Moderate-severe Chronic Obstructive Pulmonary Disease Research Articles

Association between Chronic Obstructive Pulmonary Disease and Hearing Loss with Impaired Speech Recognition: A Cross-Sectional Study

Introduction: Studies have identified a greater risk of sensory neural hearing loss in individuals with chronic obstructive pulmonary disease (COPD) compared to healthy individuals, but it is unclear whether they are at increased risk of hearing loss with impaired speech recognition. The aim of this study was to assess whether COPD is associated with hearing loss that affects speech recognition. Methods: This is a case-control study. We screened individuals from health facilities in the municipality of Jundiai. We enrolled a test group of individuals with COPD and an age-matched control group composed of individuals with asthma. The selected individuals attended an appointment with a chest physician, responded to questionnaires, and underwent tonal and speech audiometry. Adjusted binary logistic regression analysis evaluated whether COPD was associated with reduced speech recognition. Results: We enrolled 36 individuals with COPD and 72 with asthma. Individuals with COPD were more likely to have a reduced speech recognition compared to asthmatic individuals (reduced recognition of three-syllable words: adjusted OR 3.72, 95 CI [1.38–10.02]) (reduced recognition of monosyllable words: adjusted OR 4.74, 95 CI [1.52–14.76]). Conclusion: We conclude that individuals with COPD from primary and secondary healthcare facilities have at least 38% greater risk of hearing loss with reduced speech recognition compared to an age-matched control group of individuals with asthma recruited from the same facilities. We recommend that longitudinal studies evaluate whether regular screening could contribute to the prevention or early treatment of hearing loss in individuals with moderate-severe COPD.

P063 Long-term Non-invasive Ventilation in Patients with COPD: A Retrospective Cohort Study.

Abstract Introduction Domiciliary long-term non-invasive ventilation (LT-NIV) is an accepted therapy for patients with severe chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. This study aimed to characterise patients with COPD who were commenced on LT-NIV. Methods A retrospective analysis was performed of all patients prescribed LT-NIV with a primary physician-diagnosis of COPD, between June 2016 and March 2022 at an Australian tertiary hospital. Results 333 patients were commenced on LT-NIV, of whom 67 (20%) had COPD. Inpatient LT-NIV Initiation: 53/67 (79%) were commenced on LT-NIV during an inpatient admission with acute exacerbation of COPD. Patients were elderly (age, mean 69± SD 9.5 years), predominantly female (60%) with moderate-severe COPD (FEV1 37±18%) and mild-moderate comorbidity burden (Charlson Comorbidity Index Score 2.1±1.4). Prior to LT-NIV, 64% patients had a sleep study with 15% having severe OSA (AHI≥30 or ODI≥30). 30% previously required acute NIV. Pre-admission non-exacerbated PaCO2 was 58±7.3mmHg During admission, all inpatients demonstrated hypercapnia (PaCO2≥45mmHg). Peak inpatient PaCO2 was 87±20mmHg, with persistent hypercapnia on discharge 58±9.0mmHg. On discharge, IPAP and EPAP settings were 17±3.8 and 7.7cm±2.7cmH2O respectively. There was a non-significant reduction in respiratory-related and all-cause hospitalizations in the 12-months following LT-NIV initiation (p=0.66 and 0.53 respectively). Outpatient LT-NIV Initiation: [Further data collection in progress] Discussion This study illustrates the real-world prescription of LT-NIV for COPD at our centre, with the majority being initiated in the inpatient setting, rather than early outpatient reassessment. A prospective multi-centre analysis is required to better understand the nuances of LT-NIV prescription in patients with COPD.

