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RATIONALE: Pulmonary rehabilitation following hospitalizations for exacerbations of chronic obstructive pulmonary disease (COPD) improves exercise capacity and health-related quality of life, and reduces readmissions. However, post-hospitalization pulmonary rehabilitation uptake is low. To date, no trials of interventions to increase uptake have been conducted. OBJECTIVE: Effect of a co-designed education video as an adjunct to usual care on post-hospitalization pulmonary rehabilitation uptake. METHODS: An assessor- and statistician-blinded randomized controlled trial with nested qualitative interviews of participants in the intervention group. Participants hospitalized with COPD exacerbations were assigned 1:1 to receive either usual care (COPD discharge bundle including pulmonary rehabilitation information leaflet) or usual care plus the co-designed education video delivered via a handheld tablet device at discharge. Randomization used minimization to balance age, sex, forced expiratory volume in 1 second (FEV1) % predicted, frailty, transport availability and previous pulmonary rehabilitation experience. MEASUREMENTS AND MAIN RESULTS: The primary outcome was pulmonary rehabilitation uptake within 28 days of hospital discharge. 200 patients were recruited with 196 randomized (51% female, median (interquartile range) FEV1 % predicted 36(27, 48)). Pulmonary rehabilitation uptake was 41% and 34% in the usual care and intervention groups respectively (p=0.37), with no differences in secondary (pulmonary rehabilitation referral and completion) or safety (readmissions and death) endpoints. Six of the fifteen participants interviewed could not recall receiving the video. CONCLUSION: A co-designed education video delivered at hospital discharge did not improve post-hospitalization pulmonary rehabilitation uptake, referral or completion. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

We conducted a scoping review of studies on health outcomes from electronic nicotine delivery systems (ENDS). The objective was to identify, narratively synthesize, assess the strength and quality of evidence and critically appraise studies that have reported disease end points associated with the use of ENDS. We included published literature on the health impact of ENDS from 01/01/2015 until 01/02/2020 following the PRISMA guidelines using PubMed, Embase, Scopus and Google Scholar. The database search identified 755 studies, and other sources 265; 37 studies met final eligibility criteria. Levels of evidence included 24(65%) cross-sectional, one (2.7%) case–control and six (16%) case studies, four (11%) cohort studies, one (2.7%) randomized controlled trial (RCT) and one (2.7%) meta-analysis; 27(73%) studies reported only on harms, eight (22%) reported on benefits, two (2%) on benefits and harms. Quality ratings were poor in 20 (54%), fair in 9(24%) and good in 8(22%) of studies. In our review, ENDS was not shown to be causative for harmful cardiovascular disease (CVD) outcomes and shown to be beneficial for hypertensive patients. Switching from cigarettes to e-cigarettes resulted in reduced exacerbations of chronic obstructive pulmonary disease (COPD), with no evidence of long-term deterioration in lung function. Mental Health, cancer and mortality were not adequately studied to form any consensus. Our review has not demonstrated ENDS to be causative of harmful CVD outcomes; furthermore switching from cigarettes to e-cigarettes was associated with improved hypertensive control and reduced exacerbations of COPD, with no evidence of increased asthma risk or long-term respiratory harm. Mental health, cancer and mortality outcomes have not been adequately studied to form a conclusion. Overall, the findings of our review did not provide evidence to counter the consensus held by many that ENDS use is safer than the risks posed from smoking cigarettes.

Chronic obstructive pulmonary disease treatment is informed by randomised controlled trial results, but it is unclear if these findings apply to people excluded from these trials. We used data from the TORCH (TOwards a Revolution in COPD Health) randomised controlled trial to validate non-interventional methods for assessing the clinical effectiveness of chronic obstructive pulmonary disease treatment in the UK Clinical Practice Research Datalink, before applying these methods to the analysis of people who would have been excluded from TORCH.To validate the use of non-interventional Clinical Practice Research Datalink data and methods for estimating chronic obstructive pulmonary disease treatment effects against trial results, and, using validated methods, to determine treatment effects in people who would have been excluded from the TORCH trial.A historical non-interventional cohort design, including validation against randomised controlled trial results.The UK Clinical Practice Research Datalink.People aged ≥ 18 years with chronic obstructive pulmonary disease registered in Clinical Practice Research Datalink GOLD between January 2000 and January 2017. For objective 1, we prepared a cohort that was analogous to the TORCH trial cohort by applying TORCH trial inclusion/exclusion criteria followed by individual matching to TORCH trial participants. For objectives 2 and 3, we prepared cohorts that were analogous to the TORCH trial that, nevertheless, would not have been eligible for the TORCH trial because of age, asthma, comorbidity or mild disease.The long-acting beta-2 agonist and inhaled corticosteroid combination product Seretide (GlaxoSmithKline plc) [i.e. fluticasone propionate plus salmeterol (FP-SAL)] compared with (1) no FP-SAL exposure or (2) exposure to salmeterol (i.e. the long-acting beta-2 agonist) only.Exacerbations, mortality, pneumonia and time to treatment change.For objective 1, the exacerbation rate ratio was comparable to that in the TORCH trial for FP-SAL compared with salmeterol (0.85, 95% confidence interval 0.74 to 0.97, vs. TORCH trial 0.88, 95% confidence interval 0.81 to 0.95), but not for FP-SAL compared with no FP-SAL (1.30, 95% confidence interval 1.19 to 1.42, vs. TORCH trial 0.75, 95% confidence interval 0.69 to 0.81). Active comparator results were also consistent with the TORCH trial for mortality (hazard ratio 0.93, 95% confidence interval 0.65 to 1.32, vs. TORCH trial hazard ratio 0.93, 95% confidence interval 0.77 to 1.13) and pneumonia (risk ratio 1.39, 95% confidence interval 1.04 to 1.87, vs. TORCH trial risk ratio 1.47, 95% confidence interval 1.25 to 1.73). For objectives 2 and 3, active comparator results were consistent with the TORCH trial for exacerbations, with the exception of people with milder chronic obstructive pulmonary disease, in whom we observed a stronger protective association (risk ratio 0.56, 95% confidence interval 0.46 to 0.70, vs. TORCH trial risk ratio 0.85, 95% confidence interval 0.74 to 0.97). For the analysis of mortality, we saw a lack of association with being prescribed FP-SAL (vs. being prescribed salmeterol), with the exception of those with prior asthma, for whom we observed an increase in mortality (hazard ratio 1.49, 95% confidence interval 1.21 to 1.85, vs. TORCH trial-analogous HR 0.93, 95% confidence interval 0.64 to 1.32).Routinely collected electronic health record data can be used to successfully measure chronic obstructive pulmonary disease treatment effects when comparing two treatments, but not for comparisons between active treatment and no treatment. Analyses involving patients who would have been excluded from trials mostly suggests that treatment effects for FP-SAL are similar to trial effects, although further work is needed to characterise a small increased risk of death in those with concomitant asthma.Some of our analyses had small numbers.The differences in treatment effects that we found should be investigated further in other data sets. Currently recommended chronic obstructive pulmonary disease inhaled combination therapy (other than FP-SAL) should also be investigated using these methods.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inChronic obstructive pulmonary disease affects 3 million people in the UK and is characterised by breathing difficulties that get worse over time, with sudden acute symptoms (exacerbations), possibly requiring hospitalisation. The evidence for use of medicines for treating chronic obstructive pulmonary disease comes from randomised controlled trial results. Randomised controlled trials generally include younger people with severe disease who do not have any other illnesses apart from chronic obstructive pulmonary disease, meaning that the effectiveness of these trials in all people with chronic obstructive pulmonary disease is unknown. Very large databases of anonymous electronic health records captured during NHS consultations can be used to study patients excluded from trials. However, confidence in results from studies using these data can be low because of fears of unaccounted bias, as patients are not randomised to treatment. In this project, we selected a group of patients from a very large electronic health record database called the Clinical Practice Research Datalink who were very similar to participants in a well-known large chronic obstructive pulmonary disease randomised controlled trial [the TORCH (TOwards a Revolution in COPD Health) trial]. When we analysed data from these patients, we found very similar results to the TORCH trial in relation to the reduction of exacerbations, development of pneumonia and time until death, when comparing one chronic obstructive pulmonary disease treatment with another. Having shown that our methods could be trusted to produce valid results when comparing one chronic obstructive pulmonary disease treatment with another, we then went on to analyse patients in the Clinical Practice Research Datalink who would have been excluded from the TORCH trial for the following reasons: aged 80 years, having asthma as well as chronic obstructive pulmonary disease, or having only mild chronic obstructive pulmonary disease. For exacerbations, we found that, for people with milder chronic obstructive pulmonary disease, one of the treatments we studied seemed to work better than in the trial. For the analysis of mortality, we found that, for people with asthma as well as chronic obstructive pulmonary disease, one of the treatments seemed not to work so well, with more people dying. Future studies are needed in different populations (such as in a database from another country) to confirm these results.

