RU2140215C1 - Method of treating polyposis rhinosinusitis - Google Patents

Abstract

FIELD: otolaryngology. SUBSTANCE: interferon and immunologic status of patients are determined and, according to character of deviations found, correction with recombinant interferons and interferon inductors during pre- and postoperative periods is performed both in combination and as monotherapy. EFFECT: enhanced treatment efficiency. 2 cl, 2 ex

Description

 The invention relates to the field of clinical medicine, namely to the field of otorhinolaryngology.

 It is known that one of the main methods of anti-relapse treatment of polypous rhinosinusitis is the long-term use of corticosteroids. The disadvantages of using these drugs include: immunosuppressive effect, suppression of the lymphoid apparatus of the upper respiratory tract, a tendency to inflammatory processes in the nasal cavity, inhibition of the sympathoadrenal system.

 Currently, the 5th generation topical corticosteroids are most commonly used. Preparations are recommended for prolonged use for six months (A. S. Lopatin, G.Z. Piskunov, etc.). But, since polypous rhinosinusitis is often accompanied by a concomitant inflammatory process occurring against the background of immunodeficiency, the above drawbacks of the use of corticosteroids exacerbate immunodeficiency and reduce the effectiveness of their anti-relapse action.

 Also used in the postoperative period are immunomodulators (T-activin, ribomunyl, nonspecific immunostimulants - sodium nucleinate, etc.). The closest prototype of the work is an article by Portenko G.M. "Combined surgical treatment of patients with polyposis rhinosinusitis using levomizole and polysponin" (Journal of ear, nose and throat diseases N 6 p. 57 1989). The effectiveness of their anti-relapse action in diseases with an autoimmune component, such as polypous rhinosinusitis, is low, there is no antiproliferative effect, and these drugs were not widely used in the treatment of this pathology (Materials of the conference dedicated to the fifth anniversary of the Russian Society of Rhinologists, 1998).

 Since polypous rhinosinusitis is in most cases a virus-induced disease with an autoimmune component, the use of glucocorticoids, the use of plasmapheresis, etc. are a form of pathogenetic therapy. The introduction of interferon preparations with antiviral, antiproliferative, immunomodulating effects into practice would be an etiotropic approach in the treatment of polyposis rhinosinusitis.

 The aim of the present invention is to develop more effective methods of anti-relapse treatment of polypous rhinosinusitis and preoperative preparation of patients.

 This goal is achieved by the use of recombinant interferons and interferon inducers in the pre- and postoperative period.

 The basis for the use of interferon preparations was the first study of interferon and immunological statuses in patients with polypous rhinosinusitis: the interferon status is characterized by a pronounced deficiency in the production of IFN α and γ, significantly ahead of quantitative changes in the immunological status. There is a high degree of correlation between the severity of clinical manifestations and indicators of IFN status: the severity of the disease is determined by the severity of deficiency in production of IFN-α and γ and the type of IFN deficiency.

Used drugs
I. Recombinant IFN (intron -α, reaferon, viferon, Wilferon, etc.)
II. IFN Inductors (cycloferon, amixin, etc.)
As an example, the work used the most affordable and inexpensive drugs - recombinant IFN α2 - reaferon and viferon, and synthetic low molecular weight IFN inducers - cycloferon and amixin. The drugs approved by the Pharmaceutical Committee of the Ministry of Health of Russia for use in the clinic were studied.

 Treatment depends on the specific data of IFN status - the prevailing type and degree of decrease in IFN production α and γ by leukocytes, as well as the immunological status and clinical picture and is selected individually.

 Preoperative preparation.

 In the period of preoperative preparation and within 2-3 weeks after surgery with a replacement purpose, the use of recombinant IFN α2 is recommended. Duration and doses used depend on the specific data of IFN and immunological status.

