5/27/2016 Upper Respiratory Tract Infection: Practice Essentials, Background, Pathophysiology

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Upper Respiratory Tract InfectionAuthor: Anne Meneghetti, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP more...

Updated: Jul 31, 2015

Practice EssentialsUpper respiratory tract infection (URI) represents the most common acute illnessevaluated in the outpatient setting. URIs range from the common cold—typically amild, selflimited, catarrhal syndrome of the nasopharynx—to lifethreateningillnesses such as epiglottitis (see the image below).

Lateral neck radiograph demonstrates epiglottitis. Courtesy of Marilyn Goske, MD, ClevelandClinic Foundation.

Signs and symptoms

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

Viral nasopharyngitis

Patients with the common cold may have a paucity of clinical findings despitenotable subjective discomfort. Findings may include the following:

Nasal mucosal erythema and edema are commonNasal discharge: Profuse discharge is more characteristic of viral infectionsthan bacterial infections; initially clear secretions typically become cloudywhite, yellow, or green over several days, even in viral infectionsFoul breathFever: Less common in adults but may be present in children with rhinoviralinfections

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

Erythema, swelling, or exudates of the tonsils or pharynxTemperature of 38.3°C (100.9°F) or higherTender anterior cervical nodes (≥1 cm)Absence of conjunctivitis, cough, and rhinorrhea, which are symptoms thatmay suggest viral illness [2]

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

Persistent nasal discharge (any type) or cough lasting 10 days or morewithout improvementWorsening course (new or worse nasal discharge, cough, fever) after initialimprovementSevere onset (fever of 102° or greater with nasal discharge) for at least 3consecutive days

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

Epiglottitis

This condition is more often found in children aged 15 years, who present with asudden onset of the following symptoms:

Sore throat

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Drooling, difficulty or pain during swallowing, globus sensation of a lump inthe throatMuffled dysphonia or loss of voiceDry cough or no cough, dyspneaFever, fatigue or malaise (may be seen with any URI)Tripod or sniffing posture

Laryngotracheitis and laryngotracheobronchitis

Nasopharyngitis often precedes laryngitis and tracheitis by several daysSwallowing may be difficult or painfulPatients may experience a globus sensation of a lump in the throatHoarseness 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 inpitch, typically interspersed between hacking coughsThe whoop is more common in childrenCoughing often comes in paroxysms of a dozen coughs or more at a timeand is often worst at night

The 3 classic phases of whooping cough are as follows:

Catarrhal (710 days) with predominantly URI symptomsParoxysmal (16 weeks) with episodic coughConvalescent (710 days) of gradual recovery [5]

See Clinical Presentation for more detail.

Diagnosis

Tests of nasopharyngeal specimens for specific pathogens are helpful whentargeted therapy depends on the results (eg, group A streptococcal infection,gonococcus, pertussis). Specific bacterial or viral testing is also warranted in otherselected situations, such as when patients are immunocompromised, during certainoutbreaks, 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 acase, supported by results of rapiddetection assays and cultures (positiverapid 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 beappropriate if symptoms persist despite therapy or if complications (eg,extension of disease into surrounding tissue) are suspectedInfluenza: Rapid tests have over 70% sensitivity and more than 90%specificityMononucleosis: Heterophile antibody testing (eg, Monospot)Herpes simplex virus infection: Cell culture or polymerase chain reaction(PCR) assayPertussis: Rapid tests; culture of a nasopharyngeal aspirate (criterionstandard)Epiglottitis: Direct visualization by laryngoscopy, performed by anotorhinolaryngologistGonococcal pharyngitis: Throat culture for Neisseria gonorrhoeae

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

See Workup for more detail.

Management

Symptombasedtherapy represents the mainstay of URI treatment inimmunocompetent adults. Antimicrobial or antiviral therapy is appropriate inselected patients.

Epiglottitis

Immediately admit the patient to the nearest hospitalAvoid instrumentation; insertion of tongue depressors or other instrumentsmay provoke airway spasm and precipitate respiratory compromiseMonitor for respiratory fatigue, visually and with continuous pulse oximetryAdminister oxygen according to pulse oximetry resultsHave equipment and personnel available for immediate intubation ifnecessaryStart intravenous (IV) antibiotics after collecting culture specimensEmpiric coverage for Haemophilus influenzae is appropriate; commonchoices include ceftriaxone or other thirdgeneration cephalosporins,cefuroxime, and cefamandoleCorrect volume deficits with IV fluids; avoid sedatives

Laryngotracheitis

Hospitalization may be necessary, especially in infants and young childrenwho have hypoxemia, volume depletion, a risk of airway compromise, orrespiratory fatigueMild cases of croup (ie, laryngotracheobronchitis) may be managed at homewith moist air inhalationHospitalized patients require monitoring for respiratory fatigue, visually andwith continuous pulse oximetryExpertise for immediate intubation and access to the necessary equipmentare required if respiratory failure is a possibility

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Administer humidified oxygen to all hypoxemic patients. In patients who donot require oxygen therapy, a coolmist humidifier may be usedIV or oral glucocorticoids are commonly used to reduce symptoms andshorten hospitalization in patients with moderate to severe croupInhaled racemic epinephrine may temporarily dilate the airways

Rhinosinusitis

Most cases of acute rhinosinusitis, including mild and moderate bacterialsinusitis, resolve without antibiotics [6]Consider antibiotic treatment if symptoms persist without improving for 10 ormore days, or if symptoms are severe or worsening during a period of 34days or longer [7]Give firstline antibiotics for 57 days in most adults; for 1014 days inchildrenBegin treatment with an agent that most narrowly covers likely pathogens,including Streptococcus pneumoniae, nontypeable H influenzae, andMoraxella catarrhalisInitial firstline options include amoxicillin/clavulanateAlternatives in penicillinallergic patients are doxycycline and respiratoryfluoroquinolones (eg, levofloxacin, moxifloxacin)In patients who worsen or do not improve after 35 days of empirical therapy,consider resistant pathogens, structural abnormality, or noninfectious etiologyAdjunctive therapy for adults includes nasal saline irrigation and intranasalsteroids

Group A streptococcal disease

Oral penicillin or amoxicillin for 10 days for patients without an allergy topenicillinIf compliance is a concern, consider a single IM injection of benzathinepenicillin GA firstgeneration cephalosporin may be used in patients with nonanaphylactic penicillin allergyOptions for penicillinallergic patients include clindamycin or clarithromycinfor 10 days or azithromycin for 5 days [2]

See Treatment and Medication for more detail.

