Respiratory infections

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Upper respiratory infections (URIs) affect the apparatus of the upper airways, which is made up of the nose, paranasal sinuses, trachea, pharynx and larynx. Syndromes affecting these structures are sometimes associated with one another, and one upper respiratory infection can progress to another type. It can be difficult to distinguish these infections from one another because they produce similar signs and symptoms. Frequently occurring URIs include the common cold, pharyngitis, laryngitis, croup, epiglottitis and sinusitis. However, the incidence of epiglottitis has significantly decreased since the introduction of the universal Haemophilus influenzae type b (Hib) vaccine.

Common Upper Respiratory Infections
URI Causative Agent(s) Symptoms Treatment
Common cold Rhinovirus, coronavirus, respiratory syncytial virus (RSV), parainfluenza virus, influenza virus, adenovirus Nasal stuffiness, rhinorrhea, sneezing, mild sore throat, low or no fever, cough, hoarseness Symptomatic: with decongestants, antihistamines, cough suppressant, etc.; vitamin C, zinc, ipratropium (intranasal), antiviral/anti-inflammatory combination
Pharyngitis Viral: cold virus (see above), Coxsackie virus A, herpes simplex virus, Epstein-Barr virus, HIV Bacterial: Streptococcus pyogenes Viral: sore, scratchy throat, dysphagia Bacterial: high fever, pharyngeal exudate, cervical adenopathy Viral: symptomatic Bacterial: penicillin or amoxicillin as appropriate, erythromycin in penicillin- allergic patients
Laryngitis Viral: influenza virus, rhinovirus, adenovirus, parainfluenza virus, RSV Bacterial: S. pyogenes Fungal: C. albicans (in immunosuppressed patients) Lowered voice pitch, hoarseness, loss of voice (aphonia) Resting voice, moist air treatments, antibiotics/antifungals if appropriate
Simple croup Parainfluenza
viruses type 1,2,3; influenza virus; RSV
Follows URI; dry, barking cough in evening; hoarseness; shortness of breath; may progress to laryngeal obstructio Moist, humidified air; cool air; nebulized epinephrine; corticosteroids
Epiglottitis H. influenzae type B Rapid onset, fever, drooling, difficulty swallowing, sore throat, airway obstruction Medical emergency, requires the establishment of artificial airway, IV ampicillin and chloramphenicol, or cephalosporin, according to culture results
Sinusitis Acute: S. pneumoniae, H. influenzae, M. catarrhalis Chronic: S. aureus, S. pyogenes, anaerobes, resistant organisms from acute infection, P. aeruginosa, fungal infections Headache, sinus tenderness, nasal congestion, cough Analgesics, decongestants, empiric antibiotics, control allergic sinusitis, sinus irrigation, surgery

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, causing symptoms that last 1–2 weeks. In the U.S., close to $2 billion are spent annually on over-the-counter cough and cold preparations.

Rhinoviruses cause over 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 there are a large variety of cold viruses. Each type has different patterns of occurrence and all are easily spread. Colds are probably transmitted in three ways: through direct contact with secretions on skin and in the environment, in large particles of respiratory secretions transported through the air, and in infectious droplets suspended in the air. The incubation period for most cold-causing viruses is 48–72 hours.

Classic symptoms of a cold include nasal stuffiness and discharge, sneezing, and mild sore or scratchy throat. Fever is usually mild in children and rarely elevated more than one degree in adults. Cough and hoarseness often develop. In most cases, patients self-diagnose colds, and treatment targets the most bothersome symptoms. Treating nasal congestion with topical and oral adrenergic agents is effective, and long-acting products make compliance easy. Pharmacists should reinforce dosing instructions and emphasize limiting the duration of treatment with topical decongestants to prevent rebound congestion.

Rhinorrhea can be treated using cholinergic blockers to prevent glandular secretion. Intranasal ipratropium has been approved to treat this symptom. First generation antihistamines such as clemastine fumarate also decrease rhinorrhea, probably due to an anticholinergic rather than an antihistaminic activity. Second generation nonsedating antihistamines do not appear to affect common cold symptoms.

Cough during a cold is typically caused by postnasal drainage and obstruction and 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 doctor. While the effectiveness of over-the-counter cold products in young children has not been demonstrated, these products reduce symptoms in adolescents and adults.

Treatments that target the viral infection itself and the host inflammatory response are being studied. Vitamin C, once thought to have little effect on the prevention of the common cold, may actually decrease the duration of a cold episode by about one day, possibly by affecting the immune response. Well-controlled studies are needed to determine the dose and duration necessary 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 may be due in part to the wide variety of formulations, study design variations, and analysis of results. It is difficult to recommend the use of zinc lozenges routinely 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 cold infections. 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 may also be due to bacteria, primarily group A beta-hemolytic streptococcus.Streptococcal infections respond rapidly to penicillins, and serious complications such as acute rheumatic fever and glomerulo-nephritis can be avoided.

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 major complaint in these cases. Coxsackievirus infections, herpes simplex virus, infectious mononucleosis due to Epstein Barr virus, and HIV all may be accompanied by pharyngitis. Bacterial pharyngitis differs greatly among patients, depending on causative agents. Streptococcal pharyngitis in some can cause pharyngeal membrane to become fiery red with exudate, 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 compliance issues. In penicillin-allergic patients, the 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 may also fail because compliance was not adequate. Frequent daily dosing, poor patient acceptance, adverse gastrointestinal effects, improper storage, and early discontinuation of therapy due to symptomatic improvement all contribute to poor compliance. Pharmacists’ counseling can tremendously improve compliance and therapy outcome.

