Moderate COPD Research Articles

Adenosine Metabolism in COPD: A Study on Adenosine Levels, 5′-Nucleotidase, Adenosine Deaminase and Its Isoenzymes Activity in Serum, Lymphocytes and Erythrocytes

Adenosine is a signaling molecule which is produced in high concentrations during airway inflammation. Airway inflammation is a characteristic feature of COPD. Therefore, the current study was designed to evaluate the changes in adenosine metabolism in COPD and correlate these changes with severity of the disease.The study was conducted on 50 healthy controls (25 healthy non-smokers and 25 healthy smokers) and 46 COPD patients (21 moderate, 15 severe and 10 very severe). The patients were sub-divided into moderate, severe and very severe categories as per the GOLD spirometric classification. Blood was collected from each subject and serum, lymphocytes and erythrocytes were separated. The adenosine levels and activities of 5′-nucleotidase, adenosine deaminase and its isoenzymes were assessed in serum, lymphocytes and erythrocytes. The data were analyzed statistically. A p value < 0.05 was considered as significant.In healthy smokers and COPD patients the adenosine levels increased. In COPD patients 5′-nucleotidase activity increased significantly in serum, lymphocytes and erythrocytes. The activities of ADA and isoenzymes decreased significantly in serum of healthy smokers and COPD patients, in lymphocytes and erythrocytes of very severe COPD patients and of ADA and ADA2 in lymphocytes and erythrocytes of moderate and severe COPD patients. The FEV1 (% of predicted) showed a significant negative correlation with adenosine levels and 5′-nucleotidase activity in serum, lymphocytes and erythrocytes and significant positive correlation with ADA and isoenzymes activity in serum and lymphocytes of COPD patients.We conclude that the adenosine metabolism changes in COPD. The adenosine levels and 5′-nucleotidase activity increase, and ADA activity decreases with severity of the disease.

PRS23 - PERSISTENCE TO COPD THERAPIES AND IMPACT ON COSTS RELATED TO HEALTHCARE CONSUMPTION: A FRENCH CLAIMS DATA STUDY

Adherence to COPD therapies and impact on healthcare use is poorly documented in France. Our objective was to describe persistence in newly treated COPD patients in France, and to assess a potential impact of non-persistence on costs related to healthcare use. All patients aged 45 and over, having at least one delivery of bronchodilator over 3 consecutive quarters between 2007 and 2014, and without asthma markers, were selected in the Echantillon Généraliste des Bénéficiaires (EGB). It is a 1/97e random sample of the French claims database which collects details of healthcare reimbursed, for each beneficiary. Persistence was measured at 12 months in newly treated patients and assessed by non-interruption of deliveries during at least 90 days. Healthcare-related costs were compared between persistent and non-persistent patients, after matching and adjustment for available confounding factors. In 721 persistent patients to new therapy for COPD and 721 non-persistent patients, numbers of COPD therapies and visits to healthcare professionals were similar. However, medical procedures were less frequent in non-persistent patients than in persistent patients, especially pulmonary function testing, X-rays and chest scan. The total annual health care cost was higher for persistent than for non-persistent patients (€3,677 vs. €3,460), due to higher drug costs (€542 vs. €178). Hospitalisation costs were similar in both groups (€2,138 for persistent patients vs. €2,181 for non-persistent patients). In this population of mild to moderate COPD patients, no difference on health care costs was observed between persistent and non-persistent patients. It can be explained by the similar numbers of exacerbations in both groups and, as is always the case with observational data, residual confounding factors could explain part of the results (e.g. disease severity).

