A review of national guidelines for management of COPD in Europe.

The quality of care can be improved by the development and implementation of evidence-based treatment guidelines. Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years. Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process. Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden. The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines. There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia. However, there are differences in the definitions of patient subgroups and other recommended treatments.

Thermovaccination - thermoheliox as a stimulator of the immune response. Kinetics of the synthesis of antibodies and C-reactive protein in coronavirus infection.

Clinical trials of thermoheliox application (inhalation with a high-temperature mixture of oxygen and helium, 90 °C) in the treatment of the acute phase of coronavirus infection were conducted. Dynamics of disease development in infected patients (PCR test for the virus) and, dynamics of changes in blood concentration of C-reactive protein, immunoglobulin M, specific immunoglobulin G were studied. High efficiency of thermoheliox in releasing the organism from the virus and stimulating the immune response (thermovaccination effect) was shown. The kinetic model of the process is proposed and analyzed.

Chemical kinetics of the development of coronaviral infection in the human body: Critical conditions, toxicity mechanisms, "thermoheliox", and "thermovaccination".

Kinetic modeling of the behavior of complex chemical and biochemical systems is an effective approach to study of the mechanisms of the process. A kinetic model of coronaviral infection development with a description of the dynamic behavior of the main variables, including the concentration of viral particles, affected cells, and pathogenic microflora, is proposed. Changes in the concentration of hydrogen ions in the lungs and the pH -dependence of carbonic anhydrase activity (a key breathing enzyme) are critical. A significant result is the demonstration of an acute bifurcation transition that determines life or system collapse. This transition is connected with exponential growth of concentrations of the process participants and with functioning of the key enzyme carbonic anhydrase in development of toxic effects. Physical and chemical interpretations of the therapeutic effects of the body temperature rise and the potential therapeutic effect of "thermoheliox" (respiration with a thermolized mixture of helium and oxygen) are given. The phenomenon of "thermovaccination" is predicted, which involves stimulation of the immune response by "thermoheliox".

Safety and tolerability of indacaterol in asthma: a randomized, placebo-controlled 28-day study.

The safety and tolerability of indacaterol, a novel once-daily beta(2)-agonist bronchodilator with a fast onset of action, were assessed in 156 asthma patients in a multicentre, randomized, double-blind, placebo-controlled study. Patients received indacaterol 200, 400 or 600 microg or placebo once daily for 28 days. Adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, spirometry and physical examinations were monitored. Indacaterol pharmacokinetics were assessed. There was no evidence of dose-related increases in AE incidence or clinically significant hypokalaemia or hyperglycaemia in indacaterol-treated patients. Mean pulse rate changes were minor in any group, with maximum 1-h post-dose changes from baseline of -3.7, -3.3 and -2.2 bpm for indacaterol 200, 400 and 600 microg, respectively, and -2.9 bpm for placebo. Mean QTc interval was similar between groups; change from baseline >60 ms occurred in only two patients. Mean FEV(1) increased after the first indacaterol dose; baseline-adjusted pre-dose (trough) values remained >or=166 mL higher than placebo at all subsequent visits, supporting a 24-h bronchodilator effect. Pre-dose (but not post-dose) serum indacaterol concentrations indicated a slight trend for accumulation. Once-daily indacaterol 200-600 microg has a favourable therapeutic index. It is well tolerated, and is not associated with any adverse cardiac or metabolic effects, while providing effective 24-h bronchodilation.

Aspirin compared with acetaminophen in the treatment of fever and other symptoms of upper respiratory tract infection in adults: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, single-dose, 6-hour dose-ranging study.

