Chronic Rhinosinusitis with Nasal Polyps: Clinical Guidelines

List of Abbreviations

IgE – immunoglobulin E;

LTC-4, LTD-4, LTE-4 – leukotrienes C-4, D-4, E-4;

БА – bronchial asthma;

ГИБТ – biological therapy / advanced targeted therapy;

IL — interleukin;

CT – computed tomography;

MRI – magnetic resonance imaging;

PNS – paranasal sinuses;

ПРС – chronic rhinosinusitis with nasal polyps (CRSwNP);

СО – mucosa / mucous membrane;

ФЭРСХ – functional endoscopic sinus surgery;

ГИБП – biological agents / advanced targeted drugs

Terms and Definitions

Nasal polyps are benign neoplasms of the mucous membrane of the nose and paranasal sinuses.

Biological therapy is therapy using medicinal products based on protein molecules produced via genetic engineering. Biological therapies precisely target specific components of the immune system responsible for pathological processes without suppressing the entire immune system.

Remodeling of the nasal and paranasal sinus mucosa includes sequential morphological changes such as ciliated epithelium metaplasia, goblet cell hyperplasia, basement membrane thickening, fibrosis, and neoangiogenesis.

T2-endotype of CRSwNP is an inflammatory process characterized by the following features: peripheral blood eosinophilia, tissue eosinophilia, or elevated total IgE levels (CRSwNP / eosinophilic chronic rhinosinusitis; allergic fungal rhinosinusitis; CCAD — central compartment atopic disease, characterized by isolated polypoid changes in the mucosa of the superior and middle turbinates and the posterosuperior nasal septum in patients with confirmed allergies to inhalant allergens).

Cytokines are active specific proteins produced predominantly by cells of the human immune system, most often lymphocytes. Cytokines act on body tissues and influence their intercellular interactions. Cytokines include interleukins, interferons, tumor necrosis factors, growth factors, and chemokines.

Level of evidence, LoE – ranking of research designs based primarily on their internal validity.

Note 1: this method is used to determine the persuasiveness of a study.

Note: 2: various hierarchies of evidence are used to evaluate health technologies.

Level of clinical evidence (LCE) – the degree of certainty in the validity of the intervention's effect and in the fact that following the recommendations will bring more benefit than harm in a specific clinical situation.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a phenotype of chronic rhinosinusitis representing a chronic inflammation of the nasal and paranasal sinus mucosa — heterogeneous in its etiology and pathogenesis — characterized by mucosal remodeling, formation, and recurrent growth of polyps lasting more than 12 weeks [1, 3.6].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

According to current concepts, the pathophysiological mechanisms of CRSwNP involve various factors: impairments of innate and adaptive immunity, allergy, genetically determined conditions (immunodeficiency states, cystic fibrosis, primary ciliary dyskinesia, etc.), as well as alterations in intranasal anatomy and infections (bacterial, fungal, viral) which, together or individually, create the prerequisites for the onset, recurrence, and chronification of the inflammatory process in the nasal mucosa with proliferation and polyp formation [3-6, 17-19].

The key mechanism of CRSwNP formation is considered to be inflammation accompanied by infiltration of the nasal mucosa and polyp tissue by activated eosinophils, neutrophils, and plasma cells. There are differences in clinical manifestations, course, and treatment efficacy between the eosinophilic and non-eosinophilic endotypes of CRSwNP [7, 16]. A characteristic feature of eosinophils directly related to the pathogenesis of CRSwNP is their ability to release various mediators — major basic protein (accounting for 30% of total granular proteins), eosinophil cationic protein, neurotoxin, and peroxidase — which exhibit pronounced proteolytic activity not only against pathogenic microflora but also against normal tissues. The predominant involvement of eosinophils in the inflammatory process of CRSwNP (accounting for over 60% of the cellular composition of a nasal polyp) is driven by cytokines produced by Th2 lymphocytes, specifically interleukins-3 (IL-3), -5 (IL-5), and granulocyte-macrophage colony-stimulating factor (GM-CSF) [8, 9, 16]. The pro-inflammatory effects of each of these cytokines include increased vascular permeability, stimulation of transudation, and electrolyte metabolism disorders, which contribute to chronic interstitial edema of the nasal mucosa and ultimately create conditions for polyp formation [8, 9].

One variant of the specific immune response upon contact with an antigen is the development of allergic inflammation, which acts as one of the triggers for CRSwNP development [10, 11].

