Impact of Treatable Traits on Asthma Control and Quality of Life.

BACKGROUND: Many adult patients with asthma have uncontrolled disease and impaired quality of life, despite current asthma-specific drug therapies. OBJECTIVE: This study aimed to investigate the prevalence of 9 traits in patients with asthma, their associations with disease control and quality of life, and referral rates to nonmedical health care professionals. METHODS: Retrospectively, data from patients with asthma were collected in 2 Dutch hospitals (Amphia Breda and RadboudUMC Nijmegen). Adult patients without exacerbation <3 months who were referred for a first-ever elective, outpatient, hospital-based diagnostic pathway were deemed eligible. Nine traits were assessed: dyspnea, fatigue, depression, overweight, exercise intolerance, physical inactivity, smoking, hyperventilation, and frequent exacerbations. To assess the likelihood of having poor disease control or decreased quality of life, the odds ratio (OR) was calculated per trait. Referral rates were assessed by checking patients' files. RESULTS: A total of 444 adults with asthma were studied (57% women, age: 48 ± 16 years, forced expiratory volume in 1 second: 88% ± 17% predicted). Most patients (53%) were found to have uncontrolled asthma (Asthma Control Questionnaire ≥1.5 points) and decreased quality of life (Asthma Quality of Life Questionnaire <6 points). Generally, patients had 3.0 ± 1.8 traits. Severe fatigue was most prevalent (60%) and significantly increased the likelihood of having uncontrolled asthma (OR: 3.0, 95% confidence interval [CI]: 1.9-4.7) and decreased quality of life (OR: 4.6, 95% CI: 2.7-7.9). Referrals to nonmedical health care professionals were low; most referrals were to a respiratory-specialized nurse (33%). CONCLUSION: Adult patients with asthma with a first-ever referral to a pulmonologist frequently exhibit traits justifying the deployment of nonpharmacological interventions, especially in those with uncontrolled asthma. However, referrals to appropriate interventions appeared infrequent.

Patient activation is a treatable trait in patients with chronic airway diseases: An observational study.

Background: Self-management is key for reducing the burden of disease in chronical illness. However, applying self-management presupposes behavioral change. Sufficient knowledge, skills, confidence and motivation to make the needed behavior changes are important prerequisites. During the past years the Integral Diagnostic Trajectory was developed for patients with asthma or COPD which aims to identify treatable traits and activating patients for self-management. Objective: In the present study the effects of the Integral Diagnostic Trajectory on the Patient Activation Measure (PAM®) were examined. In addition, predictive variables for PAM baseline scores and change scores were sought. Materials and methods: A total of 241 patients with asthma or COPD referred to the pulmonologist at the Radboud university medical center, location Dekkerswald, Nijmegen were included. Patient activation was measured before the first visit and after the intervention with the 13-item PAM®. Additional, patient characteristics and health status were measured with the Nijmegen Clinical Screening Instrument (NCSI), modified Medical Research Council (mMRC), Asthma Control Questionnaire (ACQ), and COPD Clinical Questionnaire (CCQ). Results: Fifty percent of the patients with asthma and seventy percent of the patients with COPD had low levels of activation at baseline (PAM level 1-2). Baseline PAM scores could be explained in patients with asthma for 7% by number of severe problems in health status. And for 18% in patients with COPD by number of severe problems, age and employment status. After the intervention both groups significantly improved on the PAM (T0: 56.0 ± 13.1 vs. T1:63.3 ± 14.0 in asthma, and T0: 50.0 ± 8.8 vs. 58.4 ± 11.1 in COPD). Multivariate stepwise regression analysis showed that only 24% of the change in score could be explained by baseline PAM score and being employed in patients with asthma, and 18% of the variance in change score could be predicted by baseline PAM score in COPD. Conclusion: The present study showed that low level of activation is a common feature in patients with asthma and COPD. With a relatively short and seemingly simple intervention patients can reach higher levels of patient activation, which is a prerequisite for adopting self-management techniques in daily life.

Longitudinal Analysis of Quadriceps Muscle Strength in Patients with Previous COVID-19 Hospitalization and in Patients with Post-Acute Sequelae following Mild COVID-19.

