[Rengalin, a New Efficacious and Safe Antitussive Agent. Results of a Randomized, Comparative, Multicenter Clinical Trial in Patients with Acute Respiratory Tract Infections].

UNLABELLED: Rengalin is a release-active combination antitussive drug based on antibodies to bradykinin, to histamine and morphine. It acts at various mechanisms of cough reflex by modifying endogenous target molecules and their interaction with receptors. The drug's efficacy, as demonstrated previously in experimental and clinical studies, is mediated by specific release-activity obtained as a result of the production process. METHODS: Efficacy and safety assessment of rengalin in the treatment of cough induced by acute upper respiratory tract infections (URIs) in comparison with a complex codeine-containing drug (codelac) was performed as part of a multicenter, randomized clinical trial involving 143 patients. All the participants presented with dry/non-productive cough caused by URIs (pharyngitis, laryngitis, tracheitis, tracheobronchitis, bronchitis). The duration of cough varied between 12 hours and 7 days. Rengalin was administered in 73 patients receiving 2 tablets 3 times daily for initial three days, and half reduced doses--for the subsequent four days; codelac was administered in 70 patients who were given 1 tablet 3 times daily for the entire treatment period (7 days). Primary efficacy endpoints were time to cough resolution and reduction in the severity of the cough (scored using a Cough Severity Scale). One patient in Rengalin group and three patients in Codelac group were withdrawn from the study. The article presents treatment outcomes obtained for 139 participants who completed the study in accordance with the protocol (Per Protokol-analysis). The data analysis was based on a non-inferiority (or comparability) statistical design for efficacy endpoints. RESULTS: The antitussive effect of rengalin was significantly comparable (p < 0.025) with that of codelac; the time to complete resolution of cough (both daytime and nocturnal) was 7.2 ± 1.0 days (versus 7.0 ± 1.1 in the group of codelac). Rengalin's efficacy was evidenced by a sufficiently reduced cough severity in the initial few days after treatment onset. As a result of the entire 7-day treatment, the severity score was reduced by 3.1 ± 09 (versus 3.1 ± 1.0 in the group of codelac; p < 0.05), totaling 0.2 ± 0.5 point in both groups at the end of the administration period. The frequent non-productive/dry cough was fully resolved in 76% of patients. All the participants in Rengalin group achieved either convalescent outcomes or significant improvement; none of the patients developed secondary bacterial complications. Positive changes in the patients' state over the week were finally confirmed by evaluating the total quality of life scores, including physical and mental component scores (SF-36 questionnaire), and total sleep quality scores, which were comparative between patients treated with rengalin and codelac (p < 0.025). At the end of the administration period, the effect of rengalin was rated by the physician investigators as 'pronounced'. The Clinical Global Impression Scale-Efficacy Indices (CGI-EI) in the groups of rengalin and codelac were comparable, equating a score of 3.7 ± 0.5 (p < 0.025). The safety outcomes of rengalin treatment were assessed across all 143 randomized patients. The drug's high safety profile was confirmed by the absence of adverse events that could be reliably related to the study treatment, and by monitoring of laboratory variables. Rengalin demonstrated good tolerability and favorable compatibility with other medications for URIs with concomitant pathology. The patients showed 100% treatment compliance. CONCLUSIONS: Rengalin is a new efficacious and safe drug indicated for the treatment of URI-induced cough. The severity of daytime and nocturnal cough begins to decrease as soon as on the first day after rengalin administration, with severity reduction observed throughout the whole treatment period. At the completion of the 7-day administration, cough severity is reduced by almost 100% and its changes are comparable with the outcomes of treatment with codelac. By targeting various cough reflex mediators, rengalin enables achieving an antitussive effect in the early days after URI onset (in dry, irritative cough episodes), and a protussive effect at later points of treatment. Rengalin promotes resolution of URI-induced cough without development of secondary bacterial complications.

[Easyhalers in practice for treating patients with asthma].

A comparative investigation was conducted to study the therapeutic effect of using two powder inhalers (the new-generation device--an easyhaler as well as an aerolyser inhaler) in daily practice for treating patients with moderate asthma. It showed the pharmacological equivalence, efficiency, and safety of applying a combination of the easyhalers budesonide and formoterol, as well as the simplicity and convenience to use the inhalers of this type.

[Effect of prednisolon on trachea smooth muscle of normal rats and rats with fibrosing alveolitis].

