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Background: COPD is characterized by reduced exercise tolerance, and improving physical performance is an important therapeutic goal. A variety of exercise tests are commonly used to assess exercise tolerance, including laboratory and field-based tests. The responsiveness of these various tests to common COPD interventions is yet to be compared, but the results may inform test selection in clinical and research settings., Research Question: What exercise test possesses the greatest sensitivity to change from before to after intervention in patients with COPD?, Study Design and Methods: One hundred fifty-four patients with symptomatic COPD were recruited and randomized (2:1:1) to 6 weeks of long-acting muscarinic antagonist, pulmonary rehabilitation (PR), or usual care. Before and after intervention, participants performed an incremental cycle exercise test and constant work rate cycle test (CWRCT), incremental shuttle walk test and endurance shuttle walk test (ESWT), 6-min walk test, and 4-m gait speed test., Results: One hundred three participants (mean ± SD age, 67 ± 8 years; 75 male participants [73%]; FEV 1 , 50.6 ± 16.8% predicted) completed the study. Significant improvements in the incremental cycle exercise test, CWRCT, incremental cycle exercise test, ESWT, and 6-min walk test results were observed after PR (P < .05), with the greatest improvements seen in the constant work rate protocols (percentages change: CWRCT, 42%; ESWT, 41%)., Interpretation: The ESWT and CWRCT seemed to be the most responsive exercise test protocols to long-acting muscarinic antagonist and PR therapy. The magnitude of change was much greater after a program of rehabilitation compared with bronchodilator therapy., Clinical Trial Registry: International Standard Randomised Controlled Trial Number (ISRCTN): No. 64759523; URL: https://www.isrctn.com/ISRCTN64759523., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: R. T.-S. is a retiree and shareholder of GlaxoSmithKline since 2019. M. A. is a former employee of GlaxoSmithKline. A.H is a former employee of Boehringer Ingelheim (Canada) Ltd. M. C. S reports personal fees and non-financial support from Boehringer Ingelheim and GlaxoSmithKline, outside the submitted work. None declared (T. C.H.-D., M. M. B, M. I. P, M. R, S. A. E, M. D. M, S. J. S)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: As the prevalence of multimorbidity increases, understanding the impact of isolated comorbidities in people COPD becomes increasingly challenging. A simplified model of common comorbidity patterns may improve outcome prediction and allow targeted therapy., Objectives: To assess whether comorbidity phenotypes derived from routinely collected clinical data in people with COPD show differences in risk of hospitalisation and mortality., Methods: Twelve clinical measures related to common comorbidities were collected during annual reviews for people with advanced COPD and k-means cluster analysis performed. Cox proportional hazards with adjustment for covariates was used to determine hospitalisation and mortality risk between clusters., Measurements and Main Results: In 203 participants (age 66 ± 9 years, 60 % male, FEV 1 %predicted 31 ± 10 %) no comorbidity in isolation was predictive of worse admission or mortality risk. Four clusters were described: cluster A (cardiometabolic and anaemia), cluster B (malnourished and low mood), cluster C (obese, metabolic and mood disturbance) and cluster D (less comorbid). FEV 1 %predicted did not significantly differ between clusters. Mortality risk was higher in cluster A (HR 3.73 [95%CI 1.09-12.82] p = 0.036) and B (HR 3.91 [95%CI 1.17-13.14] p = 0.027) compared to cluster D. Time to admission was highest in cluster A (HR 2.01 [95%CI 1.11-3.63] p = 0.020). Cluster C was not associated with increased risk of mortality or hospitalisation., Conclusions: Despite presence of advanced COPD, we report striking differences in prognosis for both mortality and hospital admissions for different co-morbidity phenotypes. Objectively assessing the multi-system nature of COPD could lead to improved prognostication and targeted therapy for patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chronic Obstructive Pulmonary Disease (COPD) is a common disease associated with significant morbidity and mortality that is both preventable and treatable. However, a major challenge in recognizing, preventing, and treating COPD is understanding its complexity. While COPD has historically been characterized as a disease defined by airflow limitation, we now understand it as a multi-component disease with many clinical phenotypes, systemic manifestations, and associated co-morbidities. Evidence is rapidly emerging in our understanding of the many factors that contribute to the pathogenesis