Evidence map›Paper›PMID 35815359›Full record

ArticleTherapeutic advances in respiratory disease

Predictive modeling of COPD exacerbation rates using baseline risk factors.

Dave Singh, John R Hurst, Fernando J Martinez, Klaus F Rabe, Mona Bafadhel, Martin Jenkins, Domingo Salazar, Paul Dorinsky, Patrick Darken

10 registry-linked trialsOpen access · goldAbstract read
In one paragraph

Article in Therapeutic advances in respiratory disease. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 10 registered trials, which are not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT01854645 phase3completednot on this map

A Randomized, Double Blind, Chronic Dosing, Placebo-Controlled, Parallel Group, Multi Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD, Compared With Placebo and Spiriva® Handihaler® (Tiotropium Bromide 18 µg Open-Label) as an Active Control

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2013 to 2015Enrolled2,103ConditionsChronic Obstructive Pulmonary DiseaseArmsGFF MDI, GP MDI, FF MDI, Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®), Placebo MDI
NCT01854658 phase3completednot on this map

A Randomized, Double-Blind (Test Products and Placebo), Chronic Dosing (24 Weeks), Placebo-Controlled, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD, Compared With Placebo

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2013 to 2015Enrolled1,615ConditionsChronic Obstructive Pulmonary Disease (COPD)ArmsGFF MDI (PT003), GP MDI (PT001), FF MDI (PT005), Placebo
NCT01970878 phase3completednot on this map

A 28-Week, Multi-Center, Randomized, Double Blind, Parallel-Group, Active-Controlled Safety Extension Study to Evaluate the Safety and Efficacy of PT003, PT001, and PT005 in Subjects With Moderate to Very Severe COPD, With Spiriva® Handihaler® as an Active Control

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2013 to 2015Enrolled892ConditionsChronic Obstructive Pulmonary Disease (COPD)ArmsGFF MDI (PT 003), GP MDI (PT001), FF MDI (PT005), Open-label tiotropium bromide inhalation (Spiriva® Handihaler®)
NCT02343458 phase3completednot on this map

A Randomized, Double-Blind, Chronic Dosing (24 Weeks), Placebo-Controlled, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD, Compared With Placebo

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2015 to 2017Enrolled1,756ConditionsChronic Obstructive Pulmonary DiseaseArmsGFF MDI (PT003), FF MDI (PT005), GP MDI (PT001), Placebo MDI
NCT02465567 phase3completednot on this map

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)

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2015 to 2019Enrolled8,588ConditionsCOPDArmsBGF MDI 320/14.4/9.6 μg, GFF MDI 14.4/9.6 μg, BGF MDI 160/14.4/9.6 μg, BFF MDI 320/9.6 μg
NCT02497001 phase3completednot on this map

A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® as an Active Control in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2015 to 2018Enrolled1,902ConditionsCOPDArmsBGF MDI 320/14.4/9.6 μg, GFF MDI (PT003) 14.4/9.6 μg, BFF MDI (PT009) 320/9.6 μg, Symbicort® Turbuhaler® (TBH) Inhalation Powder
NCT02536508 phase3completednot on this map

A Randomized, Double-Blind, Parallel-Group, 52-Week, Chronic-Dosing, Multi-Center Study to Assess the Safety and Tolerability of PT010, PT009 and PT003 in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2015 to 2017Enrolled627ConditionsCOPDArmsBGF MDI 320/14.4/9.6 μg, GFF MDI 14.4/9.6 μg, BFF MDI 320/9.6 μg
NCT02727660 phase3completednot on this map

A Randomized, Double-Blind, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT009 Compared to PT005 on COPD Exacerbations Over a 52-Week Treatment Period in Subjects With Moderate to Very Severe COPD

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2016 to 2018Enrolled1,876ConditionsChronic Obstructive Pulmonary DisorderArmsBFF MDI (PT009) 320/9.6 μg, BFF MDI (PT009) 160/9.6 μg, FF MDI (PT005) 9.6 μg
NCT02766608 phase3completednot on this map

A Randomized, Double-Blind, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT009 Compared to PT005, PT008, and Open-label Symbicort® Turbuhaler®, as an Active Control, on Lung Function Over a 24-Week Treatment Period in Subjects With Moderate to Very Severe COPD