PURPOSE: To validate an algorithm for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) episodes derived in an electronic health record (EHR) database, against AECOPD episodes collected in a randomized clinical trial using an electronic case report form (eCRF).METHODS: We analyzed two data sources from the Salford Lung Study in COPD: trial eCRF and the Salford Integrated Record, a linked primary-secondary routine care EHR database of all patients in Salford. For trial participants, AECOPD episodes reported in eCRF were compared with algorithmically derived moderate/severe AECOPD episodes identified in EHR. Episode characteristics (frequency, duration), sensitivity, and positive predictive value (PPV) were calculated. A match between eCRF and EHR episodes was defined as at least 1-day overlap.RESULTS: In the primary effectiveness analysis population (n = 2269), 3791 EHR episodes (mean [SD] length: 15.1 [3.59] days; range: 14-54) and 4403 moderate/severe AECOPD eCRF episodes (mean length: 13.8 [16.20] days; range: 1-372) were identified. eCRF episodes exceeding 28 days were usually broken up into shorter episodes in the EHR. Sensitivity was 63.6% and PPV 71.1%, where concordance was defined as at least 1-day overlap.CONCLUSIONS: The EHR algorithm performance was acceptable, indicating that EHR-derived AECOPD episodes may provide an efficient, valid method of data collection. Comparing EHR-derived AECOPD episodes with those collected by eCRF resulted in slightly fewer episodes, and eCRF episodes of extreme lengths were poorly captured in EHR. Analysis of routinely collected EHR data may be reasonable when relative, rather than absolute, rates of AECOPD are relevant for stakeholders' decision making.

Background Noninvasive ventilation (NIV) is indicated to treat respiratory acidosis due to exacerbation of chronic obstructive pulmonary disease (COPD). Recent nonrandomized studies also demonstrated some physiological effects of high-flow nasal therapy (HFNT) in COPD patients. We designed a prospective, unblinded, multicenter, randomized controlled trial to assess the noninferiority of HFNT compared to NIV with respect to the reduction of arterial partial pressure of carbon dioxide (PaCO2) in patients with hypercapnic acute respiratory failure with mild-to-moderate respiratory acidosis. Methods We will enroll adult patients with acute hypercapnic respiratory failure, as defined by arterial pH between 7.25 and 7.35 and PaCO2 ≥ 55 mmHg. Patients will be randomly assigned 1:1 to receive NIV or HFNT. NIV will be applied through a mask with a dedicated ventilator in pressure support mode. Positive end-expiratory pressure will be set at 3–5 cmH2O with inspiratory support to obtain a tidal volume between 6 and 8 ml/kg of ideal body weight. HFNT will be initially set at a temperature of 37 °C and a flow of 60 L/min. At 2 and 6 h we will assess arterial blood gases, vital parameters, respiratory rate, treatment intolerance and failure, need for endotracheal intubation, time spent under mechanical ventilation (both invasive and NIV), intensive care unit and hospital length of stay, and hospital mortality. Based on an α error of 5% and a β error of 80%, with a standard deviation for PaCO2 equal to 15 mmHg and a noninferiority limit of 10 mmHg, we computed a sample size of 56 patients. Considering potential drop-outs and nonparametric analysis, the final computed sample size was 80 patients (40 per group). Discussion HFNT is more comfortable than NIV in COPD patients recovering from an episode of exacerbation. If HFNT would not be inferior to NIV, HFNT could be considered as an alternative to NIV to treat COPD patients with mild-to-moderate respiratory acidosis. Trial registration ClinicalTrials.gov, NCT03370666. Registered on December 12, 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3514-1) contains supplementary material, which is available to authorized users.

Background Only few randomized controlled trials (RCTs) for head-to-head comparison have been conducted between various combinations of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs). Our study was conducted to compare acute exacerbation and all-cause mortality among different LAMA/LABA regimens using Bayesian network meta-analysis (NMA). Methods We searched Medline, EMBASE, and the Cochrane library (search date: July 1, 2019). We included parallel-group RCTs comparing LAMA/LABA combinations with other inhaled drugs in the stable COPD for ≥ 48 weeks. Two different network geometries were used. The geometry of network (A) had nodes of individual drugs or their combination, while that of network (B) combined all other treatments except LAMA/LABA into each drug class. This study was prospectively registered in PROSPERO; CRD42019126753. Results We included 16 RCTs involving a total of 39,065 patients with stable COPD. Six combinations of LAMA/LABA were identified: tiotropium/salmeterol, glycopyrrolate/indacaterol, umeclidinium/vilanterol, tiotropium/olodaterol, aclidinium/formoterol, and glycopyrrolate/formoterol. We found that umeclidinium/vilanterol was associated with a lower risk of total exacerbations than other LAMA/LABAs in the NMA using network (A) (level of evidence: low or moderate). However, the significant differences were not present in the NMA of network (B). There were no significant differences among the LAMA/LABA combinations in terms of the number of moderate to severe exacerbations, all-cause mortality, major adverse cardiovascular events, or pneumonia. Conclusions The present NMA including all available RCTs provided that there is no strong evidence suggesting different benefits among LAMA/LABAs in patients with stable COPD who have been followed up for 48 weeks or more. Trial registration: This study was prospectively registered in PROSPERO; CRD42019126753.

Made available in DSpace on 2020-12-10T19:47:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-25 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Purpose: To compare the effects of three modalities of resistance training, two using elastic components and one using conventional weight machine on peripheral muscle strength in Individuals with chronic obstructive pulmonary disease (COPD). Effects on exercise capacity, impact of disease on health status, body composition and daily level of physical activity were investigated as secondary endpoints. Methods: Forty-eight participants were randomly allocated (Trials Registry #RBR-6V9SJJ) into Elastic band group (Theraband (R)) (EBG), Elastic tubes training using Lemgruber (R) (ETG), and Conventional training with weight machine equipment (CG). Participants were evaluated before and after 12 weeks of training regarding peripheral muscle strength by dynamometry; impact of disease on health status via COPD Assessment Test, CAT; exercise capacity by 6-min walk test, 6MWT; body composition by bioelectrical impedance; and daily level of physical activities via accelerometry. Results: Inter-group comparison of training effects did not elucidate significant differences between the modalities in muscle strength (p >= .2). Likewise, all training modalities showed similar effects on CAT, body composition and daily physical activity variables with no statistical significance observed (p >= .15). Conclusions: Modalities of resistance training using elastic components presented similar effects on muscle strength, health status, exercise capacity, body composition and daily level of physical activity in individuals with COPD. The effects of elastic resistance were similar to conventional resistance training. Sao Paulo State Univ, Dept Physiotherapy, Rua Roberto Simonsen 305, BR-19060900 Presidente Prudente, SP, Brazil Univ Estadual Londrina, Dept Physiotherapy, Londrina, Parana, Brazil Sao Paulo State Univ, Dept Physiotherapy, Rua Roberto Simonsen 305, BR-19060900 Presidente Prudente, SP, Brazil CNPq: 470742/2014-3

Objective The study aimed to evaluate whether high-flow oxygen therapy (HFOT) during training was more effective than oxygen in improving exercise capacity in hypoxemic chronic obstructive pulmonary disease (COPD). Methods A total of 171 patients with COPD and chronic hypoxemia were consecutively recruited in 8 rehabilitation hospitals in a randomized controlled trial. Cycle-ergometer exercise training was used in 20 supervised sessions at iso inspiratory oxygen fraction in both groups. Pre- and post-training endurance time (Tlim), 6-minute walking distance (6MWD), respiratory and limb muscle strength, arterial blood gases, Barthel Index, Barthel Dyspnea Index, COPD Assessment Test, Maugeri Respiratory Failure questionnaire, and patient satisfaction were evaluated. Results Due to 15.4% and 24.1% dropout rates, 71 and 66 patients were analyzed in HFOT and Venturi mask (V-mask) groups, respectively. Exercise capacity significantly improved after training in both groups with similar patient satisfaction. Between-group difference in post-training improvement in 6MWD (mean: 17.14 m; 95% CI = 0.87 to 33.43 m) but not in Tlim (mean: 141.85 seconds; 95% CI = −18.72 to 302.42 seconds) was significantly higher in HFOT. The minimal clinically important difference of Tlim was reached by 47% of patients in the V-mask group and 56% of patients in the HFOT group, whereas the minimal clinically important difference of 6MWD was reached by 51% of patients in the V-mask group and 69% of patients in the HFOT group, respectively. Conclusion In patients with hypoxemic COPD, exercise training is effective in improving exercise capacity. Impact Statement The addition of HFOT during exercise training is not more effective than oxygen through V-mask in improving endurance time, the primary outcome, whereas it is more effective in improving walking distance.

