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研究生：	黃怡菁 Huang, Yi-Ching
論文名稱：	氣喘與慢性阻塞性肺病重疊症候群病人使用吸入型皮質類固醇與產生心理精神疾病的相關性：以全國性人口為基礎的世代研究 The Association between Inhaled Corticosteroid Use and Risk of Mental Disorders among Patients with Asthma-COPD Overlap Syndrome: A Nationwide Population-based Cohort Study
指導教授：	林聖翔 Lin, Sheng-Hsiang
學位類別：	碩士 Master
系所名稱：	醫學院 - 臨床醫學研究所碩士在職專班 Institute of Clinical Medicine(on the job class)
論文出版年：	2018
畢業學年度：	106
語文別：	英文
論文頁數：	67
中文關鍵詞：	氣喘、慢性阻塞性肺病、氣喘-慢性阻塞性肺病重疊症候群、吸入型類固醇、焦慮、憂鬱
外文關鍵詞：	asthma, chronic obstructive pulmonary disease, asthma-COPD overlap syndrome, inhaled corticosteroid, anxiety, depression
相關次數：	點閱：126 下載：9
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目的：
本世代研究針對有氣喘-慢性阻塞性肺病重疊症候群的患者使用吸入型類固醇情形，探討與心理精神疾病的因果關係。
實驗設計：
這個世代研究使用臺灣中央健保署的2000年承保抽樣歸人擋，納入2000年到2011年期間年滿40歲同時有醫師診斷為氣喘和慢性阻塞性肺病的患者。統計方法是使用Cox 比例風險回歸模型和競爭風險回歸模型去估計有氣喘-慢性阻塞性肺病重疊症候群的患者使用吸入型類固醇產生心理精神疾病的風險。
結果：
氣喘-慢性阻塞性肺病重疊症候群患者相較於一般患者產生焦慮、廣泛性焦慮症、憂鬱、重度憂鬱症和輕度憂鬱症的adjusted hazard ratio (aHR) 分別為 1.56, 1.55, 1.58, 1.44 和 1.62。氣喘-慢性阻塞性肺病重疊症候群患者使用吸入型類固醇的藥品持有率增加，將增加憂鬱 (aHR: 1.45)、憂鬱 (aHR: 1.55)，和輕度憂鬱症的風險 (aHR: 1.52)。
結論：
氣喘-慢性阻塞性肺病重疊症候群患者使用吸入型類固醇產生較高心理精神疾病的風險。

Purpose:
This cohort study was to evaluate the relationship between patients with asthma-COPD overlap syndrome (ACOS) using inhaled corticosteroids (ICS) and mental disorders.
Experimental Design:
We enrolled patients aged ≥ 40 years with concurrent physician-diagnosed chronic obstructive pulmonary disease (COPD) and asthma between January 1, 2000 and December 31, 2011 from the Longitudinal Health Insurance Database 2000 for our cohort study. We performed Cox proportional hazards regression analysis and competing risks regression models to assess the risks for mental disorders in patients with ACOS receiving ICS.
Results:
The adjusted hazard ratio (aHR) was 1.56 for anxiety, 1.55 for generalized anxiety disorder, 1.58 for depression, 1.44 for major depressive disorder, and 1.62 for dysthymia separately in ACOS group when compared with comparison group. As medication possession ratio of ICS increased, there were significantly increased anxiety (aHR: 1.45), depression (aHR: 1.55), and dysthymia (aHR: 1.52).
Conclusions:
Patients with ACOS using ICS had higher risk of developing mental disorders.

ABSTRACT	                                   I-II
中文摘要	                                         III-IV
誌謝	                                              V
TABLE OF CONTENTS	                         VI-VII 
LIST OF TABLES	                               VIII-XII
LIST OF FIGURES	                                   XIII
ABBREVIATION	                                    XIV
CHAPTER 1. INTRODUCTION 	                    1-7
1.1. Asthma and chronic obstructive pulmonary disease	
                                                    1-2
1.2. Asthma-COPD overlap syndrome	            2-3
1.3. Chronic respiratory diseases and steroid	    3-4
1.4. Chronic respiratory diseases and mental disorders	
                                                    4-5
1.5. Chronic respiratory diseases, steroid and mental disorders	                                    5-6
1.6. Hypothesis, specific aims and significance	    6-7
CHAPTER 2. MATERIALS AND METHODS	           8-14
2.1. Database	                                      8
2.2. Study sample and design 	                   8-10
2.3. Matching	                                     10
2.4. Covariates 	                          10-12
2.5. Outcome	                                     12
2.6. Validation	                                  12-13
  2.7. Statistical analysis	                     13
2.8. Sensitivity analysis                            14
CHAPTER 3. RESULTS 	                          15-20
3.1. Baseline demographics of asthma, COPD, ACOS, and comparison group 	                             15
3.2. The risk of mental disorders among ACOS patients 	
                                                  15-16
3.3. The effect of inhaled corticosteroid on the risk of mental disorders	                          16-18
3.4. The risk of mental disorders among ACOS patients stratified by gender	                          18-20
CHAPTER 4. DISCUSSION 	                          21-24
4.1. The strength of our study 	                     21
4.2. The differences between our study and previous literatures 	                                  21-22
4.3. The characteristics of ACOS patients with higher risk of mental disorders	                  22-23
4.4. The limitations of our study 	          23-24
CHAPTER 5 CONCLUSIONS AND SUGGESTIONS	             25
  5.1. Conclusions	                             25
  5.2. Suggestions	                             25
CHAPTER 6. REFERENCES	                          26-31
 