 The clinical effect with the use of reaferon and viferon in the preoperative period was observed in patients of all groups, including those with a predominance of γ IFN deficiency. The most pronounced effect was observed in the group of patients with a predominant deficiency of IFN-α. In a laboratory study on days 5-7 in patients, in addition to improving indicators of IFN status, an increase in phagocytic activity and phagocytic index was noted. In addition, there is a significant decrease in IgE, CEC, which is especially important in the preoperative preparation of patients with infectious-allergic and mixed bronchial asthma. Clinically, there was a decrease in swelling of the nasal mucosa and stroma of nasal polyps (a decrease in the size of polyps), discharges from the nasal cavity stopped.

 The most difficult operation and the postoperative period occur in patients with concomitant bronchial asthma. Usually, corticosteroid drugs (hydrocortisone, prednisolone, dexamethasone intravenously drip) are used for several days before and after surgery for the preparation of surgery for patients with polyposis rhinosinusitis with concomitant bronchial asthma. The use of recombinant interferons allowed to avoid the appointment of corticosteroids during surgery in most patients. Corticosteroid drugs were prescribed only to patients who had previously received hormone therapy. In such patients, an initially sharply reduced level of serum cortisol was noted.

 We did not note significant differences in the use of reaferon and viferon.

Concrete example
Patient S., 36 l was admitted to the ENT department for recurrent polyposis of rhinosinusitis, moderate-severe infectious allergic bronchial asthma in the phase of unstable remission, asthmatic triad.

 Sick 5 years. A history of 4 polypotomies, the last polypotomy 4 months ago.

 According to the immunological status - an increase in IgE to 450 U / ml. (N <100), IgG reduction of 9.2 mg / ml (N 12.2 ± 1.56).

 When studying IFN status, the level of leukocyte production of IFN was α 80 units / ml (N 640 - 1280), IFN γ 16 units / ml (N 128 - 256), and the level of serum IFN was increased to 8 units / ml. In terms of preoperative preparation, a course of viferon was carried out at a dose of 1 million IU 2 times a day for 10 days.

 At the end of this period, there is a decrease in swelling of the nasal mucosa, the appearance of nasal breathing due to a significant decrease in the size of polyps in the nasal cavity, the discharge from the nose has stopped. In a control study of high-pressure respiratory function improved pulmonary ventilation. In the control study of IFN and immunological status - a decrease in IgE to 180 U / ml, an increase in IgG to 12 mg / ml. When studying IFN status, the level of leukocyte production of IFN α increased to 320 units / ml (N 640 - 1280), IFN γ to 64 units / ml (N 128 - 256).

 The operation was performed without the use of corticosteroid drugs. The postoperative period was uneventful. After the operation, the introduction of viferon in the previous doses was continued for 2 weeks with the subsequent transition to maintenance doses.

 The duration of the use of recombinant IFN α2 in the postoperative period depends on the dynamics of changes and IFN and immunological status, in particular, on the degree of increase in the activity of natural killers, phagocytic activity, and somewhat later on the degree of increase in IFN production.

 However, the effect during such a course of therapy is short-term, after 3 to 6 months, a decrease in the IFN system is again noted, noticeable in 25 to 30% of patients.

 In this regard, in the postoperative period, in order to prevent relapse, along with recombinant interferons, interferon inducers — cycloferon and amixin — were used. Both drugs belong to the class of synthetic low molecular weight compounds.

 In the postoperative period, these drugs were prescribed after the reactive phenomena subsided, in the 2-3 phase of the wound process. By the time of induction of IFN inducers, the main course of substitution therapy with recombinant IFN α2 was completed, or the combined use of drugs of both groups was carried out depending on the initial data of IFN and immunological status and data of dynamic examination. So, for example, with a frequently expressed response according to clinical and laboratory data to the use of recombinant interferons, as well as with a predominant deficiency of IFN γ, in some patients it is advisable to conduct monotherapy with IFN inducers.

 With the appointment of such a course of treatment, a more pronounced clinical and laboratory effect was achieved, especially in the group of patients with a pronounced symmetric decrease in the production of IFN α and γ. The effect persisted at the end of 3 months after the end of the course of treatment. No side effects have been noticed.

