The upper respiratory tract includes the sinuses, nasal passages, pharynx, and larynx, which serve as gateways to the trachea, bronchi, and pulmonary alveolar spaces. Rhinitis, pharyngitis, sinusitis, epiglottitis, laryngitis, and tracheitis are specific manifestations of URIs.

Upper respiratory tract infection (URI) represents the most common acute illness evaluated in the outpatient setting. URIs range from the common cold--typically a mild, self-limited, catarrhal syndrome (excessive

secrection of thick phlegm or mucus) of the nasopharynx--to life-threatening illnesses such as epiglottitis (infection

of the epiglottis which swells and causes obstruction of the upper airways). Viruses account for most URIs. Bacterial primary infection or superinfection may require targeted therapy.

Rhinitis - Inflammation of the nasal mucosa

Rhinosinusitis or sinusitis - Inflammation of the nares and paranasal sinuses, including frontal, ethmoid, maxillary, and sphenoid

Nasopharyngitis (rhinopharyngitis or the common cold) - Inflammation of the nares, pharynx, hypopharynx, uvula, and tonsils

Pharyngitis - Inflammation of the pharynx, hypopharynx, uvula, and tonsils

Epiglottitis (supraglottitis) - Inflammation of the superior portion of the larynx and supraglottic area

Laryngitis - Inflammation of the larynx

Laryngotracheitis - Inflammation of the larynx, trachea, and subglottic area

Tracheitis - Inflammation of the trachea and subglottic area

URIs involve direct invasion of the mucosa lining the upper airway. Person-to-person spread of viruses accounts for most URIs. Patients with bacterial infections may present in similar fashion, or they may present with a superinfection of a viral URI. Inoculation by bacteria or viruses begins when secretions are transferred by touching a hand exposed to pathogens to the nose or mouth or by directly inhaling respiratory droplets from an infected person who is coughing or sneezing.

After inoculation, viruses and bacteria encounter several barriers, including physical, mechanical, humoral (circulating in the blood stream), and cellular immune defenses. Hair lining the nose filters and traps some pathogens. Mucus coats much of the upper respiratory tract, trapping potential invaders. The angle resulting from the junction of the posterior nose to the pharynx causes large particles to impinge on the back of the throat. Ciliated cells lower in the respiratory tract trap and transport pathogens up to the pharynx, where they are then swallowed into the stomach.

Adenoids and tonsils contain immune cells that respond to pathogens. Humoral immunity (immunoglobulin A) and cellular immunity act to reduce infections throughout the entire respiratory tract. Resident and recruited macrophages, monocytes, neutrophils, and eosinophilscoordinate to engulf and destroy invaders. A host of inflammatory cytokines mediates the immune response to invading pathogens. Normal nasopharyngeal flora, including various staphylococcal and streptococcal species, help defend against potential pathogens. Patients with suboptimal humoral and phagocytic immune function are at increased risk for contracting a URI, and they are at increased risk for a severe or prolonged course of disease.

Viral agents include a vast number of serotypes, which undergo frequent changes in antigenicity, posing challenges to immune defense. Pathogens resist destruction by a variety of mechanisms, including the production of toxins, proteases (enzymes that catalyze the

splitting of protein), and bacterial adherence factors, as well as the formation of capsules that resist phagocytosis.

Incubation times before the appearance of symptoms vary among pathogens. Rhinoviruses and group A streptococci may incubate for 1-5 days, influenza and parainfluenza may incubate for 1-4 days, and respiratory syncytial virus (RSV) may incubate for a week. Pertussis typically incubates for 7-10 days or even as long as 21 days before causing symptoms. Diphtheria incubates for 1-10 days. The incubation period of Epstein-Barr virus (EBV) is 4-6 weeks.

