The Diagnosis and Treatment of Chronic Rhinosinusitis

Background: Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by local chronic inflammation of the mucous membranes of the nose and paranasal sinuses. It affects approximately 5% of the population.

Methods: This review is based on relevant publications retrieved by a selective search of the literature, with particular attention to current national and international guidelines.

Results: CRS is defined by, and diagnosed on the basis of, a combination of symptoms and objective findings of nasal endoscopy and imaging studies. It markedly impairs quality of life and gives rise to both direct and indirect health care costs. In 20–45% of cases, CRS is associated with comorbid bronchial asthma and a significantly elevated risk of further diseases (e.g., COPD, OR 1.73; depression, HR 1.50; obstructive sleep apnea, OR 1.91; carcinoma, OR 1.14–5.30). CRS is primarily treated medically with topical steroids (standardized mean difference of nasal symptoms, −0.63 (95% confidence interval [−0.89; −0.37]; standardized mean difference of quality of life as measured by SNOT −22, −5.46 [−8.08; −2.84]), as well as with nasal lavage and, as an option, systemic steroids (and antibiotics where appropriate). If appropriate medical treatment fails to bring about adequate and sustained improvement, endoscopic sinus surgery is indicated. This improves the individual symptoms, the overall symptom score, and patients’ quality of life. Severe refractory CRS with nasal polyposis can be treated with biological agents.

Conclusion: CRS calls for individually adapted medical and/or surgical treatment.

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by chronic local inflammation of the nasal mucosa and paranasal sinuses. It can impair the disease-specific and general quality of life (1). The definition of CRS requires more than three months of symptoms, as well as pathological test findings (Box 1) (2).

Box 1

Diagnostic criteria for chronic rhinosinusitis*

“Chronic rhinosinusitis” is an umbrella term comprising many different entities. A new classification of CRS is intended to take account of this fact (Figure) (2).

Figure

Chronic rhinosinusitis

Chronic rhinosinusitis can be further characterized as either primary or secondary and as focal or diffuse mucosal disease. The classification of CRS also depends on further relevant local and systemic factors that contribute to its development.

Learning objectives

This article should enable the reader to:

• define CRS and name the appropriate methods of diagnostic evaluation;
• know the elements of its medical and surgical treatment;
• classify bronchial asthma as the most common comorbidity of CRS.

Methods

Pertinent publications, including national and international guidelines, were retrieved by a selective literature search. Current German and international guidelines and consensus papers were included, as the available primary literature contains inadequate evidence on some aspects of the topic.

Pathophysiology

The pathophysiology of CRS is not fully understood. The earlier assumption that CRS develops from unhealed acute rhinosinusitis and on the basis of impaired ventilation or drainage from the paranasal sinuses is out of date (e1). CRS is now thought to result from a dysfunctional interaction between various environmental factors and the immune system (2). Dysfunction of the mucosal barrier plays a key role (1, e2, e3) in causing chronic inflammation with tissue remodeling. Three different inflammatory patterns (types 1, 2, and 3) can be seen either individually or in combination and constitute the endotype of inflammation. The endotype influences the severity of the disease, its response to treatment, and the long-term outcome (3).

The predominant cytokines and inflammatory cells determine the endotype. Type 1 is characterized by IFN-γ, type 2 by IL-4, IL-5, IL-13, eosinophils, and mast cells, and type 3 by IL-17 and neutrophils. The distinction usually drawn is between type 2 and non-type 2 inflammation (1, 2, e3, e4).

It is, however, still common practice to classify CRS as being either with or without nasal polyps (CRSwNP or CRSsNP) on the basis of the endoscopic phenotype.

Epidemiology

The reported prevalence of CRS, as determined from symptoms alone, ranges from 5% to 12%(2, 4, 5).

If endoscopic or computed tomographic findings and typical symptoms are combined to define CRS, the reported prevalence is somewhat lower, at 3–6.4% (4), and 2–3% for CRSwNP (5). Male sex, smoking, and a positive family history are risk factors for chronic rhinosinusitis (5).