Physiological predictors of resting pulmonary hypertension associated with COPD: a retrospective analysis

BackgroundResting pulmonary hypertension (PH) is not uncommon in patients with chronic obstructive pulmonary disease (COPD). In the current study, we aimed to identify physiological predictors of resting PH in patients with COPD.MethodsWe retrospectively analyzed data derived from right heart catheterization in sixty-nine stable patients with COPD. Patients were categorized into COPD-PH (n = 33) and COPD-non-PH (n = 36), based on the “6th World Symposium on PH.”ResultsDemographics, forced expiratory volume in 1 s (FEV1), lung volumes, cardiac output, and cardiac index were similar between groups, yet COPD-PH had greater pulmonary vascular resistance (PVR) and lower resting PaO2 (P < 0.05). The proportion of COPD-PH patients did not differ across the range of FEV1 (χ2 = 3.01, P = 0.22). No correlations were found between PVR and the degree of airflow obstruction or resting hyperinflation. Resting PaO2 was the only predictor of both pulmonary artery pressure and PVR.ConclusionsIncreased PVR, in response to arterial hypoxemia or directly induced by tobacco smoking, is likely the key factor that led to resting PH in the current sample of patients with moderate-severe COPD, regardless of the degree of airflow limitation or resting hyperinflation.

Airway and Systemic Prostaglandin E2 Association with COPD Symptoms and Macrophage Phenotype.

Polymorphisms and products of the cyclooxygenase (COX) pathway have been associated with the development of chronic obstructive pulmonary disease (COPD) and adverse outcomes. COX-produced prostaglandin E2 (PGE-2) may play a role in the inflammation observed in COPD, potentially through deleterious airway macrophage polarization. A better understanding of the role of PGE-2 in COPD morbidity may inform trials for therapeutics targeting the COX pathway or PGE-2. Urine and induced sputum were collected from former smokers with moderate-severe COPD. The major urinary metabolite of PGE-2 (PGE-M) was measured, and ELISA was performed on sputum supernatant for PGE-2 airway measurement. Airway macrophages underwent flow cytometry phenotyping (surface CD64, CD80, CD163, CD206, and intracellular IL-1β, TGF-β1). Health information was obtained the same day as the biologic sample collection. Exacerbations were collected at baseline and then monthly telephone calls. Among 30 former smokers with COPD (mean±SD age 66.4±8.88 years and forced expiratory volume in 1 second [FEV1] 62.4±8.37 percent predicted), a 1 pg/mL increase in sputum PGE-2 was associated with higher odds of experiencing at least one exacerbation in the prior 12 months (odds ratio 3.3; 95% confidence interval: 1.3 to15.0), worse respiratory symptoms and health status. PGE-M was not associated with exacerbations or symptoms. Neither airway PGE-2 nor urinary PGE-M was uniformly associated with an M1 or M2 polarization. Elevated levels of sputum PGE-2, rather than systemic PGE-2, is associated with increased respiratory symptoms and history of exacerbation among individuals with COPD. Additional studies focused on mechanism of action are warranted.

Decreased Cardiac Autonomic Function is Associated with Higher Exacerbation Risk and Symptom Burden in Chronic Obstructive Pulmonary Disease.

Current measures of chronic obstructive pulmonary disease (COPD) severity, including lung function, do not fully explain symptom burden, and there is a need to identify predictors of exacerbation risk and morbidity. Autonomic dysfunction may be implicated in both cardiovascular and respiratory morbidity in COPD and convey risk for exacerbations. Heart rate variability (HRV) is a marker of cardiac autonomic function that is predictive of cardiovascular health and has promise as a non-invasive COPD biomarker. The CLEAN AIR Heart study provided an opportunity to investigate the association between HRV and COPD morbidity among former smokers with moderate-severe COPD. Eighty-five participants, contributing 305 HRV measurements, underwent repeated clinical assessments over 4 study periods that included a 24-Holter monitoring assessment of HRV. HRV measures of interest were standard deviation of normal-to-normal intervals, (SDNN) (overall HRV) and root-mean-square of successive differences (RMSSD) (parasympathetic function). Exacerbation risk was assessed using negative binomial models, and mixed-effects models analyzed associations between HRV and symptoms. Decreases in SDNN (incidence rate ratio [IRR]1.40; 95% confidence interval [CI] 1.13 to1.74) and RMSSD (IRR 1.60; 95% CI 1.07 to 2.37) were associated with severe exacerbation risk. Decreases in SDNN were associated with higher St George's Respiratory Questionnaire scores, COPD Assessment Test scores, and chronic bronchitis symptoms. Findings demonstrate that HRV is associated with COPD symptom burden and exacerbation risk. HRV may represent an important biomarker with the potential to identify high-risk COPD populations.

