Navigating Common Upper Respiratory Tract Conditions

RELEASE DATE

July 1, 2023

EXPIRATION DATE

July 31, 2025

FACULTY

Leticia Shea, PharmD, BCACP
Associate Professor
Regis University School of Pharmacy
Denver, Colorado

Micheline A. Goldwire, PharmD, MS, MA, BCPS
Professor and Director, Drug Information Services
Regis University School of Pharmacy
Denver, Colorado

FACULTY DISCLOSURE STATEMENTS

Drs. Shea and Goldwire have no actual or potential conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT

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Postgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

UAN: 0430-0000-23-066-H01-P
Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge

TARGET AUDIENCE

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

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DISCLAIMER

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL

To provide pharmacists with an overview of common upper respiratory tract conditions in adults and adolescents.

OBJECTIVES

After completing this activity, the participant should be able to:

  1. Describe common upper respiratory tract conditions in adolescents and adults.
  2. Discuss common upper respiratory tract conditions and corresponding symptoms.
  3. Discuss potential management strategies for common upper respiratory tract conditions.
  4. Review recommended appropriate therapy for common upper respiratory tract conditions.

ABSTRACT: The management of respiratory illnesses, including allergic rhinitis, acute rhinosinusitis, influenza, and pharyngitis, involves a combination of pharmacologic interventions and nonpharmacologic measures. Antihistamines, intranasal corticosteroids, and intranasal decongestants offer symptom relief for allergic rhinitis. Acute rhinosinusitis may require antibiotics, nasal decongestants, and saline nasal irrigation. Influenza can be managed with antiviral medications if initiated early. Pharyngitis treatment includes pain relievers, throat lozenges, and antibiotics for bacterial infections. Nonpharmacologic recommendations such as adequate rest, hydration, and supportive care are essential for all of these conditions. Individualized treatment plans should consider the severity, underlying causes, and patient preferences to optimize outcomes and improve the overall well-being of patients.

Common respiratory illnesses affect the nose, sinuses, pharynx, and larynx and are caused by a variety of viruses and bacteria, including rhinovirus, influenza virus, coronavirus, and Streptococcus pneumoniae. These infections can range from mild to severe and can have a significant impact on one's quality of life (QOL). In addition to upper respiratory tract infections (URTIs), common respiratory conditions include the common cold and allergic rhinitis. This article will focus on the management of allergic rhinitis, acute rhinosinusitis (including the common cold, post viral, and bacterial), influenza, and pharyngitis. The management of COVID is beyond the scope of this article, and the reader should refer to recent reviews in U.S. Pharmacist.

Most people will experience a URT condition. Moreover, according to the CDC, adults in the United States experience an average of two to three URTIs per year.1 URT conditions are most common during the fall and winter months, but they can occur at any time of the year. Most of these infections are caused by viruses, with the most common ones being rhinovirus, coronavirus, and influenza, and do not necessitate antibiotics.2 However, research reveals that up to 10 million antibiotic medications are prescribed inappropriately for respiratory tract infections each year. A cohort study consisting of approximately 15,000 outpatients with acute URTIs discovered that 41% of patients prescribed antibiotics did not require them.3 The unwarranted use of antibiotics can lead to negative outcomes, including antibiotic resistance, adverse events, and added expenses. Adverse events caused by antibiotics are generally mild, such as diarrhea or rash, but can be severe, including Stevens-Johnson syndrome, Clostridioides difficile colitis, anaphylaxis, and even sudden cardiac death.4 It is crucial to differentiate between conditions that do not require antibiotics and those that almost always require them. Healthcare professionals should adopt an evidence-based method to antibiotic use for URTIs to achieve antibiotic stewardship goals of enhancing patient outcomes, minimizing unintended consequences, and preventing unnecessary healthcare expenditures.

