ArticleBMC medical research methodology2022
Relationship between risk, cumulative burden of exacerbations and mortality in patients with COPD: modelling analysis using data from the ETHOS study.
Article in BMC medical research methodology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02465567 (A Randomized, Double-Blind, Multi-Center, Parallel-Group Study to Assess the Efficacy and Safety of PT010 Relative to PT003 and PT009 on COPD Exacerbations Over a 52-Week Treatment Period in Subjects With Moderate to Very Severe COPD), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Multi-Center, Parallel-Group Study to Assess the Efficacy and Safety of PT010 Relative to PT003 and PT009 on COPD Exacerbations Over a 52-Week Treatment Period in Subjects With Moderate to Very Severe COPD (Ethos)
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Pooled it
- The Societal and Economic Burden of COPD in Saudi Arabia.Global journal on quality and safety in healthcare · 2026Article
- Mortality impact of long-term home non-invasive ventilation in COPD patients with versus without obstructive sleep apnea.Annals of the American Thoracic Society · 2026Article
- Impact of socioeconomic status and lifestyle factors on incidence of COPD and hospital readmissions: 13.7-year follow-up in UK Biobank.BMC public health · 2026Article
- Real-Life Efficacy of Single-Inhaler Triple Therapy with Budesonide/Glycopyrronium/Formoterol Fumarate in Persistent COPD Users: A Retrospective Database Study.Biomedicines · 2025Article
- Article
- Impact of intensive health education on influenza vaccination and acute exacerbations in outpatients with chronic obstructive pulmonary disease: a real-world study.Journal of global health · 2025Article
- COPD Assessment Test Score Deterioration as a Predictor of Long-Term Outcomes in Patients Hospitalised for Chronic Obstructive Pulmonary Disease Exacerbation.Journal of clinical medicine · 2025Article
- Deterioration Patterns in Patients Admitted for Severe COPD Exacerbation.Diseases (Basel, Switzerland) · 2024Article
- Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.ERJ open research · 2024Article
- Article
- Hypercapnic Failure in Acute Exacerbated COPD Patients: Severe Airflow Limitation as an Early Warning Signal.Journal of clinical medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe major drivers of cost-effectiveness for chronic obstructive pulmonary disease (COPD) therapies are the occurrence of exacerbations and deaths. Exacerbations, including acute and long-term events, can cause worsening of COPD and lead to an increased risk of further exacerbations, and ultimately may elevate the risk of death. In contrast to this, health economic models are based on COPD severity progression. In this post hoc analysis of the ETHOS study, we focus on the progression of COPD due to exacerbations and deaths.
methodsWe fitted semi-parametric and fully parametric multi-state Markov models with the following five progressive states: State 1, no exacerbation; State 2, 1 moderate exacerbation; State 3, ≥ 2 moderate exacerbations; State 4, ≥ 1 severe exacerbations; State 5, death. The models only allowed a patient to transition to a worsened health state, and transitions did not necessarily have to be to the next adjacent state. We used the multi-state models to analyse data from ETHOS, a phase III, 52-week study assessing the efficacy and safety of triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate in moderate-to-very severe COPD.
resultsThe Weibull multi-state Markov model showed good fit of the data. In line with clinical evidence, we found a higher mortality risk after a severe exacerbation (11.4-fold relative ratio increase [95% CI, 7.7-17.0], 6.4-fold increase [95% CI, 3.8-10.8] and 5.4-fold increase [95% CI, 2.9-10.3] relative to no exacerbations, 1 moderate exacerbation or ≥ 2 moderate exacerbations, respectively). One moderate exacerbation increased mortality risk 1.8-fold (95% CI, 1.1-2.9) vs no exacerbations. We also found a higher risk of severe exacerbation and mortality following ≥ 2 moderate exacerbations.
conclusionMulti-state modelling of patients with COPD in ETHOS found an acute and chronic effect of severe exacerbations on mortality risk. Risk was also increased after a moderate exacerbation. Clinical management with effective pharmacotherapies should be optimised to avoid even moderate exacerbations. Modelling with exacerbations could be an alternative to current COPD models focused on disease progression.
trial registrationNCT02465567.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.