Skip to main content
Top
Published in: Respiratory Research 1/2022

Open Access 01-12-2022 | Chronic Obstructive Lung Disease | Research

Stratification of COPD patients towards personalized medicine: reproduction and formation of clusters

Authors: Cathelijne M. van Zelst, Lucas M. A. Goossens, Jan A. Witte, Gert-Jan Braunstahl, Rudi W. Hendriks, Maureen P. M. H. Rutten-van Molken, Johannes C. C. M. in’t Veen

Published in: Respiratory Research | Issue 1/2022

Login to get access

Abstract

Background

The global initiative for chronic obstructive lung disease (GOLD) 2020 emphasizes that there is only a weak correlation between FEV1, symptoms and impairment of the health status of patients with chronic obstructive pulmonary disease (COPD). Various studies aimed to identify COPD phenotypes by cluster analyses, but behavioral aspects besides smoking were rarely included.

Methods

The aims of the study were to investigate whether (i) clustering analyses are in line with the classification into GOLD ABCD groups; (ii) clustering according to Burgel et al. (Eur Respir J. 36(3):531–9, 2010) can be reproduced in a real-world COPD cohort; and (iii) addition of new behavioral variables alters the clustering outcome. Principal component and hierarchical cluster analyses were applied to real-world clinical data of COPD patients newly referred to secondary care (n = 155). We investigated if the obtained clusters paralleled GOLD ABCD subgroups and determined the impact of adding several variables, including quality of life (QOL), fatigue, satisfaction relationship, air trapping, steps per day and activities of daily living, on clustering.

Results

Using the appropriate corresponding variables, we identified clusters that largely reflected the GOLD ABCD groups, but we could not reproduce Burgel’s clinical phenotypes. Adding six new variables resulted in the formation of four new clusters that mainly differed from each other in the following parameters: number of steps per day, activities of daily living and QOL.