Efficacy of Dexamethasone in Preventing Acute Mountain Sickness in COPD Patients: Randomized Trial

Patients with COPD may experience acute mountain sickness (AMS) and other altitude-related adverse health effects (ARAHE) when traveling to high altitudes. This study evaluated whether dexamethasone, a drug used for the prevention of AMS in healthy individuals, would prevent AMS/ARAHE in patients with COPD. This placebo-controlled, double-blind, parallel-design trial included patients with COPD and Global Initiative for Obstructive Lung Disease grade 1 to 2 who were living below 800 m. Patients were randomized to receive dexamethasone (8mg/d) or placebo starting on the day before ascent and while staying in a high-altitude clinic at 3,100m for 2days. The primary outcome assessed during the altitude sojourn was the combined incidence of AMS/ARAHE, defined as an Environmental Symptoms Questionnaire cerebral score evaluating AMS≥ 0.7 or ARAHE requiring descent or an intervention. In 60 patients randomized to receive dexamethasone (median [quartiles] age: 57 years [50; 60], FEV1 86%predicted [70; 104]; PaO2 at 760 m: 9.6kPa [9.2; 10.0]), the incidence of AMS/ARAHE was 22%(13 of 60). In 58 patients randomized to receive placebo (age: 60y [53; 64]; FEV1 94%predicted [76; 103]; PaO2: 10.0kPa [9.1; 10.5]), the incidence of AMS/ARAHE was 24%(14 of 58) (χ2 statistic vsdexamethasone, P= .749). Dexamethasone mitigated the altitude-induced PaO2 reduction compared with placebo (mean between-group difference [95%CI], 0.4kPa [0.0-0.8]; P= .028). In lowlanders with mild to moderate COPD, the incidence of AMS/ARAHE at 3,100m was moderate and not reduced by dexamethasone treatment. Based on these findings, dexamethasone cannot be recommended for the prevention of AMS/ARAHE in patients with COPD undertaking high-altitude travel, although the drug mitigated the altitude-induced hypoxemia. ClinicalTrials.gov; No.: NCT02450968; URL: www.clinicaltrials.gov.

Exacerbations of Chronic Obstructive Pulmonary Disease and Cardiac Events. A Post Hoc Cohort Analysis from the SUMMIT Randomized Clinical Trial.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, associated with acute inflammation, and may increase subsequent cardiovascular disease (CVD) risk. Determine whether AECOPD events are associated with increased risk of subsequent CVD. We performed a secondary cohort analysis of the SUMMIT (Study to Understand Mortality and Morbidity) trial, a convenience sample of current/former smokers with moderate COPD from 1,368 centers in 43 countries. All had CVD or increased CVD risk. AECOPD was defined as an increase in respiratory symptoms requiring treatment with antibiotics, systemic corticosteroids, and/or hospitalization. CVD events were a composite outcome of cardiovascular death, myocardial infarction, stroke, unstable angina, and transient ischemic attack. All CVD events were adjudicated. Cox proportional hazards models compared the hazard for a CVD event before AECOPD versus after AECOPD. Among 16,485 participants in SUMMIT, 4,704 participants had at least one AECOPD and 688 had at least one CVD event. The hazard ratio (HR) for CVD events after AECOPD was increased, particularly in the first 30 days after AECOPD (HR, 3.8; 95% confidence interval, 2.7-5.5) and was elevated up to 1 year after AECOPD. The 30-day HR after hospitalized AECOPD was more than twofold greater (HR, 9.9; 95% confidence interval, 6.6-14.9). In patients with COPD with CVD or risk factors for CVD, exacerbations confer an increased risk of subsequent CVD events, especially in hospitalized patients and within the first 30 days after exacerbation. Patients and clinicians should have heightened vigilance for early CVD events after AECOPD. Clinical trial registered with www.clinicaltrials.gov (NCT 01313676).

Management of severe COPD exacerbations: focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide.

