Rate Of Chronic Obstructive Pulmonary Disease Exacerbations Research Articles

The Association Between Rate and Severity of Exacerbations in Chronic Obstructive Pulmonary Disease: An Application of a Joint Frailty-Logistic Model.

Exacerbations are a hallmark of chronic obstructive pulmonary disease (COPD). Evidence suggests the presence of substantial between-individual variability (heterogeneity) in exacerbation rates. The question of whether individuals vary in their tendency towards experiencing severe (versus mild) exacerbations, or whether there is an association between exacerbation rate and severity, has not yet been studied. We used data from the MACRO Study, a 1-year randomized trial of the use of azithromycin for prevention of COPD exacerbations (United States and Canada, 2006–2010; n = 1,107, mean age = 65.2 years, 59.1% male). A parametric frailty model was combined with a logistic regression model, with bivariate random effects capturing heterogeneity in rate and severity. The average rate of exacerbation was 1.53 episodes/year, with 95% of subjects having a model-estimated rate of 0.47–4.22 episodes/year. The overall ratio of severe exacerbations to total exacerbations was 0.22, with 95% of subjects having a model-estimated ratio of 0.04–0.60. We did not confirm an association between exacerbation rate and severity (P = 0.099). A unified model, implemented in standard software, could estimate joint heterogeneity in COPD exacerbation rate and severity and can have applications in similar contexts where inference on event time and intensity is considered. We provide SAS code (SAS Institute, Inc., Cary, North Carolina) and a simulated data set to facilitate further uses of this method.

Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial

Few data are available for the efficacy of "triple therapy" with two long-acting bronchodilators and an inhaled corticosteroid in chronic obstructive pulmonary disease (COPD). We designed this study to assess efficacy of single-inhaler combination of an extra fine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) in COPD compared with beclometasone dipropionate and formoterol fumarate (BDP/FF) treatment. TRILOGY was a randomised, parallel group, double-blind, active-controlled study done in 159 sites across 14 countries. The sites were a mixture of primary, secondary, and tertiary care providers, and specialist investigation units. Eligible patients with COPD had post-bronchodilator forced expiratory volume in 1 s (FEV1) of lower than 50%, one or more moderate-to-severe COPD exacerbation in the previous 12 months, COPD Assessment Test total score of 10 or more, and a Baseline Dyspnea Index focal score of 10 or less. Patients who met the inclusion and exclusion criteria at screening entered a 2-week open-label run-in period where they received beclometasone dipropionate (100 μg) and formoterol fumarate (6 μg) in two actuations twice daily. Patients were then randomly assigned (1:1) with an interactive response technology system to either continue BDP (100 μg) and FF (6 μg) or step-up to BDP (100 μg), FF (6 μg), and GB (12·5 μg) in two actuations twice daily for 52 weeks via pressurised metered-dose inhaler. The three co-primary endpoints were pre-dose FEV1, 2-h post-dose FEV1, and Transition Dyspnea Index (TDI) focal score, all measured at week 26 in the intention-to-treat population (all patients who were randomly assigned and received at least one dose of study drug and had at least one post-baseline efficacy assessment). Safety outcomes were measured in the safety population (all patients who were randomly assigned and received at least one dose of study drug). Secondary endpoints included moderate-to-severe COPD exacerbation rate over 52 weeks. This study is registered with ClinicalTrials.gov number NCT01917331. Between March 21, 2014, and Jan 14, 2016, 1368 patients received either BDP/FF/GB (n=687) or BDP/FF (n=681). At week 26, BDP/FF/GB improved pre-dose FEV1 by 0·081 L (95% CI 0·052-0·109; p<0·001) and 2-h post-dose FEV1 by 0·117 L (0·086-0·147; p<0·001) compared with BDP/FF. Mean TDI focal scores at week 26 were 1·71 for BDP/FF/GB and 1·50 for BDP/FF, with a difference of 0·21 (95% CI -0·08 to 0·51; p=0·160). Adjusted annual moderate-to-severe exacerbation frequencies were 0·41 for BDP/FF/GB and 0·53 for BDP/FF (rate ratio 0·77 [95% CI 0·65-0·92]; p=0·005), corresponding to a 23% reduction in exacerbations with BDP/FF/GB compared with BDP/FF. Adverse events were reported by 368 (54%) patients with BDP/FF/GB and 379 (56%) with BDP/FF. One serious treatment-related adverse event occurred (atrial fibrillation) in a patient in the BDP/FF/GB group. We provide evidence for the clinical benefits of stepping up patients with COPD from an inhaled corticosteroid/long-acting β2-agonist combination treatment to triple therapy using a single inhaler. Chiesi Farmaceutici SpA.

