochemical research has provided information on methods by which rhinoviruses interfere with the host response, induce epithelial expression of IL-6 and IL-8, and mediate infection via activation of kinases and receptor binding activity. In a human rhinovirus type 16 volunteer study it was found that IL-18 had a protective effect against colds and asthma exacerbations. Conversely, it was noted that subjects with low nasal and bronchial IL-18 levels had increased respiratory symptoms. Similarly, research into the other viruses of the common cold has helped in the understanding of their similarities and differences, such as the cell-mediated immune response to human metapneumovirus and RSV.

In studies in children with acute upper respiratory tract infections, IL-1β, IL-8, IL-6, and tumor necrosis factor (TNF)-α were found to be elevated markedly in nasal lavage fluid. Pacifico and associates found that IL-8 concentrations and white blood cell and neutrophil counts were significantly greater in children with rhinovirus colds than in well children. In an adult volunteer study, Turner and colleagues noted a significant rank correlation between nasal obstruction severity, rhinorrhea severity, and nasal-wash albumin concentrations and the increase in IL-8 concentration from baseline to days 2 to 4 after virus challenge. In a study of 285 children with a parental history of asthma, other respiratory allergy, or both, blood specimens were obtained at birth and at 1 year of age. The cytokine responses of mononuclear cells when incubated with phytohemagglutinin, RSV, and a rhinovirus were analyzed. Vigorous IL-13 and interferon (IFN)-γ responses to phytohemagglutinin and a marked secretion of IFN-γ in response to the viruses were associated with a reduced risk for developing wheezing with viral infections in the first year of life.

Pedersen and colleagues studied nasal mucociliary transport in naturally acquired colds, noting that transport was reduced markedly during the acute illness and that slight impairment remained for approximately 1 month. They point out that because some children have four to six colds during a winter season, these children may have constantly impaired mucociliary transport.

Although viremia has been noted during infections with some of the viruses that cause colds, viremia is not known to occur during the typical common cold. The infection is restricted to the epithelial surfaces of the upper respiratory tract air passages, including the sinuses and eustachian tubes. With infection, local IFN is produced and presumably has a major role in controlling the infection. Serum antibody and secretory antibody regularly result from infection. The roles of cell-mediated factors in immunity and disease pathogenesis of colds are unknown.

Levandowski and associates noted in rhinovirus-challenged volunteers that total T cells, and particularly helper T cells, were depressed. The magnitude of this finding correlated with progression of infection and symptoms. In a study in which volunteers received rhinovirus type 39, Skoner and associates found a slight increase in helper (CD4 ⁺ ) and suppressor (CD8 ⁺ ) T cells during illness. Noting that asthma exacerbations and rhinovirus infections are associated with decreased pH and ammonium levels in exhaled breath condensates, Carraro and colleagues studied whether a direct rhinovirus infection, the host immune response to the infection, or both decreased the airway epithelial cell surface pH in vitro. They found that airway epithelial cell pH is affected partly by T-helper type 1 cytokines. This decrease in pH can provide an innate host defense, inhibiting viral replication in the lower airways. By mechanisms not well understood, within already infected cells, low pH is thought to trigger uncoating of rhinoviral RNA from within the endosome, thus enabling viral replication.

The role of antibody (serum and secretory) in the protection against reinfection and clinical colds is complicated. High levels of secretory and serum antibodies seem to be protective against reinfections. *

* References .

Unexplained constitutional factors also seem to control the clinical manifestations of colds. Although studies have shown genetic disease susceptibility patterns related to tissue types, no studies relating to common respiratory tract infections have been done. In experimental coronavirus infections in adults, clinical severity correlated with detectable immunoglobulin (Ig)E in nasal secretions. This finding suggests that atopy may be related to symptoms in colds caused by coronaviruses. Although clinical symptoms and virologic data suggest that colds are upper respiratory tract diseases, some studies of pulmonary function also have indicated occult lower respiratory tract involvement.

In children younger than 5 years of age, primary traffic pollutants, ozone, and the organic carbon fraction of a particle size of less than 2.5 µm exacerbate upper respiratory infections.

Clinical Presentation

Because the common cold is caused by more than 100 different viral types, considerable variation in the clinical manifestations occurs. As indicated in the beginning of this chapter, the limits of illness to be considered under the diagnosis of the common cold have been set arbitrarily but rigidly. A disappointing note is that although many comprehensive studies of respiratory viral illnesses of children have been done, little attention has been given to the details of upper respiratory tract infections.