The major determinant of the decline in lung function, quality of life, and the increased mortality risk in patients with COPD is represented by severe acute exacerbations of the disease, that is, those requiring patients’ hospitalization, constituting a substantial social and health care burden in terms of morbidity and medical resource utilization. Different long-term therapeutic strategies have been proposed so far in order to prevent and/or reduce the clinical and social impact of these events, the majority of which were extrapolated from trials initially focused on the effect of long-acting muscarinic antagonist and subsequently on the efficacy of long-acting β2-agonists in combination or not with inhaled corticosteroids. The option to employ all three classes of molecules combined, despite the limited amount of evidence in our possession, represents a choice currently proposed by international guidelines; however, current recommendations are often based mainly on observational studies or on the results of secondary outcomes in randomized controlled trials. The present narrative review evaluates the available trials that investigated the efficacy of inhaled therapy to prevent COPD exacerbations and especially severe ones, with a particular focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide fixed dose combination, which is the first treatment that comprises all the three drug classes, specifically tested for the prevention of moderate and severe COPD exacerbations.

Daily use of extracorporeal CO2 removal in a critical care unit: indications and results

BackgroundWhile outcome improvement with extracorporeal CO2 removal (ECCO2R) is not demonstrated, a strong pathophysiological rational supports its use in the setting of acute respiratory distress syndrome (ARDS) and COPD exacerbation. We aimed to describe our single-center experience of ECCO2R indications and outcome.MethodsPatients treated with ECCO2R in our medial ICU, from March 2014 to November 2017, were retrospectively enrolled. Primary end point was evolution of ventilator settings during the two first days following ECCO2R start.ResultsThirty-three patients received ECCO2R. Seventeen were managed with Hemolung®, 10 with Prismalung®, 4 with ILA®, and 2 with Cardiohelp®. Indications for ECCO2R were mild or moderate ARDS (n = 16), COPD exacerbation (n = 11), or uncontrolled hypercapnia due to other causes (n = 6). Four patients were not intubated at the time of ECCO2R start. Median duration of ECCO2R treatment was 7 days [5–10]. In ARDS patients, between baseline and day 2, median tidal volume and driving pressure decreased from 5.3 [4.4–5.9] mL/kg and 10 [8–15] to 3.8 [3.3–4.1] mL/kg and 9 [8–11], respectively. Prone positioning was performed in 10 of the 16 patients, without serious adverse event. In COPD patients, between baseline and day 2, median ventilation minute and PaCO2 decreased significantly from respectively 7.6 [6.6–8.7] L/min and 9.4 [8.4–10.1] kPa to 5.8 [4.9–6.2] L/min and 6 [5.3–6.8] kPa. Four out of 11 COPD patients were extubated while on ECCO2R. Device thrombosis occurred in 5 patients (15%). Hemolysis was documented in 16 patients (48%). One patient died of intracranial hemorrhage, while on ECCO2R. Twenty-four patients were discharged from ICU alive. Twenty-eight day mortality was 31% in ARDS, 9% in COPD patients, and 50% in other causes of refractory hypercapnic respiratory failure.ConclusionECCO2R was useful to apply ultra-protective ventilation among ARDS patients and improved PaCO2, pH, and minute ventilation in COPD patients.

Activation and polarization of circulating monocytes in severe chronic obstructive pulmonary disease

BackgroundThe ability of circulating monocytes to develop into lung macrophages and promote lung tissue damage depends upon their phenotypic pattern of differentiation and activation. Whether this phenotypic pattern varies with COPD severity is unknown. Here we characterize the activation and differentiation status of circulating monocytes in patients with moderate vs. severe COPD.MethodsBlood monocytes were isolated from normal non-smokers (14), current smokers (13), patients with moderate (9), and severe COPD (11). These cells were subjected to analysis by flow cytometry to characterize the expression of activation markers, chemoattractant receptors, and surface markers characteristic of either M1- or M2-type macrophages.ResultsPatients with severe COPD had increased numbers of total circulating monocytes and non-classical patrolling monocytes, compared to normal subjects and patients with moderate COPD. In addition, while the percentage of circulating monocytes that expressed an M2-like phenotype was reduced in patients with either moderate or severe disease, the levels of expression of M2 markers on this subpopulation of monocytes in severe COPD was significantly elevated. This was particularly evident for the expression of the chemoattractant receptor CCR5.ConclusionsBlood monocytes in severe COPD patients undergo unexpected pre-differentiation that is largely characteristic of M2-macrophage polarization, leading to the emergence of an unusual M2-like monocyte population with very high levels of CCR5. These results show that circulating monocytes in patients with severe COPD possess a cellular phenotype which may permit greater mobilization to the lung, with a pre-existing bias toward a potentially destructive inflammatory phenotype.

