INTRODUCTION	Section 2 of 9
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Background: The common cold is an acute respiratory tract infection (ARTI) characterized by mild coryzal symptoms, rhinorrhea, nasal obstruction, and sneezing. Although incidence cannot be clearly defined because of seasonal and location variability, the incidence of ARTI in the United States ranges from 3-6 cases per person per year. Before reaching the age of 1 year, children average 6-8 episodes of ARTI. This incidence decreases to 3-4 episodes per year by adulthood. Although the list of agents causing the common cold is large, 66-75% of cases are due to 200 antigenically distinct viruses from 8 different genera. The most common of these are the rhinoviruses (25-80% of cases), followed by coronaviruses (10-20%), influenza viruses (10-15%), and adenoviruses (5%).

Rhinoviruses are in the Picornaviridae family, which includes the human pathogens, enteroviruses, and hepadnaviruses (notably, hepatitis A). Rhinoviruses are small, nonenveloped, positive (sense) stranded RNA viruses. Their structure is an icosahedral capsid of 12 pentamers containing the 4 viral proteins. A deep cleft is involved in viral attachment. Attachment to cellular receptors can be blocked by specific antibody. More than 100 different subtypes exist, with 3 major groups based upon receptor specificity: intercellular adhesion molecule-1 (ICAM-1), low-density lipoprotein (LDL) receptors, and sialoprotein cell receptor.

Rhinovirus infections are chiefly limited to the upper respiratory tract but may include otitis media and sinusitis. Rhinovirus plays a role in exacerbations of asthma, cystic fibrosis, chronic bronchitis, and serious lower respiratory tract illness in infants, elderly persons, and patients who are immunocompromised. Although infections occur year-round, the greatest incidence is in the fall and spring. Of persons exposed to the virus, 70-80% have symptomatic disease.

Pathophysiology: Rhinoviruses are transmitted to susceptible individuals by direct contact or by aerosol particles infecting both ciliated areas of the nose and nonciliated areas of the nasopharynx through receptors, most frequently ICAM-1 (found in high quantities in the posterior nasopharynx). Few cells are actually infected by the virus, and the infection involves only a small portion of the epithelium. Symptoms develop 1-2 days after viral infection, peaking 2-4 days after inoculation, although reports have described symptoms as early as 2 hours after inoculation with primary symptoms 8-16 hours later.

Detectable histopathology causing the associated nasal obstruction, rhinorrhea, and sneezing is lacking, which leads to the hypothesis that the host immune response plays a major role in rhinovirus pathogenesis. Infected cells release interleukin-8 (IL-8), which is a potent polymorphonuclear (PMN) chemoattractant. Concentrations of IL-8 in secretions correlate proportionally with the severity of common cold symptoms. Inflammatory mediators, such as kinins and prostaglandins, may cause vasodilatation, increased vascular permeability, and exocrine gland secretion. These, together with local parasympathetic nerve-ending stimulation, lead to cold symptoms.

Deficient interferon beta production by asthmatic bronchial epithelial cells has been proposed as a mechanism for increased susceptibility to rhinoviral infections in individuals who are asthmatic.

Viral clearance is associated with the host response and is due, in part, to the local production of nitric oxide. Serotype-specific neutralizing antibodies are found 7-21 days after infection in 80% of patients. Although these antibodies persist for years, providing long-lasting immunity, recovery from illness is more likely related to cell-mediated immunity. Persistent protection from repeat infection by that serotype appears to be partially attributable to immunoglobulin A (IgA) antibodies in nasal secretions, serum immunoglobulin G (IgG), and, possibly, serum immunoglobulin M (IgM).

The virus has a limited temperature range in which it can grow (33-35°C) and cannot tolerate an acidic environment. Thus, finding the virus outside of the nasopharynx is unlikely because of the acidic environment of the stomach and the temperature elevation in both the lower respiratory and gastrointestinal tracts.

Frequency:

• In the US: Incidence of rhinoviral infection averages 1 episode every 1-2 years per person. Rhinoviruses cause up to 80% of colds during the autumn months in temperate climates.

