Chronic rhinosinusitis with nasal polyposis: Management and prognosis

INTRODUCTION — Chronic rhinosinusitis (CRS) is defined as a complex inflammatory condition involving the paranasal sinuses and linings of the nasal passages that lasts 12 weeks or longer. It is estimated to affect up to 5 percent of the population. CRS is divided into CRS with nasal polyps (CRSwNP) and CRS without NP (CRSsNP), which are distinguished by the presence or absence of nasal polyps. CRSwNP represents approximately one-third of all CRS cases. Symptoms associated with CRSwNP include loss of the sense of smell (anosmia), nasal obstruction or blockage, anterior or posterior nasal drainage, and facial pressure [1]. The disorder is associated with significant medical resource consumption and impairments in quality of life, especially during acute exacerbations [2,3].

This topic will review the medical and surgical management of CRSwNP. The clinical manifestations and diagnostic criteria for CRS are discussed separately. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)

The management and prognosis of chronic rhinosinusitis without nasal polyps are also presented separately. (See "Chronic rhinosinusitis without nasal polyposis: Management and prognosis".)

GOALS OF THERAPY — The primary goal in treating patients with CRSwNP is to reduce sinonasal symptoms and improve quality of life while minimizing medication adverse effects. Medical management of CRSwNP attempts to control the underlying inflammation that drives the growth of polyp tissue and the development of symptoms. Sinus surgery is used when initial medical management is not adequately effective. Many patients with CRSwNP require multiple therapeutic interventions to manage their symptoms adequately and need long-term and potentially indefinite treatment.

IMPORTANT COMPONENTS OF CARE

Patient education

●Setting realistic expectations – It is helpful to set expectations with patients and explain that treatments for CRSwNP are intended to:

•Improve quality of life by reducing and occasionally eliminating symptoms

•Prevent exacerbations requiring treatment with oral glucocorticoids and antibiotics, as both may have significant long-term adverse effects

However, available medical and surgical therapies rarely cure CRSwNP. Even if symptoms are completely controlled, medical therapy must be continued to prevent recurrence. Similarly, patients who undergo functional endoscopic sinus surgery (FESS) to remove polyp tissue still require diligent postoperative follow-up and medical treatment going forward to prevent regrowth of polyps [4,5]. For many patients, lifelong therapy will be needed.

●Teaching proper use of intranasal corticosteroids – There are multiple intranasal corticosteroid (INCS) delivery options, including nasal sprays, irrigations/drops, and exhalation delivery system (EDS). Each requires specific patient education for proper use. Patients may not know how to use their INCS correctly, despite having a long history of CRSwNP. The patient's technique should be reviewed and correct technique carefully demonstrated for each type of INCS delivery system used. Reduction in local adverse effects of INCS (nasal irritation) can often be achieved with proper delivery technique [6] (see "Pharmacotherapy of allergic rhinitis", section on 'Optimal use'). It is also important to counsel patients not to expect immediate results with INCS. Rather, improvement may be gradual, and INCS should be used for at least one month before assessing efficacy.

●Adherence – A critical aspect of treatment success is establishing a daily routine of sinus care to which the patient can adhere long term. Barriers to use of medications should be addressed at each visit. If a medication is not subjectively or objectively improving a patient's symptoms after a three-month trial, it should be stopped. An exception to this is the biologic therapies, as some patients may need longer than three months to respond [7]. When a therapy is efficacious, patients should be educated about the need for long-term adherence to prevent relapse of symptoms [8].

Multidisciplinary collaboration — At initial presentation, all patients with suspected CRSwNP should undergo nasal endoscopy, preferably by an otolaryngologist, to confirm the diagnosis and rule out other causes of nasal congestion and anosmia. If an otolaryngologist is not available and polyps are not clearly visible in the nasal cavities, the diagnosis should be confirmed by computed tomography (CT) to demonstrate the presence of polyps, as required for definitive diagnosis. Once the diagnosis is confirmed, treatment can be started by a generalist but usually requires the input of allergy/immunology and/or otolaryngology specialists. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis", section on 'Diagnosis'.)

Monitoring — Upon initiation of treatment, patients should be monitored at regular intervals. We usually ask patients to return three months after initiation of therapy and then every three to six months thereafter until symptoms are adequately managed. At each visit, we assess sinonasal symptoms and quality of life, perform a nasal exam (endoscopic if possible), and review any use of oral glucocorticoids or antibiotics for exacerbations. We use validated symptom questionnaires such as the Sino-Nasal Outcomes Test (SNOT-22) to assess symptom severity of CRS-related quality of life [9].

OUR APPROACH — Our approach is consistent with treatment guidelines and practice parameters published by professional otolaryngology and allergy groups worldwide [6,7,10-15]. The pace at which we move through this series of interventions depends upon how symptomatic the patient is (algorithm 1):

●Upon initial presentation, we assess the patient for coexisting disorders that may alter treatment. (See 'Coexisting disorders that may impact treatment' below.)

●Initial treatment for nearly all patients includes medical management with intranasal corticosteroids (INCS), delivered one of several ways, and nasal saline irrigation. The intensity of INCS can be increased by changing the method of delivery. (See 'Intranasal corticosteroids' below and 'Nasal saline irrigations' below.)

●If the nasal passages are completely obstructed, a short course of oral glucocorticoids can temporarily shrink polyp tissue and allow better access for topical therapies. Similarly, if there is purulent drainage, we treat for concomitant bacterial sinusitis with oral antibiotics, with culture-directed therapy when possible. (See 'Oral glucocorticoids for complete obstruction or severe symptoms' below and 'Oral antibiotics for superimposed infection' below.)

●For most patients, we offer sinus surgery when there is insufficient response to standard medical management. (See 'Surgical management' below.)

●For patients with other indications for a biologic therapy (eg, severe asthma, chronic spontaneous urticaria, or contraindications for undergoing surgery), one of three biologic therapies can be prescribed. We also offer biologic therapies to patients whose polyps have regrown after an initial surgery. (See 'Biologic therapies' below.)

COEXISTING DISORDERS THAT MAY IMPACT TREATMENT — There are several disorders that may present with or include CRSwNP that are important to identify, either through directed patient history or further specific evaluation:

●Aspirin-exacerbated respiratory disease (AERD) – AERD should be suspected in patients with severe CRSwNP who have concomitant asthma and intolerance of nonsteroidal antiinflammatory drugs (NSAIDs). The prevalence of AERD among patients with CRSwNP is estimated at 10 percent [16]. NSAID intolerance most commonly presents as sudden worsening of nasal congestion, facial flushing, conjunctival injection, and/or bronchospasm one to two hours after ingesting aspirin or other NSAIDs, although patients may be unaware of the condition because the symptoms are similar to those of CRS and asthma. Supervised NSAID challenge is sometimes required to determine if the patient has intolerance. One reason for distinguishing AERD is that treatment may include aspirin desensitization and daily aspirin therapy, which is only useful in patients with NSAID intolerance. Sinus surgery is often performed before aspirin desensitization in a coordinated fashion. Preemptive surgery decreases the load of inflammatory tissue, thus making aspirin desensitization safer. It also prevents the need to interrupt aspirin therapy if surgery is needed after the patient has been desensitized and started on daily aspirin. The clinical manifestations and management of AERD are discussed in more detail separately. (See "Aspirin-exacerbated respiratory disease".)

