Non-invasive ventilation abolishes the IL-6 response to exercise in muscle-wasted COPD patients: a pilot study.

Systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) has been related to the development of comorbidities. The level of systemic inflammatory mediators is aggravated as a response to exercise in these patients. The aim of this study was to investigate whether unloading of the respiratory muscles attenuates the inflammatory response to exercise in COPD patients. In a cross-over design, eight muscle-wasted stable COPD patients performed 40 W constant work-rate cycle exercise with and without non-invasive ventilation support (NIV vs control). Patients exercised until symptom limitation for maximally 20 min. Blood samples were taken at rest and at isotime or immediately after exercise. Duration of control and NIV-supported exercise was similar, both 12.9 ± 2.8 min. Interleukin- 6 (IL-6) plasma levels increased significantly by 25 ± 9% in response to control exercise, but not in response to NIV-supported exercise. Leukocyte concentrations increased similarly after control and NIV-supported exercise by ∼15%. Plasma concentrations of C-reactive protein, carbonylated proteins, and production of reactive oxygen species by blood cells were not affected by both exercise modes. This study demonstrates that NIV abolishes the IL-6 response to exercise in muscle-wasted patients with COPD. These data suggest that the respiratory muscles contribute to exercise-induced IL-6 release in these patients.

Maximal exercise capacity in chronic obstructive pulmonary disease: a limited indicator of the health status.

BACKGROUND: Dyspnoea and diminished functional status are pivotal features of the health status (HS) in chronic obstructive pulmonary disease (COPD). However, it is still not fully understood how pulmonary function tests and cardiopulmonary exercise testing relate to these aspects. This may be due to incomplete assessment and/or deficient definitions of HS. Especially regarding peak oxygen consumption, inconsistent results have been reported. OBJECTIVES: To determine the value of maximal cycle ergometry in relation to a broad spectrum of HS aspects. METHODS: 129 patients with COPD, stage II and III according to the GOLD classification, performed a cardiopulmonary exercise test. Sixteen independent sub-domains of HS were assessed according to the Nijmegen Integral Assessment Framework, covering physiological functioning, complaints, functional impairments and quality of life as main domains. VO(2)(max) and HS sub-domains were correlated by bivariate analysis. RESULTS: Weak correlations of VO(2)(max) with most sub-domains were found, except for exercise capacity; the other 5 sub-domains of physiological functioning did not correlate. Between different types of exercise limitation (5 types were differentiated), no significant differences were noted in the scores of 13/16 HS sub-domains. CONCLUSIONS: VO(2)(max) is indeed correlated with most aspects of HS, except for physiological variables, but associations are weak. No single exercise limitation type is associated with specific HS problems. Thus separate assessment of all HS sub-domains is advocated to ensure adequate planning of therapeutic interventions.

Physiologic limitations during daily life activities in COPD patients.

INTRODUCTION: Patients with COPD are known to be limited in their performance of activities of daily life (ADL). This observational study aims to investigate the ventilatory and metabolic demand of ADL in home settings of patients and evaluate possible mechanisms involved in physiological limitation during ADL in COPD. METHODS: In their home settings, 21 stable patients with COPD (GOLD II-IV, mean FEV(1) 43% predicted) were asked to perform their most dyspnea causing activities at their usual pace until symptoms discouraged further performance. Ten healthy control subjects, matched for age and gender, performed comparable activities. Ventilatory and metabolic demands of the ADL were studied using a portable breath-by-breath system. RESULTS: Compared with healthy controls, ADL time was shorter in patients (530 +/- 38 s vs. 318 +/- 37 s respectively) and activities resulted in important complaints of dyspnea. Oxygen consumption (V O(2)) during the activities was higher in patients compared to healthy subjects (957 +/- 51 vs. 768 +/- 63 mL/min resp.). Ventilatory demand (V E) for comparable activity (at isoV O(2)) was higher in patients and went together with complaints of dyspnea in patients, but not in healthy subjects. Ventilatory constraints like low ventilatory reserve and inspiratory reserve volume and dynamic hyperinflation occurred in more than 80% of the patients, especially in (very) severe patients. CONCLUSION: Patients with COPD experience limitations in the performance of ADL, which lead to reductions in ADL time and dyspnea complaints. There appears to be an important role for ventilatory limitations, which become more prominent as disease progresses.

Exercise in systemic sclerosis intensifies systemic inflammation and oxidative stress.

OBJECTIVE: Exercise testing can be used (i) to evaluate functional limitations of systemic sclerosis (SSc) and (ii) to study whether the inflammatory and oxidative systems are activated after a physical stimulus. The aim of this study was to determine exercise-induced inflammatory and oxidative responses in SSc compared with healthy subjects. METHODS: Eleven patients with SSc and pulmonary involvement and 10 healthy subjects underwent maximal cardiopulmonary exercise testing (CPET). Physiological responses were followed continuously during cycling. Blood samples were taken at rest, during and after maximal exercise to measure inflammatory and oxidative markers. RESULTS: In nine of the 11 SSc patients, cardiocirculatory limitation and gas exchange impairment limited exercise capacity. Basal inflammatory cells, interleukin (IL)-6, and oxidative stress were increased in SSc compared to healthy subjects and intensified after exercise. Basal and exercise-induced inflammation and oxidative stress were correlated with the modified Rodnan skin score. CONCLUSIONS: Although exercise capacity is impaired in patients with SSc, physical activity intensifies the already increased basal levels of systemic inflammation and oxidative stress. These data support the concept of a role for systemic inflammation and oxidative stress in the ongoing systemic effects of SSc.

Systemic immunological response to exercise in patients with chronic obstructive pulmonary disease: what does it mean?

Chronic obstructive pulmonary disease (COPD) is no longer seen as a pulmonary disease, but is increasingly associated with systemic effects with important clinical relevance. Systemic immunological changes in COPD patients are characterized by an increased number of circulating inflammatory cells, functional changes of the inflammatory cells, elevated plasma levels of cytokines, and oxidative stress. Physical exercise induces an abnormal systemic inflammatory and oxidative response in COPD patients, which is seen in both the circulation and the peripheral muscles. Although mechanisms and consequences of these effects are not yet fully understood, they could be harmful in COPD patients by inducing damage or functional changes in, for example, skeletal muscles. Whether these changes of the immune system can also affect the susceptibility to infections in these patients is unknown. The concept of COPD as a systemic rather than only a pulmonary disease also opens new perspectives on the development for new therapeutic interventions. The effects of new antioxidative and anti-inflammatory agents are investigated. A better understanding of the complexity of the systemic effects will aid the development of new therapies and management strategies for patients with COPD.