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INTRODUCTION

Like many other health professionals and most patients, pharmacists have only a rudimentary understanding of nasal polyps, also known as nasal polyposis. Several media reports and medical mystery shows have highlighted this condition in recent years.^1–4 A medical mystery piece in The New York Times described a 34-year-old woman who presented at the emergency department because of chest pain. The story highlights many points germane to diagnosis and treatment of nasal polyps: progressively worsening symptoms, a recent diagnosis of asthma in adulthood, poor response to inhaled medication, an apparent allergy to nonsteroidal anti-inflammatory drugs (NSAIDs), and referral to a specialist. In The New York Times case, the specialist identified Samter’s disease (now called aspirin-exacerbated respiratory disease [AERD]) and confirmed nasal polyps on computed tomography (CT) scan.⁴

Nasal polyps—benign, soft, smooth, semitranslucent, teardrop-shaped growths—develop in the nasal mucosa and paranasal sinuses.^5,6 They are the most common tumor of the nasal cavity and can be quite large, sometimes visible in or protruding from the nose but more often smaller or deep in the sinuses. Clinicians can identify annoying, irritating polyps during nasal examinations, but they may assume symptoms are the result of allergic rhinitis and not examine the nasal passages.⁵

Patients who have nasal polyps almost ubiquitously experience congestion, blockage or obstruction, or loss of taste or smell, and they often self-medicate with over-the-counter (OTC) medications. Nasal polyps can irritate the nasal passages through swelling, thereby causing distress for patients. Nasal seepage, sleep loss, and other annoying symptoms are also reported (see Table 1).^7,8

When sinonasal symptoms continue for more than 3 months, the condition becomes a type of chronic rhinosinusitis, and the subgroup of patients with chronic rhinosinusitis and nasal polyps tend to have the most severe symptoms.⁹ Comorbid allergies or asthma are common and can complicate the diagnostic process.¹⁰

Chronic rhinosinusitis with polyps is an umbrella term that covers a number of phenotypes (physical presentations) affecting the nasal and paranasal sinuses. The most common polyps seen in the United States are classified as T-helper 1 or 2 (Th1 or Th2) and aspirin-exacerbated polyps.¹²

EPIDEMIOLOGY AND CLINICAL PRESENTATION

In the United States, 11 million people have chronic rhinosinusitis, and among them, 25% to 35% have nasal polyps. Polyps are more common in men than in women. Patients are more likely to present with polyps as they age, starting in their 30s and 40s, with mean age of onset at 42 years and peak incidence in the 50s.^13–15 Unfortunately, diagnosis usually lags onset by approximately 5 years; health care practitioners often and repeatedly fail to recognize this condition.¹⁶

The incidence of nasal polyps has been increasing, and researchers are examining factors contributing to this greater risk. Nasal polyps appear to have a genetic link; a large study showed that the first- and second-degree relatives of patients who have chronic rhinosinusitis with nasal polyps are 4.1 and 3.3 times more likely to have the condition.¹⁷ Individuals who have hyperimmune responses to fungus are also at increased risk.¹⁸ Bacterial colonization secondary to impaired innate and adaptive immunity has been implicated as a contributing factor; higher IgE levels and eosinophils in nasal polyps are linked to Staphylococcus aureus colonization.^19,20 A specific risk factor—lengthy exposure to occupational dust—has been identified among workers in the textile industry.²¹

Absenteeism and presenteeism (going to work but performing below expectations because of illness) reflect this condition’s impact. Employees who have nasal polyps are absent an average of 24.6 day every year, and they are present but are unproductive on an additional 38.8 days — combined that is about one-quarter of the workdays in a year. Polyps also affect individuals’ time at home. Time spent on daily sinus care routines totals roughly 21 days annually.²² Ultimately, the productivity cost of nasal polyps averaged more than $10,000 per year in 2014, with costs increasing as the condition worsened.²²

Health care costs are also significant. In 2018, economists estimated that the cost of endoscopic sinus surgery for patient with chronic rhinosinusitis with nasal polyps was $12,800. A 2019 claims database review indicated that these patients incurred more than $26,724 in medical care costs that year. Extrapolated to the U.S. population, the overall health care cost burden of this condition would be $5.7 billion. Medical costs tend to fall after patients have sinus surgery, but unfortunately, many patients do not experience a durable response to surgery.^14,23,24

PATHOPHYSIOLOGY

Inflammation is a key component of chronic rhinosinusitis with nasal polyps and an area of current research. Biopsy of nasal polyp tissue in Western populations indicates that most polyps contain elevated eosinophil levels. Many patients have comorbid allergies, and people who are allergic to NSAIDs or have cystic fibrosis are at increased risk.^25–27 The nasal passages, covered with mucociliary fibers, are constantly presented with allergens, gram-positive and gram-negative bacteria biofilms (primarily Staphylococcus aureus), fungus, and other particles that trigger an inflammatory response by the epithelium.^12,28

