Upper Respiratory Tract Infection

Updated: Feb 17, 2017

Author: Anne Meneghetti, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP more...

OVERVIEW

Practice Essentials
Upper respiratory tract infection (URI) represents the most common acute illness
evaluated in the outpatient setting. URIs range from the common coldtypically a mild,
self-limited, catarrhal syndrome of the nasopharynxto life-threatening illnesses such as
epiglottitis (see the image below).

Lateral neck radiograph demonstrates epiglottitis. Courtesy of Marilyn Goske, MD, Cleveland Clinic
Foundation.
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Signs and symptoms

Details of the patient's history aid in differentiating a common cold from conditions that
require targeted therapy, such as group A streptococcal pharyngitis, bacterial sinusitis,
and lower respiratory tract infections. Clinical manifestations of these conditions, as well
as allergy, show significant overlap.

Viral nasopharyngitis
Patients with the common cold may have a paucity of clinical findings despite notable
subjective discomfort. Findings may include the following:

Nasal mucosal erythema and edema are common

Nasal discharge: Profuse discharge is more characteristic of viral infections than
bacterial infections; initially clear secretions typically become cloudy white, yellow,
or green over several days, even in viral infections
Foul breath
Fever: Less common in adults but may be present in children with rhinoviral
infections

Group A streptococcal pharyngitis The following physical findings suggest a high risk for
group A streptococcal disease [1] :

Erythema, swelling, or exudates of the tonsils or pharynx

Temperature of 38.3C (100.9F) or higher
Tender anterior cervical nodes (1 cm)
Absence of conjunctivitis, cough, and rhinorrhea, which are symptoms that may
suggest viral illness [2]

Acute bacterial rhinosinusitis In children, acute bacterial sinusitis is defined as a URI with
any of the following [3] :

Persistent nasal discharge (any type) or cough lasting 10 days or more without
improvement
Worsening course (new or worse nasal discharge, cough, fever) after initial
improvement
Severe onset (fever of 102 or greater with nasal discharge) for at least 3
consecutive days

In older children and adults, symptoms (eg, pain, pressure) tend to localize to the
affected sinus.

Epiglottitis

This condition is more often found in children aged 1-5 years, who present with a sudden
onset of the following symptoms:

Sore throat
Drooling, difficulty or pain during swallowing, globus sensation of a lump in the
throat
Muffled dysphonia or loss of voice
Dry cough or no cough, dyspnea
Fever, fatigue or malaise (may be seen with any URI)
Tripod or sniffing posture

Laryngotracheitis and laryngotracheobronchitis

Nasopharyngitis often precedes laryngitis and tracheitis by several days

Swallowing may be difficult or painful
Patients may experience a globus sensation of a lump in the throat
Hoarseness or loss of voice is a key manifestation of laryngeal involvement

Features of whooping cough (pertussis) are as follows:

 The classic whoop sound [4] is an inspiratory gasping squeak that rises in pitch,
typically interspersed between hacking coughs
The whoop is more common in children
Coughing often comes in paroxysms of a dozen coughs or more at a time and is
often worst at night

The 3 classic phases of whooping cough are as follows:

Catarrhal (7-10 days) with predominantly URI symptoms

Paroxysmal (1-6 weeks) with episodic cough
Convalescent (7-10 days) of gradual recovery [5]

See Clinical Presentation for more detail.

Diagnosis

Tests of nasopharyngeal specimens for specific pathogens are helpful when targeted
therapy depends on the results (eg, group A streptococcal infection, gonococcus,
pertussis). Specific bacterial or viral testing is also warranted in other selected situations,
such as when patients are immunocompromised, during certain outbreaks, or to provide
specific therapy to contacts.

Diagnosis of specific disorders is based on the following:

Group A streptococcal infection: Clinical findings or a history of exposure to a case,

supported by results of rapid-detection assays and cultures (positive rapid antigen
detection tests do not necessitate a backup culture)
Acute bacterial rhinosinusitis: Laboratory studies are generally not indicated;
Computed tomography (CT) scanning or other sinus imaging may be appropriate if
symptoms persist despite therapy or if complications (eg, extension of disease into
surrounding tissue) are suspected
Influenza: Rapid tests have over 70% sensitivity and more than 90% specificity
Mononucleosis: Heterophile antibody testing (eg, Monospot)
Herpes simplex virus infection: Cell culture or polymerase chain reaction (PCR)
assay
Pertussis: Rapid tests; culture of a nasopharyngeal aspirate (criterion standard)
Epiglottitis: Direct visualization by laryngoscopy, performed by an
otorhinolaryngologist
Gonococcal pharyngitis: Throat culture for Neisseria gonorrhoeae

Blood cultures are typically appropriate only in hospitalized patients with suspected
systemic illness. Imaging studies are warranted in patients with suspected mass lesions
(eg, peritonsillar abscess, intracranial suppurative lesions).