Illness in children must be considered under two categories—infants and older children. The latter is similar to illness in adults. In studies involving 100 young adults, Jackson and colleagues noted that virtually all patients complained of nasal discharge, nasal obstruction, and sore throat; approximately 80% had malaise, postnasal discharge, headache, and cough; slightly fewer than 50% reported a feverish feeling and chilliness; and approximately 25% noted burning eyes and nasal membranes and muscle aching. In older children, the onset of illness is heralded by dryness and irritation in the nose and a scratchy feeling in the throat. The initial symptoms are followed within a few hours by sneezing and watery nasal discharge; chilly feelings and occasionally muscular aches also are noted. Other complaints include headache, general malaise, anorexia, and low-grade fever.

After a variable period of 1 to 3 days, the illness changes; the nasal secretions become thicker and frequently develop a purulent appearance. Persistent nasal discharge, associated with the trauma of repeated blowing of the nose, leads to excoriation around the nose. Nasal obstruction leads to mouth breathing, which causes drying of the throat, increasing the discomfort in the throat. The usual duration of illness is approximately 7 days, but lingering cough and nasal discharge may persist for 2 weeks or more.

A recent review of reports relating to respiratory tract infections in children by M. Thompson and associates noted that in children 50% of the colds resolved by day 10 and 90% by day 15.

In infants, the manifestations of illness may be more varied. The onset of illness in infants is associated more often with fever (38°C to 39°C [100.4°F to 102.2°F]) than it is in older children. Nasal manifestations in infants are similar to manifestations in older children, but the only other manifestations are irritability and restlessness. Occasionally, coryza is the only symptom. Nasal obstruction may interfere significantly with feeding and sleeping. Vomiting and diarrhea also may occur.

Differential Diagnosis

Because the clinical entity of the common cold is an arbitrary grouping of signs and symptoms limited to anatomic boundaries and is caused by many different viral types, the approach to the differential diagnosis must consider clinical and etiologic criteria. Many upper respiratory tract illnesses are caused by numerous infectious agents that should not be confused with colds. A diagnosis of the common cold should not be considered if objective pharyngitis, other enanthema, or evidence of obstructive airway disease is present. Because the common cold is an acute, self-limited disease, the diagnosis should not be considered in a child who has persistent nasal signs or symptoms. Subacute or chronic illness should suggest the possibility of adenoiditis or sinusitis.

The most important differential diagnostic considerations are clinical entities of noninfectious etiology. Allergic rhinitis is a particularly important possibility in a child with “recurrent colds.” Careful attention to family history, a search for allergies, the presence or absence of nasal eosinophilia, and the serum IgE value help confirm or exclude this consideration.

Although not reported particularly in pediatric patients, mental stress can lead to vasomotor responses and rhinitis in some susceptible patients. Chemical irritants can cause coldlike symptoms; the clinical response varies greatly across individuals. Early symptoms of many illnesses, such as pertussis, croup, epiglottitis, measles, and diphtheria, are those of a cold, but in a short time, the more serious nature of the actual illness becomes apparent.

Specific Diagnosis

The epidemiologic history is the most important aspect of specific diagnosis. In children, if exposure history is requested, a contact usually is uncovered. If strict attention to clinical criteria of the common cold has been adopted, routine laboratory study is unnecessary. Frequently, the physician has an urge to take a throat culture to rule out the possibility of group A streptococcal infection. Usually, this is unnecessary because nasal symptoms are not characteristic of acute streptococcal illness except in infancy, and pharyngitis is not within the limits of the diagnosis of the common cold. The white blood cell count also is of little use.

A specific diagnosis can be made by isolating virus from nasopharyngeal secretions. It is performed best by a nasal-wash technique or a nasopharyngeal swab or aspirate. With laboratory techniques (culture or polymerase chain reaction [PCR]) of diagnostic virologic facilities in university hospitals, public health laboratories, and in reference laboratories, all known common cold viruses can be identified. (See Chapter 253 .)

Treatment

Although literally hundreds of over-the-counter (OTC) cold remedies are available, few offer benefit to the pediatric patient, and many may be harmful. *

* References .