BackgroundUpper respiratory tract infection (URI) represents the most common acute illnessevaluated in the outpatient setting. URIs range from the common cold—typically amild, selflimited, catarrhal syndrome of the nasopharynx—to lifethreateningillnesses such as epiglottitis.

Viruses account for most URIs (see Etiology). Appropriate management in thesecases may consist of reassurance, education, and instructions for symptomatichome treatment. Diagnostic tests for specific agents are helpful when targeted URItherapy depends on the results (see Workup). Bacterial primary infection orsuperinfection may require targeted therapy (see Treatment).

The upper respiratory tract includes the sinuses, nasal passages, pharynx, andlarynx, which serve as gateways to the trachea, bronchi, and pulmonary alveolarspaces. Rhinitis, pharyngitis, sinusitis, epiglottitis, laryngitis, and tracheitis arespecific manifestations of URIs. Further information can be found in the MedscapeReference articles Acute Laryngitis, Acute Sinusitis, Allergic Rhinitis, BacterialTracheitis, Croup, Epiglottitis, Pharyngitis, and Viral Pharyngitis.

Common URI terms are defined as follows:

Rhinitis: Inflammation of the nasal mucosaRhinosinusitis or sinusitis: Inflammation of the nares and paranasal sinuses,including frontal, ethmoid, maxillary, and sphenoidNasopharyngitis (rhinopharyngitis or the common cold): Inflammation of thenares, pharynx, hypopharynx, uvula, and tonsilsPharyngitis: Inflammation of the pharynx, hypopharynx, uvula, and tonsilsEpiglottitis (supraglottitis): Inflammation of the superior portion of the larynxand supraglottic areaLaryngitis: Inflammation of the larynxLaryngotracheitis: Inflammation of the larynx, trachea, and subglottic areaTracheitis: Inflammation of the trachea and subglottic area

PathophysiologyURIs involve direct invasion of the mucosa lining the upper airway. Inoculation ofbacteria or viruses occurs when a person’s hand comes in contact with pathogensand the person then touches the nose or mouth or when a person directly inhalesrespiratory 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 mechanicalbarriers include the following:

Hair lining the nose filters and traps some pathogensMucus coats much of the upper respiratory tract, trapping potential invadersThe angle resulting from the junction of the posterior nose to the pharynxcauses large particles to impinge on the back of the throatCiliated cells lower in the respiratory tract trap and transport pathogens up tothe pharynx; from there they are swallowed into the stomach

Adenoids and tonsils contain immune cells that respond to pathogens. Humoralimmunity (immunoglobulin A) and cellular immunity act to reduce infectionsthroughout the entire respiratory tract. Resident and recruited macrophages,monocytes, neutrophils, and eosinophils coordinate to engulf and destroy invaders.

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A host of inflammatory cytokines mediates the immune response to invadingpathogens. Normal nasopharyngeal flora, including various staphylococcal andstreptococcal species, help to defend against potential pathogens. Patients withsuboptimal humoral and phagocytic immune function are at increased risk forcontracting a URI, and they are at increased risk for a severe or prolonged course ofdisease.

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

Infection

Persontoperson spread of viruses accounts for most URIs. Household and childcare settings can serve as reservoirs for infection. Bacterial infections may developde novo or as a superinfection of a viral URI.

Viral agents occurring in URIs include a vast number of serotypes, which undergofrequent changes in antigenicity, posing challenges to immune defense. Pathogensresist destruction by a variety of mechanisms, including the production of toxins,proteases, and bacterial adherence factors, as well as the formation of capsulesthat resist phagocytosis.

Incubation times before the appearance of symptoms vary among pathogens.Rhinoviruses and group A streptococci may incubate for 15 days, influenza andparainfluenza may incubate for 14 days, and respiratory syncytial virus (RSV) mayincubate for a week. Pertussis typically incubates for 710 days, or even as long as21 days, before causing symptoms. Diphtheria incubates for 110 days. Theincubation period of EpsteinBarr virus (EBV) is 46 weeks.

Most symptoms of URIs—including local swelling, erythema, edema, secretions,and fever—result from the inflammatory response of the immune system toinvading pathogens and from toxins produced by pathogens.

An initial nasopharyngeal infection may spread to adjacent structures, resulting inthe following:

SinusitisOtitis mediaEpiglottitisLaryngitisTracheobronchitisPneumonia

Inflammatory narrowing at the level of the epiglottis and larynx may result in adangerous compromise of airflow, especially in children, in whom a small reductionin the luminal diameter of the subglottic larynx and trachea may be critical. Beyondchildhood, laryngotracheal inflammation may also pose serious threats to individualswith congenital or acquired subglottic stenosis.

Susceptibility

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

EtiologyMost URIs are viral in origin. Typical viral agents that cause URIs include thefollowing:

RhinovirusesCoronavirusesAdenovirusesCoxsackieviruses

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

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 3050% of colds in adults; theygrow optimally at temperatures near 32.8°C (91°F), which is the temperatureinside the human naresCoronaviruses: While they are a significant cause of colds, exact casenumbers are difficult to determine because, unlike rhinoviruses,coronaviruses are difficult to culture in the laboratoryEnteroviruses, including coxsackieviruses, echoviruses, and others

Other viruses that account for many URIs include the following:

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

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

Pharyngitis

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

Viral causes of pharyngitis include the following:

Adenovirus: May also cause laryngitis and conjunctivitisInfluenza virusesCoxsackievirusHerpes simplex virus (HSV)EBV (infectious mononucleosis)Cytomegalovirus (CMV)

Bacterial causes of pharyngitis include the following:

Group A streptococci (approximately 515% of all cases of pharyngitis inadults; 2030% in children) [2]Group C and G streptococciNeisseria gonorrhoeaeArcanobacterium ( Corynebacterium) hemolyticumCorynebacterium diphtheriaeAtypical bacteria (eg, Mycoplasma pneumoniae and Chlamydia pneumoniae;absent lower respiratory tract disease, the clinical significance of thesepathogens is uncertain)Anaerobic bacteria

Rhinosinusitis

Rhinosinusitis in an immunocompetent person is typically related to anuncomplicated viral URI. Viral causes are similar to those of viral nasopharyngitisand include the following:

RhinovirusEnterovirusCoronavirusInfluenza A and B virusPIVRSVAdenovirus

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

Streptococcus pneumoniae: 38% in adults, 2133% in childrenHaemophilus influenzae: 36% in adults, 3132% in childrenMoraxella catarrhalis: 16% in adults; 811% in childrenStaphylococcus 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 gramnegative rods.

