Upper respiratory tract infections (URIs) include a group of illnesses that can be mild to life-threatening where the upper respiratory tract is the main affected part. The infecting organism can affect the sinuses, the nasal passages, the pharynx or the larynx. Several diseases can be put under the umbrella of URIs which include rhinitis, pharyngitis, sinusitis, epiglottitis, laryngitis and tracheitis.

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influenza virus particle color

Image: “This (pseudocolored) negative-stained (false-colored) transmission electron micrograph (TEM) depicts the ultrastructural details of an influenza virus particle, or “virion”.” by Photo Credit: Cynthia Goldsmith Content Providers(s): CDC/ Dr. Erskine. L. Palmer; Dr. M. L. Martin – This media comes from the Centers for Disease Control and Prevention’s Public Health Image Library (PHIL), with identification number #10073. License: Public Domain


Definition of Upper Respiratory Tract Infection

Rhinitis can be defined as the inflammation of the nasal mucosa, which is found in some allergic conditions. Patients with sinusitis have inflammation of the paranasal sinuses which include the frontal, ethmoid, maxillary and sphenoid sinuses.

Rhinopharyngitis is the inflammation of the nasal passages, the pharynx and the tonsils. The common cold usually results in rhinopharyngitis. Patients with epiglottitis can have bacterial etiology and the condition might be life-threatening.

Epidemiology of URIs

URIs are considered as the most common infectious diseases in the population. Patients can develop the common cold up to four times per year for adults, and eight times per year for children. Viral and bacterial pharyngitis are common in children and account for 1% of the outpatient clinic visits.

epiglottitis x-ray

Image: “Acute epiglottitis; lateral view in X-ray imaging. The lateral soft-tissue radiograph reveals the “thumb sign” that indicates a swollen epiglottis, suggestive of epiglottitis. The diagnosis was confirmed on subsequent imaging and laryngoscopy. The patient recovered following treatment with predonine and ceftriaxone.” by Med Chaos – Own work. License: CC0 1.0

Sinusitis in patients with uncomplicated URIs is common and can be identified in up to 80% of the cases. Fortunately, bacterial sinusitis is only found in 2% of the cases.

Epiglottitis is usually caused by Haemophilus influenzae infection and since the introduction of Hib vaccine, the incidence of epiglottitis decreased significantly. The current incidence of acute epiglottitis is estimated to be about 0.98 case per 100,000. Pneumococcal epiglottitis is responsible for 0.28 cases of epiglottitis per 100,000.

Croup or laryngotracheobronchitis is common in children aged 6 months to 6 years. Most cases of croup occur in children aged two years. Fortunately, despite the harsh breathing sounds, the condition is self-limiting.

Pertussis is responsible for whooping cough, another URI that has significantly decreased after the introduction of pertussis vaccination. The current incidence of whooping cough due to pertussis is estimated to be 9 per 100,000.

URIs are usually seasonal and most cases occur in fall or winter. It is hypothesized that cold weather increases indoor time and therefore puts us at prolonged exposure with those already infected.

Additionally, low humidity in winter is thought to be a significant factor in the thrive and increased virulence of the different viruses implicated with URIs.

The common cold appears to be more common in young women. Epiglottitis on the other hand is more common in men. Croup, for obscure reasons, is more common in boys rather than girls.

Etiologies of URIs

URIs can be caused by several viral and bacterial pathogens. The most commonly implicated viruses with URIs are rhinoviruses, coronaviruses, adenoviruses and coxsackieviruses.

epstein-barr virus

Image: “Epstein-Barr virus taken through an electron microscope.” by Linda Bartlett (Photographer) – This image was released by the National Cancer Institute, an agency part of the National Institutes of Health, with the ID 2105. License: Public Domain

The common cold is usually related to the rhinoviruses while coronaviruses can also account for a significant number of the cases. Adenoviruses can also cause nasopharyngitis.

Pharyngitis is usually caused by viruses by the recognition of group A streptococcus. Common viruses that are implicated with pharyngitis include adenovirus, the influenza viruses, and Epstein-Barr virus.

Group A streptococcal infection is responsible for up to 15% of the cases of pharyngitis in adults and 30% in children. Therefore, the early recognition of bacterial streptococcal pharyngitis is essential to prevent complications.

Patients with rhinosinusitis usually have another viral URI such as rhinovirus, coronavirus, or influenza A or B infection. These patients can have signs of sinusitis on computed tomography, which usually goes without any complications.

Secondary bacterial infection however can happen in few cases. Common organisms are streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and staphylococcus aureus.

Epiglottitis has been historically linked to Haemophilus influenzae but since the introduction of the Hib vaccine, the incidence of acute epiglottitis decreased dramatically. On the other hand, cases of streptococcus epiglottitis are becoming more commonly identified nowadays.

Croup can be caused by parainfluenza viruses types 1, 2 and 3. In few children, the cause is the influenza viruses.

Pathophysiology of URIs

Patients need to come in contact with an infected person or with inanimate objects that have been contaminated with the infecting organism. Once the person’s hand becomes contaminated with the potential pathogen, he or she can introduce the organism to him/herself when they touch the nose or the mouth. Viral or bacterial inoculation happens which is followed by the invasion of the mucosa lining the upper respiratory airway.