See Workup for more detail.

Management

Symptom-basedtherapy represents the mainstay of URI treatment in immunocompetent

adults. Antimicrobial or antiviral therapy is appropriate in selected patients.

Epiglottitis
 Immediately admit the patient to the nearest hospital
Avoid instrumentation; insertion of tongue depressors or other instruments may
provoke airway spasm and precipitate respiratory compromise
Monitor for respiratory fatigue, visually and with continuous pulse oximetry
Administer oxygen according to pulse oximetry results
Have equipment and personnel available for immediate intubation if necessary
Start intravenous (IV) antibiotics after collecting culture specimens
Empiric coverage for Haemophilus influenzae is appropriate; common choices
include ceftriaxone or other third-generation cephalosporins, cefuroxime, and
cefamandole
Correct volume deficits with IV fluids; avoid sedatives

Laryngotracheitis

Hospitalization may be necessary, especially in infants and young children who

have hypoxemia, volume depletion, a risk of airway compromise, or respiratory
fatigue
Mild cases of croup (ie, laryngotracheobronchitis) may be managed at home with
moist air inhalation
Hospitalized patients require monitoring for respiratory fatigue, visually and with
continuous pulse oximetry
Expertise for immediate intubation and access to the necessary equipment are
required if respiratory failure is a possibility
Administer humidified oxygen to all hypoxemic patients. In patients who do not
require oxygen therapy, a cool-mist humidifier may be used
IV or oral glucocorticoids are commonly used to reduce symptoms and shorten
hospitalization in patients with moderate to severe croup
Inhaled racemic epinephrine may temporarily dilate the airways

Rhinosinusitis

Most cases of acute rhinosinusitis, including mild and moderate bacterial sinusitis,
resolve without antibiotics [6]
Consider antibiotic treatment if symptoms persist without improving for 10 or more
days, or if symptoms are severe or worsening during a period of 3-4 days or longer
[7]

Give first-line antibiotics for 5-7 days in most adults; for 10-14 days in children
Begin treatment with an agent that most narrowly covers likely pathogens, including
Streptococcus pneumoniae, nontypeable H influenzae, and Moraxella catarrhalis
Initial first-line options include amoxicillin/clavulanate
Alternatives in penicillin-allergic patients are doxycycline and respiratory
fluoroquinolones (eg, levofloxacin, moxifloxacin)
In patients who worsen or do not improve after 3-5 days of empirical therapy,
consider resistant pathogens, structural abnormality, or noninfectious etiology
Adjunctive therapy for adults includes nasal saline irrigation and intranasal steroids

Group A streptococcal disease

Oral penicillin or amoxicillin for 10 days for patients without an allergy to penicillin
If compliance is a concern, consider a single IM injection of benzathine penicillin G
A first-generation cephalosporin may be used in patients with non-anaphylactic
penicillin allergy
 Options for penicillin-allergic patients include clindamycin or clarithromycin for 10
days or azithromycin for 5 days [2]

See Treatment and Medication for more detail.

Background
Upper respiratory tract infection (URI) represents the most common acute illness
evaluated in the outpatient setting. URIs range from the common coldtypically a mild,
self-limited, catarrhal syndrome of the nasopharynxto life-threatening illnesses such as
epiglottitis.

Viruses account for most URIs (see Etiology). Appropriate management in these cases
may consist of reassurance, education, and instructions for symptomatic home treatment.
Diagnostic tests for specific agents are helpful when targeted URI therapy depends on
the results (see Workup). Bacterial primary infection or superinfection may require
targeted therapy (see Treatment).

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. Further information can be found in the Medscape Reference
articles Acute Laryngitis, Acute Sinusitis, Allergic Rhinitis, Bacterial Tracheitis, Croup,
Epiglottitis, Pharyngitis, and Viral Pharyngitis.

Common URI terms are defined as follows:

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

Pathophysiology
URIs involve direct invasion of the mucosa lining the upper airway. Inoculation of bacteria
or viruses occurs when a persons hand comes in contact with pathogens and the person
then touches the nose or mouth or when a person directly inhales respiratory droplets
from an infected person who is coughing or sneezing.