Conclusions

We could not reproduce previously identified clinical COPD phenotypes in an independent population of COPD patients. Our findings therefore indicate that COPD phenotypes based on cluster analysis may not be a suitable basis for treatment strategies for individual patients.
Appendix
Available only for authorised users
Literature
2.
go back to reference Agusti A, Calverley PM, Celli B, Coxson HO, Edwards LD, Lomas DA, et al. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Res. 2010;11:122.CrossRef Agusti A, Calverley PM, Celli B, Coxson HO, Edwards LD, Lomas DA, et al. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Res. 2010;11:122.CrossRef
3.
go back to reference Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010;182(5):598–604.CrossRef Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010;182(5):598–604.CrossRef
4.
go back to reference Nikolaou V, Massaro S, Fakhimi M, Stergioulas L, Price D. COPD phenotypes and machine learning cluster analysis: a systematic review and future research agenda. Respir Med. 2020;171: 106093.CrossRef Nikolaou V, Massaro S, Fakhimi M, Stergioulas L, Price D. COPD phenotypes and machine learning cluster analysis: a systematic review and future research agenda. Respir Med. 2020;171: 106093.CrossRef
6.
go back to reference Burgel PR, Paillasseur JL, Caillaud D, Tillie-Leblond I, Chanez P, Escamilla R, et al. Clinical COPD phenotypes: a novel approach using principal component and cluster analyses. Eur Respir J. 2010;36(3):531–9.CrossRef Burgel PR, Paillasseur JL, Caillaud D, Tillie-Leblond I, Chanez P, Escamilla R, et al. Clinical COPD phenotypes: a novel approach using principal component and cluster analyses. Eur Respir J. 2010;36(3):531–9.CrossRef
7.
go back to reference Burgel PR, Roche N, Paillasseur JL, Tillie-Leblond I, Chanez P, Escamilla R, et al. Clinical COPD phenotypes identified by cluster analysis: validation with mortality. Eur Respir J. 2012;40(2):495–6.CrossRef Burgel PR, Roche N, Paillasseur JL, Tillie-Leblond I, Chanez P, Escamilla R, et al. Clinical COPD phenotypes identified by cluster analysis: validation with mortality. Eur Respir J. 2012;40(2):495–6.CrossRef
8.
go back to reference Siedlinski M, Cho MH, Bakke P, Gulsvik A, Lomas DA, Anderson W, et al. Genome-wide association study of smoking behaviours in patients with COPD. Thorax. 2011;66(10):894–902.CrossRef Siedlinski M, Cho MH, Bakke P, Gulsvik A, Lomas DA, Anderson W, et al. Genome-wide association study of smoking behaviours in patients with COPD. Thorax. 2011;66(10):894–902.CrossRef
9.
go back to reference Cannon D, Buys N, Sriram KB, Sharma S, Morris N, Sun J. The effects of chronic obstructive pulmonary disease self-management interventions on improvement of quality of life in COPD patients: a meta-analysis. Respir Med. 2016;121:81–90.CrossRef Cannon D, Buys N, Sriram KB, Sharma S, Morris N, Sun J. The effects of chronic obstructive pulmonary disease self-management interventions on improvement of quality of life in COPD patients: a meta-analysis. Respir Med. 2016;121:81–90.CrossRef
10.
go back to reference Donesky D, Nguyen HQ, Paul SM, Carrieri-Kohlman V. The affective dimension of dyspnea improves in a dyspnea self-management program with exercise training. J Pain Symptom Manage. 2014;47(4):757–71.CrossRef Donesky D, Nguyen HQ, Paul SM, Carrieri-Kohlman V. The affective dimension of dyspnea improves in a dyspnea self-management program with exercise training. J Pain Symptom Manage. 2014;47(4):757–71.CrossRef
11.
go back to reference O’Donnell DE, Fluge T, Gerken F, Hamilton A, Webb K, Aguilaniu B, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J. 2004;23(6):832–40.CrossRef O’Donnell DE, Fluge T, Gerken F, Hamilton A, Webb K, Aguilaniu B, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J. 2004;23(6):832–40.CrossRef
12.
go back to reference van den Akker EF, ‘vantHul AJ, Chavannes NH, Braunstahl GJ, van Bruggen A, Rutten-van Molken MP, et al. Development of an integral assessment approach of health status in patients with obstructive airway diseases: the CORONA study. Int J Chron Obstruct Pulmon Dis. 2015;10:2413–22.CrossRef van den Akker EF, ‘vantHul AJ, Chavannes NH, Braunstahl GJ, van Bruggen A, Rutten-van Molken MP, et al. Development of an integral assessment approach of health status in patients with obstructive airway diseases: the CORONA study. Int J Chron Obstruct Pulmon Dis. 2015;10:2413–22.CrossRef
13.
go back to reference Brusasco V, Crapo R, Viegi G, American Thoracic S, European RS. Coming together: the ATS/ERS consensus on clinical pulmonary function testing. Eur Respir J. 2005;26(1):1–2.CrossRef Brusasco V, Crapo R, Viegi G, American Thoracic S, European RS. Coming together: the ATS/ERS consensus on clinical pulmonary function testing. Eur Respir J. 2005;26(1):1–2.CrossRef