●Allergic rhinitis and/or asthma – In addition to these specific disorders, many patients with CRSwNP have asthma, allergic rhinitis, or both. Comorbid asthma is present in approximately one-half of patients with CRSwNP in some populations [17,18]. Atopy, as defined as one or more positive skin tests to inhalant allergens, is present in >60 percent of patients with CRSwNP [17,19]. However, there may be significant geographic differences worldwide. In a study of patients in China, only 9 percent had coexistent asthma [20]. Some of the therapies for asthma and allergic rhinitis overlap with those for CRSwNP, and all three of these disorders are often driven by type 2 inflammation. The management of these problems is discussed elsewhere. (See "An overview of asthma management" and "Pharmacotherapy of allergic rhinitis".)

●Allergic fungal rhinosinusitis (AFRS) – AFRS presents with CRSwNP and should be suspected in patients who have characteristic findings on sinus computed tomography (CT; ie, one or more opacified sinuses containing hyperattenuated areas (image 1)), the presence of eosinophilic mucin on biopsy of sinus contents, pathology showing fungal hyphae and degranulating eosinophils, and evidence of immunoglobulin E (IgE) mediated allergy to fungi. The prevalence of AFRS among patients with CRSwNP has been estimated at 8 percent, although there is wide geographic variability [21]. Endoscopic sinus surgery is required early in the management of most patients. The diagnosis and management of AFRS are presented elsewhere. (See "Allergic fungal rhinosinusitis".)

There are also distinct disorders that may present with CRSwNP but should be detected as early as possible because treatment and prognostic implications are different:

●Eosinophilic granulomatosis with polyangiitis (EGPA) – EGPA usually presents with asthma, CRS (often with nasal polyposis), skin nodules, and peripheral neuropathy. It is a multisystem vasculitis, and other manifestations may include peripheral eosinophilia, weight loss, fever, myalgia, arthralgia, pulmonary opacities, cardiomyopathy, kidney disease, and gastrointestinal involvement. (See "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)", section on 'Clinical features'.)

●Cystic fibrosis (CF) – In children, the finding of nasal polyposis should prompt consideration of possible CF. The incidence of CRSwNP in patients with CF has been estimated to be above 90 percent [22,23]. Patients with concomitant pneumonias or other features of CF (table 1) should undergo specific testing, as detailed separately. (See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Sinus and nasopharyngeal disease'.)

●Primary ciliary dyskinesia (PCD) – PCD is a congenital disorder caused by several defects, or complete absence of, cilia, leading to impaired mucosal clearance. Nasal polyposis is frequently present, often involving the maxillary and ethmoid sinuses. A history of neonatal respiratory distress, early-onset and persistent, productive cough, chronic otitis media, and/or a laterality defect (eg, situs inversus or ambiguous) should raise a strong clinical suspicion for PCD. (See "Primary ciliary dyskinesia (immotile-cilia syndrome)".)

●Rare nasal tumors – The identification of a polyp on exam alone should not automatically imply a benign inflammatory disease. Inflammatory nasal polyps, like those seen in CRSwNP, are usually bilateral, with surrounding mucosal swelling and abnormal (ie, thick or discolored) mucus. However, patients with unilateral nasal polyps or polyps with an unusual appearance should be referred to an otolaryngologist for evaluation of benign or malignant tumors [24]. (See "Etiologies of nasal obstruction: An overview", section on 'Tumors'.)

INITIAL THERAPIES FOR ALL PATIENTS

Nasal saline irrigations — We instruct patients to perform daily or twice-daily, high-volume (>200 mL per nostril) nasal irrigations with a saline solution, in agreement with multiple consensus statements [11,12,15]. We recommend this for all patients with CRSwNP who can tolerate it and are not completely obstructed. Saline irrigations thin and flush out mucus, inflammatory debris, irritants, and allergens and improve mucociliary function.

●Technique – There are multiple devices available for nasal irrigation, including squeeze bottles and neti pots. Patients can make their own saline solution or purchase commercially prepared solutions. High-volume (>200 mL per nostril) saline irrigations are more effective than low-volume nasal saline sprays [25-28]. Patient instructions for saline irrigations are provided (table 2).

●Safety – Nasal saline irrigation is low risk and well tolerated by most patients. Most complaints are related to nasal drainage after irrigation and Eustachian tube obstruction or irritation. Eustachian tube complaints can be reduced by instructing patients to allow irrigation to pass into the oropharynx and out the mouth by keeping the throat and mouth relaxed. In addition, avoiding nose blowing for approximately 15 minutes after irrigation will decrease the potential for auto-insufflating the Eustachian tubes with saline. Patients should be instructed on how to ensure the device is clean (ie, sterilizing devices and adhering to replacement instructions as suggested by device manufacturers). Tap water or well water should not be used for sinus irrigations unless it is boiled first [29,30]. Transmission of life-threatening infections through nonsterilized water has been reported, as discussed in detail separately. (See "Pharmacotherapy of allergic rhinitis", section on 'Nasal saline'.)

●Unclear benefit of additives – Surfactants to disrupt biofilms have been added to nasal irrigations, although there is inadequate evidence of benefit, and a possible adverse effect is reduction in sense of smell [31-34].

Intranasal corticosteroids — Guidelines and consensus statements recommend topical intranasal corticosteroids (INCS) as first-line treatment for CRSwNP [11,14,35]. We typically start with an INCS delivered via nasal spray, many of which are available without a prescription (table 3). There are several other delivery systems in addition to nasal sprays, including rinses/irrigations, drops, and an exhalation-driven delivery system (EDS). Less common means of delivery include nasal nebulization and local injections.

The importance of proper technique — Many patients have already been using INCS nasal sprays for symptoms of nasal congestion prior to a formal diagnosis of CRSwNP, but they often are not using optimal technique (figure 1). In addition, some patients with severe CRSwNP may be so obstructed that they cannot use an INCS. In this setting, a short course of oral glucocorticoids can be given to temporarily relieve obstruction so that topical therapies can be applied. (See 'Oral glucocorticoids for complete obstruction or severe symptoms' below.)