Most symptoms of URIs, including local swelling, erythema, edema, secretions, and fever, result from the inflammatory response of the immune system to invading pathogens and from toxins produced by pathogens. An initial nasopharyngeal infection may spread to adjacent structures, resulting in sinusitis, otitis media, epiglottitis, laryngitis, tracheobronchitis, and pneumonia. Inflammatory narrowing at the level of the epiglottis and larynx may result in a dangerous compromise of airflow, especially in children, in whom a small reduction in the luminal diameter of the subglottic larynx and trachea may be critical. Beyond childhood, laryngotracheal inflammation may also pose serious threats to individuals with congenital or acquired subglottic stenosis.

The incidence of the common cold varies by age. Rates are highest in children younger than 5 years. Children who attend school or daycare are a large reservoir for URIs, and they transfer infection to those who care for them. Children have about 3-8 viral respiratory illnesses per year. Adolescents and adults have approximately 2-4 colds a year, and people older than 60 years have fewer than 1 cold per year.

Acute pharyngitis accounts for 1% of all ambulatory office visits.1 The incidence of viral and bacterial pharyngitis peaks in children aged 4-7 years.

Sinusitis is common in persons with viral URIs. Transient changes in the paranasalsinuses are noted on CT scans in more than 80% of patients with uncomplicated viral URIs.However, bacterial rhinosinusitis is a complication in only approximately 2% of persons with viral URIs.

Epiglottitis occurs at a rate of 6-14 cases per 100,000 children, according to estimates from other countries.4 This condition typically occurs in children aged 2-7 years and has a peak incidence in those aged 3 years.5

Epiglottitis is estimated to occur at annual incidence of 9.7 cases per million adults.6 The occurrence of epiglottitis has decreased dramatically in the United States since the introduction of the Haemophilus influenzaetype B (Hib) vaccine.

Croup, or laryngotracheobronchitis, may affect people of any age, but it usually occurs in children aged 6 months to 6 years. The peak incidence is in the second year of life.5

Thereafter, the enlarging caliber of the airway reduces the severity of the manifestations of subglottic inflammation. Vaccination has dramatically reduced rates of pertussis, including whooping cough. However, the incidence of whooping cough cases in the United States has increased in recent years, reaching 5.3 cases per 100,000 population in 2006.7

Adolescents and infants younger than 5 months account for many of these cases. In 2004, adults aged 19-64 years accounted for 7,008 (27%) of 25,827 reported cases of pertussis in the United States. Challenges in laboratory diagnosis and overreliance on polymerase chain reaction (PCR) tests have resulted in recent reports of respiratory illness outbreaks mistakenly attributed to pertussis.

Group A streptococcal bacteria cause approximately 5-15% of all pharyngitis infections, accounting for several million cases of streptococcal pharyngitis each year. This infection is rarely diagnosed in children younger than 2 years.

Approximately 5-20% of Americans have the flu during each flu season.9 Early presentations include symptoms of URI.

EBV infection affects as many as 95% of American adults by age 35-40 years. Childhood EBV infection is indistinguishable from other transient childhood infections. Approximately 35-50% of adolescents and young adults who contract EBV infection have mononucleosis.10

After the advent of the diphtheria vaccine, case rates dramatically decreased in the United States. Since 1980, the prevalence has been approximately 0.001 case per 100,000 population.11 Diphtheria remains endemic in developing countries. Sporadic cases have recently affected adults.

Although URIs may occur year round, in the United States, most colds occur during fall and winter. Beginning in late August or early September, rates of colds increase over several weeks and remain elevated until March or April.12

Epidemics and miniepidemics are most common during cold months, with a peak incidence in late winter to early spring. Cold weather means more time spent indoors (eg, at work, home, school) and close exposure to others who may be infected. Humidity may also affect the prevalence of colds, because most viral URI agents thrive in the low humidity characteristic of winter months. Low indoor air moisture may increase friability of the nasal mucosa, increasing a person's susceptibility to infection. Laryngotracheobronchitis, or croup, occurs in fall and winter. Seasonality does not affect rates of epiglottitis.