Nosocomial sinusitis often involves pathogens that colonize the upper respiratorytract and migrate into the sinuses. Prolonged endotracheal intubation placespatients at increased risk for nosocomial sinusitis. Methicillinresistant S aureus(MRSA) is less common than sensitive staphylococci.[7] Gramnegative bacilli (eg,Escherichia coli,Pseudomonas aeruginosa) are other causes.

Aspergillus species are the leading causes of noninvasive fungal sinusitis. Althoughfungi are part of the normal flora of the upper airways, they may cause acutesinusitis 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 Hibconjugate vaccine began in 1990, case rates in children younger than 5 years havedeclined by more than 95%. The prevalence of invasive Hib disease isapproximately 1.3 cases per 100,000 children.[12] Rates in adults have remained lowand stable; Alaskan Natives have the highest rates of disease.

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

Laryngotracheitis

Croup, or laryngotracheobronchitis, is typically caused by PIV type 1, 2, or 3. PIVsaccount for up to 80% of croup cases. PIV type 1 is the leading cause of croup inchildren.[13] Other viruses include influenza viruses and RSV. Uncommon causesinclude hMPV, adenovirus, rhinovirus, enterovirus (including coxsackievirus andenteric cytopathic human orphan [ECHO] viruses), and measles virus.

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

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

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

Corynebacterium diphtheriae, an aerobic grampositive rod that may infectonly the larynx or may represent an extension of nasopharyngeal infectionChlamydia pneumoniaeMycoplasma pneumoniaeMoraxella catarrhalisH influenzaeS aureusMycobacterium tuberculosis: Tuberculosis has been reported in renaltransplant recipients and human immunodeficiency virus (HIV) infectedpatients

Risk factors for URIs

Risk factors for contracting a URI include the following:

Contact: Close contact with small children who frequent group settings, suchas school or daycare, increases the risk of URI, as does the presence of URIin the household or familyInflammation: Inflammation and obstruction from allergic rhinitis or asthmacan predispose to infectionsTravel: The incidence of contracting a URI is increased because of exposureto large numbers of individuals in closed settingsSmoking and exposure to secondhand smoke: These may alter mucosalresistance to URIImmunocompromise that affects cellular or humoral immunity: Weakenedimmune function may result from splenectomy, HIV infection, use ofcorticosteroids, immunosuppressive treatment after stem cell or organtransplantation, multiple medical problems, or common stress; ciliadyskinesia syndrome and cystic fibrosis also predispose individuals to URIsAnatomic changes due to facial dysmorphisms, previous upper airwaytrauma, and nasal polyposisCarrier state: Although some people are chronic carriers of group Astreptococci, repeated URIs in such patients may be viral in origin [2]

EpidemiologyURIs are the most common infectious illness in the general population and are theleading cause of missed days at work or school. They represent the most frequentacute diagnosis in the office setting.[15]

Nasopharyngitis

The incidence of the common cold varies by age. Rates are highest in childrenyounger than 5 years. Children who attend school or day care are a large reservoirfor URIs, and they transfer infection to the adults who care for them. In the firstyear after starting at a new school or day care, children experience more infections,as do their family members. Children have about 38 viral respiratory illnesses peryear, adolescents and adults have approximately 24 colds annually, and peopleolder than 60 years have fewer than 1 cold per year.

Pharyngitis

Acute pharyngitis accounts for 1% of all ambulatory office visits.[15] The incidence ofviral and bacterial pharyngitis peaks in children aged 47 years.

Rhinosinusitis

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

Epiglottitis

The occurrence of epiglottitis has decreased dramatically in the United States andother developed nations since the introduction of Hib vaccine. A Swedish studydocumented that the Hib vaccination program was associated with a decrease in theoverall annual incidence of acute epiglottitis from 4.5 cases to 0.98 cases per100,000 population; the incidence decreased in children and adults. However, theannual incidence of pneumococcal epiglottitis in adults increased from 0.1 to 0.28cases per 100,000 population over the same period.[18]

Laryngitis and laryngotracheitis

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

Vaccination has dramatically reduced rates of pertussis. However, the incidence ofwhooping cough in the United States has increased steadily since 2007, reachingapproximately 9 cases per 100,000 population in 2010. Rates of pertussis arehighest in infants below age 1 year; adolescents and adults accounted forapproximately 44% of the 27,550 cases of pertussis reported in the United States in2010.[19]

Worldwide, pertussis has an estimated incidence of 48.5 million cases and causesnearly 295,000 deaths per year. In lowincome countries, the casefatality rateamong infants may be as high as 4%.[20]

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

Occurrence rate of selected pathogens

Group A streptococcal bacteria cause approximately 515% of all pharyngitisinfections,[2] accounting for several million cases of streptococcal pharyngitis eachyear. This infection is rarely diagnosed in children younger than 2 years.

Influenza affects approximately 520% 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 3540 years.Childhood EBV infection is indistinguishable from other transient childhoodinfections. Approximately 3550% of adolescents and young adults who contractEBV infection have mononucleosis.[23]

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

Seasonality

Although URIs may occur year round, in the United States most colds occur duringfall and winter. Beginning in late August or early September, rates of colds increaseover several weeks and remain elevated until March or April.[25] Epidemics andminiepidemics are most common during cold months, with a peak incidence fromlate winter to early spring.

Cold weather results in more time spent indoors (eg, at work, home, school) andclose exposure to others who may be infected. Humidity may also affect theprevalence of colds, because most viral URI agents thrive in the low humidity that ischaracteristic of winter months. Low indoor air moisture may increase friability of thenasal mucosa, increasing a person's susceptibility to infection.