Muscle weakness is a prominent symptom in post-acute sequelae of COVID-19 (PASC). However, few studies have objectively and longitudinally assessed muscle strength after varying COVID-19 severity grades. This observational study aimed to explore the prevalence, determinants, and 1.5 years change of quadriceps muscle weakness in 98 patients discharged from COVID-19 hospitalization and in 50 patients with PASC following mild COVID-19. Isometric quadriceps maximal voluntary contraction (MVC) was assessed on a computerized dynamometer at three visits. Also, in a subgroup of 14 post-COVID-19 patients with quadriceps muscle weakness, muscle thickness and echo intensity were determined by muscle ultrasound of nine upper and lower extremity muscles. Muscle weakness was found in 59% of post-hospitalized patients and in 65% of those with PASC following mild COVID-19 at ~14 weeks after acute COVID-19. Whereas during ~1.5 years follow-up MVC modestly improved, muscle weakness prevalence remained unchanged. Hospital length of stay and diabetes mellitus were identified as possible predictors of muscle weakness following COVID-19 hospitalization. No predictors could be identified in those with PASC following mild COVID-19. Ultrasound outcomes revealed no large structural abnormalities. In conclusion, clinically relevant muscle weakness is common after COVID-19 and its long-term improvement is poor. Future studies with relevant control groups are warranted to confirm our data.

Persistent Exertional Dyspnea and Perceived Exercise Intolerance After Mild COVID-19: A Critical Role for Breathing Dysregulation?

OBJECTIVE: After mild COVID-19, a subgroup of patients reported post-acute-phase sequelae of COVID-19 (PASC) in which exertional dyspnea and perceived exercise intolerance were common. Underlying pathophysiological mechanisms remain incompletely understood. The purpose of this study was to examine outcomes from cardiopulmonary exercise testing (CPET) in these patients. METHODS: In this observational study, participants were patients who were referred for the analysis of PASC after mild COVID-19 and in whom CPET was performed after standard clinical workup turned out unremarkable. Cardiocirculatory, ventilatory, and metabolic responses to and breathing patterns during exercise at physiological limits were analyzed. RESULTS: Twenty-one patients (76% women; mean age = 40 years) who reported severe disability in physical functioning underwent CPET at 32 weeks (interquartile range = 22-52) after COVID-19. Mean peak O2 uptake was 99% of predicted with normal anaerobic thresholds. No cardiovascular or gas exchange abnormalities were detected. Twenty of the 21 patients (95%) demonstrated breathing dysregulation (ventilatory inefficiency [29%], abnormal course of breathing frequency and tidal volume [57%], absent increase of end-tidal Pco2 [57%], and abnormal resting blood gases [67%]). CONCLUSION: Breathing dysregulation may explain exertional dyspnea and perceived exercise intolerance in patients with PASC after mild COVID-19 and can be present in the absence of deconditioning. This finding warrants further study on the levels of neural control of breathing and muscle function, and simultaneously provides a potential treatment opportunity. IMPACT: This study contributes to the understanding of persistent exertional dyspnea and perceived exercise intolerance following mild COVID-19, which is vital for the development of effective rehabilitation strategies.

Prevalence of hyperventilation in patients with asthma.

OBJECTIVE: Asthma is frequently accompanied by dysfunctional breathing of which hyperventilation has been recognized as a subtype. The prevalence of hyperventilation in stable asthma has been scantily studied using blood gas analysis. Hence, a reliable estimate of its prevalence is lacking. It is unknown whether the Nijmegen Questionnaire (NQ) is a useful screening tool for hyperventilation in asthma. Therefore, the primary aim of this study was to determine the prevalence of hyperventilation in a large sample of patients with asthma in a stable state of disease. Secondary aims were to compare the clinical characteristics between patients with and without hyperventilation, and, to examine the concurrent validity of the NQ to detect hypocapnia in patients with asthma. METHODS: A real-world, observational, multicenter study was conducted. Capillary blood gas analysis was performed in adults with a confirmed diagnosis of stable asthma. A subset of patients completed the NQ. RESULTS: A blood gas analysis was obtained in 1006 patients. In 17% of the patients an acute hyperventilation was found, and in another 23% a chronic hyperventilation was uncovered. Patients with a chronic hyperventilation blood gas were more often female, were younger and had a better spirometric outcomes. The NQ appeared not to correlate with PCO2. CONCLUSION: Hyperventilation is common in patients with stable asthma. Chronic hyperventilation is more often found in females of younger age and with the best spirometric outcomes compared to patients without hyperventilation. The NQ is not a suitable screening tool for the presence of hyperventilation in stable asthmatics.