Pulmonary Rehabilitation: A Retrospective Study in Eastern North Carolina.

Pulmonary rehabilitation (PR) is an evidence-based measure to benefit chronic obstructive pulmonary disease (COPD) patients. Many patients have benefitted from our robust university hospital-based PR program. We have objectively assessed the benefit of our PR program for COPD patients in Eastern North Carolina. We used retrospective chart review to collect data from all the patients who completed PR from January 1, 2012 through December 31, 2013. Data collection included quality-of-life scores using short-form 36 (SF-36) and 6-minute walk distance (6MWD) to measure exercise capacity before and after PR. We also collected data on COPD exacerbation frequency 1 year before and 1 year after PR. The data were analyzed using the statistical software Statistical Package for the Social Sciences version 22.0. We analyzed data from 51 patients with 4 categories of COPD: mild (n = 2), moderate (n = 12), severe (n = 23), and very severe (n = 14). The PR program resulted in improvement in 6MWD of an average of 263.8 feet (P < .01) and a decrease in COPD exacerbation frequency by 0.3 events per year (P < .05). There were mixed results for quality-of-life scores. Our study was conducted at 1 center and thus involved a single COPD patient population with limited sample size. We did not follow patients long term to see whether the benefits were sustained. Our PR program resulted in a positive impact on exercise capacity, COPD exacerbation rate, and some aspects of quality of life.

Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD

BackgroundMost guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA–LAMA regimen in these patients is unclear.MethodsWe conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial. Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) once daily or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily. The primary outcome was the annual rate of all COPD exacerbations.ResultsA total of 1680 patients were assigned to the indacaterol–glycopyrronium group, and 1682 to the salmeterol–fluticasone group. Indacaterol–glycopyrronium showed not only noninferiority but also superiority to salmeterol–fluticasone in reducing the annual rate of all COPD exacerbations; the rate was 11% lower in the indacaterol–glycopyrronium group than in the salmeterol–fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95% confidence interval [CI], 0.83 to 0.96; P=0.003). The indacaterol–glycopyrronium group had a longer time to the first exacerbation than did the salmeterol–fluticasone group (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; hazard ratio, 0.84 [95% CI, 0.78 to 0.91], representing a 16% lower risk; P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol–glycopyrronium group than in the salmeterol–fluticasone group (0.98 vs. 1.19; rate ratio, 0.83; 95% CI, 0.75 to 0.91; P<0.001), and the time to the first moderate or severe exacerbation was longer in the indacaterol–glycopyrronium group than in the salmeterol–fluticasone group (hazard ratio, 0.78; 95% CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (hazard ratio, 0.81; 95% CI, 0.66 to 1.00; P=0.046). The effect of indacaterol–glycopyrronium versus salmeterol–fluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. The incidence of adverse events and deaths was similar in the two groups. The incidence of pneumonia was 3.2% in the indacaterol–glycopyrronium group and 4.8% in the salmeterol–fluticasone group (P=0.02).ConclusionsIndacaterol–glycopyrronium was more effective than salmeterol–fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year. (Funded by Novartis; FLAME ClinicalTrials.gov number, NCT01782326.)

Early response to inhaled bronchodilators and corticosteroids as a predictor of 12-month treatment responder status and COPD exacerbations.

