Method of treating acute and aggravated chronic laryngitis

FIELD: medicine.

SUBSTANCE: invention refers to medicine and aims at treating acute and aggravated chronic laryngitis. What is involved is specific antibioticotherapy per os with additional examination of microflora starting from the 3^rd-5^th day of the therapy followed by instillations of specific, result-related bacteriophagues into the larynx in the amount of 0.5-1.0 ml in acute laryngitis for 7-10 days, and in aggravations for 10-14 days.

EFFECT: method provides higher clinical effectiveness ensured by a lower number of side effects and complications, and a reduced length of treatment.

16 tbl, 2 ex

The invention relates to medicine, namely to otorhinolaryngology and phoniatrics, and can be used in complex treatment of acute exacerbations of chronic laryngitis.

Issues related to the treatment of patients with acute inflammatory diseases of the upper respiratory tract, are very relevant [3]. Currently, the treatment of patients with inflammatory diseases of the larynx is difficult, in most cases megatape, long-term, requires the use of numerous combined methods using specialized equipment and highly skilled medical personnel [6].

Existing methods of treatment of various[8, 9, 12, 14, 25], but not always effective and requires treatment [10]. The increasing resistance of microorganisms and changes in the etiological structure infections larynx talk about the need for revision of therapeutic approaches, in particular regarding appropriate designation in this situation antibacterial drugs [17, 18].

There is a method of treatment of chronic hyperplastic laryngitis by direct injection into the vocal fold or podskladochny space intralaryngeal inductors of interferon - poludana or cicloferon [4].

The disadvantages of the method are:

1. Implementation of injections in the treatment tip can ladonia space is permitted only in stationary conditions, not ambulatory;

2. Injection method in vocal fold or podskladochny space dangerous complications, such as hemorrhage, abscesses, which is unacceptable for persons holosericea professions.

There is a method of treating chronic hyperplastic laryngitis by intravenous immunoglobulin "Immunovision" in the amount of 25.0 ml with the speed of 10-20 drops per minute [1].

The disadvantages of the method are:

1. Intravenous drug substances and possible complications.

2. The necessity of the treatment room and special equipment.

There is a method of treatment of acute and chronic laryngitis method of infusion of oils in the larynx [2, 3, 13]. This method also has its drawbacks:

1. Prolonged infusion of oils in the larynx leads to the development of oleum in the larynx and trachea.

2. It is impossible to start working professionals voices immediately after this procedure. The singer can continue its work only 2 hours.

Closest to the proposed is a comprehensive method for the treatment of acute and chronic laryngitis, including the infusion of various drugs in the larynx [13]. However, it has several disadvantages depending on what the drug is used.

The disadvantages of the method are:

1. Prolonged infusion solution is in antibiotics leads to the development of candidiasis mucous membrane of the larynx, which is very undesirable, especially in persons of Mature age.

2. Prolonged infusion of a suspension of hydrocortisone and other hormonal agents leads to the development of subatrophy mucous.

Combined infusion of drugs significantly increases their side effects and can cause an allergic reaction in the patient.

To combat inflammatory diseases and complications developed new types and classes of antibiotics. However, they quickly develop resistance. In this regard, many researchers say serious "crisis of antibiotic therapy" [9]. All this makes the search for new approaches to prevention and treatment of inflammatory diseases. One of these approaches was the return to the use of bacteriophages, from which the medical community has temporarily abandoned in the mid-20th century with the invention of broad-spectrum antibiotics. Over the last 5 years there has been a significant increase in the number of scientific articles in this direction. Classic and the latest clinical research and numerous experiments on animals showed that phage therapy is an effective and safe alternative to antibiotics in the treatment of bacterial infections[19, 20, 21, 22, 23, 24].

New technical problem - increasing clinical efficiency by reducing the number of is and the side effects and complications and shorten the period of disability while maintaining the availability and ease of use

To solve the problem in the treatment of acute and chronic laryngitis by conducting specific antibiotic therapy per os with 3-5 days of onset additionally, in acute laryngitis spend instillation specific bacteriophages in the form of injections into the larynx in the amount of 0.5-1.0 ml for 7-10 days, and during exacerbations within 10-14 days, while in extreme cases impose additional specific bacteriophage and 1 tablespoon 3 times a day for 2 weeks.