The figure below illustrates the peak incidences of various agents by season. Rhinoviruses, which account for a substantial percentage of URIs, are most active in spring, summer, and early autumn. Coronaviral URIs manifest primarily in the winter and early spring. Enteroviral URIs are most noticeable in summer and early fall, when other URI pathogens are at a nadir. Adenoviral respiratory infections are most common in the late winter, spring, and early summer, yet they can occur throughout the year.

Influenza season typically lasts from November until March. Some parainfluenza viruses (PIVs) have a biennial pattern. Human PIV type 1, the leading cause of croup in children, currently causes autumnal outbreaks in the United States during odd-numbered years. Human PIV type 2 may cause annual or biennial fall outbreaks. Peak activity for human PIV type 3 is during the spring and early summer months; however, the virus may be isolated throughout the year.11 Human metapneumovirus (hMPV) infection may also occur year round, peaking between December and February.

URIs cause people to spend time away from their usual daily activities. Alone, URIs rarely cause permanent sequelae (any disorder or pathological conditions

results from a preceding disease or accident) or death, although URIs may serve as a gateway to infection of adjacent structures, resulting in otitis media, bronchitis, bronchiolitis, pneumonia, sepsis, meningitis, intracranial abscess, and other infections. Serious complications may result in clinically significant morbidity and rare deaths.

Common cold: This is the leading cause of acute morbidity and missed days from school or work. The common cold is also the leading acute cause of office visits to a physician in the United States.

Untreated group A streptococcal pharyngitis: This infection can result in acute rheumatic fever (ARF), acute glomerulonephritis, peritonsillar abscess, and toxic shock syndrome. Mortality from group A streptococcal pharyngitis is rare, but serious morbidity or death may result from one of its complications. Pharyngitiswithout complications rarely poses significant risk for morbidity. However, retropharyngeal, intraorbital, or intracranial abscesses may cause serious sequelae.

Sinusitis: The condition itself is rarely life threatening, but sinusitis can lead to serious complications if the infection extends into surrounding deep tissue. Examples include orbital cellulitis, subperiosteal abscess, orbital abscess, frontal and maxillary osteomyelitis, subdural abscess, meningitis, and brain abscess.

Epiglottitis: This infection poses a risk of death due to sudden airway obstruction and other complications, including septic arthritis, meningitis, empyema, and mediastinitis. In adults, epiglottitis has a fatality rate of approximately 1%.

Selected pathogens◦ Approximately 3-6% of cases of Hib disease are fatal.

◦ Each year, more than 200,000 people are hospitalized for influenza and approximately 36,000 people die from the flu and its complications.9

◦ Complications from whooping cough, or pertussis, reported from 2001-2003 included 56 pertussis-related deaths. Fifty-one (91%) of these deaths were among infants younger than 6 months, and 42 (75%) were among infants younger than 2 months.13

◦ Approximately 5-10% of patients with diphtheria die. Fatality rates up to 20% are reported in patients younger than 5 years or older than 40 years.13

Contact: Close contact with small children who frequent group settings, such as school or daycare, increases the risk of URI.

Travel: The incidence of contracting a URI is increased because of exposure to large numbers of individuals in closed settings.

Smoking and exposure to second-hand smoke: These may alter mucosal resistance to URI.

Immunocompromise that affects cellular or humoralimmunity: This increases the likelihood of contracting a URI. Weakened immune function may result from splenectomy, HIV infection, use of corticosteroids, immunosuppressive treatment after stem cell or organ transplantation, multiple medical problems, or common stress. Cilia dyskinesia syndrome and cystic fibrosis also predispose individuals to URIs.

Anatomic changes due to facial dysmorphisms (abnormal structure), previous upper airway trauma, and nasal polyposis (numerous polyps form

in an organ or tissue) : These conditions may predispose individuals to URIs.

Carrier state: Some people are carriers for group A streptococci. Such individuals may have repeated URIs.