The Relation Between Clinical Phenotypes, GOLD Groups/Stages and Mortality in COPD Patients – A Prospective Multicenter Study

Abstract

Introduction The concept of phenotyping emerged, reflecting specific clinical, pulmonary and extrapulmonary features of each particular chronic obstructive pulmonary disease (COPD) case. Our aim was to analyze prognostic utility of: “Czech“ COPD phenotypes and their most frequent combinations, ”Spanish” phenotypes and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages + groups in relation to long-term mortality risk. Methods Data were extracted from the Czech Multicenter Research Database (CMRD) of COPD. Kaplan-Meier (KM) estimates (at 60 months from inclusion) were used for mortality assessment. Survival rates were calculated for the six elementary “Czech” phenotypes and their most frequent and relevant combinations, “Spanish” phenotypes, GOLD grades and groups. Statistically significant differences were tested by Log Rank test. An analysis of factors underlying mortality risk (the role of confounders) has been assessed with the use of classification and regression tree (CART) analysis. Basic factors showing significant differences between deceased and living patients were entered into the CART model. This showed six different risk groups, the differences in risk were tested by a Log Rank test. Results The cohort (n=720) was 73.1% men, with a mean age of 66.6 years and mean FEV 1 44.4% pred. KM estimates showed bronchiectases/COPD overlap (HR 1.425, p=0.045), frequent exacerbator (HR 1.58, p<0.001), cachexia (HR 2.262, p<0.001) and emphysematous (HR 1.786, p=0.015) phenotypes associated with higher mortality risk. Co-presence of multiple phenotypes in a single patient had additive effect on risk; combination of emphysema, cachexia and frequent exacerbations translated into poorest prognosis (HR 3.075; p<0.001). Of the “Spanish” phenotypes, AE CB and AE non-CB were associated with greater risk of mortality (HR 1.787 and 2.001; both p=0.001). FEV 1 % pred., cachexia and chronic heart failure in patient history were the major underlying factors determining mortality risk in our cohort. Conclusion Certain phenotypes (“Czech” or “Spanish”) of COPD are associated with higher risk of death. Co-presence of multiple phenotypes (emphysematous plus cachectic plus frequent exacerbator) in a single individual was associated with amplified risk of mortality.

Impacto de las exacerbaciones en la enfermedad pulmonar obstructiva crónica Exacerbaciones en la EPOC

“…De esta clasificación, se ha demostrado que el grado 4 y grupo E se asocian a mayor riesgo de mortalidad y peor pronóstico, lo que nuevamente confirma el impacto negativo de las exacerbaciones en los desenlaces del paciente . 3,15,38 Figura 1.…”

“…De manera particular, la literatura ha evidenciado que la mayor carga de la enfermedad y el mayor uso de recursos se destina a tratar las exacerbaciones debido al requerimiento de manejo más agresivo, incluyendo el uso de la sala de urgencias, hospitalización, Unidad de Terapia Intensiva (UTI) y el incremento de tratamiento farmacológico; como lo enfatizan los resultados del estudio ARTIC 26 y recientemente en el Panel Delphi de expertos mexicanos Evaluación del costo en pacientes con Enfermedad Pulmonar Obstructiva Crónica (EPOC) dentro de la perspectiva pública de salud. 38 En otro estudio 10 se encontraron costos médicos totales, en el uso de servicios de urgencias, hospitalización y de farmacia progresivamente mayores conforme progresaba la etapa GOLD y sus tasas de exacerbaciones.…”

“…Los costos directos fueron causados principalmente por el gasto en medicamentos, oxígeno y hospitalización. El Panel Delphi de expertos mexicanos de la Evaluación de costos en EPOC (Hernández Zenteno, et al 2022) 38 reportó una variación de los costos del tratamiento farmacológico en exacerbación entre las categorías 1 y 4 de la enfermedad de $28,900.00 pesos aproximadamente. Las categorías Gold 3 y 4 representan la mayor parte de la carga de la enfermedad ya que se concentra el mayor uso de recursos, la variación entre categorías es de 283.64% .…”

“…El costo anual promedio estimado para el manejo de exacerbaciones en pacientes GOLD 1 es de $16,832.30 MXN equivalente a $841 USD, GOLD 2 $ 60,693.23 MXN / $3034.66 USD, GOLD 3 $152,596.27/ $7629.81 USD y GOLD 4 $397,868.38/ $19893.41 USD. 38 Es importante señalar que el coste de una exacerbación de la EPOC puede variar mucho en función de las circunstancias individuales y de los sistemas sanitarios, y que esta estimación es específica de los costos directos relacionados con la exacerbación incluyendo los de hospitalización, medicación y honorarios médicos; pero no los indirectos, como la pérdida de productividad, días de incapacidad y rehabilitación.…”

RETRO-POPE: A Retrospective, Multicenter, Real-World Study of All-Cause Mortality in COPD

“…For example, longitudinal studies conducted in Spain and the Czech Republic have consistently shown a higher mortality risk in patients with an exacerbation phenotype (with or without chronic bronchitis), compared with NON-AE and those with ACOS. [5][6][7] Other studies have shown that a clustering approach, which groups patients based on clinical features such as comorbidities, dyspnea, and lung function, is also a useful predictor of mortality. [8][9][10][11][12] In one study, cluster analysis was found to be significantly superior to the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 spirometry classification system for predicting mortality, with similar predictive ability to other systems such as the body mass index (BMI), obstruction, dyspnea and exercise (BODE) index and the GOLD ABCD classification.…”