대한내과학회지 : 제 83 권제 4 호 2012 http://dx.doi.org/10.3904/kjm.2012.83.4.468 COPD 환자에서우울증선별검사 1 한림대학교성심병원호흡기내과, 2 고려대학교근거중심의학연구소, 3 가톨릭대학교성바오로병원정신과, 4 국립의료원호흡기내과, 5 울산대학교의과대학서울아산병원호흡기내과 황용일 1 김현정 2 원왕연 3 조준성 4 오연목 5 정기석 1 이상도 5 Screening for Depression in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review Yong Il Hwang 1, Hyun Jung Kim 2, Wang Youn Won 3, Joon Sung Joh 4, Yeon-Mok Oh 5, Ki-Suck Jung 1, and Sang-Do Lee 5 1 Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 2 Institute for Evidence-Based Medicine, Korea University, 3 Department of Psychiatry, St. Paul's Hospital, The Catholic University of Korea School of Medicine, 4 Department of International Medicine, National Medical Center, 5 Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Background/Aims: Chronic obstructive pulmonary disease (COPD) often coexists with co-morbid conditions that significantly affect the prognosis. Although depression frequently coexists with COPD, little about how to screen for depression in COPD patients is known. We report the effectiveness of depression screening in patients with COPD and of the instruments used for this purpose. Methods: We performed a systematic literature review of the domestic (Research Information Sharing Service, KoreaMed, and Kmbase) and international (Medline, Embase, Cochrane library) databases using COPD AND depression AND screening tools as key words. Results: No study directly evaluated the effectiveness of screening for depression in COPD patients. However, depression was present more frequently in patients with COPD. COPD patients with depression were also more likely to be in poor health. A total of eight screening instruments for depression were translated into Korean. All had similar reliabilities and internal consistencies. Conclusions: Screening of COPD patients for depression is necessary because individuals with this condition are more likely to suffer from depression, which has a negative impact on health. The choice of depression screening instruments may need to be based on considerations of simplicity. (Korean J Med 2012;83:468-475) Keywords: COPD; Depression; Screening Received: 2012. 4. 24 Revised: 2012. 6. 13 Accepted: 2012. 7. 26 Correspondence to Yeon-Mok Oh, M.D. Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Asanbyeongwon-gil 86, Sonpa-gu, Seoul 138-736, Korea Tel: +82-2-3010-3136, Fax: +82-2-3010-6968, E-mail: ymoh55@amc.seoul.kr Copyright c 2012 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 468 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Yong Il Hwang, et al. Screening for depression in COPD - 서론우울증은많은만성질환과관련이있다. 종합병원내과계환자들의 10-20% 에서우울증이동반되어있는것으로알려져있다 [1]. 실제로당뇨병환자의 11% [2], 보존적치료를받는암환자들의 15% [3], 심근경색환자들의 20% [4], 파킨슨병환자의 17% [5] 가우울증에이환되어있다. 우울증은질환자체가가지고있는불쾌한감정상태와는별개로동반질환의예후를나쁘게한다. 우울증은인해동반질환에대한환자들의순응도가떨어뜨리며 [6] 환자들의삶의질에영향을준다. 또한우울증은심부전 [7], 후천성면역결핍증 (HIV/AIDS) [8], 암 [9], 신부전 [10], 심근경색 [11], 뇌졸중 [12] 과같은질환의사망률을높이는것으로알려져있다. 이처럼우울증은많은만성질환에서환자들에게흔하고중요한문제로만성질환에동반된우울증의치료에대한중요성은계속강조되어오고있다. 만성폐쇄성폐질환 (chronic obstructive pulmonary disease, COPD) 은우리나라에서 2001년도에 45세이상성인에서 17.2%, 2008년도에는 40세이상의성인의 13.4% 에서 COPD에이환되어있는것으로조사될정도로흔한질환이다 [13]. COPD 는심근경색과협심증, 골다공증, 골절, 당뇨, 빈혈, 수면장애등다른질환이잘동반되며, 우울증도그중의하나로알려져있다 [14]. 하지만, 현재 COPD 환자들에게우울증의선별검사의효과와선별검사를무슨도구로시행해야하는지알려진바가전혀없는실정이다. 이에저자들은 COPD 환자에서우울증선별검사효과와우울증진단도구로일차진료의가선별검사목적으로사용할수있는것이어느것인지알아보기위해 COPD 환자에게우울증선별검사를하는것이필요한가? 와 우울증진단도구중, 일선진료의의선별검사목적으로권장할만한것은무엇인가? 라는두가지핵심질문을선정하고이에대한답을구하고자하였다. 방법저자들은위의두가지핵심질문에대한답을얻기위해체계적인문헌고찰을수행하였다. 체계적인문헌고찰을위해먼저선정된핵심질문에대한핵심용어를선정한후선정된핵심용어를바탕으로데이터베이스에서문헌검색을시행하였다. 검색된문헌은연구자들이초록을확인한후최종문헌을선택하였다. 핵심용어의선정문헌검색에사용된핵심용어는국문의경우 만성폐쇄성폐질환 AND 우울증 AND 선별검사 영문의경우는 COPD AND depression AND screening tools 였으며유사어로 chronic obstructive pulmonary disease, emphysema, chronic bronchitis, chronic obstructive lung disease, obstructive lung disease, obstructive pulmonary disease, obstructive lung diseases, obstructive pulmonary diseases, dysthymua, depressive disorder, depressive symptoms, depressive mood, diagnosis, psychometric scale, psychometric questionnaire, detection, identification 을사용하였다. 문헌검색첫번째핵심질문을위한문헌검색을위해사용한데이터베이스로는국내의경우코리아메드 (www.koreamed.org), 학술연구정보서비스 (www.riss.kr), 국내의학학술지초록검색 (kmbase.medric.or.kr) 를이용하였고국외의경우는 Medline, Embase, Cochrane Library를이용하였다. 검색하고자하는문헌의종류는메타분석, 대조임상시험, 비대조임상시험, 관찰연구모두포함하고사용된언어는영어와한국어로제한하였다. 두번째핵심질문인 COPD 환자에게적절한선별검사도구와관련하여서는국제적으로신체질환이있는환자들에게우울증선별검사로권장되는우울증선별도구 [15] 중한국어로번역되어검증이완료된선별도구에한해서만연구를진행하여국내문헌만을대상으로검색을수행하였다. 선택된문헌의질평가본연구에서포함된연구에대한문헌의질평가는무작위대조군연구의경우의질평가는 QUADAS tool, 비무작위대조군연구의질평가는 Newcastle-Ottawa Scale 을이용하여수행하였다. 또한문헌검색결과얻어진결과에대한근거수준평가는개별연구의연구디자인에따른문헌의질평가결과와연구결과의일관성, 연구결과의직접성, 효과의크기, 연구결과의정확성, 출판오류, 측정된효과의양반응, 교란변수의가능성등을고려한 GRADE 그룹 (Grading of Recommendations Assessment, Development and Evaluation [GRADE] Working Group) 에서제시하는방법론에따라평가하였다. - 469 -
