| Summary: | 碩士 === 國立陽明大學 === 藥理學研究所 === 106 === Background: Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms. Globally, there are approximately 384 million patients with COPD, which causes about 3 million deaths annually. Among patients with COPD, 12-55% patients also have features of asthma, particularly in older patients. Coexistence of COPD and asthma is associated with higher frequency of exacerbations. Exacerbations, defined as worsening respiratory symptoms, result in the use of systemic glucocorticoids/ antibiotics for at least seven days (moderate), or even result in admission to emergency department or hospitalization (severe). However, there is still no consensus criteria to diagnose patients concomitant with asthma and COPD so far. Furthermore, patients with asthma-COPD overlap (ACO) are always excluded in clinical trials. Long-acting bronchodilator is the first choice for COPD and inhaled corticosteroid (ICS) is the first choice for asthma. However, there is limited evidence to guide the treatment in ACO. Apart from asthma, increased number (or percentage) of blood eosinophils is considered a predictor of exacerbations, but the precise cut-off value to define eosinophilic COPD and to guide the treatment is controversial. The objective of our study is to evaluate the impact of asthma on patients with COPD and to select the best combined treatment for patients. Furthermore, we want to know the differences in charateristics, risk of exacerbations and response to respiratory drugs between non-eosinophilic and eosinophilic COPD.
Methods: We performed the retrospective cohort study by reviewing the medical records from patients visited the outpatient department of Taipei Veterans General Hospital. Our study was composed by three parts. In the first and second part of the study, we compared the risk of exacerbations and the effect of respiratory drugs on exacerbations of COPD-alone to ACO under different criteria. The presence of airflow limitation was not necessary for patients met the non-spirometry support criteria, but it was required under the spirometry-defined criteria. In the second part of the study, we analyzed the effect of respiratory drugs on exacerbations, and the treatment was assumed to be time-dependent covariates. In the third part of our study, we focused on eosinophilic COPD. As 2% was mostly used cut-off value in other studies to define eosinophilic COPD, we used 2% as cut-off value to compare the baseline characteristics of eosinophilic (eosinophils account for white blood cell [WBC] more or equal to 2%) to non-eosinophilic COPD (less than 2%). Also, we used different cut-off values (3%, 4% or 300/μL) to compare the risk of exacerbations and effect of treatment of eosinophilic COPD to non-eosinophilic COPD.
Results: In the first part of the study, a total of 289 patients with newly physician-diagnosed COPD met the non-spirometry support criteria, and 106 of them had diagnosis of asthma as well (ACO). There were 121 patients with persistent airflow limitation proved by standard bronchodilator tests, and 53 of them also had diagnosis of asthma. There was a trend that the patients overlapping with asthma and COPD were associated with higher risk of exacerbations in both criteria. In the second part of the study, we had the similar results under two criteria. Among patients overlapping with asthma, the prescription of inhaled corticosteroids (ICS)/ long-acting beta-2 agonist (LABA) was significantly associated with reduced risk of exacerbations. For patients without diagnosis of asthma, long-acting bronchodilators were better. In the last part of the study, although not significant, we found that patients with increased blood eosinophils tended to be older, higher proportion of ever smokers, better lung function and similar proportion of male. Besides, eosinophilic COPD was significantly associated with allergic rhinitis. By using 2% as cut-off value, we found that eosinophilic COPD was associated with decreased risk of exacerbations in comparison with non-eosinophilic COPD. As cut-off values increased, the risk of exacerbations in eosinophilic COPD became higher. Similarly, by using 2% as a cut-off value, we found that patients with eosinophilic COPD were associated with lower risk of exacerbations after the treatment. However, If the cut-off increased to 4% or 300 /μL, patients with higher eosinophils were associated with higher risk of exacerbations after the treatment. For all the 94 patients included in the third part, ICS/LABA was significantly associated with decreased risk of exacerbations.
Conclusions: Compared with COPD-alone, coexistence of asthma and COPD was associated with increased risk of exacerbations. ICS/LABA was recommended for the purpose of preventing the exacerbations. When the cut-off value to define eosinophilic COPD increased to 4% or 300/μL, eosinophilic COPD tended to have higher risk of exacerbations. Further investigations are needed in the future to confirm the effect of bronchodilators in asthma-COPD overlap. Additionally, further evidence is needed to demonstrate the difference in the risk of exacerbations and response to respiratory drugs between eosinophilic and non-eosinophilic COPD.
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