After inoculation, viruses and bacteria encounter several barriers, including physical,
mechanical, humoral, and cellular immune defenses. Physical and mechanical barriers
include the following:

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; from there they are 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
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 to 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.

Inflammation (chronic or acute) from allergy predisposes to URI. Children with allergy are
particularly subject to frequent URIs.

Infection

Person-to-person spread of viruses accounts for most URIs. Household and child care
settings can serve as reservoirs for infection. Bacterial infections may develop de novo or
as a superinfection of a viral URI.

Viral agents occurring in URIs 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,
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 URIsincluding local swelling, erythema, edema, secretions, and

feverresult 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 the

following:

Sinusitis
Otitis media
Epiglottitis
Laryngitis
Tracheobronchitis
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.

Susceptibility

Genetic susceptibility is involved in determining which patients have more severe disease
courses than others. There are some recognized candidate gene polymorphisms with
known functional changes in genes that may lead to immunosuppression. [8] It has also
been shown that host immunogenetic variation plays a role in the immune response to
H1N1 and H5N1 viruses, thereby influencing disease severity and outcome in influenza
caused by these viruses. [9, 10]

Etiology
Most URIs are viral in origin. Typical viral agents that cause URIs include the following:

Rhinoviruses
Coronaviruses
Adenoviruses
Coxsackieviruses

For the most part, similar agents cause URI in adults and children; however, Moraxella
catarrhalis and bocavirus cause URIs more commonly in children than in adults.

Nasopharyngitis

Of the more than 200 viruses known to cause the symptoms of the common cold, the
principal ones are as follows:

Rhinoviruses: These cause approximately 30-50% of colds in adults; they grow

optimally at temperatures near 32.8C (91F), which is the temperature inside the
human nares
Coronaviruses: While they are a significant cause of colds, exact case numbers are
difficult to determine because, unlike rhinoviruses, coronaviruses are difficult to
culture in the laboratory
Enteroviruses, including coxsackieviruses, echoviruses, and others

Other viruses that account for many URIs include the following:

Adenoviruses
Orthomyxoviruses (including influenza A and B viruses)
Paramyxoviruses (eg, parainfluenza virus [PIV])
RSV
EBV
Human metapneumovirus (hMPV)
Bocavirus: Commonly associated with nasopharyngeal symptoms in children [11]

Unidentified, but presumably viral, pathogens account for more than 30% of common
colds in adults. In addition, varicella, rubella, and rubeola infections may manifest as
nasopharyngitis before other classic signs and symptoms develop.
Pharyngitis

This is most often viral in origin. Recognition of group A streptococcal pharyngitis is vital
because serious complications may follow untreated disease.

Viral causes of pharyngitis include the following:

Adenovirus: May also cause laryngitis and conjunctivitis

Influenza viruses
Coxsackievirus
Herpes simplex virus (HSV)
EBV (infectious mononucleosis)
Cytomegalovirus (CMV)

Bacterial causes of pharyngitis include the following:

Group A streptococci (approximately 5-15% of all cases of pharyngitis in adults; 20-

30% in children) [2]
Group C and G streptococci
Neisseria gonorrhoeae
Arcanobacterium ( Corynebacterium) hemolyticum
Corynebacterium diphtheriae
Atypical bacteria (eg, Mycoplasma pneumoniae and Chlamydia pneumoniae;
absent lower respiratory tract disease, the clinical significance of these pathogens
is uncertain)
Anaerobic bacteria

Rhinosinusitis

Rhinosinusitis in an immunocompetent person is typically related to an uncomplicated

viral URI. Viral causes are similar to those of viral nasopharyngitis and include the
following:

Rhinovirus
Enterovirus
Coronavirus
Influenza A and B virus
PIV
RSV
Adenovirus

Bacterial causes are similar to those seen in otitis media. Bacterial pathogens isolated
from maxillary sinus aspirates of patients with acute bacterial rhinosinusitis include the
following [7] :

Streptococcus pneumoniae: 38% in adults, 21-33% in children

Haemophilus influenzae: 36% in adults, 31-32% in children
Moraxella catarrhalis: 16% in adults; 8-11% in children
Staphylococcus aureus: 13% in adults, 1% in children

Other pathogens include group A streptococci and other streptococcal species.

Uncommon causes include C pneumoniae, Neisseria species, anaerobes, and gram-
negative rods.
Nosocomial sinusitis often involves pathogens that colonize the upper respiratory tract
and migrate into the sinuses. Prolonged endotracheal intubation places patients at
increased risk for nosocomial sinusitis. Methicillin-resistant S aureus (MRSA) is less
common than sensitive staphylococci. [7] Gram-negative bacilli (eg, Escherichia
coli,Pseudomonas aeruginosa) are other causes.