BACKGROUND: Aspirin (acetylsalicylic acid) and acetaminophen (paracetamol) are frequently used to treat fever and other symptoms of upper respiratory tract infection (URTI). Both are available over the counter for use at the standard recommended doses of 500 and 1000 mg per single use. OBJECTIVE: This study investigated the efficacy, safety profiles, and tolerability of aspirin 500 and 1000 mg and acetaminophen 500 and 1000 mg compared with placebo in adult patients with acute febrile URTI of suspected viral origin. METHODS: This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group trial conducted in Ukraine and Russia. Patients with URTI and acute fever of > or =38.5 degrees C received a single dose of aspirin 500 or 1000 mg, acetaminophen 500 or 1000 mg, or matching placebo. Oral body temperature was measured in the clinic at specified time points up to 6 hours after dosing. The intensity of other symptoms of URTI was rated by patients at baseline and at 2, 4, and 6 hours after dosing (scale from 0 = none to 10 = severe). The primary efficacy measure was the AUC for the change in orally measured body temperature from the time of treatment (baseline) to 4 hours after dosing. Secondary outcome measures included the change in body temperature from baseline to specified time points between 0.5 and 6 hours after dosing, the difference between baseline and the lowest measured body temperature, the time to the lowest measured body temperature, and the intensity of other symptoms of URTI (ie, headache, sinus sensitivity to percussion, sore throat, achiness, and feverish discomfort). Tolerability was monitored by recording of adverse events. RESULTS: Three hundred ninety-two patients were enrolled (78 in both aspirin groups, 79 in both acetaminophen groups, 78 in the placebo group). Demographic and baseline characteristics were comparable in the 5 groups; 51% of patients were male, with a mean age of 37.4 years and a mean body weight of 74.3 kg. The AUC values for the change in body temperature 0 to 4 hours after dosing were 3.18 (95% CI, 2.78-3.57) for aspirin 500 mg, 4.26 (95% CI, 3.84-4.68) for aspirin 1000 mg, 3.13 (95% CI, 2.77-3.49) for acetaminophen 500 mg, 4.11 (95% CI, 3.73-4.49) for acetaminophen 1000 mg, and 0.76 (95% CI, 0.38-1.13) for placebo. In terms of the primary efficacy variable, all active treatments were significantly superior to placebo (P < 0.001, 1-sided t test), with no significant differences between them. Reductions in body temperature were significantly greater with the 1000-mg doses of both active treatments compared with the 500-mg doses (P< 0.001, 1-sided t test). The mean maximum temperature reductions were 1.32 degrees C, 1.25 degrees C, 1.67 degrees C,1.71 degrees C, and 0.63 degrees C in the respective treatment groups. Significant reductions were seen in the mean intensity of headache, achiness, and feverish discomfort with all active treatments at most time points (P < 0.001), but not in sinus sensitivity to percussion or sore throat. All treatments were equally well tolerated, and no clinically significant adverse events occurred. CONCLUSIONS: In this single-dose study, aspirin 500 and 1000 mg and acetaminophen 500 and 1000 mg were more effective against fever and other symptoms of URTI than placebo. Both active treatments showed dose-related efficacy, and there was no significant difference between equal doses of the 2 agents. Safety profiles and tolerability were also comparable between treatments.

Formoterol delivered via a new multi-dose dry powder inhaler (Certihaler) is as effective and well tolerated as the formoterol dry powder inhaler (Aerolizer) in children with persistent asthma.

The Certihaler is a new multi-dose dry powder inhaler for the delivery of formoterol (Foradil), a long-acting beta(2)-agonist. This dose-ranging study compared the efficacy and safety of formoterol 5, 10, 15 and 30 microg and placebo administered via the Certihaler or formoterol 12 microg via a single-dose dry powder inhaler (Aerolizer) in children with persistent asthma. This was a randomized, placebo-controlled, double-blind, double-dummy, incomplete block crossover, dose-finding and pharmacokinetic study. Children (5-12 years, n = 77) received four of the active treatments twice weekly (BID) for 1 week separated by 1-week single-blind washouts. The primary efficacy variable was 12-h AUC of FEV(1) after 1 week's treatment. Secondary variables included serial 12-h FEV(1). A subset of patients (n = 37) participated in a pharmacokinetic analysis. All formoterol doses resulted in significant increases in 12-h AUC of FEV(1) compared with placebo, and there was no difference between active treatments. The onset of action of formoterol was <3 min for all active treatments. Doses of formoterol > or =10 microg via the Certihaler increased FEV(1) significantly for up to 12 h compared with placebo. The 5 microcg dose via the Certihaler and 12 microg dose via the Aerolizer had a significant effect up to 8 and 7 h post-dose, respectively. Urinary excretion of formoterol via the Certihaler increased in a dose-proportional manner. All formoterol doses were well tolerated, but some patients experienced tremor at the 15 and 30 microg doses. Despite the lack of significant differences between the active doses in the overall bronchodilation, formoterol 10 microg BID via the Certihaler was the dose that provided the best balance between efficacy and tolerability: its duration of action was sustained over 12 h, contrary to that the lower dose (5 microg BID), whereas its tolerability, especially with regard to tremor, was better than the higher doses (15 and 30 microg BID). Overall, Certihaler 10 microg BID was not significantly different from formoterol 12 microg BID via Aerolizer.

Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis.