Impairments in the innate and adaptive immune systems can lead to the onset and a more severe course of the disease, especially when CRSwNP is combined with allergic rhinitis and bronchial asthma [11-16]. An indirect confirmation of the role of genetic predisposition as a risk factor for CRSwNP is the presence of nasal and paranasal sinus polyposis in genetically determined diseases such as Kartagener syndrome, cystic fibrosis, and primary ciliary dyskinesia [3, 6, 11].

Carriage of herpesviruses and human papillomavirus is playing an increasingly recognized role in the development of chronic rhinosinusitis with nasal polyps [21, 22, 23].

Various structural alterations in intranasal architecture causing obstruction of the ostiomeatal complex and frontonasal duct play a specific role in the onset and recurrence of the inflammatory process in the nasal cavity and paranasal sinuses in CRSwNP. In addition to nasal septum deviation, which is detected in 36% of patients with rhinosinusitis, anatomical variations frequently observed in this disease include concha bullosa (30%), Onodi cells (12%), Haller cells (6%), and less commonly, paradoxical curvature of the middle turbinate (3%), pneumatization of the uncinate process (2%), and others [24, 25]. These anatomical abnormalities alter the aerodynamics of the nasal cavity, causing inspiratory airflow and the microorganisms and antigens it carries to constantly interact with specific areas of the nasal cavity, thereby initiating inflammatory changes and mucosal remodeling [26, 27].

1.3 Epidemiology of the Disease or Condition

According to medical examination data, the average prevalence of CRSwNP in the population is 1.13% (ranging from 0.8% to 4.3%), while healthcare utilization data show an incidence of 1.3–13.1 per 10,000 population. Over 60% of all patients are aged 50 years and older. The proportion of men and women among CRSwNP patients is approximately equal, although healthcare seeking is higher among men under 60 years of age and among women over 60 years [28-31].

Thus, among the adult population of the Russian Federation (15 years and older), CRSwNP may affect 1.2–5 million people. However, existing estimates of CRSwNP frequency, based on medical examinations and/or healthcare utilization analysis, likely fail to reflect the true prevalence of the disease. This is supported, in particular, by autopsy data involving nasal cavity endoscopy, during which nasal polyps are found in 32% of cases [30], significantly exceeding the results of clinical and epidemiological studies.

1.4 Features of Coding the Disease or Condition

J33.0 – Polyp of nasal cavity;

J33.1 – Polypoid degeneration of sinus;

J33.8 – Other polyp of sinus;

J33.9 – Nasal polyp, unspecified.

1.5 Classification of the disease or condition

A unified classification of CRSwNP is currently lacking; however, staging systems for the pathological process have been developed and are used in clinical practice to formulate a clinical diagnosis, determine treatment tactics, and evaluate treatment efficacy. The staging of the pathological process most frequently relies on nasal endoscopy data, paranasal sinus computed tomography (CT) results, and morphological characteristics of the polyp tissue.

Clinically (endoscopically), it is recommended to distinguish 3 stages of the polypoid process [31, 32]:

1. polyps confined to the middle meatus;

2. polyps extending beyond the middle meatus;

3. polyps causing obstruction of the corresponding nasal cavity.

The LUND-KENNEDY scoring system [1] is also used for endoscopic assessment (Appendix G2):

Characteristics                                Score

Polypoid tissue, left                          0, 1, 2

Polypoid tissue, right                       0, 1, 2

Edema, left                                       0, 1, 2

Edema, right                                     0, 1, 2

Discharge, left                                 0, 1, 2

Discharge, right                             0, 1, 2

Interpretation of Lund-Kennedy scale data:

1. Polyps: 0 points — absence of polyps; 1 point — presence of polyps localized in the middle meatus; 2 points — presence of polyps extending beyond the middle meatus.

2. Edema: 0 points – no edema; 1 point – moderate edema; 2 points – significant edema.

3. Discharge: 0 points – no discharge; 1 point – clear discharge present; 2 points – thick purulent discharge visualized.

Grade 1 – 0 points (no changes);

Grade 2 – 1 point (partial sinus opacification);

Grade 3 – 2 points (complete sinus opacification).

In addition, the state of the ostiomeatal complex is determined:

0 points – intact ostiomeatal complex;

2 points – obstructed ostiomeatal complex.

Thus, the total score for all paranasal sinuses on each side ranges from 0 to 12 (overall from 0 to 24 points).