of COPD and the identification of "early" or "pre-COPD" which should provide exciting opportunities for early treatment and disease modification. In addition to breakthroughs in our understanding of the origins of COPD, we are optimizing treatment strategies and delivery of care that are showing impressive benefits in patient-centered outcomes and healthcare utilization. This special issue of Respiratory Medicine, "COPD: Providing the Right Treatment for the Right Patient at the Right Time" is a summary of the proceedings of a conference held in Stresa, Italy in April 2022 that brought together international experts to discuss emerging evidence in COPD and Pulmonary Rehabilitation in honor of a distinguished friend and colleague, Claudio Ferdinando Donor (1948-2021). Claudio was a true pioneer in the field of pulmonary rehabilitation and the comprehensive care of individuals with COPD. He held numerous leadership roles in in the field, provide editorial stewardship of several respiratory journals, authored numerous papers, statement and guidelines in COPD and Pulmonary Rehabilitation, and provided mentorship to many in our field. Claudio's most impressive talent was his ability to organize spectacular conferences and symposia that highlighted cutting edge science and clinical medicine. It is in this spirit that this conference was conceived and planned. These proceedings are divided into 4 sections which highlight crucial areas in the field of COPD: (1) New concepts in COPD pathogenesis; (2) Enhancing outcomes in COPD; (3) Non-pharmacologic management of COPD; and (4) Optimizing delivery of care for COPD. These presentations summarize the newest evidence in the field and capture lively discussion on the exciting future of treating this prevalent and impactful disease. We thank each of the authors for their participation and applaud their efforts toward pushing the envelope in our understanding of COPD and optimizing care for these patients. We believe that this edition is a most fitting tribute to a dear colleague and friend and will prove useful to students, clinicians, and researchers as they continually strive to provide the right treatment for the right patient at the right time. It has been our pleasure and a distinct honor to serve as editors and oversee such wonderful scholarly work., Competing Interests: Declaration of competing interest To the best of my knowledge as editor and corresponding author for the above manuscript, neither I nor any of the coauthors or editor have any perceived conflict of interest with respect to the subject matter of this paper. This, by necessity, must be a preliminary statement, as I assume each author must at a later date submit a personal COI statement., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Eccentric cycling (ECC) may be an attractive exercise method in COPD because of both low cardiorespiratory demand and perception of effort compared with conventional concentric cycling (CON) at matched mechanical loads. However, it is unknown whether ECC can be performed by individuals with COPD at an intensity able to cause sufficient metabolic stress to improve aerobic capacity., Research Question: What are the cardiopulmonary and metabolic responses to ECC in people with COPD and healthy volunteers when compared with CON at matched mechanical loads?, Study Design and Methods: Thirteen people with COPD (mean ± SD age, 64 ± 9 years; FEV 1 , 45 ± 19% predicted; BMI, 24 ± 4 kg/m 2 ; oxygen uptake at peak exercise [V̇O 2peak ], 15 ± 3 mL/kg/min) and 9 age-matched control participants (FEV 1 , 102 ± 13% predicted; BMI, 28 ± 5 kg/m 2 ; V̇O 2peak , 23 ± 5 mL/kg/min), performed up to six 4-min bouts of ECC and CON at matched mechanical loads of increasing intensity. In addition, 12 individuals with COPD underwent quadriceps muscle biopsies before and after 20 min of ECC and CON at 65% peak power., Results: At matched mechanical loads, oxygen uptake, minute ventilation, heart rate, systolic BP, respiratory exchange ratio (all P < .001), capillary lactate, perceived breathlessness, and leg fatigue (P < .05) were lower in both groups during ECC than CON. Muscle lactate content increased (P = .008) and muscle phosphocreatine decreased (P = .012) during CON in COPD, which was not evident during ECC., Interpretation: Cardiopulmonary and blood lactate responses during submaximal ECC were less compared with during CON at equivalent mechanical workloads in healthy participants and COPD patients, and this was confirmed at a muscle level in COPD patients. Submaximal ECC was well tolerated and allowed greater mechanical work at lower ventilatory cost. However, in people with COPD, a training intervention based on ECC is unlikely to stimulate cardiovascular and metabolic adaptation to the same extent as CON., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Cognitive