Laryngotracheobronchitis, or croup, occurs in fall and winter. Seasonality does notaffect 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 inspring, summer, and early autumn. Coronaviral URIs manifest primarily in the winterand early spring. Enteroviral URIs are most noticeable in summer and early fall,when other URI pathogens are at a nadir. Adenoviral respiratory infections canoccur throughout the year but are most common in the late winter, spring, and earlysummer.

Seasonal variation of selected upper respiratory tract infection pathogens. PIV is parainfluenzavirus, RSV is respiratory syncytial virus, MPV is metapneumovirus, and Group A Strept isgroup A streptococcal disease.

Seasonal influenza typically lasts from November until March. Some PIVs have abiennial pattern. The patterns for human PIV types 13 are as follows:

Human PIV type 1: Currently produces autumnal outbreaks in the UnitedStates during oddnumbered years; the leading cause of croup in childrenHuman PIV type 2: May cause annual or biennial fall outbreaksHuman PIV type 3: Peak activity is during the spring and early summermonths; however, the virus may be isolated throughout the year. [13]

Human metapneumovirus (hMPV) infection may also occur year round, although theinfection rates peak between December and February.

Race and sexrelated demographics

No notable racial difference is observed with URIs. However, Alaskan Natives haverates 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 andduring pregnancy may produce hyperemia of the nasal and sinus mucosaand increase nasal secretions; URI may be superimposed over these

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baseline changes and may increase the intensity of symptoms in somewomenNasopharyngitis: The common cold occurs frequently in women, especiallythose aged 2030 years [25] ; this frequency may represent increasedexposure to small children, who represent a large reservoir for URIs, buthormonal effects on the nasal mucosa may also play a roleEpiglottitis: A male predominance is reported, with a maletofemale ratio ofapproximately 3:2Laryngotracheobronchitis, or croup: More common in boys than in girls, witha maletofemale ratio of approximately 3:2

Agerelated demographics

The incidence of the common cold varies by age. Rates are highest in childrenyounger than 5 years. Children have approximately 38 viral respiratory illnesses peryear, while adolescents and adults have approximately 24 colds a year, and peopleolder than 60 years have fewer than 1 cold per year.

The agerelated occurrence of other infections is as follows:

Viral and bacterial pharyngitis: Peaks in children aged 47 years.Epiglottitis: Typically occurs in children aged 27 years and has a peakincidence in those aged 3 yearsLaryngotracheobronchitis (croup): As previously stated, it may affect peopleof any age but usually occurs in children aged 6 months to 6 years; the peakincidence is in the second year of life

PrognosisURIs 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 followinginfections (and others, as well):

Otitis mediaBronchitisBronchiolitisPneumoniaSepsisMeningitisIntracranial 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 711 days induration.[17]

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

Attendance at day care may affect the duration of symptoms in young children. Inone study, the duration of viral URIs ranged from 6.6 days for children aged 12years in home care to 8.9 days for children younger than 1 year who were in daycare. Young children in day care were also more likely to have protracted respiratorysymptoms lasting more than 15 days.[26]

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

Pharyngitis

Viral pharyngitis typically resolves in 12 weeks, but immunocompromised personsmay have a more severe course.

Untreated group A streptococcal pharyngitis can result in the following:

Acute rheumatic feverAcute glomerulonephritisPeritonsillar abscessToxic shock syndromeImpetigoCellulitis or abscessOtitisSinusitisConjunctivitisBronchitis

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

Streptococcal pharyngitis without complications rarely poses significant risk formorbidity. However, retropharyngeal, intraorbital, or intracranial abscesses maycause serious sequelae. The risk of mortality is significant in patients who progressto streptococcal toxic shock syndrome, which is characterized by multiorgan failureand hypotension.

In patients with penicillinsensitive streptococcal pharyngitis, symptomaticimprovement is expected within 2472 hours if antibiotic treatment is started in thefirst 24 hours after onset. Treatment failures are common and are mainly attributed

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to poor adherence, antibiotic resistance, and untreated close contacts, usually withinthe household or family.

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

Mononucleosis

With infectious mononucleosis from EBV, complete resolution of symptoms maytake up to 2 months. Acute symptoms rarely last more than 4 months. EBVtypically remains dormant throughout the patient's life. Reactivation of the virus isnot usually symptomatic.

Rhinosinusitis

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

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

Orbital cellulitisSubperiosteal abscessOrbital abscessFrontal and maxillary osteomyelitisSubdural abscessMeningitisBrain abscess

Epiglottitis

Epiglottitis poses a risk of death due to sudden airway obstruction and othercomplications, including septic arthritis, meningitis, empyema, and mediastinitis. Inadults, epiglottitis has a fatality rate of approximately 1%.

The prognosis is favorable with appropriate airway management, and most patientsnoticeably improve within 2448 hours after antibiotics are started. Rarely, cases ofepiglottitis may recur. Recurrent symptoms raise concern about potential underlyingdisorders, such as rheumatic conditions, sarcoidosis, and occult malignancy.

Laryngitis and laryngotracheitis

With croup, laryngotracheobronchitis typically begins to improve within 34 days.Recovery is usually complete. However, patients may have a recurrence, includingduring the same season.

Pertussis (whooping cough) leads to hospitalization in more than half of infantsyounger than 12 months and particularly in infants younger than 6 months. Infantsand young children are most susceptible to severe courses that include respiratorycompromise.

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 ofcoughing may last for several weeks.

Complications

Most URIs are selflimited and resolve completely. However, a variety of conditionsmay complicate a URI. Fluid loss may occur in patients unable to tolerate adequateoral intake because of upper airway inflammation or may result from fever. Otitismedia 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 exacerbatedasthma. Cough asthma, wherein a cough is the predominant manifestation ofreactive airways disease, may mimic ongoing infection. This may be diagnosed withpulmonary function testing.

A postinfectious cough is defined as coughing that persists 38 weeks after theonset of a URI in the absence of other clearly defined causes. Exacerbations ofchronic obstructive pulmonary disease, including emphysema and chronic bronchitis,may occur during and after a URI. Upper airways cough syndrome (postnasal drip)may result from upper airway secretions dripping onto the pharynx. Epistaxis mayalso occur.