- 대한내과학회지 : 제 83 권제 4 호통권제 626 호 2012 - 결과 COPD 환자에게우울증선별검사를하는것이필요한가? 첫번째핵심질문에대해서는총 250개의문헌이검색되었으며이중 COPD 환자에서우울증선별검사의효과에대한관찰연구 2편 [16,17], COPD 환자의우울증유병률에대한메타분석 1편 [18], 대규모역학연구 3편 [19-21] 과국내연구 4편 [22-25] 을선택하였다 (Table 1). COPD 환자들을대상으로우울증선별검사의유용성을조사한무작위대조연구는검색이되지않았지만 COPD 환자들을대상으로한우울증선별검사에대한관찰연구결과를보면우울증선별검사를통해 COPD 환자들의 11.2% [16], 12.9% [17] 에서주요우울증 (major depression) 이진단되었으며메타연구결과에서는 COPD 환자의우울증유병률은 24.6% (95% CI: 20.0-28.6%) 로조사되어대조군의유병률 11.7% (95% CI: 9.0-15.1%) 보다통계적으로의미있게높았다 [18]. 또한 COPD 환자의우울증위험도 (Odds Ratio, OR) 도 2.81에서 4.26 [18-20] 까지조사가되어 COPD 환자들이우울증에이환될위험이높을뿐만아니라 COPD 환자들은일반인들보다심리적인고통을더많이겪고있는것으로조사되었다 [21]. 우울증선별검사에대한관찰연구와메타분석사이의유병률차이에대해서는추가적인연구가필요할것이다. 국내연구결과들은외국의연구보다는우울증의유병률이높게조사가되었다. 국내 COPD 환자들은 17% [22] 에서 55% 까지우울증이동반되어있으며 [23-25] 이는일반인의우울증유병률보다높은것이다 [48]. COPD 환자들이우울증의위험도는 2.7로조사되었다 [25]. 국내연구에서는 COPD 환자들의삶의질에대해서도조사가된연구가두가지있었으며 [23,24] 우울증점수와삶의질을나타내는 St. Goerge Respiratory Questionnaire (SGRQ), COPD Assessment test (CAT) 사이에유의한상관관계가관찰되었다. 우울증진단도구중, 일선진료의의선별검사목적으로권장할만한것은무엇인가? 두번째질문에대해서는국내데이터베이스에서총 11,582 개문헌이검색되었으며중복된문헌을제외하고우울증진단을위해타당도검증을시행한문헌을추출하여총 22 개의문헌이선택되었다 [26-47]. 검사도구별로는 Hamilton Depression Rating Scale (HDRS) 1편 [26], Montgomery-Asberg Depression Rating Scale (MADRS) 1편 [27], Center for Epidemiological Studies-Depression Scale (CES-D) 4편 [28-31], Zung s Self-Rating Depression Scale (SRS) 3편 [32-34], Hospital Anxiety and Depression Scale (HADS) 1편 [35], Beck Depression Inventory (BDI) 5편 [36-40], Geriatric Depression Scale (GDS) 5편 [41-45], Patient Health Questionnaire (PHQ) 2편 [46,47] 이었다. 이중환자의자가기입이가능한도구는여섯가지이다 [28-47]. Hamilton Depression Rating Scale (HDRS) 17개의항목으로구성된관찰자평가척도로 103명의주요우울증환자를대상으로한연구에서높은내적일치도 (chronbach α = 0.76) 을보였고 MADRS 와높은상관관계를보였고 (r = 0.84, p < 0.001) BDI 와도의미있는상관관계를보였다 (r = 0.58, p < 0.001) [26]. Montgomery-Asberg Depression Rating Scale (MADRS) 10개의항목으로구성된관찰자평가척도로 107명의주요우울증환자를대상으로한연구에서높은내적일치도 (chronbach α = 0.79) 를보였고 HDRS와높은상관관계를보였고 (r = 0.82, p < 0.001) 자가보고척도인 BDI와도의미있는상관관계를보였다 (r = 0.47, p < 0.001) [27]. Center for Epidemiological Studies-Depression Scale (CES-D) 20개의항목으로구성된자가보고형평가척도로일반인을대상으로하여내적일치도를평가한네가지연구에서모두높은내적일치도를보였다 (0.84, 0.89, 0.91, 0.91) [28-31]. 