Pharmacological Interpretation of the Efficacy of Ensifentrine in Chronic Obstructive Pulmonary Disease: Insights from ENHANCE Trials.
Ontology highlight
ABSTRACT:
SUBMITTER: Calzetta L
PROVIDER: S-EPMC10806426 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Publications
Pharmacological Interpretation of the Efficacy of Ensifentrine in Chronic Obstructive Pulmonary Disease: Insights from ENHANCE Trials.
Calzetta Luigino L Cazzola Mario M Rogliani Paola P
American journal of respiratory and critical care medicine 20240101 2
Similar Datasets
Project description:Rationale: Ensifentrine is a novel, selective, dual phosphodiesterase (PDE)3 and PDE4 inhibitor with bronchodilator and antiinflammatory effects. Replicate phase III trials of nebulized ensifentrine were conducted (ENHANCE-1 and ENHANCE-2) to assess these effects in patients with chronic obstructive pulmonary disease (COPD). Objectives: To evaluate the efficacy of ensifentrine compared with placebo for lung function, symptoms, quality of life, and exacerbations in patients with COPD. Methods: These phase III, multicenter, randomized, double-blind, parallel-group, placebo-controlled trials were conducted between September 2020 and December 2022 at 250 research centers and pulmonology practices in 17 countries. Patients aged 40-80 years with moderate to severe symptomatic COPD were enrolled. Measurements and Main Results: Totals of 760 (ENHANCE-1) and 789 (ENHANCE-2) patients were randomized and treated, with 69% and 55% receiving concomitant long-acting muscarinic antagonists or long-acting β2-agonists, respectively. Post-bronchodilator FEV1 percentage predicted values were 52% and 51% of predicted normal. Ensifentrine treatment significantly improved average FEV1 area under the curve at 0-12 hours versus placebo (ENHANCE-1, 87 ml [95% confidence interval, 55, 119]; ENHANCE-2, 94 ml [65, 124]; both P < 0.001). Ensifentrine treatment significantly improved symptoms (Evaluating Respiratory Symptoms) and quality of life (St. George's Respiratory Questionnaire) versus placebo at Week 24 in ENHANCE-1 but not in ENHANCE-2. Ensifentrine treatment reduced the rate of moderate or severe exacerbations versus placebo over 24 weeks (ENHANCE-1, rate ratio, 0.64 [0.40, 1.00]; P = 0.050; ENHANCE-2, rate ratio, 0.57 [0.38, 0.87]; P = 0.009) and increased time to first exacerbation (ENHANCE-1, hazard ratio, 0.62 [0.39, 0.97]; P = 0.038; ENHANCE-2, hazard ratio, 0.58 [0.38, 0.87]; P = 0.009). Adverse event rates were similar to those for placebo. Conclusions: Ensifentrine significantly improved lung function in both trials, with results supporting exacerbation rate and risk reduction in a broad COPD population and in addition to other classes of maintenance therapies. Clinical trial registered with www.Clinicaltrialsgov and EudraCT (ENHANCE-1, www.Clinicaltrialsgov identifier NCT04535986, EudraCT identifier 2020-002086-34; ENHANCE-2, www.Clinicaltrialsgov identifier NCT04542057, EudraCT identifier 2020-002069-32).
| S-EPMC10449067 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease associated with significant morbidity and mortality. Over the past few years, there has been cumulating interest in describing this heterogeneity and using this information to group patients into different COPD phenotypes. The term phenotype is defined as single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes. It describes also the physical appearance or biochemical characteristics which result from the genotype-environment interaction. Furthermore, it clearly identifies subgroups with a significant impact in the prognosis. Recently, approaches to COPD phenotyping have been significantly enhanced in tandem with developments in understanding the disease's various pathological, clinical and genetic features. This knowledge inspired the researchers to investigate more tailored therapeutic strategies that could not only give a more potent effect but also help to avoid the traditional therapy's undesirable side effects. Eventually, it could be said that the phenotypic approach to COPD in the last decade had a huge impact on daily practice and management delivered to COPD patients. In this review, we highlight the impact of pharmacological and non-pharmacological treatment options on COPD outcomes, using a personalized treatment strategy based on different phenotypes.