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 the influenza virus, rhinovirus and adenovirus. Infectious laryngitis often correlates 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 a mild illness. The development of severe hoarseness and airway obstruction with respiratory distress, inspiratory stridor and air hunger is unusual.

The primary symptom of laryngitis is a lowered vocal pitch, hoarseness, and sometimes complete loss of voice. The physical exam 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 is essentially resting the voice. Inhaling moistened air may bring some relief. Because the etiology of laryngitis is typically viral, antibiotics are not of benefit in most cases. If the hoarseness continues beyond 2 weeks, a laryngoscopic exam must be performed to rule out other diseases.

Croup

Simple croup (acute laryngotracheobronchitis) is a viral respiratory tract infection in children that results in inflammation of the subglottic region. The severity of the case depends in part on the child’s age, infecting virus, and the predisposition of the child to develop croup. It is most frequently seen in children ages 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. Therefore, they are blocked to a greater degree than those of an older child by the inflammation and edema. The most common viral causes of croup are parainfluenza virus, influenza virus, and RSV. There are seasonal variations in the incidence of this infection. Outbreaks usually occur in the fall, winter, or early spring.

Most children have a upper respiratory infection for a few days prior to the onset of croup symptoms. There may be a slight or moderate fever, sometimes hoarseness, but few other symptoms except rhinitis or conjunctivitis. Mild cases of croup result in a characteristic “croupy” or “brassy” cough that resembles a barking noise. This cough is usually nonproductive. Symptoms usually worsen during the night, often waking the child suddenly with shortness of breath and a feeling of apprehension. The symptoms may significantly improve, even disappear, during the day but return at night. Symptoms improve slowly over several days. However, if the laryngeal obstruction progresses, inspiratory stridor and respiratory distress may follow. Small children may become agitated and cry, aggravating symptoms and making breathing even more difficult. In some children, a high fever (>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. Cold outdoor air may also adequately relieve symptoms. Once breathing becomes more comfortable, a bedroom humidifier may prevent the return of laryngeal spasm over the next few evenings. If a child does not respond to home treatment, a doctor’s office or emergency room visit is the next step. Nebulized epinephrine has been shown to improve symptoms, but the effect is transient, and patients responding to epinephrine require continued observation. In many cases, oral or parenteral steroids (typically dexamethasone) for 1 to 3 days have been used to reduce inflammatory edema. Although the efficacy of steroids remains controversial, this treatment often dramatically improves the clinical picture in patients, with 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 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 the development of croup. However, this measure has not been proven effective.

Epiglottitis

Epiglottitis is a rapidly progressing, life-threatening swelling of the epiglottis and surrounding tissues. It is usually caused by H. influenzae type b. Typically, patients are 2- to 4-year-old boys who have experienced 6–12 hours of fever and difficulty swallowing. Older children and adults complain of sore throat. The hallmark of epiglottitis (differentiating it from croup, diphtheria, angioneurotic edema or foreign body aspiration) is the patient’s appearance. Often described as “toxic,” these patients may be pallid, lethargic, irritable, hypotensive and dehydrated, with rapid heart rate and rapid breathing. They are usually in respiratory distress, leaning forward while sitting and drooling oral secretions because they cannot swallow. There may be inspiratory stridor and hoarseness. Diagnosis is made by examining the epiglottis, which appears bright red. Epiglottitis may result in complete airway obstruction within as little as 30 minutes after symptoms begin. An immediate airway must be established in these patients by endotracheal tube insertion. The tube must remain in place for 3–5 days until the inflammation and swelling of the epiglottis has subsided. Conventional treatment includes 7–10 days of an appropriate parenteral antibiotic. Household contacts under the age of 4 years should be treated with 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.

Sinusitis

Sinusitis is an infection of the paranasal sinuses that often follows a viral upper respiratory tract infection or appears as a complication of allergic rhinitis. If 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,
H. 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 it may be purulent or even clear. Many patients also complain of a 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 employed. Tests to confirm the pathogen (sinus cavity aspiration) are invasive and expensive. Oral antibiotics may be discontinued if symptoms have disappeared after 10–14 days of therapy. If symptoms linger, 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 the symptoms of sinusitis continue for more than 6 weeks. Often these infections are caused by anaerobes, S. aureus, or organisms resistant to previously used antimicrobial therapy. Treatment may require beta-lactamase inhibitors (e.g., amoxicillin/clavulanate, cephalosporin or newer macrolide antibiotics). Resistant infections may require additional diagnostics to determine appropriate antibiotic therapy. Chronic sinusitis can lead to permanent mucosal damage.

Handwashing is the most effective way to stop the spread of sinusitis. In atopic patients, controlling allergic rhinitis should help decrease episodes of acute sinusitis. Although not a proven method, prompt use of nasal decongestants when nasal stuffiness occurs may help prevent poor sinus drainage and impending infection. Adequate treatment of acute sinusitis may also prevent the development of a more chronic condition.

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