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

Viral infection and resulting inflammation may make an individual susceptible toconcomitant or sequential infection with a bacterial agent. Streptococcuspneumoniae, Staphylococcus aureus, H influenzae, and Streptococcus pyogenesare common superinfecting agents. Meningococci may cause superinfection withinfluenzal 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 oracquired subglottic stenosis. The work of breathing during epiglottitis or

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laryngotracheitis may lead to respiratory failure. Sleep apnea may occur fromhypertrophied tonsils.

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

Complications of sinusitis include the following:

Orbital cellulitisSubperiosteal abscessOrbital abscessMastoiditisFrontal or maxillary osteomyelitisSubdural abscessCavernous sinus thrombosisBrain abscess

Suspect a deep tissue infection when a patient has orbital or periorbital swelling,proptosis, impaired extraocular movements, or impaired vision. Signs of increasedintracranial 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 mayaffect the orbital plate, frontal bone, or sphenoid bone. Mucoceles are expandingcystic defects of the paranasal sinuses that may result from prolonged sinusitis.Epiglottic abscess may result from epiglottitis.

Lymphadenitis may follow or accompany URI. GuillainBarré syndrome maymanifest as an ascending polyneuropathy a few days or weeks after a URI. Inchildren or adolescents, the use of aspirin during a viral infection may rarely causeReye syndrome. Aspirin is contraindicated for the management of fevers in childrenor adolescents.

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

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

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

Hemoptysis suggests the possibility of tuberculosis. A tuberculin skin test, chestradiography, 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 complicationsinclude streptococcal toxic shock syndrome, acute rheumatic fever (ARF), acuteglomerulonephritis, and scarlet fever, as well as cutaneous infections. In addition,this pathogen is readily transmissible, especially in households, families, and otherintimate groups.

ARF affects approximately 3% of patients with strep throat, primarily occurring inpersons aged 620 years. The condition develops approximately 24 weeks afterstreptococcal pharyngitis occurs, and it may last several months. Signs of rheumaticfever include arthritis, fever, and valvular disease. Uncommon features include anexpanding truncal exanthem (erythema marginata), subcutaneous nodules, andchorea.

Poststreptococcal glomerulonephritis can affect persons of any age group, but it ismost common in children aged 37 years. Boys are affected slightly more often thangirls. Patients with glomerulonephritis may have loss of appetite, lethargy, dull backpain, and dark urine. Blood pressure may be elevated, and edema may occur.

Scarlet fever is a selflimited exanthem that spreads from the chest and abdomento the entire body. Tiny red papules create a rough skin texture similar to that ofsandpaper. 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 suddenonset or worsening of obsessivecompulsive disorder following streptococcalinfection. Associated manifestations include tics and a variety of neuropsychiatricsymptoms.[30]

Complications of mononucleosis

Complications can include the following:

Splenic ruptureHepatitisGuillainBarré syndromeEncephalitisHemolytic anemiaAgranulocytosisMyocarditis

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Burkitt lymphomaNasopharyngeal carcinomaRash (with concomitant use of ampicillin)

Complications of diphtheria

Complications may include airway obstruction, myocarditis, polyneuritis,thrombocytopenia, and proteinuria. Among patients who survive diphtheria, as manyas 20% have permanent hearing loss or other longterm sequelae.[13]

Complications from pertussis

More than half of infants younger than 12 months who contract pertussis requirehospitalization, especially those who are younger than 6 months. Complications ofpertussis 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, orsubconjunctival hemorrhages.

Complications of influenza

These include the following:

Bacterial superinfectionPneumoniaVolume depletionMyositisPericarditisRhabdomyolysisEncephalitisMeningitisMyelitisRenal failureDisseminated intravascular coagulation

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

Patient EducationAddress the patient's expectations about antibiotic therapy. Validate the patient'ssymptoms and their severity, listen to the concerns expressed, and educate thepatient about possible consequences of inappropriate antibiotic use, includingconsequences affecting him/her and the community.

Many people hold misperceptions about the duration and intensity of symptomsassociated with URI and about the benefits and risks of antibiotic therapy. Someare unaware that cold symptoms may last as long as 14 days. Some believe thatantibiotics will help them to avoid serious disease and recover more quickly thanwithout treatment.

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

Actively promote selfcare, and outline a realistic time course for the resolution ofsymptoms. Reassure the patient about access to clinical care and followup in theevent that symptoms progress. Briefly explore factors that may have contributed tothe current infection, and address prevention for the future.

Patient satisfaction is less linked to antibiotic prescriptions and more linked to thequality of the physicianpatient interaction. Reflecting understanding of the details ofthe patient's situation, expressing concern for the patient's wellbeing, explaininghow 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 coveringcoughs and sneezes. Patients who smoke should receive smoking cessationencouragement and materials. When antibiotics are prescribed, patients should beinstructed 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 contactsports for 6 weeks because of the possibility of splenic rupture.

For patient education information, see the Headache and Migraine Center, as wellas Sinus Infection and Sore Throat.

Clinical Presentation

Contributor Information and DisclosuresAuthorAnne Meneghetti, MD Assistant Professor of Medicine, Tufts University School of Medicine; MedicalBroadcaster, MyWellBeing.com

Anne Meneghetti, MD is a member of the following medical societies: National Ayurvedic Medical Association

Disclosure: Nothing to disclose.

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Chief EditorZab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine,Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild LungInstitute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of ChestPhysicians, American College of Physicians, American Federation for Medical Research, American ThoracicSociety

Disclosure: Nothing to disclose.

AcknowledgementsGregory William Rutecki, MD Professor of Medicine, Fellow of The Center for Bioethics and Human Dignity,University of South Alabama College of Medicine

Gregory William Rutecki, MD is a member of the following medical societies: Alpha Omega Alpha, AmericanCollege of Physicians, American Society of Nephrology, National Kidney Foundation, and Society of GeneralInternal Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center Collegeof Pharmacy; EditorinChief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References

1. [Guideline] Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH. Diagnosis and managementof group A streptococcal pharyngitis: a practice guideline. Infectious Diseases Society of America. ClinInfect Dis. 1997 Sep. 25(3):57483. [Medline].

2. [Guideline] Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G, et al. Clinical practiceguideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by theInfectious Diseases Society of America. Clin Infect Dis. 2012 Nov 15. 55(10):127982. [Medline]. [FullText].

3. [Guideline] Wald ER, Applegate KE, Bordley C, Darrow DH, Glode MP, Marcy SM, et al. Clinical practiceguideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years.Pediatrics. 2013 Jul. 132(1):e26280. [Medline].

4. Utah Department of Health, Bureau of Epidemiology. Whooping Cough Sound Files. Utah Department ofHealth, Bureau of Epidemiology. Available athttp://health.utah.gov/epi/diseases/pertussis/pertussis_sounds.htm. Accessed: November 29, 2012.

5. Centers for Disease Control and Prevention. Pertussis (Whooping Cough): Clinical Features. Available athttp://www.cdc.gov/pertussis/clinical/features.html. Accessed: October 27, 2013.

6. AhovuoSaloranta A, Borisenko OV, Kovanen N, Varonen H, Rautakorpi UM, Williams JW Jr, et al.Antibiotics for acute maxillary sinusitis. Cochrane Database Syst Rev. 2008 Apr 16. CD000243. [Medline].

7. [Guideline] Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJ, Hicks LA, et al. IDSA clinicalpractice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012 Apr.54(8):e72e112. [Medline]. [Full Text].

8. Chung LP, Waterer GW. Genetic predisposition to respiratory infection and sepsis. Crit Rev Clin Lab Sci.2011 SepDec. 48(56):25068. [Medline].

9. Horby P, Nguyen NY, Dunstan SJ, Baillie JK. The role of host genetics in susceptibility to influenza: asystematic review. PLoS One. 2012. 7(3):e33180. [Medline]. [Full Text].

10. Juno J, Fowke KR, Keynan Y. Immunogenetic factors associated with severe respiratory illness caused byzoonotic H1N1 and H5N1 influenza viruses. Clin Dev Immunol. 2012. 2012:797180. [Medline]. [Full Text].

11. Meriluoto M, Hedman L, Tanner L, Simell V, Mäkinen M, Simell S, et al. Association of human bocavirus 1infection with respiratory disease in childhood followup study, Finland. Emerg Infect Dis. 2012 Feb.18(2):26471. [Medline]. [Full Text].

12. National Center for Infectious Diseases. Division of Bacterial and Mycotic Diseases. Haemophilusinfluenzae serotype b (Hib) disease. Centers for Disease Control and Prevention. Available athttp://www.cdc.gov/hidisease/clinicians.html. Accessed: November 29, 2012.

13. National Center for Infectious Diseases. Respiratory and Enteric Viruses Branch. Human parainfluenzaviruses (HPIVs). Centers for Disease Control and Prevention. Available athttp://www.cdc.gov/ncidod/dvrd/revb/respiratory/hpivfeat.htm. Accessed: April 30, 2009.

14. [Guideline] Schwartz SR, Cohen SM, Dailey SH, et al. Clinical practice guideline: hoarseness (dysphonia).Otolaryngol Head Neck Surg. 2009 Sep. 141(3 Suppl 2):S1S31. [Full Text].

15. Cherry DK, Hing E, Woodwell DA, Rechtsteiner EA. National Ambulatory Medical Care Survey: 2006Summary. 2008. Available at http://www.cdc.gov/nchs/data/nhsr/nhsr003.pdf.

16. Fagnan LJ. Acute sinusitis: a costeffective approach to diagnosis and treatment. Am Fam Physician. 1998Nov 15. 58(8):1795802, 8056. [Medline].

17. Centers for Disease Control and Prevention. Accessed April 30, 2009. Nonspecific upper respiratory tractinfection. Available at http://www.cdc.gov/drugresistance/community/hcpinfosheets/adultnurti.pdf.

18. Isakson M, Hugosson S. Acute epiglottitis: epidemiology and Streptococcus pneumoniae serotypedistribution in adults. J Laryngol Otol. 2011 Apr. 125(4):3903. [Medline].

19. Centers for Disease Control and Prevention. Pertussis (Whooping Cough) Surveillance & Reporting.Available at http://www.cdc.gov/pertussis/survreporting.html. Accessed: June 12, 2012.

20. Bettiol S, Wang K, Thompson MJ, Roberts NW, Perera R, Heneghan CJ, et al. Symptomatic treatment ofthe cough in whooping cough. Cochrane Database Syst Rev. 2012 May 16. 5:CD003257. [Medline].

5/27/2016 Upper Respiratory Tract Infection: Practice Essentials, Background, Pathophysiology

http://emedicine.medscape.com/article/302460overview 13/15

21. Centers for Disease Control and Prevention. Outbreaks of respiratory illness mistakenly attributed topertussisNew Hampshire, Massachusetts, and Tennessee, 20042006. MMWR Morb Mortal Wkly Rep.2007 Aug 24. 56(33):83742. [Medline]. [Full Text].

22. CDC Centers for Disease Control and Prevention. Seasonal Influenza (Flu). Centers for Disease Controland Prevention. Available at http://www.cdc.gov/flu/about/disease/index.htm. Accessed: June 12, 2012.

23. National Center for Infectious Diseases. Division of Bacterial and Mycotic Diseases. EpsteinBarr virus andinfectious mononucleosis. Centers for Disease Control and Prevention. Available athttp://www.cdc.gov/ncidod/diseases/ebv.htm. Accessed: April 30, 2009.

24. Centers for Disease Control and Prevention. CDC. Diphtheria. Centers for Disease Control and Prevention.CDC.gov. Available at http://www.cdc.gov/ncidod/dbmd/diseaseinfo/diptheria_t.htm. Accessed: June 12,2012.

25. National Institute of Allergy and Infectious Diseases. Common Cold. National Institute of Allergy andInfectious Diseases. Available at http://www.niaid.nih.gov/topics/commoncold/Pages/default.aspx.Accessed: June 12, 2012.

26. Wald ER, Guerra N, Byers C. Upper respiratory tract infections in young children: duration of and frequencyof complications. Pediatrics. 1991 Feb. 87(2):12933. [Medline].