BACKGROUND Triple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA) for chronic obstructive pulmonary disease (COPD) have been studied at single dose levels of inhaled glucocorticoid, but studies at two dose levels are lacking. METHODS In a 52-week, phase 3, randomized trial to evaluate the efficacy and safety of triple therapy at two dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least one exacerbation in the past year, we assigned patients in a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [320 μg or 160 μg of budesonide], a LAMA [18 μg of glycopyrrolate], and a LABA [9.6 μg of formoterol]) or one of two dual therapies (18 μg of glycopyrrolate plus 9.6 μg of formoterol or 320 μg of budesonide plus 9.6 μg of formoterol). The primary end point was the annual rate (the estimated mean number per patient per year) of moderate or severe COPD exacerbations, as analyzed in the modified intention-to-treat population with the use of on-treatment data only. RESULTS The modified intention-to-treat population comprised 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-μg–budesonide triple-therapy group (2137 patients), 1.07 in the 160-μg–budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate–formoterol group (2120 patients), and 1.24 in the budesonide–formoterol group (2131 patients). The rate was significantly lower with 320-μg–budesonide triple therapy than with glycopyrrolate–formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P

PURPOSE: Poor adherence to medications is more prevalent for chronic obstructive pulmonary disease (COPD) than for other chronic conditions and is associated with unfavorable health outcomes. Few interventions have successfully improved adherence for COPD medications; none of these use unlicensed health care personnel. We explored the efficacy of lay health coaches to improve inhaler adherence and technique. METHODS: Within a randomized controlled trial, we recruited English- and Spanish-speaking patients with moderate to severe COPD from urban, public primary care clinics serving a low-income, predominantly African American population. Participants were randomized to receive 9 months of health coaching or usual care. Outcome measures included self-reported adherence to inhaled controller medications in the past 7 days and observed technique for all inhalers. We used generalized linear models, controlling for baseline values and clustering by site. RESULTS: Baseline adherence and inhaler technique were uniformly poor and did not differ by study arm. At 9 months, health-coached patients reported a greater number of days of adherence compared with usual care patients (6.4 vs 5.5 days; adjusted P = .02) and were more likely to have used their controller inhalers as prescribed for 5 of the last 7 days (90% vs 69%; adjusted P = .008). They were more than 3 times as likely to demonstrate perfect technique for all inhaler devices (24% vs 7%; adjusted P = .01) and mastery of essential steps (40% vs 11%; adjusted P

Aroub Lahham,1,2 Christine F McDonald,2–4 Anne E Holland1,2,5 1Discipline of Physiotherapy, La Trobe University, 2Institute for Breathing and Sleep, 3Department of Respiratory and Sleep Medicine, Austin Health, 4Department of Medicine, The University of Melbourne, 5Department of Physiotherapy, Alfred Health, Melbourne, VIC, Australia Background: Physical inactivity is associated with poor outcomes in COPD, and as a result, interventions to improve physical activity (PA) are a current research focus. However, many trials have been small and inconclusive.Objective: The aim of this systematic review and meta-analysis was to study the effects of randomized controlled trials (RCTs) targeting PA in COPD.Methods: Databases (Physiotherapy Evidence Database [PEDro], Embase, MEDLINE, CINAHL and the Cochrane Central Register for Controlled Trials) were searched using the following keywords: “COPD”, “intervention” and “physical activity” from inception to May 20, 2016; published RCTs that aimed to increase PA in individuals with COPD were included. The PEDro scale was used to rate study quality. Standardized mean differences (effect sizes, ESs) with 95% confidence intervals (CIs) were determined. Effects of included interventions were also measured according to the minimal important difference (MID) in daily steps for COPD (599 daily steps).Results: A total of 37 RCTs with 4,314 participants (mean forced expiratory volume in one second (FEV1) % predicted 50.5 [SD=10.4]) were identified. Interventions including exercise training (ET; n=3 studies, 103 participants) significantly increased PA levels in COPD compared to standard care (ES [95% CI]; 0.84 [0.44–1.25]). The addition of activity counseling to pulmonary rehabilitation (PR; n=4 studies, 140 participants) showed important effects on PA levels compared to PR alone (0.47 [0.02–0.92]), achieving significant increases that exceeded the MID for daily steps in COPD (mean difference [95% CI], 1,452 daily steps [549–2,356]). Reporting of methodological quality was poor in most included RCTs.Conclusion: Interventions that included ET and PA counseling during PR were effective strategies to improve PA in COPD. Keywords: pulmonary disease, chronic obstructive, physical activity, interventions

BackgroundObservational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.MethodsIn this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol.ResultsA total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV1) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group.ConclusionsAmong patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.).

Introduction During the clinical development of a fixed-dose combination of drugs, it is best practice to conduct dose-finding studies to determine the optimal dose of each component. The aims of this phase II dose-finding study were to confirm the lung function benefit of adding olodaterol to tiotropium, describe the dose–response relationship of olodaterol in combination with tiotropium 5 μg, and compare it with the dose response of olodaterol monotherapy. Methods In this double-blind, parallel-group trial, patients were randomized to receive either tiotropium 5 μg or a fixed-dose combination of tiotropium 5 μg with olodaterol 2 μg, 5 μg, or 10 μg, delivered once daily via the Respimat® for 4 weeks (NCT00696020). Patients had a diagnosis of chronic obstructive pulmonary disease and post-bronchodilator forced expiratory volume in 1 s (FEV1) ≥ 30 and

BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

Background: The purpose of this study is to determine the therapeutic efficacy of bi-level continuous positive airway pressure (BIPAP) intervention in patients with type II respiratory failure due to acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods: This review will only include randomized controlled trials (RCTs). The search strategy will be applied to 4 Chinese databases: China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Database (SinoMed); and 5 foreign literature databases: PubMed, Cochrane Library, Springer, EBSCO, and Web of Science. RCTs published from inception to October 2020 will be included. The 2 researchers will independently screen and extract the data and assess quality. The main results obtained through blood gas analysis and equipment observation, heterogeneity assessment, sensitivity analysis, funnel chart synthesis, data synthesis, and grouping analysis will be carried out using Review Manager 5.4 software. The trial sequential analysis will be completed using TSA v0.9 developed by the CTU at the Copenhagen Clinical Trial Center. Results: In the current meta-analysis, we will provide more practical and targeted results for the therapeutic efficacy of BIPAP in patients with type II respiratory failure due to acute exacerbation of COPD. Conclusion: This study will provide new evidence for the therapeutic efficacy of BIPAP in patients with type II respiratory failure due to acute exacerbation of COPD. Registration number: INPLASY2020110003 (DOI:10.37766/inplasy2020.11.0003).

Recently, clear benefits have been shown from long-term noninvasive ventilation (NIV) in stable chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure. In our opinion, these benefits are confirmed and nocturnal NIV using sufficiently high inspiratory pressures should be considered in COPD patients with chronic hypercapnic respiratory failure in stable disease, preferably combined with pulmonary rehabilitation. In contrast, clear benefits from (continuing) NIV at home after an exacerbation in patients who remain hypercapnic have not been shown. In this review we will discuss the results of five trials investigating the use of home nocturnal NIV in patients with prolonged hypercapnia after a COPD exacerbation with acute hypercapnic respiratory failure. Although some uncontrolled trials might have shown some benefits of this therapy, the largest randomized controlled trial did not show benefits in terms of hospital readmission or death. However, further studies are necessary to select the patients that optimally benefit, select the right moment to initiate home NIV, select the optimal ventilatory settings, and to choose optimal follow up programmes. Furthermore, there is insufficient knowledge about the optimal ventilatory settings in the post-exacerbation period. Finally, we are not well informed about exact reasons for readmission in patients on NIV, the course of the exacerbation and the treatment instituted. A careful follow up might probably be necessary to prevent deterioration on NIV early.

Despite the fact that metanalyses and clinical guidelines do not recommend the routine use of domiciliary non-invasive ventilation (NIV) for patients diagnosed with severe stable Chronic Obstructive Pulmonary Disease (COPD) and with chronic respiratory failure, it is common practice in some countries.We conducted an international web-survey of physicians involved in provision of long-term NIV to examine patterns of domiciliary NIV use in patients diagnosed with COPD.The response rate was 41.6%. A reduction of hospital admissions, improvements in quality of life and dyspnea relief were considered as the main expected benefits for patients. Nocturnal oxygen saturation assessment was the principal procedure performed before NIV prescription. Recurrent exacerbations (>3) requiring NIV and failed weaning from in hospital NIV were the most important reasons for starting domiciliary NIV. Pressure support ventilation (PSV) was the most common mode, with low intensity settings (PSV-low) the most popular (44.4 30.1%) compared with high intensity (PSV-high) strategies (26.9 +/- 25.9%), with different geographical preferences.COPD is confirmed to be a common indication for domiciliary NIV. Recurrent exacerbations and failed weaning from in-hospital NIV were the main reasons for its prescription.

Author(s): Orr, Jeremy E; Coleman, John; Criner, Gerard J; Sundar, Krishna M; Tsai, Sheila C; Benjafield, Adam V; Crocker, Maureen E; Willes, Leslee; Malhotra, Atul; Owens, Robert L; Wolfe, Lisa F | Abstract: Background and objectivePatients with chronic respiratory failure are increasingly managed with domiciliary non-invasive ventilation (NIV). There may be limited ability to provide NIV titration for these complex patients, and ventilatory requirements and upper airway support needs may change over time. Therefore, an automatically adjusting expiratory positive airway pressure (AutoEPAP) algorithm may offer advantages over manually adjusted EPAP for treating these patients. This study compared 4% oxygen desaturation index (ODI4%) values during the use of an AutoEPAP algorithm versus manual EPAP titration with the intelligent volume-assured pressure support (iVAPS) algorithm.MethodsThis prospective, single-blind, randomized, crossover study was conducted at six US sites. Patients with chronic respiratory failure (neuromuscular disease, chronic obstructive pulmonary disease, obesity hypoventilation and other aetiologies) and an apnoea-hypopnoea index of g5/h who were already established NIV users underwent a single night of NIV with the iVAPS manual EPAP and iVAPS AutoEPAP in the sleep laboratory in random order.ResultsA total of 38 patients constituted the study population. Mean ODI4% was statistically non-inferior with AutoEPAP versus manual EPAP (P l 0.0001). There was no difference in the effect on ODI4% across respiratory failure subgroups. Ventilation parameters and gas exchange were similar with either NIV mode, indicating equally effective treatment of respiratory failure. Sleep parameters were improved during AutoEPAP versus manual EPAP.ConclusionA single night of NIV using the iVAPS with AutoEPAP algorithm was non-inferior to a single night of iVAPS with manual EPAP titration in patients with respiratory failure.Clinical trial registrationNCT02683772 at clinicaltrials.gov.

Alpha-1 antitrypsin deficiency (AATD) is a clinically under-recognized inherited disorder affecting the lungs and the liver. The most common manifestations are pulmonary emphysema, bronchiectasis and liver disease. The recent publication of the European Respiratory Society statement on diagnosis and treatment of pulmonary diseases has replaced the 2003 American Thoracic Society and European Respiratory Society one. New outcome parameters have been introduced and validated by observational and randomized clinical trials, and new information about efficacy and safety of augmentation therapy have been published. In this narrative review we have commented the crucial points of the new European Respiratory Society statement on AATD, including a review of the literature on liver involvement and treatments.

Summary Background Evidence is scarce on the relative risk-benefit of inhaled triple therapy, consisting of inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β 2 -agonist, versus dual bronchodilation for chronic obstructive pulmonary disease (COPD). We aimed to compare a single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) versus a single-inhaler dual bronchodilator combination of indacaterol plus glycopyrronium (IND/GLY) in terms of the rate of moderate-to-severe COPD exacerbations over 52 weeks of treatment. Methods This randomised, parallel-group, double-blind, double-dummy study was done at 187 sites across 17 countries. Eligible patients had symptomatic COPD, severe or very severe airflow limitation, at least one moderate or severe exacerbation in the previous year, and were receiving inhaled maintenance medication. After a 2 week run-in period with one inhalation per day of IND/GLY (85 μg/43 μg), patients were randomly assigned (1:1), via an interactive response technology system, to receive 52 weeks of treatment with two inhalations of extrafine BDP/FF/G (87 μg/5 μg/9 μg) twice per day or one inhalation of IND/GLY (85 μg/43 μg) per day. Randomisation was stratified by country and severity of airflow limitation. The primary endpoint was the rate of moderate-to-severe COPD exacerbations across 52 weeks of treatment in all randomised patients who received at least one dose of study drug and had at least one post-baseline efficacy assessment. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02579850. Findings Between May, 29 2015, and July 10, 2017, 1532 patients received BDP/FF/G (n=764) or IND/GLY (n=768). Moderate-to-severe exacerbation rates were 0·50 per patient per year (95% CI 0·45–0·57) for BDP/FF/G and 0·59 per patient per year (0·53–0·67) for IND/GLY, giving a rate ratio of 0·848 (0·723–0·995, p=0·043) in favour of BDP/FF/G. Adverse events were reported by 490 (64%) of 764 patients receiving BDP/FF/G and 516 (67%) of 768 patients receiving IND/GLY. Pneumonia occurred in 28 (4%) patients receiving BDP/FF/G versus 27 (4%) patients receiving IND/GLY. One treatment-related serious adverse event occurred in each group: dysuria in a patient receiving BDP/FF/G and atrial fibrillation in a patient receiving IND/GLY. Interpretation In patients with symptomatic COPD, severe or very severe airflow limitation, and an exacerbation history despite maintenance therapy, extrafine BDP/FF/G significantly reduced the rate of moderate-to-severe exacerbations compared with IND/GLY, without increasing the risk of pneumonia. Funding Chiesi Farmaceutici.

Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic obstructive lung diseases with an associated high burden of disease. Asthma, which is often allergic in origin, frequently begins in infancy or childhood with variable airflow obstruction and intermittent wheezing, cough, and dyspnea. Patients with COPD, in contrast, are usually current or former smokers who present after the age of 40 years with symptoms (often persistent) including dyspnea and a productive cough. On the basis of age and smoking history, it is often easy to distinguish between asthma and COPD. However, some patients have features compatible with both diseases. Because clinical studies typically exclude these patients, their underlying disease mechanisms and appropriate treatment remain largely uncertain. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the American Thoracic Society, convened a workshop of investigators in San Francisco, California on May 14, 2016. At the workshop, current understanding of asthma-COPD overlap was discussed among clinicians, pathologists, radiologists, epidemiologists, and investigators with expertise in asthma and COPD. They considered knowledge gaps in our understanding of asthma-COPD overlap and identified strategies and research priorities that will advance its understanding. This report summarizes those discussions.

Background Chronic obstructive pulmonary disease (COPD) severely hinders quality of life for those affected and is costly to the health care system. Care gaps in areas such as pharmacotherapy, inhaler technique, and knowledge of disease are prevalent, particularly for vulnerable populations served by community clinics. Non-professionally licensed health coaches have been shown to be an effective and cost-efficient solution in bridging care gaps and facilitating self-management for patients with other chronic diseases, but no research to date has explored their efficacy in improving care for people living with COPD. Method This is multi-site, single blinded, randomized controlled trial evaluates the efficacy of health coaches to facilitate patient self-management of disease and improve quality of life for patients with moderate to severe COPD. Spirometry, survey, and an exercise capacity test are conducted at baseline and at 9 months. A short survey is administered by phone at 3 and 6 months post-enrollment. The nine month health coaching intervention focuses on enhancing disease understanding and symptom awareness, improving use of inhalers; making personalized plans to increase physical activity, smoking cessation, or otherwise improve disease management; and facilitating care coordination. Discussion The results of this study will provide evidence regarding the efficacy and feasibility of health coaching to improve self-management and quality of life for urban underserved patients with moderate to severe COPD. Trial registration ClinicalTrials.gov identifier NCT02234284 . Registered 12 August 2014.

Background: The increasing prevalence and associated cost of treating chronic obstructive pulmonary disease (COPD) is unsustainable. Health care organizations are focusing on ways to support self-management and prevent hospital admissions, including telehealth-monitoring services capturing physiological and health status data. This paper reports on data captured during a pilot randomized controlled trial of telehealth-supported care within a community-based service for patients discharged from hospital following an exacerbation of their COPD. Objective: The aim was to undertake the first analysis of system data to determine whether telehealth monitoring can identify an exacerbation of COPD, providing clinicians with an opportunity to intervene with timely treatment and prevent hospital readmission. Methods: A total of 23 participants received a telehealth-supported intervention. This paper reports on the analysis of data from a telehealth monitoring system that captured data from two sources: (1) data uploaded both manually and using Bluetooth peripheral devices by the 23 participants and (2) clinical records entered as nursing notes by the clinicians. Rules embedded in the telehealth monitoring system triggered system alerts to be reviewed by remote clinicians who determined whether clinical intervention was required. We also analyzed data on the frequency and length (bed days) of hospital admissions, frequency of hospital Accident and Emergency visits that did not lead to hospital admission, and frequency and type of community health care service contacts—other than the COPD discharge service—for all participants for the duration of the intervention and 6 months postintervention. Results: Patients generated 512 alerts, 451 of which occurred during the first 42 days that all participants used the equipment. Patients generated fewer alerts over time with typically seven alerts per day within the first 10 days and four alerts per day thereafter. They also had three times more days without alerts than with alerts. Alerts were most commonly triggered by reports of being more tired, having difficulty with self-care, and blood pressure being out of range. During the 8-week intervention, and for 6-month follow-up, eight of the 23 patients were hospitalized. Hospital readmission rates (2/23, 9%) in the first 28 days of service were lower than the 20% UK norm. Conclusions: It seems that the clinical team can identify exacerbations based on both an increase in alerts and the types of system-generated alerts as evidenced by their efforts to provided treatment interventions. There was some indication that telehealth monitoring potentially delayed hospitalizations until after patients had been discharged from the service. We suggest that telehealth-supported care can fulfill an important role in enabling patients with COPD to better manage their condition and remain out of hospital, but adequate resourcing and timely response to alerts is a critical factor in supporting patients to remain at home. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 68856013; http://www.isrctn.com/ISRCTN68856013 (Archived by WebCite at http://www.webcitation.org/6ofApNB2e) [JMIR Med Inform 2017;5(1):e8]

Introduction The use of extracorporeal CO2 removal (ECCO2R) is increasingly employed in critically ill patients. However, the clinical evidence supporting its efficacy remains currently poor. Evidence acquisition A systematic review using MEDLINE via PubMed was performed to identify eligible studies (until 30th September 2016). The amount of CO2 reduction, the effect on the duration of mechanical ventilation and weaning, the impact on patients' outcome and the occurrence of complications were evaluated. The quality of evidence was evaluated according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Evidence synthesis Six studies were included (three evaluating patients with chronic obstructive pulmonary disease [COPD]; three evaluating patients with acute respiratory distress syndrome [ARDS]), involving 279 adult patients; 142 treated with ECCO2R and 137 controls. No study on pediatric population met the inclusion criteria for analysis. The overall quality of evidence of the two randomized trials and four case-control studies varied from moderate to very low. PaCO2 was generally reduced by 25-33% within a few hours following ECCO2R initiation. One ARDS study showed a significant decrease in the duration of mechanical ventilation, although this result was only found by post-hoc analysis. The three studies on COPD demonstrated that some patients supported by ECCO2R devices could avoid endotracheal intubation, however the ICU-LOS and survival was not influenced by ECCO2R when compared to controls. Conclusions In COPD patients, a significantly reduced need for endotracheal intubation was reported. However, the use of ECCO2R has not shown significant improvement on the outcome of critically ill patients in the reviewed studies. Therefore appropriately powered, randomized, controlled studies are urgently needed.

