Clinical course of COPD in patients with Arg16Gly (rs1042713) polymorphism of ADRB2 gene.

The ADBR2 gene has been studied for its possible relationship with the development and clinical course of chronic obstructive pulmonary disease (COPD), including response to beta-2 agonists, with existing data being contentious on the subject. So, the purpose of this study was to look into the potential impact of the arginine-16-glycine (Arg16Gly) polymorphism on the clinical course and drug utilization in COPD patients. Data show that patients with Arg16Arg have a lower number of hospital admissions for exacerbations (p=0.048), but only in the total number of exacerbations, including those treated out-patients (p=0.086). Each glycine (Gly) copy was associated with a higher number of exacerbations (OR: 0.25; 95% CI: 0.00-055; p=0.048). The number of exacerbations after LABA/LAMA treatment was similar across groups, indicating that all ADRB2 variants responded well to the treatment. Furthermore, there were no statistically significant differences in mMRC and CAT values across all study visits. Interestingly, groups differed in their use of antibiotics (AB) at all visits, with Arg16Arg being associated with the least amount of AB use. There was also a link discovered between clycine copies and increased use of glucocorticoids. As a result, Arg16Gly is involved in the clinical course of COPD as well as the utilization of drug groups. Based on the findings, we can speculate that the cross-talk between the ADRB2 gene and the corticosteroid receptor is altered in patients with the Gly16Gly genotype.

Novel Budesonide Suppository and Standard Budesonide Rectal Foam Induce High Rates of Clinical Remission and Mucosal Healing in Active Ulcerative Proctitis: a Randomised, Controlled, Non-inferiority Trial.

BACKGROUND AND AIMS: Proctitis is the least extensive type of ulcerative colitis, for which rectal therapy is rarely studied and is underused. This study evaluated the efficacy, safety, and patient's preference of a novel formulation of budesonide suppository 4 mg, compared with a commercially available budesonide rectal foam 2 mg, for the treatment of mild to moderate ulcerative proctitis. METHODS: This was a randomised, double-blind, double-dummy, active-controlled trial. Patients were randomly assigned in a 1:1 ratio to receive either budesonide 4 mg suppository or budesonide 2 mg foam once daily for 8 weeks. The co-primary endpoints were changes from baseline to Week 8 in clinical symptoms, for which clinical remission was defined as having a modified Ulcerative Colitis-Disease Activity Index [UC-DAI] subscore for stool frequency of 0 or 1 and a subscore for rectal bleeding of 0, and mucosal healing, defined as having a modified UC-DAI subscore for mucosal appearance of 0 or 1. Using a more stringent criterion, we additionally analysed deepened mucosal healing, which was defined as a mucosal appearance subscore of 0. Patient's preference, physician's global assessment, and quality of life were also assessed and analysed. RESULTS: Overall, 286 and 291 patients were included in the 4 mg suppository and 2 mg foam groups, respectively. Budesonide 4 mg suppository met the prespecified criterion for non-inferiority to the 2 mg foam in both co-primary endpoints of clinical remission and mucosal healing. Secondary endpoints consistently supported the non-inferiority of the suppository. Trends in favour of the suppository were observed in the subgroup of mesalazine non-responders. More patients reported a preference for the suppository over rectal foam. CONCLUSIONS: In patients with ulcerative proctitis, budesonide 4 mg suppository was non-inferior to budesonide 2 mg foam in efficacy, and both were safe and well tolerated.

EFFICACY OF COMBINATION OF TIOTROPIUM/OLODATEROL IN PATIENTS WITH COPD IN REAL CLINICAL PRACTICE.

