Oxidative Stress Markers in COPD Patients Admitted to Pulmonary Rehabilitation

Background: Chronic obstructive pulmonary disease (COPD) is a pathology, which leads to an irreversible and progressive reduction of the airflow, usually caused by smoking, but only present in 25% of smokers. Some mechanisms involved in the onset and progression of the disease are local and systemic factors such as inflammation, exacerbated immune response and the appearance of oxidative stress. For all these reasons, the use of oxidative stress parameters as progression markers or even as a way to monitor the response of any kind of non-pharmacological interventions, like the use of pulmonary rehabilitation (PR), is feasible. Aims: The study aims to determine markers of oxidative stress levels in plasma and erythrocytes in patients with COPD through the application of a PR protocol. Methods: The study included 25 patients diagnosed with COPD according to the GOLD criteria with a medical indication of PR and attendance at the gym in San José Hospital, Santiago, Chile. Blood samples were obtained before the start of the protocol, in the 10th session, and at the end of the protocol (20th session). These samples were stored for oxidative stress determinations: FRAP (ferric reducing ability of plasma), F2-isoprostanes, reduced (GSH)/oxidized (GSSG) ratio and antioxidant enzyme activity in the erythrocyte. In all stages, associations between events and clinical parameters in patients have been observed. The clinical parameters assessed were the six-minute walking test (6MWT), maximal inspiratory and expiratory pressure, the BODE index and Saint George’s respiratory questionnaire, which includes quality of life. Results: The intracellular and extracellular capacity (GSH/GSSG and FRAP) in patients in PR at the 10th session were 53.1 and 34% higher than basal values, respectively. Only the GSH/GSSG ratio was 38.2% lower at the 20th session, related in part with higher plasma and erythrocyte lipid peroxidation at baseline. This could be due to the high concentration of reactive oxygen species in the first sessions, which has been reported in the literature as the acute effect of controlled exercise. Blood lipid peroxidation was 43.34 and 58.34% lower at the 10th and 20th sessions, respectively, demonstrating the improvements in the oxidative parameters with long-term exercise. With respect to oxidative enzyme activity, superoxide dismutase and catalase showed higher values of activity at the 10th and 20th sessions compared to the baseline. In the clinical parameters of the PR, significant changes were found in the BODE index and Saint George’s questionnaire, with these results being associated with a less predictive mortality score and a better understanding of the disease. This may be because the patients achieved longer distances in the 6MWT and better understood the disease at the end of the PR. Conclusion: The goal of this study was to contribute to the pathophysiological basis for further research on COPD patients, a disease of high prevalence in Chile. This study could support the basis for non-pharmacological strategies such a PR.

Study of Levels of Plasma Fibrinogen and its Association with Disease Severity in Patients with Chronic Obstructive Pulmonary Disease

COPD has been recognized as a component of the systemic inflammatory syndrome. A commonly used indicator of the severity and progression of the disease in COPD is expiratory volume per second (FEV1). However, it is weakly associated with symptoms and administration difficulties in elderly patients. Therefore, there is a need for other markers that are better and easy to apply to sick and elderly patients. Plasma fibrinogen can be used as a marker of disease severity. Aim: To estimate the plasma fibrinogen level in patients with COPD and Relationship of levels of plasma fibrinogen with the severity of chronic obstructive pulmonary disease using the BODE classification and GOLD staging. Place and Duration: In the Medicine Unit-II of Jinnah Hospital Lahore for one-year duration from August 2020 to August 2021. Methods: In this cross-sectional study, 110 COPD patients were assessed by measuring plasma fibrinogen correlated with disease severity using the GOLD scale, BODE index and the 6-minute walk test. Results: Plasma fibrinogen is present in all COPD patients. A significant correlation was observed between the BODE index (r = 0.69, p <0.001), gold grading (r = 0.95, p <0.001) and plasma fibrinogen levels. Most of the 110 subjects (34.5%) were Grade II, then Grade III 30.9%, 18.1% Grade IV and 14.5% Grade I. In our study, it was found that the average level of fibrinogen increased with the increase in the GOLD stage, which was statistically significant, and the p value was 0.01. Conclusions: Plasma fibrinogen levels are significantly higher in COPD and can be used as a marker correlating with disease severity in COPD. Keywords: COPD; plasma fibrinogen; GOLDEN stage; BODE index.