14.
go back to reference Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019;200(8):e70–88.CrossRef Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019;200(8):e70–88.CrossRef
15.
go back to reference Lahaije AJ, Willems LM, van Hees HW, Dekhuijzen PN, van Helvoort HA, Heijdra YF. Diagnostic accuracy of metronome-paced tachypnea to detect dynamic hyperinflation. Clin Physiol Funct Imaging. 2013;33(1):62–9.CrossRef Lahaije AJ, Willems LM, van Hees HW, Dekhuijzen PN, van Helvoort HA, Heijdra YF. Diagnostic accuracy of metronome-paced tachypnea to detect dynamic hyperinflation. Clin Physiol Funct Imaging. 2013;33(1):62–9.CrossRef
17.
go back to reference Fletcher C. Standardised questionnaire on respiratory symptoms: a statement prepared and approved by the MRC Committee on the Aetiology of Chronic Bronchitis (MRC breathlessness score). BMJ. 1960;2:1665. Fletcher C. Standardised questionnaire on respiratory symptoms: a statement prepared and approved by the MRC Committee on the Aetiology of Chronic Bronchitis (MRC breathlessness score). BMJ. 1960;2:1665.
18.
go back to reference Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999;54(7):581–6.CrossRef Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999;54(7):581–6.CrossRef
19.
go back to reference van der Molen T, Willemse BW, Schokker S, ten Hacken NH, Postma DS, Juniper EF. Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual Life Outcomes. 2003;1:13.CrossRef van der Molen T, Willemse BW, Schokker S, ten Hacken NH, Postma DS, Juniper EF. Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual Life Outcomes. 2003;1:13.CrossRef
20.
go back to reference Kon SS, Dilaver D, Mittal M, Nolan CM, Clark AL, Canavan JL, et al. The Clinical COPD Questionnaire: response to pulmonary rehabilitation and minimal clinically important difference. Thorax. 2014;69(9):793–8.CrossRef Kon SS, Dilaver D, Mittal M, Nolan CM, Clark AL, Canavan JL, et al. The Clinical COPD Questionnaire: response to pulmonary rehabilitation and minimal clinically important difference. Thorax. 2014;69(9):793–8.CrossRef
21.
go back to reference Steer RA, Cavalieri TA, Leonard DM, Beck AT. Use of the Beck Depression Inventory for Primary Care to screen for major depression disorders. Gen Hosp Psychiatry. 1999;21(2):106–11.CrossRef Steer RA, Cavalieri TA, Leonard DM, Beck AT. Use of the Beck Depression Inventory for Primary Care to screen for major depression disorders. Gen Hosp Psychiatry. 1999;21(2):106–11.CrossRef
22.
go back to reference De DA. Nederlandse versie van de Beck Depression Inventory-second edition (BDI-II-NL); handleiding. Enschede: The Psychological Corporation; 2002. De DA. Nederlandse versie van de Beck Depression Inventory-second edition (BDI-II-NL); handleiding. Enschede: The Psychological Corporation; 2002.
23.
go back to reference Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1005–12.CrossRef Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1005–12.CrossRef
24.
go back to reference Peters JB, Daudey L, Heijdra YF, Molema J, Dekhuijzen PN, Vercoulen JH. Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument. Qual Life Res. 2009;18(7):901–12.CrossRef Peters JB, Daudey L, Heijdra YF, Molema J, Dekhuijzen PN, Vercoulen JH. Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument. Qual Life Res. 2009;18(7):901–12.CrossRef
25.
go back to reference Ward JH. Hierarchical grouping to optimize an objective function. J Am Stat Assoc. 1963;58:236–44.CrossRef Ward JH. Hierarchical grouping to optimize an objective function. J Am Stat Assoc. 1963;58:236–44.CrossRef
26.
go back to reference Jolliffe IT, Cadima J. Principal component analysis: a review and recent developments. Philos Trans A Math Phys Eng Sci. 2016;374(2065):20150202. Jolliffe IT, Cadima J. Principal component analysis: a review and recent developments. Philos Trans A Math Phys Eng Sci. 2016;374(2065):20150202.
27.
go back to reference Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George’s Respiratory Questionnaire. Am Rev Respir Dis. 1992;145(6):1321–7.CrossRef Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George’s Respiratory Questionnaire. Am Rev Respir Dis. 1992;145(6):1321–7.CrossRef
28.
go back to reference Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70.CrossRef Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70.CrossRef
29.
go back to reference Yoon HY, Park SY, Lee CH, Byun MK, Na JO, Lee JS, et al. Prediction of first acute exacerbation using COPD subtypes identified by cluster analysis. Int J Chron Obstruct Pulmon Dis. 2019;14:1389–97.CrossRef Yoon HY, Park SY, Lee CH, Byun MK, Na JO, Lee JS, et al. Prediction of first acute exacerbation using COPD subtypes identified by cluster analysis. Int J Chron Obstruct Pulmon Dis. 2019;14:1389–97.CrossRef
