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.

Patients with Chronic Obstructive Pulmonary Disease Can Accurately Perform Home-Based Measurements of Inspiratory Capacity and Dynamic Hyperinflation.

Home-based lung function measurements can be used to capture day-to-day variations in symptoms in patients with chronic obstructive pulmonary disease (COPD). Although dynamic hyperinflation (DH) is clinically relevant, existing home-based measurements do not include its assessment. DH can be measured through inspiratory capacity (IC) measurements before and after metronome-paced tachypnea test (MPT). The goal of this study is to determine the accuracy of unsupervised home-based IC and DH measurements in COPD.Sixteen COPD patients performed IC and DH measurements during 4 home visits. Visit 1 was considered a training session. During all visits supervised and unsupervised IC at rest (ICREST) and after MPT (ICMPT) were measured. DH was calculated as the difference between ICREST and ICMPT, and as a percentage of ICREST. Bland-Altman analyses and ANOVA tests were performed to determine the effect of supervision and repeated measures over time.The biases between supervised and unsupervised ICREST, ICMPT, ΔIC and ΔIC% were 0.007 L, 0.007 L, 0 mL and -0.09% in the last visit, respectively. Limits of agreement of ICREST and ΔIC% decreased from ±0.261 mL to ±0.201 mL, and from ±13.84% to ±10.81% between visit 1 and 4, respectively. No significant effect of supervision or over time was found.After a robust training and a learning phase, COPD patients are able to perform IC measurements in an accurate manner in both rest and after MPT. This yield accurate assessment of DH, in an unsupervised home-based setting.

Comprehensive Health Assessment 3 Months After Recovery From Acute Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Long-term health sequelae of coronavirus disease 2019 (COVID-19) may be multiple but have thus far not been systematically studied. METHODS: All patients discharged after COVID-19 from the Radboud University Medical Center, Nijmegen, the Netherlands, were consecutively invited to a multidisciplinary outpatient facility. Also, nonadmitted patients with mild disease but with symptoms persisting >6 weeks could be referred by general practitioners. Patients underwent a standardized assessment including measurements of lung function, chest computed tomography (CT)/X-ray, 6-minute walking test, body composition, and questionnaires on mental, cognitive, health status, and quality of life (QoL). RESULTS: 124 patients (59 ±â€…14 years, 60% male) were included: 27 with mild, 51 with moderate, 26 with severe, and 20 with critical disease. Lung diffusion capacity was below the lower limit of normal in 42% of discharged patients. 99% of discharged patients had reduced ground-glass opacification on repeat CT imaging, and normal chest X-rays were found in 93% of patients with mild disease. Residual pulmonary parenchymal abnormalities were present in 91% of discharged patients and correlated with reduced lung diffusion capacity. Twenty-two percent had low exercise capacity, 19% low fat-free mass index, and problems in mental and/or cognitive function were found in 36% of patients. Health status was generally poor, particularly in the domains functional impairment (64%), fatigue (69%), and QoL (72%). CONCLUSIONS: This comprehensive health assessment revealed severe problems in several health domains in a substantial number of ex-COVID-19 patients. Longer follow-up studies are warranted to elucidate natural trajectories and to find predictors of complicated long-term trajectories of recovery.

Is the Metronome-Paced Tachypnea Test (MPT) Ready for Clinical Use? Accuracy of the MPT in a Prospective and Clinical Study.

BACKGROUND: A simple technique to measure dynamic hyperinflation (DH) in patients with chronic obstructive pulmonary disease (COPD) is the metronome-paced tachypnea test (MPT). Earlier studies show conflicting results about the accuracy of the MPT compared to cardiopulmonary exercise testing (CPET). OBJECTIVES: The focus was to investigate the diagnostic accuracy of MPT to detect DH in a prospective and clinical study. METHODS: COPD patients were included; all underwent spirometry, CPET, and MPT. DH (ΔIC) was calculated as the difference in % between inspiratory capacity (IC) at the start and end of the test divided by IC at the start. A subject was identified as a hyperinflator, if ΔIC (% of ICrest) was smaller than -10.2 and -11.1% in CPET and MPT, respectively. With these values, sensitivity and specificity were calculated. Bland-Altman plots were made of ΔIC (% of ICrest). RESULTS: In the prospective and clinical study, 107 and 48 patients were included, respectively. Sensitivity of the MPT was 85% in both studies. The specificities were 33 and 27%, respectively. In the prospective study, B = +2.6%, L = 30.6, and -25.6%. In the clinical study, B = +0.8%, L = 31.0, and -29.1%. CONCLUSION: MPT seems to be a good replacement for CPET in group studies. The mean amount of DH was not different between CPET and MPT. On an individual level, MPT cannot be used to identify hyperinflators; it should be kept in mind that MPT overdiagnoses DH. The amount of DH should not be interchanged between CPET and MPT.