COMPARISON OF THE EFFECTIVENESS OF VISUAL IMAGERY TECHNIQUE AND PROGRESSIVE RELAXATION TECHNIQUE ON ANXIETY AND DEPRESSION IN SUBJECTS WITH MODERATE CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Objectives: (1) To determine the effectiveness of visual imagery technique (VIT) on anxiety and depression in moderate chronic obstructive lung disease, (2) to determine the effectiveness of progressive relaxation technique (PRT) on anxiety and depression in moderate chronic obstructive lung disease (COPD), and (3) to compare the effectiveness of VIT and PRT on anxiety and depression in moderate COPD.Methods: Ethical clearance was obtained from the institutional ethical committee. A total of 45 stable moderate COPD patients were selected by simple random sampling, according to inclusion and exclusion criteria. 22 patients of Group A received VIT and 23 of Group B received PRT with a baseline treatment of conventional physiotherapy in both groups for 60 minutes twice a day for 5 days in the Pulmonology Department, Krishna Hospital, Karad.Result: Statistics was analyzed using paired t-test and unpaired t-test. In pre-intervention, there was no statistically significant difference seen for depression anxiety stress scale (DASS21) (p=D 0.0189, A 0.0002, S &lt;0.0001) (t=D 2.440, A 4.053, S 5.105), hospital anxiety depression scale (HADS) (p=D 0.7677, A 0.5121) (t=D 0.2973, A 0.6610), and 6-min walk test (6MWT) (p=D 0.5948, RPE 0.0658) (t=D 0.5359, RPE 1.888). On comparing, the post-interventional values between the two groups using unpaired t-test proved that there was extremely statistically significant difference seen for DASS21 (p=D 0.0011, A &lt;0.0001, S &lt;0.0001) (t=D 3.504, A 9.220, S 13.508), HADS (p=D &lt;0.0001, A &lt;0.0001) (t=D &lt;0.0001, A &lt;0.0001), and 6MWT (p=distance 0.7041, RPE &lt;0.0001) (t=distance 0.3824, RPE &lt;0.0001).Conclusion: VIT along with conventional physiotherapy was significant both statistically and clinically compared to PRT on anxiety and depression in moderate COPD patients.

Comparison of glycopyrronium versus tiotropium on the time to clinically important deteriorations in patients with COPD: a post-hoc analysis of randomized trials

Glycopyrronium is a once-daily, inhaled long-acting muscarinic antagonist (LAMA) demonstrating similar efficacy to inhaled tiotropium in patients with moderate-to-severe COPD; however, the benefit of LAMAs on COPD symptoms has been variable. COPD is a progressive disease in which many patients develop an acute or sustained deterioration. Data on the prevention of clinically important deteriorations (CID) using LAMAs are limited. A pooled analysis was performed on four Phase III trials (n = 2936) that compared the efficacy of glycopyrronium (n = 1859) with tiotropium (n = 1077). The primary endpoint was significant delay and/or reduction in the occurrence of CID. CID was defined as any of the following: ≥100 mL decrease from baseline in pre-dose forced expiratory volume in 1 second (FEV1), ≥4 point increase in St George’s Respiratory Questionnaire score or a moderate-to-severe COPD exacerbation occurring after the first dose of study medication. A sustained CID was a CID occurring on ≥2 consecutive visits 4 weeks apart or for ≥50% of all available subsequent visits. Baseline characteristics for the overall population were similar. Patients had moderate (62%) or severe (38%) COPD. Mean post-bronchodilator FEV1 was approximately 55% predicted, and mean FEV1 reversibility was 16.7 and 18.6% in the glycopyrronium and tiotropium groups, respectively. Both glycopyrronium and tiotropium significantly reduced time to CID and sustained CID versus placebo (p < 0.001). No statistically significant differences were found between the glycopyrronium and tiotropium treatment groups in time to CID or sustained CID. Glycopyrronium is effective in delaying time to clinically important deteriorations, with similar efficacy to tiotropium.

