Chronic Sinusitis: Clinical Guidelines

List of Abbreviations

CRS – chronic rhinosinusitis

PNS – paranasal sinuses

CT – computed tomography

GCS – Glucocorticosteroids

FESS – Functional Endoscopic Sinus Surgery

GERD – gastroesophageal reflux disease

VAS – visual analog scale

INCS – intranasal glucocorticosteroids (topical nasal corticosteroids; R01AD: Corticosteroids)

PPI – proton pump inhibitors

AOM – acute otitis media

OME – otitis media with effusion

PCD – primary ciliary dyskinesia

CF – cystic fibrosis

LOE – scale for grading levels of evidence

GGR – scale for grading grades of recommendation

Terms and Definitions

Chronic sinusitis (chronic rhinosinusitis) is a disease characterized by an inflammatory process in the mucosa of the paranasal sinuses lasting for more than 12 weeks, accompanied by two or more symptoms, one of which is nasal congestion/difficulty breathing through the nose or nasal discharge (anteriorly/posteriorly into the nasopharynx) ± facial pain/pressure ± reduction or loss of smell [1].

Endotype – a subtype of a disease defined by a distinct pathophysiological mechanism.

Phenotype – the set of observable characteristics of an individual's disease resulting from the interaction of genetic factors and the environment.

Functional rhinosinus surgery is a term combining, in these clinical guidelines, one or more types of surgical interventions on one or more paranasal sinuses aimed at restoring their ventilation and/or sanitation:

A16.08.017.002 - Micro-antrostomy using video-endoscopic technologies

A16.08.017.001 - Antrostomy using video-endoscopic technologies

A16.08.053 - Frontotomy

A16.08.053.001 - Endoscopic frontotomy

A16.08.070 - Opening of the ethmoid bulla using video-endoscopic technologies

A16.08.072 - Infundibulotomy using video-endoscopic technologies

A16.08.073 - Resection of the ethmoid bulla using video-endoscopic technologies

A16.27.002 - Ethmoidotomy

A16.27.002.001 - Ethmoidotomy using video-endoscopic technologies

A16.27.003 - Sphenoidotomy

A16.27.003.001 - Sphenoidotomy using video-endoscopic technologies

Often, as a generalizing term, practitioners refer to all these surgical interventions as A16.27.001.001 - Sinusotomy using video-endoscopic technologies, or when intervening on more than one group of paranasal sinuses, - A16.08.071 - Polysinusotomy using video-endoscopic technologies.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Chronic sinusitis (chronic rhinosinusitis) is a disease characterized by an inflammatory process in the mucosa of the paranasal sinuses lasting for more than 12 weeks, accompanied by two or more symptoms, one of which is nasal congestion/difficulty breathing through the nose or nasal discharge (anteriorly/posteriorly into the nasopharynx) ± facial pain/pressure ± reduction or loss of smell [1].

Retention (or true or secreting) cysts of the paranasal sinuses are cysts that form as a result of obstruction of the excretory ducts of the paranasal sinus mucosal glands. The walls of these cysts are lined on both sides by ciliated columnar epithelium [75-78].

Lymphangiectatic (or non-secreting, or false, or intramural) cysts of the paranasal sinuses are benign formations located intramurally in the mucosa, lacking an internal epithelial lining, and arising as a result of a chronic inflammatory process in the paranasal sinuses or barotrauma [75-78].

Mucocele is a benign, slowly growing cystic lesion of the paranasal sinus resulting from persistent impairment of the drainage function of the natural ostium, often accompanied by changes (stretching, less frequently destruction) of the sinus walls [79,83].

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

The etiopathogenetic mechanisms of chronic sinusitis are based on inflammatory changes in the mucosa of the nasal cavity and paranasal sinuses. To date, there are several theories regarding the etiology of chronic sinusitis. There are a number of diseases potentially associated with the development of CRS: allergic rhinitis, primary ciliary dyskinesia, cystic fibrosis, bronchial asthma, GERD, immunodeficiency, autoimmune systemic diseases, as well as a number of additional predisposing factors.

Various variants of pathological changes in the structures of the osteomeatal complex region (deviated nasal septum, presence of concha bullosa, paradoxical curvature of the middle nasal turbinate, hyperpneumatization of the ethmoid bulla, hyperpneumatization of the suprabullar cell, infraorbital cell, anatomical anomalies of the uncinate process, presence of an accessory maxillary sinus ostium, etc.), which can impair nasal ventilation and/or the pathways of mucus clearance from the nasal cavity and paranasal sinuses, are considered one of the significant risk factors for the development of CRS. In pediatric practice, and much less frequently in adult patients, CRS may be associated with adenoid hypertrophy [58].

In pediatric practice, the key etiological factor in the development of CRS, especially in preschool children, is cystic fibrosis, and less frequently primary ciliary dyskinesia syndromes. According to some domestic studies in childhood, no positive correlation has been found between CRS and a deviated nasal septum [59].

Allergically induced mucosal edema in the middle meatus due to allergen inhalation may be another factor predisposing to the development of CRS. There are numerous studies on the relationship between allergic rhinitis and chronic sinusitis; they often present as comorbid conditions.