Blood Eosinophils and Pulmonary Rehabilitation in COPD

Background. Blood eosinophils predict the response to therapy, risk of exacerbation, and readmission in COPD. This study investigates whether blood eosinophils predict pulmonary rehabilitation (PR) outcomes in COPD. Methods. We categorized patients into eosinophilic (blood eosinophils ≥300 cells/ml) or noneosinophilic (<300 cells/ml). In a retrospective design, we compared changes within and between the two groups on BODE index, 6-minute walk test (6MWT), FEV1, and mMRC dyspnea scale. Results. Of 206 patients enrolled, 176 were included for analysis; 90 were eosinophilic. BODE index improved in both groups: (MD −1.25; 95% CI (−0.45, −4.25), P ≤ 0.001 ) in the eosinophilic and (MD −1.33; 95% CI (−1.72, −0.94), P ≤ 0.001 ) in the noneosinophilic, but a higher BODE index remained in the eosinophilic (4.98); adjusted mean change (β): 0.7 (95% CI (0.15, 1.26), P = 0.01 ). 6MWT improved by 29.3 m in the eosinophilic (95% CI (14.2, 44.4), P ≤ 0.001 ) vs. 115.1 m in the noneosinophilic (95% CI (−30.4, 260.6), P = 0.12 ). FEV1 did not change in the eosinophilic (MD −0.6; 95% CI (−2.64, 1.48), P = 0.58 ), but improved by 2.5% in the noneosinophilic (MD 2.5; 95% CI (0.77, 4.17), P = 0.005 ). There were no significant between-group differences in 6MWT and FEV1; adjusted mean changes (β) were −9.69 m (95% CI (−39.51, 20.14), P = 0.52 ) and −2.31% (95% CI (−5.69, 1.08), P = 0.18 ), respectively. There were no significant within- or between-group changes in the mMRC scale. Conclusion. Although PR improves the BODE index in both eosinophilic and noneosinophilic COPD, a higher eosinophil count (≥300 cells/ml) is associated with a higher (worse) BODE index. Blood eosinophils may predict PR outcomes.

RELATIONSHIP OF MEAN PLATELET VOLUME WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ITS SEVERITY- AN OBSERVATIONAL STUDY

Background & Objectives: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and inflammation. Mean platelet volume (MPV) may be used as a marker of inflammation. We aimed to study the association between MPV and COPD patients during acute attack and relationship of MPV with severity of COPD by FEV1 (%predicted), BODE Index, PaO2, mMRC grade and 6MWD test. Methods: 100 patients with COPD (50 with acute exacerbation and 50 with stable COPD) and 30 healthy controls were enrolled in the study. Mean platelet volume (MPV), spirometry, arterial blood gases, body mass index, renal function tests and BODE index (body mass index, airflow obstruction,dyspnoea and exercise) were assessed. Level of MPV was compared between cases and controls. Results: Of 100 COPD patients, 87(87%) were male and 13(13%)were female.MPV was significantly higher in COPD patients than control and also higher in acute exacerbation group than stable COPD (p=0.001). Interpretation & Conclusions: In the present study,MPV remain in normal range in all COPD patients, but MPV values were significantly higher in COPD cases compared with control.Increased MPV was associated with acute exacerbation and also increasing with severity of COPD.

Comparative effectiveness of pneumococcal vaccination with PPV23 and PCV13 in COPD patients over a 5-year follow-up cohort study

