About Respiratory Infections

Upper respiratory infections (URIs) affect the upper airway, which includes the nose, paranasal sinuses, trachea, pharynx, and larynx. Syndromes affecting these structures can be associated with one another, and one URI can progress to another type of upper respiratory infection. It can be difficult to distinguish these infections because they cause similar signs and symptoms. Common URIs include the common cold, pharyngitis, laryngitis, croup, epiglottitis, and sinusitis. However, the incidence of epiglottitis has decreased substantially since the introduction of universal vaccination against Haemophilus influenzae type b (Hib). Understanding these infections can help patients recognize symptoms, use treatments appropriately, and know when to seek medical advice.

The Common Cold

The "common cold" is actually a group of upper respiratory infections caused by six different virus families. This infection is usually mild and self-limiting, and symptoms typically last 1-2 weeks. In the United States, close to $2 billion is spent annually on over-the-counter cough and cold preparations.

Rhinoviruses cause more than 30% of colds. Coronaviruses and respiratory syncytial virus (RSV) are also among the most common causes. "Cold season" usually begins in late August or September and ends after a spring peak in April or May. Colds frequently recur throughout the season because many different cold viruses circulate. Each virus has different patterns of occurrence, and all are easily spread. Colds are likely transmitted in three ways: by direct contact with secretions on the skin or in the environment; by large particles of respiratory secretions transported through the air; and by infectious droplets suspended in the air. The incubation period for most cold-causing viruses is 48-72 hours. Helping patients understand how colds spread can reinforce the importance of hand hygiene and respiratory etiquette.

Classic symptoms of a cold include nasal congestion and discharge, sneezing, and a mild sore or scratchy throat. Fever is usually mild in children and rarely rises by more than 1 degree in adults. Cough and hoarseness often develop. In most cases, patients self-diagnose colds, and treatment targets the most bothersome symptoms. Topical and oral adrenergic agents can effectively treat nasal congestion, and longer-acting products can make adherence easier. Pharmacists should reinforce dosing instructions and emphasize limiting the duration of treatment with topical decongestants to prevent rebound congestion.

Rhinorrhea can be treated with cholinergic blockers to reduce glandular secretion. Intranasal ipratropium has been approved to treat this symptom. First-generation antihistamines such as clemastine fumarate can also decrease rhinorrhea, likely through anticholinergic rather than antihistaminic activity. Second-generation non-sedating antihistamines do not appear to affect common cold symptoms.

Cough during a cold is typically caused by postnasal drainage and obstruction, and it may respond to an antihistamine-decongestant combination. Cough suppressants such as dextromethorphan or codeine and expectorants such as guaifenesin have not been adequately studied in the common cold. A cough that persists after other cold symptoms resolve may be due to a complication such as sinusitis or reactive airway disease. These cases should be referred to a physician. Persistent or worsening symptoms, high fever, or difficulty breathing should also prompt timely assessment by a healthcare provider.

Treatments that target the viral infection itself and the host inflammatory response are under study. Vitamin C, which was once thought to have little effect in preventing the common cold, may decrease the duration of a cold episode by about 1 day, possibly by affecting the immune response. Well-controlled studies are needed to determine the dose and duration required to produce this effect.

A promising antiviral treatment is zinc gluconate. Zinc has been shown to inhibit rhinovirus replication in vitro, but in vivo study results have been inconsistent. This inconsistency may be due, in part, to the wide variety of formulations, differences in study design, and variations in how results were analyzed. It is difficult to recommend routine use of zinc lozenges until more comparative studies are completed, but results to date are encouraging.

Other compounds studied for cold treatment include interferon, nonsteroidal anti-inflammatory agents, and ipratropium bromide. Prophylaxis with interferon has not proven effective in preventing colds. Combination products containing intranasal interferon and ipratropium with oral naproxen have shown some activity in experimentally induced colds. These products may have a greater effect than single agents alone in shortening the duration of a cold infection.

Pharyngitis

Pharyngitis is an acute inflammation of the pharynx. It most often occurs with viral infections such as the common cold or influenza. It can also be caused by bacteria, primarily group A beta-hemolytic streptococcus. Streptococcal infections respond rapidly to penicillins, and serious complications such as acute rheumatic fever and glomerulonephritis can be avoided. For clinicians and patients, distinguishing viral from bacterial pharyngitis is important because it guides antibiotic use.

