Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial

Hohlfeld, Jens M.; Vogel‐Claussen, Jens; Biller, Heike; Berliner, Dominik; Berschneider, Korbinian; Tillmann, Hanns-Christian; Hiltl, S; Bauersachs, Johann; Welte, Tobias

doi:10.1016/s2213-2600(18)30054-7

Cited by 160 publications

(137 citation statements)

References 26 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…Additionally, amelioration of DH results in a host of secondary effects with potentially additive beneficial effects on exercise capacity. Thus, DH diminution improves the lung-heart mechanical interaction, improving cardiac function 35,36 and lowers the oxygen cost of breathing 32 , freeing up blood flow from the respiratory muscles to be delivered to the periphery 37 .…”

Section: Dynamic Hyperinflationmentioning

confidence: 99%

“…However, as bronchodilators are known to increase the maximal voluntary ventilation and decrease DH 1 , W' might be increased as a result. Furthermore, unloading respiratory muscles by bronchodilator therapy increases locomotor muscle blood flow 37 and −by reducing DH− improves cardiac function as well 35,36 . Both phenomena can increase CP.…”

Section: While Patients With Primary Pah Show Extremely Inefficient Vmentioning

confidence: 99%

See 1 more Smart Citation

Exercise testing to evaluate therapeutic interventions in chronic respiratory diseases

Stringer¹,

Casaburi²

2018

BRN

View full text Add to dashboard Cite

From an evidence-based perspective, performance during standardised exercise testing is of considerable importance in the multidimensional evaluation of most respiratory diseases. In this review we aim to summarise the available evidence on the responsiveness of exercise tests to various pharmacological and non-pharmacological therapeutic interventions, as well as the underlying mechanisms associated with the improvements. A standard test to evaluate interventions has not yet been defined and therefore there are several available formats with different types of responsiveness to interventions. Thresholds for clinically important changes are available for several tests. The mechanism of improvement is different depending on the disease process: when moderate or severe airflow limitation is present, as in chronic obstructive pulmonary disease (COPD), the primary mechanisms are reduced ventilatory requirement and/or enhanced ventilatory capacity via reduction of dynamic hyperinflation; in pulmonary arterial hypertension the effect of treatment is typically associated to haemodynamic improvement, while in interstitial lung diseases, the amelioration of arterial oxygen desaturation seems to be the predominant physiological factor. (BRN Rev. 2018;4(4 ):274-86)Corresponding author: Luis Puente-Maestu, lpuente@separ.es

show abstract

Section: Dynamic Hyperinflationmentioning

confidence: 99%

Section: While Patients With Primary Pah Show Extremely Inefficient Vmentioning

confidence: 99%

Exercise testing to evaluate therapeutic interventions in chronic respiratory diseases

Stringer¹,

Casaburi²

2018

BRN

View full text Add to dashboard Cite

show abstract

“…It has been hypothesized that a reduction of pulmonary microvascular blood flow (PMBF) might not only be a result of ventilation impairment with parenchymal destruction but may itself contribute to the development of emphysema and inhibit cardiac function . Indeed, perfusion impairment measured by PMBF has been shown also in mild COPD and can be partially reversed in hyperinflated COPD patients after indacaterol/glycopyrronium inhalation .…”

mentioning

confidence: 99%

Deep semantic lung segmentation for tracking potential pulmonary perfusion biomarkers in chronic obstructive pulmonary disease (COPD): The multi‐ethnic study of atherosclerosis COPD study