Aspergillus species are the leading causes of noninvasive fungal sinusitis. Although fungi
are part of the normal flora of the upper airways, they may cause acute sinusitis in
patients with immunocompromise or diabetes mellitus.

Epiglottitis

This is a bacterial infection. In the vast majority of children, H influenzae type b (Hib) is
isolated from blood or epiglottal cultures. Since the routine use of the Hib conjugate
vaccine began in 1990, case rates in children younger than 5 years have declined by
more than 95%. The prevalence of invasive Hib disease is approximately 1.3 cases per
100,000 children. [12] Rates in adults have remained low and stable; Alaskan Natives have
the highest rates of disease.

Other bacteria, found more commonly in adults than in children, include group A
streptococci, S pneumoniae, and M catarrhalis. In adults, cultures are most likely to be
negative.

Laryngotracheitis

Croup, or laryngotracheobronchitis, is typically caused by PIV type 1, 2, or 3. PIVs

account for up to 80% of croup cases. PIV type 1 is the leading cause of croup in
children. [13] Other viruses include influenza viruses and RSV. Uncommon causes include
hMPV, adenovirus, rhinovirus, enterovirus (including coxsackievirus and enteric
cytopathic human orphan [ECHO] viruses), and measles virus.

Approximately 95% of all cases of whooping cough are caused by the gram-negative rod
Bordetella pertussis. The remaining cases result from B parapertussis.

Other forms of laryngitis and laryngotracheitis are typically caused by viruses similar to
those that cause nasopharyngitis, including rhinovirus, coronavirus, adenovirus, influenza
virus, parainfluenza virus, and RSV. Candida species may cause laryngitis in
immunocompromised hosts.

Bacterial laryngitis is far less common than viral laryngitis. [14] Bacterial causes include the
following:Group A streptococci

Corynebacterium diphtheriae, an aerobic gram-positive rod that may infect only the
larynx or may represent an extension of nasopharyngeal infection
Chlamydia pneumoniae
Mycoplasma pneumoniae
Moraxella catarrhalis
H influenzae
S aureus
Mycobacterium tuberculosis: Tuberculosis has been reported in renal transplant
recipients and human immunodeficiency virus (HIV) infected patients
Risk factors for URIs

Risk factors for contracting a URI include the following:

Contact: Close contact with small children who frequent group settings, such as
school or daycare, increases the risk of URI, as does the presence of URI in the
household or family
Inflammation: Inflammation and obstruction from allergic rhinitis or asthma can
predispose to infections
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: 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, previous upper airway trauma, and
nasal polyposis
Carrier state: Although some people are chronic carriers of group A streptococci,
repeated URIs in such patients may be viral in origin [2]

Epidemiology
URIs are the most common infectious illness in the general population and are the
leading cause of missed days at work or school. They represent the most frequent acute
diagnosis in the office setting. [15]

Nasopharyngitis

The incidence of the common cold varies by age. Rates are highest in children younger
than 5 years. Children who attend school or day care are a large reservoir for URIs, and
they transfer infection to the adults who care for them. In the first year after starting at a
new school or day care, children experience more infections, as do their family members.
Children have about 3-8 viral respiratory illnesses per year, adolescents and adults have
approximately 2-4 colds annually, and people older than 60 years have fewer than 1 cold
per year.

Pharyngitis

Acute pharyngitis accounts for 1% of all ambulatory office visits. [15] The incidence of viral
and bacterial pharyngitis peaks in children aged 4-7 years.

Rhinosinusitis

Sinusitis is common in persons with viral URIs. Transient changes in the paranasal
sinuses are noted on computed tomography (CT) scans in more than 80% of patients
with uncomplicated viral URIs. [16] However, bacterial rhinosinusitis occurs as a
complication in only about 2% of persons with viral URIs. [17]
Epiglottitis

The occurrence of epiglottitis has decreased dramatically in the United States and other
developed nations since the introduction of Hib vaccine. A Swedish study documented
that the Hib vaccination program was associated with a decrease in the overall annual
incidence of acute epiglottitis from 4.5 cases to 0.98 cases per 100,000 population; the
incidence decreased in children and adults. However, the annual incidence of
pneumococcal epiglottitis in adults increased from 0.1 to 0.28 cases per 100,000
population over the same period. [18]

Laryngitis and laryngotracheitis

Croup, or laryngotracheobronchitis, may affect people of any age but usually occurs in
children aged 6 months to 6 years. The peak incidence is in the second year of life.
Thereafter, the enlarging caliber of the airway reduces the severity of the manifestations
of subglottic inflammation.