Viral pharyngitis can occur as part of the common cold, but it is usually mild. Pharyngitis accompanying influenza, however, can be severe and is often the main complaint in these cases. Coxsackievirus infections, herpes simplex virus, infectious mononucleosis due to Epstein-Barr virus, and HIV can all be accompanied by pharyngitis. Bacterial pharyngitis varies considerably among patients, depending on the causative agent. In some people, streptococcal pharyngitis can cause the pharyngeal membrane to become intensely red with exudate, with high fever and cervical adenopathy. In others, only mild symptoms and physical findings are present.

In most cases, a definitive diagnosis cannot be made on clinical findings alone. Rapid antigen detection tests help determine the need for antibiotic therapy. Family members of patients and other close contacts who develop symptoms should also be tested. If a test is positive, a 10-day course of penicillin V or amoxicillin should be started. Amoxicillin is often chosen for young children, primarily because of its palatability. A single dose of benzathine penicillin is also acceptable and virtually eliminates adherence issues. In penicillin-allergic patients, newer macrolides such as clarithromycin and azithromycin are associated with a much lower incidence of gastrointestinal distress than erythromycin. If the antigen test is negative, the swab should be cultured to confirm the absence of streptococcus. Treatment may be started and then discontinued if the culture is negative, or it can be withheld while awaiting culture results.

If a 10-day course of penicillin fails, viral pharyngitis may be present. Treatment can also fail because adherence was inadequate. Frequent daily dosing, poor patient acceptance, adverse gastrointestinal effects, improper storage, and early discontinuation of therapy due to symptomatic improvement can all contribute to poor adherence. Pharmacists' counselling can greatly improve adherence and treatment outcomes.

Laryngitis

Infectious laryngitis is a common illness that is almost always caused by a virus. However, hoarseness can develop with bacterial respiratory infections and even candidal infections in immunocompromised patients. The most common viruses associated with laryngitis are influenza virus, rhinovirus, and adenovirus. Infectious laryngitis often occurs with symptoms such as cough and sore throat. In children, laryngitis is usually part of another upper respiratory infection, such as croup. Viral laryngitis is usually mild. Severe hoarseness and airway obstruction with respiratory distress, inspiratory stridor, and air hunger are unusual.

The primary symptom of laryngitis is a lowered vocal pitch, hoarseness, and sometimes complete loss of voice. Physical examination shows little more than pharyngeal inflammation. If the larynx is examined using laryngoscopy, the vocal cords and subglottic tissue show inflammatory edema. Treatment for laryngitis mainly involves voice rest. Inhaling humidified air may provide some relief. Because the etiology of laryngitis is typically viral, antibiotics are not beneficial in most cases. If hoarseness continues beyond 2 weeks, a laryngoscopic examination must be performed to rule out other diseases. Patients should be advised to seek care promptly if they notice progressively worsening difficulty breathing, pain, or blood in sputum.

Croup

Simple croup (acute laryngotracheobronchitis) is a viral respiratory tract infection in children that results in inflammation of the subglottic region. Severity depends in part on the child's age, the infecting virus, and the child's predisposition to develop croup. It is most frequently seen in children aged 3 months to 3 years, although it can complicate respiratory infections in older children. Young children have more difficulty with respiratory distress during croup because their airways are smaller. As a result, inflammation and edema can cause proportionally greater blockage than in an older child. The most common viral causes of croup are parainfluenza virus, influenza virus, and RSV. The incidence of this infection varies by season. Outbreaks usually occur in the fall, winter, or early spring.

Most children have an upper respiratory infection for a few days before croup symptoms begin. There may be a slight or moderate fever, sometimes hoarseness, but few other symptoms except rhinitis or conjunctivitis. Mild cases of croup cause a characteristic "croupy" or "brassy" cough that sounds like barking. This cough is usually nonproductive. Symptoms usually worsen during the night and can wake the child suddenly with shortness of breath and a feeling of apprehension. Symptoms can improve substantially, or even resolve, during the day but return at night. Symptoms usually improve slowly over several days. However, if laryngeal obstruction progresses, inspiratory stridor and respiratory distress may develop. Small children may become agitated and cry, which can aggravate symptoms and make breathing even more difficult. In some children, a high fever (>39°C (102°F)) and respiratory distress can progress to hypoxia, cyanosis, and cardiopulmonary arrest. This situation must be treated as a medical emergency.

Most patients who develop croup can be adequately treated at home. Laryngeal spasm is often relieved by placing the child in a closed bathroom and running a hot shower or bath to create a warm, humid environment. Cool outdoor air may also relieve symptoms. Once breathing becomes more comfortable, a bedroom humidifier may help prevent the return of laryngeal spasm over the next few evenings. If a child does not respond to home treatment, the next step is an appointment with a physician or a visit to the emergency department. Nebulized epinephrine has been shown to improve symptoms, but the effect is transient, and patients who respond to epinephrine require ongoing observation. In many cases, oral or parenteral steroids (typically dexamethasone) for 1 to 3 days are used to reduce inflammatory edema. Although the efficacy of steroids remains controversial, this treatment often dramatically improves the clinical picture, with a small risk of adverse effects.