The method is as follows.

Each patient performed a study of the microflora of the larynx and its sensitivity to antibiotics. The sensitivity of microorganisms to antibiotics determined by the method of disks in accordance with the "guidelines for determination of antibiotic sensitivity of microorganisms to antibiotics by the method of diffusion in agar disks", approved by the USSR Ministry of health (decree No. 535 of 22 April 1985) and Instructions for use disks for determination of sensitivity to antibiotics approved by the head of Department on the introduction of new medicines and medical equipment Ministry of health of the USSR from 12.10.84, the Biomaterial is obtained by taking a swab from the mucous membrane of the larynx in the field of vestibular folds, niceraasing space and mucosa of the vocal folds in Tim swab moistened with sterile saline. The sensitivity of microorganisms to antibiotics is determined by three degrees: sensitive to the antibiotic (S), moderately resistant to the antibiotic (I)resistant to the antibiotic (R). In the same way, reveal sensitivity to bacteriophages. Patients examined before treatment and after the course of therapy.

It is known that the chronic laryngitis begins most often with either hypothermia of the patient, or viral infection. However, as shown by numerous data[3, 8, 10, 12, 14], very quickly this process begins to play a greater role acceding bacterial infection. It is known that the microflora of the larynx and trachea differs in composition from the microflora of the upper respiratory tract - the pharynx and the nasal cavity. This is evidenced by numerous research scientists and microbiologists [5, 8, 15]. According to our data, 67% of patients it has significant differences. Therefore in the beginning of rational antibiotic conducting a study of the microflora of the larynx and determine its sensitivity to antibiotics. Ineffective treatment of systemic antibacterial drugs in the outpatient stage in patients with exacerbation of chronic laryngitis associated with the wrong choice of the antibiotic and its resistance to microorganisms[8, 11, 15].

Ant the bacterial effect of bacteriophages specific lysis of pathogenic bacteria in inflammation. Found that bacteriophages stimulate regeneration, stimulate the immune system of the patient. Positive quality of bacteriophages: no toxic effect on the organism, the development of allergies, dysbiosis [9, 16]. Injection into the larynx specific bacteriophages 0.5-1 ml due to the dimensions of the larynx. The size of the larynx in men and women have their differences. Because the larynx is a hormone body and usually the larynx in males is larger than the larynx in women.

As shown by the analysis of data from clinical observations of patients with acute exacerbation of chronic laryngitis, acute course of the disease and when expressed positive dynamics enough to hold treatment with bacteriophages within 7-10 days, and at exacerbation of chronic laryngitis appropriate designation of bacteriophages within 10-14 days. In case of severe disease, weak positive dynamics of the inflammatory process is shown an additional intake of bacteriophages inside of 1 tablespoon 3 times a day for two weeks(14 days).

As an example, here is the statement from the patient card two patients treated with the claimed method.

Clinical examples

Example 1.

Patient T in L.A. born in 1989, the treatment period of 14 days.

Diagnosis: chronic is a mini-catarrhal laryngitis. He complained of pain in the throat, hoarse voice, dry cough.

From the anamnesis: the patient is sick often, more than 4 times a year. In childhood, frequent sore throats, pneumonia 3 years ago. The patient is tall, asthenic physique, Smoking.

Objective: the larynx is marked hyperemia of the mucous laryngopharynx, the true vocal folds injected, thickened edge fusiform swelling. During phonation, the closure of the true vocal folds incomplete, nicecarolina space marked accumulation kesisoglou detachable. In the lacunae of tonsils marked accumulation of purulent-caseous plugs. Nasal breathing is free.

Auditory evaluation of voice: voice husky, hoarse, dysphonia pronounced degree (4), aspirate attack - solid.

Surveyed on flora and sensitivity to antibiotics of the larynx. As a result of sowing received concomitant microflora S. Aureus + Str. Pyogenes from the mucous membrane of the larynx, and a positive sensitivity St.Aureus revealed only to ciprofloxacin, other antibiotics: Cefotaxime, tetracycline, azithromycin and vancomycin microorganism was not sensitive. The treatment according to the proposed method: caprolactam, staphylococcal and streptococcal bacteriophage 0.5 ml topically and orally for 1 tbsp 3 times a day for 14 days. Remission was more than 3 who nazev and is still ongoing. The patient feels well, no complaints.