BackgroundEarly treatment response markers, for example, improvement in forced expiratory volume in 1 second (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score, may help clinicians to better manage patients with chronic obstructive pulmonary disease (COPD). We investigated the prevalence of clinically important improvements in FEV1 and SGRQ scores after 2-month budesonide/formoterol or formoterol treatment and whether such improvements predict subsequent improvements and exacerbation rates.MethodsThis post hoc analysis is based on data from three double-blind, randomized studies in patients with moderate-to-very-severe COPD receiving twice-daily budesonide/formoterol or formoterol alone for 6 or 12 months. Prebronchodilator FEV1 and SGRQ total score were measured before treatment and at 2 and 12 months; COPD exacerbation rates were measured during months 2–12. Responders were defined by ≥100 mL improvement in prebronchodilator FEV1 and ≥4-point decrease in SGRQ total score.ResultsOverall, 2,331 and 1,799 patients were included in the 0–2- and 0–12-month responder analyses, respectively, and 2,360 patients in the 2–12-month exacerbation rate analysis. At 2 months, 35.1% of patients were FEV1 responders and 44.3% were SGRQ responders. The probability of response was significantly greater with budesonide/formoterol than with formoterol or placebo for both parameters. Two-month responders had a greater chance of 12-month response than 2-month nonresponders for both FEV1 (odds ratio, 5.57; 95% confidence interval, 4.14–7.50) and SGRQ (odds ratio, 3.87; 95% confidence interval, 2.83–5.31). Two-month response in FEV1 (P<0.001), but not SGRQ (P=0.11), was associated with greater reductions in exacerbation risk.ConclusionEarly FEV1 and SGRQ treatment responses relate to their changes at 12 months. FEV1 response, but not SGRQ response, at 2 months predicts the risk of a future COPD exacerbation in some, but not all patients. This is potentially useful in clinical practice, although more sensitive and specific markers of favorable treatment response are required.

Functional state of the diaphragm in patients with chronic obstructive pulmonary disease on long-term oxygen therapy

Purpose. To study the functional state of the diaphragm in patients with chronic obstructive pulmonary disease (COPD) complicated by chronic hypoxemia. Materials and methods. The study included 90 patients with COPD III–IV stages, group D (GOLD, 2015): 45 patients with chronic hypoxemia and 45 normoxemic patients. The following parameters were analyzed: spirometric level, oxygen saturation and arterial blood oxygen, breathlessness (by the Modified British Medical Research Council Questionnaire), rate of COPD exacerbations. Ultrasound examination of the diaphragm was conducted. Investigations were carried out twice: at baseline and after 12 months of observation. All patients with chronic hypoxemia were prescribed long-term oxygen therapy (LTOT). Results. The study of functional indicators in COPD patients revealed that the presence of hypoxemia was characterized, as compared with normoxemic patients, not only by more severe breathlessness and airflow limitation, but the alteration of diaphragmatic function. LTOT appointment in hypoxemic patients was accompanied in a year by changes in the functional state of the diaphragm (increase in relaxation rate of the diaphragm during quiet breathing) and a reduction in the number of COPD exacerbations. Conclusion. The shift in diaphragm function could mediate the positive impact of LTOT on COPD prognosis, including the number of COPD exacerbations in patients with hypoxemia.

History of pneumonia is a strong risk factor for chronic obstructive pulmonary disease (COPD) exacerbation in South Korea: the Epidemiologic review and Prospective Observation of COPD and Health in Korea (EPOCH) study.

