Short Physical Performance Battery: Response to Pulmonary Rehabilitation and Minimal Important Difference Estimates in Patients With Chronic Obstructive Pulmonary Disease.

Objective: To determine the response to a pulmonary rehabilitation (PR) program and minimal important differences (MIDs) for the Short Physical Performance Battery (SPPB) subtests and SPPB summary score in patients with chronic obstructive pulmonary disease (COPD).

Design: Retrospective analysis using distribution- and anchor-based methods.

Setting: PR center in the Netherlands including a comprehensive 40-session 8-week inpatient or 14-week outpatient program.

Muscle fiber dysfunction contributes to weakness in inclusion body myositis.

Atrophy and fatty infiltration are important causes of muscle weakness in inclusion body myositis (IBM). Muscle weakness can also be caused by reduced specific force; i.e.

"Can do" versus "do do": A Novel Concept to Better Understand Physical Functioning in Patients with Chronic Obstructive Pulmonary Disease.

Background: Physical capacity (PC) and physical activity (PA) represent associated but separate domains of physical function. It remains unknown whether this framework may support a better understanding of the impaired physical function in patients with chronic obstructive pulmonary disease (COPD). The current study had two aims: (1) to determine the distribution of patients with COPD over the PC-PA quadrants, and (2) to explore whether differences exist in clinical characteristics between these quadrants.

Partial Neuromuscular Blockade during Partial Ventilatory Support in Sedated Patients with High Tidal Volumes.

Rationale: Controlled mechanical ventilation is used to deliver lung-protective ventilation in patients with acute respiratory distress syndrome. Despite recognized benefits, such as preserved diaphragm activity, partial support ventilation modes may be incompatible with lung-protective ventilation due to high Vt and high transpulmonary pressure. As an alternative to high-dose sedatives and controlled mechanical ventilation, pharmacologically induced neuromechanical uncoupling of the diaphragm should facilitate lung-protective ventilation under partial support modes.

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.

Assessment of dead-space ventilation in patients with acute respiratory distress syndrome: a prospective observational study.

Background: Physiological dead space (VD/VT) represents the fraction of ventilation not participating in gas exchange. In patients with acute respiratory distress syndrome (ARDS), VD/VT has prognostic value and can be used to guide ventilator settings. However, VD/VT is rarely calculated in clinical practice, because its measurement is perceived as challenging.

Strategies to optimize respiratory muscle function in ICU patients.

Respiratory muscle dysfunction may develop rapidly in critically ill ventilated patients and is associated with increased morbidity, length of intensive care unit stay, costs, and mortality. This review briefly discusses the pathophysiology of respiratory muscle dysfunction in intensive care unit patients and then focuses on strategies that prevent the development of muscle weakness or, if weakness has developed, how respiratory muscle function may be improved. We propose a simple strategy for how these can be implemented in clinical care.

EFFECTS OF EXPERIMENTAL HUMAN ENDOTOXEMIA ON DIAPHRAGM FUNCTION.

Introduction: Systemic inflammation is a well-known risk factor for respiratory muscle weakness. Studies using animal models of inflammation have shown that endotoxin administration induces diaphragm dysfunction. However, the effects of in vivo endotoxin administration on diaphragm function in humans have not been studied.

Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice.

Introduction: Controlled mechanical ventilation and endotoxemia are associated with diaphragm muscle atrophy and dysfunction. Oxidative stress and activation of inflammatory pathways are involved in the pathogenesis of diaphragmatic dysfunction. Levosimendan, a cardiac inotrope, has been reported to possess anti-oxidative and anti-inflammatory properties.

High definition bronchoscopy: a randomized exploratory study of diagnostic value compared to standard white light bronchoscopy and autofluorescence bronchoscopy.

Background: Videobronchoscopy is an essential diagnostic procedure for evaluation of the central airways and pivotal for the diagnosis and staging of lung cancer. Technological improvements have resulted in high definition (HD) images with advanced real time image enhancement techniques (i-scan).

Objectives: In this study we aimed to explore the sensitivity of HD+ i-scan bronchoscopy for detection of epithelial changes like vascular abnormalities and suspicious preinvasive lesions, and tumors.

Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients.

Rationale: The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency, and increases morbidity and duration of hospital stay. To date, the nature of diaphragm weakness and its underlying pathophysiologic mechanisms are poorly understood.

