Upper Respiratory Tract Infection Workup

Diagnostic tests for specific agents are helpful when targeted URI therapy depends on the results. Specific bacterial or viral testing is warranted only in select other situations, such as in immunocompromised patients or during epidemics. Targeted therapy is not available for most viruses that cause URI. Therefore, viral testing is rarely indicated for uncomplicated viral URIs in the outpatient setting. However, confirmation of a viral condition such as influenza may reduce inappropriate use of antibiotics.

Suspected group A streptococcal infection

The diagnosis should be pursued on the basis of clinical findings supported by results of rapid-detection assays and cultures.

Patients with a personal history of rheumatic fever or a household contact with a history of rheumatic fever are at high risk for group A streptococcal infection. In addition, the following features may raise suspicion for group A streptococcal disease^[18] :

• Erythema, swelling, or exudates of tonsils or pharynx
• Fever with a temperature of at least 38.3°C (100.9°F) in the preceding 24 hours
• Tender anterior cervical lymph nodes (1 cm or larger)
• Absence of cough, rhinorrhea, and conjunctivitis (common in viral illness)
• Patient age 5-15 years
• Occurrence in the season with highest prevalence (ie, November to May)

A 5-point decision rule for streptococcal pharyngitis likelihood incorporates the following features: absence of cough, swollen tender anterior cervical nodes, temperature over 100.4 º F (38 º C), tonsillar exudates or swelling, and age younger 14 years.^[20] Those with high scores may warrant empiric antibiotics; further testing or antibiotics are not indicated for those with low scores. Testing with rapid test and/or culture may be used to guide decision-making in those with intermediate scores.

Rapid antigen tests for group A streptococci have excellent specificity, and yield results in 10-20 minutes. Culture specimens may be obtained at the time of presentation. Negative results on rapid antigen testing have traditionally been followed up with culturing because the rapid antigen test is imperfectly sensitive. In one study of children aged 3-18 years, a culture obtained in the office had greater sensitivity (81%) than that of a rapid antigen-detection test (70%).^[21] Rapid test plus culture combined had even greater sensitivity (85%); sensitivity was higher in patients who had a higher pretest likelihood of group A streptococcus pharyngitis. As individual practice sites gain experience with newer rapid detection tests, combination rapid test plus culture is encouraged to verify level of concordance before deciding to forego confirmatory cultures for an individual practice.

Streptococcal antibodies (antistreptolysin O) levels do not peak until 4-5 weeks after the onset of pharyngitis. Therefore, testing for these antibodies has no role in the diagnosis of acute pharyngitis.

Suspected acute bacterial rhinosinusitis

Laboratory studies are generally not indicated in cases of suspected acute bacterial rhinosinusitis because the causative agents in immunocompetent individuals are well characterized. Sinus puncture is also rarely indicated in acute disease. However, maxillary sinus puncture aspirate performed by an otolaryngologist may be indicated in patients with complex and persistent disease, in those with suppurative extensions of disease, in seriously immunocompromised patients, and in those with nosocomial sinus infection. Sinus puncture is a standard diagnostic procedure; rigid nasal endoscopy is a less robust option because of specimen contamination by nasal flora. Respiratory flora also commonly contaminate nasal swabs and washes (see Procedures).

Suspected influenza

For testing and case management of suspected H1N1 or seasonal influenza, see the eMedicine article on Influenza.

Immunocompromised individuals

Specific information about infection may help tailor antimicrobial choices, herald potential complications, and aid in determining the appropriateness of hospitalization. Viral testing may be used for making the diagnosis, monitoring the patient, or predicting the prognosis in immunocompromised individuals (eg, transplant recipients).

Other situations in which testing may be considered

• Extended duration: Testing may be required if progressive symptoms last longer than 14 days and have no other identifiable cause, such as asthma or allergic rhinitis.
• Seasonal influenza: In cases of suspected influenza, confirmation of a serotype-specific diagnosis may direct options for antiviral therapy. Testing may also assist the clinician in avoiding unnecessary prescriptions for antibacterials.
• Mononucleosis: In a young person with sore throat, lymphadenopathy, hepatosplenomegaly, testing may be required to confirm infectious mononucleosis. Confirmation may be helpful in guiding outpatient care and expectations.
• HSV infection: Suspected URI due to HSV warrants diagnosis because specific therapy is available for this infection.
• Sexually transmitted disease–related oropharyngeal disease: Specific therapy exists for pathogens such as N gonorrhoeae.
• Epiglottitis: If endoscopy is performed during an evaluation for epiglottitis, a swab sample may be taken for culturing. However, because of contamination with upper airway flora, such cultures are not ideal unless an aspirate is taken from an epiglottic abscess. Therefore, blood cultures should also be ordered. Blood cultures for H influenzae are positive in more than 80% of children and in approximately 25% of adults.^[22]