30.
go back to reference Augustin IML, Spruit MA, Houben-Wilke S, Franssen FME, Vanfleteren L, Gaffron S, et al. The respiratory physiome: Clustering based on a comprehensive lung function assessment in patients with COPD. PLoS ONE. 2018;13(9): e0201593.CrossRef Augustin IML, Spruit MA, Houben-Wilke S, Franssen FME, Vanfleteren L, Gaffron S, et al. The respiratory physiome: Clustering based on a comprehensive lung function assessment in patients with COPD. PLoS ONE. 2018;13(9): e0201593.CrossRef
31.
go back to reference Vanfleteren LE, Spruit MA, Groenen M, Gaffron S, van Empel VP, Bruijnzeel PL, et al. Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187(7):728–35.CrossRef Vanfleteren LE, Spruit MA, Groenen M, Gaffron S, van Empel VP, Bruijnzeel PL, et al. Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187(7):728–35.CrossRef
32.
go back to reference Mesquita R, Vanfleteren LE, Franssen FM, Sarv J, Taib Z, Groenen MT, et al. Objectively identified comorbidities in COPD: impact on pulmonary rehabilitation outcomes. Eur Respir J. 2015;46(2):545–8.CrossRef Mesquita R, Vanfleteren LE, Franssen FM, Sarv J, Taib Z, Groenen MT, et al. Objectively identified comorbidities in COPD: impact on pulmonary rehabilitation outcomes. Eur Respir J. 2015;46(2):545–8.CrossRef
33.
go back to reference Xavier RF, Pereira A, Lopes AC, Cavalheri V, Pinto RMC, Cukier A, et al. Identification of phenotypes in people with COPD: influence of physical activity, sedentary behaviour, body composition and skeletal muscle strength. Lung. 2019;197(1):37–45.CrossRef Xavier RF, Pereira A, Lopes AC, Cavalheri V, Pinto RMC, Cukier A, et al. Identification of phenotypes in people with COPD: influence of physical activity, sedentary behaviour, body composition and skeletal muscle strength. Lung. 2019;197(1):37–45.CrossRef
34.
go back to reference Negro RWD, Carone M, Cuttitta G, Gallelli L, Pistolesi M, Privitera S, et al. Prevalence and clinical features of most frequent phenotypes in the Italian COPD population: the CLIMA Study. Multidiscip Respir Med. 2021;16(1):790. Negro RWD, Carone M, Cuttitta G, Gallelli L, Pistolesi M, Privitera S, et al. Prevalence and clinical features of most frequent phenotypes in the Italian COPD population: the CLIMA Study. Multidiscip Respir Med. 2021;16(1):790.
36.
go back to reference Stallberg B, Nokela M, Ehrs PO, Hjemdal P, Jonsson EW. Validation of the clinical COPD Questionnaire (CCQ) in primary care. Health Qual Life Outcomes. 2009;7:26.CrossRef Stallberg B, Nokela M, Ehrs PO, Hjemdal P, Jonsson EW. Validation of the clinical COPD Questionnaire (CCQ) in primary care. Health Qual Life Outcomes. 2009;7:26.CrossRef
37.
go back to reference Perez TA, Castillo EG, Ancochea J, Pastor Sanz MT, Almagro P, Martinez-Camblor P, et al. Sex differences between women and men with COPD: a new analysis of the 3CIA study. Respir Med. 2020;171: 106105.CrossRef Perez TA, Castillo EG, Ancochea J, Pastor Sanz MT, Almagro P, Martinez-Camblor P, et al. Sex differences between women and men with COPD: a new analysis of the 3CIA study. Respir Med. 2020;171: 106105.CrossRef
39.
go back to reference Jameson JL, Longo DL. Precision medicine–personalized, problematic, and promising. N Engl J Med. 2015;372(23):2229–34.CrossRef Jameson JL, Longo DL. Precision medicine–personalized, problematic, and promising. N Engl J Med. 2015;372(23):2229–34.CrossRef
40.
go back to reference Agusti A, Bel E, Thomas M, Vogelmeier C, Brusselle G, Holgate S, et al. Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J. 2016;47(2):410–9.CrossRef Agusti A, Bel E, Thomas M, Vogelmeier C, Brusselle G, Holgate S, et al. Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J. 2016;47(2):410–9.CrossRef
41.
go back to reference Faner R, Agusti A. Multilevel, dynamic chronic obstructive pulmonary disease heterogeneity. A challenge for personalized medicine. Ann Am Thorac Soc. 2016;13(Suppl 2):S466–70.CrossRef Faner R, Agusti A. Multilevel, dynamic chronic obstructive pulmonary disease heterogeneity. A challenge for personalized medicine. Ann Am Thorac Soc. 2016;13(Suppl 2):S466–70.CrossRef
Metadata
Title
Stratification of COPD patients towards personalized medicine: reproduction and formation of clusters
Authors
Cathelijne M. van Zelst
Lucas M. A. Goossens
Jan A. Witte
Gert-Jan Braunstahl
Rudi W. Hendriks
Maureen P. M. H. Rutten-van Molken
Johannes C. C. M. in’t Veen
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2022
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-022-02256-7

Other articles of this Issue 1/2022

Respiratory Research 1/2022 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine