Laboratory Tests

Because viruses cause most URIs, the diagnostic role of laboratory investigations and radiologic studies is limited. Viral culture, rapid antigen detection, or polymerase chain reaction (PCR) assay of influenza virus on a nasopharyngeal swab is indicated in patients for whom specific antiviral therapy is recommended. Similar tests are also available for adenovirus, respiratory syncytial virus, and parainfluenza virus. Experience with the use of reverse-transcriptase PCR for the diagnosis of enterovirus and rhinovirus infections is growing, but it is not currently available for daily clinical care.¹³ Serologic tests for viruses that can cause a mononucleosis-type illness should be considered in the appropriate clinical setting. Influenza serologies only have epidemiologic value and should not be used for clinical care. A pharyngeal swab for rapid antigen detection of GABHS is 90% sensitive and 95% specific in adults.^14,15 Increased antistreptolysin O titer is not helpful during the acute illness, and is usually detected several days later. Cultures obtained by paranasal sinus puncture should be reserved only for severely ill patients with acute sinusitis and intracranial or orbital complications. In patients with acute bronchitis, a normal C-reactive protein level can reasonably exclude pneumonia, but may be elevated with several other infectious and noninfectious conditions.

Imaging Studies

A lateral neck radiograph should be taken in a patient with stridor to assess the airways. However, this should not deviate attention from close monitoring for patency of the airways if epiglottitis is clinically suspected. Chest radiography should be reserved for patients with acute tracheobronchitis who have other comorbid conditions, those with abnormal vital signs or signs of consolidation on chest examination, or those with persistent symptoms for longer than 3 weeks. Plain radiography has been largely replaced by computed tomography (CT) in the evaluation of sinusitis, particularly in preparation for corrective surgery.¹⁶ Complete opacification and air-fluid level are the most specific findings for acute sinusitis. However, a large proportion of patients with the common cold have radiologic abnormalities on CT. Imaging is recommended for patients who do not respond to treatment with antibiotics and decongestants, but is not advised for the diagnosis of uncomplicated sinusitis. Mastoiditis and other intracranial complications of URIs should be evaluated by CT or magnetic resonance imaging.

Procedural Considerations

Only those experienced in endotracheal intubation should perform laryngoscopic examination of patients with suspected epiglottitis. Paranasal sinus endoscopy is not indicated for patients with uncomplicated acute sinusitis, and endoscopic cultures obtained from the middle meatus should be interpreted with caution because of potential contamination with nasal secretions.

Differential Diagnosis

Prodromal symptoms of viruses that cause systemic syndromes, such as measles and chickenpox, can mimic the common cold. Allergic rhinitis is characterized by itchy eyes and excessive lacrimation; it is often seasonally exacerbated or related to certain allergen exposure, which differentiates it from URIs. Sore throat could be a presenting symptom of acute thyroiditis, Ludwig’s angina, and gastroesophageal reflux disease, all of which should be differentiated from pharyngitis. Drug-induced mucositis can cause a noninfectious form of pharyngitis. Wegener’s granulomatosis should be considered when sinusitis does not respond to usual therapy. The most important step in the evaluation of someone with acute tracheobronchitis is to exclude pneumonia. If a cough lasts more than 3 weeks, postnasal drip, asthma, and gastroesophageal reflux disease are the most likely considerations.

Lifestyle Modifications

Rest is generally recommended for patients with URIs, mainly to allow patients to cope with their illness. There is no evidence that complete bedrest shortens the duration of illness. Voice rest is important for patients with hoarseness.

Medical Options

Symptomatic treatment for URIs should be directed to maximize relief of the most prominent symptom(s). Increased fluid intake is generally recommended in an attempt to thin respiratory secretions; however, caution about the development of hyponatremia should be considered in certain patients. Hundreds of over-the-counter (OTC) medications are available in various combinations, but none of these agents has proved to be a magic bullet.¹⁷ Americans spend more than $2 billion on OTC medications each year.