Depending on the histological structure, it is recommended to differentiate the following types of polyps:

• edematous polyps with predominantly eosinophilic (70–85% of the cell population) infiltration;

• fibrous polyps with a predominance of neutrophils;

• polyps with hyperplasia of seromucous glands;

• polyps with stromal cell atypia.

1.6 Clinical presentation of the disease or condition

Subjective manifestations of chronic rhinosinusitis with nasal polyps are characterized by nasal congestion; mucous or mucopurulent nasal discharge; post-nasal drip; a feeling of heaviness or pressure in the nasal area and the projection of the paranasal sinuses; diffuse headache; reduced or lost sense of smell. In some cases, these nasal symptoms may be accompanied by abnormal sensations (burning, irritation) in the throat, cough, hoarseness, as well as malaise, reduced working capacity, and drowsiness. At the same time, attention should be paid to the severity and duration of subjective signs.

During exacerbations of the process, these symptoms become more pronounced.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing a diagnosis of chronic rhinosinusitis with nasal polyps include: complaints, medical history, physical and instrumental examination data (anterior rhinoscopy, endoscopic endonasal examination of the nasal cavity and nasopharynx, computed tomography of the paranasal sinuses and larynx).

2.1 Complaints and Anamnesis

Complaints. When collecting complaints from patients with suspected chronic rhinosinusitis with nasal polyps, it is important to distinguish groups of complaints: nasal complaints regarding difficulty in nasal breathing, discharge from the nasal passages, absence or deterioration of olfaction; pain-related complaints (facial pain, sense of fullness or pressure in the facial area, headache, toothache); oro-nasopharyngeal complaints (halitosis, post-nasal drip, cough, ear fullness or pain); complaints regarding systemic manifestations of the disease (general malaise, increased fatigue, decreased working capacity). Distinguishing groups of complaints helps confirm the diagnosis, determine the severity grade, and identify factors that may influence the choice of treatment strategy; [1, 6].

Comments: Assessment of the patient's complaints is an important and accessible component of the diagnostic examination; however, it is characterized by a high probability of false-positive conclusions. Based on subjective manifestations, the presence of chronic rhinosinusitis with nasal polyps can be predicted with a specificity of 89% and a sensitivity of 2%, which indicates that these signs are insufficient as diagnostic criteria for chronic rhinosinusitis with nasal polyps [35]. Scoring is performed in points (from 0 – no symptom to 10 points – maximum severity of the symptom). Mild manifestations of the disease correspond to the range of 0–3 points, moderate to 3–7 points, and severe course to 7–10 points. At the same time, symptoms with a severity of 5 points or more have a significant impact on quality of life. Diagnostic specificity increases when two or more subjective symptoms are combined along with objective signs of the disease (data from nasal endoscopy, diagnostic imaging) [36, 37].

Medical history. The main tasks of this section of the examination of a patient with chronic rhinosinusitis with nasal polyps are as follows: clarifying the timing, potential causes, sequence of symptom onset, their severity, trends in the development of subjective signs from their inception to the present; factors influencing the severity and dynamics of subjective sensations; results of previously performed examinations, as well as the nature, scope, and efficacy of prior treatment.

In addition, when taking the medical history, it is necessary to clarify the following questions:

• presence/absence of a relationship between the onset or exacerbation (intensification) of symptoms upon exposure to seasonal or perennial allergens;

• presence/absence of intolerance to acetylsalicylic acid** and other nonsteroidal anti-inflammatory and antirheumatic drugs;

• presence/absence of symptoms of bronchial asthma;

• presence/absence of chronic rhinosinusitis with nasal polyps in close relatives;

• localization of nasal symptoms (unilateral, bilateral);

• presence/absence of recurrent epistaxis.

2.2 Physical Examination

Comments: During the physical examination by an otorhinolaryngologist, palpation/percussion of the paranasal sinus projection zones is of great diagnostic significance, along with checking for signs of nasal obstruction (difficulty in nasal breathing, nasal voice), viscous mucous or mucopurulent discharge from the nasal cavity, and the presence of polyps (in chronic rhinosinusitis with nasal polyps with a long-standing and widespread process, polyps may be detected upon external examination in the area of the nostrils (nasal vestibule), and in some cases, broadening of the external nasal dorsum is observed) [3, 6].