In order to clarify the possible role of N-acetylcysteine (NAC) in the treatment of patients with chronic bronchitis and chronic obstructive pulmonary disease (COPD), we have carried out a meta-analysis testing the available evidence that NAC treatment may be effective in preventing exacerbations of chronic bronchitis or COPD and evaluating whether there is a substantial difference between the responses induced by low (≤ 600 mg per day) and high (> 600 mg per day) doses of NAC. The results of the present meta-analysis (13 studies, 4155 COPD patients, NAC n = 1933; placebo or controls n = 2222) showed that patients treated with NAC had significantly and consistently fewer exacerbations of chronic bronchitis or COPD (relative risk 0.75, 95% CI 0.66-0.84; p < 0.01), although this protective effect was more apparent in patients without evidence of airway obstruction. However, high doses of NAC were also effective in patients suffering from COPD diagnosed using spirometric criteria (relative risk 0.75, 95% CI 0.68-0.82; p = 0.04). NAC was well tolerated and the risk of adverse reactions was not dose-dependent (low doses relative risk 0.93, 95% CI 0.89-0.97; p = 0.40; high doses relative risk 1.11, 95% CI 0.89-1.39; p = 0.58). The strong signal that comes from this meta-analysis leads us to state that if a patient suffering from chronic bronchitis presents a documented airway obstruction, NAC should be administered at a dose of ≥ 1200 mg per day to prevent exacerbations, while if a patient suffers from chronic bronchitis, but is without airway obstruction, a regular treatment of 600 mg per day seems to be sufficient.

Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation.

BACKGROUND: Estimation suggests that at least 4 million people die, annually, as a result of chronic respiratory disease (CRD). The Global Alliance against Chronic Respiratory Diseases (GARD) was formed following a mandate from the World Health Assembly to address this serious and growing health problem. OBJECTIVES: To investigate the prevalence of CRD in Russian symptomatic patients and to evaluate the frequency of major risk factors for CRD in Russia. METHODS: A cross-sectional, population-based epidemiological study using the GARD questionnaire on adults from 12 regions of the Russian Federation. Common respiratory symptoms and risk factors were recorded. Spirometry was performed in respondents with suspected CRD. Allergic rhinitis (AR) and chronic bronchitis (CB) were defined by the presence of related symptoms according to the Allergic Rhinitis and its Impact on Asthma and the Global Initiative for Obstructive Lung Disease guidelines; asthma was defined based on disease symptoms; chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume per 1 second/forced vital capacity ratio <0.7 in symptomatic patients, following the Global Initiative for Obstructive Lung Disease guidelines. RESULTS: The number of questionnaires completed was 7,164 (mean age 43.4 years; 57.2% female). The prevalence of asthma symptoms was 25.7%, AR 18.2%, and CB 8.6%. Based on patient self-reported diagnosis, 6.9% had asthma, 6.5% AR, and 22.2% CB. The prevalence of COPD based on spirometry in patients with respiratory symptoms was estimated as 21.8%. CONCLUSION: The prevalence of respiratory diseases and risk factors was high in Russia when compared to available data. For bronchial asthma and AR, the prevalence for related symptoms was higher than self-reported previous diagnosis.

Tobramycin inhalation powder manufactured by improved process in cystic fibrosis: the randomized EDIT trial.

BACKGROUND: Tobramycin inhalation powder (TIP) was reported to be effective in two Phase III studies in patients with cystic fibrosis (CF) chronically infected with Pseudomonas aeruginosa (Pa). The EDIT study evaluated the efficacy and safety of TIP manufactured by an improved process in CF subjects aged 6-21 years. METHODS: CF patients with a forced expiratory volume in 1 second (FEV1) ≥25% to ≤80% predicted, positive Pa cultures and inhaled antipseudomonal therapy naïve (or at least for past 4 months) were enrolled into this double-blind, multicenter trial. Patients were randomized to receive TIP or placebo (1:1) twice daily for one treatment cycle (28.5 days on drug, 28 days off drug). The primary endpoint was relative change in FEV1 percentage predicted from baseline to day 29. A pre-specified sensitivity analysis evaluated absolute change in FEV1% predicted. Other endpoints included Pa sputum density and safety. RESULTS: A total of 62 patients out of a target of 100 (mean age 12.9 years, baseline FEV1 59.2% predicted, Pa sputum density 7.4 log10 colony forming units [CFU] per gram) were randomized. Mean treatment differences (TIP - placebo) were 5.9% (p=0.148) and 4.4% (p<0.05) for relative and absolute change in FEV1% predicted respectively. TIP significantly reduced Pa sputum density by -1.2 log10 CFU (p=0.002). Treatment with TIP was well tolerated. CONCLUSIONS: Relative change in FEV1% predicted with TIP treatment was in the expected range based on the literature, but did not reach statistical significance versus placebo. Placebo control and use of treatment naïve patients led to significant recruitment challenges and an underpowered study with consequent impact on the generated data. However, significant improvements in other outcomes including absolute change in FEV1% predicted and reduction in Pa sputum density indicate that TIP is efficacious and well tolerated in CF patients. CLINICALTRIALS.GOV IDENTIFIER: NCT00918957.