MEASURES OF VENTILATION DERIVED FROM RADIOGRAPH VELOCIMETRY CORRELATE WITH SPIROMETRY IN PATIENTS WITH COPD

MEASURES OF VENTILATION DERIVED FROM RADIOGRAPH VELOCIMETRY CORRELATE WITH SPIROMETRY IN PATIENTS WITH COPD

Blood Eosinophils in Chinese COPD Participants and Response to Treatment with Combination Low-Dose Theophylline and Prednisone: A Post-Hoc Analysis of the TASCS Trial.

Background and ObjectivesThe burden of chronic obstructive pulmonary disease (COPD) disproportionately affects patients in low to middle-income countries. Although the Theophylline and Steroids in COPD Study (TASCS) showed no clinical benefit from administering low-dose theophylline and prednisone in COPD patients compared to placebo, it was hypothesized that those with elevated blood eosinophil counts would receive clinical benefit from the intervention.MethodsThis was a post-hoc analysis of the TASCS dataset – a double-blinded, placebo-controlled trial conducted in patients with moderate–severe COPD in China. Participants were allocated 1:1:1 to low-dose oral theophylline (100mg bd) and prednisone (5mg qd; PrT), theophylline (100mg bd) and prednisone-matched placebo (TP), or double-matched placebo (DP) groups and followed-up for 48 weeks. A baseline count of ≥300 eosinophils/µL blood was categorized as elevated/eosinophilic, and the primary outcome was the annualized moderate-severe exacerbation rate.ResultsOf 1487 participants eligible for analysis, 325 (22%) were eosinophilic. These participants were predominantly male (82%), had a mean (SD) age of 64 (±8) years and a predicted forced expiratory volume in 1s (FEV1) of 43% (±16). The annualized moderate–severe exacerbation rate was significantly higher in the PrT group compared to the pooled results of the TP and DP groups (incidence rate ratio = 1.6; ([95% CI 1.06–1.76]) p = 0.016). Changes in spirometry values and reported disease impact scores (St. George’s Respiratory Questionnaire and COPD Assessment Test) at week 48 were not significantly different between groups.ConclusionCombination low-dose theophylline and prednisone was associated with a significant increase in the annual moderate-severe exacerbation rate in participants with a blood eosinophil count ≥300 cells/µL compared to placebo.

Spatial Dependence of CT Emphysema in Chronic Obstructive Pulmonary Disease Quantified by Using Join-Count Statistics.

Background Existing CT emphysema measurements quantify the extent or clustering of emphysema voxels in chronic obstructive pulmonary disease (COPD); however, these measurements do not quantify how those voxels are clustered. Purpose To develop a CT measurement to quantify the "compactness" of emphysema voxels, called the normalized join count (NJC), and to determine whether the NJC measurement differentiates COPD disease severity and correlates with lung function and visual emphysema scores. Materials and Methods In this secondary analysis of a prospective study, lung function and CT images were obtained from the Canadian Cohort Obstructive Lung Disease study visit 1 from 2009 to 2013. Participants were categorized as never-smokers, at risk, mild COPD, or moderate-severe COPD. Diffusion capacity for carbon monoxide/alveolar volume was measured. CT emphysema was scored visually by radiologists. CT measurements included the percentage low-attenuation area with attenuation less than -950 HU (%LAA-950insp), low-attenuation cluster (LAC), and lowest 15th percentile point of the CT lung density histogram. NJC was developed to measure compactness of CT emphysema voxels. An analysis of variance determined differences between groups. Multivariable ridge regression determined association between CT measurements with lung function and radiologist scores. Results A total of 1294 participants (750 men; mean age, 67 years ± 10) were analyzed (277 never-smokers, 306 at risk, 427 mild COPD, and 284 moderate-severe COPD). NJC, %LAA-950insp, and LAC measurements were higher in moderate-severe COPD than in never-smokers and at-risk participants (P < .05 for all comparisons), but only NJC was different between mild and ;moderate-severe COPD (mean, 1.98% ± 3.61 vs 1.44% ± 2.14; P < .05). In multivariable regression analysis, among all CT measurements NJC had the greatest relative contribution to diffusion capacity for carbon monoxide/alveolar volume (P = .002) and visual emphysema score (P < .001). Conclusion The relationship of normalized join count with severity of chronic obstructive pulmonary disease may indicate that the assessment of this disease is dependent on the number of low attenuating voxels or the size of clusters and the spatial arrangement of such voxels. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Grenier in this issue.