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2016 to 2017Enrolled2,389ConditionsChronic Obstructive Pulmonary DisorderArmsBFF MDI 320/9.6 μg, BFF MDI 160/9.6 μg, FF MDI 9.6 μg, BD MDI 320 μg, Symbicort® TBH 400/12 μg BID
NCT03262012 phase3completednot on this map

A Randomized, Double-Blind, Parallel-Group, 28-Week, Chronic-Dosing, Multi-Center, Extension Study to Assess the Safety and Efficacy of PT010, PT003, and PT009 in Japanese Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) Compared With Symbicort® Turbuhaler® as an Active Control

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2016 to 2018Enrolled416ConditionsCOPDArmsBGF MDI (PT010), GFF MDI (PT003), BFF MDI (PT009), Symbicort® Turbohaler® Inhalation Powder
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Short-acting βERJ open research · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Investigation of the Methodology of Specific Airway Resistance Measurements in COPD.International journal of chronic obstructive pulmonary disease · 2023
    Article
  14. Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 7 institutions in 3 countries.

Dave SinghMedicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Hospitals Trust, Manchester M23 9QZ, UK.ORCID 0000-0001-8918-7075
John R HurstUCL Respiratory, University College London, London, UK.
Fernando J MartinezJoan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Klaus F RabeLungenClinic Grosshansdorf and Christian-Albrechts University Kiel, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.ORCID 0000-0002-7020-1401
Mona BafadhelRespiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Martin JenkinsAstraZeneca, Cambridge, UK.
Domingo SalazarAstraZeneca, Cambridge, UK.
Paul DorinskyFormerly of AstraZeneca, Durham, NC, USA.
Patrick DarkenAstraZeneca, Gaithersburg, MD, USA.
AstraZeneca (United Kingdom) · GBAstraZeneca (United States) · USCornell University · USGerman Center for Lung Research · DEUniversity College London · GBUniversity of Manchester · GBUniversity of Oxford · GB

Funding

Department of Health
6 · The paper itself

Abstract

backgroundDemographic and disease characteristics have been associated with the risk of chronic obstructive pulmonary disease (COPD) exacerbations. Using previously collected multinational clinical trial data, we developed models that use baseline risk factors to predict an individual's rate of moderate/severe exacerbations in the next year on various pharmacological treatments for COPD.

methodsExacerbation data from 20,054 patients in the ETHOS, KRONOS, TELOS, SOPHOS, and PINNACLE-1, PINNACLE-2, and PINNACLE-4 studies were pooled. Machine learning was used to identify predictors of moderate/severe exacerbation rates. Important factors were selected for generalized linear modeling, further informed by backward variable selection. An independent test set was held back for validation.

resultsPrior exacerbations, eosinophil count, forced expiratory volume in 1 s percent predicted, prior maintenance treatments, reliever medication use, sex, COPD Assessment Test score, smoking status, and region were significant predictors of exacerbation risk, with response to inhaled corticosteroids (ICSs) increasing with higher eosinophil counts, more prior exacerbations, or additional prior treatments. Model fit was similar in the training and test set. Prediction metrics were ~10% better in the full model than in a simplified model based only on eosinophil count, prior exacerbations, and ICS use.

conclusionThese models predicting rates of moderate/severe exacerbations can be applied to a broad range of patients with COPD in terms of airway obstruction, eosinophil counts, exacerbation history, symptoms, and treatment history. Understanding the relative and absolute risks related to these factors may be useful for clinicians in evaluating the benefit: risk ratio of various treatment decisions for individual patients.Clinical trials registered with www.clinicaltrials.gov (NCT02465567, NCT02497001, NCT02766608, NCT02727660, NCT01854645, NCT01854658, NCT02343458, NCT03262012, NCT02536508, and NCT01970878).

Indexed as

Disease ProgressionPulmonary Disease, Chronic ObstructiveAdultAgedAged, 80 and overFemaleHumansLinear ModelsMaleMiddle AgedMulticenter Studies as TopicRandomized Controlled Trials as TopicRisk Factorschronic obstructive pulmonary diseaseexacerbationsICS/LAMA/LABAmachine learningprediction modeltriple therapy

Identifiers

PMID35815359
PMCPMC9340368
OpenAlexW4285040856

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

and 4 more above

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.