The upper respiratory tract includes structures like the sinuses, nasal passages, and larynx. Upper respiratory tract infections (URIs) range from mild illnesses like the common cold to more severe infections. Viruses cause most URIs, though some bacterial infections may require treatment. Common manifestations of URIs include rhinitis, sinusitis, pharyngitis, laryngitis, and others resulting from inflammation in different areas of the upper respiratory tract. URIs spread through person-to-person contact and begin when viruses or bacteria are able to bypass the body's defenses in the nose and throat and multiply in the upper respiratory mucosa.

2.  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.

5.  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.

6.  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

7.  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

9.  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.

10.  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.

11.  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 eosinophils
coordinate 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.

12.  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.

13.  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.

14.  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.

15.  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.

16.  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.

17.  Sinusitis is common in persons with viral
URIs. Transient changes in the paranasal
sinuses 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.

18.  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 influenzae
type B (Hib) vaccine.

19.  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

20.  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.

21.  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.

22.  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.

23.  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.

25.  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.

26.  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.

27.  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. Pharyngitis
without 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.

28.  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%.

29.  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

30.  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 humoral
immunity: 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.

31.  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.