DIAGNOSIS

Allergic Rhinitis

Allergic rhinitis (AR) is an atopic immunoglobulin E–mediated disorder characterized by nasal congestion, clear rhinorrhea, sneezing, postnasal drip, and nasal pruritus.5 Patients may also present with itchy eyes, sore throat, and ear fullness. The frequency of symptoms determines classification.5 Intermittent AR occurs less than 4 days/week or for less than 4 weeks/year and persists for 4 or more days/week and for 4 or more weeks/year. Symptoms may be classified as mild, not interfering with QOL, or as moderate-to-severe, interfering with QOL, including sleep disturbance, impairment of work or school, and/or impairment of daily activities, such as leisure activities or sports.5 Symptom presentation varies, with sore throat more likely with persistent AR.5, 6 An outlier that helps to delineate AR from the common cold is pruritus, which occurs more often with AR and includes nasal, pharyngeal, and/or bilateral ocular pruritus.6 Diagnosis is typically made based on a thorough history and physical examination, including allergy testing to identify specific allergens that trigger symptoms.7 Other diagnostic tools, such as nasal cytology, may be used to support the diagnosis. TABLE 1 provides common signs and symptoms of URTI conditions.

Upper Respiratory Tract Infections

The clinical diagnosis of URTI is typically based on symptoms such as nasal congestion, rhinorrhea, cough, or sore throat lasting 7 to 14 days.8 URTI is a diagnosis of exclusion in patients with high-risk comorbidities, such as immunodeficiencies or chronic disease. The differential diagnosis for URTI includes more serious illnesses such as pneumonia, epiglottitis, pertussis, meningitis, bacterial rhinosinusitis, noninfectious rhinitis, AR, and vasomotor rhinitis. Testing is usually not needed for diagnosis, but assessments to consider include rapid antigen detection testing or throat culture for Streptococcus, rapid antigen testing for influenza, pulse oximetry to assess for hypoxia and lower respiratory tract infection, and chest x-ray for pneumonia. Chest x-rays should be reserved for patients with clinical suspicion of pneumonia, acute upper airway infection with comorbid conditions, or symptoms persisting >3 weeks.

Rhinosinusitis, a term used to describe inflammation of the nose and paranasal sinuses, often presents with nasal congestion, nasal discharge (anterior and/ or posterior nasal drip), and facial pressure or pain.6,9 AR is different from rhinosinusitis, although symptom overlap exists, such as rhinorrhea and nasal congestion. The cold is a form of rhinosinusitis or acute rhinosinusitis (ARS) and may be described as viral, postviral, or bacterial. Viral ARS is defined as when symptoms last up to 10 days.9 Postviral ARS is defined by episodes that last longer than 10 days but less than 12 weeks.9 Bacterial ARS (often referred to as bacterial sinusitis) is determined by symptoms that worsen after 5 to 7 days or last longer than 10 days with exacerbations.9 Bacterial ARS symptoms include three of the following: fever >102.2°F (39°C), discolored mucus, double-sickening (recovery from initial illness), elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ERP), and local severe pain (often unilateral in presentation).4,9,10

Pharyngitis

Pharyngitis is inflammation of the pharynx or a sore throat. It may be infectious or noninfectious, and corresponding symptoms are important to determine appropriate care. Pharyngitis is most often viral in origin.2 Additionally, co-occurrences of SARS-CoV-2 and bacterial streptococcal pharyngitis are possible, so monitoring and testing, as indicated, are imperative.11 If symptoms are persistent beyond 10 days or worsen after 7 days, bacterial etiology is possible.4 Bacterial pharyngitis is most often caused by group A Streptococcus (GAS) infection and is commonly referred to as strep throat.2

Influenza

Influenza, caused by a single-stranded, segmented, negative-sense, RNA virus of the Orthomyxoviridae family, is a major cause of mortality and morbidity worldwide. Seasonal epidemics in adults and children are associated with an estimated 3 million to 5 million cases of severe illness and about 290,000 to 650,000 deaths annually.12 Transmission occurs via respiratory droplets and fomites, with an incubation period of 1 to 4 days. Complicated or severe disease is more likely in persons with chronic medical conditions or immunosuppression, pregnant women, residents of nursing homes or long-term care facilities, American Indians/Alaska Natives, and persons with morbid obesity.12 Major complications include primary influenza pneumonia, secondary bacterial pneumonia, and exacerbation of underlying chronic medical conditions.12 Diagnosis of influenza is crucial, as antivirals are most effective when given early in the course of the disease.13 Clinical diagnosis based on symptoms alone can be made when influenza prevalence is high, with a 75% accuracy rate in adults during influenza season. Nasopharyngeal swabs are preferred for influenza testing due to their high sensitivity and specificity. Symptoms include an abrupt onset of fever, headache, myalgia, and malaise.2,12

