Method for treatment and prevention of oral complications caused by hormonal preparation inhalations in patients suffering bronchial asthma

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to dentistry, and may be used for treating oral candidiasis caused by hormonal preparation inhalations in the patients suffering bronchial asthma. For this purpose, the dental clinical-laboratory analysis and diagnosing of candidiasis is followed by prescribing 1% antimycotic agent of imidazole derivatives for oral preparation 2-3 times a day, a preparation with the active substance GMDP (glucosaminyl-muramyl dipeptide) 10 mg once a day 30 minutes before meals for 10 days, and using a toothpaste and Elmex mouthwash.

EFFECT: method enables higher clinical effectiveness in candidiasis ensured by enhancing the oral local immunity.

2 cl,1 tbl,1 ex

 

The present invention relates to medicine, namely to the dentist, and can be used for treatment of dental diseases, caused by taking inhaled hormonal drugs in patients with bronchial asthma.

Dentist quite often in the treatment of inflammatory periodontal diseases, dental caries and its complications deals with symptomatic manifestations of various diseases of internal organs in the oral cavity. The underestimation of the total somatic pathology can lead to complications during the treatment of the sick and poor dental care. The relationship between somatic illness and the condition of the oral cavity is carried out via various kinds of homeostasis (metabolic, immunologic, and others), the violation of which can lead to various diseases, as the whole body, and the mouth. In recent years, increasing attention is being given to improving methods of diagnosis and treatment of comorbidity (see global strategy for treatment and prevention of bronchial asthma. Edited Chuchalin A.G. Publishing house Atmosphere, Moscow, 2006)

Bronchial asthma (BA) is a serious problem in all countries of the world, including in Russia, which is connected with a distinct increase in the frequency of occurrence, number of complications, outages is of course of this disease, and with significant progress in diagnosis and treatment. Studies conducted in recent years showed that about 7 million people suffer from bronchial asthma, of whom about 1 million have a severe form of the disease. In pediatric populations BA is 10%. Among the adult population suffering from BA, 30% of patients with mild disease, a 50% moderate and 20% of patients with severe asthma. BA leads to early disability and huge economic loss (Chuchalin A.G. guidelines. Pulmonology. Publisher GEOTAR-Media, Moscow, 2007).

The disease can occur at any age; about half of patients with BA develops up to 10 years, and another third to 40 years. BA is more common among the urban population, and among people living in cold climates and in industrial areas.

With medication BA used two groups of drugs. For relief of asthma BA use inhaled glucocorticosteroids (IGCs), which are the priority. With their help maintain remission, quickly and effectively reduced exacerbations in severe BA. In the mechanisms of asthma action IGX leading value have anti-inflammatory effect, the ability to reduce adren rychecky imbalance and immunosuppressive action. In medical practice used EGCS that have both system and local action.

However, along with positive action, these drugs cause a decrease in natural protective barrier of the mucosa of the mouth and dysfunction of the systems of immune defense. With long-term use IGX arise dysphonia, hoarseness, candidiasis of the oral cavity, at least - osteoporosis (see M.A. Haritos, K.A. Ramazanova "Modern ideas about the treatment of bronchial asthma," J. Terra Medina Nova, No. 12001,). In this regard, the development of an adequate integrated methods for the prevention and treatment of complications in the oral cavity caused by exposure to inhalation of hormonal drugs in patients with BA is timely and relevant.

The known method of prevention and treatment of dental diseases in children with bronchial asthma (Z. No. 2002133830/14 from 15.12.2002,, publ. from 20.06.2004, IPC AC 6/02).