Laboratory techniques

• Nasopharyngeal samples for bacteria: Culturing of throat swabs, nasal swabs or washes, or nasal aspirates remains the standard for confirming bacterial URI pathogens (see Procedures). Samples should be taken from the posterior pharynx or tonsils, not the oral cavity. Nasopharyngeal aspirates are recommended for pertussis.^[23] Cultures may be falsely negative for group A streptococci because of inadequate specimen collection, covert use of antibiotics, or suboptimal laboratory practices. Prolonged illness may reduce the sensitivity of culture. Specimens are optimally obtained in the first 4 days of illness. Some patients may be chronically colonized with group A streptococcus.
• Nasopharyngeal samples for viruses: Viral cultures remain the standard for confirming infection. Throat swabs, nasal swabs or washes, or sputum may be cultured on special viral media to detect influenza virus, PIV, adenovirus, RSV, and other viruses. Culturing may require days to weeks.
• Rapid tests for bacteria: Rapid antigen tests for group A streptococci have excellent specificity and yield results in 10-20 minutes; individual practices wherein excellent correlation has been verified between rapid tests and culture results may choose not to routinely culture in every instance. Rapid direct fluorescent antibody testing is available to test for pertussis. PCR testing for pertussis is emerging as a sensitive detection tool. However, recent respiratory illness outbreaks mistakenly attributed to pertussis highlight the limitations of relying solely on PCR tests to confirm pertussis. The positive predictive value is lower when PCR testing is used as a screening tool without culture confirmation during a suspected pertussis outbreak.^[8]
• Rapid tests for viruses: Various antigen, immunofluorescence, and PCR assays are available to detect viruses in secretions. Rapid tests for influenza can be conducted on specimens from nasopharyngeal swabs, washes, or aspirates, yielding results within 30 minutes. Most rapid tests to detect influenza that are performed in a physician's office are approximately greater than 70% sensitive and approximately greater than 90% specific. Therefore, viral culture may yield a positive result in up to 30% of the cases with negative rapid influenza test results.^[24] Enzyme immunoassays are available to detect PIV. Reverse transcriptase PCR may detect various viruses in nasopharyngeal samples. PCR detection of various viruses from blood samples is emerging as a way to track certain viral infections.
• Titer comparison: Antibody titers compared between paired specimens obtained weeks apart may help in retrospectively identifying a particular pathogen in immunocompetent patients. The first sample should be obtained during the first week of illness, and the second should be obtained 2-4 weeks later.
• Monospot: In a patient with symptoms of infectious mononucleosis due to EBV, a positive result on a monospot heterophile antibody test is diagnostic. levels are moderate to high in the first month of illness and decrease rapidly thereafter. Monospot results are positive in more than 85% of cases. False-positive results are seen in a few patients; false-negative results are seen in 10-15% of patients, primarily in children younger than 10 years.^[10]

Special laboratory considerations for specific pathogens

• Pertussis: This infection is clinically diagnosed on the basis of symptoms of whooping cough. When bacteriologic confirmation is sought, the receiving laboratory should be contacted for special instructions on specimen collection. Culture of a nasopharyngeal aspirate is the criterion standard, although PCR and serology are available.^[23] Nasopharyngeal aspirates are ideally collected 0-2 weeks after symptom onset, but may provide accurate results for as long as 4 weeks in infants or unvaccinated patients. Serology is optimally timed 2-8 weeks post symptom onset, when antibody titers are highest, yet testing may be performed on specimens as long as 12 weeks after symptom onset.
• Diphtheria: Special selective growth media are required for C diphtheriae. This organism must be distinguished from the diphtheroids that commonly inhabit the nasopharynx.
• HSV: In patients with mucocutaneous lesions suggestive of HSV infection, isolation of the virus in cell culture is the preferred virologic testing strategy. As lesions begin to heal, the sensitivity of culturing rapidly declines. Cytologic detection of cellular changes of HSV infection is insensitive and nonspecific and should not be relied on for diagnosis of HSV infection.^[25] PCR is available in some laboratories.
• Gonorrhea: N gonorrhoeae requires special culture media.
• Atypical bacteria: Insufficient evidence suggests that testing for atypical bacteria, such as C pneumoniae or M pneumoniae, would improve clinical outcomes in persons with pharyngitis.^[26]

Other laboratory tests

• CBC count with differential: Patients with URIs may have an increased WBC count with a left shift. Atypical lymphocytes, lymphocytosis, or lymphopenia may be seen in some viral infections. However, a CBC count is not likely to be helpful in differentiating the infectious agent or in directing therapy in uncomplicated URIs in the outpatient setting.
• Blood cultures: These are appropriate in hospitalized patients.

Nasopharyngitis and pharyngitis

Imaging studies are not indicated for the common cold. Suspected mass lesions, such as a peritonsillar abscess or intracranial suppurative lesions, warrant imaging. If the patient's history and physical findings suggest lower respiratory tract disease, chest imaging may be useful.