| S-EPMC7723612 | biostudies-literature
Project description:Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Little is known about the prevalence and clinical profiles of patients with COPD-PH. We report the clinical characteristics, hemodynamic profiles, and prognosis in a large population of patients with COPD referred for right heart catheterization (RHC). We extracted data from all patients referred for RHC between 1997 and 2017 in Vanderbilt's deidentified medical record. PH was defined as mean pulmonary artery pressure >20 mmHg. Pre- and postcapillary PH were defined according to contemporary guidelines. COPD was identified using a validated rules-based algorithm requiring international classification of diseases codes relevant to COPD. We identified 6065 patients referred for RHC, of whom 1509 (24.9%) had COPD and 1213 had COPD and PH. Patients with COPD-PH had a higher prevalence of diabetes, atrial fibrillation, and heart failure compared with COPD without PH. Approximately 55% of patients with COPD-PH had elevated left ventricle (LV) filling pressure. Pulmonary function testing data from individuals with COPD-PH revealed subtype differences, with precapillary COPD-PH having lower diffusion capacity of the lungs for carbon monoxide (DLCO) values than the other COPD-PH subtypes. Patients with COPD-PH had significantly increased mortality compared with COPD alone (hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.28-2.26) with the highest mortality among the combined pre- and postcapillary COPD-PH subgroup (HR: 2.39; 95% CI: 1.64-3.47). PH is common among patients with COPD referred for RHC. The etiology of PH in patients with COPD is often mixed due to multimorbidity and is associated with high mortality, which may have implications for risk factor management.
| S-EPMC9052979 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease, featured by airflow obstruction. Recently, a comprehensive analysis of the transcriptome in lung tissue of COPD patients was performed, but the heterogeneity of the sample was not seriously considered in characterizing the mechanistic dysregulation of COPD. Here, we established a new transcriptome analysis pipeline using a deconvolution process to reduce the heterogeneity and clearly identified that these transcriptome data originated from the mild or moderate stage of COPD patients. Differentially expressed or co-expressed genes in the protein interaction subnetworks were linked with mitochondrial dysfunction and the immune response, as expected. Computational protein localization prediction revealed that 19 proteins showing changes in subcellular localization were mostly related to mitochondria, suggesting that mislocalization of mitochondria-targeting proteins plays an important role in COPD pathology. Our extensive evaluation of COPD transcriptome data could provide guidelines for analyzing heterogeneous gene expression profiles and classifying potential candidate genes that are responsible for the pathogenesis of COPD.
| S-EPMC6459164 | biostudies-literature
Project description:Diaphragm muscles in Chronic Obstructive Pulmonary Disease (COPD) patients undergo an adaptive fast to slow transformation that includes cellular adaptations. This project studies the signaling mechanisms responsible for this transformation. Keywords: other
2003-07-16 | GSE475 | GEO
Project description:Cachexia and muscle wasting are well recognized as common and partly reversible features of chronic obstructive pulmonary disease (COPD), adversely affecting disease progression and prognosis. This argues for integration of weight and muscle maintenance in patient care. In this review, recent insights are presented in the diagnosis of muscle wasting in COPD, the pathophysiology of muscle wasting, and putative mechanisms involved in a disturbed energy balance as cachexia driver. We discuss the therapeutic implications of these new insights for optimizing and personalizing management of COPD-induced cachexia.
| S-EPMC4799856 | biostudies-other
Project description:The Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study, which began in 2007, is an ongoing multicenter observational cohort study of more than 10,000 current and former smokers. The study is aimed at understanding the etiology, progression, and heterogeneity of chronic obstructive pulmonary disease (COPD). In addition to genetic analysis, the participants have been extensively characterized by clinical questionnaires, spirometry, volumetric inspiratory and expiratory computed tomography, and longitudinal follow-up, including follow-up computed tomography at 5 years after enrollment. The purpose of this state-of-the-art review is to summarize the major advances in our understanding of COPD resulting from the imaging findings in the COPDGene study. Imaging features that are associated with adverse clinical outcomes include early interstitial lung abnormalities, visual presence and pattern of emphysema, the ratio of pulmonary artery to ascending aortic diameter, quantitative evaluation of emphysema, airway wall thickness, and expiratory gas trapping. COPD is characterized by the early involvement of the small conducting airways, and the addition of expiratory scans has enabled measurement of small airway disease. Computational advances have enabled indirect measurement of nonemphysematous gas trapping. These metrics have provided insights into the pathogenesis and prognosis of COPD and have aided early identification of disease. Important quantifiable extrapulmonary findings include coronary artery calcification, cardiac morphology, intrathoracic and extrathoracic fat, and osteoporosis. Current active research includes identification of novel quantitative measures for emphysema and airway disease, evaluation of dose reduction techniques, and use of deep learning for phenotyping COPD.