As noted, the 2 most common types of nasal polyps in the United States are classified as Th1 and Th2. The Th1 type occurs more often in patients who have chronic rhinosinusitis with nasal polyps, chronic obstructive pulmonary disease, psoriasis, or Crohn’s disease. The Th2 type is more likely to occur in patients who have asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps with a hyperplastic component, or ulcerative colitis. Inflammation that results in nasal polyps has been associated with mast cell release that stimulates cytokines such as interleukin (IL) 4, IL-5, and IL-13.²⁹

This inflammatory component explains the close association between chronic rhinosinusitis with nasal polyps and severe asthma and hypersensitivity to NSAIDs; 83% of patients with AERD reported this correlation.^11,30 For this reason, guidelines recommend asking affected individuals about salicylate intake from NSAIDs and dietary sources (e.g., blueberries, apples, avocadoes, mushrooms, cauliflower, coffee, and nuts such as almonds, peanuts, pine nuts, macadamia nuts and pistachios).⁹ One-third of patients with chronic rhinosinusitis with polyps and AERD reported that alcohol consumption exacerbated symptoms.³⁰ Researchers at the University of Virginia examined alcohol’s connection to AERD, finding that red wine was more likely to aggravate symptoms than white wine or clear spirits. These result suggest that the offending agent may not be the alcohol but rather the polyphenols generated during the processes used in making red wine.³¹

Two diseases—Churg-Strauss syndrome (a rare genetic condition characterized by vessel inflammation) and cystic fibrosis (CF)—are closely associated with systemic nasal polyposis, but they are generally associated with neutrophilic (as opposed to eosinophilic) inflammation.³² Up to three-quarters of patients with Churg–Strauss syndrome develop nasal polyposis, as do roughly 45% of patients with CF. In the latter case, nasal polyps may be a symptom that suggests CF in undiagnosed young patients and reinforces the need for screening to rule out this inherited respiratory and digestive genetic defect.^16,34

DIAGNOSIS

Presentation of chronic rhinosinusitis with nasal polyps is highly variable, ranging from asymptomatic to extensive effects on patients’ quality of life.⁶ Diagnosing chronic rhinosinusitis with nasal polyps requires listening to patients as they describe symptoms and conducting a thorough physical examination using nasal endoscopy and CT scan (Table 2). On a normal CT scan, the maxillary sinuses are full of air, and these appear black on the scan. In a patient who has chronic rhinosinusitis with nasal polyps, the maxillary sinuses are opaque and in the most serious cases, the entire sinus will appear gray.¹⁶ Nasal polyps are usually bilateral, so if polyps are present in one nasal passage only, clinicians should consider the rare possibility of malignant tumors.³⁵

CASE STUDY: Gerry Lafitte is a 45-year-old man who has had “sinus trouble” for at least 5 years. After many misdiagnoses, his primary care provider referred him to an otolaryngologist, who conducted several tests and ordered a CT scan. Gerry presents at the pharmacy with a prescription for an intranasal corticosteroid and shares with the pharmacist his CT scan, pointing out that the areas where his sinuses are gray, indicating blockage. He also has directions for nasal irrigation. He asks you if you have information on how to do the irrigation. He also has concerns about how long these treatments will take and whether they will work.

TREATMENT OPTIONS

Experts recommend 4 treatment goals for patients with chronic rhinosinusitis with nasal polyps³⁶:

• Control inflammation
• Maintain sinus ventilation and drainage
• Treat colonizing or infecting microorganisms
• Reduce exacerbations

Currently, clinicians follow a standard algorithm that steps up care in a rational manner based on the patient’s response.³⁷ In patients who have allergies or experience watery discharge, antihistamines can help control symptoms. Many patients who develop nasal polyps will need surgery, but some treatment approaches can alleviate symptoms in patients with mild-to-moderate disease. Two simple interventions that are used include intranasal glucocorticoids and saline irrigation.^9,38 Saline irrigation, although lacking research evidence, can soothe symptoms.⁹ High-volume, low-pressure nasal saline irrigations—which are inexpensive—can increase the clearance of antigen, biofilm, and inflammatory mediators.⁶

Intranasal glucocorticoids (e.g., budesonide, fluticasone, mometasone) can reduce polyp size and rhinorrhea and partially or completely restore sense of smell.^37,38 These agents are often underprescribed, with prescribers using doses too low or administered too infrequently (once daily rather than twice daily) to be effective for nasal polyps.^6,39

Patients also tend to underuse these products when they are prescribed.³⁹ The 2021 International Consensus Statement on Allergy and Rhinology: Rhinosinusitis indicates that intranasal products vary in cost but tend to be inexpensive or of moderate cost. Common adverse effects include epistaxis (nosebleeds), local irritation, and headache.¹⁶

Increasingly, researchers are looking for better, more effective means of intranasal drug delivery. Topical glucocorticoid drops or solutions are useful in patients with moderate-to-severe symptoms.⁹ Large-volume nasal steroid rinses administered using plastic squeeze bottles are superior to traditional steroid sprays because they reach areas of the nasal structures that spray cannot (albeit at higher cost).^10,16,37 Table 3 summarizes the delivery mechanisms for corticosteroids used in reduction of polyp size and nasal congestion.

