I 비흡연 COPD 정지예, 김영삼 연세대학교의과대학세브란스병원호흡기내과 A considerable proportion of COPD is originated from never-smokers and many factors other than smoking contributed to the development of COPD. Biomass fuels, occupational exposures, pulmonary tuberculosis, asthma, outdoor air pollution, and low socioeconomic status are well known risk factors of COPD. However, there is limited information on the risk factors associated with spirometrically diagnosed COPD in never-smokers from the general population. Very few studies have reported phenotypes of COPD in never-smokers or have made comparisons with phenotypes of COPD in smokers. Elucidating phenotypes of COPD with further research may improve our understanding of COPD in never-smokers. Here, we reviewed the evidences for the association of COPD with various risk factors other than smoking, phenotypes of COPD in never- smokers, and several reports in Korea. Key Words: Chronic obstructive pulmonary disease, Never-smoker, Risk factors, Phenotype Corresponding author: Ji Ye Jung, Ph.D. Division of Pulmonary, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea Tel: +82-2-2228-1980, Fax: +82-2-393-6884, E-mail: stopyes@yuhs.ac 1. 서론 비흡연자 COPD 의사회적질병부담이적지않음에도불구하고, 비흡자에서 COPD 발생에대해폭넓은연구가진행되지못했다. 초기연구들은 COPD 와유사한호흡기증상발생유무에대한영향을주로보고하였고, 폐기능검사를통해진단된 COPD 발병에대한연구가적어, 비흡연 COPD 의위험요인이무엇인지정확한근거가부족하다. 이에따라, 본연구자들은비흡연 COPD 발생의다양한위험인자에대해살펴보고, 비흡연 COPD 환자들의임상적특징, 그리고국내비흡연 COPD 환자들에대한연구결과들을소개하고자한다. 2. 본론 1) 비흡연자 COPD 발생 1958년, Fairbairn과 Reid 1 이대기오염이여러호흡기질환의주요인자임을보고한이후, 1963 년, Phillips 2 는만성기관지염발생의위험요인으로흡연이외다른주요인자들을발표했다. COPD 환자에서비흡연자의비율은 15 45% 로선진국혹은개발도상국가여부와상관없이높은빈도를보여준다 3-20. 1
2) 실내공기오염전세계가정의 50%, 지방지역거주자의 90% 에서바이오매스연료 ( 나무, 숯, 식물성물질, 그리고동물의배설물 ) 를사용하고있다. 30억인구가바이오매스에노출이되고, 10억인구가흡연에노출이된다고가정하면, COPD 발생에바이오매스가미치는영향이적지않을것임을예상할수있다 21. 바이오매스는연소효율이매우낮아, 유해물질의실내농도를빠른속도로높인다 22. 바이오매스에노출되는여성은그렇지않은여성에비해 COPD 발병과유사한호흡기증상을호소하는비율이높고, 폐기능의감소속도도빠르다 23. 메타분석결과에따르면, 바이오매스연기에노출될경우 COPD 발생위험도가 2.3 배높다 24. 터키여성에서는바이오매스연료로요리를하는여성이다른연료를이용하는경우보다 COPD 발생비율이 2배높았으며, 30년간바이오매스연기에노출되면 6.6배, 흡연연기에노출시 4.5배의 COPD 발생위험도를보인다고보고하였다 25,26. 개발도상국에서는주로여성이아기를등에업고음식을준비하는데, 이때바이오매스연기노출은여성뿐만아니라, 아이들에게영향을미친다. 과테말라에서는바이오매스연기에노출된산모에서출생한아기의몸무게가 60 70 g 적었다 27. 