In the approach to a child with a cold, the best assumption is that no therapy is indicated in most cases. On occasion, specific symptomatic care can be added in the individual case when it appears to be needed. Many children and adults feel miserable when they have a cold, and therapy with an analgesic often is used. Because aspirin is a risk factor for Reye syndrome in children, the use of acetaminophen rather than aspirin is prudent. The dose per single administration of acetaminophen by year of age is as follows: younger than 1 year, 60 mg; 1 to 3 years, 60 to 120 mg; 3 to 6 years, 120 mg; 6 to 12 years, 150 to 300 mg; older than 12 years, 325 to 650 mg. Administration may be repeated every 6 to 8 hours in young children and every 4 hours in older children. Acetaminophen rarely should be given to infants younger than 6 months of age.

In adult volunteers with rhinovirus infections, acetaminophen was found to be associated with suppression of the serum neutralizing antibody response, and an increase in nasal symptoms was noted, in contrast to subjects who received a placebo. In another adult volunteer study, administration of naproxen resulted in a reduction in headache, malaise, myalgia, and cough in contrast to placebo. Choi and colleagues looked at five studies to compare the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) versus acetaminophen in symptom relief for the common cold. They found no difference in effectiveness between NSAIDs and acetaminophen in common cold symptom relief.

OTC cough and cold medications that contain antihistamines, antitussives, expectorants, decongestants, and antipyretics/analgesics in various combinations are readily available for children. Results of the Slone Survey noted that in a 1-week period, 10.1% of children in the United States received an OTC cough/cold medication. Adverse events and deaths in children younger than 6 years have been observed. In 2007, a U.S. Food and Drug Administration (FDA) advisory group recommended that OTC cough and cold medications not be used in children younger than 2 years. Unfortunately, a large number of parents and other caregivers are not aware of the FDA recommendations on OTC cough and cold medications. The American Academy of Pediatrics in 2008 recommended that OTC cough and cold medications should not be used in children younger than 6 years.

Relief of nasal obstruction is the most important therapeutic consideration in young children. Locally applied or orally administered systemically active decongestants are used frequently, but neither their true efficacy nor their adverse effects have been evaluated carefully. Excessive use of sprays and drops with vasoconstrictive drugs can lead to rebound obstruction, which prolongs the illness. The associated drying effect of vasoconstrictive drugs administered orally can be expected to be deleterious to normal mechanisms of clearance. In young infants, sympathomimetic-antihistamine mixtures in oral drop dosage forms particularly are dangerous because respiratory depression may occur. In addition, in a controlled trial, brompheniramine maleate–phenylpropanolamine hydrochloride was found to be no better than a placebo in relieving cold symptoms in children 6 months to 5 years of age. If vasoactive drugs are used, their use should be restricted to times when maximum benefit would occur (i.e., bedtime), and they should be discontinued within 3 days.

The use of isotonic saline drops and gentle aspiration may be effective in the temporary relief of nasal obstruction in an infant. However, a Cochrane Collaboration review noted that available data were not sufficient to demonstrate efficacy of saline nasal irrigation. It also noted that 40% of babies did not tolerate nasal saline drops. The general humidification of room air may be useful because this moisture tends to dilute tenacious nasal mucus and facilitate its elimination. In a Cochrane Collaboration review, steam inhalation was not shown to offer any consistent benefits in the treatment of the common cold.

Antibiotics have no place in the routine therapy of common colds. In children, persistent cough occasionally is a problem of such magnitude that it disturbs sleep. For cough, codeine and dextromethorphan often are used. No well-controlled studies support either the efficacy or the safety of codeine or dextromethorphan as an antitussive in children, however. Eccles suggested that the apparent efficacy of liquid cough syrups may be due to the sweetness of the products rather than their active ingredients. The proposed mechanism is that a sweet taste may affect cough at the level of the nucleus tractus solitarius by stimulating the production of endogenous opioids.

In the past, antihistamines were often given to children with colds, but efficacy had not been demonstrated. In more recent years, first-generation antihistamines, but not second-generation products, have been shown to lessen rhinorrhea in adults with colds. Doxylamine succinate, clemastine fumarate, chlorpheniramine maleate, and brompheniramine have been shown to offer benefit in controlled trials. The effect of these antihistamines is due to their anticholinergic properties. To date, no studies in children have been reported.