Indacaterol/glycopyrronium reduces the risk of clinically important deterioration after direct switch from baseline therapies in patients with moderate COPD: a post hoc analysis of the CRYSTAL study.

PurposeCOPD is a progressive disease characterized by exacerbations and a decline in health status and lung function. Clinically important deterioration (CID) is a composite endpoint used to evaluate treatment efficacy. This analysis evaluated the impact of a direct switch to once-daily indacaterol/glycopyrronium 110/50 µg (IND/GLY) from previous monotherapy with a long-acting β2-agonist (LABA) or long-acting muscarinic antagonist (LAMA) or with an LABA and an inhaled corticosteroid (LABA + ICS) on reducing CID.MethodsCRYSTAL was a 12-week, prospective, multicenter, randomized, open-label study conducted in clinical practice settings. Three definitions of CID (D1–D3) were used, including: 1) ≥100 mL decrease in trough forced expiratory volume in 1 second (FEV1), 2) ≥1 point decrease in transition dyspnea index (TDI) and/or ≥0.4 points increase in clinical COPD questionnaire score (CCQ), or 3) an acute moderate/severe exacerbation (AECOPD). In D1 and D2, either TDI or CCQ was evaluated along with FEV1 and AECOPD, whereas in D3, all 4 parameters were included. ClinicalTrials.gov number: NCT01985334.ResultsOf the 2,159 patients analyzed, 1,622 switched to IND/GLY and 537 continued their baseline treatments. The percentage of patients with a CID was significantly lower after a direct switch to IND/GLY versus LABA or LAMA using all 3 CID definitions (D1: odds ratio [OR] 0.41 [95% CI: 0.30–0.55]; D2: OR 0.41 [95% CI: 0.31–0.55]; D3: OR 0.39 [95% CI: 0.29–0.52]). Compared with LABA + ICS, IND/GLY also reduced the risk of CID (D1: OR 0.76 [95% CI: 0.56–1.02]; D2: OR 0.75 [95% CI: 0.56–1.00]; D3: OR 0.67 [95% CI: 0.51–0.89]).ConclusionIn this analysis, IND/GLY reduced the risk of a CID in moderate COPD patients after direct switch from LABA + ICS or LABA or LAMA in real-life clinical practice.

СОСТОЯНИЕ СОСУДОДВИГАТЕЛЬНОЙ ФУНКЦИИ ЭНДОТЕЛИЯ У БОЛЬНЫХ ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНЬЮ ЛЕГКИХ В СОЧЕТАНИИ С ОСТРЫМ ИНФАРКТОМ МИОКАРДА

The aim of the study is to investigate a vasomotor function of patients with COPD against the development of acute myocardial infarction (AMI) with an elevation of the ST segment of the electrocardiogram. The brachial artery reactivity was studied in 42 patients with COPD during the course of treatment in the Amur Regional Clinical Hospital. All the patients were divided into two groups: 1st group (22 patients) with COPD and AMI with an elevation of the ST segment; 2nd group (20 patients) - with moderate COPD. The control group included 15 healthy people without cardiovascular diseases and respiratory pathology. The study was done at the ultrasonic device Toshiba Aplio XG with the linear probe of 10MHz using the method by D.S.Celermajer et al. (1992). The following results were obtained: the majority of COPD patients demonstrate vasomotor endothelial dysfunction that can cause atherosclerosis; in case of COPD and AMI comorbidity an endothelial dysfunction redoubles; development of AMI coincides with the “peak” of endothelial dysfunction determined with the help of endothelium-dependent vasodilatation. The method of endothelial dysfunction determination is non-invasive and accurate to predict cardiovascular diseases in COPD patients.