Correlates of variability in endurance shuttle walk test time in patients with chronic obstructive pulmonary disease.

BACKGROUND: The endurance shuttle walk test (ESWT) is used to evaluate exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). The recommended pre-intervention tolerated duration (Tlim) is between 3-8 minutes for optimal interpretation of treatment effects. However, this window may be exceeded and factors determining ESWT Tlim are not completely understood. Therefore, we aimed to determine whether pulmonary function, physical and incremental shuttle walk test (ISWT) performance measures are associated with ESWT Tlim in COPD patients. METHODS: Assessment data from patients eligible for pulmonary rehabilitation was retrospectively analyzed. Inclusion criteria were: diagnosis of COPD and complete data availability regarding ESWT and ISWT. Patients performed an ESWT at 85% of ISWT speed and were divided into three groups (ESWT Tlim: <3 minutes, 3-8 minutes, >8 minutes). Subject characteristics, severity of complaints, pulmonary function, physical capacity and activity, exercise tolerance and quadriceps muscle strength were evaluated. RESULTS: 245 COPD patients (FEV1 38 (29-52)% predicted) were included. Median ESWT Tlim was 6.0 (3.7-10.3) minutes, 41 (17%) patients walked <3 minutes and 80 (33%) patients walked >8 minutes. Body mass index, maximal oxygen consumption, Tlim on constant work rate cycle test, physical activity level, maximal ISWT speed, dyspnoea Borg score at rest and increase of leg fatigue Borg score during ISWT independently predicted Tlim in multivariate regression analysis (R2 = 0.297, p<0.001). CONCLUSION: This study reported a large variability in ESWT Tlim in COPD patients. Secondly, these results demonstrated that next to maximal ISWT speed, other ISWT performance measures as well as clinical measures of pulmonary function, physical capacity and physical activity were independent determinants of ESWT Tlim. Nevertheless, as these determinants only explained ~30% of the variability, future studies are needed to establish whether additional factors can be used to better adjust individual ESWT pace in order to reduce ESWT Tlim variability.

"Can Do" Versus "Do Do" in Patients with Asthma at First Referral to a Pulmonologist.

BACKGROUND: Pharmacotherapy is key in asthma control, including preventing lung function decline, in primary care. However, patients' physical functioning (eg, physical capacity [PC] [=can do] and physical activity [PA] [=do do]) correlates poorly with lung function. Therefore, a better insight into the physical function of patients with asthma is needed, using the "can do, do do" concept. OBJECTIVE: To explore the "can do, do do" concept in adult patients with asthma at referral for the first time to an outpatient consultation of a pulmonologist. METHODS: PC was measured using the six-minute walk test and PA by using an accelerometer. Patients were classified into quadrants: low PC (6-minute walking distance <70% predicted), low PA (<7000 steps/d, "'can't do, don't do"); preserved PC, low PA ("can do, don't do"); low PC, preserved PA ("'can't do, do do"); or preserved PC, preserved PA ("can do, do do"). RESULTS: A total of 479 patients with asthma had a median (interquartile range) 6-minute walking distance of 74% (66%-82%) predicted, and walked 6829 (4593-9075) steps/d. Only 29% were classified as "can do, do do," whereas 30% were classified as "can't do, don't do." The Asthma Control Questionnaire and the Asthma Quality of Life Questionnaire scores were worst in the "can't do" groups. CONCLUSIONS: Low PC and/or PA was found in most patients with asthma at the index referral to a pulmonologist. An impaired PC is accompanied by a significantly reduced asthma control and disease-specific quality of life. This justifies further studies on safety and efficacy of nonpharmacological interventions, such as physiotherapy.