The known method of prevention and treatment of dental diseases in children with bronchial asthma includes training individual personal oral hygiene, professional oral hygiene, sanitation of the oral cavity, the purpose of preventive diet, prenosological diagnostics, medical examinations, selection of hygiene products patients, the complex of therapeutic and preventive measures. Spend a shrub is tological clinical and laboratory examination, determine the pathological changes of the organs of the mouth, are the dispensary groups with regard to diagnosis and determining the severity of bronchial asthma, and taking into account the revealed pathological changes in the organs of the oral cavity determine the tactics of groups. In tactics first group of patients include professional oral hygiene twice a year, the sanitation of the oral cavity twice a year, the use of therapeutic-prophylactic complex twice a year under the scheme: treatment with f-containing liquids teeth on a quarterly basis, during the year, 2 times per week 5 procedures, application neutral calcification gel model "Saliva" during the year on a quarterly basis, for 20 days, after brushing in the morning and evening, lysozyme 100% in the morning and evening on an empty stomach in the form mouth trays. In the tactics of the second group include professional hygiene of the oral cavity three times per year, irrigation of the oral cavity 3%solution of soda or alkaline mineral water after using the inhaler, the use of therapeutic-prophylactic complex three times a year under the scheme: treatment with f-containing liquids teeth on a quarterly basis, during the year two times in week 5 of treatment, applique neutral calcification gel model "Saliva" during the year, quarterly, 20 days after brushing in the morning and evening, lysozyme 100% in the morning on an empty stomach and the Assembly is ω in the form mouth trays. In the tactics of the third group include occupational hygiene four times a year, the sanitation of the oral cavity four times per year, irrigation of the oral cavity 3%solution of soda or alkaline mineral water after using the inhaler, the use of therapeutic-prophylactic complex four times a year under the scheme: treatment with f-containing liquids teeth on a quarterly basis during the year 2 times per week 5 procedures, application neutral calcification gel model "Saliva" during the year, quarterly for 20 days after brushing in the morning and evening, lysozyme 100% in the morning and evening on an empty stomach in the form mouth trays, children in paroxysmal period prescribed asthma treatment oral antiseptic solution 6-8 times a day, processing of the marginal gingiva of the oxygen jet 3-4 times a day for 3-5 minutes, rinse the mouth alkaline mineral water or 3%solution of hydrogen after using the inhaler, lysozyme 100% in the morning and evening on an empty stomach in the form mouth trays, additionally carry out sanitary-educational work among children and their parents, if necessary, appoint a Spa treatment, in addition, appoint basic therapy with nonsteroidal anti-inflammatory drugs in inhalation form, inhaled and systemic corticosteroids.

However, the known method does not take into account on the agnostic and treatment of the main complications in the oral cavity, caused by the use of inhaled corticosteroids, such as candidiasis. The known method a long time and does not provide opportunities to assess the effectiveness of the treatment.

A prototype of the invention is selected there is a method of treatment of complications of the oral cavity caused by the admission of inhalation of hormonal drugs in bronchial asthma patients, including dental clinical and laboratory research and follow-up treatment (see www/phid/EN/Lisser/17675/newfspx).

The known method is that the conduct of dental clinical and laboratory research and identify manifestations of chronic generalized periodontitis (HGP) in patients with BA, receiving inhalation hormones, depending on its clinical pathogenetical options, duration and age. Explore the nonspecific factors of protection and local immunity to the antigen of the periodontium and the number of CEC, identify metabolic chemical elements in patients with BA in various biological environments. Determine the periodontal index. In the complex treatment of patients with BA in the stage of exacerbation and remission with HGP to normalize the metabolism of potassium, zinc, copper and calcium in various biological environments using complexes of chemical elements and vitamins with regard to and the content in the plasma, cells and saliva.

In the known method is carried out a comprehensive assessment of the state of health of the periodontium. in bronchial asthma patients receiving inhaled steroids. However, the known method does not cover fully the condition of the mucous membranes of the oral cavity and complications arising in the oral cavity in patients given somatic pathology. As already mentioned, HGP is not the only complication that is caused by taking IGCs in patients with BA. With long-term use IGX arise dysphonia, hoarseness, candidiasis of the oral cavity. Also known method does not provide estimates of the effectiveness of the treatment.

The task of the invention is to provide a method of treatment of complications in the oral cavity, caused by taking IGX, namely candidiasis in patients with bronchial asthma.

The problem is solved in that in the known method of treatment of candidiasis of the oral cavity caused by the admission of inhalation of hormonal drugs in bronchial asthma patients, including dental clinical and laboratory investigations and subsequent comprehensive treatment, the patient BA with a diagnosis of candidiasis designate 1% solution antifungal agents imidazole derivatives for treatment of the mouth 2-3 times a day, the drug with the active substances of the m GMDP (glucosaminilmuramildipeptide) 10 mg 1 time per day 30 minutes before meals for 10 days, and the use of toothpaste and mouthwash for oral Elmex, while the patient with bronchial asthma before and after treatment are conducting studies to determine the concentrations of Pro - and anti-inflammatory cytokines IL-1, IL-4, and the effectiveness of the treatment is evaluated according to changes in the concentration of Pro - and anti-inflammatory cytokines IL-1, IL-4.