If symptoms do not adequately improve after one to three months of therapy, we consider changing delivery modalities to a nasal corticosteroid irrigation or EDS, depending on patient preference and cost/availability of these options for the patient.

Efficacy — Based on a systematic review, practice parameters for the medical management of CRSwNP recommend the use of INCS delivered by spray, irrigation, or EDS (rather than no INCS) for patients with CRSwNP, although this was based on low certainty of evidence given the small-to-moderate treatment effect size [10]. Numerous studies and meta-analyses also show general improvement in sinonasal symptoms, polyp size reduction, and quality of life with INCS for CRSwNP, but the benefit is often modest [36-38].

Comparison of different delivery systems — When patients do not achieve adequate relief from INCS nasal sprays, we typically change to either irrigations or EDS. Head-to-head clinical trials comparing the three delivery systems have not been performed, but standard INCS sprays may not reach target regions, such as the ostiomeatal complex and middle meatus, where polyps form [39-41].

●A 2022 systematic review and network meta-analysis analyzed randomized controlled trials of different INCS delivery systems based on sinus-related quality of life (Sino-Nasal Outcomes Test [SNOT-22]) scores and nasal obstruction symptoms [42]. A minimum clinically important difference in the SNOT-22 score is a reduction of 8.9 points. Reductions were -3.63 (95% CI -9.27 to 2.04) with nasal sprays, -6.83 (95% CI -11.94 to -1.71) with irrigations, and -7.86 (-14.64 to -1.08) with EDS. The level of certainty in the evidence was low or very low. No differences in adverse effects were noted [42].

●Direct evidence that EDS provides benefit beyond standard nasal sprays is limited, although, in a post-hoc sensitivity analysis of pooled data from two studies of EDS-fluticasone [43,44], 45 percent of patients were using standard INCS sprays at study entry, and these patients had comparable improvement to those not on INCS sprays initially, suggesting that EDS did result in additional symptom control [45].

Nasal sprays

●Available preparations and dosing – Specific INCS sprays include beclomethasone, flunisolide, budesonide, fluticasone propionate, mometasone furoate, fluticasone furoate, and ciclesonide. Doses and details about the specific preparations are reviewed in the table (table 3). Several INCS sprays are available without a prescription. Differences in efficacy among INCS sprays have not been demonstrated [46].

●Adverse effects – In general, INCS sprays are well tolerated by patients with CRSwNP. Nasal mucosal irritation can lead to mild epistaxis. Rare nasal septal perforation is an important adverse effect. Employing proper nasal spray technique and tapering to the lowest effective dose can reduce these risks (figure 1).

Exhalation delivery system

●Available products – A commercially available EDS (brand name: Xhance) with fluticasone propionate 93 mcg/spray is approved for treatment of CRSwNP in adults aged 18 years and older. The EDS uses a sealing nosepiece and flexible mouthpiece to administer the INCS with exhalation, which effectively increases the pressure in the sinonasal compartments. The patient places the pump into one nostril and blows forcefully into the mouthpiece of the device. The recommended daily dose is one spray in each nostril twice daily for a total dose of fluticasone propionate of 372 mcg daily.

●Efficacy – It is reasonable to "step up" therapy to EDS-fluticasone in patients who have not benefitted from INCS sprays. Compared with INCS sprays, the EDS provides better medication deposition to the superior and posterior regions of the sinonasal cavity [47]. However, there is only indirect evidence comparing the efficacy of INCS sprays and the EDS. (See 'Comparison of different delivery systems' above.)

●Specific advantages of EDS – EDS-fluticasone is preferred by some patients with eustachian tube dysfunction who have increased symptoms of ear blockage with corticosteroid irrigations (see 'Corticosteroid irrigations/drops' below). It can also be more convenient for patients who travel frequently.

●Adverse effects – Similar to INCS sprays, common adverse reactions with the EDS include epistaxis, nasal septal ulceration, and nasal mucosal erythema [48]. In addition, close monitoring for glaucoma and cataracts is also recommended because of the higher doses of fluticasone delivered closer to the orbit. We advise patients to have yearly eye exams for this reason. In patients with a history of glaucoma or cataracts, we consult with the patient's ophthalmologist before using the EDS system.

Corticosteroid irrigations/drops

●Available products – In the United States, there are no Food and Drug Administration (FDA) approved intranasal steroid irrigations or drops. Corticosteroid irrigations/drops may help the medication reach the recesses of the nasal cavity, including the superior and posterior regions.

Corticosteroid solutions, such as budesonide and mometasone intended for use in nebulizers, can be diluted into saline and used to irrigate the sinuses (irrigations) or instilled undiluted directly into the nostrils (drops). Drops are uncommonly used and generally reserved for patients with more severe symptoms that do not adequately respond to irrigations or for acute exacerbations.

●Technique – Corticosteroid irrigations, also referred to as rinses or flushes, involve adding an aqueous preparation of corticosteroid to the large-volume (ie,> 200 mL per nostril) saline irrigations.

•Instructions for performing saline nasal irrigations are described in the table (table 2). Patients should add the prescribed corticosteroid solution to the amount of saline used each time, rather than make up a large amount of the solution and store it.

•Nasal drops can be administered using several head positions. It is not clear that head position impacts how well drops in surgery-naïve patients, while there is some evidence that head position improves efficacy in postsurgical patients [49].

●Adverse effects – The safety of corticosteroid irrigations has been evaluated in several studies that did not find evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, development of cataracts, or increased intraocular pressures, although studies only evaluated small numbers of patients [50-53]. In addition, it is possible that concurrent use of multiple topical steroid preparations (ie, INCS plus inhaled glucocorticoids for patients with CRSwNP and asthma) may lead to HPA axis suppression in some patients [51]. As with EDS-fluticasone, we recommend that patients using corticosteroid irrigations or drops have yearly eye exams. In patients with a history of glaucoma or cataracts, we consult with the patient's ophthalmologist before starting corticosteroid irrigations or drops.

THERAPIES FOR SPECIFIC SITUATIONS — Some patients may benefit from brief courses of oral glucocorticoids or oral antibiotics.

Oral glucocorticoids for complete obstruction or severe symptoms — Short courses of oral glucocorticoids can be used to temporarily shrink nasal polyps, which is helpful for patients who present with such severe nasal blockage that they cannot effectively use an intranasal corticosteroid (INCS) [37,54,55] or in the setting of severe symptoms of nasal congestion or anosmia.

We usually treat adults with prednisone, 40 to 60 mg daily initially, and then gradually reduce the dose over 10 to 14 days. Doses are sometimes reduced for older adults or those who had adverse effects with previous use:

●One suggested regimen for adults is oral prednisone 40 mg for 5 days, followed by 20 mg daily for 5 days (10 days of treatment).