[Medicinal intervention for COPD; even in patients with mild or moderate COPD?]. / Medicamenteuze interventie bij COPD, ook bij patiënten met lichte en matige COPD?

The classification of COPD based only on the presence of airway obstruction fails to provide insight into the burden of the disease, quality of life and prognosis. The severity of symptoms, degree of exercise intolerance and presence of comorbidity are also determinants for classifying the severity of the disease. COPD starts with abnormalities in the bronchiolar compartment which cause obstruction in the airways. This results in incomplete expiration; first during exercise and later, also at rest. This is called dynamic hyperinflation or air trapping. Such changes in the mechanics of breathing occur early in course of the disease, even in mild COPD (the GOLD I stage), and contribute to physical inactivity and deconditioning. Maximal bronchodilation--more precisely: bronchiolodilation--reduces the mechanism of dynamic hyperinflation inasmuch as the condition allows. This has a positive effect on the symptoms of dyspnoea during exercise and thus on exercise capacity and trainability, even early on in the disease. Medicinal therapy has a positive effect on the progression of COPD, also in the early stages of disease.

Resting and ADL-induced dynamic hyperinflation explain physical inactivity in COPD better than FEV1.

BACKGROUND: Physical activity and health status deteriorate early in the course of chronic obstructive pulmonary disease (COPD). This can only partially be explained by the degree of airflow limitation. Changes in (resting and dynamic) lung volumes are known to be associated with functional impairments and thus might influence physical activity level. The aim of the present cross-sectional study was to explore the contribution of dynamic hyperinflation during daily life activities (ADL) in the decline in physical activity. METHODS: Airflow limitation and inspiratory capacity at rest to total lung capacity ratio (IC/TLC) as a measure of resting hyperinflation were measured in 59 patients with COPD (GOLD I-IV). Mean daily physical activity was assessed with a tri-axial accelerometer. Measurements of dynamic hyperinflation during ADL (ΔIC and inspiratory reserve volume at end ADL) were performed at patients' home using a portable breath-by-breath system. RESULTS: Multiple regression analysis showed that resting as well as ADL-induced dynamic hyperinflation independently contributed to decreased daily physical activity, together explaining 45.8% of the variance in physical activity. In contrast to hyperinflation, the severity of airflow limitation (FEV1) appeared to have no unique part in explaining how physically (in-) active patients were. CONCLUSIONS: The presence of resting hyperinflation and occurrence of dynamic hyperinflation during ADL contribute to reduced physical activity levels in patients with COPD, independently of the degree of airflow limitation.

Diagnostic accuracy of metronome-paced tachypnea to detect dynamic hyperinflation.

INTRODUCTION: This prospective study was carried out to investigate if metronome-paced tachypnea (MPT) can serve as an accurate diagnostic tool to identify patients with chronic obstructive pulmonary disease (COPD) who are susceptible to develop dynamic hyperinflation during exercise. Commonly, this is assessed by measuring change in inspiratory capacity (IC) during cardiopulmonary exercise testing (CPET), which, however, is complex and laborious. METHODS: Fifty-three patients with COPD (FEV(1) 58 ± 22%pred) and 20 age-matched healthy subjects were characterized by lung function testing and performed CPET (reference standard) and MPT. The repeatability coefficient of IC (10·2%) was used as cut-off to classify subjects as hyperinflators during CPET. Subsequently, dynamic hyperinflation was measured after MPT. With receiver operating characteristic analysis, the optimal cut-off for MPT-induced dynamic hyperinflation was determined and sensitivity and specificity of MPT to identify hyperinflators were evaluated. RESULTS: With 10·2% decrease in IC as cut-off for CPET-induced dynamic hyperinflation, the optimal cut-off for MPT was 11·1% decrease in IC. Using these cut-offs, MPT had a sensitivity of 85% and specificity of 85% to identify the subjects who hyperinflated during CPET. CONCLUSIONS: The MPT test shows good overall accuracy to identify subjects who are susceptible to develop dynamic hyperinflation during CPET. Before considering the use of MPT as a screening tool for dynamic hyperinflation in COPD, sensitivity and specificity need further evaluation.

