Chronic rhinosinusitis (CRS) is a common clinical problem in rhinology and the focus of long-term research. The disease has become one of the major diseases affecting people’s health, causing a serious negative impact on patients’ quality of life and leading to huge medical expenses, which brings a heavy burden to the society and economy. Thus, the standardized treatment of CRS and the rational use of medication are gaining more and more attention, and surgical treatment is considered only when standardized medication is ineffective or complications arise.
Chronic rhinosinusitis is a chronic inflammation of the mucous membrane of the nasal cavity and sinuses, with nasal symptoms lasting more than 12 weeks and not completely relieved or even aggravated.
I. Etiology.
The main causes of CRS are: 1. anatomical structure abnormalities: abnormal development of anatomical structures such as nasal septum deviation, middle turbinate inversion, middle turbinate pneumatization, and hooked hypertrophy pneumatization causing drainage obstruction of sinus passages. 2. bacterial infection: invasion of pathogenic microorganisms. 3. bacterial biofilms: bacterial biofilms (bacterial biofilms) are bacteria that grow in unfavorable environments through 99% of bacteria exist in the form of biofilms, and 65% of human infections and diseases involve bacterial biofilms. Once the biofilm is formed, it is extremely resistant to antibiotics and causes intermittent episodes of sinusitis by intermittently releasing planktonic bacteria. 4. bacterial superantigen: the irregular use of antimicrobial agents causes bacterial superantigenicity. 5. immune abnormalities: abnormalities in the body’s immunity cause abnormalities in the secretion of mucus in the sinus mucosa that affect the movement of mucosal cilia in the sinus. 6. osteitis of the maxilla and sieve bone and other pathogenic Factors.
2. Sinusitis pathophysiology.
2.1. The human mucous cilia clearance system is mainly distributed in: 1. the posterior 2/3 of the nasal cavity, sinuses, nasopharynx, trachea, bronchus, and mucosa of fine bronchi. 2. the mucosa of the middle ear eustachian tube
2.2. Composition of mucus cilia clearance system: The mucus cilia clearance system is mainly composed of cup cells, plasma gland cells and ciliated cells. cup cells and plasma gland cells – form a mucus blanket. It generates 1-2 liters of mucus per day, and forms mucus layer and plasma layer respectively according to the thickness ratio of 1:3: mucus layer (2μm thick): contains IgA, lysis enzymes, albumin, etc., with immunocidal effect, covering the free surface of ciliated epithelium, lubricating and protecting epithelium. Plasma layer (6μm thick): provides cilia with effective oscillation space, contains minimal glycoproteins, ensures fluid mobility. Ciliated cells – transport mucus blanket
2.3. The role of mucus blanket: mainly has four major functions: transport, barrier, immunity, and wetting.
1, transport – through a certain frequency is transferred and removed, unfavorable to the growth and reproduction of pathogenic bacteria, prevented the occurrence of infection
2, barrier – to prevent epithelial dehydration, ionic imbalance, penetration of toxic substances.
3. Immunity – with secreted immunoglobulin A, complement system, interferon, lysozyme and other immunologically active substances, acting as immune to various antigens.
4, wetting – so that the mucous membrane is often kept moist, the role of warming and humidification of inhaled gases.
2.4 The function of ciliated cells transporting mucus blanket: the tip of the cilia touch the mucus layer, 16 times per second coordinated (direction, frequency) oscillation, the average clearance rate of 6mm/min, every 20 minutes to renew the mucus blanket. Direction of mucus cilia removal in the nasal cavity and sinuses: sinus: towards the sinus opening, nasal cavity: towards the pharynx. Cough up or swallow the cleared mucus blanket.
2.5 The pathophysiology of sinusitis is related to 3 factors: 1) the degree of sinus orifice patency; 2) cilia function; and 3) mucus secretion function. Changes in any single or multiple factors will lead to sinusitis .
1, sinus orifice is not open to prevent sinus drainage, so that the mucus secreted by the sinus stays in the sinus cavity and becomes the best carrier for bacterial growth. The sinus infection is further aggravated by the persistent swelling of the sinus mucosa, which in turn aggravates the sinus mouth obstruction.
2, sinus secretion retention, mucosal swelling and low oxygen tension damage the clearance function of mucus cilia. Cilia dysfunction is mainly manifested as a weakening of cilia oscillation force and slowing of frequency, the most common cause is direct damage to cilia by mucosal infection or inflammation.
3, mucus composition abnormalities also affect the strength and frequency of cilia oscillation, mucus composition abnormalities are also a direct result of mucosal infection or inflammation.
4, eosinophilic inflammation caused by tissue edema leads to sinus mouth obstruction, epithelial damage leads to mucus cilia clearance function is impaired, so that the secretion retention, for bacterial colonization to create a suitable environment, thus secondary bacterial infection or make the original infection for a long time . Bacteria are present in the vicious circle of local pathophysiology of the nasal cavity and sinuses, therefore, elimination and expulsion of bacteria is an important part of sinusitis treatment.
The result of the inflammatory reaction of the nasal cavity and sinuses: leads to obstruction of ventilation and drainage of the nasal cavity and sinuses, destruction of the mucociliary clearance function and invasion of pathogenic microorganisms, which aggravates the obstruction of ventilation and drainage and further destroys the mucociliary clearance function, thus forming a vicious circle.
Third, the principles of standardized treatment of chronic rhinosinusitis.
1. eliminate pathogenic microorganisms: restore ventilation and drainage; 2. restore the structure and function of the damaged mucus cilia clearance system: smooth mucus drainage; 3. restore the rheology of secretions with the pathological changes of restoring normal mucosal properties: restore the surface acidity and alkalinity.
IV. Measures of standardized treatment of chronic rhinosinusitis.
The standardized treatment of CRS includes: 1. antimicrobial therapy; 2. anti-inflammatory therapy; 3. therapy to restore the mucus cilia clearance system; 4. anti-metabolic therapy; 5. decongestants; 6. herbal medicine; 7. nasal lavage.
4.1. Antimicrobial treatment of chronic rhinosinusitis: Possible mechanisms of bacterial biofilm pathogenesis include biofilm itself and intermittent release of planktonic bacteria. As far as the biofilm life cycle is concerned, on the one hand, bacteria have the above-mentioned causes leading to drug resistance, and on the other hand, intermittently released bacteria act continuously to produce continuous inflammation of the mucosa, making anti-inflammation particularly important, as well as the selection of antibiotics that can penetrate the biofilm and destroy both bacteria and planktonic bacteria within the biofilm, which is one of the bases for antibiotic use.
Antibiotics in the treatment of CRS: The treatment of CRS should include pharmacotherapy and surgical treatment, pharmacotherapy is the basis of treatment of CRS, the core of treatment is to eliminate mucosal inflammation and restore cilia function. the etiology of CRS has not been completely elucidated, the direct pathogenic role of bacteria in CRS is also insufficient evidence, relative to acute sinusitis, the efficacy of antibiotics on CRS is difficult to determine, but In clinical practice, antibiotic therapy is still one of the main measures of treatment.
Macrolides: commonly used varieties include erythromycin, roxithromycin, clarithromycin, azithromycin, etc. Strong antibacterial effect on gram-positive bacteria, no cross-resistance with penicillin, mainly used for gram-positive bacteria (especially Staphylococcus aureus) infections resistant to penicillin.
4.2, anti-inflammatory treatment of chronic rhinosinusitis: In recent years, some scholars have reported that long-term low-dose application of macrolide antibiotics can help control CRS, and determined that the mechanism of action is immunomodulatory, rather than the traditional antibacterial mechanism . Some studies have also found that such antibiotics inhibit the formation of bacterial biofilms in the sinuses, allowing the infectivity of bacteria to be controlled, thus, some of the previous concepts of antibiotic application have been newly challenged.
Anti-inflammatory effects of antibiotics: Prospective randomized controlled studies have shown that long-term oral administration of macrolide antibiotics (14 metacyclic) improves the signs and symptoms of CRS with similar efficacy to nasal endoscopic surgery. Moreover, the efficacy increased with longer dosing time (>12 weeks), which may be related to the anti-inflammatory effect of macrolides rather than their purely antibacterial effect.
In animal experiments macrolides can increase cilia transport, reduce cupped cell secretion and accelerate neutrophil apoptosis, thus reducing the chronic inflammatory response. Long-term application of macrolides can reduce the pathogenicity and damage to tissues by uncleared chronic bacterial colonies .
It is now believed that CRS is a chronic inflammatory response process and its main causative factor, although not bacterial infection, has been clearly targeted for treatment should be anti-inflammatory, but there is also literature confirming the prevalence of bacteria in CRS. A large number of clinical studies have now confirmed the significant efficacy of long-term, low-dose administration of macrolide antibiotics in patients with refractory sinusitis who have failed to respond to surgical and glucocorticoid therapy.