In South Korea, chronic obstructive pulmonary disease (COPD) is one of the ten leading causes of death. COPD exacerbations are significantly associated with mortality in COPD patients. This study was conducted to investigate the epidemiology of COPD in South Korea, specifically the clinical characteristics of South Korean COPD patients, the COPD exacerbation rate and the risk factors associated with COPD exacerbations. This study covers a 2-year interval. One year was data collected retrospectively and the second year was prospectively obtained data. A total of 1,114 subjects were enrolled in the study. These subjects were observed for a period of 1 year from the enrollment, and a total of 920 subjects completed the study. A total of 1,357 COPD exacerbations occurred in 711 subjects (63.8%) out of the total of 1,114 subjects during the study period of 2 years. Multivariate logistic regression results showed that if patients had had a pneumonia before the retrospective year of analysis, they had a 18 times greater chance of having an exacerbation during the prospective year when other variables were controlled. Also, the subjects who had a history of two or more exacerbations during the retrospective year were approximately 6 times more likely to experience the COPD exacerbation compared to those who did not. This study examined the demographic and clinical characteristics of South Korean COPD patients and found that a history of pneumonia and two or more occurrences of exacerbation within 1 year was significantly associated with a higher rate of COPD exacerbation.

Air pollution and hospital admission in patients with chronic obstructive pulmonary disease in Tehran, Iran

Objective: There are many communities at risk by a series of air pollution episodes. Tehran is one of the most polluted cities in the world. The presence of one or more air pollutants with a certain concentration in a particular period of time can cause several adverse effects on human and animals’ well-being that can cause much morbidity. There are several pollutants in the air but some of them can cause severe adverse effects on the lungs and air ways.Methods: In this retrospective cross-sectional study 1958 patients with exacerbation of chronic obstructive pulmonary disease (COPD) who were admitted in the emergency department (ED) of Rasol Akram hospital between March 2004 and March 2006 entered the study. Data such as number of admissions, air pollution particles (CO, SO2, O3, NO2, PM10) according to available documents were analyzed.Results: From 1958 patients who enrolled in this study, 887 (53.5%) were male and 771 (46.5%) were female. According to statistical analysis, we could observe a significant correlation between the concentration of Co, PM10, So2 with ED admission rate of COPD exacerbation (P: 0.031, 0.008, and 0.001 respectively). The effect of PM10, So2 and Co was more significant respectively in logistic regression on ED admission.Conclusion: There was significant correction between concentrations of air pollutants with number of ED admission for COPD exacerbation.

Efficacy and tolerability of budesonide/formoterol added to tiotropium compared with tiotropium alone in patients with severe or very severe COPD: A randomized, multicentre study in East Asia.

Triple combination therapy with tiotropium plus budesonide/formoterol has improved lung function and reduced exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) in Western countries, but no such data exist for East Asian patients. This study aimed to evaluate the efficacy and tolerability of adding budesonide/formoterol to tiotropium compared with tiotropium alone in East Asian patients with severe/very severe COPD. This 12-week, randomized, parallel-group, multicentre, open-label study was conducted in East Asia. After a 14-day run-in period during which patients received tiotropium 18 μg once daily, patients were randomized to tiotropium (18 μg once daily) + budesonide/formoterol (160/4.5 μg 2 inhalations twice daily) or tiotropium alone (18 μg once daily). The primary endpoint was change from baseline in pre-dose forced expiratory volume in 1 s (FEV1 ) to the mean of values measured at Weeks 1, 6 and 12. Pre-dose FEV1 significantly increased from baseline with tiotropium plus budesonide/formoterol (n = 287) versus tiotropium alone (n = 291) (5.0% vs 0.6%; treatment difference: 4.4% (95% CI: 1.9-6.9), P = 0.0004). Triple therapy also reduced the COPD exacerbation rate by 40.7% (P = 0.0032) and prolonged time to first exacerbation (38.6% risk reduction, P = 0.0167) versus tiotropium alone and markedly improved health-related quality of life (HRQoL), measured using the St George's Respiratory Questionnaire. Incidence of adverse events was 26% for both groups. In East Asian patients with severe/very severe COPD, adding budesonide/formoterol to tiotropium was associated with significant improvements in FEV1 and HRQoL and lower COPD exacerbation rates. Treatment was generally well tolerated. NCT01397890 at Clinicaltrials.gov.