Winther

Gutberlet

Hundt³

et al. 2019

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Background Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality. Identification of imaging biomarkers for phenotyping is necessary for future treatment and therapy monitoring. However, translation of visual analytic pipelines into clinics or their use in large‐scale studies is significantly slowed by time‐consuming postprocessing steps. Purpose To implement an automated tool chain for regional quantification of pulmonary microvascular blood flow in order to reduce analysis time and user variability. Study Type Prospective. Population In all, 90 MRI scans of 63 patients, of which 31 had a COPD with a mean Global Initiative for Chronic Obstructive Lung Disease status of 1.9 ± 0.64 (μ ± σ). Field Strength/Sequence 1.5T dynamic gadolinium‐enhanced MRI measurement using 4D dynamic contrast material‐enhanced (DCE) time‐resolved angiography acquired in a single breath‐hold in inspiration. [Correction added on August 20, 2019, after first online publication: The field strength in the preceding sentence was corrected.] Assessment We built a 3D convolutional neural network for semantic segmentation using 29 manually segmented perfusion maps. All five lobes of the lung are denoted, including the middle lobe. Evaluation was performed on 61 independent cases from two sites of the Multi‐Ethnic Study of Arteriosclerosis (MESA)‐COPD study. We publish our implementation of a model‐free deconvolution filter according to Sourbron et al for 4D DCE MRI scans as open source. Statistical Test Cross‐validation 29/61 (# training / # testing), intraclass correlation coefficient (ICC), Spearman ρ, Pearson r, Sørensen–Dice coefficient, and overlap. Results Segmentations and derived clinical parameters were processed in ~90 seconds per case on a Xeon E5‐2637v4 workstation with Tesla P40 GPUs. Clinical parameters and predicted segmentations exhibit high concordance with the ground truth regarding median perfusion for all lobes with an ICC of 0.99 and a Sørensen–Dice coefficient of 93.4 ± 2.8 (μ ± σ). Data Conclusion We present a robust end‐to‐end pipeline that allows for the extraction of perfusion‐based biomarkers for all lung lobes in 4D DCE MRI scans by combining model‐free deconvolution with deep learning. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:571–579.

show abstract

“…Whereas significant knowledge exists about the interaction between dynamic acute lung hyperinflation and cardiac function during exercise [7,10,12], only 2 studies have evaluated the effect of pharmacological decrease of hyperinflation on pulmonary tests and cardiac function at rest in patients with COPD [15][16][17]. Using magnetic resonance imaging (MRI) to measure cardiac chamber volume and function at rest, the study by Stone et al showed that 1 week of once-daily inhaled fluticasone furoate/vilanterol (an inhaled corticosteroid [ICS]/long-acting beta 2 -agonist [LABA]) decreased resting lung volumes and increased right ventricular end-diastolic volume index, as well as cardiac index, without changes in intrinsic cardiac function [15].…”

Section: Introductionmentioning

confidence: 99%

Metabolic and cardiorespiratory effects of decreasing lung hyperinflation with budesonide/formoterol in COPD: a randomized, double-crossover, placebo-controlled, multicenter trial

et al. 2020

View full text Add to dashboard Cite

Background: Studies suggest that acute decreases in lung hyperinflation at rest improves cardiac function and increases lung vascular perfusion from decompression of a compromised heart. In those studies, changes in resting oxygen uptake induced by medications, an alternative explanation for compensatory increased cardiac function, were not explored.Methods: This double-blind, multicenter, double-crossover study enrolled adults with chronic obstructive pulmonary disease, resting hyperinflation, and > 10% improvement in inspiratory capacity after 2 inhalations of budesonide/formoterol 160/4.5 μg. Metabolic, cardiac, and ventilatory function were measured 60 min pre−/postdose at each visit. Primary endpoint was change in resting oxygen uptake for budesonide/formoterol versus placebo.Results: Fifty-one patients (median age: 63 years) received treatment. Compared with placebo, budesonide/ formoterol significantly increased resting oxygen uptake (mean change from baseline: 1.25 vs 11.37 mL/min; P = 0.007) as well as tidal volume and minute ventilation. This occurred despite improvements in the inspiratory capacity, forced vital capacity, and expiratory volume in 1 s. No significant treatment differences were seen for oxygen saturation, respiratory rate, and resting dyspnea. There was a numerical increase in oxygen pulse (oxygen uptake/heart rate). Correlations between inspiratory capacity and oxygen pulse were weak. Conclusions: Budesonide/formoterol treatment in resting hyperinflated patients with COPD results in significant deflation. The increase in oxygen uptake and minute ventilation at lower lung volumes, without changes in heart rate and with minimal improvement in oxygen pulse, suggests increased oxygen demand as a contributor to increased cardiac function.Trial registration: ClinicalTrials.gov identifier: NCT02533505.

show abstract

Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial

Cited by 160 publications

References 26 publications

Exercise testing to evaluate therapeutic interventions in chronic respiratory diseases

Exercise testing to evaluate therapeutic interventions in chronic respiratory diseases

Deep semantic lung segmentation for tracking potential pulmonary perfusion biomarkers in chronic obstructive pulmonary disease (COPD): The multi‐ethnic study of atherosclerosis COPD study

Metabolic and cardiorespiratory effects of decreasing lung hyperinflation with budesonide/formoterol in COPD: a randomized, double-crossover, placebo-controlled, multicenter trial

Contact Info

Product

Resources

About