Effect of prednisolone on isolated preparations of trachea of normal rats and rats with fibrosing alveolitis was studied. Prednisolone at a concentration of 0.4 microg/l decreased responses of smooth muscle on stimulation of preganglionar nerve fibers at trachea areas with intramural ganglia in rats with acute alveolitis by 48%, while in normal rats--by 19% of control. In trachea preparations without ganglia, prednisolone at a dose of 10 microg/l decreased responses of muscle to the nerve fiber stimulation by 21.3%. The higher prednisolone doses were less efficient: 0.1-10 microg/l glucocorticoid practically did not affect the smooth muscle responses produced by stimulation of muscle cells. In rats with fibrosing alveolitis, 10 microg/l prednisolone restored the smooth muscle responses to control values in preparations of trachea with intramural ganglia. After the prednisolone treatment, amplitude of the rat trachea muscle contraction in response to the nerve fiber electric stimulation did not differ statistically significantly from control and 0.1-10 microg/l prednisolone did not change the response value. The conclusion is made that prednisolone affected the diseased rats more efficiently than the healthy animals. The character of the glucocorticoid effect depends on the presence of intramural ganglia in the trachea wall.

[Endobronchial biopsy in the diagnosis of pulmonary sarcoidosis].

Bronchofiberscopy (BFS) with endobronchial biopsy (EBB) was performed in 66 patients with pulmonary sarcoidosis (PS). Transbronchial biopsy (TBB) was made in 49 patients from this group to compare the diagnostic value of EBB and TBB. The normal endoscopic picture was observed in 19.6% of patients. Bronchial mucosal hypervascularization and thickening were found in 25.7% of cases; the signs of enlarged bronchopulmonary lymph nodes were detected in 13.6%; catarrhal endobronchitis in 10.6%, and tuberosity changes in 4.5%. Epithelioid granulomas in the bronchial mucosa were identified in 37.8% of cases (30.75 and 39.6% in the intact and abnormal mucosa, respectively). The diagnostic value of TBB was 65.3%. EBB could reveal epithelioid-cell granulomas in 4 of the 17 patients with negative TBB. The findings suggest that BFS with EBB should be included as a necessary diagnostic method for the examination of patients with PS.

[Early diagnosis of pulmonary hemodynamic disorders in patients with pulmonary sarcoidosis].

A hundred and eleven patients with pulmonary sarcoidosis (PS) were examined to detect early impairments of pulmonary hemodynamics and myocardial function. A package of examinations included Doppler echocardiography at rest and with the Valsalva test, as well as electrocardiography and myocardial scintigraphy. In patients with early PS, right ventricular diastolic dysfunction is shown to be preceded by systolic dysfunction, as manifested itself in the altered ratio of different phases of right ventricular filling. As a method for early diagnosis of latent hypertension, the authors propose to use the Valsalva test to create a short-term volume overload of the right cardiac cavities. The study has indicated that left cardiac dilatation, decreased ejection fraction, left ventricular diastolic dysfunction, and the presence of large focal portions of fibrosis in the ventricular myocardium, interventricular septum, and papillary muscles can be considered to be early Doppler echocardiographic signs of sarcoidosis of the heart in patients with PS.

[Monitoring and treatment of severe bronchial ashma in adults: results of national multicenter trial NABAT].

AIM: To study quality of monitoring, features of a course and therapy of severe bronchial asthma (BA) in Russia. MATERIALS AND METHODS: The trial recruited 378 patients with severe bronchial asthma (SBA) in 7 cities of Russia. Each center participating in the study filled in individual case sheets recording demographic, clinical, monitoring, pharmacotherapeutic data. A special focus was on factors influencing the disease course. The chi-square and Mann-Witney criteria were used. RESULTS: It was found that current recommendations of BA patients' management are not used in full. Most of the patients do not receive adequate therapy. Phenotypes of uncontrolled course of severe BA are prevalent. The key role of adequate management of severe BA patients in control of the disease is shown. CONCLUSION: Wider use of updated recommendations on therapy and monitoring of BA with special focus on patients with uncontrolled course of the disease is urgent. Fulfilment of all the components of management of a patient with bronchial asthma recommended by GINA including the patient education and control over the disease triggers contribute much to effective treatment and control over BA.

[Weight-reducing diet therapy in the combined treatment of pulmonary sarcoidosis]. / Razgruzochno-dieticheskaia terapiia v kompleksnom lechenii sarkoidoza legkikh.