Montelukast, a leukotriene receptor antagonist, can also relieve symptoms, although the evidence concerning its effectiveness is scarce and conflicting.^16,41 The agent has about the same level of effect as intranasal glucocorticoids; it can be used alone or in combination with intranasal glucocorticoids.¹⁶

If topical treatment fails to produce the desired relief in 4 to 6 weeks (which is common), patients may need a short course of oral steroids. Using oral glucocorticoids for 2 to 3 weeks can reduce polyp size, alleviate symptoms, and improve quality of life. Unfortunately, the relief may last only 3 to 6 months, at which point patients may need another course of systemic glucocorticoids.^25–27 Administered in regimens lasting 8 to 12 weeks, systemic oral steroids have substantial benefit when monitored closely, according to the 2021 International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Adverse effects include gastrointestinal irritation, transient adrenal suppression, insomnia, and increased bone turnover. Long-term use of oral steroids is never recommended, and patients should have a maximum of only 2 or 3 short courses of oral steroids annually.²⁸ If patients respond to systemic steroids, they should return to inhaled or topical corticosteroids when they end the course of oral steroids with a goal of maintaining control.³⁷

If this first level of medical treatment fails, the next step in clinical management of nasal polyps is usually endoscopic surgery. However, surgery is not curative.⁴² Available guidelines are not specific about which treatments should be used and for how long before considering surgery. Delaying surgery has been associated with a greater likelihood of asthma later in life.⁴³

Many patients (20% to 50%) require revision surgery since polyps are prone to recur.⁴⁴ This surgery’s main purpose is to restore sinus ventilation, improve penetration of the mucosa by topically applied agents, and debulk severe polyposis (multiple polyps). Complications of surgery are rare, but bleeding, cerebrospinal fluid leak, infection, intracranial injury, hyposmia/anosmia, lacrimal system injury, orbital injury, scarring, septal perforation, vascular injury, and vision changes or blindness are possible.¹⁶

A few weeks after surgery, recurrence of polyps can be prevented by aspirin desensitization in patients with adequate pulmonary function. This can improve quality of life, make patients less reliant on systemic steroids, and reduce the likelihood of additional surgery (surgical revision). Desensitization starts with gradually increasing doses of aspirin administered orally or intranasally; the highest dose of aspirin that does not trigger symptoms is continued as maintenance therapy. Aspirin’s well known adverse effects (e.g., gastric bleeding or pain, impaired renal function, nausea) and antiplatelet effects are problems for many patients, and approximately 50% of patients are unable to persist with aspirin doses for more than a few months.^16,37

Clinicians must watch for Staphylococcus aureus, as about half of patients with chronic rhinosinusitis with nasal polyps have colonization of this pathogen. It is unclear whether colonization causes or exacerbates nasal polyps. If it appears that the infection is bothersome, clinicians can employ methylprednisolone to decrease inflammation and/or a 3-week course of doxycycline.^45,46

Biologics

As noted, approximately 80% of patients with chronic rhinosinusitis with nasal polyps have a Th2 eosinophilic inflammation.²⁸ Elevated IL-4, IL-5, and IL-13 levels can aggravate nasal polyps and have been identified as biologic targets. The U.S. Food and Drug Administration (FDA) has approved 2 biologic agents for this condition, dupilumab in 2019 and omalizumab in 2020. Both decrease polyp burden and improve symptoms, making them useful for patients whose chronic rhinosinusitis with nasal polyps is not adequately managed by first-line agents and for many patients, surgical interventions.^32,47,48

Dupilumab

Dupilumab, also FDA-approved for atopic dermatitis and eosinophilia asthma, inhibits IL-4 and IL-13 signaling. Dupilumab’s approval was based on 2 pivotal trials, both of which enrolled large percentages of participants who had comorbid asthma (59%) and NSAID-exacerbated disease (28%).

These trials, LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52, enrolled 276 and 448 participants, respectively, with bilateral chronic rhinosinusitis with nasal polyps and symptoms despite intranasal corticosteroid use, receiving systemic corticosteroids in the preceding 2 years, or having had prior sinonasal surgery.⁴⁹

In the smaller trial, participants were randomized to dupilumab 300 mg or placebo every 2 weeks for 52 weeks, dupilumab 300 mg every 2 weeks for 24 weeks. The larger trial used groups randomized (1:1:1) dupilumab 300 mg every 2 weeks for 52 weeks, dupilumab 300 mg every 2 weeks for 24 weeks and then every 4 weeks for the remaining 28 weeks, or placebo every 2 weeks for 52 weeks.⁴⁹

The trials used 2 primary endpoints to assess safety and efficacy in an intention-to-treat population⁴⁹:

• Changes from baseline to week 24 in nasal polyp score (an unvalidated score to measure polyp size with 0 = no blockage on 1 side and 4 = total blockage on 1 side [total possible score is 8, indicating complete blockage on both sides]), nasal congestion, or obstruction
• Sinus Lund-Mackay CT scores (at Japanese centers)

Dupilumab significantly improved the coprimary endpoints in both LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 as early as week 4 of treatment.⁵⁰ Compared with placebo, least square mean nasal polyp scores were 2.06 points lower with active therapy (95% CI –2.43 to –1.69; P <0.0001) in SINUS-24 and 1.80 points (–2.10 to –1.51; P <0.0001) in SINUS-52. In LIBERTY NP SINUS-24, polyps tended to recur when treatment was withdrawn. Patient-reported outcomes improved significantly, and the need for surgical intervention was reduced by 83%.⁴⁹