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.

The efficacy of magnesium sulphate in chronic obstructive pulmonary disease (COPD) was assessed by conducting a systematic review of published randomized clinical trials through extensive searches in MEDLINE and SCOPUS with no date limits, as well as manual review of journals. Outcome measures varied depending on route(s) of administration of magnesium sulphate and medications co-administered. Risk of bias was evaluated and quality of evidence was graded. Four (4) randomized trials were included. All trials had a moderate risk of bias and were of average methodological quality. Magnesium sulphate given intravenously did not seem to have an immediate bronchodilatory effect; however it appears to potentiate the bronchodilatory effect of inhaled beta-2 agonists. Increase in peak expiratory flow rate (PEFR) at 30 and 45 min was greater in those who received magnesium sulphate compared to placebo (P = 0.03), although the mean percentage change in PEFR was just 24%, without significant differences in dyspnoea scores, hospital admission rates, or emergency department readmission rates compared to placebo. Nebulized magnesium sulphate with salbutamol versus nebulized salbutamol with saline placebo showed no significant differences is forced expiratory volume in 1 s (FEV 1 ) measured at 90 min after adjustment for baseline FEV 1 (P = 0.34) or differences in the need for hospital admission. Combined inhalational and intravenous magnesium sulphate versus intravenous saline placebo and nebulized ipratropium bromide were comparable in terms of hospital admission, intubation and death, but the ipratropium bromide group showed better bronchodilator effect and improvement in arterial blood gas parameters. Overall, trial evidence for trial evidence for magnesium sulphate in acute exacerbation of COPD is poor, and further well-designed trials are needed.

IntroductionNon-communicable diseases (NCDs) are the leading cause of death globally. Even though NCD disproportionally affects low-to-middle income countries, these countries including South Africa, often have limited capacity for the prevention and control of NCDs. The standard evidence-based care for the long-term management of NCDs includes rehabilitation. However, evidence for the effectiveness of rehabilitation for NCDs originates predominantly from high-income countries. Despite the disproportionate disease burden in low-resourced settings, and due to the complex context and constraints in these settings, the delivery and study of evidence-based rehabilitation treatment in a low-resource setting is poorly understood. This study aims to test the design, methodology and feasibility of a minimalistic, patient-centred, rehabilitation programme for patients with NCD specifically designed for and conducted in a low-resource setting.Methods and analysisStable patients with cancer, cardiovascular disease, chronic respiratory disease and/or diabetes mellitus will be recruited over the course of 1 year from a provincial day hospital located in an urban, low-resourced setting (Bishop Lavis, Cape Town, South Africa). A postponed information model will be adopted to allocate patients to a 6-week, group-based, individualised, patient-centred rehabilitation programme consisting of multimodal exercise, exercise education and health education; or usual care (ie, no care). Outcomes include feasibility measures, treatment fidelity, functional capacity (eg, 6 min walking test), physical activity level, health-related quality of life and a patient-perspective economic evaluation. Outcomes are assessed by a blinded assessor at baseline, postintervention and 8-week follow-up. Mixed-method analyses will be conducted to inform future research.Ethics and disseminationThis study has been approved by the Health Research and Ethics Council, Stellenbosch University (M17/09/031). Information gathered in this research will be published in peer-reviewed journals, presented at national and international conferences, as well as local stakeholders.Trial registration numberPACTR201807847711940; Pre-results.

Airflow limitation in chronic obstructive pulmonary disease (COPD) is associated with influx of various inflammatory cells (e.g. eosinophils, neutrophils, lymphocytes, macrophages) into the airways. Approximately one-third of stable COPD patients and one in five COPD exacerbations are associated with eosinophilic bronchitis that usually responds to inhaled or ingested corticosteroids [1]. Specific anti-eosinophil agents like mepolizumab, a humanised monoclonal antibody against interleukin 5 (IL-5), reduce severe asthma exacerbations and improve lung function [2–4]. The improvement in forced expiratory volume in 1 s (FEV1) is also associated with a decrease in biomarkers of airway remodelling, such as sputum hyaluronan and versican, over a 6-month treatment period [5]. It is not known if the same benefits are observed in patients with COPD and eosinophilia in whom the airflow obstruction is due to cigarette smoke-related bronchitis and emphysema. Airflow limitation in chronic obstructive pulmonary disease (COPD) is associated with influx of various inflammatory cells (e.g. eosinophils, neutrophils, lymphocytes, macrophages) into the airways. Approximately one-third of stable COPD patients and one in five COPD exacerbations are associated with eosinophilic bronchitis that usually responds to inhaled or ingested corticosteroids [1]. Specific anti-eosinophil agents like mepolizumab, a humanised monoclonal antibody against interleukin 5 (IL-5), reduce severe asthma exacerbations and improve lung function [2–4]. The improvement in forced expiratory volume in 1 s (FEV1) is also associated with a decrease in biomarkers of airway remodelling, such as sputum hyaluronan and versican, over a 6-month treatment period [5]. It is not known if the same benefits are observed in patients with COPD and eosinophilia in whom the airflow obstruction is due to cigarette smoke-related bronchitis and emphysema.

Although a number of studies have suggested that the use of Telemonitoring (TM) in patients with Chronic Obstructive Pulmonary Disease (COPD) can be useful and efficacious, its real utility in detecting Acute Exacerbation (AE) signaling the need for prompt treatment is not entirely clear. The current study aimed to investigate the benefits of a TM system in managing AE in advanced-stage COPD patients to improve their Health-Related Quality of Life (HRQL) and to reduce utilization of healthcare services. A 12-month Randomised Controlled Trial (RCT) was conducted in the Veneto region (Italy). Adult patients diagnosed with Class III-IV COPD in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification were recruited and provided a TM system to alert the clinical staff via a trained operator whenever variations in respiratory parameters fell beyond the individual’s normal range. The study’s primary endpoint was HRQL, measured by the Italian version of the two Short Form 36-item Health Survey (SF36v2). Its secondary endpoints were: scores on the Hospital Anxiety and Depression Scale (HADS); the number and duration of hospitalizations; the number of readmissions; the number of appointments with a pulmonary specialist; the number of visits to the emergency department; and the number of deaths. Three hundred thirty-four patients were enrolled and randomized into two groups for a 1 year period. At its conclusion, changes in the SF36 Physical and Mental Component Summary scores did not significantly differ between the TM and control groups [(-2.07 (8.98) vs -1.91 (7.75); p = 0.889 and -1.08 (11.30) vs -1.92 (10.92); p = 0.5754, respectively]. Variations in HADS were not significantly different between the two groups [0.85 (3.68) vs 0.62 (3.6); p = 0.65 and 0.50 (4.3) vs 0.72 (4.5); p = 0.71]. The hospitalization rate for AECOPD and/or for any cause was not significantly different in the two groups [IRR = 0.89 (95% CI 0.79–1,04); p = 0.16 and IRR = 0.91 (95% CI 0,75 – 1.04); p = 0.16, respectively]. The readmission rate for AECOPD and/or any cause was, however, significantly lower in the TM group with respect to the control one [IRR = 0.43 (95% CI 0.19–0.98); p = 0.01 and 0.46 (95% CI 0.24–0.89); p = 0.01, respectively]. Study results showed that in areas where medical services are well established, TM does not significantly improve HRQL in patients with COPD who develop AE. Although not effective in reducing hospitalizations, TM can nevertheless facilitate continuity of care during hospital-to-home transition by reducing the need for early readmission. Retrospectively registered on January 2012, ClinicalTrials.gov Identifier: NCT01513980 .

