RU2410028C2 - Method of treating chronic rhinosinusitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: motion parameters of ciliated epithelium cilia are measured. The value Vc=9.6-11.3 mm/min corresponds to a normal functioning of mucociliary transport (MCT). Chronic rhinosinusitis requires a complex conventional therapy that involves administering mucoactive preparations. The therapy is continued with such mucoactive preparation that caused the highest speed of the cilia.

EFFECT: method allows individual prescription to a patient of the mucoactive preparation and provides higher local clinical effectiveness.

2 cl, 2 ex

Description

The invention relates to medicine, namely to otorhinolaryngology, and may find application in the treatment of diseases of the upper respiratory tract.

Rhinosinusitis is an inflammation of the nasal mucosa and paranasal sinuses due to a bacterial or viral infection, physical trauma, chemical trauma, an allergic reaction, and a number of other factors. Rhinosinusitis is divided into acute (duration of symptoms <4 weeks), subacute (duration of symptoms from 4 to 12 weeks) and chronic (duration of symptoms> 12 weeks). Relapses of acute rhinosinusitis or exacerbation of chronic rhinosinusitis may be observed.

To detail the nature of the lesion of the sinuses allow special examination methods. Such methods include instrumental endoscopy, panoramic radiography and computed tomography of the paranasal sinuses, acoustic rhinometry and anterior active rhinomanometry.

The main points in the treatment of rhinosinusitis are the restoration of the drainage function of the sinus anastomosis and the suppression of inflammation (viral or bacterial), therefore, effective treatment of rhinosinusitis requires techniques that ensure the active evacuation of the pathological secretion from the affected sinuses, and correctly selected antibiotic therapy.

There is a method of treating chronic rhinosinusitis by using antibiotics (see Arefieva N.A. et al. Rhinogenic sinusitis (diagnosis and treatment), Methodological recommendations. - Ufa, 1997. - 19 p.).

There is also a method of treating chronic purulent rhinosinusitis by administering the antibiotic Amoxiclav (see patent RU No. 2178676, A61B 17/24, 2002).

The disadvantages of the known methods is that there are a number of problems that otolaryngologists face when prescribing antibiotics. First of all, it is the constantly growing resistance (resistance) of microorganisms to antibiotic therapy and a high risk of complications associated with the use of antibiotics. In addition, one of the disadvantages of local antibiotic therapy is the inhibition of mucociliary transport, which provides drainage function of the paranasal sinuses. The noted deficiencies may be the causes of the transition of inflammation into a chronic form and increase the risk of treatment failure.

It is also well known to use aerosols or nasal drops to reduce swelling. Vasoconstrictor drops in the nose have the only advantage - the speed of action. However, the vasoconstrictor effect leads to a decrease in blood flow in the nasal mucosa and sinuses, suppresses mucociliary clearance and secretion of immunoglobulins (protection factors), violate the sinus drainage (cleansing) mechanisms, and also cause addiction.

There is a risk of an overdose of drops, which can lead to tachycardia (increased heart rate), arterial hypertension (increased blood pressure), and depression of the central nervous system (brain).

With the ineffectiveness of drug treatment, they resort to surgical interventions. However, radical methods of surgical intervention violate the normal anatomical structure and the basic protective physiological functions of the nose and paranasal sinuses and do not always lead to healing.

At present, it is generally recognized that the most promising combination of surgical treatment with conservative treatment aimed at restoring the protective functions of the nasal mucosa and paranasal sinuses. At the same time, it is known that the manifestation of the inflammatory process in the paranasal sinuses in each case has its own individual characteristics and morphofunctional characteristics.

To make a diagnosis and prescribe an adequate treatment for the disease, it is very important to assess the condition of the mucous membrane of the respiratory tract or the so-called mucociliary system. In the mucociliary system, the secretory processes interact with the motor activity of the cilia (cilium) on the surface of the ciliated epithelium. These components make up a single morpho-functional system.

Mucociliary transport (hereinafter - MTC) is one of the most important mechanisms of mucociliary clearance. Translated into Russian, the word "clearance" means "cleansing." The respiratory tract using mucus is cleared of tissue decay products, microorganisms, foreign particles of organic and inorganic origin (dust) through phagocytosis and ICT.