In addition to the virulence of the infecting organism, the person’s genetic susceptibility also plays a role in determining who is more likely to get sick once in contact with someone with URIs. Certain polymorphisms related to the immune system put the patient at an increased risk of developing severe influenza illness once exposed to the H1N1 or the H5N1 influenza viruses.

Clinical Presentation of URIs

The symptoms of Influenza, other URIs and allergies can overlap. Patients with the common cold usually develop it within 2 to 3 days after exposure and include rhinorrhea, nasal congestion and sneezing. Patients can also complain from a sore throat and painful swallowing. Cough can be a symptom in some cases. Patients might develop a fever for a day or two.

symptoms of influenza

Image: “Main symptoms of influenza.” by Mikael Häggström. License: Public Domain

Patients with influenza virus infection develop body aches, high fever, severe sore throat and headaches. Patients with severe or progressive pharyngitis might have streptococcal pharyngitis.

Patients with bacterial pharyngitis might have a low-grade fever. Children can develop a skin rash. Unfortunately, history taking alone is usually not sufficient to exclude streptococcal pharyngitis.

The presence of anterior cervical lymphadenopathy is not characteristic of bacterial infection. The presence of tonsils exudates, tender anterior cervical lymph nodes and the absence of conjunctivitis, cough and rhinorrhea are suggestive of bacterial rather than viral pharyngitis.

Patients with bacterial sinusitis can develop persistent nasal discharge for more than 10 days, worsening of their cough and fever, or develop severe cough and fever from the start for three consecutive days.

Patients with epiglottitis usually complain of sore throat, muffled sound, fever, drooling and can present within the tripod position.

Diagnostic Workup in URIs

The identification of the exact infecting organism should be attempted only when specific treatment can be provided or in the immunocompromised patient. Rapid tests are available for the detection of influenza and parainfluenza viruses. Viral cultures are the standard criterion for the identification of the viral etiology of the URI but the results are usually available too late to alter the medical treatment, two to four weeks.

Complete blood count is helpful in excluding possible bacterial infections which are characterized by neutrophilia. Unfortunately, leukocytosis is rarely seen in URIs and complete blood count is usually not helpful in most cases.

Patients presenting with symptoms consistent with the common cold should not be offered routine imaging studies. Patients presenting with high fever, tender neck examination and signs suggestive of peritonsillar abscess need specific imaging studies including x-rays.

Patients with suspected group A streptococcal infection should undergo throat swab testing for group A streptococcus detection by rapid antigen testing, culture or both. Positive rapid antigen detection testing for group A streptococcus is highly specific and warrants specific treatment.

On the other hand, negative results should be backed up by a negative throat swab culture. Routine testing for streptococcal antibodies including the antistreptolysin O antibody is not helpful in the identification of acute infection because these antibodies usually peak 5 weeks after the infection.

Patients with suspected bacterial sinusitis should undergo computed tomography imaging of the sinuses. Computed tomography imaging should be preserved only for bacterial cases because it can be positive in up to 80% of the cases of uncomplicated rhinosinusitis.

Pertussis is usually a clinical diagnosis. Rapid direct fluorescent antibody testing can be used to confirm the diagnosis if needed. Patients with possible epiglottitis should undergo neck x-ray which is usually enough to exclude the diagnosis.

Treatment of URIs

Treatment of URIs is usually symptomatic but can be sometimes specific to the exact etiology or disease process.

Treatment of the common cold

Patients with symptoms consistent with uncomplicated common cold should drink plenty of water, might benefit from steamy baths and can use nasal decongestants for a limited period of time. Nonsteroidal anti-inflammatory drugs can be used to alleviate pain and inflammation. No specific antiviral treatment is usually indicated.

Treatment of influenza

Antiviral therapy can be helpful early in the disease as it was found to decrease the duration and the severity of the illness. Additionally, annual influenza vaccination not only decreases the risk of developing influenza during the season but also decreases the severity of the symptoms if one acquires the infection. Nonsteroidal anti-inflammatory drugs, drinking plenty of water and decongestants are also helpful.

Treatment of rhinosinusitis

amoxicillin 3d structure

Image: “3D structure of amoxicillin.” License: Public Domain

Symptomatic treatment of viral rhinosinusitis is usually sufficient. Patients with suspected bacterial sinusitis should receive high dose amoxicillin/clavulanate as first line therapy. Patients allergic to penicillins can receive doxycycline or levofloxacin. Patients who are not responsive to initial antibiotic treatment should undergo culture and sensitivity testing to confirm the infecting organism and its resistance profile.

Treatment of croup

Inhaled corticosteroids in addition to intravenous steroids are helpful in alleviating the symptoms of croup. Additionally, fluid replacement therapy should be started in children to avoid dehydration. Inhaled racemic epinephrine can also provide symptomatic relief.

Treatment of epiglottitis

Intravenous administration of antibiotics is indicated and should be started before the availability of the culture results. Ceftriaxone and cefuroxime are common first-line therapies for epiglottitis. Close contacts of the patient should also receive prophylactic antibiotic therapy.

Treatment of group A streptococcus pharyngitis

Group A streptococcus is sensitive to amoxicillin and penicillin. Therefore, oral administration of one of these two antibiotics is usually sufficient. Patients with non-anaphylactic shock to penicillins can receive a first generation cephalosporin. Patients with severe allergies should receive clindamycin, azithromycin or clarithromycin.

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