Purpose: To assess whether dynamic ventilation and perfusion (Q) biomarkers derived by phase-resolved functional lung (PREFUL) MRI can measure treatment response to 14-day therapy with indacaterol-glycopyrronium (IND-GLY) and correlate to clinical outcomes including lung function, symptoms, and cardiac function in patients with chronic obstructive pulmonary disease (COPD), as determined by spirometry, body plethysmography, cardiac MRI, and dyspnea score measurements.
Materials And Methods: The cardiac left ventricular function in COPD (CLAIM) study enrolled patients aged 40 years or older with COPD, stable cardiovascular function, and hyperinflation (residual volume > 135% predicted). Dynamic MRI data of these patients were retrospectively analyzed using the PREFUL technique to assess the effect of 14-day IND-GLY treatment versus placebo on regional measurements of ventilation dynamics.
Background: Lung function impairment in COPD is known to be related to reductions of left heart size, while short-term interventional trials with bronchodilators showed positive effects on cardiac parameters. We investigated whether COPD maintenance therapy has analogous long-term effects.
Methods: Pooled data of GOLD grade 1-4 patients from visits 1 and 3 (1.
The proteasome is the main proteolytic system for targeted protein degradation in the cell and is fine-tuned according to cellular needs. Here, we demonstrate that mitochondrial dysfunction and concomitant metabolic reprogramming of the tricarboxylic acid (TCA) cycle reduce the assembly and activity of the 26S proteasome. Both mitochondrial mutations in respiratory complex I and treatment with the anti-diabetic drug metformin impair 26S proteasome activity.
View Article and Find Full Text PDFAm J Respir Crit Care Med
May 2019
In the CLAIM study, dual bronchodilation with indacaterol/glycopyrronium (IND/GLY) significantly reduced hyperinflation, which translated into improved cardiac function, measured by left ventricular end-diastolic volume and cardiac output. Pulmonary microvascular blood flow (PMBF) is reduced in chronic obstructive pulmonary disease (COPD); however, the effect of reduced lung hyperinflation on PMBF remains unknown. To determine the effect of lung deflation with IND/GLY on PMBF and regional pulmonary ventilation using magnetic resonance imaging (MRI) in hyperinflated patients with COPD.
View Article and Find Full Text PDFBackground: Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with reduced biventricular end-diastolic volumes and increased morbidity and mortality. The combination of a long-acting β agonist (LABA) and a muscarinic antagonist (LAMA) is more effective in reducing hyperinflation than LABA-inhaled corticosteroid combination therapy but whether dual bronchodilation improves cardiac function is unknown.
Methods: We did a double-blind, randomised, two-period crossover, placebo-controlled, single-centre study (CLAIM) at the Fraunhofer Institute of Toxicology and Experimental Medicine (Hannover, Germany), a specialty clinic.