The most common adverse events with dupilumab included nasopharyngitis, worsening of nasal polyps and asthma, headache, epistaxis, and injection-site erythema; patients who were treated with placebo were more likely to experience these adverse events.⁴⁹

Dupilumab’s labeling reflects these common adverse reactions, listing injection site reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, and conjunctivitis.⁵¹

Omalizumab

Also indicated for allergic asthma and chronic idiopathic urticaria, omalizumab is approved by FDA for add-on maintenance treatment of nasal polyps in adults with inadequate responses to nasal corticosteroids. Pivotal trials of this anti-IgE antibody included POLYP 1 (n = 138) and POLYP 2 (n = 127). These studies enrolled adults with chronic rhinosinusitis with nasal polyps who had inadequate responses to intranasal corticosteroids.⁵²

Participants were randomized (1:1) to omalizumab or placebo plus intranasal mometasone for 24 weeks. The primary end points were NPS change from baseline to week 24 and Nasal Congestion Score (NCS). Secondary end points included a patient-reported outcome measure, the Sino-Nasal Outcome Test-22 (SNOT-22).

At baseline in these trials, participants had severe chronic rhinosinusitis with nasal polyps and substantial quality of life impairment (mean NPS higher than 6 and SNOT-22 score of approximately 60).⁵² Previous surgeries were common (nearly 60% of participants), and 12% to 29% of patients had used systemic corticosteroids in the prior year. Comorbid asthma was common (up to 61% of participants) and 27.2% of participants had NSAID- or aspirin-exacerbated disease.⁵²

Both studies met the coprimary end points, with decreases in NPS of 1 to 2 points among omalizumab-treated participants.⁵² Omalizumab-treated participants had better patient-reported outcome measures, sense of smell, postnasal drip, and runny nose than placebo-treated patients at the study’s end. In POLYP 1 and POLYP 2, the respective mean changes from baseline at week 24 for omalizumab versus placebo were as follows: NPS, –1.08 versus +0.06 (P <0.0001) and –0.90 versus –0.31 (P = 0.0140); NCS, –0.89 versus –0.35 (P = 0.0004) and –0.70 versus –0.20 (P = 0.0017); and SNOT-22, –24.7 versus –8.58 (P <0.0001) and –21.6 versus –6.55 (P <0.0001).⁵²

Adverse events were similar between the groups. Placebo-treated patients were more likely to report adverse events than omalizumab-treated patients (58.5% versus 50.4% of participants reporting treatment-emergent adverse events, respectively). In general, the researchers graded adverse events as mild to moderate in intensity, and most occurred within 24 hours of administration.⁵²

Omalizumab’s labeling indicates that in patients with nasal polyps, adverse reactions in at least 3% of patients include headache, injection site reaction, arthralgia, upper abdominal pain, and dizziness. The product labeling includes a boxed warning concerning potential anaphylaxis (bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue).⁵³

Investigational Biologics

Two additional monoclonal antibodies are in the pipeline for use in patients with chronic rhinosinusitis with nasal polyps: mepolizumab (which is under FDA review) and benralizumab (which is pending submission for FDA review). Both products block IL-5.

The randomized, double-blind, placebo-controlled, phase 3 SYNAPSE trial included 407 adults with recurrent, refractory, severe, bilateral nasal polyp symptoms (nasal obstruction symptom visual analogue scale [VAS] score greater than 5).⁵⁴ Participants were also eligible for repeat nasal surgery despite standard of care treatment and had at least 1 nasal surgery in the past 10 years (33% of participants had 3 or more prior surgeries). The percentages of participants with asthma and NSAID-exacerbated disease were also high (71% and 26%, respectively). Researchers randomized participants (1:1) to receive either mepolizumab 100 mg subcutaneously or placebo once every 4 weeks; participants continued with necessary standard of care for 52 weeks. End points were change from baseline in total endoscopic nasal polyp score at week 52 and change in mean nasal obstruction VAS score during weeks 49 to 52.⁵⁴

Over 18 months, 206 participants received mepolizumab and 201 received placebo. At week 52, mepolizumab-treated participants’ total endoscopic nasal polyp scores significantly improved compared with placebo-treated participants’ scores (adjusted difference in medians –0.73, 95% CI –1.11 to –0.34; P <0·0001).⁵⁴ Similarly, nasal obstruction VAS scores measured in weeks 49 to 52 also significantly improved (–3.14, –4.09 to –2.18; P <0.0001). Adverse events were reported by 15% of mepolizumab-treated patients and 9% placebo-treated patients. Overall, 6% of experienced on-treatment serious adverse events, but none in the mepolizumab arm were considered related to treatment. The need for surgery and systemic steroids decreased by 50% and 42%, respectively.⁵⁴

The researchers concluded that mepolizumab treatment improved nasal polyp size and nasal obstruction compared with placebo. No new safety concerns were identified.⁵⁴

Benralizumab is under study for its effects on nasal polyps in adult patients with severe eosinophilic asthma. The phase 3b ANDHI trial assessed benralizumab’s efficacy, onset of effect, impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms using a randomized, controlled, double-blind, parallel-group, placebo-controlled design.⁵⁵