The odontogenic etiology of sinusitis is associated with both pathological changes in tooth structure and the consequences of dental treatment interventions. Chronic maxillary sinusitis can be a complication of periodontitis or periodontal disease. One of the common factors in the development of maxillary sinusitis is endodontic treatment, when infected debris or fragments of filling material enter the sinus cavity through the root canals. Dental implantation and preceding surgical interventions for bone augmentation can provoke an inflammatory process in the sinus. A characteristic feature of odontogenic sinusitis is the predominance of anaerobic microorganisms as the causative agents of the infectious process.

GERD may also contribute to the development of chronic rhinosinusitis. Direct contact of the refluxate with the mucosa of the nasal cavity and nasopharynx causes mucosal inflammation and impaired mucociliary clearance, which in turn can lead to obstruction of the osteomeatal complex and impaired aeration. It is known that pH fluctuations affect ciliary motility in the respiratory mucosa.

Smoking should also be considered an important risk factor for the development of CRS.

Tobacco is toxic to the nasal mucosa and also contributes to mucosal dryness and changes in the rheological properties of mucus [2-13,20,22].

Retention cysts form as a result of the obstruction of glandular excretory ducts in the mucosa; however, the relationship between retention cysts and inflammatory pathology of the nasal cavity, trauma, and other pathological conditions has not been proven to date [77,80].

The most likely etiological factor for lymphangiectatic cysts is a chronic inflammatory reaction of the mucosa of the nasal cavity and paranasal sinuses (primarily of an allergic nature). There is also data on increased risks of lymphangiectatic cysts when conditions for maxillary sinus hyperventilation are created or with a history of barotrauma [77,81].

Odontogenic cysts of the maxillary sinus have various developmental mechanisms depending on their type. A radicular (periapical) cyst forms as a result of necrosis from epithelial granulomas at the apex of the root of a carious tooth; the cyst grows as a result of the atrophy of the surrounding bone. As it grows, the dental cyst may displace the floor of the maxillary sinus, reducing the true volume of the sinus or penetrating into it. Follicular cysts develop very slowly from the dental follicle due to a disturbance in tooth bud development [82,85].

There are various etiological theories regarding the origin of mucoceles. In the vast majority of cases, mucoceles are the consequence of paranasal sinus interventions. Other causes of mucoceles can include trauma, chronic inflammatory processes of the paranasal sinuses, tumors, and radiation therapy. In more than 1/3 of cases, mucoceles are considered idiopathic. Clinical cases of congenital paranasal sinus mucoceles have been described [79,83]. In children, the main cause of paranasal sinus mucoceles is secondary chronic sinusitis associated with cystic fibrosis [86,87].

1.3 Epidemiology of the Disease or Condition

The average global prevalence of chronic sinusitis in the general population is 11.61 ± 5.47% [14]. According to Yu.K. Yanov et al. (2002), about 10 million people suffer from sinusitis annually in Russia, and this pathology accounts for 15 to 36% of patients hospitalized in ENT departments [15]. According to the Medical Statistics Bureau of the Moscow Healthcare Department for 2012, the prevalence of sinusitis was 1,420 cases per 100,000 adult population (1.42%) [16]. According to A.I. Kryukov et al. (2017), from 1998 to 2015, the number of patients seeking medical care for CRS in Moscow outpatient clinics accounted for 0.74% of the total number of patients with upper respiratory tract pathology per year. There was an increase in the number of patients with CRS from 2012 to 2015, reaching 52,112 patients, which amounted to 3.17% of the total number of patients treated in Moscow outpatient clinics. From 2009 to 2015, the number of patients hospitalized with CRS decreased by 23.8% to reach 2,816 patients (8.3% of the total number of patients in ENT inpatient departments) [19].

There are currently no exact data on the epidemiology of CRS in the pediatric population. Isolated data from North American studies cannot be accepted because they included patients with clinical manifestations of adenoid hypertrophy and chronic adenoiditis in the chronic rhinosinusitis group, and also extended the definition of childhood up to 20 years of age [58]. According to an epidemiological study based on outpatient visits to children's polyclinics in Moscow, the proportion of patients with CRS ranged from 0.005% to 0.13% [59].

There are no exact data on the epidemiology of cysts and mucoceles. Paranasal sinus cysts are considered common and, according to various sources, are found in 1.4 to 35.6% of people in the general population, being more common in adults than in children [76-78,81,84]. According to some studies, the incidence of cysts in patients under 18 years of age is only about 3% of that in adulthood [84]. Mucoceles are much less common than paranasal sinus cysts and occur more frequently in individuals over 30 years of age [83].

1.4 Features of Coding the Disease or Condition

J32.0 - Chronic maxillary sinusitis

J32.1 - Chronic frontal sinusitis

J32.2 - Chronic ethmoidal sinusitis

J32.3 - Chronic sphenoidal sinusitis

J32.4 - Chronic pansinusitis

J32.8 - Other chronic sinusitides

J32.9 - Chronic sinusitis, unspecified

J34.1 - Cyst or mucocele of nose and nasal sinus

1.5 Classification of the disease or condition

There are several classifications of chronic sinusitis, depending on etiology, localization, and the nature of the pathological process.

Classification based on localization with the indication of the respective side (right-sided, left-sided, or bilateral):

- Maxillary

- Ethmoidal

- Frontal

- Sphenoidal

When the inflammatory process involves the sinuses on only one side, the term "hemisinusitis" is used. When multiple paranasal sinuses are inflamed, the term "polysinusitis" is used.

The classification well-established in clinical practice, which determines the type of chronic sinusitis depending on the presence or absence of polyps: polypoid rhinosinusitis and sinusitis without polyps.