Background chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) frequently coexist in older people, reducing patients' quality of life (QoL) and increasing morbidity and mortality. Objective we studied the feasibility and efficacy of an integrated telerehabilitation home-based programme (Telereab-HBP), 4 months long, in patients with combined COPD and CHF. The primary outcome was exercise tolerance evaluated at the 6-min walk test (6MWT). Secondary outcomes were time-to-event (hospitalisation and death), dyspnoea (MRC), physical activity profile (PASE), disability (Barthel) and QoL (MLHFQ and CAT). Study design randomised, open, controlled, multicenter trial. Methods the Telereab-HBP included remote monitoring of cardiorespiratory parameters, weekly phone-calls by the nurse, and exercise programme, monitored weekly by the physiotherapist. All outcomes were studied again after 2 months of a no-intervention period. Results in total, 112 patients were randomised, 56 per group. Their mean (SD) age was 70 (9) years, and 92 (82.1%) were male. After 4 months, the IG were able to walk further than at baseline: mean (95% CI) Δ6MWT was 60 (22.2,97.8) m; the CG showed no significant improvement: -15 (-40.3,9.8) m; P = 0.0040 between groups. In IG, the media time to hospitalisation/death was 113.4 days compared with 104.7 in the CG (P = 0.0484, log-rank test). Other secondary outcomes: MRC (P = 0.0500), PASE (P = 0.0015), Barthel (P = 0.0006), MLHFQ (P = 0.0007) and CAT (P = 0.0000) were significantly improved in the IG compared with the CG at 4 months. IG maintained the benefits acquired at 6 months for outcomes. Conclusions this 4-month Telereab-HBP was feasible and effective in older patients with combined COPD and CHF.

This document reviews 1) the measurement properties of commonly used exercise tests in patients with chronic respiratory diseases and 2) published studies on their utilty and/or evaluation obtained from MEDLINE and Cochrane Library searches between 1990 and March 2015. Exercise tests are reliable and consistently responsive to rehabilitative and pharmacological interventions. Thresholds for clinically important changes in performance are available for several tests. In pulmonary arterial hypertension, the 6-min walk test (6MWT), peak oxygen uptake and ventilation/carbon dioxide output indices appear to be the variables most responsive to vasodilators. While bronchodilators do not always show clinically relevant effects in chronic obstructive pulmonary disease, high-intensity constant work-rate (endurance) tests (CWRET) are considerably more responsive than incremental exercise tests and 6MWTs. High-intensity CWRETs need to be standardised to reduce interindividual variability. Additional physiological information and responsiveness can be obtained from isotime measurements, particularly of inspiratory capacity and dyspnoea. Less evidence is available for the endurance shuttle walk test. Although the incremental shuttle walk test and 6MWT are reliable and less expensive than cardiopulmonary exercise testing, two repetitions are needed at baseline. All exercise tests are safe when recommended precautions are followed, with evidence suggesting that no test is safer than others. Hosp Univ Gregorio Maranon, Serv Neumol, Madrid, Spain Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain Univ Complutense Madrid, Fac Med, Madrid, Spain Sapienza Univ Roma, Dipartimento Sanita Pubbl & Malattie Infett, Rome, Italy Harbor UCLA Med Ctr, Rehabilitat Clin Trials Ctr, Div Pulm & Crit Care Physiol & Med, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA Univ Paris 06, Neurophysiol Resp Exp & Clin UMRS1158, Sorbonne Univ, INSERM, Paris, France Grp Hosp Pitie Salpetriere Charles Foix, AP HP, Serv Explorat Fonct Respirat Exercice & Dyspnee, Paris, France Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada Queens Univ, Lab Clin Exercise Physiol, Div Resp & Crit Care Med, Kingston, ON, Canada Kingston Gen Hosp, Kingston, ON, Canada Univ Fed Sao Paulo, Div Respirol, Clin Exercise Physiol Unit, Sao Paulo, Brazil Queens Univ, Resp Invest Unit, Div Resp & Crit Care Med, Kingston, ON, Canada ASL1 Sassari, Osped Civile Alghero, Alghero, SS, Italy Univ Edinburgh, ELEGI Colt Lab, Ctr Inflammat Res, Queens Med Res Inst, Edinburgh, Midlothian, Scotland Univ Leeds, Fac Biol Sci, Leeds, W Yorkshire, England Univ Hosp Leciester NHS Trust, Ctr Exercise & Rehabil Sci, Glenfield Hosp, Leciester, England Katholieke Univ Leuven, Dept Rehabil Sci, Leuven, Belgium Univ Hosp Gasthuisberg, Resp Rehabil Div, Leuven, Belgium Human Bioenerget Res Ctr, Crickhowell, Wales Univ Fed Sao Paulo, Div Respirol, Clin Exercise Physiol Unit, Sao Paulo, Brazil Web of Science

Patients with Chronic Obstructive Pulmonary Disease (COPD) and tracheostomy are at high risk for exacerbations and hospitalizations. Macrolide treatment has shown to reduce exacerbations in moderate-to-severe COPD. To evaluate the safety and the efficacy of long-term azithromycin use in outpatients with severe COPD and tracheostomy. A multicenter, randomized, uncontrolled, pilot trial evaluating the safety and the efficacy of azithromycin 500 mg three day-a-week for 6 months (AZI) vs. standard of care (SC) in severe COPD outpatients with tracheostomy. Patients were monitored for six months of treatment plus six months of follow up. The primary outcome was the reduction in the number of exacerbations and hospitalizations. A total of 22 patients was randomized (11 to SC and 11 to AZI). Patients in AZI had a significant lower cumulative number of exacerbations after the first 3 months of treatment when compared to patients in SC (p = 0.001), as well as hospitalizations (p = 0.02). Kaplan-Meier survival curves for time to first exacerbation showed a significant reduction in AZI of the rates of first exacerbation when compared to SC (log rank test = 12.14, p < 0.001), as well as to first hospitalization (log-rank = 4.09, p = 0.04). Azithromycin significantly improved the quality of life in comparison to SC. No serious adverse events in the AZI group were reported. Long-term azithromycin treatment seems to be safe and effective in severe COPD outpatients with tracheostomy in reducing exacerbations, hospitalizations, as well as in improving quality of life. © 2009 Elsevier Ltd. All rights reserved.

Background, Objectives, and MeasurementsPatients with chronic airway obstruction (CAO) frequently experience dyspnea and fatigue during activities performed by accessory muscles of ventilation, which competitively participate in arm elevation. This systematic review of randomized controlled trials (RCTs) concerning patients with CAO addresses the effects of upper-extremity exercise training (UEET), added to lower-extremity training or comprehensive pulmonary rehabilitation, on the following patient-centered outcomes: exercise capacity, symptoms, ability to perform daily activities, and health-related quality of life.MethodsStudies were retrieved using comprehensive database and hand-search strategies. Two independent reviewers determined study eligibility based on inclusion criteria. A detailed description of treatments was mandatory. Reviewers rated study quality and extracted information on study methods, design, intervention, and results.ResultsForty publications were evaluated. Four RCTs met the inclusion criteria but had serious methodological limitations, which introduce possible biases that reduce their internal validity. The outcomes measured were heterogeneous, and the results were inconsistent regarding maximal exercise capacity, dyspnea, and health-related quality of life. No effect of UEET was demonstrated for measures of arm fatigue.Limitations and ConclusionsThe limited methodological quality of the studies retrieved prevented us from performing a meta-analysis, the results of which could be misleading. This systematic review shows that there is limited evidence examining UEET and that the evidence available is of poor quality. Therefore, a recommendation for the inclusion or exclusion of UEET in pulmonary rehabilitation programs for individuals with CAO is not possible. Further research is needed to definitively ascertain the effects of this training modality on patient-centered outcomes.

Purpose: Update of a clinical practice guideline for the physiotherapy management of patients with chronic obstructive pulmonary disease supporting the clinical decision-making process.Methods: A systematic computerized literature search was performed on different modalities for improving physical exercise capacity, reducing exertional dyspnoea, improving airway clearance and encouraging changes in physical activity behaviour. Methodological quality was scored with the PEDro Scale. Scientific conclusions were graded according to the criteria of the `Dutch Evidence Based Guideline Development Platform'. These, together with practical considerations, were used to formulate recommendations for clinical practice.Results: A total of 103 studies were included in the systematic review, consisting of five meta-analyses of randomized controlled trials, 84 randomized controlled trials and 14 uncontrolled studies. Twenty scientific conclusions supported six recommendations on physical exercise training. Nineteen scientific conclusions supported eight recommendations on interventions for reducing dyspnoea. Five scientific conclusions supported seven recommendations concerning treatment modalities to improve mucus clearance, and two scientific conclusions supported two recommendations on strategies for encouraging permanent changes in physical activity behaviour.Conclusions: Strong recommendations support the use of physical exercise training to improve health-related quality of life and functional exercise capacity. Future research should investigate whether additional interventions for reducing exertional dyspnoea have a place as adjuncts to physical exercise training in selected patients. In addition, treatment of impaired mucus clearance, especially during acute exacerbations, requires further research. With the advance of new technologies for objective measurements of physical activities in daily life more research is needed concerning interventions to initiate and maintain physical activity behaviour change during and after supervised physical exercise training programmes

