Subtypes of patients experiencing exacerbations of COPD and associations with outcomes

Inmaculada Arostegui, Cristobal Esteban, Susana García-Gutierrez, Marisa Bare, Nerea Fernández-de-Larrea, Eduardo Briones, José M Quintana, IRYSS-COPD Group, Jesús Martínez-Tapias, Alba Ruiz, Eduardo Briones, Silvia Vidal, Emilio Perea-Milla, Francisco Rivas, Maximino Redondo, Javier Rodríguez Ruiz, Marisa Baré, Concepción Montón, Manel Lujani, Amalia Moreno, Josune Ormaza, Javier Pomares, Juli Font, Cristina Estirado, Joaquín Gea, Elena Andradas, Juan Antonio Blasco, Nerea Fernández-de-Larrea, Esther Pulido, Mikel Sánchez, Jose Luis Lobo, Luis Alberto Ruiz, Miren Gastaminza, Ramón Agüero, Gabriel Gutiérrez, Belén Elizalde, Felipe Aizpuru, Inmaculada Arostegui, Amaia Bilbao, Cristóbal Esteban, Nerea González, Susana Garcia, Iratxe Lafuente, Urko Aguirre, Irantzu Barrio, Miren Orive, Edurne Arteta, Jose M Quintana, Inmaculada Arostegui, Cristobal Esteban, Susana García-Gutierrez, Marisa Bare, Nerea Fernández-de-Larrea, Eduardo Briones, José M Quintana, IRYSS-COPD Group, Jesús Martínez-Tapias, Alba Ruiz, Eduardo Briones, Silvia Vidal, Emilio Perea-Milla, Francisco Rivas, Maximino Redondo, Javier Rodríguez Ruiz, Marisa Baré, Concepción Montón, Manel Lujani, Amalia Moreno, Josune Ormaza, Javier Pomares, Juli Font, Cristina Estirado, Joaquín Gea, Elena Andradas, Juan Antonio Blasco, Nerea Fernández-de-Larrea, Esther Pulido, Mikel Sánchez, Jose Luis Lobo, Luis Alberto Ruiz, Miren Gastaminza, Ramón Agüero, Gabriel Gutiérrez, Belén Elizalde, Felipe Aizpuru, Inmaculada Arostegui, Amaia Bilbao, Cristóbal Esteban, Nerea González, Susana Garcia, Iratxe Lafuente, Urko Aguirre, Irantzu Barrio, Miren Orive, Edurne Arteta, Jose M Quintana

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition characterized by occasional exacerbations. Identifying clinical subtypes among patients experiencing COPD exacerbations (ECOPD) could help better understand the pathophysiologic mechanisms involved in exacerbations, establish different strategies of treatment, and improve the process of care and patient prognosis. The objective of this study was to identify subtypes of ECOPD patients attending emergency departments using clinical variables and to validate the results using several outcomes. We evaluated data collected as part of the IRYSS-COPD prospective cohort study conducted in 16 hospitals in Spain. Variables collected from ECOPD patients attending one of the emergency departments included arterial blood gases, presence of comorbidities, previous COPD treatment, baseline severity of COPD, and previous hospitalizations for ECOPD. Patient subtypes were identified by combining results from multiple correspondence analysis and cluster analysis. Results were validated using key outcomes of ECOPD evolution. Four ECOPD subtypes were identified based on the severity of the current exacerbation and general health status (largely a function of comorbidities): subtype A (n = 934), neither high comorbidity nor severe exacerbation; subtype B (n = 682), moderate comorbidities; subtype C (n = 562), severe comorbidities related to mortality; and subtype D (n = 309), very severe process of exacerbation, significantly related to mortality and admission to an intensive care unit. Subtype D experienced the highest rate of mortality, admission to an intensive care unit and need for noninvasive mechanical ventilation, followed by subtype C. Subtypes A and B were primarily related to other serious complications. Hospitalization rate was more than 50% for all the subtypes, although significantly higher for subtypes C and D than for subtypes A and B. These results could help identify characteristics to categorize ECOPD patients for more appropriate care, and help test interventions and treatments in subgroups with poor evolution and outcomes.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Graphical displays of the first…
Figure 1. Graphical displays of the first component derived from the multiple correspondence analysis.
Full legend: Maps created by the second (a) and the third (b) components with respect to the first one, respectively. Black dots represent the categories of the active variables. The closer the points are, stronger is the relationship between the categories. The horizontal axis in both graphs represents the first component, interpreted as observed (left side) vs. missing (right side) arterial blood gases. (a) The second component, vertical axis, represents the severity of the exacerbation or the acute COPD process, more acute (bottom side) vs. less acute (top side). (b) The third component, vertical axis, represents the comorbidity status, more severe (bottom side) vs. less severe (top side). Blue dots represent the relative position of the outcomes.
Figure 2. Map created by the second…
Figure 2. Map created by the second and third components derived from the multiple correspondence analysis.
Full legend: The horizontal axis, second component, can be interpreted as an index of the severity of the exacerbation or the acute COPD process, more acute (left side) vs. less acute (right side). The vertical axis, third component, can be interpreted as an index of the comorbidity status, more severe (bottom) vs. less severe (top). Black dots in the plane represent the categories of the active variables included in the multiple correspondence analysis, only the most representative ones were labeled. The closer the points are, stronger is the relationship between the categories. Relative positions of the subjects in this plane are represented by different colors, depending on the subtype provided by the cluster analysis. Large blue dots represent the relative position of the outcomes.
Figure 3. Partial dendrogram obtained from the…
Figure 3. Partial dendrogram obtained from the cluster analysis.
Full legend: The dendogram represents the results from the cluster analysis performed with the three components obtained from the multiple correspondence analysis. The graphical display includes an easy interpretation of the partition and a brief description of the resulting groups.