The present invention meets the criteria of the invention of "novelty" and "inventive step", as held patent information research has not revealed when conducting patent information research on the patent and scientific literature sources prejudicial to the novelty of the proposed method, as well as technical solutions with the essential features of the proposed method.

As a means for local use, use antifungal agents derived imidazole - 1% solution "Candida". Solution "Candide" is an antifungal drug with a wide spectrum of action for local use, violates the synthesis of ergosterol, which is included in the composition of cell membranes of fungi that causes a change in its properties and leads to lysis of the cells (see instructions for use).

As a drug with the active substance GMDP (glucosaminilmuramildipeptide) apply "Likopid", biological activity which is due to the availability of the m-specific binding sites (receptors) to GDP, localized in endoplasmic phagocytes and T-lymphocytes. The drug stimulates the functional (bacteriological, cytotoxic activity of phagocytes (neutrophils, macrophages), enhances the proliferation of T - and b-lymphocytes, increases the synthesis of specific antibodies. Pharmacological action is carried out by increasing the production of interleukins, factors tumor necrosis-alpha, gamma interferon, colony-stimulating factors. Indicated for use in the treatment of conditions involving secondary immunodeficiency (see instructions for use).

As toothpaste and mouthwash for oral use toothpaste and mouthwash Elmex. Toothpaste contains organic aminopterin (AmF) olaflur, which is the active ingredient for protection against caries, fluoride, effective in the fight against tooth decay than calcium-containing toothpastes. Elmex toothpaste is seriesproduction. Rinse Elmex - treatment-and-prophylactic care to remineralize and protect teeth that do not require cultivation. Highly efficient aminopterin strengthens the enamel and protects it from exposure to acids, especially in hard to clean places. Remineralizes and strengthens even demineralized enamel.

To assess the effectiveness of treatment in our study we have selected two cytokine is, one of which is anti-inflammatory (IL-4), another Pro-inflammatory (IL-1). For airway inflammation in ad is characterized by an increase in the mucosa and the lumen of the bronchial tree the number of activated eosinophils, mast cells, macrophages and T-lymphocytes, which, in turn, under the influence of many immunological mechanisms that produce IL-4. IL-4 is a Central cytokine allergic response, which controls the involvement of leukocytes in the cascade developing allergic reaction events. In this regard, the concentration of this cytokine is important to assess the phenomena of Allergy and autoimmunity. IL-1 is a proinflammatory cytokine, the greatest activity which is associated with T-helper cells that produce IL-4. By increasing the concentration of IL-4 is achieved lock and spontaneous and induced production of proinflammatory IL-1, which is one of the mediators of inflammation in this immunological chain.

The technical result of the invention is to increase the effectiveness of treatment of candidiasis, caused by taking IGCs in patients with BA, which is expressed in the absence of a patients symptoms of candidiasis after treatment, and the lack of a sufficient number of colonies ka the bits in a smear for diagnosis of candidiasis of the oral cavity. The proposed method improves local immunity of the oral cavity, as evidenced by increased levels of lysozyme in the mixed saliva and increase the level of anti-inflammatory IL-4. Monitoring the status of the immunological status of the oral cavity before and after treatment provides an objective assessment of its effectiveness. In addition, the proposed method involves treatment of immunological drugs that markedly increase the efficiency of the main drugs prescribed for the treatment and prevention of complications in the oral cavity in patients with bronchial asthma.

To confirm the obtained technical result, studies have been conducted of patients with pulmonary Department of the clinical hospital №5 of Nizhny Novgorod. Dental clinical and laboratory studies carried out at the Department of propaedeutic dentistry GBOU VPO "Nigga".

A random sample of patients aged 21-45 years of age were randomized into 4 groups: the status of the underlying disease (bronchial asthma) - 3 groups, depending on the experience of the disease (group 1 - the experience of the disease from one year to three years, group 2 - three to five years, group 3 - more than 5 years) 20 people each, a total of 60 people, a control group of 15 people (healthy people without asthma and Seirawan the second cavity of the mouth).

To determine the immunological status of the oral cavity of patients with bronchial asthma receiving inhaled hormonal drugs, investigated changes in the concentration of Pro - and anti-inflammatory cytokines IL-1 and IL-4 before and after treatment. As the material for the study were samples of mixed saliva of man. The collection of saliva was performed by Slavyane in the tube in the morning on an empty stomach, slimy teeth. Usually 1.5-2 ml of mixed saliva. In saliva was determined salivary cytokines IL-1 and IL-4 enzyme-linked immunosorbent method using test systems produced by LLC "Protein component" and LLC "Cytokine" (Saint-Petersburg) before and after treatment.