●Another, slightly longer regimen is 60 mg daily for 5 days, followed by 40 mg daily for 3 days, then 30 mg for 3 days, then 20 mg daily for 3 days (14 days of treatment).

Methylprednisolone can be used instead of prednisone (8 mg of methylprednisolone is equivalent to 10 mg of prednisone).

●Short-term efficacy – Multiple studies, including systematic reviews and randomized trials, have shown the substantial benefit of oral glucocorticoids in reducing nasal polyps size and improving sense of smell and sinonasal symptoms in the first two to three weeks after therapy [54-57]. However, by 10 to 12 weeks after the oral glucocorticoid course, the reduction in symptoms is not sustained in most patients [54-56].

●Guidelines regarding limited use – Repeated administrations of oral glucocorticoids should be avoided given the significant long-term side effects that can occur [12]. The requirement of two or more courses of oral glucocorticoids per year or long-term treatment with low-dose oral glucocorticoids were included as indications for biologic treatment for CRSwNP by an expert panel [7]. Significant adverse effects with short-term use are uncommon but can be serious, including hyperglycemia in people with diabetes or prediabetes, acute mood changes, and arrythmias. Patients should be counseled about these possibilities in advance. (See "Major side effects of systemic glucocorticoids" and "Patient education: Oral steroid medicines (The Basics)".)

In a patient who has recurrent disease despite a short course of oral glucocorticoids and sustained INCS use, alternative treatments such as functional endoscopic sinus surgery (FESS) or biologic therapy are recommended. (See 'Functional endoscopic sinus surgery' below and 'Biologic therapies' below.)

Oral antibiotics for superimposed infection — Existing guidelines do not support the use of antibiotics for treatment of CRSwNP, except in the instance of acute infections [12,15]. CRSwNP is not primarily an infectious disorder, and, as such, antibiotics are not routinely used for management of chronic inflammation in CRSwNP. However, for some patients, uncontrolled sinonasal inflammation can predispose to recurrent or difficult-to-control infections, which may contribute to the persistence and severity of chronic disease.

●We reserve antibiotics for acute exacerbations of CRSwNP in which bacterial infection is suspected. We select an antibiotic based on culture of material obtained endoscopically from a sinus cavity whenever possible. (Note that cultures obtained by swabbing the nasal cavities generally reflect skin flora and are not useful.) If culture is not possible, then the choice of antibiotics is empiric and guided by additional factors such as local resistance patterns and potential for adverse effects. We usually give a 10- to 14-day course, occasionally extending it if the patient is not fully improved or purulence persists at the end of 14 days. Empiric choices of antibiotics for CRS are reviewed in more detail elsewhere. (See "Microbiology and antibiotic management of chronic rhinosinusitis", section on 'Empiric regimen selection'.)

●Staphylococcus aureus has been identified in >60 percent of patients with aspirin-tolerant CRSwNP and 80 percent of patients with aspirin-exacerbated respiratory disease (AERD) [58]. However, the evidence for use of antibiotics to eradicate S. aureus in the treatment of CRSwNP is lacking, and we do not give antibiotics for this reason.

Antihistamines for patients with allergic rhinitis — For patients with CRSwNP and concomitant allergic rhinitis, we administer nonsedating, second-generation antihistamines, such as cetirizine 10 mg orally twice daily. Cetirizine 20 mg daily for three months reduced rhinorrhea, sneezing, and, to a lesser extent, nasal congestion in a small, randomized, placebo-controlled trial of patients with CRSwNP with and without allergic rhinitis [59]. There was no effect on polyp size. Other therapies for patients with allergic rhinitis include antihistamine nasal sprays and combination corticosteroid/antihistamine nasal sprays. (See "Pharmacotherapy of allergic rhinitis", section on 'Antihistamine nasal sprays' and "Pharmacotherapy of allergic rhinitis", section on 'Combination corticosteroid/antihistamine sprays'.)

Aspirin therapy for AERD — Patients with aspirin-exacerbated respiratory disease (AERD), the triad of adult-onset asthma, CRSwNP, and upper and/or lower respiratory reactions to nonsteroidal antiinflammatory drugs (NSAIDs), have particularly severe CRSwNP [60,61]. Aspirin desensitization and daily aspirin therapy is a treatment option that is only appropriate for patients with AERD. It is typically carried out by clinicians with experience in drug desensitization. Notably, aspirin therapy is not efficacious for patients with CRSwNP who do not have aspirin sensitivity. The management of AERD and aspirin desensitization are reviewed in detail elsewhere. (See "Aspirin-exacerbated respiratory disease" and "Diagnostic challenge and desensitization protocols for NSAID reactions".)

Antileukotriene agents for some patients with asthma — Leukotriene-modifying agents include leukotriene receptor antagonists (ie, montelukast, zafirlukast) and the 5-lipoxygenase inhibitor (zileuton) (table 4). These agents are not approved specifically for the treatment of CRSwNP. However, they can be helpful with both sinonasal and pulmonary symptoms in some patients, although they are not adequate as monotherapy [62-65].

There are two subgroups of patients with asthma and CRSwNP who seem to benefit most consistently from antileukotriene agents: those with AERD and those with both asthma and allergic rhinitis. In such patients, we prescribe a three-month trial and assess for improvement in sinonasal and asthma symptoms; we discontinue treatment if there is no benefit in this timeframe.

●In patients with AERD, we offer a trial of zileuton. AERD is a phenotype of CRSwNP marked by overproduction of cysteinyl leukotrienes [66,67]. In a randomized, placebo-controlled study of patients with AERD treated with zileuton or placebo for six weeks, zileuton-treated patients had improvement in smell and reductions in rhinorrhea and congestion compared with placebo-treated patients [68]. Dosing and administration of zileuton in AERD is discussed in more detail separately. (See "Aspirin-exacerbated respiratory disease", section on 'Leukotriene-modifying agents'.)

●Patients with coexistent asthma and allergic rhinitis sometimes benefit from montelukast, as shown in a small, prospective cohort study [69]. We offer a trial of montelukast or zafirlukast, which require less monitoring than zileuton.

There is a US Food and Drug Administration (FDA) boxed warning on montelukast advising that all patients should be warned about potential behavior and mood-related changes. In light of the boxed warning, we weigh risks and benefits of antileukotriene agents carefully for patients with CRSwNP prior to drug initiation. (See "Antileukotriene agents in the management of asthma", section on 'Adverse effects'.)