We have studied the effect of therapeutic fasting in 76 patients with pulmonary sarcoidosis (28, 45 and 3 patients with stage I, II and III, respectively). Fifty-two patients with PS stage I, II and minimal clinical symptoms received fasting alone. Twenty-four patients with PS stage II, III and frequent recurrences received combined treatment (fasting and oral corticosteroids). The efficacy of the treatment was evaluated by clinical symptoms, X-ray picture, pulmonary capillary blood flow and immunological parameters. We have found that therapeutic fasting reduced clinical symptoms in 85% of the patients, improved x-ray picture in 62% of the patients. Positive trend was also registered in immunological parameters. Therapeutic fasting produced maximal positive effect in patients with PS stage I, II and duration of the disease less than 1 year. Patients with PS stage II, III and the disease duration more than 1 year should be treated with fasting in combination with corticosteroids.

[Steroid hormone and trace element content of the blood in patients with disseminated processes of the lungs]. / Soderzhanie steroidnykh gormonov i mikroélementov v krovi bol'nykh s disseminirovannymi protsessami v legkikh.

Blood testosterone, estradiol, hydrocortisone, iron, zinc, and copper levels in males and female patients with lung sarcoidosis, idiopathic fibrosing alveolitis and histiocytosis X were studied. The female patients were in the menopause. A significant decrease in the levels of testosterone and zinc and an increase in the levels of estradiol and copper were revealed in the patients with alveolitis and histiocytosis X. In the patients with lung sarcoidosis a significant decrease in the content of zinc and an increase in the contents of estradiol and copper were stated. There was a relationship between the magnitude of the changes in hormone and trace element levels and the respiratory failure severity.

[Disseminated processes in the lungs--a current problem of modern pulmonology]. / Disseminirovannye protsessy v legkikh--aktual'naia problema sovremennoi pul'monologii.

A total of 453 patients with pulmonary disseminations were investigated. A clinico-statistical study of 16,000 adults estimated at 93.7 per 100,000 the prevalence of disseminated pulmonary conditions among the adult population. The referral and clinical diagnoses coincided in 17.4% of cases only, while the time between the emergence of the first symptoms and the final diagnosis averaged 21 +/- 3.3 months. The most valuable diagnostic signs were identified using the association criterion. They were: dyspnea, labored inspiration, hemoptysis, crepitation, spontaneous pneumothorax, roentgenologic evidence of raised diaphragmatic vaults and enlarged mediastinum lymph nodes, as well as certain neutrophil and lymphocyte levels in lavage fluid (Chuprov's coefficient between 0.32 and 0.42). Major management principles are developed with reference to stages of fibrosing alveolitis and granulomatosis.

[Total pulmonary lavage in the treatment of alveolar proteinosis]. / Total'nyi lavazh legkikh v lechenii al'veoliarnogo proteinoza.

Total pulmonary lavage through a two-lumen intubation tube is an effective method for therapy of alveolar proteinosis ensuring the removal of alveolar proteopexy and improving respiratory function.

[Clinico-functional characteristics of idiopathic fibrosing alveolitis (Hamman-Rich syndrome)]. / Kliniko-funktsional'nye osobennosti idiopaticheskogo fibroziruiushchego al'veolita (bolezn' Khammena-Richa).

The clinical and functional features of idiopathic fibrosing alveolitis (IFA) were analyzed in 31 patients. In 24 patients, the diagnosis was confirmed by histological study of the pulmonary tissue obtained by means of open lung biopsy or at autopsy. Progressive dyspnea was the earliest clinical symptom of IFA. High temperature, weight loss, cyanosis and other symptoms were characteristic of an acute disease course. Crepitation was the most characteristic symptom as far as the objective data are concerned. Detailed examination of respiratory function with the use of spirography, general plethysmography, forced oscillation technique, study of the diffuse capacity of the lungs and blood gases, and other methods showed that the most characteristic functional features of pulmonary respiration in IFA involved a decrease in the static pulmonary volumes, an increase in elastic pulmonary resistance, normal patency of the large and medium bronchi, and a diminution of the diffuse capacity of the lungs during respiratory arrest, as well as that of the diffuse capacity of the alveolocapillary membrane. The data obtained indicate that today one can discuss only the most characteristic rather than the pathognomonic clinical and functional symptoms of IFA.