Laryngoscopies picture and auditory assessment of the voice of the patient in the dynamics: before treatment indicators correspond pronounced degree (3). After treatment, the voice has recovered to normal (0-1) in a very short period of 14 days (table 1).

Computer analysis of the vote showed improvement on some objective criteria: the indicator signal to noise ratio HNR increased from 17.8 to 24.9 dB dB (40%). Indicators of Jitter and Shimmer decreased to the optimal values: Jitter - 1,48 to 0.33, Shimmer - from 7.35 to 0.84, which determines the positive dynamics of changes in the functional status of the patient (table 2).

According to the electronic stroboscope, the index of the vibrator failure (IVN) decreased on average from 1.2 to 1, which corresponds to the norm (table 3).

The dynamics of the blood tests are positive: the number of leukocytes decreased by 19% (table 4).

Thus, all subjective and objective indicators as a result of treatment improvement occurred. A period of disability -14 days.

On a set of clinical and paraclinical data of the result of the treatment were assessed as "improvement" in the shortest possible time, without complications.

Example 2.

Patient sh-A.G., 1981 birth, dates of treatment, 28.05.10 - 06.06.10,

Diagnosed with Acute laryngitis.

He complained of the lack of votes for 2 x DN is th, pain during phonation, shortness of breath, dry cough, sore in the shed.

From the anamnesis: 5 days ago suffered ARI, worried about the pain in the throat when swallowing, fever up S, chills, malaise.

Objective: larynx - hyperemic mucosa, the lumen of the larynx moderately narrowed, the true vocal folds pink color, thickened, closing full.

Auditory evaluation of voice: voice husky, hoarse, nevynoslivuyu-dysphonia pronounced degree (III), aspirate attack - solid.

Computer analysis of voice: the indicator signal to noise ratio HNR amounted to 18.0 dB indicators Jitter 0,70, Shimmer - 3.2.

Laryngostroboscopy - asynchronous oscillations, determined by changes in the phase of opening and closing, changes in the amplitude and synchrony of oscillations, stroboscopic comfort is negative.

Clinical and laboratory data did not reveal significant changes

Thyroid ultrasound - norm

Bacterial analysis - S.Aureus

Treatment according to the proposed method: Voice calm. General and local anti-inflammatory drug treatment in accordance with the standards. As well as the installation of staphylococcal bacteriophage 1 ml endolaryngeal within 10 days.

Treatment the patient endured well. The 4-5 day treatment felt better in his voice. Health and good mood.

On superseniority voice has improved. Auditory evaluation of voice (2) a moderate degree of disponee normalized to (0), i.e. the norm. Laryngoscopies picture totally improved from 2.0 to 0 points (table 5).

Computer analysis of the vote showed improvement by objective indicators: indicator signal to noise ratio HNR reached values greater than the 22.6 dB. Indicators of Jitter and Shimmer decreased to the optimal values: Jitter is lower than 0.4; Shimmer - less than 2.4, which characterizes the dynamics of changes in the patient's condition as positive (table 6).

According to the electronic laryngoscopy, the index of the vibrator failure to 1.4 before treatment is set to 1, which corresponds to the average (table 7).

The dynamics of the blood tests are positive: the number of leukocytes decreased by 15%, the number of lymphocytes by 21% (table 8).

Thus, all subjective and objective indicators as a result of treatment improvement occurred. The incapacity period of 10 days.

On a set of clinical and paraclinical data, the treatment outcome is rated as "improved" with a minimum period of disability.

Clinical trial performed on 104 patients. We investigated two groups of patients: patients with exacerbation of chronic laryngitis (47 people), the treatment which was carried out by the proposed method with the use of antibiotics and bacteriotherapy; and similar is sick, treated by the traditional method in accordance with existing standards (21). Treatment contributed to the actual disappearance or significant reduction of clinical symptoms with exacerbations of chronic laryngitis (table 9).