LIST OF TABLES
Table 1. Demographic characteristics and comorbidities (anxiety prior to index date excluded) for the cohort of sampled patients by age, sex, index year matching	
                                                  32-33
Table 2. Demographic characteristics and comorbidities (depression prior to index date excluded) for the cohort of sampled patients by age, sex, index year matching	
                                                  34-35
Table 3. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients during the follow-up years (ACOS, Asthma, COPD vs. Comparison)	                                     36
Table 4. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients during the follow-up years (ACOS, Asthma, COPD vs. Comparison)	                                     37
Table 5. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients during the follow-up years (ACOS vs. Asthma, COPD)	                                             38
Table 6. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients during the follow-up years (ACOS vs. Asthma, COPD)	                                             39
Table 7. Demographic characteristics and comorbidities (anxiety prior to index date excluded) for the cohort of sampled ACOS patients with and without ICS use by index year and propensity score matching	          40-41
Table 8. Demographic characteristics and comorbidities (depression prior to index date excluded) for the cohort of sampled ACOS patients with and without ICS use by index year and propensity score matching	  42-43
Table 9. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients with and without ICS use during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	                     44
Table 10. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients with ICS use (MPR ≥50% vs. 0<MPR<50% vs. MPR=0%) during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	     45
Table 11. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients with ICS use (MPR ≥50% vs. 0<MPR<50%) during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	             46
Table 12. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients with ICS use by quartile during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	                     47
Table 13. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients with ICS use by quartiles as continuous variables during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	
                                                     48
Table 14. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients with ICS use (MPR > median vs. 0<MPR≤ median) during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	     49
Table 15. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients with and without ICS use during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	                     50
Table 16. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients with ICS use (MPR ≥50% vs. 0<MPR<50% vs. MPR=0%) during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	     51
Table 17. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients with ICS use (MPR ≥50% vs. 0<MPR<50%) during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	             52
Table 18. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients with ICS use by quartile during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	                     53
Table 19. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients with ICS use by quartiles as continuous variables during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	
                                                     54
Table 20. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients with ICS use (MPR > median vs. 0<MPR≤ median) during the follow-up years (till 2013) by index year and propensity score matching, stratified by gender	     55
Table 21. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients with and without ICS use during one-year follow-up by index year and propensity score matching, stratified by gender	                             56
Table 22. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients with and without ICS use during one-year follow-up by index year and propensity score matching, stratified by gender	                             57
Table 23. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients with and without ICS use during two-year follow-up by index year and propensity score matching, stratified by gender	                             58
Table 24. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients with and without ICS use during two-year follow-up by index year and propensity score matching, stratified by gender	                             59
Table 25. Multivariable-adjusted Cox regression models hazard ratios of anxiety among the cohort of sampled patients with and without ICS use during three-year follow-up by index year and propensity score matching, stratified by gender	                             60
Table 26. Multivariable-adjusted Cox regression models hazard ratios of depression among the cohort of sampled patients with and without ICS use during three-year follow-up by index year and propensity score matching, stratified by gender	                             61
 
LIST OF FIGURES
Figure 1. Kaplan-Meier curves of anxiety-free rate in ACOS cohort with and without ICS use in propensity score-matched models till 2013	                     62
Figure 2. Kaplan-Meier curves of anxiety-free rate in ACOS cohort with and without ICS use in propensity score-matched models during one-year follow-up	     63
Figure 3. Kaplan-Meier curves of anxiety-free rate in ACOS cohort with ICS use divided by MPR in propensity score-matched models till 2013    	             64
Figure 4. Sensitivity analysis estimated HR of anxiety in ACOS cohort with and without ICS use till 2013	     65
Figure 5. Sensitivity analysis estimated HR of anxiety in ACOS cohort with and without ICS use during one-year follow-up 	                                     66
Figure 6. Sensitivity analysis estimated HR of anxiety in ACOS cohort with ICS use divided by MPR till 2013	
                                                     67
                                    

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校內：2023-02-09公開
校外：2023-02-09公開

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