Classification based on the etiological agent:

• bacterial;

• fungal;

• - bacterial-fungal.

Classification by the pattern of the course (based on the total severity of disease symptoms according to the visual analogue scale (VAS)) (see Appendix G1):

• - mild form (0-3)

• - moderate form (4-7)

• - severe form (8-10)

The classification approved by the EPOS working group in 2020 is based on the theory of "endotypes" and "phenotypes" of sinusitis and distinguishes the following types of chronic sinusitis:

Primary chronic sinusitis:

- Unilateral (localized)

Subclassified, depending on the endotype, into type 2 inflammation ("type 2") or type 1 or type 3 inflammation ("non-type 2").

Additionally subclassified into allergic fungal sinusitis and isolated sinusitis (named after the affected sinus)

- Bilateral (diffuse)

Primary bilateral (diffuse) sinusitis is also subclassified into two endotypes depending on the type of inflammation, and into eosinophilic or non-eosinophilic phenotype.

Secondary chronic sinusitis:

- Unilateral (localized)

Secondary localized sinusitis may be represented by an odontogenic process, mycetoma ("fungal ball"), or tumor with concomitant inflammatory process.

- Bilateral (diffuse)

Bilateral chronic sinusitis is subclassified into several endotypes: mechanical, inflammatory, immune-mediated, and, in turn, into several phenotypes: PCD – primary ciliary dyskinesia; cystic fibrosis, GPA – granulomatosis with polyangiitis (Wegener's granulomatosis); EGPA – eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome), selective immunodeficiency [20].

In Russia, the classification of cysts proposed by M.I. Kadymova [75] is most commonly used, distinguishing:

• - retention (or true, or secreting) cysts;

• - lymphoectatic (or non-secreting, or false, or intramural) cysts;

• - odontogenic (or radicular) cysts of the maxillary sinus;

• - developmental cysts.

By localization, cysts can be located in the maxillary sinus (more than 90% of cysts), sphenoid sinus (about 5%), and extremely rarely in the frontal sinus and ethmoid labyrinth cells. In more than 80% of cases, cysts are unilateral, and less frequently bilateral. Multiple cysts (more than 1) are observed in only ¼ of patients [84].

Mucoceles are usually classified by the localization of the lesion: most commonly the frontal sinuses, less frequently the ethmoid labyrinth cells, maxillary and sphenoid sinuses [2]. Some authors identify the frontoethmoidal localization as the most common. The literature also describes extremely rare localizations of mucoceles such as the inferior orbital floor, pterygoid space, middle and inferior nasal conchae [79,83].

1.6 Clinical presentation of the disease or condition

The clinical presentation of CRS is non-specific and includes the following symptoms: nasal obstruction, anterior and posterior rhinorrhea, headache and/or facial pain, as well as a possible decrease or loss of sense of smell, or a subjective sensation of a foul odor in the nose. The key symptoms of CRS, which are most common in patients with this pathology and have the greatest impact on well-being, are nasal obstruction and rhinorrhea. In children, cough associated with posterior rhinorrhea (post-nasal drip) is also highlighted as a key symptom of CRS. The key difference between CRS and acute sinusitis is the persistence of symptoms for more than 12 weeks without complete resolution [20,28].

Paranasal sinus cysts are often asymptomatic and are an incidental finding on head imaging studies [77,78,82,84]. When large, a cyst most commonly causes symptoms such as headache and/or facial pain. Much less frequently, rare symptoms such as sudden discharge of amber fluid from the nose (due to spontaneous rupture of the cyst), upper lip numbness, and toothache are associated with cysts [77]. Patient complaints of nasal breathing difficulty, rhinorrhea, or cough resulting from the sensation of mucus dripping down the back of the pharynx are most likely related to concomitant allergic rhinitis and/or chronic rhinosinusitis [77,84].

In patients with paranasal sinus mucoceles, clinical manifestations depend on the localization and size of the affected sinus. According to several authors, the main symptoms are headache, sensation of facial pressure, nasal congestion, nasal discharge, and periorbital pain. When small, a mucocele may be asymptomatic, but this is significantly less common than in the case of paranasal sinus cysts [79].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for diagnosing chronic sinusitis in adults: presence of two or more of the following symptoms for 12 weeks or more, one of which must be nasal congestion / nasal breathing difficulty / nasal cavity discharge (anterior / post-nasal drip):

• ± "pain or sensation of fullness in the projection areas of the paranasal sinuses";

• ± reduction or loss of sense of smell;

duration of ≥ 12 weeks;

and/or

endoscopic signs:

- polyps in the nasal cavity,

and/or

- mucopurulent discharge predominantly from the middle meatus and/or

- mucosal edema / obstruction predominantly in the middle meatus

and/or

CT changes:

- mucosal changes in the osteomeatal complex and/or sinuses

Criteria for diagnosing chronic sinusitis in children: presence of two or more symptoms for 12 weeks or more:

• nasal breathing difficulty,

• pain or sensation of fullness in the projection areas of the paranasal sinuses,

• nasal discharge or post-nasal drip,

• cough;

and/or

endoscopic signs:

- polyps in the nasal cavity,

and/or

- mucopurulent discharge predominantly from the middle meatus and/or

- mucosal edema / obstruction predominantly in the middle meatus

and/or

CT changes:

- changes in the mucous membrane of the ostiomeatal complex and/or sinuses [20].