COPD Anno 2011: emphasis on bronch(iol)odilation.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of disability and death worldwide. Although COPD is considered to be a preventable and treatable disease, there are concerns that COPD remains substantially underdiagnosed and undertreated. Even in mild disease, patients suffer from significant impairments in health status, which places a considerable burden on patients as well as society. Symptomatic patients are likely to progress to more advanced disease. To avoid breathlessness, they adapt and gradually reduce their activities, which, inevitably, leads to further deconditioning. As a consequence, a progressive deterioration in physical activity with increasing severity of COPD can be observed. Because physical activity is closely related to exacerbation rate, hospitalization, and mortality in patients with COPD, it is important to recognize the role of pharmaceutical interventions in enabling patients to stay physically active. Bronch(iol)odilation not only has important direct effects (symptom relief), but also exerts indirect effects on exercise capacity, exacerbation rate, health status, and mortality. In patients with COPD, the latter effects may be even more important than the direct effects. In this review the current view on causes and consequences of activity limitation in COPD is summarized. From this perspective, the rationale behind bronch(iol)odilator therapy as the cornerstone of treatment for patients with COPD will be discussed.

Similar dynamic hyperinflation during arm and leg exercise at similar ventilation in chronic obstructive pulmonary disease.

PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) report more dyspnea during arm than during leg exercise. One of the major causes of dyspnea is dynamic hyperinflation (DH), which is caused by airflow limitation as well as increase in ventilation. The aims of our study were to compare DH at equal ventilation (isoventilation) during arm and legwork and to investigate the effects of breathing pattern on DH. METHODS: Thirteen clinically stable patients with mild to very severe COPD (forced expiratory volume in 1 s = 59% ± 21%) participated in this study. Arm and leg constant work rate (CWR) ergometry were performed in random order with ventilation equal to that at 50% of peak armload. The corresponding leg load of that level of ventilation was determined from the incremental leg test. Respiratory physiology was measured breath-by-breath. Change in inspiratory capacity, measured at rest and at 2-min intervals, was used to reflect DH. RESULTS: At steady-state isoventilation (37 ± 2 and 36 ± 2 L · min for arm and leg CWR tests, respectively, P > 0.05), armload was 29 ± 5 W and leg load was 52 ± 6 W (P < 0.001). The level of DH, 0.32 ± 0.09 and 0.27 ± 0.08 L during arm and leg exercises, respectively, was not significantly different. However, breathing frequency was greater during arm than during leg exercise (24 ± 1 vs 21 ± 1 breaths per minute, P < 0.01), and the opposite was true for tidal volume (1.56 ± 0.15 vs 1.69 ± 0.14 L, P < 0.01). CONCLUSIONS: At similar ventilation, we found a similar degree of DH during arm and leg CWR tests in patients with mild to very severe COPD. Although differences in breathing pattern were observed between arm and leg exercises, these did not affect the level of DH.

Heart failure and COPD: partners in crime?

Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are both common diseases with major impact and seem to coexist more frequently than expected from their separate population prevalences. However, estimates of combined prevalence must be interpreted carefully because of imperfections and difficulties in assessment of both diseases. This review aims to highlight HF prevalence in patients with COPD and vice versa, with a critical analysis of studies performed. First, definition, diagnosis, and prevalence of COPD and of HF will be discussed. Subsequently, an overview of important studies concerning combined prevalence with their limitations will be presented. Finally, pathogenic mechanisms and diagnostic considerations in clinical practice will be discussed.

Dynamic hyperinflation during daily activities: does COPD global initiative for chronic obstructive lung disease stage matter?

