Dataset Information

Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease.

ABSTRACT:

Background

We hypothesized that heterogeneity exists within the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 spirometric category and that different subgroups could be identified within this GOLD category.

Methods

Pre-randomization study participants from two clinical trials were symptomatic/asymptomatic GOLD 1 chronic obstructive pulmonary disease (COPD) patients and healthy controls. A hierarchical cluster analysis used pre-randomization demographics, symptom scores, lung function, peak exercise response and daily physical activity levels to derive population subgroups.

Results

Considerable heterogeneity existed for clinical variables among patients with GOLD 1 COPD. All parameters, except forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC), had considerable overlap between GOLD 1 COPD and controls. Three-clusters were identified: cluster I (18 [15%] COPD patients; 105 [85%] controls); cluster II (45 [80%] COPD patients; 11 [20%] controls); and cluster III (22 [92%] COPD patients; 2 [8%] controls). Apart from reduced diffusion capacity and lower baseline dyspnea index versus controls, cluster I COPD patients had otherwise preserved lung volumes, exercise capacity and physical activity levels. Cluster II COPD patients had a higher smoking history and greater hyperinflation versus cluster I COPD patients. Cluster III COPD patients had reduced physical activity versus controls and clusters I and II COPD patients, and lower FEV1/FVC versus clusters I and II COPD patients.

Conclusions

The results emphasize heterogeneity within GOLD 1 COPD, supporting an individualized therapeutic approach to patients.

Trial registration

www.clinicaltrials.gov. NCT01360788 and NCT01072396.

SUBMITTER: Gagnon P

PROVIDER: S-EPMC4407903 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease.

Gagnon Philippe P Casaburi Richard R Saey Didier D Porszasz Janos J Provencher Steeve S Milot Julie J Bourbeau Jean J O'Donnell Denis E DE Maltais François F

PloS one 20150423 4

<h4>Background</h4>We hypothesized that heterogeneity exists within the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 spirometric category and that different subgroups could be identified within this GOLD category.<h4>Methods</h4>Pre-randomization study participants from two clinical trials were symptomatic/asymptomatic GOLD 1 chronic obstructive pulmonary disease (COPD) patients and healthy controls. A hierarchical cluster analysis used pre-randomization demographics, symptom ...[more]

PMID: 25906326

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Project description:BackgroundPulmonary rehabilitation (PR) is a cornerstone in the management of chronic obstructive pulmonary disease (COPD), targeting skeletal muscle to improve functional performance. However, there is substantial inter-individual variability in the effect of PR on functional performance, which cannot be fully accounted for by generic phenotypic factors. We performed an unbiased integrative analysis of the skeletal muscle molecular responses to PR in COPD patients and comprehensively characterized their baseline pulmonary and physical function, body composition, blood profile, comorbidities, and medication use.MethodsMusculus vastus lateralis biopsies were obtained from 51 COPD patients (age 64 ± 1 years, sex 73% men, FEV1 , 34 (26-41) %pred.) before and after 4 weeks high-intensity supervised in-patient PR. Muscle molecular markers were grouped by network-constrained clustering, and their relative changes in expression values-assessed by qPCR and western blot-were reduced to process scores by principal component analysis. Patients were subsequently clustered based on these process scores. Pre-PR and post-PR functional performance was assessed by incremental cycle ergometry and 6 min walking test (6MWT).ResultsEight molecular processes were discerned by network-constrained hierarchical clustering of the skeletal muscle molecular rehabilitation responses. Based on the resulting process scores, four clusters of patients were identified by hierarchical cluster analysis. Two major patient clusters differed in PR-induced autophagy (P < 0.001), myogenesis (P = 0.014), glucocorticoid signalling (P < 0.001), and oxidative metabolism regulation (P < 0.001), with Cluster 1 (C1; n = 29) overall displaying a more pronounced change in marker expression than Cluster 2 (C2; n = 16). General baseline characteristics did not differ between clusters. Following PR, both 6 min walking distance (+26.5 ± 8.3 m, P = 0.003) and peak load on the cycle ergometer test (+9.7 ± 1.9 W, P < 0.001) were improved. However, the functional improvement was more pronounced in C1, as a higher percentage of patients exceeded the minimal clinically important difference in peak workload (61 vs. 21%, P = 0.022) and both peak workload and 6 min walking test (52 vs. 8%, P = 0.008) upon PR.ConclusionsWe identified patient groups with distinct skeletal muscle molecular responses to rehabilitation, associated with differences in functional improvements upon PR.

Project description:PURPOSE:Results from the Danish cluster-randomized trial of telehealthcare to 1,225 patients with chronic obstructive pulmonary disease (COPD), the Danish Telecare North Trial, concluded that the telehealthcare solution was unlikely to be cost-effective, by applying international willingness-to-pay threshold values. The purpose of this article was to assess potential sources of variation across subgroups, which could explain overall cost-effectiveness results or be utilized in future economic studies in telehealthcare research. METHODS:First, the cost-structures and cost-effectiveness across COPD severities were analyzed. Second, five additional subgroup analyses were conducted, focusing on differences in cost-effectiveness across a set of comorbidities, age-groups, genders, resource patterns (resource use in the social care sector prior to randomization), and delivery sites. All subgroups were investigated post hoc. In analyzing cost-effectiveness, two separate linear mixed-effects models with treatment-by-covariate interactions were applied: one for quality-adjusted life-year (QALY) gain and one for total healthcare and social sector costs. Probabilistic sensitivity analysis was used for each subgroup result in order to quantify the uncertainty around the cost-effectiveness results. RESULTS:The study concludes that, across the COPD severities, patients with severe COPD (GOLD 3 classification) are likely to be the most cost-effective group. This is primarily due to lower hospital-admission and primary-care costs. Telehealthcare for patients younger than 60 years is also more likely to be cost-effective than for older COPD patients. Overall, results indicate that existing resource patterns of patients and variations in delivery-site practices might have a strong influence on cost-effectiveness, possibly stronger than the included health or sociodemographic sources of heterogeneity. CONCLUSION:Future research should focus more on sources of heterogeneity found in the implementation context and the way telehealthcare is adopted (eg, by integrating formative evaluation into cost-effectiveness analyses). TRIAL REGISTRATION:Clinicaltrials.gov, NCT01984840.

Dataset Information

Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease.

Background

Methods

Results

Conclusions

Trial registration

Publications

Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease.

Similar Datasets

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