References

    1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: revised 2011. Available: .goldcopd.org/uploads/users/files/GOLD_Report_2011_Jan21.pdf
    1. Dornhorst AC (1955) Respiratory insufficiency. Lancet 268: 1185–1187.
    1. Miravitlles M, Soler-Cataluña JJ, Calle M, Molina J, Almagro P, et al. (2014) Spanish Guidelines for COPD (GesEPOC). Update 2014. Arch Bronconeumol 50: 1–16.
    1. Turino GM (2008) COPD and biomarkers: the search goes on. Thorax 63: 1032–4.
    1. Burgel PR, Paillasseur JL, Caillaud D, Tillie-Leblond I, Chanez P, et al. (2010) Clinical COPD phenotypes: a novel approach using principal component and cluster analyses. Eur Respir J 36: 531–539.
    1. Burgel PR, Paillasseur JL, Peene B, Dusser D, Roche N, et al. (2012) Two Distinct Chronic Obstructive Pulmonary Disease (COPD) Phenotypes Are Associated with High Risk of Mortality. PLOS One 7: e51048.
    1. Garcia-Aymerich J, Gómez FP, Benet M, Farrero E, Basagaña X, et al. (2011) Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes. Thorax 66: 430–437.
    1. Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, et al. (2010) Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 363: 1128–1138.
    1. Esteban C, Quintana JM, Moraza J, Aburto M, Egurrola M, et al. (2009) Impact of hospitalisations for exacerbations of COPD on health-related quality of life. Respir Med 103: 1201–1208.
    1. Anzueto A, Leimer I, Kesten S (2009) Impact of frequency of COPD exacerbations on pulmonary function, health status and clinical outcomes. Int J Chron Obstruct Pulmon Dis 4: 245–251.
    1. Perera PN, Armstrong EP, Sherrill DL, Skrepnek GH (2012) Acute Exacerbations of COPD in the United States: Inpatient Burden and Predictors of Costs and Mortality. COPD 9: 131–141.
    1. Pozo-Rodríguez F, López-Campos JL, Álvarez-Martínez CJ, Castro-Acosta A, Agüero R, et al. (2012) Clinical Audit of COPD Patients Requiring Hospital Admissions in Spain: AUDIPOC Study. Plos One 7(7): e42156 10.1371/journal.pone.0042156
    1. Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, et al. (2011) Acute Exacerbations of Chronic Obstructive Pulmonary Disease Identification of Biologic Clusters and Their Biomarkers. Am J Respir Crit Care Med 84: 662–671.
    1. Gao P, Zhang J, He X, Hao Y, Wang K, et al. (2013) Sputum inflammatory cell-based Classification of patients with acute exacerbation of chronic obstructive pulmonary disease. Plos One 8(5): e57678 10.1371/journal.pone.0057678
    1. Quintana JM, Esteban C, Barrio I, Garcia S, González N, et al. (2011) The IRYSS-COPD Appropriateness Study: Objectives, Methodology, and Description of the Prospective Cohort. BMC Health Serv Res 11: 322 10.1186/1472-6963-11-322
    1. Benzécri JP (1969) Statistical analysis as a tool to make patterns emerge from data. In: Watanabe S. Methodologies of Pattern Recognition. New York: Academic Press, 35–74.
    1. Greenacre M (1992) Correspondence analysis in medical research. Stat Methods Med Res 1: 97–117.
    1. Teasdale G, Jennett B (1974) Assessment of coma and impaired consciousness. A practical scale. Lancet 2: 81–84.
    1. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40: 373–383.
    1. Jambu M (1978) Classification Automatique pour l'Ánalyse des Données. Tome 1: Méthodes et Algoritmes. Paris: Dunod.
    1. Ward JH (1963) Hierarchical grouping to optimize an objective function. J Am Stat Assoc 58: 236–244.
    1. R development Core Team (2010) R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing, Vienna, Austria, 2010; software available at .
    1. López-Varela MV, Montes de Oca M, Halbert R, Muiño A, Tálamo C, et al. (2013) Comorbidities and Health Status in Individuals With and Without COPD in Five Latin American Cities: The PLATINO Study. Arch Bronconeumol 49: 468–474.
    1. Lange P, Marott JL, Vestbo J, Olsen KR, Ingebrigtsen TS, et al. (2012) Prediction of the clinical course of chronic obstructive pulmonary disease, using the new GOLD classification: a study of the general population. Am J Respir Crit Care Med 186: 975–978.
    1. Mannino DM, Thorn D, Swensen A, Holguin F (2008) Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J 32: 962–969.
    1. Vanfleteren LE, Spruit MA, Groenen M, Gaffron S, van Empel VP, et al. (2013) Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 187: 728–735.
    1. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, et al. (2008) Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 178: 218–224.
    1. Weatherall M, Travers J, Shirtcliffe PM, Marsh SE, Williams MV, et al. (2009) Distinct clinical phenotypes of airways disease defined by cluster analysis. Eur Respir J 34: 812–818.
    1. Arostegui I, Quintana JM, Urkaregi A (2006) Different statistical techniques to synthesise explicit criteria developed by an expert panel. Methods Inf Med 45: 622–630.
    1. Esteban C, Arostegui I, Moraza J, Aburto M, Quintana JM, et al. (2011) Development of a decision tree to assess the severity and prognosis of stable COPD. Eur Respir J 38: 1294–1300.

Source: PubMed

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