impairment (CI) is prevalent in COPD and is associated with poor health-related quality of life. Recovery of cognition following an acute exacerbation of COPD (AECOPD), the impact of CI on pulmonary rehabilitation (PR) uptake and the effect of PR on CI are not fully understood., Methods: This 6-week prospective study analysed 67 people with stable COPD symptoms who completed PR (PR group) and the recovery of 45 people admitted for AECOPD (AECOPD group). All participants were assessed for cognitive function (Montreal Cognitive Assessment [MoCA]), health status (COPD Assessment Test, Chronic Respiratory Questionnaire), lower extremity function (Short Physical Performance Battery), and psychological well-being (Hospital Anxiety and Depression Score). Follow up assessments were carried out after a 6-week recovery post-discharge in AECOPD group and after PR in the PR group., Results: AECOPD group showed no improvement in MoCA following a 6-week recovery post-discharge (Δ-0.8 ± 3.2, p = 0.205), despite improvements in all other clinical outcomes. PR uptake among the AECOPD group was not associated with the presence of CI (p = 0.325). Participants in the PR group with CI at baseline showed a significant improvement in MoCA score following PR (Δ1.6 ± 2.4, p = 0.004)., Conclusions: Cognition does not improve following 6-week recovery post-AECOPD, and CI may influence patients' response to PR referral as an inpatient. PR improves cognition in people with stable COPD symptoms and CI. People with AECOPD should be actively encouraged to attend PR irrespective of mild-moderate cognition but may require additional support or opportunities to take part., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Despite the wide-ranging benefits of pulmonary rehabilitation, conflicting results remain regarding whether people with COPD can improve their peak oxygen uptake (V˙O 2peak) with aerobic training., Research Question: The goal of this study was to investigate the effect of aerobic training and exercise prescription on V˙O 2peak in COPD., Study Design and Methods: A systematic review was performed by using MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases for all studies measuring V˙O 2peak prior to and following supervised lower-limb aerobic training in COPD. A random effects meta-analysis limited to randomized controlled trials comparing aerobic training vs usual care was conducted. Other study designs were included in a secondary meta-analysis and meta-regression to investigate the influence of program and patient factors on outcome., Results: A total of 112 studies were included (participants, N = 3,484): 21 controlled trials (n = 489), of which 13 were randomized (n = 288) and 91 were uncontrolled (n = 2,995) studies. Meta-analysis found a moderate positive change in V˙O 2peak (standardized mean difference, 0.52; 95% CI, 0.34-0.69) with the intervention. The change in V˙O 2peak was positively associated with target duration of exercise session (P = .01) and, when studies > 1 year duration were excluded, greater total volume of exercise training (P = .01). Similarly, the change in V˙O 2peak was greater for programs > 12 weeks compared with those 6 to 12 weeks when adjusted for age and sex. However, reported prescribed exercise intensity (P = .77), training modality (P > .35), and mode (P = .29) did not affect V˙O 2peak . Cohorts with more severe airflow obstruction exhibited smaller improvements in V˙O 2peak (P < .001)., Interpretation: Overall, people with COPD achieved moderate improvements in V˙O 2peak through supervised aerobic training. There is sufficient evidence to show that programs with greater total exercise volume, including duration of exercise session and program duration, are more effective. Reduced effects in severe disease suggest alternative aerobic training methods may be needed in this population., Clinical Trial Registration: PROSPERO; No.: CRD42018099300; URL: https://www.crd.york.ac.uk/prospero/., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Patients with moderate exacerbations of COPD and the eosinophilic phenotype have better outcomes with prednisolone. Whether this outcome is similar in patients hospitalized with a severe exacerbation of COPD is unclear. We investigated the rate of recovery of eosinophilic and noneosinophilic exacerbations in patients participating in a multicenter randomized controlled trial assessing health outcomes in hospitalized exacerbations., Methods: Patients were recruited at presentation to the hospital with an exacerbation of COPD. They were stratified into groups according to eosinophilic exacerbations if the peripheral blood eosinophil count on admission was ≥ 200 cells/μL and/or ≥ 2% of the total leukocyte count. Admission details, serum C-reactive protein levels, length of stay, and subsequent