The relation of CRSsNP and CRSwNP to allergic rhinitis remains unclear because of inconsistent study findings (e5).

CRS gives rise to major direct and indirect health-care costs (2, e6). It markedly impairs the quality of life, to an extent comparable to Parkinson‘s disease, moderate asthma, or chronic obstructive pulmonary disease (3, e7, e8).

CRS is associated with a number of serious diseases for which it is considered an important risk factor (eTable 1).

eTable 1

Diseases that are significantly associated with CRS (incomplete selection, alphabetical listing)

Symptoms

The cardinal symptoms of CRS are nasal obstruction, anterior or posterior rhinorrhea (increased flow of nasal secretions from the nose or the back of the throat), pain or a feeling of pressure on the paranasal sinuses, and an impaired sense of smell (Box 1). The quality of life is impaired by a number of local and general secondary symptoms, including otalgia, cough, fatigue, and disturbed sleep (e9). The definition of CRS includes a requirement for a symptom duration of more than 12 weeks, distinguishing it from acute and subacute rhinosinusitis (6). No studies have been published on the spontaneous course of untreated CRS.

Diagnosis

The basic diagnostic evaluation includes a detailed patient history and nasal endoscopy. It should include an assessment of the severity of symptoms and impairment of the quality of life.

The basic evaluation is supplemented by further tests depending on the nature and severity of CRS in the individual case (Box 2).

Box 2

Diagnostic evaluation for suspected chronic rhinosinusitis (2, 6, 10)

The symptoms of CRS show a high sensitivity, but a low specificity for the diagnosis of CRS and therefore should be combined with objective findings (2, 6, 7).

Endoscopy

Nasal endoscopy is an essential and indispensable component of the rhinological diagnostic work-up and increases diagnostic precision beyond history-taking alone (8, 9). The endoscopic signs of CRS include edema, mucus or pus, and polyps in the middle nasal meatus or nasal cavity (Figures a, b). Endoscopy can also provide initial hints to differential diagnoses, such as cancer or an inverted papilloma.

Imaging

The imaging method of choice is a low-dose computed tomography (CT) scan or, alternatively, digital volume tomography (2, 6, 10, e10).

The CT findings should always be correlated with the patient‘s clinical symptoms, because incidental findings are common (4, 11). CT is also used to assess the individual anatomy before paranasal sinus surgery (e11).

MRI can be used rather than CT in individual cases, particularly in children, because it does not expose the patient to radiation (10, 12).

Plain x-rays are no longer indicated (e10).

In patients with definitively diagnosed CRS, a CT scan should only be obtained after unsuccessful conservative treatment (2). On the other hand, if the symptoms are typical but the endoscopic findings are normal, a CT scan is recommended to confirm the diagnosis (e11).

Typical CT findings include partial or complete opacification of the ostiomeatal unit and the affected paranasal sinuses, and, depending on the severity, polyposis of the nasal cavity as well (Figures c,d).

In case of unclear and/or isolated findings, e.g., if there is suspicion of cancer or an inverted papilloma, magnetic resonance imaging (MRI) should be added and a biopsy should be performed if necessary.

Olfactory testing

A test of the sense of smell is not absolutely necessary for diagnosing CRS, but it is a criterion for the success of treatment, e.g., with biologics, and it is also recommended for preoperative documentation (13).

Quality of life and subjective assessment

It is important to assess the patient’s quality of life and the subjective severity of symptoms. Questionnaires on the general and disease-specific quality of life can be used to assess the severity of disease and the outcome of treatment (14, 15). The one most commonly used is the Sino-Nasal Outcome Test–22 (SNOT-22) (16).

The intensity of the individual symptoms of nasal obstruction and hyposmia, and of overall sinonasal symptoms, in the past 4 weeks should also be recorded on a visual analog scale (VAS) ranging from 0 to 10 (17).

Comorbidity: bronchial asthma

Asthma is a chronic inflammatory disease of the lower respiratory tract, clinically characterized by bronchial hyperreactivity and variable bronchoconstriction with intermittent respiratory symptoms. It is usually due to type 2 inflammation, whose laboratory biomarkers—fractional exhaled NO (FeNO) > 25 ppb and blood eosinophils > 150/µL –can be used to confirm the diagnosis (18).

CRS and asthma often occur together and influence each other. 20–45% of patients with CRS have asthma (19), as do as many as 40–67% of those with CRSwNP (20). Conversely, 11–51.1% of adults with severe asthma and 4.9–23.3% of adults with CRSwNP have CRS (21). The pathophysiological mechanisms of type 2 inflammation in these two conditions also have much in common, hence the postulation of a single entity—“united airway disease”—comprising both (e12).

The simultaneous presence of asthma and CRS is associated with an increased risk of severe disease and frequent exacerbations (e1, e13, e14). Comorbid asthma is also a risk factor for the early recurrence of CRSwNP after surgical treatment (e15).

A distinction is drawn between asthma of allergic origin, which arises in early childhood and is often associated with other IgE-mediated diseases (such as allergic rhinoconjunctivitis), and intrinsic eosinophilic asthma of adulthood (peak incidence around the age of 50), which is associated with markedly elevated type-2 inflammatory markers and is more often seen in combination with CRSwNP. Intrinsic asthma is also more common in persons with Samter‘s triad (CRSwNP, asthma, and intolerance to non-steroidal anti-inflammatory drugs) (18).

Patients with asthma and CRSwNP who have markedly elevated type-2 inflammatory markers, especially blood eosinophils over 1500/μL, may have a systemic disease such as hypereosinophilic syndrome (HES) or eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome). These diseases cause generalized symptoms and can affect all organ system.

In patients with CRS and asthma, endoscopic sinus surgery (ESS) relieves symptoms and prevents asthma exacerbations in the short term (22). Both CRS and asthma often respond to biologic agents (collateral efficacy) (22). Therefore, both entities should be treated in an interdisciplinary fashion, considering both at in the selection of the mode(s) and sequence of treatment(s). Note that the criterion of severe, uncontrolled disease as an indication for treatment with biologic agents will not always be met for both entities at once.

Pharmacotherapy

The basic treatment for uncomplicated CRS, so-called appropriate medical therapy (2, 6, 10, e16), consists of topical steroids, adjunctive nasal rinsing, and optional systemic steroids and antibiotics (2, 23) (Box 3).

Box 3

Simplified stepwise approach to the treatment of chronic rhinosinusitis*

Topical steroids

Topical steroids are the basic treatment (2, 6, 10). They have been clearly shown to alleviate the patient‘s subjective symptoms (especially nasal obstruction and rhinorrhea), to reduce polyp size and the risk of polyp recurrence after surgery, and to improve the patient‘s quality of life (both general and disease-specific) (2, 6) (Table). The potential side effects include epistaxis, local irritation, and headache. The duration of therapy should be at least 4 (6) or 12 weeks (2, 24), with a dose of 2 × 1–2 puffs daily (6).

Table

Summarized evaluation of treatments for chronic rhinosinusitis based on the highest-level evidence available*1

Nasal rinsing

Nasal rinsing with saline solution is the standard adjunctive treatment for CRS (2, 6, 10). It removes viscous mucus, crusts, and inflammatory mediators, and improves mucociliary clearance. Studies reveal improvement in symptoms, endoscopy findings, and quality of life (Table). Isotonic saline solution should be used first. Hypertonic saline solution has been shown to yield better results in some studies but is more likely to cause local irritation (25). High-volume rinsing (>60 mL) and compressible nasal douching systems are recommended (6, e17). Possible side effects include local irritation, burning, and itching, as well as otalgia and epistaxis.