Physiologically important mucociliary cleansing is ensured by the functioning of the cilia of the ciliated epithelium, as well as by the optimal quality, quantity and transportability of mucus. A thin (about 2 microns) layer of mucus secretion (gel layer) covering the epithelium is produced mainly by goblet cells - the glands of the mucous membrane. Synchronized beating of the cilia sets in motion a layer of mucus (gel layer) above them with the particles in it and remove them from the respiratory tract.

Mucociliary transport is carried out by coordinated strokes of the cilia in the periciliary (sol layer) layer and consists of an effective and restorative stroke. During an effective stroke, the cilia reach the gel layer and move it outward. Cilia, the surrounding layer of mucus (sol) and the gel layer form a biologically functional unity. An increase in viscosity and adhesion, a decrease in the elasticity of mucus during inflammation, leads to a change in its rheological properties, which causes a violation of the motor activity of the cilia.

It is known that a violation of the ICT is one of the first and main causes of the occurrence of chronic inflammatory diseases of the respiratory tract, including rhinosinusitis. Environmental troubles associated with air pollution from industrial waste, radioactive substances, occupational hazards, as well as bad habits (smoking), and a genetic predisposition lead to disruptions in both the mucociliary transport system and mucociliary transport.

Due to chronic rhinosinusitis, the balance between the secretion production in goblet cells and serous-mucous glands and the secretion evacuation by cells of the ciliated epithelium is disturbed, which leads to a decrease in the effectiveness of physiologically important mucociliary cleansing.

Taking medications with a differentiated effect on the production of secretions, or on reducing the viscosity of mucus, or on the function of the cilia allows you to restore impaired mucociliary cleansing.

Thus, the inclusion of adequate correction by drugs of mucociliary transport disorders in an integrated method for chronic rhinosinusitis can significantly increase the effectiveness of the treatment of the disease. However, the choice of conservative treatment should be determined by a scientifically based method that allows to give reliable and objective characterization of mucociliary transport disorders.

Currently, there is a transition from mass therapy to individual therapy, which allows to cure a specific patient.

There is a known method of studying MCT by means of television microscopy, in which the motor activity of cilia (pili) is studied, observing the beating of cilia (VV Shabalin and other Biophysical methods for studying the MCT of the upper and lower respiratory tract in normal and pathological conditions. In the book. " Problems of therapeutic and surgical pulmonology ", collection of materials conf. St. Petersburg, 1997, pp. 44-45).

To do this, use a biopsy of the mucous membrane of the upper respiratory tract. The biopsy is placed in a culture medium that provides intravital study of tissues. The movements of the cilia (frequency and amplitude of oscillations) are evaluated using the method of television microscopy (the method of intravital television microscopy of drugs in surviving tissues). In this case, under an optical microscope, the eyepiece is replaced with a portable video camera connected to a computer.

The advantage of the method of television microscopy is the ability to study in living tissues both the function and structure of the ciliary apparatus. The advantage of television microscopy also lies in the fact that instead of using the human eye, using a video camera with a radiation detector in the form of a CCD matrix overcomes the limitation on the useful magnification of the microscope. This is achieved due to the greater (2-4 times depending on the type of video camera) resolution of the CCD matrix as compared to the human eye.

The disadvantage of this method is that to obtain the material of the ciliary epithelium of the mucous membrane of the respiratory tract using a biopsy. This intervention injures the epithelium, brings the moving cilia into a state of stress. Taking a biopsy requires the use of painkillers, usually local anesthetics, which significantly slow down the frequency of beating of the cilia of the ciliated epithelium. In addition, visual inspection in a television microscope does not allow to give an in-depth description of the movements of the cilia, to calculate their parameters and the relationship with the environment - mucus.

Thus, this method can be used mainly to establish the presence of a norm or a deep violation in the system of the mucociliary apparatus and does not allow verification of more subtle features of the ciliary apparatus for norm and pathology.

Closest to the technical nature of the claimed solution is a method of choosing a treatment strategy for chronic and acute rhinosinusitis, which consists in determining disorders of mucociliary transport (MCT) by measuring the movement parameters of cilia of the ciliated epithelium, at least the speed of mucociliary transport (see patent RU No. 2254805, A61B 5/11, G01N 33/483, 2005).