A meta-analysis of the literature has shown that nasal symptoms improve after treatment with α-adrenergic agonists such as oxymetazoline HCl, anticholinergic (parasympatholytic) agents such as ipratropium bromide, and first-generation antihistamines such as chlorpheniramine maleate. Only the first dose of decongestants has been proved to be effective, and repeated use may result in a rebound phenomenon—rhinitis medicamentosa—after discontinuation. The sedating effect of first-generation antihistamines can be hazardous in people driving cars or operating heavy machinery, but the effect may be desirable in patients who have difficulty falling asleep at night as a result of their symptoms.

The role of antitussives and expectorants in the treatment of URIs remains controversial. Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful for relieving fever, headache, and malaise, but these agents may be associated with gastrointestinal irritation. In addition, two cyclooxygenase 2 (COX-2) selective NSAIDS, rofecoxib and valdecoxib, have been withdrawn from the market because of increased cardiovascular risks. Warm saline gargles and steam inhalation are inexpensive and relatively safe measures that provide temporary relief of throat symptoms. Camphor and menthol also have been used in various concentrations for temporary relief of various URI symptoms. Mast cell stabilizers such as cromolyn sodium are widely used in preventing asthma attacks, but their role in treating URIs remains unknown. Topical nasal steroids such as fluticasone propionate improve the clinical success rates of patients with chronic or recurrent sinusitis who present with acute exacerbations.¹⁸ Systemic steroids should not be used for the treatment of URIs.

After several decades of debate and numerous studies, the role of vitamin C for the treatment of URIs remains controversial. It appears that large doses of vitamin C are necessary to achieve its beneficial effect as an antioxidant in activated leukocytes. However, doses in excess of 4 g/day have been associated with diarrhea. The average benefit in studies using 2 to 4 g/day of vitamin C has been a decrement of about half a day (15%) in the duration of illness.¹⁹

Similarly, the role of zinc salts remains controversial, and the specific mechanism of action is unknown. Duration of illness was reduced by about 1 day in studies that showed benefit.^20,21 The ionic bioavailability of zinc salts is an important factor in producing a beneficial effect.²² Bad taste occurs in up to 80% of patients receiving zinc lozenges, and nausea in about 20%. The long-term effects of cumulative doses of zinc are unknown, and altered lipid metabolism and copper deficiency are potential concerns. An intranasal formulation of zinc gel appears to have the same beneficial effect as oral zinc lozenges, with significantly fewer side effects. If considered, zinc lozenges or intranasal zinc gel should be started within 24 to 48 hours of the onset of cold symptoms.

The therapeutic effectiveness of echinacea in the treatment of URIs has not been established because of the heterogeneous nature of the preparations evaluated in published studies.^23–25 Reports of echinacea-related anaphylaxis in patients with atopy raise the concern of using it in such a common illness. Other traditional medicines, such as troxerutin,²⁶ Androgrophis paniculata,²⁷ and elderberry syrup²⁸ have been shown in small studies to shorten the duration and decrease the severity of URIs. Because herbal agents are neither patentable nor regulated by the U.S. Food and Drug Administration (FDA), dosages and formulations are not standardized.

Although viruses cause most URIs, antibiotics continue to be inappropriately widely prescribed for these illnesses.²⁹ Unnecessary adverse effects of antibiotics and the development of antimicrobial resistance can be reduced by judicious use of these drugs.³⁰ Health care providers should educate their patients about the self-limited nature of most URIs and the hazards of inappropriate use of antibiotics for the individual and the community.