CHOOSING BETWEEN SURGERY AND BIOLOGIC THERAPY — In most cases, we refer surgery-naïve patients to an otolaryngologist for consideration of functional endoscopic sinus surgery (FESS) prior to initiation of a biologic therapy. The rationale for this preference is based upon a cohort study in which the efficacy of FESS was compared with that of three biologic therapies (dupilumab, omalizumab, and mepolizumab), as reported in randomized trials of each biologic compared with placebo [70]. A potential source of bias in this study was the significant drop off of FESS patients during follow-up. However, direct, head-to-head studies of surgery versus biologic therapy have not been done and likely will not be due to issues of consent and blinding.

The multicenter cohort study evaluated outcomes at 24 and 52 weeks in 111 patients with CRSwNP undergoing FESS (with subsequent medical therapy) after initial medical management proved insufficient [70]. At 24 weeks, FESS resulted in greater improvement in SNOT-22 scores than dupilumab (in one of two trials) and omalizumab (two of two trials). At 52 weeks, dupilumab and FESS yielded similar improvements in Sino-Nasal Outcomes Test (SNOT-22) scores. FESS was also more effective than mepolizumab. At both time points, FESS reduced polyp burden to a greater degree than the biologics (as would be expected). In addition, FESS appeared to be more cost effective than biologic therapy because biologics need to be continued indefinitely in theory [71-74].

Although we prefer FESS for most patients with CRSwNP before initiating a biologic therapy (see 'Biologic therapies' below), there are several important exceptions:

●Those with a contraindication to surgery

●Those with such poorly controlled asthma that a biologic therapy is indicated for management of asthma regardless of sinus symptoms

●Those who decline surgery after shared decision making

SURGICAL MANAGEMENT — This discussion of surgical management is focused on CRSwNP specifically. A more detailed discussion of the surgical management of CRS in general, including a description of the procedures, risks, and complications, is found separately. (See "Chronic rhinosinusitis without nasal polyposis: Management and prognosis", section on 'Functional endoscopic sinus surgery'.)

Functional endoscopic sinus surgery — Functional endoscopic sinus surgery (FESS), when applied to patients with CRSwNP, is intended to remove polypoid material and inflammatory debris and maximize physiologic sinus ventilation and drainage to facilitate the gradual resolution of mucosal disease. In addition, widening of the outflow tracts allows for improved penetration by topical medications following surgery. Mucosal preservation is the universally accepted technique for both CRS with and without polyps to avoid excessive scarring and to maintain normal mucociliary clearance. In most cases, polyps within the olfactory cleft are only partially removed to avoid scarring of the olfactory epithelium and permanent smell loss. The changes that result from FESS are illustrated in the figure (figure 2).

Indications — For most patients with CRSwNP, we offer sinus surgery when there is insufficient improvement with standard medical management. Specific indications for surgical intervention include the following:

●Failure of the initial medical therapies discussed above

●Severe symptoms or inability to use topical medication due to polyposis

●Bony erosion or extension of disease beyond the sinus cavities

Safety and complications — FESS for CRS of all types is safe in general, with minor complications in up to 6 percent and major complications in 1.5 percent [75]. Complication rates may be higher for CRSwNP than chronic rhinosinusitis without nasal polyposis (CRSsNP) since patients with severe polyp disease require more extensive surgery. Oral glucocorticoids prior to surgery are suggested in consensus statements to improve visualization of normal anatomy and reduce the propensity for bleeding in patients with CRSwNP [11].

Medical management after FESS — Because functional endoscopic sinus surgery (FESS) does not directly treat the underlying inflammatory disorder, sinus surgery must be followed by medical therapy to control inflammatory processes, or symptoms will invariably return [5]. This typically consists of intranasal corticosteroid (INCS) sprays or irrigations. Studies of the efficacy of medical therapy in preventing regrowth of polyps are mixed, with some showing benefit [76-79] and others not [79-81]. In patients with CRSwNP, polyps usually reaccumulate within a few years without ongoing medical therapy, and they may recur despite it [5,82]. Patients with aspirin-exacerbated respiratory disease (AERD), in particular, may have recurrence of nasal polyposis following FESS, even with diligent INCS use [83].

The overall improvement in quality of life for patients with CRSwNP can be relatively long lasting after FESS and subsequent medical maintenance therapy. In several studies, improvements were sustained over five years, possibly due to the removal of significant obstructive symptoms related to polyps [84,85].

Patients with polyp recurrence after FESS — In patients with CRSwNP who begin to experience worsening symptom control and have evidence of polyp recurrence, options include biologic agents, more intensive INCS, or revision surgery for polyp removal.

More intensive INCS includes glucocorticoid irrigations (if not already tried), exhalation delivery system (EDS) fluticasone, or glucocorticoid-eluting stents that are designed to be inserted in the ethmoid cavity after prior surgery has been performed. The stents can be placed under endoscopic guidance in the office setting. Clinical trials using this device have shown short-term efficacy [86], but no studies have directly compared these stents with glucocorticoids delivered by irrigations or EDS.

BIOLOGIC THERAPIES — Targeted biologic therapies are a newer treatment option for patients with CRSwNP (table 5) [13,87-90]. Three have been approved by the US Food and Drug Administration (FDA) for CRSwNP: dupilumab, omalizumab, and mepolizumab. The real-world and long-term use of biologics in CRSwNP is an area of active research.

Indications — Most CRS guidelines suggest offering respiratory biologic therapy for patients who have previously undergone functional endoscopic sinus surgery (FESS) with recurrence of disease following surgery [70,72-74].

As mentioned above, the patients to whom we preferentially offer biologic therapy prior to surgery are:

●Those with a contraindication to surgery

●Those with such poorly controlled asthma that biologic therapy is indicated for management of asthma regardless of sinus symptoms

●Those who decline surgery after shared decision making

The 2020 European position paper on rhinosinusitis proposed specific indications for biologic therapy for CRSwNP [7]. They were further modified in 2023 [91]. The authors identified biologic candidates as patients who had previously undergone FESS or were not candidates for FESS and met at least three of the five criteria:

●Evidence of type 2 inflammation (sinus tissue eosinophil count ≥10 eosinophils per high-powered field or peripheral blood eosinophils ≥150 cells/uL or total IgE ≥100 international units/mL)

●Need for oral glucocorticoids ≥2 courses per year or ≥3 months of low-dose oral glucocorticoids or a contraindication for systemic glucocorticoids

●Significant impairment in quality of life (Sino-Nasal Outcomes Test [SNOT-22] score ≥40)

●Significant loss of smell (anosmia on objective smell testing)

●Diagnosis of comorbid asthma (requiring at least a regular controller inhaled glucocorticoid)

Pretreatment testing — We usually measure peripheral blood eosinophil counts and serum IgE levels, which are markers of type 2 inflammation, prior to initiation of biologic therapy as elevations in these parameters may help support the choice of biologic. In addition, therapy can modify these biomarkers, making it harder to assess them once the patient is on therapy. In patients with peripheral blood eosinophilia, nasal polyps, and asthma, it is important to consider the alternative diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) because treatment with a biologic may improve nasal and pulmonary symptoms and mask the underlying vasculitis. (See "Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Treatment and prognosis" and "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)".)