The method includes taking material for research in the form of ciliated epithelial cells and recording the vibrational movements of the cilia in the human respiratory tract through intravital television microscopy. In this case, the material for the study is taken from the surface of the mucous membrane of the respiratory tract, and the speed of movement of the tip of the cilia is obtained on the basis of mathematical modeling with subsequent calculations by the formula

,

,

where V _c is the speed of the tip of the cilia [μm · s ^-1 ];

K ₁ , K ₂ , α are calculated as average values characteristic of each of the considered conditions of the human body: healthy, sick with acute or chronic sinusitis according to the developed model of cilia movement; K ₁ - the curvature of the working length of the cilia, the constant is 1/38 μm ^-1 ; K ₂ - the curvature of the cilia from the working length to the tip [μm ^-1 ]; α is the angle of inclination of the cilia relative to the vertical position [deg];

π = 3.1417 is a constant;

L, T _p and T _e - parameters measured individually for each patient; L is the length of the cilia [μm]; T _p - time from the start of movement to the maximum straightening of the tip of the cilia [s]; T _e - effective impact time [s], given that the value of V _c = 9.6-11.3 mm / min corresponds to the normal functioning of the MCT.

This invention made it possible to compose an algorithm for the diagnosis of a pathological process. Based on the definition of the main parameters of ICT in patients with clinically pronounced purulent and acute sinusitis, a method for their treatment is selected.

For patients with chronic purulent sinusitis (without exacerbation), accompanied by a violation of the ICT, complex treatment is prescribed: surgical treatment with the help of endoscopic microsurgery of the paranasal sinuses; the use of drugs (gelomirtol) with secretolytic and secretory action.

For patients with chronic purulent sinusitis (without exacerbation), not accompanied by a violation of the ICT, surgical treatment is prescribed using endoscopic microsurgery of the paranasal sinuses.

All patients with acute sinusitis with an ICT disorder as part of complex conservative therapy are prescribed secretolytic and secretory drugs normalizing the ICT.

The disadvantage of this invention is that with the complex treatment of chronic rhinosinusitis, it is impossible to predict which drug is most preferred for a particular patient.

The technical result of the proposal is to increase the effectiveness of complex treatment of patients with chronic rhinosinusitis by individual selection of a mucoactive drug of local effect, which most clearly improves mucociliary transport.

To achieve the specified technical result in a method for the treatment of chronic rhinosinusitis, including the determination of mucociliary transport disorders (MTC) by measuring the motion parameters of the cilia of the ciliated epithelium, at least the speed of the mucociliary transport, while the speed of the cilia tip is obtained on the basis of mathematical modeling with subsequent calculations using the formula

,

,

where V _c is the speed of the tip of the cilia [μm · s ^-1 ];

K ₁ , K ₂ , α are calculated as average values characteristic of each of the considered conditions of the human body: healthy, sick with acute or chronic sinusitis according to the developed model of cilia movement; K ₁ - the curvature of the working length of the cilia, the constant is 1/38 μm ^-1 ; K ₂ - the curvature of the cilia from the working length to the tip [μm ^-1 ]; α is the angle of inclination of the cilia relative to the vertical position [deg];

π = 3.1417 is a constant;

L, T _p and T _e - parameters measured individually for each patient; L is the length of the cilia [μm]; T _p - time from the start of movement to the maximum straightening of the tip of the cilia [s]; T _e - time effective strike [s]

and, given that the value of V _c = 9.6-11.3 mm / min corresponds to the normal functioning of the ICT, for patients with chronic rhinosinusitis accompanied by a violation of the ICT, a complex conservative treatment is prescribed, including: conventional therapy, such as antibiotic therapy, decongestant and desensitizing therapy , as well as the appointment of drugs with a mucoactive effect, according to the proposal, a drug is prescribed, after which for a day on the mucous membrane of the patient’s nose the ICT study is detected lo large positive dynamics cilia tip speed V _c, e.g. designate one of the preparations: Rinofluimutsil or Sinupret 15 drops three times a day in each nostril 30 days.

The method is as follows.