The diagnostic criteria for a paranasal sinus "cyst" include the detection on computed tomography or magnetic resonance imaging of: rounded, homogeneous, soft-tissue lesions on a broad base, with clear borders, without signs of bone destruction and without marked deformation of the sinus walls [77]. Differential diagnosis between retention and lymphoectatic cysts can only be made by morphological examination of the cyst wall removed during surgery [77,78,84]. The diagnosis of "odontogenic cyst of the maxillary sinus" is established based on computed tomography data (presence of a homogeneous soft-tissue lesion on a broad base on the inferior wall of the maxillary sinus, with clear borders, a bone-density capsule, and a connection to the roots of the maxillary teeth) + the conclusion of a dental surgeon or maxillofacial surgeon regarding the presence of pathological conditions in the teeth adjacent to the affected sinus.

The diagnosis of paranasal sinus "mucocele" is established based on computed tomography data: detection of a lesion within the paranasal sinus cavity with a smooth, rounded contour and homogeneous internal content (in the absence of calcification and heterogeneous inclusions within the mucocele cavity), possible thinning of the bone structures in adjacent areas with the lesion prolapsing into neighboring anatomical regions [83].

2.1 Complaints and Anamnesis

Complaints of patients with chronic sinusitis may vary depending on the localization of the inflammatory process.

Adult patients typically present with the following complaints: nasal breathing difficulty, persistent, unilateral, or alternating; presence of mucous or mucopurulent nasal discharge, the need to blow the nose, or post-nasal drip along the posterior pharyngeal wall, most pronounced upon awakening in the morning or constant throughout the day. Complaints of an unpleasant odor in the nose and/or nasopharynx. Complaints of decreased olfaction, up to complete anosmia, or worsened sense of smell. In chronic sphenoiditis, complaints of periodic pain in the parieto-occipital region may occur. Chronic frontitis is characterized by intense pain in the projection area of the frontal sinuses during exacerbations or with changes in atmospheric pressure, corresponding to the affected side. Complaints of a feeling of "pressure" behind the nasal bridge and behind the eyeballs, most pronounced during periods of exacerbation of chronic sinusitis, may occur.

In young children, symptom collection can be carried out from the words of parents/guardians: complaints of multiple prolonged episodes of "runny nose", nasal breathing difficulty, mucous nasal discharge, and cough, predominantly at night and/or in the supine position.

When cyst-like lesions are detected by diagnostic imaging in a patient, it is first necessary to clarify the presence of complaints (headache and/or facial pain), their persistence, and factors provoking the appearance/worsening of symptoms. When taking the medical history, it is necessary to clarify whether nasal surgery and/or dental interventions were performed in the past.

2.2 Physical Examination

2.3 Laboratory Diagnostics

Comments: the optimal material for microbiological examination is an aspirate directly from the affected sinus, obtained via puncture (of the maxillary sinus) or intraoperatively.

2.4 Instrumental Diagnostics

Comments: computed tomography is the most informative diagnostic method for chronic sinusitis in both adults and children. CT makes it possible to identify an isolated inflammatory process, impaired outflow and blockage of the sinus ostium(a), a foreign body in the paranasal sinuses, a diffuse fungal process or mycetoma, a nasal cavity neoplasm, visualize developmental anomalies of the paranasal sinuses and impaired pneumatization, and suggest an odontogenic etiology of sinusitis. Characteristic CT signs of CRS include thickening of the mucous membrane and/or decreased pneumatization in the area of the sinus ostia.

It is advisable to perform CT of the paranasal sinuses no later than 6 months prior to surgical treatment, in order to plan the scope of the surgical intervention.

Comments: for patients with paranasal sinus mucoceles in cases where differential diagnosis with other space-occupying lesions of the sinonasal region is difficult, it is advisable to perform computed tomography of the paranasal sinuses with intravenous bolus contrast enhancement. The use of contrast enhancement helps to reliably establish the diagnosis due to contrast accumulation by the mucosa or fibrous capsule of the mucocele without involving the contents [83].

2.5 Other Procedures

Not indicated.

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

Taking into account the complex etiological structure of CRS and the potential simultaneous influence of several etiological factors on the clinical course of the disease, a personalized approach to choosing treatment tactics must be preferred for each individual patient [20].

3.1 Conservative Treatment

The basis of conservative treatment for patients with CRS is drug therapy. All drug therapy options, in the presence of indications and absence of contraindications, can be prescribed, including for patients after functional rhinosinus surgery [20,42-44].

To date, there is no evidence of the efficacy of conservative treatment for paranasal sinus cysts and mucoceles. Reduction of disease symptoms in these patients is only possible if medical treatment of concomitant pathology (chronic rhinosinusitis or allergic rhinitis) is effective [77-79,83].

Comments: irrigation therapy in patients with CRS is important not only as a mainstay of conservative treatment, but also as an element of complex therapy in the postoperative period [20,42-45,52].

Comments: currently, there is no standardized strategy regarding the dosages, frequency, and duration of INCS use in CRS in adults and children, which makes it possible to recommend both "low-dose" and "high-dose" INCS therapy. There is also no consensus regarding the duration of therapy, but to assess its effectiveness, it is advisable to continue treatment for at least 3 months [1,20].

The incidence of side effects such as epistaxis caused by mucosal dryness is higher with high-dose INCS therapy. The only nasally administered spray officially indicated for chronic rhinosinusitis is based on mometasone (ATX code: R01AD09), a metered nasal spray for adults and children older than 12 years at 2 doses (100 mcg) into each nasal nostril 2 times a day (400 mcg/day).

Comment: in outpatient practice, the starting drug for the treatment of acute exacerbation of chronic sinusitis in children and adults is Amoxicillin + Clavulanic acid** (ATX Code: J01CR02). The drug is prescribed orally in children aged 3 months to 12 years or weighing less than 40 kg at a dosage of 40 mg/kg/day (the daily dose is divided into 3 doses every 8 hours) for oral suspension forms of 125 mg + 31.25 mg / 5 ml and 250 mg + 62.5 mg / 5 ml; the suspension of 400 mg + 57 mg / 5 ml is dosed at 45 mg/kg/day divided into 2 doses. In case of a high risk of infection caused by multidrug-resistant pneumococcal strains, it is advisable to use the powder for oral suspension form of 600 mg + 42.9 mg / 5 ml as initial empirical therapy with a calculated amoxicillin dose of 90 mg/kg/day divided into 2 doses. In children weighing more than 40 kg and patients older than 12 years, the drug is preferably prescribed orally in the form of film-coated tablets of 500 mg + 125 mg 3 times a day or 875 mg + 125 mg 2 times a day.

For mild forms of allergy to penicillins (ATX Code: J01C) in anamnesis, it is advisable to use oral 3rd generation cephalosporins. In children under 12 years of age or weighing less than 50 kg, cefixime (ATX Code: J01DD08) is used orally at 8 mg/kg/day 1 time per day, in patients over 12 years of age – at 400 mg 1 time per day.

If the patient is intolerant to the entire group of beta-lactams or has a history of severe allergic reactions to penicillins (ATX Code: J01C), adult outpatients may be considered for treatment with III–IV generation fluoroquinolones: #Levofloxacin** (ATX Code: J01MA12) orally 500 mg once daily, #Moxifloxacin** (ATX Code: J01MA14) orally 400 mg once daily for a 10-14 day course [52]. Treatment of pediatric patients with exacerbation of chronic rhinosinusitis who need systemic antibacterial therapy, if it is impossible to use drugs from the group of beta-lactam antibacterial drugs, penicillins (ATX Code: J01C), it is advisable to treat in a hospital setting, choosing an antibacterial drug taking into account the severity of the patient's condition, the localization and prevalence of the inflammatory process and the sensitivity data of the isolated microorganism to antibacterial and/or other medicinal products.

If the initial outpatient antibiotic therapy fails, it is advisable to consider the need to route the patient to the inpatient otorhinolaryngology department via emergency care channels.

Patients hospitalized with moderately severe disease are preferably prescribed oral medications, or parenteral formulations if oral administration is not feasible. Patients with severe (including complicated) exacerbations of chronic sinusitis must receive intravenous antibacterial drugs.

If Amoxicillin + Clavulanic acid** (ATX Code: J01CR02) is ineffective at the outpatient stage of treatment, it is advisable to use 3rd generation cephalosporins: for patients older than 12 years or patients with a body weight of 50 kg or more – cefixime (ATX Code: J01DD08) orally 400 mg 1 time per day or ceftriaxone** (ATX Code: J01DD04) IV or IM 1-2 g 1 time per day or cefotaxime** (ATX Code: J01DD01) IV or IM 1 g every 12 hours; for children under 12 years of age or weighing less than 50 kg - cefixime (ATX Code: J01DD08) 8 mg/kg/day 1 time per day, ceftriaxone ** (ATX Code: J01DD04) 75-80 mg/kg/day 1 time per day or cefotaxime** (ATX Code: J01DD01) at 100-200 mg/kg/day in 2-4 doses.

If 3rd generation cephalosporins are ineffective and/or resistant strains of bacterial pathogens are isolated against the aforementioned antibacterial drugs, it is advisable to prescribe an antimicrobial drug from reserve groups (4th generation cephalosporins, carbapenems, oxazolidinones, glycopeptides, etc.), taking into account the sensitivity data of the isolated microorganism.

The effect of the prescribed antibacterial therapy should appear on the third day from the start of the drug use; if there is a positive trend, the use of the antibacterial drug is continued for 10-14 days [15,20,48,49].

Comments: the clinical effect of topical antibacterial drugs should be evaluated by a physician 3-4 days after the start of therapy; if there is no positive effect, consider the need for systemic antibacterial drugs.

The following intranasal sprays are approved for use in the Russian Federation for CRS: framycetin (ATX Code: R01AX08) – a nasal antibacterial spray for use in children from the first years of life, and a topical combination drug containing Dexamethasone + Neomycin + Polymyxin B + Phenylephrine (ATX Code: R01AD53), approved for use in patients aged 2.5 years and older. Despite the lack of literature reports on toxic effects of nasal sprays containing aminoglycosides, the single and daily doses of these drugs specified in their instructions must be strictly observed. The duration of use of these drugs for exacerbation of CRS should not exceed 7 days for framycetin (ATX Code: R01AX08) and 10 days for the combination drug Dexamethasone + Neomycin + Polymyxin B + Phenylephrine (ATX Code: R01AD53).

It is necessary to exclude from practice the administration of antibiotic solutions intended for intramuscular or intravenous administration into the nasal cavity and paranasal sinuses. Due to their pharmacokinetics, they are not adapted for these purposes and have a negative effect on the ciliated epithelium of the upper respiratory tract mucosa. Thiamphenicol glycinate acetylcysteinate (ATX Code: J01BA02) can be used for administration into the sinus cavity [50-52].