Vaccination has dramatically reduced rates of pertussis. However, the incidence of

whooping cough in the United States has increased steadily since 2007, reaching
approximately 9 cases per 100,000 population in 2010. Rates of pertussis are highest in
infants below age 1 year; adolescents and adults accounted for approximately 44% of the
27,550 cases of pertussis reported in the United States in 2010. [19]

Worldwide, pertussis has an estimated incidence of 48.5 million cases and causes nearly
295,000 deaths per year. In low-income countries, the case-fatality rate among infants
may be as high as 4%. [20]

Although pertussis is a nationally notifiable disease in the United States, many cases
likely go undiagnosed and unreported. On the other hand, challenges in laboratory
diagnosis and overreliance on polymerase chain reaction (PCR) assays have resulted in
reports of respiratory illness outbreaks mistakenly attributed to pertussis. [21]

Occurrence rate of selected pathogens

Group A streptococcal bacteria cause approximately 5-15% of all pharyngitis infections,

[2]
accounting for several million cases of streptococcal pharyngitis each year. This
infection is rarely diagnosed in children younger than 2 years.

Influenza affects approximately 5-20% of the US population during each flu season. [22]
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. [23]

Diphtheria rates fell dramatically in the United States after the advent of diphtheria
vaccine. Since 1980, the prevalence of diphtheria has been approximately 0.001 case
per 100,000 population. A confirmed case of the disease has not been reported in the
United States since 2003. [24] However, diphtheria remains endemic in developing
countries.
Seasonality

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. [25] Epidemics and mini-epidemics
are most common during cold months, with a peak incidence from late winter to early
spring.

Cold weather results in 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 that is 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 can occur throughout the
year but are most common in the late winter, spring, and early summer.

Seasonal variation of selected upper respiratory tract infection pathogens. PIV is parainfluenza
virus, RSV is respiratory syncytial virus, MPV is metapneumovirus, and Group A Strept is group A
streptococcal disease.
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Seasonal influenza typically lasts from November until March. Some PIVs have a biennial
pattern. The patterns for human PIV types 1-3 are as follows:

Human PIV type 1: Currently produces autumnal outbreaks in the United States
during odd-numbered years; the leading cause of croup in children
Human PIV type 2: May cause annual or biennial fall outbreaks
Human PIV type 3: Peak activity is during the spring and early summer months;
however, the virus may be isolated throughout the year. [13]
Human metapneumovirus (hMPV) infection may also occur year round, although the
infection rates peak between December and February.

Race- and sex-related demographics

No notable racial difference is observed with URIs. However, Alaskan Natives have rates
of Hib disease higher than those of other groups. [12]

Sexual disparities among URIs are as follows:

Rhinitis: Hormonal changes during the middle of the menstrual cycle and during
pregnancy may produce hyperemia of the nasal and sinus mucosa and increase
nasal secretions; URI may be superimposed over these baseline changes and may
increase the intensity of symptoms in some women
Nasopharyngitis: The common cold occurs frequently in women, especially those
aged 20-30 years [25] ; this frequency may represent increased exposure to small
children, who represent a large reservoir for URIs, but hormonal effects on the
nasal mucosa may also play a role
Epiglottitis: A male predominance is reported, with a male-to-female ratio of
approximately 3:2
Laryngotracheobronchitis, or croup: More common in boys than in girls, with a
male-to-female ratio of approximately 3:2

Age-related demographics

The incidence of the common cold varies by age. Rates are highest in children younger
than 5 years. Children have approximately 3-8 viral respiratory illnesses per year, while
adolescents and adults have approximately 2-4 colds a year, and people older than 60
years have fewer than 1 cold per year.

The age-related occurrence of other infections is as follows:

Viral and bacterial pharyngitis: Peaks in children aged 4-7 years.

Epiglottitis: Typically occurs in children aged 2-7 years and has a peak incidence in
those aged 3 years
Laryngotracheobronchitis (croup): As previously stated, it may affect people of any
age but usually occurs in children aged 6 months to 6 years; the peak incidence is
in the second year of life

Prognosis
URIs cause people to spend time away from their usual daily activities, but alone, these
infections rarely cause permanent sequelae or death. URIs may, however, serve as a
gateway to infection of adjacent structures, resulting in the following infections (and
others, as well):

Otitis media
Bronchitis
Bronchiolitis
Pneumonia
Sepsis
Meningitis
 Intracranial abscess

Serious complications may result in clinically significant morbidity and rare deaths.