Participants were 656 adults aged 18–75 years with severe eosinophilic asthma who had at least 2 exacerbations in the prior year despite use of high-dose inhaled corticosteroid plus additional controllers.⁵⁵ In addition, enrollees had screening blood eosinophil counts of 150 cells per μL or more and an Asthma Control Questionnaire 6 (ACQ-6) score of at least 1.5. Participants — stratified by previous exacerbation count, maintenance oral corticosteroid use, and region — were randomized (2:1) to benralizumab 30 mg or placebo every 4 weeks for 3 doses and then every 8 weeks for 24 weeks.⁵⁵

Benralizumab reduced exacerbation risk by 49% compared with placebo (RR estimate 0.51, 95% CI 0.39–0.65; P <0.0001) over the treatment period. Improvements in health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms were clinically meaningful and statistically significant and occurred early during benralizumab treatment (during weeks 1 to 4).⁵⁵

Overall, 271 (63%) benralizumab-treated participants experienced adverse events, with nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]) most common.⁵⁵ Similarly, 143 (62%) of placebo-treated participants reported adverse events. Serious adverse events were less likely in the benralizumab arm (23 [5%]) than the placebo arm (25 [11%]); 9 (2%) participants in the benralizumab arm and 9 (4%) participants in the placebo arm reported worsening asthma.⁵⁵

The researchers concluded that benralizumab provided early clinical benefits in patient-reported outcomes, health-related quality of life, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma.⁵⁵

CASE STUDY: After several years of treatment (during which he has been periodically nonadherent), Gerry Lafitte returns to the pharmacy and reports he had surgery to remove bilateral nasal polyps 10 days ago. The surgeon implanted a corticosteroid-eluting stent. Gerry says, “I wish they had done this from the get-go. I got my sense of smell back and I feel like I can breathe again!” Realizing that Gerry is overly optimistic and probably doesn’t realize that he will need to continue his sinus care routine, the pharmacist prepares to counsel him on what to expect, the need for adherence, and future treatment options.

IMPLICATIONS FOR PHARMACISTS

To appreciate the need for long-term treatment of chronic rhinosinusitis with nasal polyps, patients must understand that this condition is a manifestation of chronic inflammation and airway lining dysfunction. Making patients aware of treatment goals also helps them understand the treatment strategy, including the need for therapy to improve symptoms in the nose as well as upper and lower airways and facilitate topical delivery of medications.

Treatment adherence is probably the most important area for pharmacist involvement.^6,39 Patients with comorbid lower airway disease are more adherent when pharmacists and others on the care team stress the idea of unified airway disease and the relationship between upper and lower airway inflammation. Some specialists describe this condition to patients as “asthma of the nose.”⁵⁶ This term helps patients understand that nasal polyps, like asthma, are chronic and incurable and must be managed accordingly.

Patients may need education on how to use nasal irrigation products. The prescriber will recommend a device, which might be a neti pot, a squeeze bottle, or a bulb syringe. When preparing saline solutions at home, patients should purchase distilled water or sterilize tap water by boiling (and cooling before use). Irrigation solutions are administered by standing over a sink or in the shower, tilting the head to one side, and squeezing or pouring the solution into the upper nostril. Used properly, the solution drains out of the lower nostril and not into the throat or mouth. Tilting the head in the other direction, the process is repeated with the other nostril. Patients should breathe from their mouths during the process. Patients will need experience gained through trial and error to determine the best position to prevent the solution from running into the throat. Once the process is complete, patients should blow their noses gently; if they had recent surgery, the surgeon will probably tell them not to do this step for up to 1 week.⁵⁷ Online video sites such as YouTube are good resources to find demonstrations of administration of nasal irrigations.

Patients using intranasal products also benefit from counseling on proper administration technique. This education should be repeated and/or reassessed periodically as patient technique often worsens over time. Proper administration of intranasal products reduces the chance of epistaxis (bloody nose), which is common adverse effect in patients who have chronic rhinosinusitis with nasal polyps.³⁶

When use of short courses of oral corticosteroids is warranted, patients should know that improvements can be expected in health-related quality of life and symptom severity, but these are short term, usually disappearing within 3 months.^58,59 Most experts indicate that patients should receive no more than 3 short courses of oral corticosteroids annually.^16,36 This recommendation is based on a longitudinal observation study that enrolled patients with asthma; it showed that receiving more than 2.5 short courses of oral corticosteroids per year was associated with a significantly larger loss of bone marrow density than that observed in patients who received fewer annual courses.⁶⁰

Some interventions, particularly those prescribed by otolaryngologists, require compounded nasal saline irrigations with added medications that address inflammatory processes within the sinuses.⁶ If the patient’s regular pharmacy does not compound, patients will need referrals to appropriate compounding pharmacies.

Managing expectations around the time of surgery is critical, as polyp recurrence is likely. Patients should not expect a cure.