Systemic steroids

Short-term systemic steroids are a treatment option for patients with severe CRSwNP (2, 24). They can rapidly reduce polyp size, alleviate the cardinal symptoms of CRS, and improve the quality of life, while also relieving comorbid bronchial asthma. The optimal dose and duration of treatment are unclear, with reported doses ranging from 30 to 60 mg of prednisolone equivalent for 1 to 3 weeks (23). The benefit subsides within days to a few weeks after the end of treatment (e18), and the side effects, which may be severe (e.g. hyperglycemia, osteoporosis, glaucoma, cataracts, adrenal cortex suppression), can occur both with long-term use and with repeated administration (e19). In patients with asthma, dose-dependent adverse effects have been observed at cumulative doses of 1–2.5 g. Some adverse effects, such as diabetes mellitus and hypertension, have been seen at cumulative doses as low as 0.5–1 g (e20). The European position paper EPOS 2020 therefore recommends a maximum of two courses of systemic steroid treatment per year (2). In an updated statement from EUFOREA (the European Forum for Research and Education in Allergy and Airway Diseases), two or more courses in a singe year are designated as (relatively) contraindicated, and meticulous consideration of the indications is recommended (16).

There is no evidence of sufficient quality to support systemic steroid treatment for CRSsNP (6, 10).

Antibiotics

The treatment of CRS with antibiotics is classified as either short-term (<3 weeks) or long-term (>3 weeks). Short-term treatment is recommended only for acute exacerbations (2, 6).

The rationale for long-term therapy is the anti-inflammatory effect of the substances used, rather than their antibiotic effect. Macrolides are of uncertain efficacy, according to randomized, placebo-controlled trials; in some cases, low-dose macrolides may be considered in patients with CRS who have low serum and tissue eosinophilia and low total IgE (6, e21). The dosage and duration of therapy are unclear, and the potential side effects, such as cardiac arrythmias, must be considered. Long-term treatment of CRS with non-macrolide antibiotics is not supported by adequate evidence and is not recommended (6).

Biologics

Biologics are human antibodies that are designed to reduce the immune response and chronic inflammation by binding to pro-inflammatory cytokines or inflammatory mediators. Three substances, dupilumab (anti IL-4/IL-13), mepolizumab (anti IL-5), and omalizumab (Anti IgE), have been approved for the treatment of severe bilateral CRSwNP as an add-on to topical steroids, if the disease cannot be adequately controlled with systemic corticosteroids and/or surgery (dupilumab, mepolizumab) or with intranasal corticosteroids (omalizumab) (German Federal Joint Committee, October 2019, November 2021, July 2020) (2, 6, 10, 24, 26).

According to the European position paper/EUFOREA, biologics are indicated for the treatment of severe bilateral CRSwNP after previous sinus surgery and if at least three further criteria are met (21, 23):

• evidence of type 2 inflammation (eosinophilia in tissue and/or serum, elevated total IgE)
• need for systemic steroid administration or contraindications to systemic steroid therapy
• markedly impaired quality of life
• markedly impaired sense of smell
• comorbid bronchial asthma

No biomarkers have been identified that can predict the success of biologic therapy or favor the choice of one biologic agent over another (e22).

Randomized, placebo-controlled trials have shown that biologics reduce polyp size, alleviate symptoms, and improve the quality of life (27) (Table).

The indications for treatment and its outcome must be documented (2, 6, 26, 28) (documentation aid: www.register.awmf.org/de/leitlinien/detail/017–049, supplementary document S2K guideline on rhinosinusitis).

The outcome of treatment should be reviewed at six months, whereupon one of the following should be decided upon (13):

• continuation of treatment;
• adding on treatment of comorbid disease;
• switching to another biologic;
• providing additional surgical treatment; or
• discontinuing treatment.

Treatment with biologics is a long term with considerable costs. The annual cost per patient is 15 776.80 euros (dupilumab), 14 927.68 euros (mepolizumab), or 3654.72–27 413.92 euros (omalizumab) (prices according to the Red List, accessed on June 16, 2024). It remains unclear whether, and under what conditions, the interval between drug administrations can be prolonged without reducing the efficacy of treatment (e23).

Although the biologics are considered to be well tolerated on the basis of the approval studies, side effects associated with the new indication for use should be noted (e24, e25, e26, e27, e28).