2.3 Laboratory Diagnostics

Comments: in cases where an allergic component is pronounced, an increase in the eosinophil count > 10% per visual field is characteristic [40].

2.4 Instrumental Diagnostics

Comments: The use of endoscopic endonasal examination of the nasal cavity and nasopharynx allows for a more thorough investigation of the nasal cavity, in particular the state of the middle nasal meatus, sphenoethmoidal recess, and nasopharynx, and clarifies the nature of changes (edema, hypertrophy, polyposis). In addition, endoscopic endonasal examination of the nasal cavity and nasopharynx makes it possible to differentiate chronic rhinosinusitis with nasal polyps from pathological conditions with similar symptoms, such as tumors, adenoid hypertrophy, or hypertrophy of the posterior ends of the inferior turbinates. The use of endoscopic endonasal examination of the nasal cavity and nasopharynx, along with clarifying complaints and anamnesis data, significantly increases the probability of recognizing chronic rhinosinusitis with nasal polyps – the specificity and sensitivity of the method are estimated at 84% and 66%, respectively [42–44].

Comments: cone-beam computed tomography of the nose and paranasal sinuses can be performed in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) as an alternative to multislice computed tomography to reduce radiation exposure during serial examinations (with a viewing window volume of 15 cm × 15 cm × 15 cm and local roentgen densitometry) over time. This avoids exceeding the annual radiation dose limit for a single anatomical region compared to multislice computed tomography [46].

Comments: Routine radiography of the paranasal sinuses, despite its low cost and availability, has limited diagnostic value in CRSwNP compared to CT.

2.5 Other Procedures

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Both medical and surgical treatments for chronic rhinosinusitis with nasal polyps significantly and almost equally improve the quality of life of examined patients, which confirms the priority importance of adequate pharmacotherapy for CRSwNP.

3.1 Medical treatment

Comments: When choosing a specific medicinal product, preference should be given to drugs with high topical activity, low bioavailability, and consequently a high safety profile during long-term use. The advantages of corticosteroids include: reduction in polyp size during nasal endoscopy; reduction or disappearance of nasal obstruction symptoms; improved sense of smell; prevention of CRSwNP recurrence; and improved patients' quality of life [50-51].

The drug of choice is the topical glucocorticosteroid mometasone nasal spray (ATC code: R01AD09) at a dose of 100 mcg in each nostril twice daily; the duration of treatment is 3–6 months. After achieving a clinical effect, it is recommended to reduce the dose to 2 puffs in each nostril once daily (total daily dose of 200 mcg). If symptom relief is not achieved after 5–6 weeks of treatment, the advisability of surgical treatment should be considered [52].

Comments: Systemic corticosteroids (ATC: H02) are recommended for short-term treatment of ARS (glucocorticosteroid tablets - prednisolone** from 30 mg to 60 mg per day for 14 days) in case of insufficient control of ARS symptoms with corticosteroid nasal sprays (ATC: R01AD) [55, 56]. It should be noted that prolonged or frequent use of systemic corticosteroids in ARS may increase the risk of adverse events and complications [57, 58].

Comments: The potential use of macrolides (ATC code: J01FA) in CRSwNP is currently associated with the immunomodulating properties of this group of systemic antibacterial drugs, their ability to inhibit the production of proinflammatory cytokines and chemokines, minimize proliferation, differentiation, and collagen production by fibroblasts, and reduce eosinophil infiltration of the nasal mucosa [62]. However, the lack of data on the optimal drug, dosage, and duration of therapy based on available evidence does not allow for a definitive conclusion regarding the efficacy of macrolides in the treatment of chronic rhinosinusitis with nasal polyps [63].

Comments: Advancing understanding of the pathogenesis of CRSwNP contributes to the development and introduction into modern clinical practice of personalized pharmacotherapy principles for this disease using targeted biological drugs. Biological drugs – are recombinant fully human or humanized monoclonal IgG antibodies capable of selectively binding to human IgE or to interleukins or their receptor subunits (IL-5, IL-4/13).