Roflumilast: A Review of Chronic Obstructive Pulmonary Disease (COPD) Treatment

Abstract Chronic Obstructive Pulmonary Disease (COPD) is a chronic airway inflammation with resulting progressive airflow limitation that has a high incidence, morbidity, and mortality. Roflumilast is an oral phosphodiesterase-4 inhibitor as a therapy to decrease the risk of COPD exacerbations in patients with moderate-severe COPD with a history of chronic bronchitis. Roflumilast can be given orally once daily as a single or combination drug. It can be used as COPD moderate-severe but also more beneficial as COPD mild treatment. The efficacy of Roflumilast can prevent exacerbations of repetition and can fixed lung function both in terms of FEV1 and vital capacity to force. The incidence of side effects, which are diarrhea and digestive disorders. The cost-effectiveness showed that Quality of life patient with Roflumilast is better than the group without additional. This paper aimed to review systematically Roflumilast as COPD treatment for the clinical application.Keywords : COPD, Roflumilast, phosphodiesterase-4 inhibitorCorrespondence : fauna@staff.ubaya.ac.id

Bronchiectasis in patients with chronic obstructive pulmonary disease in a tertiary care center in North-East India

Bronchiectasis in patients with chronic obstructive pulmonary disease in a tertiary care center in North-East India

Evaluation of sleep quality and daytime somnolence in patients with chronic obstructive pulmonary disease in pulmonary rehabilitation

BackgroundDyspnea, fatigue, and decline in sleep quality are symptoms of chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation programs have been shown to ameliorate dyspnea and fatigue. However, only a few studies have investigated the effects of pulmonary rehabilitation on the sleep quality of COPD patients. In this study, we analyzed the benefits of a pulmonary rehabilitation program to sleep quality and daytime somnolence in COPD patients.MethodsThis study was a study of 30 moderate-severe COPD patients. All patients were evaluated by a pulmonologist and underwent polysomnography before participating in the study. For this study, we selected only ex-smokers and patients with sleep apnea were referred to the sleep clinic. These participants were prospectively recruited and not selected based on program completion. Before the start of the program, sleep quality and daytime somnolence of the participants were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS), respectively. Rehabilitation program consisted of muscular training sessions conducted at the gym 3 times per week for 12 weeks. After rehabilitation program, the patients were reassessed and their sleep quality and daytime somnolence were reevaluated using the PSQI and the ESS, respectively.ResultsBefore rehabilitation, PSQI evaluation revealed that 73% of the participants had poor sleep quality, and ESS evaluation showed that 86.7% of the participants experienced daytime somnolence. After pulmonary rehabilitation, the PSQI specifically improved in terms of subjective sleep quality and sleep duration (< 0.001), habitual sleep efficiency (0.001), and sleep latency and sleep alterations (0.002) and there was also improvement in the ESS (< 0.001).ConclusionPulmonary rehabilitation program of gradually increasing intensity has the potential to provide sleep-related benefits to patients with COPD who have poor sleep quality and daytime somnolence.Trial registrationRegistro Brasileiro de Ensaios Clínicos (ReBEC) RBR62b4z2.