The following principles should be followed in the selection of macrolide antibiotics: moderate oral bioavailability and protein binding (not too high or too low), moderate half-life (not too long or too short), choice of distribution site, and size of adverse effects. For this reason the order in the selection of drugs should be: clarithromycin, roxithromycin.
Clarithromycin: 250 mg per day for adults and 7.5 mg/kg per day for children, 1 dose.
Roxithromycin: 150 mg/day for adults and 2.5-5 mg/kg/day for children in 1 dose.
Most treatment strategies are to discontinue the drug after 3-6 months of use and observe changes in the disease.
In recent years, topical nasal glucocorticoids for CRS or allergic rhinitis have become the first-line mainstay of treatment, and longer-term evidence-based clinical investigations in Europe have determined that there are no significant toxic side effects. The effect of these drugs on the innate immune function of the nasal sinus mucosa as well as the local effect is complex, and there are reports of mucosal damage in China, raising doubts about the use of these drugs in terms of time, duration and safety.
4.3. Treatment of chronic rhinosinusitis to restore the mucus cilia clearance system: conditions for the normal working of the mucus cilia clearance system: structural integrity of the three components and normal interrelationship: 1. normal pH value and appropriate viscosity are the keys to ensure the adsorption and shielding of foreign bodies; 2. normal activity and effective oscillation of cilia are the prerequisites to ensure the timely renewal of the mucus blanket; 3. maintaining the normal mucus blanket ratio is to provide space for effective cilia oscillation.
The use of mucus promoter is the key to restore the mucus cilia clearance system, the mucus promoter commonly used in clinical practice are: standard myrtle oil, amylin, etc.
4.4, chronic rhinosinusitis anti-allergic treatment: the treatment of non-infectious and chronic rhinosinusitis with mainly allergic reactions is mainly the use of anti-allergic drugs, together with immunotherapy and other therapies. Among them, intranasal hormones have been commonly used as the main drugs for the treatment of this type of rhinosinusitis at home and abroad because of their good anti-inflammatory and anti-allergic effects and low side effects.
4.5 .Chinese medicine treatment for chronic rhinosinusitis: There is no Chinese medicine treatment in the EU standard, but it is found in long-term clinical practice that the use of Chinese medicine in the treatment of patients with chronic rhinosinusitis has certain efficacy in promoting the drainage of mucus. Commonly used drugs include: Sinusitis Oral Liquid, Nasal Abyssal Oral Liquid, Tongkang Rhinitis Granules, etc.
4.6, nasal lavage treatment for chronic rhinosinusitis: saline or hypertonic saline rinse is recommended as a safe, simple and effective adjunctive treatment method in the treatment process. It has multiple effects such as removing nasal secretions, improving ventilation, and protecting mucous membranes, and is especially suitable for children, the elderly, and pregnant women, etc. For milder nasal diseases, saline or hypertonic saline nasal rinses alone can be used for therapeutic purposes. Physiological seawater is available for purchase in the market.
4.7, chronic rhinosinusitis surgical treatment: is not the main or preferred method of treatment of chronic rhinosinusitis, surgery itself does not remove inflammation, but to create favorable conditions for the remission of inflammation, the content of surgery is mainly to correct the abnormal structure affecting the nasal cavity, sinus ventilation and drainage disorders, remove irreversible lesion tissue, remove pathogenic microorganisms and their metabolites in the sinus cavity, preoperative, postoperative It should also be combined with standardized drug therapy. The surgery is usually performed under the nasal endoscope, and the normal structures are not destroyed and the recoverable mucosa and its functions are preserved as much as possible, so as to achieve the ideal results with less trauma. The main indications for surgical treatment of sinusitis are: 1. It is not conducive to the early remission of inflammation and should be surgically removed from the sinus lesions; 4. In CT films, the sinus anatomy is abnormal, the drainage of the sinus is obstructed, the course of the disease is long, the symptoms are obvious, and the effect of conservative treatment is poor, so surgery should be considered; 5. Chronic sinusitis, the mucosa in the sinus cavity has soft tissue density images (possibly mucosal hypertrophy, sinus polyps), surgery can be considered; 6. treatment, with the possibility of faster results, surgery can be considered. However, children and minors, generally should not be treated surgically, or functional endoscopic surgery can be considered.