Rhinosinusitis

• Routine acute rhinosinusitis: Defined as the first 4 weeks of symptoms, it does not require imaging. Greater than 80% of patients with the common cold have transient abnormalities of the paranasal sinuses on CT scans.^[27] Imaging studies do not help in distinguishing bacterial from viral disease because no diagnostic signs are unique to bacterial sinus infection. Therefore, images must always be interpreted in the context of the clinical picture. A negative study may be helpful in ruling out rhinosinusitis.
• Complicated or persistent disease: If rhinosinusitis symptoms persist despite therapy or if complications (eg, extension of disease into surrounding tissue) are suspected, sinus imaging may be appropriate to evaluate the anatomy. Signs or symptoms consistent with intracranial extension of infection warrant CT scanning to evaluate the possibility of an intracranial abscess or other suppurative complication. Such symptoms may include proptosis, impaired intraocular movements, decreased vision, papilledema, changes in mental status, or other neurologic findings.
• Choice of sinus imaging: The lack of fully developed sinuses in children poses challenges in image interpretation. The frontal sinuses do not typically appear until age 5-8 years, and they may not develop fully in all individuals.
• CT scanning: This study yields more detailed information than plain radiography, especially regarding the ostiomeatal complex. Such information may be relevant to surgical planning. Although sinus CT scanning is highly sensitive, its specificity for demonstrating acute sinusitis is low because 40% of asymptomatic patients and 87% of those with common colds have sinus abnormalities.^[2] Common CT findings include mucosal thickening, air-fluid levels, and obstruction of the ostiomeatal complex. Not all patients with acute rhinosinusitis have air-fluid levels. The image below reveals sinusitis on a CT scan. See the image below. CT scan of the sinuses demonstrates maxillary sinusitis. The left maxillary sinus is completely opacified (asterisk), and the right has mucosal thickening (arrow). Courtesy of Omar Lababede, MD, Cleveland Clinic Foundation.
• Plain radiography: If a patient cannot tolerate CT scanning, a plain radiographic Waters view of the frontal and maxillary sinuses may be considered. Most cases of rhinosinusitis involve the maxillary and frontal sinuses, so views that include these sinuses are important. Common radiographic findings include air-fluid levels and mucosal thickening, although not all sinusitis patients have air-fluid levels.
• Ultrasonography: Sinus ultrasonography may be considered when pregnancy or radiation exposure is a concern. Ultrasonography may also be useful in the intensive care unit to evaluate nosocomial sinusitis.^[28]
• MRI: This may be optimal for evaluation of suspected fungal sinusitis or suspected tumor.

Epiglottitis

• Direct visualization by laryngoscope: This is the standard for confirming epiglottitis. Before ordering radiography, consider whether imaging may unnecessarily delay patient care. Note that patients with epiglottitis breathe most comfortably when they are upright; the supine position may precipitate respiratory compromise. For patients in whom the diagnosis of epiglottitis is uncertain, a lateral neck image obtained in the erect position with soft tissue technique may be indicated.
• Lateral neck radiographs: In one small retrospective study, neck films were 33% specific for epiglottitis, with a positive predictive value of only 50%; the negative predictive value was 100%.^[29] Given the high false-positive rate, the authors concluded that the role of radiography was limited. However, neck imaging may help rule out epiglottitis. Radiographic findings include a swollen epiglottis with a shape similar to the human thumb. The image below illustrates epiglottitis on a neck radiograph.
• CT scanning: This study may be superior in delineating the soft tissue structures in the upper airway. However, CT scanning may unnecessarily delay therapeutic management, and recumbent positioning may precipitate respiratory compromise. See the image below. Lateral neck radiograph demonstrates epiglottitis. Courtesy of Marilyn Goske, MD, Cleveland Clinic Foundation.

Laryngitis

Radiographs are of little use except to exclude foreign-body aspiration.

Laryngotracheitis and laryngotracheitis

Laryngotracheitis in a patient with typical symptoms that respond appropriately to treatment does not require imaging. In croup, soft tissue neck images may reveal the classic steeple sign that represents subglottic narrowing. However, this sign is not always present and is not specific for croup.

Diagnostic procedures include throat swabs, nasal washes, sinus puncture and aspiration, and laryngoscopy.

Throat swab

For pharyngitis, a throat swab may be performed by vigorously rubbing a dry swab over the posterior pharynx and both tonsils to obtain a sample of exudates, if any. Avoid touching other surfaces of the oropharynx. Samples should be transported dry.

Nasal wash

To perform a nasal wash, a small syringe (3-5 mL) is filled with sodium chloride solution and attached to a short length of flexible tubing. The solution is rapidly instilled into the nostril, with the patient's head tilted back. Secretions are immediately aspirated back into the syringe and transferred to laboratory specimen containers.

Sinus puncture and aspiration

An otorhinolaryngologist may perform this procedure in complex, persistent cases of rhinosinusitis. However, sinus puncture and aspiration has no role in the routine assessment of acute rhinosinusitis.

Laryngoscopy

In cases of suspected epiglottitis, aggressive instrumentation may precipitate spasm and airway compromise. If the diagnosis is suspected in patients not in extremis, an otorhinolaryngologist may perform direct visualization to confirm the disease. Immediate access to intubation and cricothyroidotomy equipment is required. This diagnostic procedure is often performed in the operating room. In cases of laryngotracheitis, laryngoscopy may be considered if the patient is not in extremis. Laryngoscopy provides an opportunity for obtaining culture samples; however, contamination of the samples by upper airway flora is common.