In the total group of patients with chronic laryngitis, after treatment according to the claimed method, the number of patients without signs of active inflammation was increased more than 2 times. Confirmation improve the condition of patients in the use of the claimed method served as the dynamics of these computer voice analysis (table 10). It is revealed that after treatment indicator signal to noise ratio HNR increased from 18.07 to 20,05 dB (at 10%). Indicators of Jitter and Shimmer decreased to the optimal values: Jitter - from 0.71 to 0.53, Shimmer - between 6.08 to 4.24, which determines the positive dynamics of changes in the condition of the patients.

Comparative results of the proposed and traditional methods in the treatment of patients with exacerbation of chronic laryngitis are shown in Table 11. One of the most important advantages of the claimed method is that the risk of complications is reduced to 0.

Indicators of blood as a result of treatment by the claimed method decreased and entered the range of acceptable values (table 12).

Treatment contributed factual is th disappearance of clinical manifestations in patients with acute laryngitis (table 13).

It is revealed that after treatment indicator signal to noise ratio HNR increased from 18,05 to 19,97 (10%). Indicators of Jitter and Shimmer decreased to the optimal values: Jitter from 0,99 to 0.41 (59%), Shimmer - with up to 6.19 of 3.31 (47%)that determines the positive dynamics of changes in the condition of the patients (table 14).

Indicators of blood as a result of treatment by the claimed method in patients with acute laryngitis decreased and entered the range of acceptable values (table 15).

Comparative results of the proposed and traditional methods in the treatment of patients with acute laryngitis shown in Table 16. One of the most important advantages of the claimed method is that the risk of complications is reduced to 0.

Comparing the results of treatment according to the claimed method of treatment in accordance with the existing standard and the treatment of the prototype (table 11 and table 16) revealed the shortest duration of treatment in the proposed method, the occurrence of clinical effect already after the first procedure of bacteriotherapy, a higher percentage of the complete restoration of function of the vocal apparatus, and the absence of complications such as mucosal dysbiosis. All of the above demonstrates the advantages of the proposed method.

Sources of information

1. Aznabaeva L. F., Danov A.N., Aref'eva N.A., Sharipov R.A. Method of treatment is hronicheskogo hyperplastic laryngitis. // Pat. 2297847; publ. 27.04.2007

2. Babiak VI, Nakata AA Clinical otorhinolaryngology // SPb.: The Hippocrates. - 2005. - 835 S.

3. Vasilenko US a Voice. Politicheskie aspects. // M: Energoizdat. 2002. - 480 S.

4. Grigoryan, S., Demchenko E.V., Ivanchenko GF a Method of treating chronic hyperplastic laryngitis. // Pat. 2214249; publ. 20.10.2003.

5. Gusev M.V., Mineeva L.A. Microbiology.// M.: Publishing center "Academy". - 2003. - 464 S.

6. Demchenko E.V., Ivanchenko GP, Nowakowski DL Modern aspects of clinical and laboratory diagnosis and treatment of chronic hyperplastic laryngitis. // The quality of life. Medicine. - 2007. - p.35-38.

7. Zaritsky L.A., Trinos VA, Trinos L.A. Practical phoniatrie // Kiev. - 1984. - 165 C.

8. Kudelska D., ALEXANDER Gurov Possible use of azalides in ENT practice. // Medical business. - 2010. No. 4. - 7 S.

9. Lazarev E.B. Bacteriophages and pectins in the correction of violations of microbiocenosis in pyo-inflammatory processes.: Abstract. Diss. Prof. the honey. Sciences. // M - 2007. - 18 S.

10. Osipenko E.V. anti-Inflammatory therapy in the treatment of patients with chronic laryngitis. // The Bulletin of otorhinolaryngology. - 2009. No. 4. - p.63-65.

11. Ryabova M.A., Dumb O.V. Chronic laryngitis: a pathogenetic principles of treatment. // SPb. - 2010. - 139 C.

12. Svetushkin V.M. Empirical antibacterial therapy for ostrichfeather diseases of the upper respiratory tract. // Russian medical journal. - 2005. - v.13. No. 4. - p.57-61.

13. Soldiers IB Guide otorhinolaryngology // M - 1997. - 607 S. (prototype).

14. Sturov NV, Ushkalov E. efficacy and safety of azithromycin in the treatment of infections of the upper respiratory tract. // Farmateka - 2008. No. 4. - p.65-68.