Nasopharyngitis

A common cold may last up to 14 days, with symptoms averaging 7-11 days in duration.
[17]

Fever, sneezing, and sore throat typically resolve early, whereas cough and nasal
discharge are among the symptoms that last longest.

Attendance at day care may affect the duration of symptoms in young children. In one
study, the duration of viral URIs ranged from 6.6 days for children aged 1-2 years in
home care to 8.9 days for children younger than 1 year who were in day care. Young
children in day care were also more likely to have protracted respiratory symptoms
lasting more than 15 days. [26]

Most patients with influenza recover within a week, although cough, fatigue, and malaise
may persist for up to 2 weeks. For newborns, elderly persons, and patients with chronic
medical conditions, the flu may be life threatening. More than 200,000 people per year
are hospitalized because of complications of the flu, with 0.36 deaths per 100,000
patients occurring annually. [27] Influenza may be followed by bacterial superinfection.

Pharyngitis

Viral pharyngitis typically resolves in 1-2 weeks, but immunocompromised persons may
have a more severe course.

Untreated group A streptococcal pharyngitis can result in the following:

Acute rheumatic fever

Acute glomerulonephritis
Peritonsillar abscess
Toxic shock syndrome
Impetigo
Cellulitis or abscess
Otitis
Sinusitis
Conjunctivitis
Bronchitis

Mortality from group A streptococcal pharyngitis is rare, but serious morbidity or death
may result from one of its complications.

Streptococcal pharyngitis without complications rarely poses significant risk for morbidity.
However, retropharyngeal, intraorbital, or intracranial abscesses may cause serious
sequelae. The risk of mortality is significant in patients who progress to streptococcal
toxic shock syndrome, which is characterized by multiorgan failure and hypotension.

In patients with penicillin-sensitive streptococcal pharyngitis, symptomatic improvement is

expected within 24-72 hours if antibiotic treatment is started in the first 24 hours after
onset. Treatment failures are common and are mainly attributed to poor adherence,
antibiotic resistance, and untreated close contacts, usually within the household or family.

A chronic carrier state may develop with group A streptococcal infection. Eradicating the
pathogen is difficult in these cases; however, carriers without active symptoms are
unlikely to spread group A streptococci, and they are at low risk for developing rheumatic
fever.

Mononucleosis

With infectious mononucleosis from EBV, complete resolution of symptoms may take up
to 2 months. Acute symptoms rarely last more than 4 months. EBV typically remains
dormant throughout the patient's life. Reactivation of the virus is not usually symptomatic.

Rhinosinusitis

The prognosis is generally favorable for acute rhinosinusitis, and many cases appear to
resolve even without antibiotic therapy. As many as 70% of immunocompetent adults
with rhinosinusitis begin to improve within 2 weeks of presentation without antibiotics.
With antibiotics, up to 85% have improvement at 2 weeks. Complete resolution may take
weeks to months.

Sinusitis itself is rarely life threatening, but it can lead to serious complications if the
infection extends into surrounding deep tissue, including the following:

Orbital cellulitis
Subperiosteal abscess
Orbital abscess
Frontal and maxillary osteomyelitis
Subdural abscess
Meningitis
Brain abscess

Epiglottitis

Epiglottitis 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%.

The prognosis is favorable with appropriate airway management, and most patients
noticeably improve within 24-48 hours after antibiotics are started. Rarely, cases of
epiglottitis may recur. Recurrent symptoms raise concern about potential underlying
disorders, such as rheumatic conditions, sarcoidosis, and occult malignancy.

Laryngitis and laryngotracheitis

With croup, laryngotracheobronchitis typically begins to improve within 3-4 days.

Recovery is usually complete. However, patients may have a recurrence, including
during the same season.

Pertussis (whooping cough) leads to hospitalization in more than half of infants younger
than 12 months and particularly in infants younger than 6 months. Infants and young
children are most susceptible to severe courses that include respiratory compromise.
Of infants who are hospitalized with pertussis, approximately 50% have apnea, 20%
develop pneumonia, 1% have seizures, 1% die, and 0.3% have encephalopathy. [28]
Recovery from whooping cough is typically complete. However, paroxysms of coughing
may last for several weeks.