Comments: effective drugs with pronounced secretolytic, secretomotor, and anti-inflammatory effects for the treatment of CRS exacerbation are combined herbal preparations containing extracts of gentian root (Gentiana lutea), primrose flower (Primula veris), curly dock herb (Rumex crispus), elderberry flower (Sambucus nigra), and vervain herb (Verbena officinalis) (ATX code: R05X), and myrtol standardized (ATX code: R05C).

Comments: naphazoline (ATC code: R01AA08) has pronounced toxic effects and should not be used in otorhinolaryngological practice. Based on the balance between potency and duration of action, preference should be given to oxymetazoline (ATC code: R01AA05) 0.01-0.05% and xylometazoline** (ATC code: R01AA07) 0.05-0.1%. Decongestants should be used in the treatment of patients with nasal obstruction, but strictly as prescribed and under medical supervision. Their use must be limited to 5-7 days due to the risk of rhinitis medicamentosa [66].

Comments: there is evidence regarding the use of carbocisteine-based medications (ATC code: R05CB03) as adjunctive therapy in the complex treatment of patients with CRS. Carbocisteine preparations (ATC code: R05CB03) can be prescribed in short courses (up to 2-3 weeks) for the symptomatic treatment of CRS exacerbation in patients who exhibit an accumulation of thick secretions in the nasal cavity [67]. It is also possible to consider longer courses (approximately 3 months) of carbocisteine (ATC code: R05CB03) in combination therapy with other agents possessing anti-inflammatory effects on the nasal mucosa to reduce the severity of disease symptoms [68-70]. Simultaneous administration of carbocisteine (ATC code: R05CB03) with other expectorant mucolytic agents (including topical ones) should be avoided to prevent worsening of post-nasal drip.

Comments: in children under 6 years of age with CRS, only two drugs may be used for analgesia and fever management: paracetamol** (ATC code: N02BE01) up to 60 mg/kg/day or ibuprofen** (ATC code: M01AE01) up to 30 mg/kg/day.

3.2 Surgical Treatment

For patients with severe CRS exacerbations, including rhinogenic, orbital, and intracranial complications, surgical treatment is performed as an urgent and emergency medical care procedure. For moderate exacerbations unresponsive to conservative treatment, the prompt execution of minimally invasive therapeutic procedures may also be considered.

For all other patients with CRS, elective surgical treatment is performed when indications are present.

In the absence of indications or in the presence of contraindications to surgical treatment, patients undergo conservative therapy and follow-up by an otorhinolaryngologist.

Since the list of medical interventions enumerates individual surgical procedures for each corresponding sinus, these guidelines group procedures such as frontotomy, ethmoidotomy, sphenoidotomy, maxillary sinusotomy, and elements of nasal cavity surgery under the term "functional rhinosinus surgery." In adult patients, given appropriate technical equipment in the operating room, preference should be given to functional rhinosinus surgery using video-endoscopic techniques. In pediatric patients, the use of video-endoscopic techniques is a mandatory requirement during elective functional rhinosinus surgery.

Surgical treatment of paranasal sinus cysts and uncomplicated mucoceles is performed electively. The same techniques of functional rhinosinus surgery are frequently used to open the affected sinus and remove cysts. In some cases of maxillary sinus cysts and frontal sinus mucoceles, micro-maxillary sinusotomy and anterior wall frontotomy of the paranasal sinuses may be employed.

Comments: maxillary sinus puncture allows for washing the affected sinus with an antiseptic solution, removing pathological secretions, and administering an antibacterial agent.

A mandatory prerequisite for maxillary sinus puncture is the availability of diagnostic imaging results of the nasal cavity and paranasal sinuses confirming the absence of sinus hypoplasia and maxillary sinus atelectasis, as well as radiological signs of fluid accumulation within the sinus cavity.

In many cases of severe CRS exacerbation, puncture is not a full substitute for sinus-clearing surgery.

Given the invasive nature of the procedure, in pediatric practice, maxillary sinus puncture should be performed exclusively in hospitalized patients.

To drain the paranasal sinuses in patients with CRS exacerbation, the placement of sinus catheters or catheterization of the paranasal sinuses via natural ostia may be considered [71,72].

Comments: adenotomy in children is performed electively in the absence of contraindications to surgery. Considering the specifics of pediatric age, adenotomy in children should preferably be performed under general anesthesia in an inpatient otorhinolaryngology department or a short-stay surgical unit. When appropriate department equipment is available, adenoidectomy using video-endoscopic techniques should be preferred.

Comments: functional endoscopic sinus surgery in children is performed electively in the absence of contraindications to surgery. Functional endoscopic sinus surgery does not affect the future growth and development of the paranasal sinuses and maxillofacial structures. There are certain specific features of sinus surgery in children: the risks of scarring and restenosis are higher than in adult patients, while the smaller size of sinonasal structures and surgical corridors account for the technical complexity of pediatric surgeries and the need for advanced equipment.

Comments: regardless of the condition of the adenoids, if CT scans reveal signs of a localized inflammatory process in one of the sinuses presenting as total or subtotal opacification, or signs of a marked decrease in pneumonization of one of the sinuses, accompanied by symptoms characteristic of chronic sinusitis. It is advisable to maintain high oncological suspicion regarding any potential neoplasms on paranasal sinus CT scans in children, with the exception of cysts with clearly defined characteristic features and no tendency to grow over time.