 In 12 patients, the results of IFN status were analyzed one year after the operation. The maximum effect of the treatment was observed in patients who underwent combined support IFN therapy within 3 months after surgery, taking into account the data from the control analysis of IFN status, a repeated support course of treatment with IFN drugs and their inducers 6 months after the operation. The duration of the second course was 1.5 - 2 months.

Concrete example
Patient B., 52 years old, was admitted to the ENT department for recurrent polypous ethmoiditis, infectious-allergic bronchial asthma. Sick 5 years. 17 times the patient underwent nasal polypotomy. Notes a worsening during the year when, after pneumonia, the course of bronchial asthma and nasal breathing worsened. Over the past year, 5 times the patient underwent nasal polypotomy, 2 times in stationary conditions. Previous operation - 2 months ago.

 According to the immunological status - an increase in IgE to 380 U / ml (N <100), an increased level of IgA to 4.1 mg / ml, a decrease in IgG of 11.2 mg / ml (N 12.2 ± 1.56), an increase in CD4 / CD8 up to 2.5 (N 1.0 - 2.3). In a clinical blood test, eosinophils are elevated to 13.

When studying IFN status, the level of leukocyte production of IFN is α 40 units / ml (N 640 - 1280), IFN γ 32 units / ml (N 128 - 256), the level of serum IFN is increased to 16 units / ml. In terms of preoperative preparation, a course of reaferon at a dose of 500 1 • 10 ( ^* 6) IU was carried out 2 times a day for 7 days. Upon achieving significant clinical improvement, polypoetmoidotomy was performed with an expansion of natural anastomoses with maxillary and frontal sinuses. In the postoperative period, a course of reaferon was proposed for another 7 days, then the patient received maintenance doses of reaferon 2 times a week for 2 weeks, then 1 time per week for 3 months after surgery. At the same time, 14 days after the operation, cycloferon 250 mg was prescribed after 48 hours for 2 weeks, followed by a transition to a maintenance dose 1 time per week for 3 months after the operation. After 6 months, a second course of interferon therapy was carried out, also under the control of IFN status. During the year, a gradual normalization of the morphology of the nasal mucosa was noted, and the course of bronchial asthma significantly improved.

 One of the most difficult problems of modern rhinology is the treatment of allergic fungal sinusitis. We have found in such patients a sharp decrease in the production of interferon by lymphocytes, especially γ IFN.

 When conducting a combined course of treatment with IFN preparations and their inducers in combination with antifungal drugs for patients with concomitant fungal lesions of the nasal cavity and sinuses, a pronounced clinical effect was obtained that significantly exceeded that when only antifungal therapy was carried out and which made it possible, in some cases, to recover patients.

 To compare the results of treatment with the use of IFN preparations and their inducers and with the use of topical glucocorticoids (flixonase, and in patients with bronchial asthma, beconase or becotide, depending on the severity of the disease), IFN- and immunological status were analyzed in 10 patients of the control group. Glucocorticoids were prescribed to patients in the absence of any pronounced inflammatory phenomena in the nasal cavity. In 2 patients, negative dynamics were observed during treatment with corticosteroids. A positive clinical effect was observed in 6 patients, but a short-term and unstable pronounced clinical effect was observed in 2 patients with an initial significant decrease in cortisol levels and a history of corticosteroids for bronchial asthma. Significant changes in the IFN and immunological status in a dynamic study was not observed. Since these patients were clinically prone to recurrence of the disease, in the future, IFN therapy was prescribed to patients. A more pronounced and persistent clinical effect was obtained.

Claims (1)

 A method of treating polypous rhinosinusitis by using a combination of surgical treatment of patients with the use of immunomodulating drugs in the pre- and postoperative period, characterized in that they determine the interferon and immunological status in patients and, depending on the nature of the deviations, carry out correction with recombinant interferons and interferon inducers in pre- and postoperative period, both combined and as monotherapy.