Vaccination against Streptococcus pneumoniae is among the most effective measures for preventing pneumonia and reducing the rate of chronic obstructive pulmonary disease (COPD) exacerbations. The objective of this work was to evaluate the long-term effectiveness of PCV13 and PPV23 for preventing pneumonia and COPD exacerbations. The open-label, prospective, observational cohort study involved 302 male patients aged ≥ 45 years: PCV13 group (n = 123); PPV23 group (n = 32); and vaccine-naïve group (n = 147). The primary endpoint included the frequency of pneumonia episodes and COPD exacerbations per year over a 5-year follow-up period. The secondary endpoints included the dynamics of dyspnea severity (MMRC), the BODE index, FEV1, the CAT index, the SGRQ score, and the results of 6-min walk test. Vaccination with PCV13 and PPV23 significantly reduces the total rate of pneumonia during the first year after vaccination. Starting with the second year, clinical effectiveness in PPV23 group decreases compared with both PCV13 group and vaccine-naïve patients. Pneumonia by year 5 after vaccination was registered in 47% of patients in the PPV23 group, versus 3.3% of patients in the PCV13 group (p < 0.001); COPD exacerbations—in 81.3% versus 23.6%, respectively (p < 0.001). Vaccination with PCV13 significantly reduced and maintained the BODE index over the 5-year follow-up period. Although both vaccines have comparable clinical effects during the first year after vaccination, only PCV13 is characterized by persistent clinical effectiveness during the 5-year follow-up period. Patients older than 55 years who received PPV23 have significantly higher risks of having pneumonia episodes more frequently during the long-term follow-up.

Endobronchial Valve (Zephyr) Treatment in Homogeneous Emphysema: One-Year Results from the IMPACT Randomized Clinical Trial

<b><i>Rationale:</i></b> The long-term safety and effectiveness of bronchoscopic lung volume reduction with Zephyr endobronchial valves in subjects with severe homogeneous emphysema with little to no collateral ventilation beyond 3 months have yet to be established. <b><i>Methods:</i></b> Ninety-three subjects were randomized to either bronchoscopic lung volume reduction with Zephyr valves or standard of care (SoC) (1:1). Zephyr valve subjects were assessed at 3, 6, and 12 months. SoC subjects were assessed at 3 and 6 months; they were then offered crossover to Zephyr valve treatment. <b><i>Results:</i></b> The mean group difference (Zephyr valve – SoC) for change in FEV₁ from baseline to 6 months was 16.3 ± 22.1% (mean ± SD; <i>p</i> &#x3c; 0.001). Secondary outcomes showed the mean between-group difference for the six-minute walk distance of +28.3 ± 55.3 m (<i>p</i> = 0.016); St. George’s Respiratory Questionnaire, −7.51 ± 9.56 points (<i>p</i> &#x3c; 0.001); modified Medical Research Council, −0.42 ± 0.81 points (<i>p</i> = 0.019); BODE index, −0.85 ± 1.39 points (<i>p</i> = 0.006); and residual volume of −430 ± 830 mL (<i>p</i> = 0.011) in favor of the Zephyr valve group. At 6 months, there were significantly more responders based on the minimal clinically important difference for these same measures in the Zephyr valve versus the SoC group. The clinical benefits were persistent at 12 months. The percentage of subjects with respiratory serious adverse events was higher in the Zephyr valve group compared to SoC during the first 30 days post-procedure but not statistically different for the Zephyr valve and SoC groups from 31 days to 6 months, and stable in the Zephyr valve group out to 12 months. There were 2 deaths in the SoC group in the 31-day to 6-month period and none in the Zephyr valve group out to 12 months. <b><i>Conclusions:</i></b> Bronchoscopic lung volume reduction with Zephyr valves in subjects with severe homogeneous emphysema and little to no collateral ventilation provides clinically meaningful change from baseline in lung function, quality of life, exercise capacity, dyspnea, and the BODE index at 6 months, with benefits maintained out to 12 months.

Efficacy and Safety of Modified Bushen Yiqi Formulas(MBYF) as Add-On To Formoterol and Budesonide in The Management of COPD: Study Protocol for A Multi-Center, Double-Blinded, Placebo-Controlled, Parallel-Group, Randomized Clinical Trial