Comments: most experts consider surgical intervention inexpedient in patients with incidentally detected asymptomatic cysts. In many cases, paranasal sinus cysts (except odontogenic ones) tend to undergo slow spontaneous regression or maintain their previous dimensions [77,78].

Comments: to date, marsupialization of mucocele using endoscopic endonasal rhinosinus surgery is recognized as the best treatment method for frontal localization, including the stage of anterior ethmoidectomy and Draf frontotomy. However, in case of a more lateral location, defects of the anterior wall of the frontal sinus, and large volumes of the lesion with extension into the cranial cavity, it is advisable to use an external approach [83].

3.3 Other Treatment

Patients with secondary chronic rhinosinusitis, in whom changes in the nasal cavity and paranasal sinuses are a manifestation of comorbid pathology, should be followed up by a specialized physician and receive appropriate treatment for the underlying disease.

Treatment of patients with odontogenic cysts of the maxillary sinus is carried out in collaboration with a dental surgeon or maxillofacial surgeon.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: as part of postoperative follow-up, patients with chronic sinusitis require a standard otorhinolaryngological examination 7–14 days after discharge from the hospital. In addition, the patient must be examined by an otorhinolaryngologist several times during the subsequent year to monitor the course of the disease and timely adjust the treatment tactics [73]. Postoperative examinations are necessary to monitor the condition of the nasal cavity (in the postoperative period, if nasal cavity care is inadequate, there is a risk of crusting and synechiae formation), to identify and/or prevent the formation of complications, and for the physician to perform otorhinolaryngological procedures if necessary.

The physician must convey to the patient the information about the need to follow a protective regimen for a month after the surgical intervention. The main principle of establishing restrictions in the postoperative period is to avoid an increase in blood pressure and other factors potentially contributing to bleeding. Intense physical exertion, overheating, or hypothermia should be restricted. Also, for the prevention of acute upper respiratory tract infections transmitted by airborne droplets, it is advisable not to visit crowded places, giving preference to a home-based regimen.

5. Prevention and Dispensary Observation

Prevention of chronic diseases and minimization of their consequences through individualized treatment is a fundamental principle of preventive medicine.

Primary prevention of CRS is aimed at preventing exposure to negative environmental factors.

Secondary prevention of CRS consists in identifying the disease at the earliest stages.

Methods of chronic sinusitis prevention include timely treatment of dental inflammatory processes, timely treatment of identified gastroesophageal reflux, smoking cessation, and adherence to safety regulations when working with materials potentially hazardous to the upper respiratory tract [46,47].

Prevention of mucocele formation can be considered adherence to the principles of functional rhinosinus surgery in patients during rhinosurgical interventions [83]. Timely and adequate treatment of chronic inflammatory pathology of the nasal cavity can reduce the risk of lymphangiectatic cyst formation [75,81]. The main direction for reducing the probability of radicular odontogenic cyst formation is timely and adequate treatment of maxillary tooth diseases [82].

6. Organization of Medical Care

Medical care for patients with chronic sinusitis and patients with paranasal sinus cysts or mucoceles is provided primarily by an otorhinolaryngologist, if necessary, jointly with related specialists: an allergist-immunologist, gastroenterologist, rheumatologist, dental surgeon, or maxillofacial surgeon.

Conservative treatment of chronic sinusitis and mild exacerbation therapy are performed on an outpatient basis.

Indications for emergency hospitalization in the otorhinolaryngology department:

1) Development of intracranial and/or intraorbital complications during exacerbation of chronic sinusitis.

2) Severe exacerbation of chronic sinusitis, as well as moderate exacerbations in patients with ineffectiveness of adequate outpatient treatment within 5-7 days, or with progressive deterioration of the condition at any time.

Indications for elective hospitalization in a medical organization for surgical treatment:

1) Presence of chronic sinusitis confirmed by diagnostic studies, refractory to adequate conservative therapy for 6 months.

2) Resurgence of symptoms and clinical presentation of chronic sinusitis after previously performed surgical intervention.

3) Persistent complaints, diagnostic and clinical signs of chronic sinusitis in children who have undergone adenoidectomy.

4) Signs of an isolated inflammatory process with subtotal or total decrease in pneumatization according to CT data for 2 months.

5) Suspected paranasal sinus neoplasm of unknown morphological nature according to paranasal sinus CT in adults and children.

6) Signs of maxillary sinus pneumatization impairment — "silent sinus syndrome" according to paranasal sinus CT in adults and children.

7) Patients with paranasal sinus cysts in the presence of constant or intermittent symptoms.

8) Patients with paranasal sinus mucoceles.

Indications for patient discharge from a medical organization:

1) Surgical treatment performed to the necessary extent.

2) Satisfactory general condition of the patient after the performed surgical treatment, absence of local and systemic acute inflammatory processes caused by an infectious agent.

7. Additional Information

Chronic sinusitis is a multifactorial pathological process. The prospects for successful treatment of chronic sinusitis depend on many factors: features of the anatomical structure of the sinonasal region in a particular patient, presence/absence of chronic systemic diseases, active and/or passive smoking, presence/absence of occupational hazards affecting the upper respiratory tract, climatic and ecological living conditions of the patient, and the level of patient adherence to treatment.