Role of endotyping — Endotypes refer to classifications of CRS based on pathophysiology and profiles of underlying inflammation, as determined by biomarkers and gene expression [92]. In contrast, phenotype refers to observable clinical characteristics. CRSwNP classifications based on phenotypes (eg, nonsteroidal antiinflammatory drug [NSAID] hypersensitivity in patients with aspirin-exacerbated respiratory disease [AERD]) can inform some management decisions for CRSwNP. However, phenotypic distinctions do not always reveal the underlying inflammatory mechanisms leading to CRSwNP, and respiratory biologics targeting type 2 inflammation are not uniformly efficacious in patients with CRSwNP [93,94].

In the US and Europe, CRSwNP is most frequently a type 2 inflammatory process characterized by type 2 cytokine production, tissue eosinophilia, mast cell infiltrates, type 2 innate lymphoid cells (ILC2s), and local IgE synthesis [95,96]. However, at the tissue level, some patients have type 1 inflammation (driven by interferon gamma and interleukin [IL] 12), type 3 inflammation (driven by IL-17), or mixed inflammatory endotypes [96-98].

Current guidelines for use of biologic therapy for treatment of CRSwNP recommend selecting patients with evidence of type 2 inflammation: tissue and peripheral blood eosinophil levels (polyp tissue eosinophils ≥10/high-power field or blood eosinophils ≥150 cells/mcL) and serum IgE levels (total IgE ≥100 international units/mL) [7,91] (see 'Indications' above). However, subgroup analyses of biologic therapy for the management of CRSwNP have shown efficacy of therapy regardless of baseline eosinophil level, aspirin sensitivity, comorbid asthma [99], or comorbid allergic rhinitis. Thus, further study is needed to define characteristics that predict which medication is most likely to be effective for a given patient.

Selecting among biologic agents — There are three "respiratory" (ie, effective for asthma) biologics that are also approved for treatment of CRSwNP in the United States and Europe: dupilumab, omalizumab, and mepolizumab (table 5). There are no completed head-to-head studies comparing these agents for treatment of CRSwNP. However, dupilumab was consistently found to be the most effective in multiple systematic reviews and indirect comparisons [100-103].

All three agents are approved for moderate-to-severe asthma. In addition, specific laboratory features and patient comorbidities can help to guide biologic selection; in patients with dual indications for biologic therapy such as atopic dermatitis, eosinophilic esophagitis, or chronic urticaria, the secondary indication can help direct the choice of a specific biologic. At present, the use of endotyping to guide selection of respiratory biologic agents requires further study [104,105]. (See 'Role of endotyping' above.)

●In a systematic review of 10 randomized trials of dupilumab, omalizumab, and mepolizumab for CRS (nearly all of whom had CRSwNP), the investigators assessed the impact of biologic treatment on health-related quality of life as measured by the SNOT-22 score, disease severity, and serious adverse events. SNOT-22 scores improved 19.6 points with dupilumab, 15.6 points with omalizumab, and 13.3 points with mepolizumab [103]. The minimal clinically important difference (MCID) in the SNOT-22 score of 8.9 points was achieved for all three agents.

●Dupilumab was superior to omalizumab, except SNOT-22 scores were similar between the groups, in an indirect treatment comparison study of CRSwNP [100]. A head-to-head comparison of omalizumab versus dupilumab for treatment of CRSwNP is underway (NCT04998604).

Anti-IL-4RA (dupilumab) — Dupilumab, a monoclonal antibody targeting interleukin 4 receptor alpha (IL-4R-alpha), inhibits signaling of the cytokines IL-4 and IL-13, two pivotal drivers of type 2 inflammation that are important in diseases such as CRSwNP and asthma. Dupilumab reduces nasal congestion/blockage, endoscopic and radiologic sinus inflammation, rhinorrhea, postnasal drip, need for oral glucocorticoids, and need for FESS and improves sense of smell in patients with CRSwNP [106,107]. Dupilumab may be particularly efficacious in patients with AERD, as patients with AERD have near universal improvement with dupilumab [108,109]. As such, we typically choose dupilumab for patients with AERD who need biologic therapy for treatment of CRSwNP. It is also approved as a treatment for asthma, eosinophilic esophagitis, atopic dermatitis, and prurigo nodularis (table 5).

●Administration – Self-administered dupilumab 300 mg subcutaneously every 14 days is approved for treatment of CRSwNP. A loading dose is not indicated for treatment of CRSwNP (table 5). Based on data from the SINUS-52 study [106], a real-world study [110], and our clinical experience, there are some patients that require less frequent dosing to achieve adequate symptom control, but this is off-label dosing. One author (KB) offers a three-month trial of every 28-day dosing to patients who have complete control of symptoms on an every 14-day regimen and no other comorbidities requiring more frequent dosing.

●Adverse effects – Dupilumab is well tolerated by patients with CRSwNP. The most common side effects in the CRSwNP population include injection-site reactions, peripheral blood eosinophilia, insomnia, toothache, gastritis, arthralgias, and noninfectious conjunctivitis [111]. Preliminary reports have described an increased risk of developing several T helper type 17 (Th17) driven diseases, including seronegative arthritis, psoriasis, enthesitis/enthesopathy, and iridocyclitis in dupilumab-treated patients [112,113]. In our experience, these adverse effects improve when the drug is discontinued, but published data are lacking, and longer-term safety analyses are needed.

●Efficacy – In two international, multicenter, phase-III studies of dupilumab in 724 patients with CRSwNP (SINUS-24 and SINUS-52), dupilumab significantly improved the co-primary endpoints, endoscopic measurement of nasal polyp size, the nasal polyp score (NPS), and patient-reported nasal congestion as measured by nasal congestion score (NCS) at 24 weeks [106]. Patients age 18 years and over were included if they had an endoscopic nasal polyp score of at least 5 (out of maximum of 8) despite treatment with intranasal corticosteroids (INCS), prior treatment with oral glucocorticoids or FESS within the two years preceding enrollment in the study, and inadequately controlled symptoms. More than 50 percent of patients in the study had comorbid asthma, and more than 25 percent had AERD. No specific eosinophil cutoff point was included for entry into the study.