• Internationally: Rhinoviruses have been found in all countries, even in remote areas such as the Kaluhi Islands and the Amazon. In Brazil, rhinoviruses reportedly cause 46% of acute respiratory infections.

Mortality/Morbidity: Although not associated with fatal disease, rhinoviruses are associated with significant morbidity rates. Acute respiratory infections, predominantly rhinovirus infections, are estimated to cause 30-50% of time lost from work by adults and 60-80% of time lost from school by children. Complications of rhinovirus infections include otitis media, sinusitis, chronic bronchitis, and exacerbations of reactive airway disease in children and adults. These viruses are possibly involved in lower respiratory tract infections in elderly persons, infants, patients with cystic fibrosis, and patients who are immunosuppressed. The true impact of lower respiratory tract infection is not clear. Recovery of rhinovirus in these patients may be a marker of an underlying disease process or a precursor to a bacterial infection.

Race: No difference in susceptibility to infection or disease course has been described amongst different races.

Sex: Some reports indicate a male predominance of infection in children younger than 3 years, which switches to a female predominance in children older than 3 years. No difference in rates of infection in adults is apparent.

Age: Disease occurs most frequently in children, with decreasing incidence as they approach adulthood. Children are instrumental in transmission of infection, commonly passing infection to family members after contracting the virus in nurseries, day care facilities, or schools.

	CLINICAL	Section 3 of 9
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History: Rhinoviral infections are typically indistinguishable from colds of other viral etiologies. Individual patients exhibit a wide variety of signs and symptoms.

• The incubation period is 12-72 hours, averaging 8-16 hours after viral inoculation of the nose. Symptomatic complaints 2 hours after viral inoculation have been described.

• Illness initially begins with a sore throat, which is frequently the most bothersome of the early symptoms. This is followed by nasal discharge, nasal congestion, and sneezing, which intensify over the next 2-3 days.

• Other associated complaints include headache, facial and ear pressure, and loss of smell and taste.

• Cough occurs in 30% of patients and hoarseness in 20%, both of which may persist up to a week, although they seldom become bothersome until nasal symptoms improve.

• Systemic signs and symptoms, such as fever and malaise, are unusual. If they are present, consider an alternative diagnosis.

• Symptoms generally last 7-11 days, although they persist up to 2 weeks in a quarter of patients. Rarely, patients may complain of lingering symptoms that last more than 30 days.

• Infants and toddlers may display only nasal discharge.

• Most patients have obstruction and mucosal abnormalities of sinuses, eustachian tubes, and middle ear, which causes a predisposition to secondary bacterial infection in up to 2% of patients.

• Infection may exacerbate underlying asthma and chronic pulmonary disease.

• People who smoke do not appear to have more frequent rhinovirus infections; however, their infections are more severe with longer duration of symptoms.

Physical: The physical examination is typically unimpressive compared to the subjective complaints of the patient.

• Red nose with dripping nasal discharge may be present.

• Nasal mucous membranes have a glistening, glassy appearance without obvious erythema and edema. Yellow or green nasal discharge does not indicate bacterial infection because a large number of white blood cells migrate to the site of viral infection.

• If marked erythema, edema, exudates, or small vesicles are observed in the oropharynx or if conjunctivitis or polyps in the nasal mucosa occur, consider other etiologies, including adenovirus, herpes simplex virus, mononucleosis, diphtheria, Coxsackie A virus, or group A streptococcus (GAS).

• Auscultation of the chest may reveal rhonchi.

Causes:

• Rhinovirus transmission occurs with close exposure to infected respiratory secretions, including hand-to-hand, self-inoculation of eyes or nose, and, possibly, large- and small-particle aerosolization. The virus has been cultured from the skin for up to 2 hours and up to 4 days on inanimate objects in ideal conditions. Donors are typically symptomatic with a cold at the time of transmission, and virus is detected on their hands and nasal mucosa.

• Higher rates occur in humid, crowded conditions, as found in nurseries, day care centers, and schools, especially during cooler months in temperate regions and rainy season in tropical regions.

• Transmission does not appear to be related to cold temperature exposure, fatigue, or sleep deprivation.