A major controversy relates to the efficacy of vitamin C in the common cold prophylactically and therapeutically. In two carefully controlled volunteer studies, the administration of 3 g of ascorbic acid per day did not prevent or alter the symptoms of experimental colds. In addition, several large controlled trials in which vitamin C and placebo preparations were used to prevent and to treat colds were conducted. Benefit was reported in some of these studies, whereas in others, no efficacy was noted. The reported benefits probably are a result of statistical artifacts and placebo effect owing to poor study design, rather than specific pharmacologic drug effects. The antihistaminic action of vitamin C probably afforded relief to some patients with allergic rhinitis who thought that their illnesses were colds. Because of the many toxic effects of ascorbic acid, and because its use in treating respiratory illnesses is questionable at best, giving children vitamin C in excess of normal daily requirements seems unwarranted.

For many years, efforts have been made to develop effective rhinovirus chemotherapy, but showing convincing efficacy in natural infection has been a challenge. IFN alfa-2b administered intranasally has been shown to have some efficacy in the prevention of rhinovirus colds in controlled clinical trials. The effect is variable, however, and adverse effects of the medication are frequent occurrences. Intranasal IFN alfa-2b was ineffective in the treatment of naturally occurring colds but showed some benefit in experimental coronavirus colds. Studies in adults using an antiviral antiinflammatory combination for treatment of the common cold showed some benefit in contrast to either agent used alone. However, the irritation caused by intranasal IFN alfa-2b and the drowsiness associated with first-generation antihistamines render these drug combinations suboptimal.

Zinc lozenges have been used to treat the common cold; the Internet and lay literature are full of claims of efficacy, although in well-done, controlled studies, efficacy has not been shown. However, a recent Cochrane Collaboration review noted that zinc administered within 24 hours of onset of symptoms reduced the duration and severity of the common cold in healthy people. It also noted that prophylactic use reduced the incidence of colds and decreased school absenteeism and antibiotic use in children. The use of intranasal zinc preparations also is not well validated and raises some concern because of the possible development of the zinc-induced anosmia syndrome. In a double-blind, placebo-controlled trial, the use of intranasal corticosteroid (fluticasone propionate) offered no clinical benefit in young adults with colds and induced prolonged shedding of rhinovirus.

In a controlled trial in adults, a soluble intercellular adhesion molecule-1 product (tremacamra) reduced the severity of rhinovirus colds. The antiviral pleconaril induced an early reduction in severity of symptoms in adults with colds caused by rhinovirus. Pleconaril is an antipicornavirus drug that interacts directly with viral capsid proteins. It blocks attachment of virus to cells through intercellular adhesion molecule-1 and subsequent uncoating and release of viral RNA.

In another randomized, double-blind, placebo-controlled trial, the symptomatic efficacy of pleconaril was linked to its in vivo antiviral effects and to the drug susceptibility of the infecting virus. In March 2002, the Antiviral Drugs Advisory Committee of the FDA voted against recommending pleconaril for approval of its use in the treatment of the common cold in adults. This decision was based on drug interactions, poor risk-to-benefit ratio, and concerns of development of resistant virus.

Clarithromycin, a macrolide antibiotic, enhances mucosal immunity in mice by increasing levels of IL-12, IgA, and IgG. In a controlled trial, however, clarithromycin had no effect on the severity of cold symptoms. The intranasal administration of nedocromil sodium has been observed to have a beneficial effect on rhinoviral infections in adult volunteers. Mucolytics have emerged as potential therapeutics for modulating the function of airway epithelial cells and altering the course of viral infections. Leukoprotease inhibitors and pulmonary surfactant have been shown to be upregulated by ambroxol, a mucolytic and antioxidant agent.

In one study, adults who took sauna baths once or twice per week were found to have fewer colds than did members of a non–sauna-bathing control group. In two studies, volunteers with colds did not benefit from inhaling heated vapor.

The list of available and proposed complementary and alternative medicines thought to be useful for prevention and treatment of the common cold is long. *

* References .

In a controlled trial, Taylor and associates evaluated Echinacea for the treatment of upper respiratory tract infections in children aged 2 to 11 years. No benefit was noted, and the Echinacea -treated children had an increased occurrence of rash. Preparations of North American ginseng have been reported to decrease the frequency of colds in adults. In a study of North American ginseng extract involving children 3 to 12 years of age, no treatment benefit was noted.

In a 2010 study in children 2 to 11 years of age, Paul and associates found that the application of Vicks VapoRub to the child’s neck and chest at bedtime gave symptomatic relief from nocturnal cough, congestion, and sleep difficulty caused by an upper respiratory tract infection. This was a controlled study that compared the children treated with Vicks VapoRub with those who had received petrolatum to the chest and those who had no treatment.