In this issue of Respiration , Johnson-Warrington et al. [7] report on a sub-analysis of data from a larger randomized controlled trial to explore incremental shuttle walk test (ISWT) performance near the time of hospital discharge. Their data provide interesting insight into some of these questions. From 52 eligible ISWT-naive patients, 39 (75%) patients with AECOPD were able and willing to complete repeat ISWTs despite this period of heightened symptom severity. The majority of patients performed exercise testing only a few days after hospital admission, and only 5 declined repeat testing due to severe symptoms. This information is, in its own right, valuable for the respiratory clinician as it demonstrates both the feasibility and acceptability of early mobilization in these acute patients. Of primary interest, the magnitude of test-retest change in ISWT distance was variable (approx. 50% improved and 50% did not), with repeat test performance potentially affected by a modest learning effect (mean difference 14 m) and/or insufficient recovery from the initial test. Despite this variability, however, the authors were able to predict repeat ISWT distance with remarkable accuracy (multiple regression analysis explaining 98.8% of the variance) using easily obtainable clinical data. Predicted and actual distances walked did not significantly differ and demonstrated good agreement, although the data were understandably derived from predominantly low total Hospitalizations due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are characterized by prolonged bed rest, physical inactivity [1] and peripheral muscle wasting [2] that does not fully recover after discharge [3] . Given the risk of adverse health outcomes associated with these ‘acquired’ comorbidities (e.g. re-exacerbation, mortality) [4–6] and the role of physical activity in preventing these acute events [5, 6] , it is unsurprising to observe strong interest in tailoring exercise prescription to individual needs as early as possible – even during the period of hospitalization. The period of inpatient hospitalization does, after all, offer benefits in terms of environment, staff and resources to conduct assessments of exercise performance. Performing such testing during this time does not, however, come without challenge. Compared to the stable disease state, AECOPDs are associated with significantly worsened respiratory symptoms, enhanced airflow obstruction and systemic inflammation, and poorer exercise tolerance. These differences raise important questions that have not yet been answered regarding its appropriateness. For example, is it safe to perform (near maximal) exercise tests during an AECOPD? Can such tests be performed to satisfactory standards during the acute disease state? Should they be performed according to the same guidelines as during the stable state (e.g. are repeat tests necessary)? Published online: September 4, 2015

Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence. This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma−chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations., This paper summarises key changes in the GINA global strategy report, a practical new resource for asthma care http://ow.ly/ObvYi

To the Editor: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition (1). The identification of COPD phenotypes may allow stratified treatment approaches that modulate discrete disease mechanisms. Peripheral blood eosinophilia is both a common and repeatable finding in COPD (2). In addition, the presence of a blood/sputum eosinophilia is associated with a significant proportion of COPD exacerbations (3, 4) and a favorable response to systemic steroids (5). However, the role of blood eosinophils in stratifying treatment response to inhaled corticosteroid/long-acting β-agonist combinations is poorly understood. The FORWARD (Foster 48-Week Trial to Reduce Exacerbations in COPD) study was a randomized, double-blind, parallel group trial that compared 48 weeks of treatment with extrafine beclomethasone dipropionate plus formoterol fumarate (BDP/FF), 100/6 μg pressurized metered-dose inhaler, two inhalations twice a day, versus FF 12 μg pressurized metered-dose inhaler, one inhalation twice a day, in patients with severe COPD with a history of exacerbations (clinical trial registered with www.clinicaltrials.gov [NCT 00929851]). The results of the study have been reported (6) and showed a significant reduction in exacerbation rate (28%) and improvement in lung function with BDP/FF compared with FF treatment. Here we evaluate the hypothesis that these treatment differences differ according to the baseline blood eosinophil count by performing a post hoc analysis on the FORWARD study data. Methods The median (quartile 1; quartile 3) baseline blood eosinophil count was 181.6 (110.4; 279.8), and the distribution of counts is shown in Figure E1 in the online supplement. The patients (n = 1,184) were stratified into quartile groups on the basis of the baseline eosinophil count. The clinical characteristics of the study population across the quartiles of baseline blood eosinophils are reported in Table E1. The following endpoints were analyzed: COPD exacerbation rate over the course of 48 weeks, using a negative binomial model for adjusted exacerbation rates, Kaplan-Meier analysis, and Cox proportional hazard model for time to first exacerbation event; change from baseline in predose morning FEV1 at 48 weeks, using a linear mixed model for repeated measurements; and change from baseline in St. George’s Respiratory Questionnaire total score at 48 weeks, using an analysis of covariance model. Further details of the models are provided in the online supplement. Additional analyses using percentage eosinophil count thresholds and considering absolute counts as a continuous variable were also performed. A predictive model (see online supplement for details) for future COPD exacerbation rate was estimated, accounting for a variety of baseline factors that may influence exacerbations (7). The effect of baseline blood eosinophil count on adverse events, and in particular pneumonia, was also evaluated.

Resistance training (RT) is thought to be effective in preventing muscle depletion, whereas endurance training (ET) is known to improve exercise capacity and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD). Our objectives were to assess the efficiency of combining RT with ET compared with ET alone. We identified eligible studies through a systematic multi-database search. One author checked titles and abstracts for relevance using broad inclusion criteria, whilst two independent authors checked the full-text copies for eligibility. Two authors independently extracted data, and we assessed the risk of bias and quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation guidelines. We included 11 randomized controlled trials (331 participants) and 2 previous systematic reviews. The meta-analyses showed equal improvements in HRQoL, walking distance and exercise capacity. However, we found moderate quality evidence of a significant increase in leg muscle strength favouring a combination of RT and ET (standardized mean difference of 0.69 (95% confidence interval: 0.39–0.98). In conclusion, we found significantly increased leg muscle strength favouring a combination of RT with ET compared with ET alone. Therefore, we recommend that RT should be incorporated in rehabilitation of COPD together with ET.

Background The incidence of chronic diseases, including diabetes mellitus (DM), heart failure (HF) and chronic obstructive pulmonary disease (COPD) is on the rise. The existing health care system must evolve to meet the growing needs of patients with these chronic diseases and reduce the strain on both acute care and hospital-based health care resources. Paramedics are an allied health care resource consisting of highly-trained practitioners who are comfortable working independently and in collaboration with other resources in the out-of-hospital setting. Expanding the paramedic’s scope of practice to include community-based care may decrease the utilization of acute care and hospital-based health care resources by patients with chronic disease. Methods/Design This will be a pragmatic, randomized controlled trial comparing a community paramedic intervention to standard of care for patients with one of three chronic diseases. The objective of the trial is to determine whether community paramedics conducting regular home visits, including health assessments and evidence-based treatments, in partnership with primary care physicians and other community based resources, will decrease the rate of hospitalization and emergency department use for patients with DM, HF and COPD. The primary outcome measure will be the rate of hospitalization at one year. Secondary outcomes will include measures of health system utilization, overall health status, and cost-effectiveness of the intervention over the same time period. Outcome measures will be assessed using both Poisson regression and negative binomial regression analyses to assess the primary outcome. Discussion The results of this study will be used to inform decisions around the implementation of community paramedic programs. If successful in preventing hospitalizations, it has the ability to be scaled up to other regions, both nationally and internationally. The methods described in this paper will serve as a basis for future work related to this study. Trial registration ClinicalTrials.gov: NCT02034045. Date: 9 January 2014. Electronic supplementary material The online version of this article (doi:10.1186/1745-6215-15-473) contains supplementary material, which is available to authorized users.

Background: Despite progress in pharmacological and non-pharmacological treatment in recent years, the burden of disease among patients with asthma and chronic obstructive pulmonary disease (COPD) is high and patients are frequently hospitalized due to exacerbations. Reasons for uncontrolled diseases are manifold, but are often associated with poor inhalation technique and non-adherence to the prescribed treatment plan. This causes substantial mortality, morbidity, and costs to the healthcare system. In this respect, the study of causes for non-adherence and the development of measures to increase and maintain treatment adherence in chronic diseases is of major clinical importance. Objective: The primary objective of this study is to investigate the impact of using specific, validated electronic devices on adherence to inhaled medication in patients with chronic obstructive lung diseases such as asthma and COPD. Furthermore, it aims to assess the impact of a reminder and close supervision of the course of disease and quality of life. Methods: In this ongoing prospective, single-blind, randomized controlled study, adherence to inhaled medication is analyzed over a 6-month period in at least 154 in- and outpatients with asthma or COPD who have experienced at least 1 exacerbation during the last year. Adherence is measured using electronic data capture devices, which save the date and time of each inhalative device actuation and transfer these data daily via a wireless connection to a Web-based database. Patients are randomly assigned to either the intervention or the control group. The clinical intervention consists of an automated and personal reminder. The intervention group receives an audio reminder and support calls in case medication has not been taken as prescribed or if rescue medication is used more frequently than pre-specified in the study protocol. During the study, participants are assessed every 2 months in the form of clinical visits. Results: Recruitment started in January 2014. To date, a total of 169 patients have been recruited. Follow-up assessments are still ongoing. The study will be concluded in the first quarter of 2017. Data analysis will take place during 2017. Conclusions: Few studies have investigated medication adherence in patients with chronic obstructive lung diseases. With this prospective study design and the use of state-of-the-art devices for measuring adherence, we expect scientifically relevant and clinically meaningful results that will have a substantial and positive impact on the provision of healthcare in chronically ill patients suffering from asthma or COPD. Trial Registration: ClinicalTrials.gov: NCT02386722; https://clinicaltrials.gov/ct2/show/NCT02386722 (Archived by WebCite at http://www.webcitation.org/6oJq1fel0) [JMIR Res Protoc 2017;6(10):e204]