27. CDC. Centers for Disease Control and Prevention. Seasonal Influenza (Flu): Seasonal InfluenzaAssociated Hospitalizations in the United States. Centers for Disease Control and Prevention. Available athttp://www.cdc.gov/flu/about/qa/hospital.htm. Accessed: November 29, 2012.

28. CDC. Centers for Disease Control and Prevention. Pertussis (Whooping Cough): Clinical Complications.Available at http://www.cdc.gov/pertussis/clinical/complications.html. Accessed: June 12, 2012.

29. Arola M, Ruuskanen O, Ziegler T, Mertsola J, NäntöSalonen K, PuttoLaurila A, et al. Clinical role ofrespiratory virus infection in acute otitis media. Pediatrics. 1990 Dec. 86(6):84855. [Medline].

30. Shulman ST. Pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS):update. Curr Opin Pediatr. 2009 Feb. 21(1):12730. [Medline].

31. National Institute of Allergy and Infectious Diseases. Common Cold: Symptoms. Available athttp://www.niaid.nih.gov/topics/commonCold/Pages/symptoms.aspx. Accessed: October 17, 2013.

32. [Guideline] Division of STD Prevention, CDC. Gonococcal Infections. Sexually Transmitted DiseasesTreatment Guidelines, 2010. Centers for Disease Control and Prevention. Available athttp://www.cdc.gov/std/treatment/2010/gonococcalinfections.htm. Accessed: November 29, 2012.

33. Vincent MT, Celestin N, Hussain AN. Pharyngitis. Am Fam Physician. 2004 Mar 15. 69(6):146570.[Medline].

34. CDC. Centers for Disease Control and Prevention. Pertussis (Whooping Cough): Specimen Collection. Fulltext: http://cid.oxfordjournals.org/content/early/2012/09/06/cid.cis629.full. Available athttp://www.cdc.gov/pertussis/clinical/diagnostictesting/specimencollection.html. Accessed: October 17,2013.

35. Chow AW. Acute sinusitis: current status of etiologies, diagnosis, and treatment. Curr Clin Top Infect Dis.2001. 21:3163. [Medline].

36. [Guideline] Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWRRecomm Rep. 2006 Aug 4. 55:194. [Medline]. [Full Text].

37. CDC. Centers for Disease Control and Prevention. Pertussis (Whooping Cough): Diagnostic Testing.Centers for Disease Control and Prevention. Available at http://www.cdc.gov/pertussis/clinical/diagnostictesting/index.html. Accessed: November 29, 2012.

38. Adult epiglottitis: best practice of medicine [Internet database]. April, 2000;

39. Ragosta KG, Orr R, Detweiler MJ. Revisiting epiglottitis: a protocolthe value of lateral neck radiographs. JAm Osteopath Assoc. 1997 Apr. 97(4):2279. [Medline].

40. MacReady N. AAP Releases New Principles for URI Antibiotics. Medscape Medical News. Available athttp://www.medscape.com/viewarticle/814533. Accessed: November 26, 2013.

41. Hersh AL, Jackson MA, Hicks LA. Principles of Judicious Antibiotic Prescribing for Bacterial UpperRespiratory Tract Infections in Pediatrics. Pediatrics. 2013 Nov 18. [Medline].

42. Little P, Moore M, Kelly J, et al. Delayed antibiotic prescribing strategies for respiratory tract infections inprimary care: pragmatic, factorial, randomised controlled trial. BMJ. 2014 Mar 6. 348:g1606. [Medline].[Full Text].

43. Kissoon N, Mitchell I. Adverse effects of racemic epinephrine in epiglottitis. Pediatr Emerg Care. 1985Sep. 1(3):1434. [Medline].

44. Weber JE, Chudnofsky CR, Younger JG, Larkin GL, Boczar M, Wilkerson MD, et al. A randomizedcomparison of heliumoxygen mixture (Heliox) and racemic epinephrine for the treatment of moderate tosevere croup. Pediatrics. 2001 Jun. 107(6):E96. [Medline].

45. [Guideline] Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Brightling CE, et al. Diagnosisand management of cough executive summary: ACCP evidencebased clinical practice guidelines. Chest.2006 Jan. 129(1 Suppl):1S23S. [Medline].

46. Update: influenza activity United States, September 28, 2008January 31, 2009. MMWR Morb MortalWkly Rep. 2009 Feb 13. 58(5):1159. [Medline]. [Full Text].

47. van den Aardweg MT, Boonacker CW, Rovers MM, Hoes AW, Schilder AG. Effectiveness ofadenoidectomy in children with recurrent upper respiratory tract infections: open randomised controlled trial.BMJ. 2011 Sep 6. 343:d5154. [Medline]. [Full Text].

48. Harvey R, Hannan SA, Badia L, Scadding G. Nasal irrigation with saline (salt water) for the symptoms ofchronic rhinosinusitis. Cochrane Database Syst Rev. January 24, 2007. Issue 3:[Medline]. [Full Text].

49. Rabago D, Zgierska A, Mundt M, Barrett B, Bobula J, Maberry R. Efficacy of daily hypertonic saline nasalirrigation among patients with sinusitis: a randomized controlled trial. J Fam Pract. 2002 Dec. 51(12):104955. [Medline]. [Full Text].

5/27/2016 Upper Respiratory Tract Infection: Practice Essentials, Background, Pathophysiology

http://emedicine.medscape.com/article/302460overview 14/15

50. Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM Jr. Effect of honey, dextromethorphan,and no treatment on nocturnal cough and sleep quality for coughing children and their parents. ArchPediatr Adolesc Med. 2007 Dec. 161(12):11406. [Medline]. [Full Text].

51. Sharfstein JM, North M, Serwint JR. Over the counter but no longer under the radarpediatric cough andcold medications. N Engl J Med. 2007 Dec 6. 357(23):23214. [Medline].

52. Food and Drug Administration. FDA Statement Following CHPA's Announcement on Nonprescription OvertheCounter Cough and Cold Medicines in Children. FDA: U.S. Food and Drug Administration. Available athttp://www.fda.gov/bbs/topics/NEWS/2008/NEW01899.html. Accessed: May 10, 2009.