우울증환자에서의내적일치도도 0.89로높게측정되었다 [30]. 우울증진단을위한절단점 (cut-off point) 은외국의경우일반적으로는 16점이상을우울증선별을위한값으로사용하나우울증, 정신분열증, 알코올의존환자들의 CED-D 를비교한초기연구에서는 16점이상인환자의비율이우울증에서는 100%, 정신분열증에서는 61%, 알코올의존증에서는 52% 로조사되어 16점보다는높은값의필요성이제기되었고 [28] 이후연구에서는 24점을절단점으로사용할경우민감도 94%, 특이도 100% 로조사되었으며 [29] 또다른연구에서는정신과환자들을대상으로사용할경우에는 25점, 일반인을대상으로사용할경우에는 21점을절단점으로제시하였다 [30]. - 470 -
- 황용일외 6 인. COPD 환자에서우울증선별검사 - Table 1. Prevalence of depression in COPD patients Author/year Design Sample size Definition Results Julian, et al. 2009 Lamers, et al. 2008 Zhang, et al. 2011 Cross-sectional COPD, n = 188 COPD = physician diagnosis Cross-sectional Meta-analysis COPD, n = 118 8 studies included COPD, n = 39,587 Control, n = 39,431 Depression = MINI International Neuropsychiatric Inventory COPD = physician diagnosis Depression = MINI International Neuropsychiatric Inventory COPD = chronic obstructive pulmonary disease; COPD; chronic obstructive airway disease; COAD; chronic obstructive lung; chronic airway obstruction; chronic bronchitis; emphysema [This does not follow the format used elsewhere and the meaning of the second COPD and the final disorders is unclear.] 11.2% 12.9% COPD = 24.6% vs. control =11.7% Pooled odds ratio: 2.81 (95% CI: 1.69-4.66) Egede. 2007 Cross-sectional General population n = 30,801 Wilhelm K, et al. 2003 Wagena EJ, et al. 2005 Chin HJ, et al. 2008 Ryu YJ, et al. 2007 Hwang YI, et al. 2010 Ryu YJ, et al. 2010 Cross-sectional COPD n = 1,681 General population n = 10,641 Cross-sectional COPD, n = 118 General population, n = 500 Psychiatric outpatients, n = 500 Depression = depress COPD = self reported Depression = SIDI-SF Chronic bronchitis = self reported Depression: DSM- IV COPD: Gold guideline No or mild depression: BDI < 15 Moderate-to-severe depression: BDI 15 Cross-sectional COPD, n = 59 COPD: Gold guidelines Cross-sectional COPD, n = 72 Control, n = 50 Depression: CES-D 21 COPD: GOLD guidelines Depression: BDI 21 Cross-sectional COPD, n = 803 COPD: GOLD guidelines Cross-sectional COPD, n = 84 Control, n = 73 Depression: PHQ-9 10 COPD: GOLD guidelines Depression: No or mild depression: BDI < 16 Moderate-to-severe depression: BDI 16 15.4% (13.6,17.4) OR = 3.21 (95% CI: 2.72-3.79) (COPD vs. no health problem) OR = 4.26 (95% CI: 