Complications

Most URIs are self-limited and resolve completely. However, a variety of conditions may
complicate a URI. Fluid loss may occur in patients unable to tolerate adequate oral intake
because of upper airway inflammation or may result from fever. Otitis media may
complicate 5% of colds in children and up to 2% of colds in adults [29]

Airway hyperreactivity may increase after a URI, resulting in new or exacerbated asthma.
Cough asthma, wherein a cough is the predominant manifestation of reactive airways
disease, may mimic ongoing infection. This may be diagnosed with pulmonary function
testing.

A postinfectious cough is defined as coughing that persists 3-8 weeks after the onset of a
URI in the absence of other clearly defined causes. Exacerbations of chronic obstructive
pulmonary disease, including emphysema and chronic bronchitis, may occur during and
after a URI. Upper airways cough syndrome (post-nasal drip) may result from upper
airway secretions dripping onto the pharynx. Epistaxis may also occur.

Lower respiratory tract disease and sepsis represent serious complications, especially in
patients with immunocompromise. Lower respiratory tract disease should be considered
when symptoms such as fever, cough, sputum, and malaise worsen progressively or
after initial transient improvement. Tachypnea and dyspnea are also signs of lower
respiratory involvement.

Viral infection and resulting inflammation may make an individual susceptible to

concomitant or sequential infection with a bacterial agent. Streptococcus pneumoniae,
Staphylococcus aureus, H influenzae, and Streptococcus pyogenes are common
superinfecting agents. Meningococci may cause superinfection with influenzal infections.

Inflammation of the larynx and trachea area may lead to airway compromise, especially
in children and in patients with narrowed airways due to congenital or acquired subglottic
stenosis. The work of breathing during epiglottitis or laryngotracheitis may lead to
respiratory failure. Sleep apnea may occur from hypertrophied tonsils.

Deep tissue infection may occur by extension of the infection into the orbit, middle ear,
cranium, or other areas. Peritonsillar abscess (quinsy) may complicate bacterial
pharyngitis, leading to difficulty swallowing and pain radiating to the ear. Retropharyngeal
abscess may also complicate pharyngitis. Lemierre syndrome is an extension of
pharyngitis that leads to a suppurative thrombophlebitis of the internal jugular vein; septic
thromboemboli may then spread throughout the body.

Complications of sinusitis include the following:

Orbital cellulitis
Subperiosteal abscess
Orbital abscess
Mastoiditis
Frontal or maxillary osteomyelitis
 Subdural abscess
Cavernous sinus thrombosis
Brain abscess

Suspect a deep tissue infection when a patient has orbital or periorbital swelling,
proptosis, impaired extraocular movements, or impaired vision. Signs of increased
intracranial pressure (eg, papilledema, altered mental status, neurologic findings) may
suggest intracranial involvement.

Encephalitis, meningitis, or subarachnoid hemorrhage may follow a URI. Osteomyelitis

may complicate persistent or recurrent sinusitis. Osteomyelitis may affect the orbital
plate, frontal bone, or sphenoid bone. Mucoceles are expanding cystic defects of the
paranasal sinuses that may result from prolonged sinusitis. Epiglottic abscess may result
from epiglottitis.

Lymphadenitis may follow or accompany URI. Guillain-Barr syndrome may manifest as

an ascending polyneuropathy a few days or weeks after a URI. In children or
adolescents, the use of aspirin during a viral infection may rarely cause Reye syndrome.
Aspirin is contraindicated for the management of fevers in children or adolescents.

URI, especially with fever, may increase the work of the heart, adding strain to persons
with suboptimal cardiovascular status, and can lead to cardiovascular decompensation.
Myositis or pericarditis may result from viral infection.

Hyperglycemia may occur during a URI in patients with diabetes. Rib fracture may be
seen following an episode of severe coughing, such as that associated with whooping
cough. Hernia may develop following an episode of severe coughing.

Cutaneous complications such as rash, cellulitis, and toxic shock syndrome may occur
with group A streptococcus. This pathogen can also be associated with
glomerulonephritis, acute rheumatic fever, and PANDAS syndrome (Pediatric
Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections).

Hemoptysis suggests the possibility of tuberculosis. A tuberculin skin test, chest

radiography, or both are appropriate in these patients.

Complications of specific conditions

Complications of group A streptococcal disease

Group A streptococcal pharyngitis is of special concern because its complications include

streptococcal toxic shock syndrome, acute rheumatic fever (ARF), acute
glomerulonephritis, and scarlet fever, as well as cutaneous infections. In addition, this
pathogen is readily transmissible, especially in households, families, and other intimate
groups.