rehospitalization data were compared between groups., Results: A total of 243 patients with COPD (117 men) with a mean age of 71 years (range, 45-93 years) were recruited. The inpatient mortality rate was 3% (median time to death, 12 days; range, 9-16 days). The median absolute eosinophil count was 100 cells/μL (range, 10-1,500 cells/μL), and 25% met our criteria for an eosinophilic exacerbation; in this population, the mean length of stay (in days) was shorter than in patients with noneosinophilic exacerbations (5.0 [range, 1-19] vs 6.5 [range, 1-33]; P = .015) following treatment with oral corticosteroids and independent of treatment prior to admission. Readmission rates at 12 months were similar between groups., Conclusions: The study patients presenting to the hospital with a severe eosinophilic exacerbation of COPD had a shorter length of stay. The exacerbations were usually not associated with elevated C-reactive protein levels, suggesting that better treatment stratification of exacerbations can be used., Trial Registry: http://www.isrctn.com/ISRCTN05557928., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Pulmonary Rehabilitation (PR) reduces hospital admissions following an acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD) but adherence is known to be poor. Patients' illness perceptions may affect adherence to disease-management strategies but to date have not been explored following an exacerbation. The study aim is two-fold; firstly to prospectively explore acceptance and uptake of post-exacerbation PR and secondly to identify possible clusters of patients' illness perceptions following hospitalisation for an exacerbation of COPD., Methods: Patients admitted to hospital with an exacerbation of COPD were recruited to a prospective observational study. Self-reported illness perceptions, mood, health status and self-efficacy were assessed. Acceptance and uptake of PR were recorded at six months. Cluster analysis of Illness Perceptions Questionnaire-Revised data was used to establish groups of patients holding distinct beliefs., Results: 128 patients were recruited. Acceptance and uptake of PR following an acute exacerbation was poor with only 9% (n = 11) completing the programme. Cluster analysis revealed three distinct groups: Cluster 1 'in control' (n = 52), Cluster 2 'disengaged' (n = 36) and Cluster 3 'distressed' (n = 40). Significant between-cluster differences were observed in mood, health status and self-efficacy (p < 0.01). Acceptance and uptake of PR did not differ between clusters., Conclusions: Acceptance/uptake of post-exacerbation PR was found to be poor. Three distinct illness schema exist in patients following an acute exacerbation. This information may be useful in developing novel psychologically-informed interventions designed to reduce feelings of distress and perhaps facilitate a PR intervention for this vulnerable population., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Quadriceps dysfunction in COPD may be mediated by inflammatory mechanisms or impaired satellite cell function. Resistance training is of proven efficacy in these patients, but data on muscle inflammatory and satellite cell response to resistance exercise in COPD are lacking.We aimed to examine the inflammatory and satellite cell profile of the quadriceps in patients with COPD and healthy control subjects at rest and after acute and chronic resistance exercise., Methods: Seventeen patients with COPD and 10 healthy control subjects underwent 8 weeks ofbilateral lower-limb, high-intensity resistance training, thrice weekly, on an isokinetic dynamometer.Quadriceps muscle biopsy specimens from the dominant thigh were obtained at baseline,24 h following the fi rst exercise bout, and after 8 weeks 24 h after the last exercise bout. Glycolmethacrylate-embedded muscle biopsy specimens were analyzed using immunohistochemistry to identify neutrophils, macrophages, and satellite cells., Results: Neutrophils were significantly elevated in the quadriceps of patients with COPD at baseline compared with healthy control subjects ( P 5 .03). Inflammatory cells were increased significantly at 24 h in both groups but were similar to baseline values at week 8, with no difference detectable between healthy control subjects and patients with COPD. Satellite cell numbers were comparable between patients and control subjects at baseline, tended to increase at 24 h, and remained elevated at week 8., Conclusions: Inflammatory cells are elevated in the resting quadriceps of patients with COPD. Acute resistance exercise leads to an inflammatory myositis, which is attenuated with regular training. Satellite cells in patients and control subjects are comparable and are increased in response to exercise., Trial Registry: ISRCTN Register ; No.: ISRCTN22764439; URL: www.controlled-trials.com.