Efficacy and safety of once-daily glycopyrronium in predominantly Chinese patients with moderate-to-severe chronic obstructive pulmonary disease: the GLOW7 study [Corrigendum

BACKGROUND Glycopyrronium is a once-daily (od) long-acting muscarinic antagonist for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The GLOW7 study evaluated the efficacy and safety of od glycopyrronium 50 μg in predominantly Chinese patients with moderate-to-severe COPD. METHODS In this 26-week, multi-center, double-blind, placebo-controlled, parallel-group study, men and women ≥40 years with moderate-to-severe COPD were randomized to glycopyrronium 50 μg od or placebo (2:1). The primary objective was to confirm the significant improvement of trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment with glycopyrronium compared with placebo. Secondary objectives included the effect of glycopyrronium on health status (St George's Respiratory Questionnaire), breathlessness (Transition Dyspnea Index), other lung function parameters, rescue medication use, and COPD exacerbations. Safety and tolerability were also evaluated. RESULTS Of the 460 patients randomized, 459 were included in the full analysis set (glycopyrronium, n=306; placebo, n=154; mean age 64.7 years; mean post-bronchodilator FEV1: 50.8% predicted); 425 (92.4%) completed the study. At Week 12, glycopyrronium signifcantly improved trough FEV1 with a least square means treatment difference of 141 mL (95% confidence interval 111 mL, 171 mL; P<0.001) compared with placebo. The mean treatment effect of glycopyrronium was greater than the minimum clinically important difference versus placebo in both St George's Respiratory Questionnaire total score (-4.92; P<0.001) and Transition Dyspnea Index focal score (1.0; P<0.001) at week 26. Glycopyrronium reduced the risk of exacerbations in terms of time to first moderate or severe exacerbation by 28% (P=0.153) and rate of moderate or severe COPD exacerbation by 29% (P=0.119) compared with placebo. Incidence of death was 1.3% with glycopyrronium and 0% in placebo during the treatment period. Overall incidence of adverse events (glycopyrronium 43.6%; placebo 47.4%) and serious adverse events (glycopyrronium 5.6%; placebo 9.1%) were similar. CONCLUSION In predominantly Chinese patients with moderate-to-severe COPD, od glycopyrronium 50 μg significantly improved lung function, dyspnea, and health status compared with placebo. The safety and tolerability profile of glycopyrronium was comparable to placebo.

Economic efficacy of vaccination of patients with chronic obstructive pulmonary disease and coronary heart disease

The aim of this study was prospective evaluation of clinical and economic efficacy of vaccination with conjugate pneumococcal vaccine PCV13 in patients with chronic obstructive pulmonary disease (COPD) and with comorbidity of COPD and coronary heart disease (CHD) during two consecutive years. Methods. The study involved 306 male patients (mean age, 62.09 ± 9.22 yrs). Clinical and laboratory examination was performed in all patients. Dyspnea was assessed using MRC scale. Hospitalisation rate related to COPD exacerbation and number of pneumonia were analyzed. Patients were vaccinated with PCV13. The study was conducted in 2012–2014. Results. COPD exacerbation rate became 8 times lower and hospitalisation rate became 4 times lower after vaccination in patients with comorbidity of COPD and CHD. Healthcare cost saving was 64% in one year after vaccination and 70% in 1.5 years after vaccination. Healthcare cost saving in patients with comorbidity of COPD and CHD was 82.1% in two years. On contrary, effect of vaccination with PPV23 declined with time; the healthcare cost saving was 55% and 47% in 1 year and 1.5 years after vaccination, respectively. Conclusion. Vaccination of patients with COPD and CHD using pneumococcal vaccine PCV13 could reduce healthcare costs.

INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD.