Introduction Inhaled glucocorticoid Corticosteroids(ICS), long-acting β2-adrenoceptor agonists(LABA)and other drugs have limited therapeutic effects on COPD with significant individual differences. Traditional Chinese Medicine (TCM) modified Bushen Yiqi formulas༈MBYF༉demonstrates advantages in COPD management in China. This study aims to confirm the related genes affecting the therapeutic effect in the treatment of COPD and evaluate the efficacy and safety of MBYF as an add-on to budesonide/ formoterol on COPD patients. Methods and analysis In this multicenter, randomized, double-blinded, placebo-controlled, parallel-group study, eligible patients with COPD will randomly receive 360-day placebo or MBYF as an add-on to budesonide/ formoterol in 1:1 ratio, and followed-up bimonthly. The primary outcomes are frequency, times and severity of acute exacerbation of COPD (AECOPD), COPD assessment test (CAT) score, pulmonary function tests(PFTs). The secondary outcomes include the modified medical research council (mMRC) dyspnea scale、six minutes walking test (6MWT)、BODE index、quantitative scores of TCM syndrome、inflammation indexes and hypothalamic pituitary adrenaline (HPA) axis function. We also test the genotype to find the relationship between drugs and efficacy. All the data will be recorded in case report forms(CRFs) and analyzed by SPSS V.20.0. Trial registration number ChiCTR1900026124, Prospective registration. Protocol version 2019-09-15

Comparative Effectiveness of Pneumococcal Vaccination With PPV23 and PCV13 in COPD Patients Over a 5-Year Follow-Up Cohort Study

BackgroundVaccination against Streptococcus pneumoniae is among the most effective measures for preventing pneumonia and reducing the rate of chronic obstructive pulmonary disease (COPD) exacerbations. The objective of this work was to evaluate the long-term effectiveness of PCV13 and PPV23 for preventing pneumonia and COPD exacerbations.MethodsThe open-label, prospective, observational cohort study involved 302 male patients aged ≥45 years: PCV13 group (n=123); PPV23 group (n=32); and vaccine-naïve group (n=147). The primary endpoint included the frequency of pneumonia episodes and COPD exacerbations per year over a 5-year follow-up period. The secondary endpoints included the dynamics of dyspnea severity (MMRC), the BODE index, FEV1, the CAT index, the SGRQ score, and the results of 6-min walk test.ResultsVaccination with PCV13 and PPV23 significantly reduces the total rate of pneumonia during the first year after vaccination. Starting with the second year, clinical effectiveness in PPV23 group decreases compared with both PCV13 group and vaccine-naïve patients. Pneumonia by year 5 after vaccination were registered in versus 47% of patients in the PPV23 group 3.3% of patients in the PCV13 group (p<0.001); COPD exacerbations – in 81.3% versus 23.6%, respectively (p<0.001). Vaccination with PCV13 significantly reduced and maintained the BODE index over the 5-year follow-up period.ConclusionAlthough both vaccines have comparable clinical effects during the first year after vaccination, only PCV13 is characterized by persistent clinical effectiveness during the 5-year follow-up period. Patients older than 55 years on PPV23 have significantly higher risks of having pneumonia episodes more frequently during the long-term follow-up.

The Maugeri daily activity profile: a tool to assess physical activity in patients with chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) report reduced physical activity (PA). There are only few tools available to assess PA and sedentary behavior in these patients, and none of them aims to differentiate between sedentary and active patterns. The aim of the study was to evaluate an easy tool to profile daily activity time in a cohort of patients with COPD, compared to healthy subjects; the study was set at the Istituti Clinici Scientifici Maugeri (ICS), IRCCS of Tradate and Lumezzane, Italy, and at the Ente Ospedaliero Cantonale Novaggio, Switzerland (Italian Speaking). The populations were inpatients with COPD, healthy subjects. The items of the Maugeri Daily Activity (MaDA) profile were chosen based on literature, interviews with patients and health professionals. Time spent during sleep (ST), when awake (AT), active (ACT) or in sedentary behavior (SET) were recorded. Lung function tests, arterial blood gases, the modified Medical Research Council (mMRC), the six-minute walking distance test (6MWD), the COPD Assessment Test (CAT), and the body-mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index were also assessed in patients. Sixty patients with COPD and 60 healthy controls filled in the questionnaire. As compared to controls, patients showed longer AT and SET. Active time of patients was significantly correlated with mMRC, CAT, Bode Index and 6MWD, but not with demographics, anthropometrics or stages of disease. Using this tool, we found that patients with COPD spent longer time awake and in sedentary behavior. The MaDA may be useful to evaluate PA in patients with COPD.