2.47-7.34) (Chronic bronchitis: present vs. absent) 29.6% Total SCL-90-R score: COPD 153.7 ± 53.7 vs. general population 119.4 ± 33.4 (p 0.01) 17% Significant correlation between CES-D and SGRQ scores COPD = 36% vs. control = 6% (p < 0.0001) 23.8% Significant correlation between PHQ-9 and CAT scores COPD = 55% vs. healthy control = 30% (p < 0.05) OR = 2.7(COPD vs. control, p = 0.004) - 471 -
- The Korean Journal of Medicine: Vol. 83, No. 4, 2012 - Zung s Self-Rating Depression Scale (SDS) 20개의문항으로구성된자가보고형도구로초기연구에서우울증환자의증상평가에도움이되었고 [32] 일반인과우울증환자모두에게서높은내적일치도를보인다 ( 일반인 0.84, 우울증환자 0.77) [33,34]. 또한 BDI와도높은상관계수를보였다 (r = 0.72, p = 0.0001) [34]. Geriatric Depression Scale (GDS) 30개의문항으로구성된자가보고형도구로노인환자들을대상으로사용이된다. GDS는정상인과노인환자에서모두높은내적일치도를보이며 [41,44,45] 다른우울증선별도구인 BDI, SDS, CES-D, HRDS 등과도높은상관관계를보인다 [44,45]. 하지만연구마다다양한절단점을보인다 (Table 2). Hospital Anxiety and Depression Scale (HADS) 14개의문항으로구성된자가보고형도구로정상인, 우울장애환자, 불안장애환자를대상으로한연구에서내적일치도는 0.86, BDI 와의상관계수는 0.80이었다. 절단점을 8점으로할경우민감도는 89.2% 특이도는 82.5% 였다 [35]. Beck Depression Inventory (BDI) 21개의항목으로구성된자가보고가가능한도구로여러집단을대상으로한연구에서모두높은내적일치도를보이고있다 [36-40]. 다만연구대상마다절단점값이차이가있어일반인을대상으로한경우에는 21점 [36], 다른연구에서는남자 23점, 여자 24점 [37] 이제시되었고일차진료의를찾아오는만성질환환자에서는 14점 [39] 이제시되었다. 정신과환자들의경우에도남자 23점, 여자 24점을제시한연구 [39] 와 22점을제시한연구 [40] 가있다. Patient Health Questionnaire-9 (PHQ-9) 9개의문항으로구성된자가보고형도구로정상인, 만성질환환자, 정신과외래환자들모두에서높은내적일치도를보이며절단점은 9점, 9.5점으로제시되고있다 [46,47]. 고찰본연구에서 COPD 환자의우울증유병률은 11.2% [16] 에서 55% [25] 까지다양하였지만 COPD 환자들은우울증의위험성이높은것으로조사되었다 [18-20,25]. 이러한유병률의차이는선택된문헌의연구방법의차이에기인한것으로생각되지만보다정확한유병률을구하기위한노력이필요할것이다. COPD 환자들에서우울증이잘동반되는이유로는환자들의나이, 폐기능, 연령과같은임상지표들보다는 COPD 자체의증상이나 COPD로인한삶의질저하등이우울증 Table 2. Depression screening instruments (translated into Korean) Items Cut-off point Sensitivity Specificity PPV Hamilton Depression Rating Scale 17 NR NR NR NR Montgomery Asberg Depression Rating Scale 10 NR NR NR NR Center for Epidemiological Studies-Depression Scale a 20 25 (for patients) 21 (for epidemiology) 24 91.3% 95.7% 94%% 78.8% 69.5% 100% Zung s Self-Rating Depression a 20 SDS index: 56 76% 72% 93% Hospital Anxiety and Depression Scale a 14 8 89.2% 82.5% NR Beck Depression Inventory a 21 14 23 (males)/24 (females) Geriatric Depression Scale a 30 18 10 19 Patient Health Questionnaire 9 a 9 9 9.5 NR, not reported; PPV, positive predictive value. a Self reported instrument. 77.7% 66.7% 65.6% 71.7% 91% 90.9% 85% 82.4% 82.9% 64.9% 60.6% 82% 87.0 % 52% NR 95.5 NR NR - 472 -