Retention cysts are often asymptomatic and are an incidental finding during various diagnostic imaging methods. They tend to undergo slow spontaneous regression or maintain their previous dimensions. Odontogenic cysts have no tendency to spontaneous self-resolution and require an interdisciplinary approach in treatment. Paranasal sinus mucocele is a slowly growing cyst-like lesion leading to stretching and sometimes destruction of the sinus wall, which always requires surgical treatment.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Zyabkin IV, Dr. Med. Sci., Member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

2. Averbukh VM, Cand. Med. Sci., Associate Professor, Member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

3. Svistushkin VM, Dr. Med. Sci., Professor, Member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

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

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

6. Vakhrushev SG, Dr. Med. Sci., Professor, Member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

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

8. Zavaliy MA, Dr. Med. Sci., Professor, Member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

9. Karpova E.P., MD, Professor, Member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

10. Gurov A.V., MD, Member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

11. Tulupov D.A., PhD, Associate Professor, Member of the National Medical Association of Otorhinolaryngologists, no conflict of interest.

Conflict of interest: none.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Otorhinolaryngologist;

2. Otorhinolaryngologist-audiologist;

3. Allergist-immunologist;

4. Pediatrician;

5. Urban (district) pediatrician;

6. District pediatrician;

7. General practitioner (internist);

8. Adolescent therapist;

9. District general practitioner;

Methods used for evidence collection/selection:

• electronic database searching.

Description of methods used for evidence collection/selection:

• the evidence base for the recommendations includes publications included in the Cochrane Library, EMBASE, and MEDLINE databases.

Table 1. Scale for assessing the levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing the levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Rating scale for grades of recommendation (GR) for preventive, diagnostic, therapeutic, and rehabilitation methods (interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, 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

1. Order of the Ministry of Health of the Russian Federation No. 103n dated February 28, 2019, "On Approval of the Procedure and Timeframes for the Development of Clinical Practice Guidelines, Their Revision, the Standard Form of Clinical Practice Guidelines, and Requirements for Their Structure, Composition, and Scientific Validity of the Information Included Therein."

2. Order of the Russian Ministry of Health No. 905n dated November 12, 2012, "On Approval of the Procedure for Providing Medical Care to the Population in the Profile of 'Otorhinolaryngology'."

3. Order of the Ministry of Health of the Russian Federation No. 203n dated May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care."

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

The attending physician must convey the following information to the patient:

chronic sinusitis is difficult to treat, but the intensity of its symptoms can be reduced. People with chronic rhinosinusitis usually require lifelong management and monitoring to minimize symptoms. There are several treatment options, but the specific treatment tactics are determined by the otorhinolaryngologist, in some cases jointly with other specialists.

Depending on the type of chronic rhinosinusitis, the severity of symptoms, and the presence of other conditions (e.g., allergies or asthma), various combinations of treatment methods may be recommended.

An important part of therapy is lifestyle modification. For people with chronic rhinosinusitis, quitting or minimizing smoking is extremely important. If an allergic component is present, the principles of a "hypoallergenic environment" must be observed.

Adherence to prescribed therapy, compliance with dosages, correct drug administration techniques, and irrigation also play an important role.

Indications for surgical treatment of chronic sinusitis are determined by the otorhinolaryngologist. Surgical treatment is performed on an elective basis. The physician must clearly justify and explain to the patient the necessity of the surgery, the expected outcome, and the potential risks of surgical treatment. The final decision is made by the patient based on the information provided by the otorhinolaryngologist recommending the surgical stage of treatment.

Cysts are a frequent incidental finding in patients undergoing various diagnostic imaging modalities. These are benign formations not prone to malignant transformation, often running an asymptomatic course. Cysts have no conservative treatment options. Surgical treatment is performed by an otorhinolaryngologist on an elective basis only in cases of paranasal sinus cysts accompanied by constant or periodic symptoms (primarily facial and head pain). When an odontogenic origin of a maxillary sinus cyst is suspected, the choice of treatment tactics is based on interdisciplinary interaction between the otorhinolaryngologist and an oral and maxillofacial surgeon or maxillofacial surgeon.

Mucocele is a benign formation, but it has a tendency towards slow progressive growth with expansion of the paranasal sinus walls, up to their destruction. Mucoceles have no conservative treatment options and, upon detection, are an indication for elective surgical treatment (in the absence of contraindications), which is performed by an otorhinolaryngologist in a specialized inpatient department setting.

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

Appendix G1. Visual Analog Scale (VAS)

Russian title: Visual Analog Scale (VAS).

Original title (if any): Visual Analog Scale.

Source (official website of developers, validation publication): Hayes M. H. S., Patterson D. G. (1921). Experimental development of the graphic rating method. Psychol. Bull. 18, 98–99.

Type (underline): rating scale.

Purpose: intended for measuring pain intensity.

Content (template): it is a continuous scale in the form of a horizontal or vertical line 10 cm in length with two extreme points located on it: "no pain" and "worst pain imaginable".

Key (interpretation): the patient is asked to make a mark on it corresponding to the intensity of pain they are currently experiencing. The distance between the start of the line ("no pain") and the mark made is measured in centimeters and rounded to the nearest whole number. Each centimeter on the line corresponds to 1 point. A mark up to 2 cm classifies the pain as mild, from 2 to 4 cm as moderate, from 4 to 6 cm as severe, from 6 to 8 cm as very severe, and up to 10 cm as excruciating.