53. Wiklund L, Stierna P, Berglund R, Westrin KM, Tonnesson M. The efficacy of oxymetazoline administeredwith a nasal bellows container and combined with oral phenoxymethylpenicillin in the treatment of acutemaxillary sinusitis. Acta Otolaryngol Suppl. 1994. 515:5764. [Medline].

54. Hayden FG, Diamond L, Wood PB, Korts DC, Wecker MT. Effectiveness and safety of intranasalipratropium bromide in common colds. A randomized, doubleblind, placebocontrolled trial. Ann InternMed. 1996 Jul 15. 125(2):8997. [Medline].

55. Turner RB, Sperber SJ, Sorrentino JV, O'Connor RR, Rogers J, Batouli AR, et al. Effectiveness ofclemastine fumarate for treatment of rhinorrhea and sneezing associated with the common cold. Clin InfectDis. 1997 Oct. 25(4):82430. [Medline].

56. [Guideline] American Academy of Pediatrics. Clinical practice guideline: management of sinusitis.Pediatrics. 2001 Sep. 108(3):798808. [Medline].

57. Zalmanovici A, Yaphe J. Steroids for acute sinusitis. Cochrane Database Syst Rev. 2007 Apr 18.CD005149. [Medline].

58. American Academy of Pediatrics. Use of codeine and dextromethorphancontaining cough remedies inchildren. American Academy of Pediatrics. Committee on Drugs. Pediatrics. 1997 Jun. 99(6):91820.[Medline].

59. Wing A, VillaRoel C, Yeh B, Eskin B, Buckingham J, Rowe BH. Effectiveness of corticosteroid treatmentin acute pharyngitis: a systematic review of the literature. Acad Emerg Med. 2010 May. 17(5):47683.[Medline].

60. Hirt M, Nobel S, Barron E. Zinc nasal gel for the treatment of common cold symptoms: a doubleblind,placebocontrolled trial. Ear Nose Throat J. 2000 Oct. 79(10):77880, 782. [Medline].

61. United States Food and Drug Administration. Accessed June 16, 2009. Zicam cold remedy nasal products(Cold Remedy Nasal Gel, Cold Remedy Nasal Swabs, and Cold Remedy Saws, Kids Size). MedWatchPublic Health Advisory. Available athttp://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm166996.htm.

62. Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2011 Feb 16. 2:CD001364.[Medline].

63. Taylor JA, Weber W, Standish L, Quinn H, Goesling J, McGann M, et al. Efficacy and safety of echinaceain treating upper respiratory tract infections in children: a randomized controlled trial. JAMA. 2003 Dec 3.290(21):282430. [Medline].

64. Barrett B, Brown R, Rakel D, Mundt M, Bone K, Barlow S, et al. Echinacea for treating the common cold:a randomized trial. Ann Intern Med. 2010 Dec 21. 153(12):76977. [Medline].

65. Brinckmann J, Sigwart H, van Houten Taylor L. Safety and efficacy of a traditional herbal medicine (ThroatCoat) in symptomatic temporary relief of pain in patients with acute pharyngitis: a multicenter, prospective,randomized, doubleblinded, placebocontrolled study. J Altern Complement Med. 2003 Apr. 9(2):28598.[Medline].

66. D'Souza AL, Rajkumar C, Cooke J, Bulpitt CJ. Probiotics in prevention of antibiotic associated diarrhoea:metaanalysis. BMJ. 2002 Jun 8. 324(7350):1361. [Medline].

67. Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, et al. Position statement. Part one: Immunefunction and exercise. Exerc Immunol Rev. 2011. 17:663. [Full Text].

68. Kretsinger K, Broder KR, Cortese MM, Joyce MP, OrtegaSanchez I, Lee GM, et al. Preventing tetanus,diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellularpertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) andrecommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee(HICPAC), for use of Tdap among healthcare personnel. MMWR Recomm Rep. 2006 Dec 15. 55:137.[Medline]. [Full Text].

69. [Guideline] Workowski KA, Levine WC. Sexually transmitted diseases treatment guidelines: 2002 [Centersfor Disease Control and Prevention Web site]. MMWR. 2002. 51(RR06):180. [Full Text].

70. American Academy of Pediatrics. Prevention of pertussis among adolescents: recommendations for use oftetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. Pediatrics. 2006 Mar.117(3):96578. [Medline].

71. [Guideline] Safer Healthier PeopleCenters for Disease Control and Prevention. Pertussis: Summary ofVaccine Recommendations. Safer Healthier People. Available at http://www.cdc.gov/vaccines/vpdvac/pertussis/recssummary.htm. Accessed: 02/10/2011.

72. US Food and Drug Administration. FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax)and the risk of potentially fatal heart rhythms. Available athttp://www.fda.gov/drugs/drugsafety/ucm341822.Htm. Accessed: March 12, 2013.

73. Broder J. Vitamin D ineffective for respiratory tract infections. Medscape Medical News. Available athttp://www.medscape.com/viewarticle/771953. Accessed: October 15, 2012.

74. Choby BA. Diagnosis and treatment of streptococcal pharyngitis. Am Fam Physician. 2009 Mar 1.79(5):38390. [Medline].

75. Hickner JM, Bartlett JG, Besser RE, Gonzales R, Hoffman JR, Sande MA, et al. Principles of appropriateantibiotic use for acute rhinosinusitis in adults: background. Ann Intern Med. 2001 Mar 20. 134(6):498505.[Medline].

76. Murdoch DR, Slow S, Chambers ST, Jennings LC, Stewart AW, Priest PC, et al. Effect of vitamin D3supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled

5/27/2016 Upper Respiratory Tract Infection: Practice Essentials, Background, Pathophysiology

http://emedicine.medscape.com/article/302460overview 15/15

Medscape Reference © 2011 WebMD, LLC

trial. JAMA. 2012 Oct 3. 308(13):13339. [Medline].

77. Tanz RR, Gerber MA, Kabat W, Rippe J, Seshadri R, Shulman ST. Performance of a rapid antigendetection test and throat culture in community pediatric offices: implications for management ofpharyngitis. Pediatrics. 2009 Feb. 123(2):43744. [Medline].