Eficacia de la budesonida/formoterol comparado con la fluticasona/salmeterol en la mejoría de la capacidad pulmonar de personas mayores con Enfermedad Pulmonar Obstructiva Crónica: revisión sistemática de literatura

Introducción. La Enfermedad Pulmonar Obstructiva Crónica (EPOC) es una patología no transmisible, caracterizada por una limitación de flujo de aire en las vías respiratorias debido a una respuesta inmunológica anormal frente a partículas. Objetivo. Conocer la eficacia que tiene la budesonida/formoterol comparado con la fluticasona/salmeterol en la mejoría de la capacidad pulmonar en personas mayores de 40 años con Enfermedad Pulmonar Obstructiva Crónica. Materiales y métodos. Se realizó una revisión sistemática de documentos producidos entre el año 2000 y 2018 en distintas bases de datos, donde se incluyeron ensayos clínicos. Se identificaron cuatro artículos para el análisis final. Resultados. Durante la evaluación comparativa de budesonida con formoterol, los artículos muestran un total de 709 personas evaluadas, con un promedio de edad de 53,5 años. El 65,4 % eran varones, el 21 % manifestaba no haber consumido tabaco, todos con diagnóstico de Enfermedad Pulmonar Obstructiva Crónica moderada-severa, según la escala GOLD (Global Initiative For Chronic Obstrutive Lung Disease). Los estudios determinaron que al administrar budesonida/formoterol de 400/12 mcg y 320/9 mcg, los pacientes tuvieron una leve mejoría en el Volumen Espiratorio Forzado del primer segundo (VEF1). Solo dos pacientes presentaron efectos adversos. No obstante, para los resultados mencionados anteriormente no se encontró diferencias significativas. Conclusiones. El uso de budesonida/formoterol es eficaz al mejorar la capacidad ventilatoria pulmonar, disminuye el número de exacerbaciones anuales y genera un adecuado control de los síntomas, sin embargo, es igual de efectivo a la fluticasona/salmeterol.

Functional Status of Patients with COPD Assessed by London Chest Activity of Daily Living Scale: Gender Association and Validity of a Cutoff Point.

Whether the difference in the impact of chronic obstructive pulmonary disease (COPD) on the functional status of men and women stems from clinical distinctions or to the measuring instrument used is unclear. Like most instruments for assessing functional limitation in COPD, the interpretation of the results of the London Chest Activity of Daily Living (LCADL) scale is limited because a lack of a valid cutoff point to this scale. For that, this study sought to compare the functional status between men and women with COPD; and propose a cutoff point for LCADL capable of discriminating the prognosis of these individuals. A sample of 138 subjects with moderate-severe COPD was evaluated by the LCADL. The percentage of the individual maximum score was used to obtain a cutoff point capable of discriminating patients with the worse prognosis according to the BODE Index. The cutoff point was also tested in an independent sample (n = 70). Regarding the total score, domestic and leisure domains of the LCADL, men had better scores than women (P ≤ 0.01). The cutoff point found was 37% (area under the curve = 0.70, 95% confidence interval = 0.60-0.80, sensitivity = 0.55 and specificity = 0.74). Individuals who scored ≥ 37% had a worse prognosis and level of physical activities of daily living than those who scored below (P ≤ 0.02). When evaluated by the LCADL, men and women with COPD present difference in the functional status. The established cutoff point (37%) adequately discriminates individuals regarding the prognosis, contributing to improve the interpretation capacity of the LCADL.

Physical activity associates with disease characteristics of severe asthma, bronchiectasis and COPD.