Background: Patients with COPD have a high prevalence of anxiety and depression. The efficacy of pulmonary rehabilitation (PR) in treating more severe anxiety and depression is unknown. The study aimed to explore the effectiveness of PR in reducing symptoms of anxiety and depression across a spectrum of severities., Methods: The study used principles of comparative effectiveness research. Data was analysed from 518 patients with COPD [57.5% male, mean (SD) age 69.2 years (± 8.8 years)]. Patients were categorised into 3 groups based on their hospital anxiety and depression scale (HADS) scores pre PR ('none' 0-7, 'probable' 8-10 and 'presence' 11-21). A responder was defined as achieving a change of ≥ 48 m on the incremental shuttle walk test (ISWT). Patients were categorised as 'completers' if they attended their discharge assessment for PR., Results: Anxiety and depression did not reduce following PR in patients with no symptoms (p > 0.05). Patients with a 'probable' or 'presence' of symptoms had significant reductions (both p < 0.001). There was a difference between sub-groups in change for anxiety and depression with patients scoring highest on the HADS having the greatest reductions (p < 0.001). There was no correlation between anxiety or depression and completion of PR (p > 0.05). Responders and non-responders did not differ in their anxiety or depression levels (p > 0.05)., Conclusion: PR is effective in reducing symptoms of anxiety and depression. Previous studies may have underestimated the effectiveness of the PR programme in improving mood., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The BODE index has been shown to predict mortality in COPD. The index includes the 6 min walking test as the measure of exercise capacity. The incremental shuttle walking test (ISWT) is an alternative measure of exercise capacity which can be used to prescribe exercise and has been found to correlate well with peak VO2. The objective of the study was to evaluate the incorporation of the ISWT within the BODE index (named the i-BODE) to predict mortality in COPD., Methods: Data was analysed from 633 patients with COPD attending pulmonary rehabilitation over an 11 year period, and mortality determined a minimum of one year on from initial assessment. An i-BODE score was calculated using ISWT(m) then Cox regression analysis evaluated the capacity of the index to predict risk of death., Results: BMI, ISWT (m), MRC dyspnoea score, pack years and age were all significantly associated with mortality. Cox regression revealed the i-BODE index was an independent and significant predictor of mortality (hazard ratio 1.27 (CI 1.17-1.35), p < 0.001) and Kaplan Meier survival analysis showed each quartile increase in severity in i-BODE score was significantly associated with increased mortality (p < 0.001 by log rank test)., Conclusion: We have found the i-BODE index to be an independent predictor of mortality in COPD, even when other strong predictors such as age and pack years are adjusted for. We conclude that the ISWT can be successfully substituted for the 6MWT as an alternative measure of exercise capacity within the BODE index., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In COPD, skeletal muscle ATP resynthesis may be insufficient to meet demand during exercise due to excessive anaerobic and reduced oxidative (mitochondrial) energy production, leading to metabolic stress. We investigated the effect of outpatient pulmonary rehabilitation (PR) on the metabolic response (measured by exercise-induced accumulation of plasma ammonia) and determined whether this response predicted functional improvement following PR. 25 subjects with stable COPD [mean (SD) age 67 (8)years and FEV(1) 47 (18)% predicted] performed maximal cycling ergometry before and after PR. Plasma ammonia was measured at rest, during exercise and 2 min post-exercise. Following PR, there were significant increases in peak cycle WR and ISWT performance (Mean (SEM) changes 13.1 (2.0) W and 93 (15) m respectively, p < 0.001). Mean (SEM) rise in plasma ammonia was reduced at peak (Pre vs Post-PR: 29.0 (4.5) vs 20.2 (2.5) μmol/l, p < 0.05) and isotime (Pre vs Post-PR: 29.0 (4.5) vs 10.6 (1.7) μmol/l, p < 0.001) exercise. Improvements in exercise performance after PR were similar among subgroups who did versus those who did not show a rise in ammonia at baseline. The results suggest that muscle cellular energy production was better matched to the demands of exercise following PR. We conclude that a pragmatic outpatient PR programme involving high intensity walking exercise results in significant adaptation of the skeletal muscle metabolic response with a reduction in exercise-related metabolic stress. However, the outcome of PR could not be predicted from baseline metabolic response., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Patients with Chronic Heart Failure (CHF) develop similar symptoms of exertional breathlessness and fatigue as patients with COPD. Although pulmonary (exercise based) rehabilitation (PR) is an integral part of the management of COPD, the potential for exercise rehabilitation (ER) to assist patients with CHF may not be as readily appreciated. We investigated whether combined ER for patients with CHF and COPD was feasible and effective using the model of PR., Methods: 57 patients with CHF were randomized 2:1 to 7 weeks ER (CHF-ER) or 7 weeks of usual care (CHF-UC). As a comparator 55 patients with COPD were simultaneously recruited to the same ER program (COPD-ER). The primary outcome measure was the Incremental Shuttle Walk Test (ISWT) and the secondary outcome measures were the Endurance Shuttle Walk Test (ESWT), isometric quadriceps strength and health status., Results: 27 CHF and 44 COPD patients completed ER and 17 patients with CHF completed UC. The CHF-ER group made significant improvements, compared to CHF-UC, in the mean (95%CI) ISWT distance; 62(35-89)m vs -6(-11 to 33)m p < 0.001. The CHF-ER group also made statistically significant improvements in health status. The improvements in exercise performance and health status were similar between patients with CHF and COPD, treated with ER., Conclusion: Patients with CHF who undergo ER improve similarly in their exercise performance and health status to COPD. Combined training programs for COPD and CHF are effective and feasible, such that service provision could be targeted around common disability rather than the primary organ disease.

