A Real-World Study on the Day and Night-Time Symptoms Among Greek COPD Patients Who Recently Initiated Treatment with Dual Bronchodilation: The DANICO Study.

Purpose: The rationale of this study was to investigate the prevalence of daily and night symptoms and quality of sleep in Greek COPD patients as a means to evaluate their response to treatment with the fixed dose combination of aclidinium/formoterol (administered through the Genuair® device). Patients and Methods: This study was a multicenter, nationwide, non-interventional, observational study in 2105 patients suffering from COPD, who have recently started treatment with aclidinium/formoterol. Patients were attending to two visits, one baseline and a final visit, 3 months later. Different variables have been collected on either the baseline or the final visit or both: demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, COPD assessment test (CAT), COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach proposed by the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD), COPD treatment report, and severity of early-morning, daytime and night-time COPD-related symptoms. Reasons for prescribing aclidinium/formoterol, satisfaction of patients to the treatment, as well as their compliance have also been recorded. Results: After 3 months on aclidinium/formoterol, 50.1% of the patients experienced an improvement in their early-morning symptoms. Furthermore, 49.9% of them experienced an improvement in their daily symptoms, 44.9% improved their night-time symptoms and 43.2% reduced the frequency of overnight sleep disruptions due to COPD symptoms. These favorable outcomes apply mainly to GOLD Groups B-D. Treatment with aclidinium/formoterol improved on average the pre-bronchodilation FEV1% pred by 3.18%, the post-bronchodilation FEV1% pred by 2.78% and reduced CAT score by 5.22 points. Satisfaction with using aclidinium/formoterol across patients was high, as well as compliance to therapy. Conclusion: Aclidinium/formoterol provided significant benefits on the quality of life of COPD patients by reducing the morning, daytime and the night-time symptoms and symptom burden in GOLD Groups B-D, and activity impairment under real-life conditions in all GOLD ABCD groups.

Comparative mortality risk of tiotropium administered via handihaler or respimat in COPD patients: are they equivalent?

BACKGROUND: Tiotropium bromide, once daily, long-acting anticholinergic bronchodilator is either administered by handihaler metered dose inhaler or by respimat soft mist inhaler. It has been proved to improve lung function, daily symptoms and quality of life and to decrease the exacerbation and hospitalisation rate of patients with Chronic Obstructive Pulmonary Disease (COPD). Although the efficacy of both formulations is undeniable, concerns have been raised on their effect on cardiovascular and general mortality. METHODS: Two independent authors systematically reviewed Medline, Scopus, Cochrane Library and ClinicalTrials.gov to collect clinical trials, observational studies and meta-analyses studying the safety of tiotropium. The reference list of all the included studies were also reviewed. RESULTS: Limited, early studies suggested a potential increase in cardiovascular and general mortality associated with tiotropium handihaler, but these data were outweighed by following larger trials, real-life studies and meta-analyses which proved the opposite. On the other hand, data on tiotropium respimat (5 µg) have been contradictory, with different studies suggesting increased cardiovascular and general mortality compared to handihaler (18 µg) or placebo, especially in patients with comorbid diseases. TIOSPIR trial suggests comparable safety of the two formulations. However the exclusion of patients with pre-existing unstable cardiovascular disease, moderate or severe kidney disease or any other significantly disease may limit the generizability of these results. CONCLUSION: Although the two tiotropium formulations have similar efficacy, current data cannot prove safety equivalence, since respimat may be associated with increased cardiovascular and general mortality, especially in patients with comorbid diseases.

Tiotropium HandiHaler improves the survival of patients with COPD: a systematic review and meta-analysis.

BACKGROUND: Tiotropium HandiHaler (TioH) has been shown to improve lung function, exacerbations, and quality of life when added to the pharmacotherapy of patients with stable chronic obstructive pulmonary disease (COPD). The purpose of this meta-analysis was to synthesize current evidence regarding the impact of TioH on the survival rate of these patients, which is still controversial. METHODS: A systematic search in the electronic databases of the Cochrane Library, Medline, Scopus, EMBASE, PschINFO, CINAHL, and Web of Science was conducted by two independent authors (December 2012). Randomized clinical trials (RCTs) comparing inhaled TioH versus control (placebo or open control) were included. Data on total mortality were extracted, and missing data were obtained from authors. Relative risk (RR) for total mortality was calculated for each study and pooled. Heterogeneity, the risk of bias, and the publication bias were assessed in accordance with Cochrane's guidance. RESULTS: Twenty-eight RCTs, evaluating 33,538 patients, met the inclusion criteria. Data were nonheterogeneous, so fixed-effects model analysis was used. The effect of TioH versus placebo was assessed in 19 RCTs, with a total population of 19,826 patients (31,914 patient years), of whom 1,018 died during the study period. A statistically significant decrease in all-cause mortality was associated with the administration of TioH [RR 0.86, 95% confidence interval (CI) 0.76-0.98]. The number needed to treat to prevent one fatality was estimated to be 64 (95% CI 56-110). Comparisons of tiotropium against six more comparators were identified, but the insufficient sample size did not allow robust comparisons with respect to mortality. CONCLUSION: Our meta-analysis of RCTs showed that TioH prolongs the survival of COPD patients compared with placebo. Further RCTs are needed to confirm the potential superiority of prescriptions with versus without TioH in mortality reduction.

Impact of long-term treatment with low-dose inhaled corticosteroids on the bone mineral density of chronic obstructive pulmonary disease patients: aggravating or beneficial?

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by a low-level systemic chronic inflammatory activity that is responsible for many of the disease's extra-pulmonary manifestations, including osteoporosis and fragility fractures. These manifestations are also well-documented side-effects of oral corticosteroids. It was hypothesized that low levels of inhaled corticosteroids, due to their anti-inflammatory properties and their low circulating levels, might preserve the bone mineral density (BMD) of COPD patients. METHODS: Two hundred and fifty-one male ex-smokers with COPD patients grouped on the basis of their diffusion capacity value as predominantly bronchitic or predominantly emphysematic and 313 male controls with similar age and smoking history were enrolled in the study. Each of the patient's categories was randomized into two separate subgroups. Patients enrolled in subgroups B(neg) (n = 91, 36%) and E(neg) (n = 37, 14.7%) were treated with long-acting ß2-agonists and anticholinergics, while subgroups B(ICS) (n = 87, 35%) and E(ICS) (n = 38, 15.1%) were additionally receiving low-dose inhaled corticosteroids. Patients and controls were evaluated by clinical examination, lung function testing and BMD measurement every 6 months for 4 years. RESULTS: According to the findings, emphysematic patients demonstrated an increased rate of BMD loss compared with bronchitic patients (P = 0.01). Furthermore, a reduction of the annual BMD loss in bronchitic patients on inhaled corticosteroids (P = 0.02) was measured, without a corresponding benefit for the emphysematics (P = not significant). CONCLUSIONS: Long-term administration of low-dose inhaled corticosteroids decelerates the annual BMD loss in bronchitic patients, possibly by reducing both pulmonary and systemic chronic inflammation caused by COPD.