Criteria for prescribing biological therapy for patients with CRSwNP in the presence of bilateral nasal polyposis and a history of surgical interventions (3 criteria required) [1, 64]:

• Signs of T2 inflammation (tissue eosinophils ≥ 10/high-power field OR blood eosinophils ≥ 150 cells/mcL, OR total IgE ≥ 100 IU/mL)

• Need for systemic corticosteroids or presence of contraindications to systemic corticosteroids (≥ 2 courses in the past year OR long-term use [> 3 months])

• Significant impairment of quality of life (SNOT-22 ≥ 40)

• Significant loss of sense of smell (anosmia confirmed by olfactory testing)

• Diagnosis of comorbid bronchial asthma (bronchial asthma requiring regular use of inhaled corticosteroids)

Response criteria for biological therapy [1, 65]:

• Reduction in nasal polyp size

• Decreased need for systemic corticosteroids

• Improved quality of life

• Improved sense of smell

• Reduced impact of comorbidities

The severity of treatment response is evaluated based on a combination of criteria:

• Good − complete response: 4–5 criteria

• Moderate response: 2–3 criteria

• No response − poor response: 0–1 criterion

Efficacy is evaluated at 6 months and 1 year after the start of treatment. If there is no response, the diagnosis should be reassessed, treatment discontinued, and, if necessary, switched to another biological drug [1, 65].

Biological therapy is long-term; interrupting the treatment course may lead to disease recurrence. Biological drugs should be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. Considering the benefits of breastfeeding for the child and the benefits of continued drug therapy for the mother, a decision should be made whether to discontinue breastfeeding or to stop the biological drug during the breastfeeding period [66].

Biological drugs approved for the treatment of CRSwNP:

Dupilumab** (ATC code: D11AH05) – administered subcutaneously, 150 mg/mL, 2.0 mL (300 mg) once every 2 weeks in patients aged 18 years and older. If treatment is interrupted, it is recommended to resume it as soon as possible. No dose adjustment is required in elderly patients.

Omalizumab** (ATC code: R03DX05) – administered subcutaneously. The dose and frequency of administration are determined based on the baseline IgE concentration (IU/mL) measured before treatment initiation, as well as the patient's body weight (kg). Depending on these parameters, the recommended dose ranges from 75 to 600 mg every 2 or 4 weeks. Dose adjustment is necessary in case of significant changes in body weight during treatment.

Mepolizumab (ATC code: R03DX09) is prescribed to adult patients with poorly controlled severe chronic rhinosinusitis with nasal polyps and targets interleukin-5 (IL-5). The dose for treating chronic rhinosinusitis with nasal polyps is 100 mg of mepolizumab administered as a subcutaneous injection once every 4 weeks; it is intended for long-term therapy.

Genetically engineered biological drugs can be used for long-term therapy. The necessity of continuing therapy with drugs from the targeted biologic therapy group is assessed by the physician based on the patient's disease severity and the results of exacerbation control [1, 67, 68].

3.2 Surgical Treatment

Medical treatment of chronic rhinosinusitis with nasal polyps does not always lead to the desired outcome; in such cases, surgical intervention is a more radical method of treatment.

Comments: The optimal surgical intervention for chronic rhinosinusitis with nasal polyps is the concept of functional endoscopic sinus surgery (FESS), which involves the removal of polyps (polypoidally altered mucosa of the nasal cavity and paranasal sinuses), restoration of the patency of natural ostia, and elimination of anatomical abnormalities in the nasal cavity, most commonly including septoplasty and/or turbinate resection using video-endoscopic technologies, and resection of the ethmoid bulla using video-endoscopic technologies.

Depending on the severity and nature of pathological changes, minimally invasive interventions ensuring drainage and aeration of the paranasal sinuses may be used [1, 3, 6, 69].

The effectiveness of surgical treatment for chronic rhinosinusitis with nasal polyps largely depends on preoperative medical therapy.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: comprehensive rehabilitation includes: prescribing a protective regimen for 10-14 days or more after surgery; sanitation of the nasal cavity and paranasal sinuses under endoscopic control using an "irrigation-aspiration" mode in the early postoperative period; atraumatic removal of dense inflammatory products and fibrin deposits to prevent synechia formation; irrigation of the nasal cavity with 0.9% sodium chloride solution** (ATC: B05CB01) in the presence of excessive thick secretions or drying crusts to improve contact of topical medications with the surface of the nasal mucosa [3, 6, 71].

5. Prevention and Dispensary Observation

Comments: There are no specific prevention measures for chronic rhinosinusitis with nasal polyps. During pre- and postoperative medical therapy using corticosteroid - nasal sprays (ATC: R01AD) for 6–12 months, a reduction in the severity of nasal mucosal inflammation, improvement in patients' quality of life, a decrease in the likelihood of chronic rhinosinusitis with nasal polyps relapses, and an increase in the duration of disease remission are observed in the majority of cases [70 - 72].