For patients whose treatment includes biologics, adherence is an equally important element of counseling. It is also prudent to remind patients not to discontinue corticosteroids abruptly once they start a biologic. Dupilumab’s labeling includes patient information, and reviewing that information with patients can guide a comprehensive discussion. This biologic is administered subcutaneously (300 mg every other week), and patients need education on injection technique.⁵¹ Omalizumab’s dosing is 75 to 600 mg subcutaneously every 2 or 4 weeks, with the dose and dosing frequency calculated based on total serum IgE level and body weight. For omalizumab, FDA requires a health care providers to give patients a Medication Guide before starting treatment and before each subsequent treatment, which is again included in its approved labeling.⁵³ Patients should also know that disease-modifying effects have not been demonstrated for currently available biologics, so polyps may return if patients stop these products.³⁶

Pharmacists can assist prescribers in choosing appropriate therapies. Emphasizing patient preference and dexterity can help narrow the choices; some patients may be unable to irrigate their sinuses without help, for example, and inhalers have different features that require various levels of eyesight, dexterity, breathing ability, and coordination. For the long-term treatment usually required for chronic rhinosinusitis with nasal polyps, second-generation intranasal corticosteroids (e.g., budesonide, fluticasone propionate, mometasone) are preferred because they are less likely to cause systemic adverse effects common with first-generation agents (e.g., beclomethasone, flunisolide, triamcinolone).³⁶ Lack of insurance coverage and formulary restrictions can be a barrier to obtaining biologic agents; pharmacists can help identify and navigate patient assistance programs.

Comorbidities can lead to a preference for one biologic over another. In addition to add-on maintenance treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyposis, dupilumab is approved for moderate-to-severe atopic dermatitis and moderate-to-severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid dependent asthma.⁵¹ FDA has approved omalizumab for moderate-to-severe persistent asthma in patients 6 years of age and older with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids (atopic asthma) and chronic idiopathic urticaria.⁵³ Switching to the other biologic is a reasonable step in cases of nonresponse to the initial choice.

Table 4 lists key counseling points to stress for patients who have nasal polyps. This condition can sometimes be managed, but surgery is a frequent necessity.^9,61

CONCLUSION

While an entertaining topic for a medical mystery in newspaper articles, chronic rhinosinusitis with nasal polyps can be undiagnosed for years, undertreated once it is diagnosed, and the cause of considerable suffering for patients. A standard of care for this condition offers considerable relief if followed with rigor. Pharmacists can help patients by recommending simple saline irrigation, intranasal glucocorticoids, and biologics when appropriate, and emphasizing during counseling the chronic nature of this disease. Pharmacists can also help manage patients’ expectations when surgery is needed and provide advice to prescribers when a medication change is necessary.