Two mucoactive drugs are sequentially prescribed to a patient with chronic rhinosinusitis: rinofluimucil and sinupret with local effects on the mucous membrane of the nasal cavity. The ciliary apparatus is taken for examination before exposure to mucolytics on the mucous membrane of the nasal cavity and after.

On the first day, rinofluimucil is prescribed 15 drops in each half of the nose three times a day. Evaluation of mucociliary transport is carried out the day after taking the drug.

In this case, the speed of movement of the tip of the cilia is measured on the basis of mathematical modeling with subsequent calculations by the formula

,

,

where V _c is the speed of the tip of the cilia [μm · s ^-1 ];

K ₁ , K ₂ , α are calculated as average values characteristic of each of the considered conditions of the human body: healthy, sick with acute or chronic sinusitis according to the developed model of cilia movement; K ₁ - the curvature of the working length of the cilia, the constant is 1/38 μm ^-1 ; K ₂ - the curvature of the cilia from the working length to the tip [μm ^-1 ]; α is the angle of inclination of the cilia relative to the vertical position [deg];

π = 3.1417 is a constant;

L, T _p and T _e - parameters measured individually for each patient;

L is the length of the cilia [μm]; T _p - time from the start of movement to the maximum straightening of the tip of the cilia [s]; T _e - effective impact time [s], given that the value of V _c = 9.6-11.3 mm / min corresponds to the normal functioning of the MCT.

Then, on the third day, a sinupret of 15 drops is prescribed three times a day for a day. Evaluation of mucociliary transport is carried out by the above method on the day after taking the drug.

For treatment, the patient is prescribed a drug with a more pronounced positive effect on the performance indicators of mucociliary transport (speed V _c and coefficient K _t ).

Scheme of drug administration: rinofluimucil or sinupret 15 drops three times a day in each half of the nose for 30 days.

In isolated cases, when both drugs did not show a pronounced positive effect on the effectiveness of MCT, the mucolytic drug helomirtol forte was prescribed for conservative treatment and its effectiveness was evaluated after a course of therapy.

The method is illustrated by the following examples.

Example 1

Patient U., 28 years old, was admitted to the Federal State Institution "SPb Research Institute of ENT Department of Rosmedtechnology" on May 13, 2008 with a diagnosis of chronic purulent rhinosinusitis (exacerbation) for conservative treatment.

In addition to the generally accepted clinical examination of the patient, a study of mucociliary transport was conducted.

For calculations, the formula was used:

,

,

The relevant parameters were measured:

L is the length of the cilia - 6.5 microns.

T _e - effective impact time - 0.22 s.

T _p - time from the start of movement to the maximum straightening of the tip of the cilia - 0.12 s.

K ₁ - the curvature of the working length of the cilia, a constant equal to 1/38 μm ^-1 .

K ₂ - the curvature of the cilia from the working length to the tip [μm ^-1 ].

α is the angle of inclination of the cilia relative to the vertical position 250.

For calculations, the formula was used:

An objective assessment of the speed of mucociliary transport found that the rate was equal to V _c = 3.35 mm / min, which was significantly less than the norm (in healthy).

After preliminary administration of mucolytics, it was found that the day after daily intake of rinofluimucil, the mucociliary transport rate was V _c = 4.12 mm / min.

The relevant parameters were measured:

L is the length of the cilia is 8 microns.

T _e - effective impact time - 0.12 s.

T _p - time from the start of movement to the maximum straightening of the tip of the cilia - 0.09 s.

K ₁ - the curvature of the working length of the cilia, a constant equal to 1/38 μm ^-1 .

K ₂ - the curvature of the cilia from the working length to the tip 1/9 [μm ^-1 ].

α is the angle of inclination of the cilia relative to the vertical position 400.

For calculations, the formula was used:

On the day after the daily intake of sinupret, the speed of mucociliary transport was V _c = 10.62 mm / min.

The relevant parameters were measured:

L is the length of the cilia is 8 microns.

T _e - effective impact time - 0.10 s.

T _p - time from the start of movement to the maximum straightening of the tip of the cilia - 0.07 s.

K ₁ - the curvature of the working length of the cilia, a constant equal to 1/38 μm ^-1 .

K ₂ - the curvature of the cilia from the working length to the tip 1/9 [μm ^-1 ].