Physical activity (PA) in obstructive airway diseases (OAD) is likely to be impaired but this has not been extensively studied outside of chronic obstructive pulmonary disease (COPD). We describe PA levels in severe asthma and bronchiectasis compared to moderate-severe COPD and to controls, and tested the cross-sectional associations of PA (steps/day) with shared disease characteristics in the OAD group. Adults with OAD (severe asthma = 62, COPD = 67, bronchiectasis = 60) and controls (n = 63) underwent a multidimensional assessment, including device-measured PA levels. The OAD group included 189 participants (58.7% females), with median (interquartile range) age of 67 (58-72) years and mean forced expiratory volume in the first second (FEV1 ) % predicted of 69.4%. Demographic characteristics differed between groups. Compared to controls (52.4% females, aged 55 (34-64) years, median 7640 steps/day), those with severe asthma, bronchiectasis and COPD accumulated less steps/day: median difference of -2255, -2289, and -4782, respectively (P ≤ 0.001). Compared to COPD, severe asthma and bronchiectasis participants accumulated more steps/day: median difference of 2375 and 2341, respectively (P ≤ 0.001). No significant differences were found between the severe asthma and bronchiectasis group. Exercise capacity, FEV1 % predicted, dyspnoea and systemic inflammation differed between groups, but were each significantly associated with steps/day in OAD. In the multivariable model adjusted for all disease characteristics, exercise capacity and FEV1 % predicted remained significantly associated. PA impairment is common in OAD. The activity level was associated with shared characteristics of these diseases. Interventions to improve PA should be multifactorial and consider the level of impairment and the associated characteristics.

Regional expiratory time constants in severe respiratory failure estimated by electrical impedance tomography: a feasibility study

BackgroundElectrical impedance tomography (EIT) has been used to guide mechanical ventilation in ICU patients with lung collapse. Its use in patients with obstructive pulmonary diseases has been rare since obstructions could not be monitored on a regional level at the bedside. The current study therefore determines breath-by-breath regional expiratory time constants in intubated patients with chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS).MethodsExpiratory time constants calculated from the global impedance EIT signal were compared to the pneumatic volume signals measured with an electronic pneumotachograph. EIT-derived expiratory time constants were additionally determined on a regional and pixelwise level. However, regional EIT signals on a single pixel level could in principle not be compared with similar pneumatic changes since these measurements cannot be obtained in patients. For this study, EIT measurements were conducted in 14 intubated patients (mean Simplified Acute Physiology Score II (SAPS II) 35 ± 10, mean time on invasive mechanical ventilation 36 ± 26 days) under four different positive end-expiratory pressure (PEEP) levels ranging from 10 to 17 cmH2O. Only patients with moderate-severe ARDS or COPD exacerbation were included into the study, preferentally within the first days following intubation.ResultsSpearman’s correlation coefficient for comparison between EIT-derived time constants and those from flow/volume curves was between 0.78 for tau (τ) calculated from the global impedance signal up to 0.83 for the mean of all pixelwise calculated regional impedance changes over the entire PEEP range. Furthermore, Bland-Altman analysis revealed a corresponding bias of 0.02 and 0.14 s within the limits of agreement ranging from − 0.50 to 0.65 s for the aforementioned calculation methods. In addition, exemplarily in patients with moderate-severe ARDS or COPD exacerbation, different PEEP levels were shown to have an influence on the distribution pattern of regional time constants.ConclusionsEIT-based determination of breath-by-breath regional expiratory time constants is technically feasible, reliable and valid in invasively ventilated patients with severe respiratory failure and provides a promising tool to individually adjust mechanical ventilation in response to the patterns of regional airflow obstruction.Trial registrationGerman Trial Register DRKS 00011650, registered 01/31/17.

The relationship between fear of movement, pain and fatigue severity, dyspnea level and comorbidities in patients with chronic obstructive pulmonary disease