The Indacaterol: Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/Fluticasone to Indacaterol (INSTEAD) study investigated the effect of switching patients at low risk of chronic obstructive pulmonary disease (COPD) exacerbations from salmeterol/fluticasone (SFC; inhaled corticosteroid (ICS) regimen) to indacaterol monotherapy (non-ICS regimen). This 26-week, double-blind, double-dummy, parallel-group, phase IV study, randomised 581 patients with moderate COPD to indacaterol 150 μg once daily or SFC 50/500 μg twice daily. Patients had been receiving SFC 50/500 μg for ≥3 months, with no COPD exacerbations for more than a year before the study (patients for whom ICS is not recommended). The primary objective was to demonstrate non-inferiority of indacaterol to SFC, measured by trough forced expiratory volume in 1 second (FEV₁) after 12 weeks (non-inferiority margin of 0.06 L). The primary objective was met, with a mean treatment difference of 9 mL (95% CI -45-26 mL). There were no significant differences between treatments in terms of breathlessness (transition dyspnoea index) or health status (Saint George's Respiratory Questionnaire) at weeks 12 or 26, or rescue medication use or COPD exacerbation rates over 26 weeks. Safety profiles of both treatments were as expected. This study demonstrated that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC to indacaterol 150 μg with no efficacy loss.

Seebri Breezhaler (glikopironis) – itin greitos veikimo pradžios, didžiausio selektyvumo M3 receptoriams, ilgai veikiantis inhaliuojamasis anticholinerginis vaistas LOPL gydyti

Glikopironio bromidas (glikopironis) – itin greitos veikimo pradžios, didžiausio selektyvumo M3 receptoriams, ilgai veikiantis inhaliuojamasis anticholinerginis bronchus plečiantis vaistas LOPL gydyti. Tai vieną kartą per parą vartojamas miltelių pavidalo vaistas, patvirtintas LOPL gydyti. Glikopironiui būdinga itin greita veikimo pradžia – jo bronchus plečiantis poveikis pasireiškia per 5 minutes po pirmosios dozės. Bronchus plečiantis glikopironio bromido poveikis trunka 24 valandas ir nemažėja vaistą nuolat vartojant ilgą laiką. Glikopironis yra toks pat efektyvus, saugus ir gerai toleruojamas kaip ir kitas žinomas ilgai veikiantis anticholinerginis vaistas – tiotropio bromidas. Glikopironio bromidas taip pat reikšmingai sumažina vidutinio sunkumo ir sunkių LOPL paūmėjimų dažnumą bei pagalbinių trumpai veikiančių bronchus plečiančių vaistų kiekį. Taigi, vieną kartą per parą vartojamas glikopironis (Seebri Breezhaler) yra naujas pasirinkimas gydant LOPL sergančius pacientus.

Impact of a functional polymorphism in the PAR-1 gene promoter in COPD and COPD exacerbations.

Proteinase-activated receptor-1 (PAR-1) plays a key role in mediating the interplay between coagulation and inflammation in response to injury. The aim of this study was to investigate the role of the promoter single-nucleotide polymorphism (SNP) rs2227744G>A in modulating PAR-1/F2R gene expression in the context of chronic obstructive pulmonary disease (COPD) and COPD exacerbations. The function of the rs2227744G>A SNP was investigated by using reporter gene assays. The frequency of the polymorphism in the UK population was assessed by genotyping 8,579 healthy individuals from the Whitehall II and English Longitudinal Study of Ageing cohorts. The rs2227744G>A SNP was genotyped in a carefully phenotyped cohort of 203 COPD cases and matched controls. The results were further replicated in two different COPD cohorts. The minor allele of the rs2227744G>A polymorphism was found to increase F2R expression by 2.6-fold (P < 0.001). The rs2227744G>A SNP was not significantly associated with COPD, or with lung function, in all cohorts. The minor allele of the SNP was found to be associated with protection from frequent exacerbations (P = 0.04) in the cohort of COPD patients for which exacerbation frequency was available. Considering exacerbations as a continuous variable, the presence of the minor allele was associated with a significantly lower COPD exacerbation rate (3.03 vs. 1.98 exacerbations/year, Mann-Whitney U-test P = 0.04). Taken together, these data do not support a role for the rs2227744G>A F2R polymorphism in the development of COPD but suggest a protective role for this polymorphism from frequent exacerbations. Studies in separate cohorts to replicate these findings are warranted.