In terms of co-primary endpoints, the least squares mean difference in NPS for dupilumab-treated patients versus placebo was –2.06 (95% CI –2.43 to –1.69) and –1.80 (–2.10 to –1.51) in the SINUS-24 and 52 studies, respectively [106]. The least squares mean difference for NCS for dupilumab-treated patients versus placebo was –0.89 (–1.07 to –0.71) and –0.87 (–1.03 to –0.71) in the two studies. The dupilumab-treated patients also had improvement in objective smell testing scores, patient-reported sense of smell, radiologic sinus inflammation scores, and quality-of-life scores compared with placebo-treated patients. There was a 74 percent reduction in time to oral glucocorticoid use and an 83 percent reduction in time to FESS in the dupilumab-treated group compared with the placebo group.

In SINUS-24, dupilumab was discontinued after 24 weeks, and some treatment effects (eg, NCS, NPS) showed signs of worsening by 12 weeks off therapy, highlighting the need for ongoing treatment. After 24 weeks of treatment in the SINUS-52 study, a subset of patients was transitioned to every 28-day dosing of dupilumab. They continued to have improvement in NPS and NCS compared with placebo [106].

Anti-IgE (omalizumab) — Local immunoglobulin E (IgE) is present in nasal polyp tissue, and IgE levels are higher in patients with more severe CRSwNP [95,114]. Earlier observational studies and more recent randomized, placebo-controlled studies have shown that patients with CRSwNP treated with omalizumab have improvement in sinonasal symptoms and nasal polyp burden [115-117]. Omalizumab is also effective for allergic asthma and chronic spontaneous urticaria.

●Administration – The anti-IgE monoclonal antibody omalizumab is approved by the US FDA for adult patients age 18 years and above as an add-on maintenance treatment of CRSwNP in patients with inadequate response to INCS and an IgE level of 30 to 1500 international units/mL (table 5) [116-118]. Omalizumab is administered by subcutaneous injection every two to four weeks, with the dose determined based on body weight and serum IgE levels. Several guidelines recommend evaluating response to biologic therapy for CRSwNP after four to six months of treatment [13,87,110]. Omalizumab is available for in-office or at-home self-administration in the United States. Patients selected for self-administration of omalizumab should have no prior history of anaphylaxis to omalizumab or other agents such as food and drugs, should receive at least three doses of omalizumab in an observed setting without hypersensitivity reactions, should be able to recognize and treat anaphylaxis appropriately, and should be capable of performing subcutaneous injections with a prefilled syringe [119]. (See "Anti-IgE therapy", section on 'Home administration'.)

●Efficacy – In two replicate, phase-III studies (POLYP 1 and POLYP 2) of omalizumab as an add-on therapy to intranasal mometasone for 265 patients with inadequate response to INCS, co-primary endpoints (change from baseline to 24 weeks, NPS and NCS) were met, with statistically significant improvements at 24 weeks in NPS and NCS for omalizumab versus placebo. Improvements were observed as early as week 4 [117].

In a pooled analysis of the two phase-III studies, a greater percentage of omalizumab-treated patients had a ≥1-point or (56.3 versus 28.7 percent) or ≥2-point (31.3 versus 11.6 percent) improvement in nasal polyp score compared with placebo [117]. A ≥1-point improvement in nasal congestion score was observed in a higher percentage of omalizumab-treated patients versus placebo-treated patients (44.4 versus 21.4 percent). In addition to reductions in NPS and NCS, omalizumab-treated patients had improvement in objective smell tests, quality-of-life measures, and patient-reported sense of smell, postnasal drip, and rhinorrhea compared with placebo. Specifically, SNOT-22 scores improved in both studies (-16.12 and -15.04 points in POLYP 1 and POLYP 2, respectively, with an MCID of 8.9). Scores of olfactory impairment were more modest, improving slightly less than 4 points on objective testing with the 40-item University of Pennsylvania Smell Identification Test (UPSIT; with an MCID generally regarded to be 4 points [120]).

The studies above did not identify specific patient characteristics that predicted a good response to omalizumab. Subgroup analyses of the two phase-III studies of omalizumab for CRSwNP showed overall clinical improvement in terms of NCS, NPS, and other patient-reported outcomes in omalizumab-treated patients compared with placebo in patients with and without asthma, with and without prior sinonasal surgery, with and without aspirin sensitivity, and regardless of blood eosinophil count (ie, >300 and ≤300 cells/μL) [121]. Similarly, an earlier study found that both atopic and nonatopic patients with CRSwNP responded similarly to omalizumab [116]. In the 24-week open-label extension study, omalizumab discontinuation led to worsening of symptoms and NPS [122].

The efficacy of omalizumab for asthma and patient selection are discussed in greater detail separately. (See "Anti-IgE therapy", section on 'Efficacy' and "Anti-IgE therapy", section on 'Indications and patient selection'.)

Anti-IL-5 (mepolizumab) — Mepolizumab targets interleukin (IL) 5, a key survival and activation factor for eosinophils. Eosinophils are known to be elevated in nasal polyp tissue and play a role in the underlying inflammation causing CRSwNP [123]. Mepolizumab improves nasal congestion, overall quality of life, and NPS for patients with CRSwNP when compared with placebo [93]. It is also used for eosinophilic asthma, hypereosinophilic syndrome, and eosinophilic granulomatosis with polyangiitis (EGPA).

●Administration – Mepolizumab 100 mg every four weeks is administered subcutaneously (table 5). It can be administered in a medical facility or self-administered at home with a prefilled syringe or auto-injectors in appropriately trained patients [124]. The most common adverse effects reported in patients with CRSwNP are oropharyngeal pain and arthralgias. Herpes zoster infections have occurred in a small number of patients receiving mepolizumab for treatment of severe asthma. We administer the varicella-zoster vaccine to adults age 50 years or older four weeks prior to initiation of mepolizumab who otherwise have no contraindication to vaccination.

●Efficacy – A multinational, randomized, placebo-controlled phase-III study (SYNAPSE) included 414 patients with recurrent, severe bilateral nasal polyps and history of one prior FESS in the past 10 years. Patients received mepolizumab 100 mg subcutaneously or placebo every four week for 52 weeks in additional to standard-of-care saline nasal irrigations and INCS. Mepolizumab-treated patients had decreased NPS (adjusted difference in median endoscopic NPS -0.73, 95% CI -1.11 to -0.34) and nasal obstruction visual analog scale score (-3.14, 95% CI -4.09 to -2.18) compared with placebo. However, sense of smell did not improve in mepolizumab-treated patients [93].

Monitoring — Guidelines suggest that patients receiving a biologic therapy for CRSwNP be reevaluated four months after starting treatment, with monitoring at regular intervals thereafter [7]. Parameters that prescribers should monitor include improvement in quality of life and sense of smell, interim need for oral glucocorticoid use, reduction in nasal polyp size (if endoscopy can be performed), and impact on comorbidities such as asthma [7,13].

