Chest
Volume 147, Issue 4, April 2015, Pages 999-1007
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Original Research COPD
Hospitalized Exacerbations of COPD: Risk Factors and Outcomes in the ECLIPSE Cohort

https://doi.org/10.1378/chest.14-0655Get rights and content

Abstract

OBJECTIVE: Exacerbations of COPD requiring hospital admission have important clinical and societal implications. We sought to investigate the incidence, recurrence, risk factors, and mortality of patients with COPD exacerbations requiring hospital admission compared with those without hospital admission during 3-year follow-up. Patients with COPD (N = 2,138) were identified from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) observational cohort.

METHODS: An analysis of time to first event of hospital admission was performed using Kaplan-Meier curves and Cox proportional hazard regression adjusting for possible confounders.

RESULTS: Of the 2,138 patients, 670 (31%) reported a total of 1,452 COPD exacerbations requiring hospital admission during the study period; 313 patients (15%) reported multiple events. A prior history of exacerbation of COPD requiring hospital admission was the factor associated with the highest risk of a new hospitalization for exacerbation (hazard ratio, 2.71; 95% CI, 2.24-3.29;P< .001). Other risk factors included more severe airflow limitation, poorer health status, older age, radiologic evidence of emphysema, and higher WBC count. Having been hospitalized for exacerbation significantly increased the risk of mortality (P< .001).

CONCLUSIONS: Exacerbations of COPD requiring hospital admission occur across all stages of airflow limitation and are a significant prognostic factor of reduced survival across all COPD stages. Patients with COPD at a high risk for hospitalization can be identified by their past history for similar events, and other factors, including the severity of airflow limitation, poor health status, age, presence of emphysema, and leukocytosis.

TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00292552; URL: www.clinicaltrials.gov

Section snippets

Study Design and Ethics

The design of the ECLIPSE study (SCO104960, NCT00292552) has been published elsewhere.9 In brief, patients between 40 and 75 years old were included if they had a history of ≥ 10 pack-years of smoking, as well as an FEV1< 80% of predicted value and a ratio of FEV1to FVC ≤ 0.7; both were measured after bronchodilator use. COPD severity for each subject was graded according to GOLD (Global Initiative for Chronic Obstructive Lung Disease).3 The study was conducted in accordance with the

Baseline Measurements

The methodology used in the ECLIPSE study has been described in detail elsewhere.9 Briefly, standardized questionnaires were used to measure dyspnea (modified Medical Research Council dyspnea scale),13 health status (St. George's Respiratory Questionnaire for patients with COPD),14 fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue Questionnaire)15 and depression (Center for Epidemiologic Studies of Depression Scale).16 Likewise, information on symptoms of cough, sputum

Follow-up and Exacerbation Ascertainment

Subjects were followed-up at 3 months, 6 months, and every 6 months thereafter for a maximum of 3 years. All patients had their vital status confirmed 3 years after recruitment.

Information on COPD exacerbations was collected at scheduled visits by investigators using the case report forms and based on either subjects' recall of exacerbation events or available medical records for exacerbation events, supplemented by monthly phone calls. For the purpose of the current analysis, we focused on

Statistical Analysis

To investigate the prespecified goals of the study, we used the following analyses: (1) baseline differences between patients with and without hospitalized exacerbation during follow-up were tested using analysis of variance or Wilcoxon rank-sum test for continuous variables, and χ2test for categorical variables; (2) the incidence (first hospitalized exacerbation during the prospective follow-up) and recurrence (second hospitalized exacerbation during the prospective follow-up) of hospitalized

Results

Figure 1 presents the flow diagram of the study. In total, 2,138 patients with COPD with complete exacerbation data during follow-up were included in the analysis. Overall, the patient population baseline characteristics were similar to those of the entire ECLIPSE COPD population (N = 2,164).22

Discussion

The main findings of this study are (1) COPD exacerbations requiring hospital admission are relatively frequent events occurring in about 30% of patients during the 3-year follow-up; (2) past history of hospitalized exacerbations is most predictive of future events, and other risk factors include the severity of airflow limitation, poor health status, radiologic evidence of emphysema, older age, and presence of systemic inflammation; and (3) a history of hospitalized exacerbations heralds poor

Acknowledgments

Author contributions:H. M. had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects, and served as principal author. H. M., D. J. M., and N. L. contributed to drafting the manuscript; H. M., D. J. M., N. L., J. V., J. R. H., J. A. W., A. Agusti, and A. Anzueto contributed to study conception and design; H. M. and N. L. contributed to data analysis; and H. M., D. J. M., N.

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    Dr Wedzicha is currently at the National Heart and Lung Institute, Imperial College London (London, England).Funding/Support:The ECLIPSE study was funded by GlaxoSmithKline. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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