α is the angle of inclination of the cilia relative to the vertical position 550.

For calculations, the formula was used:

Given that a more positive dynamics of the speed of mucociliary transport was obtained after taking sinupret (3.35 mm / min before administration and 4.12 mm / min after administration of rinofluimucil and 10.62 after administration of sinupret), the patient was prescribed a course of treatment with sinupred according to the above pattern for 30 days.

Assessment of the speed of mucociliary transport after treatment with sinupret revealed an increase in its effectiveness to V _c = 11.12 mm / min compared to the initial value before cure, V _c = 3.35 mm / min, which indicated objective positive dynamics after treatment, which coincided with objective indicators of clinical improvement.

The relevant parameters were measured:

L is the length of the cilia is 8 microns.

T _e - effective impact time - 0.06 s.

T _p - time from the start of movement to the maximum straightening of the tip of the cilia - 0.09 s.

K ₁ - the curvature of the working length of the cilia, a constant equal to 1/38 μm ^-1 .

K ₂ - the curvature of the cilia from the working length to the tip 1/6 [μm ^-1 ].

α is the angle of inclination of the cilia relative to the vertical position 550.

For calculations, the formula was used:

Example 2

Patient H., 30 years old, was admitted to the Federal State Institution “SPb Research Institute of ENT Department of Rosmedtechnology” on April 12, 2008 with a diagnosis of chronic purulent rhinosinusitis (exacerbation) for conservative treatment. In addition to the generally accepted clinical examination, the patient was studied mucociliary transport.

An objective assessment of the speed of mucociliary transport found that the rate was equal to V _c = 4.0 mm / min, which was significantly less than the norm (in healthy).

After preliminary administration of mucolytics, it was found that on the day after daily intake of rinofluimucil, the speed of mucociliary transport was V _c = 6.2 mm / min.

The day after the daily intake of sinupret, the mucociliary transport rate was V _c = 4.2 mm / min.

Given that the positive dynamics of the speed of mucociliary transport was obtained after taking rinofluimucil (4.0 mm / min before administration and 6.2 mm / min after administration), the patient was prescribed a course of treatment with rinofluimucil according to the above schedule for 30 days.

Assessment of the speed of mucociliary transport after treatment revealed an increase in its efficiency to V _c = 9 mm / min compared to the initial value V _c = 4.0 mm / min before treatment, which indicated objective positive dynamics after treatment, which coincided with objective indicators clinical improvement.

Claims (2)

1. A method for the treatment of chronic rhinosinusitis, including the determination of mucociliary transport disorders (MCT) by measuring the cilia of the ciliated epithelium, at least the speed of the mucociliary transport, and the speed of the cilia tip is obtained based on mathematical modeling with subsequent calculations by the formula

where V _with - the speed of the tip of the cilia, μm · s ^-1 ;
K ₁ , K ₂ , α are calculated as average values characteristic of each of the considered states of the human body: healthy, sick with acute or chronic sinusitis according to the developed model of cilia movement; K ₁ - the curvature of the working length of the cilia, the constant is 1/38 μm ^-1 ; To ₂ - the curvature of the cilia from the working length to the tip, μm ^-1 ; α is the angle of inclination of the cilia relative to the vertical position, deg;
π = 3.1417 is a constant;
L, T _p and T _e - parameters measured individually for each patient;
L is the length of the cilia, microns; T _p - time from the start of movement to the maximum straightening of the tip of the cilia, s; T _e - time effective strike, s,
and, given that the value of V _c = 9.6-11.3 mm / min corresponds to the normal functioning of the ICT, for patients with chronic rhinosinusitis accompanied by a violation of the ICT, a complex conservative treatment is prescribed, including: conventional therapy, such as antibiotic therapy, decongestant and desensitizing therapy , as well as the appointment of drugs with a mucoactive effect, characterized in that they prescribe a drug, after exposure to which during the day on the mucous membrane of the patient’s nasal cavity, an ICT study Lo large positive dynamics, the speed of the tip of the cilia (V _c ). 2. A method of treating chronic rhinosinusitis according to claim 1, characterized in that one of the drugs is prescribed: rinofluimucil or sinupret 15 drops three times a day in each half of the nose for 30 days.