Investigational biologic agents — Benralizumab and tezepelumab, which are both approved by the US FDA for treatment of severe asthma, are under investigation for treatment of CRSwNP [125-127].

TREATING ACUTE EXACERBATIONS — Acute exacerbations of CRS have been defined as transient worsening of CRS that returns to baseline either without intervention or after intervention with antibiotics and/or systemic glucocorticoids [7,11]. The cause of acute exacerbations of CRSwNP is likely multifactorial and includes viral infections (likely the most frequent cause), bacterial infections, medication nonadherence, and allergen or irritant exposure.

●Antibiotics are frequently used to treat exacerbations of CRS, though the frequency that bacterial infections contribute to CRSwNP is unknown. When a bacterial infection is suspected (symptoms lasting more than seven days, purulent nasal drainage), we suggest an endoscopically obtained sinus culture, when possible, to guide antibiotic therapy. Patients with CRSwNP with uncomplicated bacterial infections can be treated similarly to an acute uncomplicated bacterial sinusitis (algorithm 2). (See "Uncomplicated acute sinusitis and rhinosinusitis in adults: Treatment".)

●For some patients with acute exacerbations, a 10- to 15-day tapering course of oral glucocorticoids provides sufficient relief of symptoms and allows the patient to return to their prior intranasal corticosteroid (INCS) regimen with control of symptoms. If patients are requiring frequent treatment with oral glucocorticoids for acute flares of CRSwNP, functional endoscopic sinus surgery (FESS) or biologic therapy should be considered to minimize long-term cumulative effects of oral glucocorticoid exposure.

●In some patients, a brief escalation of therapy from a corticosteroid nasal spray to undiluted budesonide respules can be sufficient to alleviate symptoms of an acute exacerbation (see 'Corticosteroid irrigations/drops' above). Following resolution of the acute exacerbation, the patient should return to their usual INCS delivery mode to minimize potential adverse effects of the concentrated budesonide.

PROGNOSIS — Long-term outcomes in patients with CRSsNP are poorly studied. An international registry has been established to collect data on the natural history of the disorder and treatment outcomes [128].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic rhinosinusitis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Nasal polyps (The Basics)" and "Patient education: Chronic sinusitis (The Basics)" and "Patient education: How to rinse out your nose with salt water (The Basics)")

●Beyond the Basics topic (see "Patient education: Chronic rhinosinusitis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a complex inflammatory condition involving the paranasal sinuses and linings of the nasal passages, with the presence of nasal polyps, which lasts 12 weeks or longer. Symptoms include loss of the sense of smell (anosmia), nasal obstruction or blockage, anterior or posterior nasal drainage, and facial pressure. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)

●Components of care – Patient education is critical and involves setting realistic expectations for living with a condition that usually requires indefinite treatment, ensuring that patients use optimal technique for intranasal therapies, and establishing a daily routine of sinus care to which the patient can adhere long term. (See 'Important components of care' above.)

Treatment can be started by a generalist, but the input of allergy/immunology and/or otolaryngology specialists is usually required. (See 'Multidisciplinary collaboration' above.)

●Evaluate for coexisting conditions – There are several conditions that can present with CRSwNP but are important to recognize because they may impact treatment options and strategies, including aspirin-exacerbated respiratory disease (AERD), allergic rhinitis and asthma, and allergic fungal rhinosinusitis. Disorders that can present with similar symptoms and nasal polyposis but are treated differently include eosinophilic granulomatosis with polyangiitis (EGPA), cystic fibrosis (CF), primary ciliary dyskinesia (PCD), and rare nasal tumors. (See 'Coexisting disorders that may impact treatment' above.)

●Treatment approach – Our treatment approach is depicted in the algorithm and is consistent with multiple guidelines (algorithm 1). (See 'Our approach' above.)

•Initial treatment – We suggest intranasal corticosteroids (INCS) as initial therapy (Grade 2C). INCS are usually delivered via nasal sprays initially, in conjunction with daily saline nasal irrigation (table 3 and table 2). Limited data suggest that INCS provide modest benefit in most patients. It is uncertain which delivery system is best; thus, when patients have insufficient benefit from nasal sprays, we try other delivery systems, such as irrigations or exhalation delivery systems (EDS). (See 'Intranasal corticosteroids' above.)

For patients with nasal obstruction that precludes the use of intranasal therapies, we suggest a short course of oral glucocorticoids prior to INCS (Grade 2C). Oral glucocorticoids shrink the polyps temporarily and allow INCS to penetrate the nasal passages better. However, the effect is always short lived, and repeated courses should be avoided because of the risk of long-term adverse effects. (See 'Oral glucocorticoids for complete obstruction or severe symptoms' above.)

•Patients who require additional therapy – When symptoms are not adequately controlled with INCS, we suggest functional endoscopic sinus surgery (FESS) rather than biologic therapy as the next step in treatment (Grade 2B). FESS is somewhat more effective for relief of symptoms, is less costly, and provides immediate improvement. The anatomic alterations resulting from FESS are illustrated in the figure (figure 2). FESS must be followed by maintenance INCS, or polyps will often grow back. (See 'Choosing between surgery and biologic therapy' above.)

•Role of biologics – Biologic agents are a reasonable alternative to FESS for patients with severe or uncontrolled asthma who also need biologic therapy for their asthma, those with other conditions that could be simultaneously treated with a specific biologic, and those who refuse or cannot safely undergo surgery. (See 'Indications' above.)

For patients with recurrent polyps after FESS, we suggest a biologic therapy rather than more intensive INCS therapy or revision sinus surgery (Grade 2C).

•Choosing among biologics – Three respiratory biologics are approved for treatment of CRSwNP in the United States and Europe: dupilumab, omalizumab, and mepolizumab (table 5). For most patients, we suggest dupilumab (Grade 2C), except in patients who have concomitant chronic urticaria, for whom we choose omalizumab.

•Monitoring – Patients should be reevaluated every three to six months and assessed for improvements in quality of life, sense of smell, interim need for oral glucocorticoid use, reduction in nasal polyp size (if nasal endoscopy can be performed), and impact on comorbidities such as asthma. (See 'Selecting among biologic agents' above.)

●Managing acute exacerbations – CRSwNP can worsen periodically due to viral or bacterial infections, medication nonadherence, and allergen or irritant exposure. Symptoms sometime spontaneously return to baseline, but, if not, the choice of treatment (oral glucocorticoids, antibiotics, or a temporary change to a more intense form of INCS) depends on the clinical scenario as described above. (See 'Treating acute exacerbations' above.)

●Prognosis – There is no known cure for CRSwNP, and long-term outcomes are poorly studied. Many patients require indefinite treatment. (See 'Prognosis' above.)