The issue of the frequency of examinations for patients is decided individually. During the first year after surgery, follow-up examinations should be performed every 3 months. In case of a relapse of chronic rhinosinusitis with nasal polyps requiring reoperation, or suspicion of a complicated course of the disease, a CT scan of the paranasal sinuses is indicated.

6. Organization of Medical Care

Diagnostic and therapeutic procedures for patients with chronic rhinosinusitis with nasal polyps can be performed in both outpatient and inpatient settings.

Patients are hospitalized for planned surgical treatment (FESS with/without single-stage correction of intranasal structures) in the absence of contraindications to surgery. Indications for planned hospitalization may also include the need for selection and adjustment of therapy, as well as systemic therapy using genetically engineered biological drugs/monoclonal antibodies in day and 24-hour inpatient settings.

Indications for patient discharge after surgical intervention include a satisfactory general condition, and improvement or restoration of nasal breathing.

7. Additional Information

The primary task of the otorhinolaryngologist is to provide comprehensive treatment that ensures control of chronic rhinosinusitis with nasal polyps symptoms and improves the patient's quality of life. In some cases, repeated gentle endoscopic interventions in the nasal cavity and paranasal sinuses are necessary. Patients with chronic rhinosinusitis with nasal polyps require daily use of corticosteroid nasal sprays (ATC: R01AD), often for life, with short breaks.

The follow-up by an otorhinolaryngologist must be systematic, at least once every 3 months. The effectiveness of treatment depends not only on a successfully performed surgical intervention and the surgeon's experience, but also on the patient's adherence to treatment and careful execution of given recommendations.

Criteria for Evaluating the Quality of Medical Care

Criteria for assessing the quality of primary health care for patients with chronic rhinosinusitis with nasal polyps (ICD-10 J33.0, J33.1, J33.8, J33.9)

Criteria for assessing the quality of specialized medical care for patients with chronic rhinosinusitis with nasal polyps (ICD-10 J33.0, J33.1, J33.8, J33.9)

References

Appendix A1. Working Group Composition

Kim I.A., MD, Professor, Member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

Nosulya EV, Dr. Med. Sci., Professor, Member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

Ryazantsev S.V., MD, Professor, member of the National Medical Association of Otorhinolaryngologists, no conflict of interest

Egorov V.I., MD, Professor, member of the National Medical Association of Otorhinolaryngologists, no conflict of interest

Karpishchenko S.A., MD, Professor, member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

Karneeva O.V., MD, Professor, member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

Svistushkin V.M., MD, Professor, member of the National Medical Association of Otorhinolaryngologists, no conflict of interest

Abdulkerimov Kh.T., MD, Professor, member of the National Medical Association of Otorhinolaryngologists, no conflict of interest

Averbukh V.M., PhD, member of the National Medical Association of Otorhinolaryngologists, no conflict of interest

Tkachuk I.V., PhD, member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. otorhinolaryngologists;

2. allergists-immunologists;

3. pulmonologists;

4. medical students, residents, postgraduate students.

Table 1. Scale for assessing levels of reliable evidence (LRE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LE) for methods of prevention, treatment, and medical rehabilitation, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)

Table 3. Scale for assessing the grades of recommendation (GR) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The update mechanism for clinical guidelines provides for their systematic revision—at least once every three years, as well as upon the emergence of new evidence-based data regarding the diagnosis, treatment, prevention, and rehabilitation of specific conditions, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines have been developed taking into account the following regulatory and legal documents:

1. Federal Law No. 323-FZ of November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation";

2. Order of the Russian Ministry of Health dated November 12, 2012, No. 905n "On approval of the rules for the provision of medical care to the population in the profile 'otorhinolaryngology'";

3. Order of the Russian Ministry of Health dated May 10, 2017, No. 203n "On approval of criteria for assessing the quality of medical care";

4. Order of the Russian Ministry of Health dated February 28, 2019, No. 103n "On Approval of the Procedure and Deadlines for the Development of Clinical Practice Guidelines, Their Revision, the Standard Template of Clinical Practice Guidelines, and Requirements for Their Structure, Composition, and Scientific Validity of Information Included in Clinical Practice Guidelines";

5. Order of the Ministry of Health of Russia No. 804n dated October 13, 2017, "On Approval of the Nomenclature of Medical Services";

6. Order of the Russian Ministry of Health dated May 2, 2023, No. 205n (as amended on December 4, 2023) "On approval of the Nomenclature of positions of medical workers and pharmaceutical workers".