Objectives: We hypothesized that diaphragm muscle fibers of mechanically ventilated critically ill patients display atrophy and contractile weakness, and that the ubiquitin-proteasome pathway is activated in the diaphragm.

Smoking-induced skeletal muscle dysfunction: from evidence to mechanisms.

Smoking is the most important risk factor for the development of chronic obstructive pulmonary disease (COPD). Patients with COPD commonly suffer from skeletal muscle dysfunction, and it has been suggested that cigarette smoke exposure contributes to the development of skeletal muscle dysfunction even before overt pulmonary pathology. This review summarizes the evidence that muscles of nonsymptomatic smokers are weaker and less fatigue resistant than those of nonsmokers.

Unaffected contractility of diaphragm muscle fibers in humans on mechanical ventilation.

Several studies have indicated that diaphragm dysfunction develops in patients on mechanical ventilation (MV). Here, we tested the hypothesis that the contractility of sarcomeres, i.e.

Hypercapnia attenuates ventilator-induced diaphragm atrophy and modulates dysfunction.

Introduction: Diaphragm weakness induced by prolonged mechanical ventilation may contribute to difficult weaning from the ventilator. Hypercapnia is an accepted side effect of low tidal volume mechanical ventilation, but the effects of hypercapnia on respiratory muscle function are largely unknown. The present study investigated the effect of hypercapnia on ventilator-induced diaphragm inflammation, atrophy and function.

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.

Monitoring of the respiratory muscles in the critically ill.

Evidence has accumulated that respiratory muscle dysfunction develops in critically ill patients and contributes to prolonged weaning from mechanical ventilation. Accordingly, it seems highly appropriate to monitor the respiratory muscles in these patients. Today, we are only at the beginning of routinely monitoring respiratory muscle function.

Diaphragm weakness in pulmonary arterial hypertension: role of sarcomeric dysfunction.

We previously demonstrated that diaphragm muscle weakness is present in experimental pulmonary arterial hypertension (PH). However, the nature of this diaphragm weakness is still unknown. Therefore, the aim of this study was to investigate whether changes at the sarcomeric level contribute to diaphragm weakness in PH.

Bortezomib partially protects the rat diaphragm from ventilator-induced diaphragm dysfunction.

Objective: Controlled mechanical ventilation leads to diaphragmatic contractile dysfunction and atrophy. Since proteolysis is enhanced in the diaphragm during controlled mechanical ventilation, we examined whether the administration of a proteasome inhibitor, bortezomib, would have a protective effect against ventilator-induced diaphragm dysfunction.

Design: Randomized, controlled experiment.

Toll-like receptor 4 signaling in ventilator-induced diaphragm atrophy.

Background: Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor 4 signaling in the development of ventilator-induced diaphragm atrophy.

Titin and diaphragm dysfunction in mechanically ventilated rats.

Purpose: Diaphragm weakness induced by mechanical ventilation may contribute to difficult weaning from the ventilator. For optimal force generation the muscle proteins myosin and titin are indispensable. The present study investigated if myosin and titin loss or dysfunction are involved in mechanical ventilation-induced diaphragm weakness.

Selective diaphragm muscle weakness after contractile inactivity during thoracic surgery.

Rationale: Postoperative pulmonary complications are significant contributors to morbidity in patients who have undergone upper abdominal, thoracic, or cardiac surgery. The pathophysiology of these complications might involve postoperative inspiratory muscle weakness. The nature of postoperative inspiratory muscle weakness is unknown.

The calcium sensitizer levosimendan improves human diaphragm function.

Rationale: Acquired diaphragm muscle weakness is a key feature in several chronic conditions, including chronic obstructive pulmonary disease, congestive heart failure, and difficult weaning from mechanical ventilation. No drugs are available to improve respiratory muscle function in these patients. Recently, we have shown that the calcium sensitizer levosimendan enhances the force-generating capacity of isolated diaphragm fibers.

Plasma from septic shock patients induces loss of muscle protein.

Introduction: ICU-acquired muscle weakness commonly occurs in patients with septic shock and is associated with poor outcome. Although atrophy is known to be involved, it is unclear whether ligands in plasma from these patients are responsible for initiating degradation of muscle proteins. The aim of the present study was to investigate if plasma from septic shock patients induces skeletal muscle atrophy and to examine the time course of plasma-induced muscle atrophy during ICU stay.