H.A.C. van Helvoort

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.

Can COPD Patients Who Hyperinflate During Daily Life Activities Be Identified by Laboratory Tests

Background: Identification of patients with chronic obstructive pulmonary disease (COPD) who develop dynamic hyperinflation (DH) during activities in daily life (ADL) is important, because of the association between DH and dyspnea and exercise limitation. Objective: We aimed to answer the question whether measurements of DH during metronome-paced tachypnea (MPT) or cardiopulmonary exercise testing (CPET) can be used to identify patients who develop DH during ADL. Methods: DH was measured by tracking changes in inspiratory capacity during CPET, MPT and ADL. Bland-Altman plots were used to evaluate agreement in DH between methods. With a receiver operating characteristic (ROC) analysis, the overall accuracy of MPT and CPET to identify patients who hyperinflate during ADL was assessed. Results: There are broad limits of agreement in DH between methods. ROC curve analyses showed good overall accuracy of both CPET and MPT to identify patients who hyperinflate during ADL. For CPET, area under the curve (AUC) = 0.956 (95% CI 0.903-1.009). For MPT, AUC = 0.840 (95% CI 0.699-0.981). Sensitivity and specificity to identify patients who hyperinflate during ADL with CPET were 96 and 83%, respectively, and with MPT, they were 89 and 77%, respectively. Conclusion: Both CPET and MPT can serve as screening tools to identify patients who are susceptible to developing DH during ADL. In practice, MPT is the most simple and inexpensive surrogate. However, the sensitivity of MPT is not optimal. When DH does not occur during CPET, it is unlikely to occur during ADL.

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. v̇O2max and HS sub-domains were correlated by bivariate analysis. Results: Weak correlations of v̇O2max 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: v̇O2max 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.

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.

The role of equal pressure points in understanding pulmonary diseases

the respiratory system is composed of a conducting part and a respiratory part. The conducting airways, i.e., the trachea, bronchi, and bronchioles, differ in architecture. Both trachea and bronchi are surrounded by rings of hyaline cartilage for support, whereas the bronchiolar wall does not