Severity of chronic obstructive pulmonary disease and presenting rhythm in patients with out-of-hospital cardiac arrest

IntroductionChronic obstructive pulmonary disease (COPD) is associated with a non-shockable rhythm as presenting rhythm in out-of-hospital cardiac arrest (OHCA). Whether the severity of the underlying disease is related to presenting rhythm is unknown. We hypothesized that increased severity of COPD in OHCA patients is associated with an increased prevalence of non-shockable rhythm. MethodsThis study included OHCA patients ≥40 years from the Danish Cardiac Arrest Registry (2001–2014). Population-based registries were used to identify chronic diseases and drug prescriptions. COPD was defined as a COPD diagnosis or pharmacological therapy for COPD. The severity of COPD was based on either 1) pharmacological therapy (mild/moderate/severe), 2) admission for exacerbation, 3) prescription for corticosteroids, or 4) forced expiratory volume in 1 s (FEV1). For each of these, a multivariable logistic regression model was used to estimate odds ratios (ORs) for a non-shockable rhythm. ResultsOf 33,228 patients with OHCA 7789 (23.4%) had COPD. Of these 6702 (86.0%) had a non-shockable rhythm. Compared to patients without COPD, mild COPD was associated with a non-shockable rhythm (OR = 1.46, 95%CI 1.29–1.65). This association was more pronounced for moderate (OR = 1.78, 95%CI 1.45–2.19) and severe COPD (OR = 2.01 95%CI 1.82–2.20). Recent admission for exacerbation (OR = 2.12, OR 95%CI 1.81–2.49) or prescription for corticosteroids (OR = 1.82, 95%CI 1.55–2.14) was also associated with a non-shockable rhythm. FEV1 ≤ 50% was associated with a non-shockable rhythm compared to FEV1 > 50% (OR = 1.74, 95%CI 1.07–2.82, n = 1122). ConclusionIncremental severity of COPD is associated with increasing prevalence of a non-shockable rhythm as presenting rhythm in OHCA patients.

An opportunity to improve pulmonary capillary circulation in patients with chronic obstructive pulmonary disease and comorbidity

This study was aimed at investigating pathogenesis of pulmonary vascular abnormalities in COPD with systemic features, and ways to treat these circulatory disorders. Methods. We analyzed pulmonary vascular parameters, molecular markers of endothelial dysfunction, pulmonary artery pressure (PAP) and gas exchange in patients with moderate (n = 64) and severe (n = 70) COPD treated with basic therapy with or without an endothelial protector. Results. The results showed that perfusion disorders could appear in different parts of the lungs, probably, due to different mechanisms of these abnormalities. Localization of perfusion disorders was related to blood levels of molecular markers of endothelial dysfunction: adhesion molecules sP-selectin and sVCAM-1 were related to perfusion abnormalities in the upper lobes, VEGF-A was related to perfusion abnormalities in the lower lobes, and diffuse perfusion abnormalities were related to endothelin-1. Additional treatment with sulodexide improved endothelial function and pulmonary circulation, decreased PAP and blood concentrations of molecular markers of endothelial dysfunction. Conclusion. Predominant localization of microcirculatory abnormalities in COPD patients, especially in the lower lobes, is related to ventilation abnormalities, could predict clinical course of the disease and indicates the need in endotheliotropic therapy.

Indacaterol/glycopyrronium (IND/GLY) reduces the risk of clinically important deterioration (CID) in patients with moderate COPD: Results from the CRYSTAL study