OBJECTIVE: The aim: Show the efficacy of the Tiotropium / olodaterol combination in real clinical practice. PATIENTS AND METHODS: Materials and methods: 100 patients with the diagnosis of COPD were included onto the study during the period of 2019-2020, an average age was 64.09±1.94 years, 66 were men (66 %) and 34 were women (34 %). There were 68 % of smokers with the average smoking experience of 24.44±4.84 pack-years. Average COPD duration was 9.35±2.42 years. There were 3 visits in the study - visit 1 (baseline), visit 2 (4-6 weeks) visit 3 (1 year). Source documentation was assessed at visit 1 and visit 3 for amount of exacerbations, antibiotic, glucocorticosteroid, methylxanthines use; mMRC and CAT were assessed at all visits. RESULTS: Results: Combined therapy with tiotropium/olodaterol improves clinical course of COPD, which is characterized by the significant decreased of the amount of exacerbations (2.63±0.29 to 1.63±0.21) and hospital admissions (1.2±0.2 tо 0.37±0.11). Improvement of symptoms and amount of exacerbation leads to much less use of antibiotics and glucocorticosteroids. A part of patients that used antibiotics decreased from 86±6.9 % to 67±9.3 %, amount of antibiotic courses from 1.37±0.17 tо 0.88±0.15, duration of treatment with antibiotics from 10.85±1.53 to 6.12±1.17 days. Part of the patients that used glucocorticosteroids decreased from 50±9.9 % tо 30±9.1 %, duration of treatment with antibiotics reduced from 3.97±1.06 tо 1.86±0.91 days. There also was a tendency towards a lesser used of methylxanthines. Combined therapy with tiotropium/olodaterol significantly decreased symptoms of COPD according to the mMRC (2.3±0.14 to 1.87±0.15) and САТ (23.28±1.71 to 15.77±1.58). CONCLUSION: Conclusions: Tiotropium/olodaterol combination showed its efficacy in real clinical practice. There was significant reduction in amount of exacerbation and antibiotic, gluco¬corticosteroid use during the study, which was also accompanied by the reduction is symptoms.

Exacerbation of chronic obstructive pulmonary diseases as a risk factor of the skeletal muscle dysfunction.

BACKGROUND: Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) contributes to increased systemic inflammation, oxidative stress, hypoxia, hypercapnia and other risk factors of the skeletal muscle dysfunction. AIMS AND OBJECTIVES: This study aimed to determine whether the frequency of the COPD exacerbations promotes deterioration of the skeletal muscle dysfunction in patients with COPD and to figure out which characteristics of the muscles will reflect this changes. MATERIALS AND METHODS: We examined 98 male COPD patients, mean age 60.4±11.2 years, GOLD groups B, C, D. To assess the degree of skeletal muscle dysfunction we used hand-grip strength, 6-minute walk test, bioelectrical impedance analysis. Quality of life was evaluated using St. George's respiratory questionnaire (SGRQ). RESULTS: Increase in the frequency of COPD exacerbations was associated with the decrease in the 6-minute walk test distance (r= -0.214, P = 0.034) and with the rise of sarcopenia according to the results of bioelectrical impedance analysis - lower fat-free mass index (r = -0.201, P = 0.047). Frequency of COPD exacerbations had a weak correlation with the degree of the activity limitation component of SGRQ (r = 0.436, P < 0.001). CONCLUSIONS: COPD exacerbation plays an important role in progression of the skeletal muscle dysfunction. It decreases endurance of the skeletal muscles, diminishing their size, which manifests itself in reduced exercise tolerance. Increase in the frequency of the COPD exacerbations also worsens all components of the life quality.

Budesonide Suppositories Are Effective and Safe for Treating Acute Ulcerative Proctitis.

BACKGROUND & AIMS: Although proctitis is the most limited form of ulcerative colitis, it causes unpleasant symptoms. Topical mesalamine, the standard treatment, is not always effective. We conducted a randomized phase 2 trial to determine the efficacy and safety of 2 doses of a budesonide suppository vs mesalamine suppositories vs combined budesonide and mesalamine suppositories for proctitis. METHODS: We performed a prospective, double-blind, double-dummy, multicenter trial in 337 patients with active proctitis to compare the efficacies of 4 different suppository treatments. Patients were randomly assigned to groups given 2 mg budesonide suppositories (2 mg BUS; n = 89 patients), 4 mg BUS (n = 79), 1 g mesalamine suppositories (1 g MES; n = 81), or the combination of 2 mg BUS and 1 g MES (n = 88). The study was performed from November 2013 through July 2015 at 36 study sites in Europe and Russia. The primary end point was the time to resolution of clinical symptoms, defined as the first of 3 consecutive days with a score of 0 for rectal bleeding and stool frequency. RESULTS: The mean time to resolution of symptoms in the 4 mg BUS (29.8 days) and combination of 2 mg BUS and 1 g MES (29.3 days) groups resembled that of the standard 1 g MES treatment (29.2 days), but was significantly longer in the 2 mg BUS group (35.5 days). Furthermore, proportions of patients with deep, clinical, and endoscopic remission, as well as mucosal healing, were similar among the 1 g MES, 4 mg BUS, and combination therapy groups, but significantly lower in the group that received 2 mg BUS. No safety signals were observed, and the patients' treatment acceptance was high (67%-85% of patients). CONCLUSIONS: In a multicenter randomized trial, we found that the efficacy and safety of 4 mg BUS in treatment of active proctitis did not differ significantly from those of 1 g MES. Budesonide suppositories offer an alternative therapy to mesalamine for topical treatment of proctitis. Clinicaltrialsregister.eu no: 2012-003362-41.