MANAGEMENT

Allergic Rhinitis

The American Academy of Allergy, Asthma, and Immunology (AAAAI) and the American College of Allergy, Asthma, and Immunology (ACAAI) joined to provide guidance on seasonal AR and created a 2017 guideline, with updated, guidance consensus-based-statements for rhinitis in 2020 (FIGURE 1).5,14 Medications used in the management of AR include antihistamines (oral and nasal), decongestants (oral and nasal), intranasal corticosteroids (INCS), ipratropium, and the oral leukotriene montelukast (TABLE 2).5,14

Evidence-based guidance is organized based on the type and severity of AR, with intermittent AR having different guidance than that of persistent AR.5 For intermittent AR, first-line recommendations include oral antihistamines (second generation) or intranasal antihistamines (INAH).5 When symptoms are reported as moderate/severe, first-line recommendations include INAH or oral second-generation antihistamines; first-generation oral antihistamines are not recommended.5 This differs with persistent AR, first-line recommendations for which are INCS monotherapy for mild symptom management and INCS and INAH dual therapy for moderate/severe symptoms.5

First-line management of seasonal AR includes INCS and INAH therapy.5 INCS provide relief for all symptoms associated with AR, including congestion, rhinorrhea, and pruritus. If sufficient symptom control is not attained with INCS monotherapy, the AAAAI/ ACAAI guidelines recommend adding an INAH, which includes azelastine and olopatadine (TABLE 2).5,14 Although extremely popular and widely available, second-generation oral antihistamines have fallen out of favor for persistent symptoms. In addition, second-generation antihistamines provide minimal if any additional clinical benefit when added to an INCS.5,14 When INCS monotherapy is insufficient, addition of an INAH is recommended.14 While some studies may show some symptom relief when adding an oral second-generation antihistamine to INCS, the evidence as a whole does not support a significant clinical benefit.14 Importantly, INCS and INAH alleviate congestion, whereas oral antihistamines do not. Oral second-generation antihistamines may provide benefit for targeted symptom management of pruritus and rhinorrhea, and are recommended as a first-line option for intermittent AR.5,14 In addition, oral second-generation antihistamines are best reserved for acute therapy when exposure to allergen will be short-term (e.g., an individual with cat allergy having dinner at a home with a cat).5,14

Other medication includes ipratropium and montelukast. Intranasal ipratropium is recommended for patients who continue to experience significant rhinorrhea while utilizing INCS therapy.5 The oral leukotriene montelukast may be considered in patients not responding or appropriate for other AR medications; however, montelukast now comes with a boxed warning of caution with mental health side effects.15 Specifically, montelukast should be reserved for patients who do not respond sufficiently to other available AR medications or are unable to tolerate other AR medications.14

A Cochrane review of studies using nasal saline irrigation for treatment of AR showed possible benefit in patient-reported symptom resolution compared with no saline. Saline irrigation improved disease severity compared with no saline at up to 4 weeks (standardized mean difference in score [SMD] -1.32, 95% CI, -1.84 to -0.81; 407 participants; 6 studies; low-quality evidence) and between 4 weeks and 3 months (SMD -1.44, 95% CI -2.39 to -0.48; 167 participants; 5 studies; low-quality evidence).16 If patients would like to try nasal irrigation, sterile water should be used, as tap water may contain the amoeba Naegleria fowleri.5 If tap water is used, it should be boiled for 1 to 5 minutes and cooled.

Common Cold

The common cold can be difficult to provide evidence-based recommendations for due to numerous variabilities. Such variabilities include the causative viruses, differing presentation in the young and old, expansive options for treatment, and comorbidities that may impact treatment and presentation.8,9 FIGURE 2 depicts the timeline associated with acute viral rhinosinusitis and medication management options in alignment with corresponding symptoms.