Purpose: Dyspnea, sedentary lifestyle, and comorbid diseases may reduce the desire to engage in physical movement in chronic obstructive pulmonary disease (COPD). The aims of this study were to assess levels of kinesiophobia among stable COPD patients and evaluate the relationship between kinesiophobia and pain and fatigue severity, dyspnea level, and comorbidities in this patient group.Material and Methods: Thirty-one patients with moderate/severe COPD and thirty-one age- and sex-matched healthy controls participated in the study. All participants were assessed using Visual Analog Scale for pain severity, Fatigue Severity Scale, modified Medical Research Council Dyspnea Scale, Charlson Comorbidity Index, and Tampa Scale of Kinesiophobia.Results: Ninety-three percent of the patients with COPD had a high degree of kinesiophobia (Tampa Scale of Kinesiophobia score >37). The modified Medical Research Council Dyspnea Scale, Charlson Comorbidity Index, and Tampa Scale of Kinesiophobia scores of patients with COPD was significantly higher than those of healthy subjects (p < 0.001). Tampa Scale of Kinesiophobia score was significantly associated with modified Medical Research Council Dyspnea Scale score (r = 0.676, p < 0.001), Charlson Comorbidity Index score (r = 0.746, p < 0.001) and fatigue severity level (r = 0.524, p = 0.005).Conclusion: Most moderate/severe COPD patients express fear of movement. Kinesiophobia is strongly associated with dyspnea perception, fatigue severity, multisystemic comorbidities in COPD. Further studies are needed to determine the effects of kinesiophobia on the success of pulmonary rehabilitation.Implications for rehabilitationMost of moderate-to-severe chronic obstructive pulmonary disease patients have fear of movement.Increase fear of movement in moderate–severe chronic obstructive pulmonary disease is associated with increased dyspnea perception and fatigue severity and multisystemic comorbidities.

Disturbed blood flow worsens endothelial dysfunction in moderate-severe chronic obstructive pulmonary disease

The aims of this study were: (1) to test whether oscillatory shear stress further exacerbates endothelial dysfunction in patients with moderate-severe COPD, and (2) to test whether low flow oxygen administration improves endothelial function and is protective against oscillatory shear stress-induced endothelial dysfunction in patients with moderate-severe COPD. In 17 patients and 10 age-matched non-smoking control subjects we examined brachial artery flow-mediated dilation (FMD) and circulating microparticles before and after 20 minutes of experimentally-induced oscillatory shear stress. COPD patients performed this intervention a second time following a 20-minute wash in period of low flow supplemental oxygen to normalize arterial oxygen saturation. COPD patients had ~six-fold greater baseline retrograde shear rate (P < 0.05) and lower FMD (P < 0.05). The oscillatory shear stress intervention induced significant decreases in brachial artery FMD of all groups (P < 0.05). Oscillatory shear stress elevated circulating markers of endothelial cell apoptosis (CD31+/CD41b− microparticles) in COPD patients, but not age-matched controls. Supplemental oxygen administration abrogated the oscillatory shear stress-induced increase in CD31+/CD41b− microparticles, and improved FMD after accounting for the shear stress stimulus. We have demonstrated that acutely disturbed blood flow with increased retrograde shear stress further deteriorates the already impaired endothelial function with attendant endothelial apoptosis in patients with moderate-severe COPD.

Reproducibility of inspiratory muscle endurance testing using PowerBreathe for COPD patients.

Assessing the strength and endurance of respiratory muscles is fundamental for characterizing respiratory muscle dysfunction. Although a variety of tests are used to evaluate respiratory muscle endurance, not all of them are applicable in clinical practice. Assessments can be made using a practical device called PowerBreathe®, but its reproducibility has not been tested in chronic obstructive pulmonary disease (COPD) patients. To verify the reproducibility of the inspiratory muscle endurance test using a manometer and PowerBreathe® in COPD patients. A cross-sectional study was used. In total, 19 moderate-severe COPD patients, male and female, aged 50 to 80years took part in the research. This evaluation consisted of 2 tests: an incremental test and a constant one held on the same day and repeated after 48hr. The incremental test started with 10-cm H2 O, adding 10-cm H2 O every 2min and taking 1min of rest before increasing the load. The highest load that could be sustained for at least 1min was considered the sustained maximum inspiratory pressure (SMIP) value. The constant test was performed at an intensity of 80% of the SMIP and the maximum time limit was 30min. In the incremental test, there was a significant increase in the SMIP compared to the test-retest (61±24/64.7±23.8; p=.015); the value of the relative reproducibility was 0.96, the standard error of the absolute measurement was 4.7 (95% confidence interval 9.2), and the minimum detectable difference was 10.9. In the Bland-Altman analysis, the mean error was 4.2 (confidence interval -7.6 to 16.1). The constant test was not reproducible. It was observed that the incremental test was reproducible to evaluate inspiratory muscle endurance in COPD patients. Furthermore, 2 tests needed to be carried out due to the learning effect.

