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Original article
Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes
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  1. Judith Garcia-Aymerich1,2,3,4,
  2. Federico P Gómez5,6,
  3. Marta Benet1,2,4,
  4. Eva Farrero7,
  5. Xavier Basagaña1,2,4,
  6. Àngel Gayete8,
  7. Carles Paré9,
  8. Xavier Freixa9,
  9. Jaume Ferrer6,10,
  10. Antoni Ferrer2,6,11,16,
  11. Josep Roca5,6,
  12. Juan B Gáldiz12,
  13. Jaume Sauleda6,13,14,
  14. Eduard Monsó6,11,15,
  15. Joaquim Gea2,3,6,16,
  16. Joan A Barberà5,6,
  17. Àlvar Agustí5,6,14,
  18. Josep M Antó1,2,3,4 on behalf of the PAC-COPD Study Group
  1. 1Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
  2. 2Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain
  3. 3Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
  4. 4CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
  5. 5Department of Pneumology, Institut del Tòrax, Hospital Clínic-Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
  6. 6CIBER de Enfermedades Respiratorias (CIBERES), Bunyola, Spain
  7. 7Department of Pneumology, Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain
  8. 8Department of Radiology, Hospital del Mar-IMIM, Barcelona, Spain
  9. 9Department of Cardiology, Hospital Clínic-Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
  10. 10Department of Pneumology, Hospital General Universitari Vall D'Hebron, Barcelona, Spain
  11. 11Department of Pneumology, Hospital de Sabadell, Corporació Parc Taulí, Sabadell, Spain
  12. 12Department of Pneumology, Hospital Universitario de Cruces, UPV, Barakaldo, Spain
  13. 13Department of Pneumology, Hospital Universitari Son Dureta, Palma de Mallorca, Spain
  14. 14Fundació Caubet-Cimera, Bunyola, Spain
  15. 15Department of Pneumology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
  16. 16Department of Pneumology, Hospital del Mar-IMIM, Barcelona, Spain
  1. Correspondence to Judith Garcia-Aymerich, Centre for Research in Environmental Epidemiology (CREAL), Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain; jgarcia{at}creal.cat

Abstract

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes.

Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up.

Results Three COPD groups were identified: group 1 (n=126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV1) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n=125, 69 years) showed milder airflow limitation (FEV1 63% predicted); and group 3 (n=91, 67 years) combined a similarly milder airflow limitation (FEV1 58% predicted) with a high proportion of obesity, cardiovascular disorders, diabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p<0.001) and higher all-cause mortality (HR 2.36, p=0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p=0.014).

Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated: ‘severe respiratory COPD’, ‘moderate respiratory COPD’, and ‘systemic COPD’.

  • Pulmonary disease
  • chronic obstructive
  • Epidemiology
  • classification
  • cluster analysis
  • COPD epidemiology

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Footnotes

  • See Editorial, p 363

  • Linked article 155564.

  • FPG and MB contributed equally to this work.

  • The ‘Phenotype and Course of COPD (PAC-COPD)’ Study Group: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Josep M Antó (Principal Investigator), Judith Garcia-Aymerich (project coordinator), Marta Benet, Jordi de Batlle, Ignasi Serra, David Donaire-Gonzalez, Stefano Guerra; Hospital del Mar-IMIM, Barcelona, Joaquim Gea (centre coordinator), Eva Balcells, Àngel Gayete, Mauricio Orozco-Levi, Ivan Vollmer; Hospital Clínic-Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Joan Albert Barberà (centre coordinator), Federico P Gómez, Carles Paré, Josep Roca, Robert Rodriguez-Roisin, Àlvar Agustí, Xavier Freixa, Diego A Rodriguez, Elena Gimeno, Karina Portillo; Hospital General Universitari Vall D'Hebron, Barcelona, Jaume Ferrer (centre coordinator), Jordi Andreu, Esther Pallissa, Esther Rodríguez; Hospital de la Santa Creu i Sant Pau, Barcelona, Pere Casan (centre coordinator), Rosa Güell, Ana Giménez; Hospital Universitari Germans Trias i Pujol, Badalona, Eduard Monsó (centre coordinator), Alicia Marín, Josep Morera; Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Eva Farrero (centre coordinator), Joan Escarrabill; Hospital de Sabadell, Corporació Parc Taulí, Institut Universitari Parc Taulí (Universitat Autònoma de Barcelona), Sabadell, Antoni Ferrer (centre coordinator); Hospital Universitari Son Dureta, Palma de Mallorca, Jaume Sauleda (centre coordinator), Bernat Togores; Hospital Universitario de Cruces, UPV, Barakaldo, Juan Bautista Gáldiz (centre coordinator), Lorena López; Instituto Nacional de Silicosis, Oviedo, José Belda.

  • Funding The PAC-COPD Study is funded by grants from Fondo de Investigación Sanitaria (FIS PI020541), Ministry of Health, Spain; Agència d'Avaluació de Tecnologia i Recerca Mèdiques (AATRM 035/20/02), Catalonia government; Spanish Society of Pneumology and Thoracic Surgery (SEPAR 2002/137); Catalan Foundation of Pneumology (FUCAP 2003 Beca Marià Ravà); Red RESPIRA (RTIC C03/11); Red RCESP (RTIC C03/09); Fondo de Investigación Sanitaria (PI052486); Fondo de Investigación Sanitaria (PI052302); Fondo de Investigación Sanitaria (PI060684); Fundació La Marató de TV3 (no. 041110); and Novartis Farmacèutica, Spain. CIBERESP and CIBERES are funded by the Instituto de Salud Carlos III, Ministry of Health, Spain. JG-A has a researcher contract from the Instituto de Salud Carlos III (CP05/00118), Ministry of Health, Spain. FPG was supported by a Programme of Established Career Scientist Award from the Generalitat de Catalunya. No involvement of funding sources in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Researchers are independent of funders.

  • Competing interests JMA reports that his institution received a €12 000 grant from Novartis Farmacèutica, Spain. No other potential conflict of interest relevant to this article was reported.

  • Ethics approval This study was conducted with the approval of the Ethics Committees of the participating hospitals and coordinating centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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