The ones most commonly encountered are injection-site reactions (redness, itching, swelling), conjunctivitis, arthralgia, myalgia, rash, headache, and fatigue.

Aspirin desensitization

Aspirin desensitization is considered an effective preventive treatment to prevent recurrence after sinus surgery in patients with Samter‘s triad (6, 24, 29, e31). The repeated administration of acetylsalicylic acid (ASA) is thought to induce tolerance to analgesics, with a subsequent reduction in symptoms and improvement in quality of life (Table). It is limited by gastrointestinal side effects, the necessary long-term daily intake of ASA, and aggravated by the fact that the dose needed for efficacy has not been conclusively identified (e29, e30, e31).

Surgery

The initial goal of treatment is to control the disease (13, 17), which, from the patient‘s point of view, means a reduction of sinonasal symptoms to < 5 on a 0–10 visual analog scale (VAS) (2, 17) and/or a reduction of the disease-specific quality of life score (SNOT-22) to < 40 or ≤ 20 (2, 23).

The long-term goal is remission, i.e., the absence of symptoms and endoscopic findings of active disease for at least 12 months (13).

If the symptoms cannot be sufficiently controlled by appropriate medical treatment with the additional addressing of comorbidities and trigger factors, then endoscopic sinus surgery (ESS) may be indicated (2, 6, 13, 24, e16) (Box 3), depending on other patient-specific factors. The same criteria apply to the indication for (extended) revision surgery, although the risk–benefit ratio should be considered with special care in this case (6).

The basic goals of ESS for CRS are to remove an obstruction and establish permanent drainage, and, if necessary, to remove pronounced inflammatory changes (e.g., polyposis, mucus impaction, possibly fibrosis and osteoneogenesis) and open up the sinuses for future topical therapy (6, 12, 30).

Simple polyp removal for CRSwNP is not recommended (24). The goal of extended ESS is to eliminate the burden of inflammation itself in order to remove the inflammatory load in the mucosa and thereby control the disease (30).

ESS brings about marked improvement in individual and overall symptoms (6, 31, 32, e32) as well as in the overall and disease-specific quality of life (33, 34, e33).

Many studies have shown that extended ESS leads to better outcomes and a lower revision rate than functional surgery in severe forms of CRS, without an increase in surgical complications (28, 30, 35, e34) (Table).

Although polyp recurrence is seen in 35 to 80% of patients, especially in severe cases, in the long term (more commonly if the treated polyposis was severe) (2), this does not mean that every recurrence is symptomatic ort requires revision surgery. Rather, 15–25% of the affected patients undergo revision surgery within 5–10 years (31, 36, 37, e32).

In the long term, ESS is not only effective but also cost-effective (33, e35, e36), in comparison with either continued medical treatment (e38, e35) or biologics(e37, e39, e5). A first cost–benefit analysis over 36 years showed that dupilumab treatment was more than 10 times as expensive as surgery, while the two treatments were of comparable efficacy (8.95 vs.s 9.80 quality-adjusted life years (QALY)) (e38).

In a second analysis relating to a period of 10 years, the calculated cost of dupilumab was $691 691 per additional QALY, with surgery being more cost-effective in all calculations (e39). Surgery significantly reduces work absences and loss of productivity from impaired work performance due to illness (23). ESS improves the quality of life to an extent comparable to biologics (e36).

Pediatric chronic rhinosinusitis

The symptoms of pediatric chronic rhinosinusitis (PCRS) are non-specific and overlap with those of other upper respiratory tract diseases in children, such as allergic rhinitis or adenoids. In younger children, the main symptoms are cough and nasal secretions; older children tend to complain of nasal congestion and a feeling of pressure or facial pain (38). PCRS can be distinguished from self-limiting upper respiratory tract infections (which last 7–10 days) or acute rhinosinusitis (which lasts <4 weeks) by the symptom duration of more than 12 weeks (2). The prevalence of chronic rhinosinusitis in children is 0.3–4%, which is lower than in adults (2). The inflammatory patterns in children with PCRS differ from those in adults with CRS. Tissue eosinophilia is only seen in exceptional cases.