Children who have had croup appear to be predisposed to future episodes. These children may have hyperreactive airways with an allergic component to their symptoms. This theory is based on the frequent finding of positive skin tests and a family history of allergies in children who are predisposed to croup. It is often recommended that these patients use a bedroom humidifier during any upper respiratory infection to help prevent croup. However, this measure has not been proven effective.

Epiglottitis

Epiglottitis is a rapidly progressive, life-threatening swelling of the epiglottis and surrounding tissues. It is usually caused by Haemophilus influenzae type b. Typically, patients are boys aged 2 to 4 years who have had 6-12 hours of fever and difficulty swallowing. Older children and adults complain of sore throat. The hallmark of epiglottitis (which differentiates it from croup, diphtheria, angioneurotic edema, or foreign body aspiration) is the patient's appearance. These patients are often described as "toxic" and may be pallid, lethargic, irritable, hypotensive, and dehydrated, with tachycardia and tachypnea. They are usually in respiratory distress, leaning forward while sitting and drooling oral secretions because they cannot swallow. Inspiratory stridor and hoarseness may be present. Diagnosis is made by examining the epiglottis, which appears bright red. Epiglottitis may cause complete airway obstruction within as little as 30 minutes after symptoms begin. An airway must be established immediately by endotracheal tube insertion. The tube must remain in place for 3-5 days, until inflammation and swelling of the epiglottis subside. Conventional treatment includes 7-10 days of an appropriate parenteral antibiotic. Household contacts under the age of 4 years should receive rifampin prophylaxis 20 mg/kg/day (maximum 600 mg/day) for 4 days. Patients should be discharged with the same regimen to prevent reintroduction of the organism into the household. Routine Hib vaccination has made epiglottitis less common in many regions, but any suspected case still requires emergency care.

Sinusitis

Sinusitis is an infection of the paranasal sinuses that often follows a viral upper respiratory tract infection or occurs as a complication of allergic rhinitis. If it is not effectively treated, sinusitis can lead to serious infections such as bacterial meningitis, subdural or epidural abscess, or brain abscess.

Sinusitis may be acute or chronic. Most acute cases are due to Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Anaerobic bacteria and Staphylococcus aureus are predominant causes of chronic sinusitis and its intracranial complications. Pseudomonas aeruginosa causes sinusitis in immunocompromised patients or those with nasal tubes or catheters, and fungi can be the culprit in HIV-infected patients.

Acute sinusitis is often accompanied by greenish-yellow nasal discharge, although discharge may be purulent or even clear. Many patients also report cough and postnasal drip from sinus drainage, low-grade fever, headache, and decreased appetite. There may be tenderness over the maxillary or frontal sinuses and areas of opacity on sinus x-rays. Empiric use of ampicillin or amoxicillin for 10-20 days is commonly used. Tests to confirm the pathogen (sinus cavity aspiration) are invasive and expensive. Oral antibiotics may be discontinued if symptoms have resolved after 10-14 days of therapy. If symptoms persist, an additional 10-14 days of treatment may be necessary. Decongestants (topical or systemic) and oral antihistamines are useful in patients with allergic rhinitis. Intranasal steroids may increase the risk of developing fungal sinusitis.

Chronic sinusitis is diagnosed when symptoms continue for more than 6 weeks. These infections are often caused by anaerobes, Staphylococcus aureus, or organisms resistant to previously used antimicrobial therapy. Treatment may require beta-lactamase inhibitors (for example, amoxicillin/clavulanate), a cephalosporin, or newer macrolide antibiotics. Resistant infections may require additional diagnostics to determine appropriate antibiotic therapy. Chronic sinusitis can lead to permanent mucosal damage.

Complications and When to Seek Urgent Care

Although most upper respiratory infections are self-limited, they can occasionally lead to serious complications. The table below summarizes selected complications mentioned in this article and highlights situations in which urgent assessment is important.

Handwashing is the most effective way to reduce the spread of sinusitis. In atopic patients, controlling allergic rhinitis should help decrease episodes of acute sinusitis. Although it is not a proven method, prompt use of nasal decongestants when nasal congestion occurs may help prevent poor sinus drainage and impending infection. Adequate treatment of acute sinusitis may also prevent progression to a more chronic condition. Across all upper respiratory infections, careful symptom monitoring and early contact with a healthcare provider when concerns arise can improve safety and outcomes.