Impact of Acute Exacerbation and Its Phenotypes on the Clinical Outcomes of Chronic Obstructive Pulmonary Disease in Hospitalized Patients: A Cross-Sectional Study

Abstract

Acute exacerbations of COPD (AECOPD) are clinically significant events having therapeutic and prognostic consequences. However, there is a lot of variation in its clinical manifestations described by phenotypes. The phenotypes of AECOPD were categorized in this study based on pathology and exposure. In our cross-sectional study, conducted between 1 January 2016 to 31 December 2020, the patients were categorized into six groups based on pathology: non-bacterial and non-eosinophilic; bacterial; eosinophilic; bacterial infection with eosinophilia; pneumonia; and bronchiectasis. Further, four groups were classified based on exposure to tobacco smoke (TS), biomass smoke (BMS), both, or no exposure. Cox proportional-hazards regression analyses were performed to assess hazard ratios, and Kaplan-Meier analysis was performed to assess survival, which was then compared using the log-rank test. The odds ratio (OR) and independent predictors of ward admission type and length of hospital stay were assessed using binomial logistic regression analyses. Of the 2236 subjects, 2194 were selected. The median age of the cohort was 67.0 (60.0 to 74.0) and 75.2% were males. Mortality rates were higher in females than in males (6.2% vs. 2.3%). AECOPD-B (bacterial infection) subjects [HR 95% CI 6.42 (3.06-13.46)], followed by AECOPD-P (pneumonia) subjects [HR (95% CI: 4.33 (2.01-9.30)], were at higher mortality risk and had a more extended hospital stay (6.0 (4.0 to 9.5) days; 6.0 (4.0 to 10.0). Subjects with TS and BMS-AECOPD [HR 95% CI 7.24 (1.53-34.29)], followed by BMS-AECOPD [HR 95% CI 5.28 (2.46-11.35)], had higher mortality risk. Different phenotypes have different impacts on AECOPD clinical outcomes. A better understanding of AECOPD phenotypes could contribute to developing an algorithm for the precise management of different phenotypes.

Keywords: AECOPD; COPD; acute exacerbation; biomass; mortality; phenotype; tobacco.

Figure 1

Flowchart of the study describing the categorization of AECOPD phenotypes based on exposure and pathology and their mortality. Red: Expired, Green: Alive, AECOPD: Acute exacerbation of chronic obstructive pulmonary diseases, NBE: No bacterial infection and no eosinophilia, B: Bacterial infection, E: Eosinophilia and no bacterial infections, BE: Bacterial infection with eosinophilia, P: Pneumonia, BC: Bronchiectasis, NTS and NBMS: Non-tobacco smoke and non-biomass smoke AECOPD, TS: Tobacco smoke, BMS: Biomass smoke, TS and BMS: Tobacco smoke and biomass smoke.

Figure 2

Kaplan–Meier survival curve for phenotypes based on pathology. AECOPD: Acute exacerbation of chronic obstructive pulmonary diseases, NBE: No bacterial infection and no eosinophilia, B: Bacterial infection, E: Eosinophilia and no bacterial infections, BE: bacterial infection with eosinophilia, P: Pneumonia, and BC: Bronchiectasis.

Figure 3

Kaplan–Meier survival curve for phenotypes based on exposure. Definition of abbreviations: AECOPD: Acute exacerbation of chronic obstructive pulmonary diseases, NTS and NBMS: Non-tobacco smoke and non-biomass smoke, TS: Tobacco smoke, BMS: Biomass smoke, and TS and BMS: Tobacco smoke and biomass smoke.