References

1. Mayo Clinic. Nasal polyps tend to return, so monitor for them regularly. Chicago Tribune. September 26, 2019.
2. Sanders L. A runner suddenly developed asthma. It was stranger than it seemed: diagnosis. New York Times. December 12, 2019. https://www.nytimes.com/2019/12/12/magazine/aspirin-exacerbated-respiratory-disease-aerd.html
3. Boodman SG. Her doctor said she had the flu. It took years to find the real, and strange, illness. The Washington Post. June 23, 2018. https://www.washingtonpost.com/national/health-science/her-doctor-said-she-had-the-flu-it-took-years-to-find-the-real-and-strange-illness/2018/06/22/6d30a504-5862-11e8-858f-12becb4d6067_story.html
4. Gaddis T. Medical Mystery for Chapter 2. Hinds Community College. April 23, 2017. https://hindscc.instructure.com/courses/270738/assignments/3447030
5. Dhringa PL, Dhingra S. Diseases of the ear, nose and throat, and head and neck surgery. 7^th edition. Elsevier India. September 25, 2017.
6. del Toro E. Nasal polyps. StatPearls. August 8, 2020. https://www.statpearls.com/ArticleLibrary/viewarticle/25545
7. Gliklich RE, Metson R. The health impact of chronic sinusitis in patients seeking otolaryngologic care. Otolaryngol Head Neck Surg. 1995;113:104–109.
8. Abdalla S, Alreefy H, Hopkins C. Prevalence of Sinonasal Outcome Test (SNOT-22) symptoms in patients undergoing surgery for chronic rhinosinusitis in the England and Wales national prospective audit. Clin Otolaryngol. 2012;37:276–282.
9. Hopkins C. Chronic rhinosinusitis with nasal polyps. N Engl J Med. 2019;381:55–63.
10. Moore A. Nasal polyps. June 28, 2019. American Academy of Allergy, Asthma, & Immunology. https://www.aaaai.org/conditions-and-treatments/library/allergy-library/nasal-polyps
11. Khan A, Huynh TMT, Vandeplas G, et al. The GALEN rhinosinusitis cohort: chronic rhinosinusitis with nasal polyps affects health-related quality of life. Rhinology. 2019;57(5):343–351. doi:10.4193/Rhin19.15810
12. Kern RC, Conley DB, Walsh W, et al. Perspectives on the etiology of chronic rhinosinusitis: an immune barrier hypothesis. Am J Rhinol. 2008;22(6):549–559. doi:10.2500/ajr.2008.22.322813.
13. Larsen K, Tos M. The estimated incidence of symptomatic nasal polyps. Acta Otolaryngol. 2002;122(2):179–182.
14. Bhattacharyya N, Villeneuve S, Joish VN, et al. Cost burden and resource utilization in patients with chronic rhinosinusitis and nasal polyps. Laryngoscope. 2019;129(9):1969–1975. doi:10.1002/lary.27852
15. Stevens WW, Schleimer RP, Kern RC. Chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract. 2016;4(4):565–572. doi:10.1016/j.jaip.2016.04.012
16. Orlandi RR, Kingdom TT, Smith TL, et al. International consensus statement on allergy and rhinology: rhinosinusitis 2021. Int Forum Allergy Rhinol. 2021;11(3):213–739. doi:10.1002/alr.22741
17. Oakley GM, Curtin K, Orb Q, Schaefer C, Orlandi RR, Alt JA. Familial risk of chronic rhinosinusitis with and without nasal polyposis: genetics or environment. Int Forum Allergy Rhinol. 2015;5(4):276–282. https://doi.org/10.1002/alr.21469.
18. Cohen NA, Widelitz JS, Chiu AG, Palmer JN, Kennedy DW. Familial aggregation of sinonasal polyps correlates with severity of disease. Otolaryngol Head Neck Surg. 2006;134(4):601–604.
19. Song WJ, Lee JH, Won HK, Bachert C. Chronic rhinosinusitis with nasal polyps in older adults: clinical presentation, pathophysiology, and comorbidity. Curr Allergy Asthma Rep. 2019;19(10):46.
20. Hulse KE, Stevens WW, Tan BK, Schleimer RP. Pathogenesis of nasal polyposis. Clin Exp Allergy. 2015;45(2):328–346.
21. Veloso-Teles R, Cerejeira R, Roque-Farinha R, von Buchwald C. Higher prevalence of nasal polyposis among textile workers: an endoscopic based and controlled study. Rhinology. 2018;56(2):99–105.
22. Rudmik L, Smith TL, Schlosser RJ, Hwang PH, Mace JC, Soler ZM. Productivity costs in patients with refractory chronic rhinosinusitis. Laryngoscope. 2014;124(9):2007–2012. doi:10.1002/lary.24630
23. Purcell PL, Beck S, Davis GE. The impact of endoscopic sinus surgery on total direct healthcare costs among patients with chronic rhinosinusitis. Int Forum Allergy Rhinol. 2015;5(6):498–505. doi:10.1002/alr.21482
24. Rosati D, Rosato C, Pagliuca G, et al. Predictive markers of long-term recurrence in chronic rhinosinusitis with nasal polyps. Am J Otolaryngol. 2020;41(1):102286. doi:10.1016/j.amjoto.2019.102286
25. Van Zele T, Gevaert P, Holtappels G, et al. Oral steroids and doxycycline: two different approaches to treat nasal polyps. J Allergy Clin Immunol. 2010;125(5):1069–1076.e4.
26. Martinez-Devesa P, Patiar S. Oral steroids for nasal polyps. Cochrane Database Syst Rev. 2011 Jul 6. CD005232.
27. Kirtsreesakul V, Wongsritrang K, Ruttanaphol S. Clinical efficacy of a short course of systemic steroids in nasal polyposis. Rhinology. 2011;49(5):525–532.
28. Ta NH. Will we ever cure nasal polyps? Ann R Coll Surg Engl. 2019;101(1):35–39. doi:10.1308/rcsann.2018.0149
29. Corren J. New targeted therapies for uncontrolled asthma. J Allergy Clin Immunol Pract. 2019;7(5):1394–1403. doi:10.1016/j.jaip.2019.03.022
30. De Schryver E, Derycke L, Campo P, et al. Alcohol hyper-responsiveness in chronic rhinosinusitis with nasal polyps. Clin Exp Allergy. 2017;47(2):245–253.
31. Eschenbacher W, Borish L, Payne S, Lawrence M. Alcohol sensitivity in AERD: polyphenols causing problems. 59^th Annual Swineford Allergy Conference. April 9, 2021. https://med.virginia.edu/cme/wp-content/uploads/sites/262/2021/04/0409.1115.Eschenbacher-1.pdf