- Yong Il Hwang, et al. Screening for depression in COPD - 발생에더욱기여하는것으로알려져있다 [18,49]. 또한우울증은 COPD 환자들의삶의질에나쁜영향을끼쳐 [23,24] COPD 환자들은일반인들보다심리적인고통을더많이겪고있다 [21]. 실제로 2010년국내에서시행된실태조사결과를보면우울증이동반이될경우 COPD Assessment Test (CAT) 로측정한삶의질평가에서 97.9% 의환자들이 CAT 점수가 10점이상으로삶의질에나쁜영향을받는것으로조사되었다 [14,24]. 따라서 COPD 환자들에게서우울증은중요한문제이며우울증의조기발견과치료를위한노력이필요하다. 일반인들에게일률적인우울증선별검사가우울증의진단, 치료, 예후에큰영향을끼치지는않지만 [50], 영국의 National Institute for Health and Clinical Excellence (NICE) 지침에서만성질환이동반된환자들에게우울증치료를강조하고있고 [15], 미국의 U.S. Preventive Services Task Force (USPSTF) 에서도우울증발견후진단, 치료, 추적관찰이가능할경우에는일반성인에서도우울증선별검사를권장하고있으므로 [51] COPD 환자들에게우울증선별검사를시행하는것이필요할것이다. COPD와같은만성질환환자들에게서정확한우울증의진단은중요한문제이다. 하지만신경정신과의사들이아닌의사들이우울증을진단하는것은쉽지않다. 일차진료의들을대상으로한연구에서만성질환이동반된환자들에게서우울증을진단할수있는확률은 23% 로만성질환이없을경우의 94% 와큰차이를보인다 [52]. 따라서우울증발견을위한적절한선별검사의사용이필요하다. 영국의 NICE 지침에서는 13가지의선별검사도구를제시하고있으며각도구는모두비슷한진단적정확도를보이고있으며 [15] 어떤한도구가다른도구보다우월하다는연구는없다 [50]. 본연구에서는우울증선별검사도구중한글로번역이되어있는 8개도구의신뢰도, 타당도를조사하였다. 한글화된각각의도구들은 10-30개의문항으로이루어져있었으며모두높은내적일치도를보이고있다. 자가기입이가능한 6개의도구들은모두비슷한정도의민감도와특이도를보이고있다 (Table 2). 한글화된도구들은한가지도구를여러연구자가서로다르게번역하거나연구에따라서는우울증진단의황금률 (Golden Standard) 이불명확한경우가있기는하나일선진료현장에서사용하는데는무리가없을것으로판단된다. 국내와같이바쁜외래진료환경을고려하면환자의자가기입이가능하고문항수가상대적으로적은 선별도구의사용이유리할것으로생각된다. 결론적으로 COPD 환자에서우울증은흔한동반질환이고 COPD가있을경우우울증의발생또한높아진다. 우울증이동반이될경우 COPD 환자의삶의질은더욱나쁘게되므로 COPD 환자에게우울증선별검사가필요하다. 우울증선별검사도구중한글화되어있는도구는 8가지가있으며각각의도구는비슷한정도의신뢰도와타당도를가진다. 우울증의선별을위해서한글화된 8가지도구도사용이모두가능하나문항수가적고환자의자가기입이가능한도구가현재의진료현실에서는적합할것으로생각된다. 요약목적 : 우울증은 COPD 환자들에게흔하게동반되는질환이다. 하지만현재 COPD 환자들에게우울증의선별검사의효과와선별검사를무슨도구로시행해야하는지알려진바가전혀없는실정이다. 이에체계적문헌고찰을통해 COPD 환자의우울증선별검사효과와도구에대해서알아보고자하였다. 방법 : COPD 환자에서우울증선별검사효과와우울증진단도구로일차진료의가선별검사목적으로사용할수있는것이어느것인지알아보기위해 COPD 환자에게우울증선별검사를하는것이필요한가? 와 우울증진단도구중, 일선진료의의선별검사목적으로권장할만한것은무엇인가? 라는두가지핵심질문을선정하고이에대한답을구하고자하였다. 문헌검색을위한데이터베이스로는국내의경우국내의학학술지초록검색 (kmbase.medric.or.kr), 학술연구정보서비스 (www.riss.kr), 코리아메드 (www.koreamed.org) 를이용하였고국외의경우는 Medline, Embase, Cochrane Library 를이용하였다. 결과 : COPD가있을경우우울증의발생또한높아진다. 우울증이동반이될경우 COPD 환자들이삶의질에나쁜영향을받았다. 우울증선별검사도구중한글화되어있는도구는 8가지가있으며각도구는비슷한정도의신뢰도와타당도를가진다. 결론 : COPD 환자에서우울증의선별검사는필요하며우울증선별을위해서한글화된 8가지도구사용이모두가능하다. 그중에서문항수가적고환자의자가기입이가능한도구가현재의진료현실에서는적합할것으로생각된다. - 473 -
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