Randomised controlled trial of adjunctive inspiratory muscle training for patients with COPD.

BACKGROUND: This study aimed to investigate whether adjunctive inspiratory muscle training (IMT) can enhance the well-established benefits of pulmonary rehabilitation (PR) in patients with COPD. METHODS: 219 patients with COPD (FEV1: 42%±16% predicted) with inspiratory muscle weakness (PImax: 51±15 cm H2O) were randomised into an intervention group (IMT+PR; n=110) or a control group (Sham-IMT+PR; n=109) in this double-blind, multicentre randomised controlled trial between February 2012 and October 2016 (ClinicalTrials.gov NCT01397396). Improvement in 6 min walking distance (6MWD) was a priori defined as the primary outcome. Prespecified secondary outcomes included respiratory muscle function and endurance cycling time. FINDINGS: No significant differences between the intervention group (n=89) and the control group (n=85) in improvements in 6MWD were observed (0.3 m, 95% CI -13 to 14, p=0.967). Patients who completed assessments in the intervention group achieved larger gains in inspiratory muscle strength (effect size: 1.07, p<0.001) and endurance (effect size: 0.79, p<0.001) than patients in the control group. 75 s additional improvement in endurance cycling time (95% CI 1 to 149, p=0.048) and significant reductions in Borg dyspnoea score at isotime during the cycling test (95% CI -1.5 to -0.01, p=0.049) were observed in the intervention group. INTERPRETATION: Improvements in respiratory muscle function after adjunctive IMT did not translate into additional improvements in 6MWD (primary outcome). Additional gains in endurance time and reductions in symptoms of dyspnoea were observed during an endurance cycling test (secondary outcome) TRIAL REGISTRATION NUMBER: NCT01397396; Results.

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.

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.

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.

Exercises commonly used in rehabilitation of patients with chronic obstructive pulmonary disease: cardiopulmonary responses and effect over time.

OBJECTIVES: To compare conventional exercise-based assessment of pulmonary rehabilitation (PR) with improvement in training exercises employed during a PR program, and to describe the cardiopulmonary response of different training exercises during PR of patients with chronic obstructive pulmonary disease (COPD). DESIGN: Observational study. SETTING: Inpatient PR. PARTICIPANTS: Patients with moderate to very severe COPD (N=18). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Cardiopulmonary responses to interval cycling, arm exercise, and a test of functional activities of daily living (ADLs) were evaluated during the PR training program using a mobile telemetric breath-by-breath system. The effects of PR were evaluated by comparing pre-PR and post-PR training activities, incremental and constant work-rate cycling, and a 6-minute walk test. RESULTS: Interval cycling and the ADLs test were moderate-intensity to heavy-intensity exercises (70%-80% of maximal oxygen consumption), while the arm exercise was a low-intensity activity (40% of maximal oxygen consumption). After 12 weeks of PR, cycle load, arm weights, and walking distances during training activities had increased alongside increased muscle mass. At iso-intensities, no cardiopulmonary changes in the training exercises were observed. Exercise duration of constant work-rate cycling and 6-minute walk distance increased by 160% and 14%, respectively, after PR, with concurrent right-shifts of anaerobic threshold and a decrease in heart rate. CONCLUSIONS: Supervised increases in weight, load, and walking distance during training activities were useful clinical outcomes for patients, demonstrating the beneficial effects of progressive training on physical performance. However, for physiologic evaluation of PR, conventional tests, such as maximal incremental cycling, endurance cycling, and a 6-minute walk test, had greater validity. Physiologic evaluation of the training exercises showed that the training program complied with the training recommendations for PR.