Seebri Breezhaler (glikopironis) – didelio afiniteto inhaliuojamasis anticholinerginis vaistas LOPL gydyti

Klinikinėje praktikoje pradėtas vartoti naujas didelio afiniteto inhaliuojamasis ilgai veikiantis anticholinerginis bronchus plečiantis vaistas glikopironio bromidas (glikopironis). Tai miltelinis vieną kartą per parą vartojamas vaistas, patvirtintas LOPL gydyti. Glikopironiui būdinga greita veikimo pradžia – jo bronchus plečiantis poveikis pasireiškia per 5 minutes po pirmosios dozės inhaliacijos. Bronchus plečiantis glikopironio bromido poveikis trunka 24 valandas ir nesilpnėja vaistą nuolat vartojant ilgą laiką. Glikopironis yra toks pat efektyvus, saugus ir gerai toleruojamas kaip ir kitas vienintelis iki šiol turėtas ilgo veikimo anticholinerginis vaistas tiotropio bromidas. Glikopironio bromidas irgi reikšmingai sumažina vidutinio sunkumo bei sunkių LOPL paūmėjimų skaičių ir pagalbinių trumpo veikimo vaistų vartojimą. Taigi vieną kartą per parą vartojamas glikopironis (Seebri Breezhaler) gali būti alternatyva šiuo metu kompensuojamam ilgo veikimo anticholinerginiam vaistui tiotropiui LOPL sergantiems pacientams gydyti.

Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine

The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a “multilevel cycle” responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of “multilevel cycle” helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results.

The Effect of Cold Temperature on Increased Exacerbation of Chronic Obstructive Pulmonary Disease: A Nationwide Study

BackgroundSeasonal variations in the acute exacerbation of chronic obstructive pulmonary disease (COPD) have been reported. However, the influence of air temperature and other meteorological factors on COPD exacerbation remains unclear.MethodsNational Health Insurance registry data from January 1, 1999 to December 1, 2009 and meteorological variables from the Taiwan Central Weather Bureau for the same period were analyzed. A case-crossover study design was used to investigate the association between COPD exacerbation and meteorological variables.ResultsA total of 16,254 cases who suffered from COPD exacerbation were enrolled. We found that a 1°C decrease in air temperature was associated with a 0.8% increase in the exacerbation rate on event-days (95% confidence interval (CI), 1.015–1.138, p = 0.015). With a 5°C decrease in mean temperature, the cold temperature (28-day average temperature) had a long-term effect on the exacerbation of COPD (odds ratio (OR), 1.106, 95% CI 1.063–1.152, p<0.001). In addition, elderly patients and those who did not receive inhaled medication tended to suffer an exacerbation when the mean temperature dropped 5°C. Higher barometric pressure, more hours of sunshine, and lower humidity were associated with an increase in COPD exacerbation.ConclusionsThis study demonstrated the effect of cold temperatures on the COPD exacerbation rate. Elderly patients and those without inhaled medicine before the exacerbation event were affected significantly by lower mean temperatures. A more comprehensive program to prevent cold stress in COPD patients may lead to a reduction in the exacerbations rate of COPD.

Safety and efficacy of the once-daily anticholinergic BEA2180 compared with tiotropium in patients with COPD