Introduction: Decline in health status, lung function, and exacerbations are important determinants of disease progression of COPD patients (pts). CID has been proposed as a composite endpoint to evaluate COPD treatment effects. We report effect of IND/GLY on CID in pts with moderate COPD, after direct switch from LABA+ICS, or a LABA or a LAMA monotherapy. Methods: CRYSTAL, a 12-week, prospective, multicentre, randomised, open-label, pragmatic trial, evaluated the effect of IND/GLY or GLY after a direct switch from previous treatments in moderate COPD pts. CID was defined as a ≥100 mL decrease in trough FEV 1 or a ≥1 point decrease in transition dyspnoea index (TDI) or a ≥0.4 point increase in clinical COPD questionnaire (CCQ) score or a moderate/severe exacerbation. Results: Of 2,159 pts analysed in the IND/GLY treatment arms, 1,622 switched to IND/GLY and 537 continued their baseline treatment. The percentage of pts experiencing a CID was significantly lower in pts who switched to IND/GLY vs pts who continued on LABA+ICS, or on a LABA or a LAMA, using different CID definitions (Table) . Subgroup analyses according to different baseline characteristics were consistent with the overall results. Conclusion: Indacaterol/glycopyrronium significantly reduced the risk of CID in moderate COPD patients, after direct switch from LABA/ICS, or a LABA or a LAMA.

Chest wall strapping increases expiratory airflow and detectable airway segments in computer tomographic scans of normal and obstructed lungs.

Chest wall strapping (CWS) induces breathing at low lung volumes but also increases parenchymal elastic recoil. In this study, we tested the hypothesis that CWS dilates airways via airway-parenchymal interdependence. In 11 subjects (6 healthy and 5 with mild to moderate COPD), pulmonary function tests and lung volumes were obtained in control (baseline) and the CWS state. Control and CWS-CT scans were obtained at 50% of control (baseline) total lung-capacity (TLC). CT lung volumes were analyzed by CT volumetry. If control and CWS-CT volumetry did not differ by more than 25%, airway dimensions were analyzed via automated airway segmentation. CWS-TLC was reduced on average to 71% of control-TLC in normal subjects and 79% of control-TLC in subjects with COPD. CWS increased expiratory airflow at 50% of control-TLC by 41% (3.50 ± 1.6 vs. 4.93 ± 1.9 l/s, P = 0.04) in normals and 316% in COPD(0.25 ± 0.05 vs 0.79 ± 0.39 l/s, P = 0.04). In 10 subjects (5 normals and 5 COPD), control and CWS-CT scans at 50% control-TLC did not differ more than 25% on CT volumetry and were included in the airway structure analysis. CWS increased the mean number of detectable airways with a diameter of ≤2 mm by 32.5% (65 ± 10 vs. 86 ± 124, P = 0.01) in normal subjects and by 79% (59 ± 19 vs. 104 ± 16, P = 0.01) in subjects with COPD. There was no difference in the number of detectable airways with diameters 2-4 mm and >4 mm in normal or in COPD subjects. In conclusion, CWS enhances the detection of small airways via automated CT airway segmentation and increases expiratory airflow in normal subjects as well as in subjects with mild to moderate COPD. NEW & NOTEWORTHY In normal and COPD subjects, chest wall strapping(CWS) increased the number of detectable small airways using automated CT airway segmentation. The concept of dysanapsis expresses the physiological variation in the geometry of the tracheobronchial tree and lung parenchyma based on development. We propose a dynamic concept to dysanapsis in which CWS leads to breathing at lower lung volumes with a corresponding increase in the size of small airways, a potentially novel, nonpharmacological treatment for COPD.

Inhaled therapies in patients with moderate COPD in clinical practice: current thinking.

COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups.

Association between respiratory impedance measured by forced oscillation technique and exacerbations in patients with COPD.