15. Pozdeev O.K. Medical Microbiology. Ed. Weaponammo. - 4th ed., wiped. // - M: GEOTAR-Media. - 2008. - 768 S.

16. Fattakhov BUT the Use of eubacteria in the treatment and prevention of wound infection of the eye: author. Diss. Kida. the honey. Sciences. // Ufa., 1999. - S

17. Esposito S, Bosis S, Begliatti E, et al. Acute tonsillopharyngitis associated with atypical bacterial infection in children: natural history and impact of macrolide therapy. // Clin Infect Dis 2006. - 43 (2).: 206-09.

18. Sliwa-Dominiak J, Witkowska M, Deptula W. Biological alternatives to antibiotics Przegl Epidemiol. // 2010 - 64(3): - 399-403. Review. Polish.

19. Uchiyama J, Takemura I, Hayashi I, Matsuzaki S, Satoh M, Ujihara T, Murakami M, Imajoh M, Sugai M, Daibata, M. Characterization of lytic enzyme open reading frame 9 (ORF9) derived from Enterococcus faecalis bacteriophage phiEF24C. Appl Environ Environ. // 2011. - Jan; 77(2): 580-5. Epub 2010 Nov 19.

20. Sunagar R, Patil SA, Chandrakanth RK. Environ Res. Bacteriophage therapy for Staphylococcus aureus bacteremia in streptozotocin-induced diabetic mice. // 2010 - Dec; 161(10): 854-60. Epub 2010 Sep 22.

21. Daniel A, Euler C, Collin M, Chahales P, Gorelick KJ, Fischetti VA. Antimicrob Agents Chemother. / Synergism between a novel chimeric lysin and oxacillin protects against infection by methicillin-resistant Staphylococcus aureus. / 2010 - Apr; 54(4): 1603-12. Epub 2010 Jan 19.

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Application

Table 1

Dynamics data laryngoscopies picture and auditory evaluation of voice (in points)

Table 2

Dynamics data computer voice analysis

Table 3

The dynamics of these electronic laryngostroboscopy

Table 4

Dynamics of indicators of the General analysis of blood

Table 5

Dynamics data laryngoscopies pictures and hearing evaluation voice

Table 6

Dynamics data computer voice analysis

Table 7

The dynamics of these electronic laryngostroboscopy

Table 8

Dynamics of indicators of the General analysis of blood

Table 9

The dynamics of the intensity of the main clinical manifestations of inflammatory diseases of the larynx in the treatment according to the claimed method in points (n=58),

where:* M₁- average; m₁- error of the mean before treatment; M₂and m₂- after treatment, p - significance differences at the level of statistical significance 95%

Table 10

The dynamics of the original modified performance computer analysis of voice treatment for the claimed method (n=58)

the figure 11

Comparative results of use in the treatment of patients with exacerbation of chronic laryngitis different methods of treatment,

where:* reliability of differences between the claimed method and the comparison group

Table 12

The dynamics of the original altered blood counts if treatment for the claimed method in patients with chronic laryngitis (n=47)

Table 13

The dynamics of the intensity of the main clinical manifestations of inflammatory diseases of the larynx in the treatment according to the claimed method in points (n=23) (acute),

where:* M₁- average; m₁- error of the mean before treatment; M₂and m₂- after treatment, p - significance differences at the level of statistical significance 95%

Table 14

The dynamics of the original modified performance computer analysis of voice treatment for the claimed method (n=23),.

(acute)

Table 15

The dynamics of the original altered blood counts if treatment for the claimed method in patients with acute laryngitis (n=23),

where: * P less than 0.05

Table 16

Comparative results of the proposed and traditional methods in the treatment of patients with acute laryngitis,

where:* reliability of differences between the claimed method and the comparison group.

1. A method of treating acute and chronic laryngitis by conducting specific antibiotic therapy per os, characterized in that 3-5 days of onset is additionally conducting a study of the microflora with subsequent instillation specific, according to the results of a study of bacteriophages in the larynx in the amount of 0.5-1.0 ml in acute laryngitis within 7-10 days, and during exacerbations within 10-14 days.
2. The method according to claim 1, characterized in that in complicated cases impose additional specific bacteriophage per os and 1 tablespoon 3 times a day for 2 weeks.