Objective: It is well documented that plasma ammonia accumulates during exercise under conditions of metabolic stress. Metabolic stress (when skeletal muscle ATP supply fails to meet demand) occurs at low work rates during cycling in patients with COPD, but not been described during walking. Walking is an important activity for many patients with COPD and is commonly prescribed in pragmatic outpatient pulmonary rehabilitation programmes. In this study we explored whether metabolic stress occurs during incremental walking at the low work rates these patients achieve., Methods: Twenty-nine subjects with stable COPD [mean(SD) age 68(7)years, FEV(1) 50(19)% predicted] performed maximal cardiopulmonary exercise tests on a cycle ergometer and treadmill. Plasma ammonia concentration was measured at rest, 1 and 2min of exercise, peak exercise and 2min recovery., Results: Subjects achieved mean(SD) cycle work rate of 57(20)W with VO(2max) 15.5(4.6)ml/min per kg, and treadmill distance 284(175)m with VO(2peak) 16.8(4.2)ml/min per kg. Plasma ammonia concentration rose significantly (p<0.001) with walking [mean(SEM) change 24.7(3.8)micromol/l] and cycling [mean(SEM) change 35.2(4.3)micromol/l], but peak exercise ammonia was lower in walking (p<0.01). In a subgroup of subjects (n=7) plasma ammonia did not rise during either cycling or walking despite similar lactate rise and peak exercise indices., Conclusion: Our data indicate that failure of muscle ATP re-synthesis to meet demand and development of metabolic stress can occur during walking in COPD patients at the low work rates these patients achieve. This may therefore be a factor contributing to exercise limitation independent of ventilatory limitation.

Background: Impaired skeletal muscle function contributes to exercise intolerance in patients with COPD. Exercise-induced oxidative stress may initiate or accelerate impaired muscle function. Dichloroacetate (DCA) activates muscle pyruvate dehydrogenase complex (PDC) at rest, reducing inertia in mitochondrial energy delivery at the onset of exercise and thereby diminishing anaerobic energy production. This study aimed to determine whether DCA infusion also may reduce exercise-induced systemic oxidative stress and inflammatory response in patients with COPD., Methods: A randomized, double-blind crossover design was used in which 13 patients with COPD performed maximal cycle exercise after an IV infusion of DCA (50 mg/kg body mass) or saline solution (placebo). Venous blood was sampled before exercise, and immediately, 30 min, and 2 h after exercise. Urine samples were obtained before and 2 h after exercise., Results: Peak workload improved significantly after DCA infusion compared to placebo (10%; p < 0.01). Urinary uric acid levels after exercise were significantly lower in the DCA condition than in the placebo condition, whereas no significant difference was observed for urinary malondialdehyde levels. Oxidized glutathione (GSSG) levels were significantly increased 2 h after exercise in the placebo condition (p < 0.02) but not after DCA infusion. No changes in reduced glutathione (GSH), GSSG/GSH ratio, and superoxide dismutase activity were observed. Plasma interleukin (IL)-6 levels significantly increased 2 h after exercise only in the DCA condition (p < 0.01)., Conclusions: This study shows that improved performance after a pharmacologic intervention known to activate PDC was accompanied by an enhanced IL-6 response and a limited reduction in exercise-induced systemic oxidative stress.

The effects of increasing the fractional concentration of oxygen in the inspired gas to 1.0 on intrapulmonary shunting (Qsp) was evaluated in 82 intubated cardiovascularly stable patients in intensive care, regardless of airway pressure therapy or preexistent pulmonary pathologic abnormalities. Intrapulmonary shunting following administration of 100 percent oxygen increased in 132 of 140 measurements, decreased in seven, and remained unchanged in one measurement. The direction of change of Qsp with 100 percent oxygen shows no correlation with either airway pressure therapy or preexisting pulmonary disease.