BackgroundIt is well known that increased airflow limitation as measured by spirometry is associated with the risk of exacerbation in patients with COPD. The forced oscillation technique (FOT) is a noninvasive method used to assess respiratory impedance (resistance and reactance) with minimal patient cooperation required. The clinical utility of the FOT in assessing the risk of exacerbations of COPD is yet to be determined. We examined the relationship between respiratory impedance as measured by FOT and exacerbations in patients with COPD.Materials and methodsAmong 310 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages I–IV) who presented at the outpatient clinic of the Showa University Hospital from September 2014 through January 2015, 119 were collected and assigned into 2 groups according to their history of exacerbation: exacerbators and nonexacerbators. Respiratory resistance components and respiratory reactance components, as measured by FOT, were compared between the two groups.ResultsExacerbators were significantly older and had a higher white blood cell count than nonexacerbators. Resistance at 20 Hz, reactance at 5 Hz (X5), resonant frequency (Fres), and area of low reactance (ALX) differed significantly between the two groups. In addition, among patients with stage II COPD, there were significant differences in X5, Fres, and ALX between the two groups despite no significant differences in respiratory function as assessed by spirometry. Finally, receiver operating characteristic curve analysis revealed that the reactance components rather than the resistance components were associated with the risk of exacerbation.ConclusionThere were significant differences in respiratory impedance between exacerbators and nonexacerbators in patients with moderate COPD. FOT is a promising tool for assessing future exacerbations in patients with COPD.

INDACATEROL/GLYCOPYRRONIUM REDUCES THE RISK OF CLINICALLY IMPORTANT DETERIORATION IN PATIENTS WITH MODERATE COPD: RESULTS FROM THE CRYSTAL STUDY

RespirologyVolume 22, Issue S3 p. 179-180 APSR Poster Abstracts INDACATEROL/GLYCOPYRRONIUM REDUCES THE RISK OF CLINICALLY IMPORTANT DETERIORATION IN PATIENTS WITH MODERATE COPD: RESULTS FROM THE CRYSTAL STUDY First published: 23 November 2017 https://doi.org/10.1111/resp.13207_247Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 179-180 RelatedInformation

Sensory-mechanical effects of a dual bronchodilator and its anticholinergic component in COPD

This randomized, double-blind, crossover study examined the physiological rationale for using a dual long-acting bronchodilator (umeclidinium/vilanterol (UME/VIL)) versus its muscarinic-antagonist component (UME) as treatment for dyspnea and exercise intolerance in moderate COPD. After each 4-week treatment period, subjects performed pulmonary function and symptom-limited constant-work rate cycling tests with diaphragm electromyogram (EMGdi), esophageal (Pes), gastric (Pga) and transdiaphragmatic (Pdi) pressure measurements. Fourteen subjects completed the study. Both treatments improved spirometry and airway resistance. UME/VIL had larger increases in FEV1 (+0.14±0.23L, p<0.05) but no added reduction in lung hyperinflation compared with UME. Isotime during exercise after UME/VIL versus UME (p<0.05): “unpleasantness of breathing” fell 0.8±1.3 Borg units; mean expiratory flow and ventilation increased; Pdi and Pga decreased. There were no treatment differences in endurance time, breathing pattern, operating lung volumes, inspiratory neural drive (EMGdi) or respiratory muscle effort (Pes swings) during exercise. UME/VIL compared with UME was associated with reduced breathing unpleasantness reflecting improved airway and respiratory muscle function during exercise.

Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD.

Inhaled corticosteroid-containing medications reduce the frequency of COPD exacerbations (mainly infectious in origin) while paradoxically increasing the risk of other respiratory infections. The aim was to determine the effects of inhaled corticosteroids on airway microbial load in COPD patients and evaluate the influence of the underlying inflammatory profile on airway colonisation and microbiome.This is a proof-of-concept prospective, randomised, open-label, blinded endpoint study. Sixty patients with stable moderate COPD were randomised to receive one inhalation twice daily of either a combination of salmeterol 50 μg plus fluticasone propionate 500 μg or salmeterol 50 μg for 12 months. The primary outcome was the change of sputum bacterial loads over the course of treatment.Compared with salmeterol, 1-year treatment with salmeterol plus fluticasone was associated with a significant increase in sputum bacterial load (p=0.005), modification of sputum microbial composition and increased airway load of potentially pathogenic bacteria. The increased bacterial load was observed only in inhaled corticosteroid-treated patients with lower baseline sputum or blood eosinophil (≤2%) levels but not in patients with higher baseline eosinophils.Long-term inhaled corticosteroid treatment affects bacterial load in stable COPD. Lower eosinophil counts are associated with increased airway bacterial load.