   Appendix A3.1 Explanation of notes

7. ** – a medicinal product included in the List of Vital and Essential Drugs for medical use for 2024 (Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019, as amended on April 16, 2024)

8. # – off-label use outside the indications registered in the medicine's instructions is carried out by decision of the medical commission, with the permission of the Local Ethics Committee of the medical organization (if any), subject to the signed informed consent of the parents (legal representative) and the patient over 15 years of age.

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

CRSwNP is a chronic disease whose pathogenesis involves multiple causal factors. Both medical and surgical treatments are used in the management of CRSwNP.

In most cases, a combined approach is used. From the perspective of modern guidelines, the main objective of pharmacotherapy in CRSwNP is to ensure symptom control, prevent disease recurrence, and improve the patient's quality of life. In some cases, repeated conservative endoscopic interventions in the nasal cavity and paranasal sinuses are necessary. Patients with CRSwNP require daily use of corticosteroids, often lifelong, with brief interruptions.

Otorhinolaryngologist follow-up should be systematic, at least once every 3 months. In the presence of concomitant bronchial asthma, follow-up by an allergist-immunologist is required. Treatment efficacy depends not only on the prescription of baseline therapy, successfully performed surgery, and the surgeon's experience, but also on the patient's adherence to treatment and careful implementation of the recommendations provided.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix A1. Visual Analogue Scale

Russian title: Visual Analogue Scale

Original title (if applicable): Visual analog scale (VAS)

Source: Lim M, Lew-Gor S, Darby Y, Brookes N, Scadding G, Lund VJ. The relationship between subjective assessment instruments in chronic rhinosinusitis. Rhinology. 2007 Jun;45(2):144-7.

Type (underline):

rating scale

index

questionnaire

other (specify):

Prescription:

Assessment of the severity of the patient's complaints and subjective sensations as a whole, including various aspects of quality of life (nighttime sleep, work capacity, physical activity, etc.).

Content (template):

The Visual Analogue Scale (VAS) is a horizontal graduated line 10 cm in length (Fig.), on which the patient marks with a vertical line their assessment of the disease's impact on their well-being, scored from 0 to 10 (0 points – no symptom, 10 points – maximum symptom severity).

Key (interpretation):

Mild manifestations of the disease correspond to the range of 0–3 points, moderate to 3–7 points, and severe to 7–10 points. At the same time, a significant impact on quality of life is exerted by symptoms with a severity of 5 points or more.

Appendix A2 Endoscopic examination of ENT organs using the Lund-Kennedy scale

Russian name:

Endoscopic examination of ENT organs using the Lund-Kennedy scale

Original title (if applicable): Lund-Kennedy Endoscopic Scoring

Source: Fokkens W.J., Lund V.J., Hopkins C., Hellings P.W., Kern R., Reitsma S., et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020; 58 (29): 1-464. doi: 10.4193/Rhin20.600.

Type (underline):

rating scale

index

questionnaire

other (specify):

Prescription:

For characterizing the pathological process during endoscopic examination according to the criteria "discharges, edema, polyps"

Content (template):

Key (interpretation):

1. Polyps: 0 points – absence of polyps; 1 point – presence of polyps localized in the middle meatus; 2 points – presence of polyps extending beyond the middle meatus;

2. Edema: 0 points – no edema; 1 point – moderate edema; 2 points – marked edema;

3. Discharge: 0 points – no discharge; 1 point – clear discharge present; 2 points – thick purulent discharge visualized.

Appendix A3 Computed tomography of the paranasal sinuses and larynx using the Lund-Mackay scale

Russian name:

Computed tomography of the paranasal sinuses and larynx using the Lund-Mackay scale

Original title (if applicable): Lund-Mackay Score

Source: Lund V, Mackay I.S. Staging in chronic rhinosinusitis // Rhinology 1993. № 31: 183-184.

Type (underline):

rating scale

index

questionnaire

other (specify):

Prescription:

Assessment of the degree of decreased pneumatization of the paranasal sinuses based on computed tomography results of the paranasal sinuses

Content (template):

Key (interpretation):

Score for all PNS on each side – from 0 to 12 (total – from 0 to 24 points).