Pathogenesis

Differentiating inflammation of hyperplastic adenoids (adenoiditis) from PCRS can be difficult. Biofilms apparently play an important role (e40).

There is evidence of links between PCRS and gastroesophageal reflux disease (GERD), immune deficiencies, and environmental factors (especially exposure to tobacco smoke) (39). Cystic fibrosis (CF), primary ciliary dyskinesia (PCD), and immune deficiency syndromes should be considered in the differential diagnosis.

Diagnosis

The diagnosis of PCRS is not always clear-cut, particularly when it must be distinguished from adenoiditis, as the symptoms of the two diseases (nasal obstruction and secretion, coughing) overlap to a large extent. On the other hand, the conservative treatment of both is essentially the same. Nasal endoscopy is important and helpful, but often cannot be performed to a sufficient standard in younger patients.

Tomographic imaging (CT, MRI) should usually only be performed after the failure of conservative treatment (38). MRI is increasingly being used instead of CT to limit radiation exposure.

Management

Conservative treatment

Antibiotics should only be given in complicated and severe cases (38) (eTable 2). Topical steroids are the first-line treatment for PCRS (2). The additional use of nasal lavage with saline solution is also recommended (2).

eTable 2

Evidence table for the treatment of pediatric chronic rhinosinusitis*

eTable 3

Evaluation of treatments for chronic rhinosinusitis based on the highest-level evidence available (long version)

Surgery

Adenotomy (adenoidectomy) – Adenoidectomy is the first-line surgical treatment option. It has a success rate of 50–71% as a single treatment (e41, e42). The symptoms of PCRS are the deciding factor for the indication, regardless of the size of the adenoids (e43). Adenoidectomy alone is less effective beyond age 6 (38).

Endoscopic paranasal sinus surgery (ESS) – ESS is the treatment of choice when conservative treatment or adenoidectomy is insufficient. The success rate of ESS in children is 71–100% (40). Biologics have not been approved for the treatment of CRSwNP in children.

Conclusion

CRS is a common disease that markedly impairs the quality of life. Medical treatment and surgery, tailored to the pheno- and endotype of the disease, has the primary purpose of disease control. Individualized treatment will become increasingly important in the coming years.

Conflict of interest statement
IB has received lecture honoraria from GlaxoSmithKline and Sanofi Aventis for company-sponsored continuing medical education events. He is a member of the board of the Pediatric ENT Working Group of the German ENT Society.

TH has received payment for continuing medical education events from Sanofi, Novartis, and GSK.

KMK has served as a paid consultant for AstraZeneca, Chiesi, GSK and Sanofi. She has received payment for continuing medical education events from AstraZeneca, Chiesi, GSK, Novartis, and Sanofi. She is a spokesman for the Asthma, Allergology, Immunology section of the German Respiratory Society.

RW has received honoraria for preparing scientific papers from GSK, Hommel Pharma, Infectopharm, Karl Storz, Sanofi-Aventis, Sidroga, Spiggle & Theis, and Stryker. He has been reimbursed for travel expenses for events including lectures by GSK, Infectopharm, Karl Storz, Sanofi-Aventis, Sidroga, and Stryker. He is a member of the board of directors of the Rhinology/Rhinosurgery Working Group of the German Society of Oto-Rhino-Laryngology and Head and Neck Surgery.

Manuscript submitted on 7 May 2024, revised version accepted on 31 July 2024.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
PD Dr. med. Tanja Hildenbrand
Klinik für Hals-, Nasen- und Ohrenheilkunde
Universitätsklinikum Freiburg
Killianstr. 5, D-79106 Freiburg

Cite this as:
Hildenbrand T, Milger-Kneidinger K, Baumann I, Weber R: The diagnosis and treatment of chronic rhinosinusitis.
Dtsch Arztebl Int 2024; 121: 643–53. DOI: 10.3238/arztebl.m2024.0167

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