ARF affects approximately 3% of patients with strep throat, primarily occurring in persons
aged 6-20 years. The condition develops approximately 2-4 weeks after streptococcal
pharyngitis occurs, and it may last several months. Signs of rheumatic fever include
arthritis, fever, and valvular disease. Uncommon features include an expanding truncal
exanthem (erythema marginata), subcutaneous nodules, and chorea.

Poststreptococcal glomerulonephritis can affect persons of any age group, but it is most
common in children aged 3-7 years. Boys are affected slightly more often than girls.
Patients with glomerulonephritis may have loss of appetite, lethargy, dull back pain, and
dark urine. Blood pressure may be elevated, and edema may occur.

Scarlet fever is a self-limited exanthem that spreads from the chest and abdomen to the
entire body. Tiny red papules create a rough skin texture similar to that of sandpaper.
The rash is typically blanching. Although it commonly affects the face, circumoral pallor is
present. During recovery, the skin on the fingers and toes peels. Streptococcal toxic
shock syndrome may also occur, affecting skin and mucosa.

PANDAS is a rare syndrome in children and adolescents, who experience sudden onset
or worsening of obsessive-compulsive disorder following streptococcal infection.
Associated manifestations include tics and a variety of neuropsychiatric symptoms. [30]

Complications of mononucleosis

Complications can include the following:

Splenic rupture
Hepatitis
Guillain-Barr syndrome
Encephalitis
Hemolytic anemia
Agranulocytosis
Myocarditis
Burkitt lymphoma
Nasopharyngeal carcinoma
Rash (with concomitant use of ampicillin)

Complications of diphtheria

Complications may include airway obstruction, myocarditis, polyneuritis,

thrombocytopenia, and proteinuria. Among patients who survive diphtheria, as many as
20% have permanent hearing loss or other long-term sequelae. [13]

Complications from pertussis

More than half of infants younger than 12 months who contract pertussis require
hospitalization, especially those who are younger than 6 months. Complications of
pertussis in hospitalized infants include the following [28] :

Apnea (50%)
Pneumonia (20%)
Seizures (1%)
Encephalopathy (0.3%)
Death (1%)

In addition, severe cough may result in rib fractures, hernia, incontinence, or

subconjunctival hemorrhages.

Complications of influenza

These include the following:

Bacterial superinfection
 Pneumonia
Volume depletion
Myositis
Pericarditis
Rhabdomyolysis
Encephalitis
Meningitis
Myelitis
Renal failure
Disseminated intravascular coagulation

As with any systemic infection, the flu poses a risk of worsening underlying medical
conditions, such as heart failure, asthma, or diabetes. After influenzal infection, children
may experience sinus problems or otitis media.

Patient Education
Address the patient's expectations about antibiotic therapy. Validate the patient's
symptoms and their severity, listen to the concerns expressed, and educate the patient
about possible consequences of inappropriate antibiotic use, including consequences
affecting him/her and the community.

Many people hold misperceptions about the duration and intensity of symptoms
associated with URI and about the benefits and risks of antibiotic therapy. Some are
unaware that cold symptoms may last as long as 14 days. Some believe that antibiotics
will help them to avoid serious disease and recover more quickly than without treatment.

Patients may expect to receive antibiotics solely based on the severity of their symptoms,
and they may not appreciate the negative consequences of using antibiotics in viral
disease. Negative results on a rapid strep test may provide reassurance about the
appropriateness of supportive care.

Actively promote self-care, and outline a realistic time course for the resolution of
symptoms. Reassure the patient about access to clinical care and follow-up in the event
that symptoms progress. Briefly explore factors that may have contributed to the current
infection, and address prevention for the future.

Patient satisfaction is less linked to antibiotic prescriptions and more linked to the quality
of the physician-patient interaction. Reflecting understanding of the details of the patient's
situation, expressing concern for the patient's well-being, explaining how
recommendations are appropriately tailored to the individual's current condition, and
providing reassurance are important to patient satisfaction.

Patients should be counseled on handwashing and proper methods of covering coughs

and sneezes. Patients who smoke should receive smoking cessation encouragement
and materials. When antibiotics are prescribed, patients should be instructed to complete
the full course of antibiotic therapy.

Patients should be instructed to follow up when indicated or if symptoms worsen. Finally,

patients with infectious mononucleosis should be instructed to avoid contact sports for 6
weeks because of the possibility of splenic rupture.
For patient education information, see the Headache and Migraine Center, as well as
Sinus Infection and Sore Throat.

Clinical Presentation