Oral first-generation antihistamines may provide benefit for Days 1 and 2 following symptom onset.9 Unlike AR, histamine levels are not elevated in nasal secretions with the common cold.17 First-generation (not second-generation) antihistamines exhibit competitive antagonism of acetylcholine at neuronal and neuromuscular muscarinic receptors, which explains their benefit in reducing cold symptoms.17 In a study evaluating persons with colds, no differences were observed between loratadine and placebo regarding viral shedding rates, viral titers, overall infection rates, illness rates, or symptom scores.17 Therefore, second-generation antihistamines do not provide any benefit for the common cold. Ipratropium bromide may be used when rhinorrhea symptoms are present with the common cold, although it provides no benefit for nasal congestion.9

Short-term use of oral and nasal decongestants provides beneficial effect for congestion symptoms.5,9 Intranasal decongestants are recommended for short-term use (<5 days) to avoid rebound congestion (rhinitis medicamentosa) from alpha-receptor tachyphylaxis.5 These agents provide rapid relief of congestion by decreasing nasal mucosal edema. INCS may have a role in the management of symptoms in those presenting with postviral ARS.9

A Cochrane systematic review evaluated current cold product effectiveness with various antihistamine/decongestant/analgesic combinations. Results showed that the odds of treatment failure favored decongestant-antihistamine combinations over placebo on the last day of therapy (odds ratio [OR] 0.31, CI 0.20-0.48; 6 trials, 565 adults; moderate-certainty evidence), while decongestant-antihistamine-analgesic combinations showed benefit over placebo the following morning after an evening dose in adults only (OR 0.47, CI 0.33-0.67; 2 trials, 548 adults; low-certainty evidence).18 Benefits should be weighed against adverse effects from the first-generation antihistamines (no benefit is found with second-generation antihistamines in the setting of a common cold). Properties and side effects specific to each drug are provided in TABLE 2.

Pharyngitis

If symptoms persist beyond 10 days or worsen after 7 days, bacterial etiology is possible.4 Bacterial pharyngitis is most often caused by GAS infection and is commonly referred to as strep throat.2 If bacterial pharyngitis is suspected, GAS testing should be performed prior to prescribing antibiotics.2,4 Antibiotics appropriate for management of GAS pharyngitis are penicillin or amoxicillin.4 In patients with penicillin allergies but no history of anaphylaxis (from penicillin), cephalexin or cefadroxil is recommended.4 If a history of penicillin anaphylaxis exists, then clindamycin, clarithromycin, or azithromycin may be used.4

Pain management is an important component in the care of pharyngitis. Systemic analgesics provide the best level of pain management but may not be appropriate for patients with comorbidities or receiving medications for those comorbidities that may further interact (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs] and congestive heart failure, NSAIDs with medications for the management of heart failure, or blood pressure–lowering medications). Pain management may include oral analgesics and/or topical analgesics. Interestingly, acetaminophen may possibly aid with congestion, but not pain, including that associated with sore throat.9 There are several OTC sprays and lozenges that enable almost immediate, albeit short-term, relief for sore throat (TABLE 3).

Conjunctivitis

The presentation of allergies in the eye, termed allergic conjunctivitis, impacts QOL significantly, and recognizing appropriate management strategies is important to mitigate worsening symptoms. Nonpharmacologic recommendations are fundamental: avoid allergen, avoid eye rubbing, apply cold compresses over the eyes, bathing/showering before bedtime, eyelid cleanser use to remove allergen, frequent clothes washing, hypoallergenic bedding, refrigerated artificial tears, and sunglasses as barrier to airborne allergens19 The American Academy of Ophthalmology recommends the combined dual-action antihistamine/mast cell stabilizers as first-line options for the management of allergic conjunctivitis, including for chronic use, although single-ingredient agents may be used (TABLE 4).19 Single-ingredient agents are only available via prescription and may not provide as fast an improvement as seen with the dual-action agents.19 Caution patients about combination ocular antihistamine/vasoconstrictors due to risk of rebound and diminished efficacy.19 Caution should also be taken with the use of oral antihistamines (including second generation) in patients who suffer from allergic conjunctivitis. Oral antihistamines may worsen dry eye syndrome and impair the tears film protective barrier, in turn worsening the conjunctivitis.19 If oral antihistamines are continued, artificial tears may help alleviate tear deficiency and diminish the allergens (inflammation) on the ocular surface.