BACKGROUND: One of the contributors to exercise limitation in COPD is dynamic hyperinflation. Although dynamic hyperinflation appears to occur during several exercise protocols in COPD and seems to increase with increasing disease severity, it is unknown whether dynamic hyperinflation occurs at different severity stages according to the Global initiative for chronic Obstructive Lung Disease (GOLD) in daily life. The present study, therefore, aimed to compare dynamic hyperinflation between COPD GOLD stages II-IV during daily activities. METHODS: Thirty-two clinically stable patients with COPD GOLD II (n = 10), III (n = 12), and IV (n = 10) participated in this study. Respiratory physiology during a daily activity was measured at patients' homes with Oxycon Mobile. Inspiratory capacity maneuvers were performed at rest, at 2-min intervals during the activity, and at the end of the activity. Change in inspiratory capacity is commonly used to reflect change in end-expiratory lung volume (DeltaEELV) and, therefore, dynamic hyperinflation. The combination of static and dynamic hyperinflation was reflected by inspiratory reserve volume (IRV) during the activity. RESULTS: Overall, increase in EELV occurred in GOLD II-IV without significant difference between the groups. There was a tendency for a smaller DeltaEELV in GOLD IV. DeltaEELV was inversely related to static hyperinflation. IRV during the daily activity was related to the level of airflow obstruction. CONCLUSIONS: Dynamic hyperinflation occurs independent of GOLD stage during real-life daily activities. The combination of static and dynamic hyperinflation, however, increases with increasing airflow obstruction.

Six-minute walking-induced systemic inflammation and oxidative stress in muscle-wasted COPD patients.

BACKGROUND: Systemic inflammation and oxidative stress are potential mechanisms for muscle wasting in COPD patients. Six-minute walking testing (6MWT) has been suggested as simple and valid exercise test in COPD that is well tolerated, and reflective of activities of daily living. The present study investigated physiologic and systemic immunologic responses to a 6MWT in muscle-wasted patients with COPD and compared them with maximal cardiopulmonary exercise testing (CPET). METHODS: Ten patients with muscle-wasted COPD were included (fat-free mass index [FFMI]: men, < 16 kg/m2; women, < 15 kg/m2). 6MWT and CPET were performed in random order. The physiologic response was followed by a mobile oxycon. Arterial blood was obtained at rest and after exercise to measure blood gases and markers of systemic inflammation and oxidative stress. RESULTS: In these patients (FEV1 55 +/- 4% of predicted [mean +/- SE]), the 6MWT was a submaximal, albeit intense, exercise as reflected by oxygen uptake (VO2), minute ventilation, heart rate, and lactate values. Leukocytosis was less intense after 6MWT compared to CPET. Contrary, the increase in interleukin-6, free radical release by neutrophils, oxidation of proteins and lipids, and the reduction in antioxidant capacity were similar after both exercises. FFMI was inversely related to 6MWT-induced increases in protein and lipid peroxidation. CONCLUSIONS: This study shows that a 6MWT induces a systemic immunologic response in muscle-wasted patients with COPD, which is comparable to CPET-induced responses. The correlation between systemic oxidative stress and the degree of muscle wasting supports a possible causal relation between systemic inflammation, oxidative stress, and muscle wasting.

Exercise-induced systemic effects in muscle-wasted patients with COPD.