The Accuracy of Tidal Volume Measured With a Smart Shirt During Tasks of Daily Living in Healthy Subjects: Cross-sectional Study.

BACKGROUND: The Hexoskin is a smart shirt that can take continuous and objective measurements and could be part of a potential telemonitoring system. OBJECTIVE: The aim of this study was to determine the accuracy of the calibrated Hexoskin in measuring tidal volumes (TVs) in comparison to spirometry during various tasks. METHODS: In a cross-sectional study, the TV of 15 healthy subjects was measured while performing seven tasks using spirometry and the Hexoskin. These tasks were performed during two sessions; between sessions, all equipment was removed. A one-time spirometer-based calibration per task was determined in session 1 and applied to the corresponding task in both sessions. Bland-Altman analysis was used to determine the agreement between TV that was measured with the Hexoskin and that measured with spirometry. A priori, we determined that the bias had to be less than ±5%, with limits of agreement (LOA) of less than ±15%. Lung volumes were measured and had to have LOA of less than ±0.150 L. RESULTS: In the first session, all tasks had a median bias within the criteria (±0.6%). In the second session, biases were ±8.9%; only two tasks met the criteria. In both sessions, LOA were within the criteria in six out of seven tasks (±14.7%). LOA of lung volumes were greater than 0.150 L. CONCLUSIONS: The Hexoskin was able to correctly measure TV in healthy subjects during various tasks. However, after reapplication of the equipment, calibration factors were not able to be reused to obtain results within the determined boundaries. TRIAL REGISTRATION: Netherlands Trial Register NL6934; https://www.trialregister.nl/trial/6934.

"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.

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.

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.

Telemonitoring Techniques for Lung Volume Measurement: Accuracy, Artifacts and Effort.

Telemonitoring becomes more important in pulmonary research. It can be used to decrease the pressure on the health care system, to lower the costs of health care and to increase quality of life of patients. Previous studies show contradictory results regarding the effectiveness of telemonitoring. According to multiple researchers, inefficiency can be a result of poor study design, low data quality and usability issues. To counteract these issues, this review proves for an in-depth explanation of four (potential) telemonitoring systems in terms of work principle, accuracy, disturbing factors and usability. The evaluated systems are portable spirometry/breath-by-breath analyzers, respiratory inductance and magnetic plethysmography and electrical impedance tomography. These insights can be used to select the optimal technique for a specific purpose in future studies.

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.

Respiratory constraints during activities in daily life and the impact on health status in patients with early-stage COPD: a cross-sectional study.

In patients with chronic obstructive pulmonary disease (COPD), exercise capacity is reduced, resulting over time in physical inactivity and worsened health status. It is unknown whether ventilatory constraints occur during activities of daily life (ADL) in early stages of COPD. The aim of this study was to assess respiratory mechanics during ADL and to study its consequences on dyspnoea, physical activity and health status in early-stage COPD compared with healthy controls. In this cross-sectional study, 39 early-stage COPD patients (mean FEV1 88±s.d. 12% predicted) and 20 controls performed 3 ADL: climbing stairs, vacuum cleaning and displacing groceries in a cupboard. Respiratory mechanics were measured during ADL. Physical activity was measured with accelerometry. Health status was assessed by the Nijmegen Clinical Screening Instrument. Compared with controls, COPD patients had greater ventilatory inefficiency and higher ventilatory requirements during ADL (P<0.05). Dyspnoea scores were increased in COPD compared with controls (P<0.001). During ADL, >50% of the patients developed dynamic hyperinflation in contrast to 10-35% of the controls. Higher dyspnoea was scored by patients with dynamic hyperinflation. Physical activity was low but comparable between both groups. From the patients, 55-84% experienced mild-to-severe problems in health status compared with 5-25% of the controls. Significant ventilatory constraints already occur in early-stage COPD patients during common ADL and result in increased dyspnoea. Physical activity level is not yet reduced, but many patients already experience limitations in health status. These findings reinforce the importance of early diagnosis of COPD and assessment of more than just spirometry.

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.