To determine the safety and efficacy of BEA2180, an anticholinergic agent in patients with chronic obstructive pulmonary disease (COPD). Smokers or ex-smokers ≥40 years with COPD and a postbronchodilator forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≤70% participated in this multinational, randomised, double-blind, parallel study. Patients received BEA2180 (50, 100 or 200 μg), tiotropium (5 μg) or placebo once daily via Respimat Soft Mist™. The primary endpoint was trough FEV1 after 24 weeks. Secondary endpoints included Transition Dyspnoea Index (TDI) focal score, St George's Respiratory Questionnaire (SGRQ) total score, exacerbations and adverse events. Patients (n = 2080, 64.5% male) had a mean age of 64.2 years and a baseline FEV1 of 1.2 L. Trough FEV1 at 24 weeks with all BEA2180 doses (0.044-0.087 L) and tiotropium 5 μg (0.092 L) was significantly higher (p < 0.0001) than placebo (-0.034 L) and BEA2180 (200 μg) was noninferior to tiotropium. Mean TDI focal scores were higher with BEA2180 (1.43-1.48) or tiotropium (1.46) versus placebo (0.94; p ≤ 0.01 for all). Mean SGRQ total scores also improved with BEA2180 (40.1-40.7) or tiotropium (39.5) compared with placebo (43.0, p < 0.01 for all). COPD exacerbation rates were reduced for all active treatments, reaching statistical significance for BEA2180 (50 and 200 μg) (p < 0.05, for both). All study doses of BEA2180 improved lung function, reduced symptoms and exacerbations, and improved health status in COPD; all treatments were well tolerated. Clinical trial identifier: NCT00528996.

Systematic review and meta-analysis of prophylactic antibiotics in COPD and/or chronic bronchitis [Review article

Exacerbations contribute substantially to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). To assess whether prophylactic antibiotic treatment reduces exacerbations in patients with COPD and/or chronic bronchitis. Medline, EMBASE, Cochrane Central Register of Controlled Trials, Koreamed and references from relevant publications were searched up to October 2011. Randomised controlled trials comparing the effect of any prophylactic antibiotics with placebo for at least 3 months were included. The co-primary outcomes were the frequency of exacerbations of COPD or chronic bronchitis and adverse treatment events. A total of 19 trials involving 3932 subjects were included in the analysis: 5 recent trials included patients with moderate to severe COPD, whereas 14 older trials included patients with chronic bronchitis. The use of antibiotics significantly reduced the rate of COPD exacerbations (risk ratio [RR] 0.73, 95%CI 0.66-0.82), the number of chronic bronchitis exacerbations (standardised mean difference -0.23, 95%CI -0.35--0.11) and the proportion of patients with exacerbations of chronic bronchitis (RR 0.93, 95%CI 0.87-0.99). Prophylactic antibiotic treatment has a significant effect in reducing exacerbations in patients with COPD and/or chronic bronchitis.

Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? the REACT study protocol

BackgroundMany patients with chronic obstructive pulmonary disease (COPD) continue to suffer exacerbations, even when treated with maximum recommended therapy (eg, inhaled combinations of long-acting β2-agonist and high dose inhaled corticosteroids, with or without a long-acting anticholinergic [long-acting muscarinic antagonist]). Roflumilast is approved to treat severe COPD in patients with chronic bronchitis – and a history of frequent exacerbations – as an add-on to bronchodilators.PurposeThe REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment) study (identification number RO-2455-404-RD, clinicaltrials. gov identifier NCT01329029) will investigate whether roflumilast further reduces exacerbations when added to inhaled combination therapy in patients still suffering from frequent exacerbations.Patients and methodsREACT is a 1-year randomized, double-blind, multicenter, phase III/IV study of roflumilast 500 μg once daily or placebo on top of a fixed long-acting β2-agonist/inhaled corticosteroid combination. A concomitant long-acting muscarinic antagonist will be allowed at stable doses. The primary outcome is the rate of moderate or severe COPD exacerbations. Using a Poisson regression model with a two-sided significance level of 5%, a sample size of 967 patients per treatment group is needed for 90% power. COPD patients with severe to very severe airflow limitation, symptoms of chronic bronchitis, and at least two exacerbations in the previous year will be recruited.ConclusionIt is hypothesized that because roflumilast (a phosphodiesterase-4 inhibitor) has a different mode of action to bronchodilators and inhaled corticosteroids, it may provide additional benefits when added to these treatments in frequent exacerbators. REACT will be important to determine the role of roflumilast in COPD management. Here, the design and rationale for this important study is described.