PURPOSE: Physical exercise is known to induce an acute inflammatory response and oxidative stress in healthy subjects and patients with chronic obstructive pulmonary disease (COPD). Increasing evidence associates systemic inflammation and oxidative stress with muscle wasting and muscle dysfunction in COPD. In the present study, it was hypothesized that exercise-induced systemic inflammatory and oxidative responses in muscle-wasted COPD patients are increased compared with non-muscle-wasted patients and healthy subjects. METHODS: Pulmonary function, body composition, and quadriceps muscle strength were measured in 10 muscle-wasted (fat-free mass index (FFMI) < 16 kg x m(-2) (men), < 15 kg x m(-2) (women)), 10 non-muscle-wasted COPD patients, and 10 healthy subjects. Systemic inflammation (C-reactive protein (CRP), leukocytes, cytokines) and oxidative stress (production of reactive oxygen species (ROS) by neutrophils, plasma antioxidant capacity, protein oxidation, lipid peroxidation, oxidized to reduced glutathione ratio (GSSG/GSH)) were determined before and after maximal and submaximal (50% of maximal work rate) cycle ergometry. RESULTS: Low-grade systemic inflammation was significantly (P < 0.05) elevated in all COPD patients and tended to be highest in muscle-wasted patients. A decreased antioxidant status (plasma antioxidant capacity, P < 0.05; GSH, P < 0.05) and increased protein oxidation (P < 0.001) reflected increased basal oxidative stress in muscle-wasted COPD patients compared with both other groups. Both maximal and submaximal exercise caused increased inflammatory (IL-6, +1.1 pg. x mL(-1) vs rest, P < 0.05) and oxidative responses (ROS release by neutrophils, + 32%; GSSG/GSH + 29%; lipid peroxidation, + 30% vs rest) in muscle-wasted COPD patients, which were less pronounced or not observed in non-muscle-wasted patients and healthy subjects. CONCLUSIONS: These data indicate that both maximal and submaximal exercise induce increased systemic inflammatory and oxidative responses in muscle-wasted COPD patients compared with non-muscle-wasted patients and healthy subjects.

Supplemental oxygen prevents exercise-induced oxidative stress in muscle-wasted patients with chronic obstructive pulmonary disease.

RATIONALE: Although oxygen therapy is of clear benefit in patients with severe chronic obstructive pulmonary disease (COPD), recent studies have shown that short-term supplementary oxygen may increase oxidative stress and inflammation within the airways. OBJECTIVE: We investigated whether systemic inflammation and oxidative stress at rest and during exercise in patients with COPD are influenced by supplemental oxygen. METHODS: Nine normoxemic, muscle-wasted patients with moderate to very severe COPD were studied. Plasma markers of systemic inflammation (leukocyte counts, interleukin 6 [IL-6]) and oxidative stress (lipid peroxidation, protein oxidation, antioxidant capacity) were measured after treatment with either supplemental oxygen (nasal, 4 L . min(-1)) or compressed air, both at rest (1 h treatment) and after submaximal exercise (40 W, constant work rate). In addition, free-radical production by neutrophils and ATP-degradation products were determined before and after exercise. RESULTS: Short-term oxygen breathing at rest did not influence systemic low-grade inflammation and oxidative stress. The IL-6 response to exercise was attenuated during cycling with supplemental oxygen. Exercise-induced lipid and protein oxidation were prevented by treatment with supplemental oxygen. This was associated with both decreased free-radical production by neutrophils and reduced formation of (hypo)xanthine and uric acid. CONCLUSION: Short-term supplementary oxygen does not affect basal systemic inflammation and oxidative stress but prevents exercise-induced oxidative stress in normoxemic, muscle-wasted patients with COPD, and attenuates plasma IL-6 response. Inhibition of neutrophil activation and ATP degradation appears to be involved in this effect.

Systemic inflammatory response to exhaustive exercise in patients with chronic obstructive pulmonary disease.

Systemic inflammation may be present in patients with chronic obstructive pulmonary disease (COPD). Exercise is known to elicit an inflammatory response. We hypothesized that the systemic inflammatory response to exercise might be exaggerated in COPD patients compared to healthy subjects. Sixteen COPD patients and 11 healthy subjects performed a maximal incremental bicycle test. Before and at maximal exercise arterial blood samples were taken to determine circulating catecholamines, (subsets of) leukocytes, acute phase proteins, creatine kinase and myoglobin. At rest, increased levels of norepinephrine and systemic inflammation were present in COPD. The response of catecholamines to exercise was lower in COPD patients (P<0.01), which in part was due to the lower maximal exercise capacity of these patients (P<0.01). Exercise-induced leukocytosis showed similar responses in both groups, but occurred at higher levels in COPD. Although patients had increased levels of CRP at rest (P<0.001), exercise did not affect acute phase proteins. No systemic signs of muscle damage were found. The present study shows that COPD patients are exposed to systemic inflammation that is intensified by exhaustive exercise. The inflammatory response in COPD is not exaggerated compared to healthy subjects but occurs at a higher level and is observed at lower external workload.