32. Chaaban MR, Walsh EM, Woodworth BA. Epidemiology and differential diagnosis of nasal polyps. Am J Rhinol Allergy. 2013;27(6):473–478. doi:10.2500/ajra.2013.27.3981
33. Bacciu A, Bacciu S, Mercante G et al. Ear, nose and throat manifestations of Churg–Strauss syndrome. Acta Otolaryngol. 2006;126(5):503–509.
34. Brihaye P, Clement PA, Dab I et al. Pathological changes of the lateral nasal wall in patients with cystic fibrosis (mucoviscidosis). IntJ Pediatr Otorhinolaryngol 1994;28(2–3):141–147.
35. Lund VJ, Clarke PM, Swift AC, et al. Nose and paranasal sinus tumours: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol. 2016 ;130(S2):S111–S118.
36. Ranford D, Hopkins C. Safety review of current systemic treatments for severe chronic rhinosinusitis with nasal polyps and future directions [published online ahead of print, 2021 May 18]. Expert Opin Drug Saf. 2021;1–13. doi:10.1080/14740338.2021.1926981
37. Naclerio R, Baroody F, Bachert C, et al. Clinical research needs for the management of chronic rhinosinusitis with nasal polyps in the new era of biologics: a National Institute of Allergy and Infectious Diseases workshop. J Allergy Clin Immunol Pract. 2020;8(5):1532–1549.e1. doi:10.1016/j.jaip.2020.02.023
38. Chong LY, Head K, Hopkins C, Philpott C, Burton MJ, Schilder AG. Different types of intranasal steroids for chronic rhinosinusitis. Cochrane Database Syst Rev. 2016;4:CD011993.
39. Rudmik L, Xu Y, Liu M, Bird C, Kukec E, Quan H. Utilization patterns of topical intranasal steroid therapy for chronic rhinosinusitis: a Canadian population-based analysis. JAMA Otolaryngol Head Neck Surg. 2016;142(11):1056–1062.
40. Lelegren MJ, Bloch RA, Lam KK. Intraoperative applications of topical corticosteroid therapy for chronic rhinosinusitis [published online ahead of print, 2020 Nov 10]. Ear Nose Throat J. 2020;145561320970100. doi:10.1177/0145561320970100
41. Smith TL, Sautter NB. Is montelukast indicated for treatment of chronic rhinosinusitis with polyposis? Laryngoscope. 2014;124(8):1735–1736.
42. Ernst FR, Imhoff RJ, DeConde A, Manes RP. Budget impact of a steroid-eluting sinus implant versus sinus surgery for adult chronic sinusitis patients with nasal polyps. J Manag Care Spec Pharm. 2019;25(8):941–950. doi:10.18553/jmcp.2019.18285
43. Benninger MS, Sindwani R, Holy CE, Hopkins C. Impact of medically recalcitrant chronic rhinosinusitis on incidence of asthma. Int Forum Allergy Rhinol. 2016;6(2):124–129.
44. DeConde AS, Mace JC, Levy JM, Rudmik L, Alt JA, Smith TL. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017;127(3):550–555. doi:10.1002/lary.26391
45. Van Zele T, Gevaert P, Holtappels G, et al. Oral steroids and doxycycline: two different approaches to treat nasal polyps. J Allergy Clin Immunol. 2010;125(5):1069–1076.
46. Ou J, Wang J, Xu Y, et al. Staphylococcus aureus superantigens are associated with chronic rhinosinusitis with nasal polyps: a meta-analysis. Eur Arch Otorhinolaryngol. 2014;271:2729–2736.
47. Laidlaw TM, Buchheit KM. Biologics in chronic rhinosinusitis with nasal polyposis. Ann Allergy Asthma Immunol. 2020;124(4):326–332. doi:10.1016/j.anai.2019.12.001
48. Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019;394(10209):1638–1650.
49. Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials [published correction appears in Lancet. 2019 Nov 2;394(10209):1618]. Lancet. 2019;394(10209):1638–1650. doi:10.1016/S0140-6736(19)31881-1
50. Trial Site Staff. SINUS-24 trial results. Trial Site News. February 25, 2019. https://trialsitenews.com/sinus-24-trial-results/
51. Dupixent [product labeling]. sanofi-aventis U.S. January 2021.
52. Gevaert P, Omachi TA, Corren J, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials [published correction appears in J Allergy Clin Immunol. 2021 Jan;147(1):416]. J Allergy Clin Immunol. 2020;146(3):595–605. doi:10.1016/j.jaci.2020.05.032
53. Xolair PI [product labeling]. Genentech, Inc. November 2020.
54. Han JK, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial [published online ahead of print, 2021 Apr 16]. Lancet Respir Med. 2021;S2213–2600(21)00097-7. doi:10.1016/S2213-2600(21)00097-7
55. Harrison TW, Chanez P, Menzella F, et al. Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial [published correction appears in Lancet Respir Med. 2021 Jan 25]. Lancet Respir Med. 2021;9(3):260–274. doi:10.1016/S2213-2600(20)30414-8
56. ‘Asthma of the nose’ — tackling allergic rhinitis and its symptoms. The Medical Independent. March 14, 2017. https://www.medicalindependent.ie/asthma-of-the-nose-tackling-allergic-rhinitis-and-its-symptoms/
57. How to do a sinus flush at home. Healthline. January 28, 2019. https://www.healthline.com/health/sinus-flush#how-to
58. Head K, Chong LY, Hopkins C, et al. Short-course oral steroids alone for chronic rhinosinusitis. Cochrane Database Syst Rev. 2016 Apr 26; CD011991.
59. Head K, Chong LY, Hopkins C, et al. Short-course oral steroids as an adjunct therapy for chronic rhinosinusitis. Cochrane Database Syst Rev. 2016 Apr 26; CD0011992.
60. Matsumoto H, Ishihara K, Hasegawa T, et al. Effects of inhaled corticosteroid and short courses of oral corticosteroids on bone mineral density in asthmatic patients: a 4-year longitudinal study. Chest. 2001;120(5):1468–1473. doi:10.1378/chest.120.5.146869
61. Mayo Clinic Staff. Nasal polyps. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/nasal-polyps/symptoms-causes/syc-20351888

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