IL-1, PG/mlIL-4, PG/ml
Before the treatment122,22±1,44*20,22±2,42*
After the treatment105,16±4.26 deaths**36,7±1,12*
* - statistically significant values (p<0,01);
** - statistically significant values (p<0,05).
The proposed method is carried out following the way.

The patient BA, host IGX for diagnosis of candidiasis and evaluation of the immunological status of the oral cavity, hold the dental clinical and laboratory research. Microbicides oral determined by conducting scraping with the mucosa on Candida. The fence material is produced on an empty stomach on slimy teeth. When the crops on liquid nutrient media, growth of yeast colonies over 1000 per 1 g of the material under investigation suggests that the selected fungi are the causative agent of the disease. 10-100 colonies per 1 g of pathological material are not a criterion for diagnosis of candidiasis, and only the signal for continuing the search for the causative agent. The presence of the pathogen in all the drugs in large quantities and active in combination with a typical clinical picture suggest patients with candidal infection. To determine the immunological status of the oral cavity of patients with bronchial asthma receiving inhaled hormones, exploring changes in the concentration of Pro - and anti-inflammatory cytokines IL-1 and IL-4 before and after treatment in the saliva of the patient. Collection of saliva is made by

Slavyane in the tube in the morning on an empty stomach, slimy teeth. Get 1.5-2 ml of mixed saliva and determine salivary cytokines IL-1 and IL-4 tverdova is owned by an enzyme immunoassay using test systems produced by LLC "Protein component" and LLC "Cytokine" (Saint-Petersburg) before and after treatment.

The patient diagnosed with candidiasis designate 1% solution antifungal agents imidazole derivatives for treatment of the mouth 2-3 times a day, the drug with the active substance GMDP (glucosaminilmuramildipeptide) 10 mg 1 time per day 30 minutes before meals for 10 days, and the use of toothpaste and mouthwash for oral Elmex, the effectiveness of the treatment is evaluated according to changes in the concentration of Pro - and anti-inflammatory cytokines IL-1, IL-4.

A specific example of implementation is given in the form of extracts from the patient card.

Patient T., 64 years old, was hospitalized in the city clinical hospital №10, Nizhny Novgorod with a primary diagnosis of asthma, mixed, severe stage, the stage of exacerbation. The experience of the disease 30 years, takes inhalation hormones for 20 years. Appealed to the dentist complaining of a burning sensation in the mucous membranes of the oral cavity, in the presence of a white, curd-like patches on the back of the tongue and transitional crease in the lower jaw.

Collectively, complaints, symptoms, objective data and the severity of primary somatic diseases, the patient was diagnosed with Acute pseudomembranous candidiasis. Immunological status of the oral cavity before treatment: IL-1 -31,69, IL-4 -16,60.

Was assigned to the following treatment:

1. % R-R Candide - applications to the affected areas 3 times a day, from 3 to 7 days until symptoms resolve;

2. Likopid 10 mg 1 tablet per day, the course of treatment is 10 days;

3. The observing modes and hygienic measures the mouth after taking inhaled corticosteroids with the use of preventive and curative complex Elmex (toothpaste and mouthwash).

Immunological status after treatment: IL-1 - 4,67, IL-4 - 43,41.

1. A method of treatment of candidiasis of the oral cavity caused by the admission of inhalation of hormonal drugs in bronchial asthma patients, including dental clinical and laboratory investigations and subsequent comprehensive treatment, wherein the patient BA with a diagnosis of candidiasis designate 1%solution of antifungal agents imidazole derivatives for treatment of the mouth 2-3 times a day, the drug with the active substance GMDP (glucosaminilmuramildipeptide) 10 mg 1 time per day 30 minutes before meals for 10 days and the use of toothpaste and mouthwash for oral Elmex.

2. The method according to claim 1, characterized in that in a patient with bronchial asthma before and after treatment are conducting studies to determine the concentrations of Pro - and anti-inflammatory cytokines IL-1, IL-4, and the effectiveness of the treatment is evaluated according to changes in the concentration of Pro - and protivovospalitel what's the cytokines IL-1, IL-4.



 

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