Bacterial Rhinosinusitis

Most ARS occurrences are viral in origin, and bacterial rhinosinusitis is much less common.4,9,10,20 Bacterial ARS occurs as a secondary infection from ARS in less than 2% of patients with viral ARS.4 Symptoms include persisting or worsening ARS symptoms over 10 days plus more severe symptoms such as a fever, facial pain lasting >3 days, dental pain (especially unilateral), and purulent nasal discharge.4,9,10 A patient with bacterial sinusitis often has symptoms associated with viral ARS; however, the duration and persistence of symptoms suggest bacterial etiology. Management of bacterial ARS includes the same symptomatic management as with the common cold plus consideration of antibiotics. First-line antibiotics include amoxicillin with or without clavulanate, or if the patient has a bactam allergy, doxycycline, levofloxacin, or moxifloxacin.20

Influenza

Treatment of influenza involves symptomatic care. The CDC recommends the use of antiviral medications for the treatment of influenza in individuals with confirmed or suspected influenza who are at high risk of complications, including those who are hospitalized, have severe or progressive illness, or are at high risk for complications due to underlying medical conditions.13 Medications can help reduce the duration and severity of symptoms and prevent complications and hospitalization. Antiviral treatment should be initiated as soon as possible, ideally within 48 hours of symptom onset for treatment. Prophylaxis may also be warranted in times of outbreaks, e.g., at long-term care facilities and hospitals, provided drug therapy is initiated within 48 hours of exposure. Antiviral medications currently recommended for treatment and/or prophylaxis include the following:

Oseltamivir (Tamiflu): Oral capsule or liquid formulation; 75 mg either twice daily for 5 days (treatment) or 10 days after the last known exposure (prophylaxis); dosage adjustment required in renal dysfunction.13

Zanamivir (Relenza): Inhaled powder; two 5-mg inhalations either twice daily (treatment) or once daily for 10 days after last known exposure (prophylaxis).

Peramivir (Rapivab): IV infusion; 600 mg over at least 15 minutes for treatments; not recommended for prophylaxis.

Baloxavir (Xofluza): Oral tablet; <80 kg: 40-mg dose, >80 kg: 80-mg dose once for treatment or prophylaxis; avoid coadministration with dairy products, calcium-fortified beverages, polyvalent cation–containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc).

Live attenuated influenza vaccine should not be given if oseltamivir or zanamivir was administered within 48 hours of planned vaccination, if peramivir was administered within 5 days of planned vaccination, or if baloxavir was administered within 17 days of planned vaccination.13

The CDC recommends that healthcare providers use clinical judgment when deciding whether to prescribe antiviral medications to otherwise healthy individuals with confirmed or suspected influenza who are not at high risk of complications.13 In general, antiviral treatment is more likely to be beneficial in these individuals when initiated within the first 48 hours of illness onset.2,13 It is important to note that antiviral medications are not a substitute for vaccination against influenza, which is the most effective way to prevent influenza illness and its complications.

TESTING AND ROLE OF THE PHARMACIST

The pharmacist's role in point-of-care testing (POCT) has expanded over the past decade. Positive results from Clinical Laboratory Improvement Amendments (CLIA)–waived POC influenza tests can be used to diagnose infection and begin appropriate infection control measures and antiviral therapy. This may avoid unnecessary diagnostic testing and antibiotics and facilitate early detection and control of communicable infectious diseases, improving patient health outcomes.21,22

A retrospective study of data from Nebraska pharmacy chains in which pharmacists performed POCT for influenza and/or GAS showed that 251 (38%) visited the pharmacy outside of normal clinic hours and 355 (53.7%) did not have a primary insurance. Results indicated that 91 (16.9%) tested positive for GAS and 19 (22.9%) tested positive for influenza, with 64 (77.1%) testing negative.21

CRP is elevated with bacterial infections.9 The use of CRP-guided therapy has been associated with a decrease in unnecessary antibiotics without impairing outcomes.9 At-home rapid-testing CRP kits are available and may be a useful tool to determine if a doctor visit is needed. An Australian community pharmacy showed that CRP testing by community pharmacists served as a triage point for URTIs.23

CONCLUSION

The management of URT conditions, such allergic rhinitis, acute rhinosinusitis (including the common cold, postviral, and bacterial), influenza, and pharyngitis, requires evidence-based methods to differentiate appropriate therapy. Pharmacologic treatment is an essential component in managing these conditions. As symptomology overlaps between conditions, a thorough patient history ensures the best possible therapy. Nonpharmacologic interventions, such as rest, hydration, and symptom-relief strategies, can also aid management.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

REFERENCES

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