Background The effectiveness of clinic-based pulmonary rehabilitation in advanced COPD is well established, but few data exist for less severe patients treated in alternative settings. The purpose of this study was to investigate whether a novel, community-based exercise program (CBE) was feasible and effective for patients with moderate COPD. Methods Nineteen patients with moderate COPD (mean FEV1 62%) and self-reported exercise impairment were randomized to 12-weeks of progressive endurance and strength training at a local health club under the guidance of a certified personal trainer, or to continuation of unsupervised habitual physical activity. Outcomes assessed at baseline and 12 weeks included session compliance, intensity adherence, treadmill endurance time, muscle strength, dyspnea, and health status. Results Compliance was 94% and adherence was 83%. Comparisons between CBE and control groups yielded the following mean (SEM) differences in favor of CBE: endurance time 134 (74) seconds versus -59 (49) seconds (P = 0.041) and TDI 5.1 (0.8) versus -0.2 (0.5) (P

Dear editor Determination of prognosis of exacerbation of chronic obstructive pulmonary disease (AECOPD) is a key cornerstone for health cost, organization, systems, and influences determinations of rationale in the use of non-invasive ventilation (NIV).1 However, systemic complexity of AECOPD makes it difficult to establish a “gold and perfect” prognosis model.1 Recently, a growing number of biological parameters such as anemia and health performance score evaluations are becoming decisive factors for NIV decisions.2 In an interesting study, Haja Mydin et al determined that anemia, and performance status based on World Health Organization performance status (WHO-PS) were independent prognostic markers in acute hypercapnic respiratory failure (AHRF) due to AECOPD.3 The authors considered the major findings were that WHO-PS >3, and anemia, were the best prognostic factors to identify patients unlikely to benefit from NIV. We believe that the study makes a useful contribution to the establishment of predictors of poor prognosis in patients with AECOPD and it may help to make appropriate decisions for rational use of NIV. However, there are some concerns related to this study. Firstly, the mechanism of anemia in chronic obstructive pulmonary disease (COPD) and its impact on survival are still unclear; principally it may be associated with acute systemic inflammation in COPD. Nevertheless, anemia prevalence shows a wide range among studies (7.5%–34%) and many confounding factors associated to comorbidities may exist.4,5 Particularly, the major prevalence of women in this study as sex–factor, could be a conditioning factor. Furthermore, the study did not specify if anemia was associated with hospital readmission.5 Secondly, a high frequency of hospital admissions for AECOPD had no prognostic significance in this study, but it was not clarified if previous episodes needed NIV or endotracheal intubation.6 Previous reports show that the use of NIV during AECOPD may improve long-term outcomes, in comparison with traditional therapy, including endotracheal intubation.5,6 Thirdly, the authors consider that the APACHE II score7 is rarely used outside of the intensive care unit (ICU), in favor of more simple parameters. We do not agree with this interpretation, and believe it deserves some consideration as other studies have demonstrated the usefulness of the APACHE II score7 as a solid independent predictor of hospital mortality on multiple regression analysis studies, and a marker for NIV response and health organization in AECOPD, and at large. To our knowledge there are no studies showing that it is not useful in assessing prognosis. Low performance status is an established prognostic factor for poor outcomes for patients with AECOPD, but this information was well known before the widespread use of NIV in general hospitals.8 Finally, the patient population included in this study may be too low with not enough representation to perform a suitable search for independent prognostic markers of a varied clinical condition such as AECOPD. A previous study9 recruited a larger number of patients with a wider spectrum of severity eg, 1,033 consecutive patients in the multicenter Confalonieri et al study. Moreover, it was noted that the mortality rate was very high (33.8%), in comparison with the majority of randomized clinical trials on NIV in patients with acute hypercapnic failure due to COPD exacerbation, and even more than past studies including ICU patients before the NIV era.5,9 In conclusion, we agree that anemia and a low performance status could have a negative impact on the outcome of patients with AECOPD, but possible patient selection bias and the lack of a control group make the interpretation of the results less firm for Haja Mydin et al,3 with regards to the decision to use or not use NIV for ventilatory treatment.

Randomized Controlled Trials (RCTs) are the "gold standard" for evaluating treatment outcomes providing information on treatments "efficacy". They are designed to test a therapeutic hypothesis under optimal setting in the absence of confounding factors. For this reason they have high internal validity. The strict and controlled conditions in which they are conducted, leads to low generalizability because they are performed in conditions very different from real life usual care. Conversely, real life studies inform on the "effectiveness" of a treatment, that is, the measure of the extent to which an intervention does what is intended to do in routine circumstances. At variance to RCTs, real life trials have high generalizability, but low internal validity. Recently the number of real life studies has been rapidly growing in different areas of respiratory medicine, particularly in asthma and COPD. The role of such studies is becoming a hot topic in respiratory medicine, attracting research interest and debate. In the first part of this review we discuss some of the advantages and disadvantages of different types of RCTs and analyze the strengths and weaknesses of real life trials, considering the recent examples of some studies conducted in COPD. We then discuss methodological approaches and options to overcome some of the limitations of real life studies. Comparing the conclusions of effectiveness and efficacy trials can provide important pieces of information. Indeed, these approaches can result complementary, and they can guide the interpretation of each other results.

Summary Background Long-acting bronchodilators are first-line treatment for chronic obstructive pulmonary disease (COPD), and their efficacy on lung function and clinical parameters is recognized. Objective To explore the available evidence about the effects of long acting bronchodilators on Health Related Quality of Life (HRQoL) and Health Status (HS) in clinical research. Methods Randomized controlled trials published till December 2012 evaluating HRQoL/HS in COPD by means of validated questionnaires were analysed. Results Fifty-one trials on Long acting β 2 agonist (LABA) and Long acting Anticholinergic (LAMA) met the inclusion criteria. A total of 37,225 moderate-severe COPD patients testing 6 drugs, 12 different devices and 22 different dosages, with a study duration ranging from 4 weeks to 4 years were studied. A statistical significant HRQoL/HS improvement was reached in 93% of the studies. Nevertheless, the Minimal Important Difference (MID) was reached in 70,6% of the studies considering the difference between baseline and end of the study, and in 50% when comparing active treatment and placebo. Conclusions The data coming from the review support the efficacy of long acting bronchodilators in improving HRQoL/HS of COPD patients. Further research evaluating HRQoL/HS as primary outcome and according to guidelines on Patient Reported Outcomes is needed.

Contains fulltext : 97853.pdf (Publisher’s version ) (Open Access) PURPOSE: Spirometry has become an indispensable tool in primary care to exclude, diagnose, and monitor chronic respiratory conditions, but the quality of spirometry tests in family practices is a reason for concern. Aim of this study was to investigate whether a combination of e-learning and bimonthly performance feedback would improve spirometry test quality in family practices in the course of 1 year. METHODS: Our study was a cluster trial with 19 family practices allocated to intervention or control conditions through minimization. Intervention consisted of e-learning and bimonthly feedback reports to practice nurses. Control practices received only the joint baseline workshop. Spirometry quality was assessed by independent lung function technicians. Two outcomes were defined, with the difference between rates of tests with 2 acceptable and repeatable blows being the primary outcome and the difference between rates of tests with 2 acceptable blows being the secondary outcome. We used multilevel logistic regression analysis to calculate odds ratios (ORs) for an adequate test in intervention group practices. RESULTS: We analyzed 1,135 tests. Rate of adequate tests was 33% in intervention and 30% in control group practices (OR = 1.3; P=.605). Adequacy of tests did not differ between groups but tended to increase with time: OR = 2.2 (P = .057) after 3 and OR = 2.0 (P = .086) in intervention group practices after 4 feedback reports. When ignoring test repeatability, these differences between the groups were slightly more pronounced: OR = 2.4 (P = .033) after 3 and OR=2.2 (P = .051) after 4 feedback reports. CONCLUSIONS: In the course of 1 year, we observed a small and late effect of e-learning and repeated feedback on the quality of spirometry as performed by family practice nurses. This intervention does not seem to compensate the lack of rigorous training and experience in performing spirometry tests in most practices. 6 p.

A pilot trial to compare the efficacy of two different procedures to prevent postoperative air-leak in chronic obstructive pulmonary disease (COPD) patients submitted to upper lobectomy for non-small cell lung cancer. Sixty patients with COPD and lung cancer at the upper pulmonary lobes eligible for lobectomy were enrolled and randomly assigned either to standard treatment (ST) with stapling device or to electrocautery dissection and application of a collagen patch coated with human fibrinogen and thrombin (TachoSil) (experimental treatment [ET]) for the intra-operative completion of their fused fissures. Thirty patients were enrolled in each group during a three-year period. Preoperative characteristics were similar between the two groups. Statistically significant reduction of air-leak was registered in the ET group when overall incidence of postoperative air-leak (55% vs. 96%; P=0.03), postoperative air-leak (mean 1.63+/-1.96 vs. 4.33+/-4.12 days; P=0.0018), chest-drain (mean 3.53+/-1.59 vs. 5.90+/-3.72 days; P=0.0021) and hospital stay duration (mean 5.87+/-1.07 vs. 7.50+/-3.20 days; P=0.01) were considered. The use of TachoSil to prevent postoperative air-leak after interlobar fissure completion in patients with COPD submitted to upper lobectomy seems to be safe and more effective than the ST based on stapling device application.