Benefits of Long-Term Pulmonary Rehabilitation Maintenance Program in Patients with Severe Chronic Obstructive Pulmonary Disease. Three-Year Follow-up.

In chronic obstructive pulmonary disease (COPD), the benefits of pulmonary rehabilitation (PR) tend to wane over time. Whether maintenance techniques may help sustain the benefits achieved after completion of the initial PR program remains controversial. To determine whether a long-term (3-yr) maintenance program after PR preserves the short-term effects on outcomes in patients with COPD. This was a multicenter prospective randomized trial including 143 patients with moderate-severe COPD, with 3 years of PR maintenance following an 8-week outpatient PR program. Patients were randomized to maintenance intervention group (IG) and standard monitoring program or control group (CG). The effects on BODE index, 6-minute-walk test distance (6MWD), and health-related quality of life were compared at 12, 24, and 36 months. A total of 138 (96.5%) completed the 8-week program. At this time, all outcomes (BODE, 6MWD, and health-related quality of life) showed clinically and statistically significant improvements (P ≤ 0.001). During the follow-up period, the magnitude of change in 6MWD differed between IG and CG (P = 0.042), with a slight initial increase in the IG during the first year and smaller decline afterward. The BODE index changes differed between baseline and measurements at Month 24 (P = 0.043). At 3 years, the adherence rate of IG patients was 66% and 17% for the CG group (P < 0.001). This study shows a 2-year beneficial effect of a program of rehabilitation maintenance on the BODE index and 6MWD when compared with a standard strategy. This effect vanishes after the second year of follow-up. Clinical trial registered with www.clinicaltrials.gov (NCT 01090999).

Airway inflammation in COPD after long-term withdrawal of inhaled corticosteroids.

Long-term treatment with inhaled corticosteroids (ICS) might attenuate lung function decline and decrease airway inflammation in a subset of patients with chronic obstructive pulmonary disease (COPD), and discontinuing ICS treatment could result in further lung function decline. We hypothesised that airway inflammation increases after ICS withdrawal following long-term ICS treatment in COPD.In the GLUCOLD-1 study (GL1), 114 patients with moderate-severe COPD were randomised to 6-month or 30-month treatment with fluticasone propionate (500 µg twice daily), 30-month treatment with fluticasone/salmeterol (500/50 µg twice daily) or placebo. During the 5-year follow-up study (GL2), patients were followed prospectively while being treated by their physician. Bronchial biopsies and induced sputum were collected at baseline, at 30 months (end of GL1) and at 7.5 years (end of GL2) to assess inflammatory cell counts. Data were analysed using linear mixed-effects models.In patients using ICS during GL1 and using ICS 0-50% of the time during GL2 (n=61/85), there were significant increases in GL2 bronchial CD3+ (fold change per year calculated as GL2 minus GL1 2.68, 95% CI 1.87-3.84), CD4+ (1.91, 95% CI 1.33-2.75) and CD8+ cells (1.71, 95% CI 1.15-2.53), and mast cells (1.91, 95% CI 1.36-2.68). The sputum total cell counts increased significantly in GL2 (1.90, 95% CI 1.42-2.54), as did counts of macrophages (2.10, 95% CI 1.55-2.86), neutrophils (1.92, 95% CI 1.39-2.65) and lymphocytes (2.01, 95% CI 1.46-2.78).ICS discontinuation increases airway inflammation in patients with moderate-severe COPD, suggesting that the anti-inflammatory effects of ICS in COPD are not maintained after ICS discontinuation.