| S-EPMC6363977 | biostudies-literature
Project description:Investigation of whole genome gene expression level changes of the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10, compared to the normal people and stable COPD patients. A five chip study using total RNA recovered from Peripheral Blood Mononuclear Cell of Peripheral Blood.Evaluating the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10 after the hospital admission, to compared with healthy controls or patients with stable COPD. Slides were scanned at 5 μm/pixel resolution using an Axon GenePix 4000B scanner (Molecular Devices Corporation) piloted by GenePix Pro 6.0 software (Axon). Scanned images (TIFF format) were then imported into NimbleScan software (version 2.5) for grid alignment and expression data analysis. Expression data were normalized through quantile normalization and the Robust Multichip Average (RMA) algorithm included in the NimbleScan software. The Probe level (*_norm_RMA.pair) files and Gene level (*_RMA.calls) files were generated after normalization.
2014-08-14 | E-GEOD-60399 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD) is a common and progressive disease that is influenced by both genetic and environmental factors. For many years, knowledge of the genetic basis of COPD was limited to Mendelian syndromes, such as alpha-1 antitrypsin deficiency and cutis laxa, caused by rare genetic variants. Over the past decade, the proliferation of genome-wide association studies, the accessibility of whole-genome sequencing, and the development of novel methods for analyzing genetic variation data have led to a substantial increase in the understanding of genetic variants that play a role in COPD susceptibility and COPD-related phenotypes. COPDGene (Genetic Epidemiology of COPD), a multicenter, longitudinal study of over 10,000 current and former cigarette smokers, has been pivotal to these breakthroughs in understanding the genetic basis of COPD. To date, over 20 genetic loci have been convincingly associated with COPD affection status, with additional loci demonstrating association with COPD-related phenotypes such as emphysema, chronic bronchitis, and hypoxemia. In this review, we discuss the contributions of the COPDGene study to the discovery of these genetic associations as well as the ongoing genetic investigations of COPD subtypes, protein biomarkers, and post-genome-wide association study analysis.
| S-EPMC6775891 | biostudies-literature
Project description:Telehealth (TH) interventions with Chronic Obstructive Pulmonary Disease (COPD) management were introduced in the literature more than 20 years ago with different labeling, but there was no summary for the overall acceptance and dropout rates as well as associated variables. This review aims to summarize the acceptance and dropout rates used in TH interventions and identify to what extent clinical settings, sociodemographic factors, and intervention factors might impact the overall acceptance and completion rates of TH interventions. We conducted a systematic search up to April 2021 on CINAHL, PubMed, MEDLINE (Ovid), Cochrane, Web of Sciences, and Embase to retrieve randomized and non-randomized control trials that provide TH interventions alone or accompanied with other interventions to individuals with COPD. Twenty-seven studies met the inclusion criteria. Overall, the unweighted average of acceptance and dropout rates for all included studies were 80% and 19%, respectively. A meta-analysis on the pooled difference between the acceptance rates and dropout rates (weighted by the sample size) revealed a significant difference in acceptance and dropout rates among all TH interventions 51% (95% CI 49% to 52; p < 0.001) and 63% (95% CI 60% to 67; p < 0.001), respectively. Analysis revealed that acceptance and dropout rates can be impacted by trial-related, sociodemographic, and intervention-related variables. The most common reasons for dropouts were technical difficulties (33%), followed by complicated system (31%). Current TH COPD interventions have a pooled acceptance rate of 51%, but this is accompanied by a high dropout rate of 63%. Acceptance and dropout levels in TH clinical trials can be affected by sociodemographic and intervention-related factors. This knowledge enlightens designs for well-accepted future TH clinical trials. PROSPERO registration number CRD4201707854.
| S-EPMC8156037 | biostudies-literature