Antibiotics have no role in the management of the common cold or any mild URI.³¹ However, almost 75% of adults with URIs are prescribed antibiotics by their physicians.³² This results in 41 million antibiotic prescriptions per year in the United States, accounting for more than 20% of all antibiotic prescriptions to adults. In addition, 68% of those receiving antibiotics are given nonrecommended, more expensive, broad-spectrum agents, a trend that has been increasing over time.²⁹ Unnecessary antibiotic prescriptions for treatment of URIs cost approximately $700 million per year. Several symptoms predictive of physicians’ behavior to prescribe antibiotics for URIs actually have poor predictive value with respect to the efficacy of antibiotics. These include cough productive of yellow sputum, sore throat, fever, and colored nasal discharge. About 75% of patients with URIs who seek medical attention expect to receive antibiotics, particularly if they have sinus pain. However, studies have shown that patient satisfaction with an office visit is independent of a patient’s initial belief about antibiotics and whether antibiotics were prescribed.³³ Satisfaction is more closely related to whether health care providers addressed patients’ concerns. Providing patients with written information, in addition to verbal advice about the lack of evidence to support the use of antibiotics, has been found to be valuable.³⁴ Another approach might involve giving the patient a prescription for an antibiotic, with instructions to fill it only after 3 days if symptoms fail to improve.³⁵

Patients with clinical and epidemiologic features consistent with GABHS-related pharyngitis should be started on antimicrobial therapy pending microbiologic confirmation.² Oral penicillin or erythromycin (in penicillin-allergic persons), given for 10 days, remains the preferred agent. Fortunately, no resistance to penicillin has been reported so far in GABHS-related pharyngitis patients.

Patients with only mild symptoms of acute sinusitis improve with topical nasal steroids and decongestants. Oral amoxicillin, trimethoprim-sulfamethoxazole, or doxycycline, given for 3 to 10 days, are the recommended first-line antibiotics for the treatment of moderate to severe acute sinusitis.^2,36 The incidence of penicillin-resistant S. pneumoniae and beta-lactamase–producing organisms causing acute sinusitis has been steadily increasing in the community. However, larger doses of amoxicillin, up to 3 g daily, or a combination of amoxicillin and clavulanate remain effective in most cases caused by resistant organisms.^3,10,11,36 Alternative agents include cefpodoxime, cefuroxime, and cefdinir. Factors predisposing patients to have antibiotic-resistant organisms include recent antibiotic use and exposure to children who attend daycare centers. Second-line, broad-spectrum, and more expensive agents, including the newer macrolides clarithromycin and azithromycin, and the “respiratory” fluoroquinolones—levofloxacin, gatifloxacin, and moxifloxacin—are no more effective than amoxicillin.³⁷ These agents should be reserved for use in individuals who are allergic or intolerant to first-line agents, those who do not respond to first-line agents within 3 days, or for confirmed microbiologic resistance. This approach would help contain ever-increasing health care costs and, most importantly, curtail the emergence of drug-resistant organisms as a result of selection pressure.

Treating acute tracheobronchitis with antibiotics is not recommended, because most cases are viral and thus resolve spontaneously.^4,38 In adults with persistent cough who report exposure to a patient with confirmed or suspected pertussis, erythromycin or trimethoprim-sulfamethoxazole should be administered for 14 days. This decreases contagion from bacterial shedding, but it is not expected to improve resolution of symptoms, unless started within 10 days of the onset of illness. Selective β-agonist bronchodilators offer symptomatic relief for cough.

Four agents are currently available for the treatment of influenza. Mild and nonfebrile influenza-like illness should not be treated with antiviral agents. The adamantanes, amantadine and rimantadine, are M2 ion channel blockers that are only active against influenza A and are associated with a high incidence of gastrointestinal and neuropsychiatric side effects, as well as development of viral resistance. The neuraminidase inhibitors (NAIs), oseltamivir and zanamivir, are active against both influenza A and B and have fewer side effects and less propensity to induce viral resistance than the adamantanes, but are considerably more expensive. In January 2006, a report of resistance to the adamantanes in 92% of circulating influenza isolates resulted in a national recommendation to use only NAI until this resistance pattern is reversed, hopefully in the coming years. Anti-influenza agents should be started within 1 to 2 days of onset of illness and continued for 5 days for maximum benefit.

Several antiviral agents with activity against rhinovirus or other viruses that cause URIs have been studied. Interferon is a powerful antiviral drug approved for the treatment of hepatitis B and C virus infections. It has no role in the treatment of viral URIs at this time. Other investigational agents such as pleconaril, a viral capsid inhibitor,³⁹ and tremacamra, a soluble intercellular adhesion molecule,⁴⁰ have shown some promise.