3) 직업성노출직업현장에서노출되는독성가스, 농장내곡물분진, 그리고공장내분진과연기는 COPD 발생과밀접한관계가있다는것은널리알려져있다 28-30. 2003 년, 미국흉부학회에서는 COPD 발생의 15% 가직업성노출과관련이있다고발표하였다 31. 또한 COPD 발생에대한직업성노출의인구기인위험도는 9 31% 까지보고된바있다 32. 4) 결핵폐결핵은진단당시, 치료중, 그리고치료가종료된이후에 COPD 표현형과유사한만성기류제한을보인다 33-36. 폐결핵감염은기도의섬유화증과결핵균에대한면역반응에따른기도염증이 COPD 의성격을보이게된다. 기류제한은영상학적으로폐결핵의병변범위, 가래양, 그리고진단혹은치료후경과기간과연관되어있었고, 폐결핵환자의 28 68% 에서기류제한이보고되었다 36,37. 남아프리가공화국에서는 COPD 발병의위험도가폐결핵과거력이있는남성에서 4.6배, 여성에서 6.6배라고보고하였고, 라틴아메리카에서는남성에서 4.1배, 여성에서 1.7배의위험도를보고하였다 13,14. 매년 20억인구가결핵균에감염되고, 920만명의새로운결핵환자가발생하기때문에, 폐결핵과 COPD 발병과의관련성은더욱밀접할것으로예상된다. 5) 천식 1961년, Kreukniet와 Orie 38 은천식과 COPD 가동일한배경을갖고있지만, 환경적요인과개체요인에의해두가지질환으로발전하게된다고주장하였다. 천식에서만성기도염증과기류제한, 그리고증가되어있는기도과민성은기도벽의증식과섬유화로폐의리모델링을일으키고, 비가역적그리고진행하는기류제한을통해 COPD 를유발하게된다. 적절한치료를하지않은천식이나중증천식의일부는흡연에의한기류제한과유사함을보였다 39. 15년간추적관찰한덴마크코호트연구에서, 대다수의천식환자들은정상폐기능을보였지만, 일부천식환자들은천식이없는사람보다기저 FEV 1 이낮았고, FEV 1 의감소율은높았다 40. 3,000 여명을 20년간추적관찰한미국연구에서는천식환자가천식이없는사람보다만성기관지염증상발생과폐기종발생위험도가각각 10배그리고 17배라고보고하였다 39. 6) 실외대기오염영국에서공기오염이높은지역에서근무하는우체부가오염이낮은지역에서근무하는우체부보다 COPD 발병이높았고, 미국에서는교통량이많은지역에거주하는사람이적은지역에거주하는사람에비해폐기능이낮았다 1,41. 또한대기오염이높을경우 COPD 급성악화발생이증가하는것으로알려져있지만, 새로운 COPD 발병과의관련성에대해서는좀더연구가필요하다 42. 2
7) 사회경제적요인 낮은사회경제적지위는 COPD 의독립적인위험인자로, 자궁내발육지연, 영양실조, 거주환경, 유아기호흡기감염, 흡연이나바이오매스연기노출, 그리고직업환경과연관성이있다 43. 8) 비흡연 COPD 환자의특징비흡연 COPD 환자의표현형에대한연구는많지않다. Ramírez-Venegas 등 44 은바이오매스연기노출로 COPD 가발생한여성이흡연에의해 COPD가발생한여성과유사한임상적특징, 삶의질, 그리고사망률을보인다고보고하였다. 그러나 Shavelle 등 45 은미국내비흡연 COPD 환자가흡연으로발생한 COPD 환자보다기대수명단축이짧다고하였다. Moran-Mendoza 등 46 은바이오매스연기로인한 COPD 여성에서폐섬유화반응과색소침착이더많고, 폐동맥내막도더두꺼워져있는반면에, 흡연으로인한 COPD 여성에서는폐기종과상피조직파괴가더많았다고보고하였다. Tan 등 47 은흡연자와비흡연자내에서각각 COPD 환자와비COPD 환자를비교하였다. 흡연자와비흡연자모두 COPD 환자에서비COPD 환자보다다양한호흡기증상발생빈도가높았으나, 흡연자에서만 COPD 환자에서폐기능검사상 DL CO /Va가감소되어있고, 흉부컴퓨터단층촬영상폐기종이더관찰되었다. 따라서, 비흡연 COPD 환자의표현형을살펴보기위한지속적인연구가필요하다. 9) 국내비흡연 COPD 환자 2001년 2차국민건강영양조사결과에따르면, 전체 COPD 환자에서비흡연 COPD 환자의비율은 32.1% 였다 16. 2007년부터 2009년까지진행된 4차국민건강영양조사결과에서비흡연자중 COPD 유병률은 7.6% 였다. 비흡연 COPD 발생에대한위험요인에는기관지확장증 (6.0배), 결핵과거력 (4.5배), 남성 (4.2배), 60세이상 (3.8배), 낮은 BMI (BMI<18.5 kg/m 2 ; 3.1배 ), 직업성노출 (2.6 배 ), 그리고낮은교육수준 (2.0 배 ) 이관련되어있었다 48. 2007년부터 2011년까지진행된 4, 5차국민건강영양조사결과에서는비흡연 COPD 환자와흡연 COPD 환자비교시, 비흡연 COPD 환자에서여성의비율 (73.9% vs. 6.9%), BMI (23.7 kg/m 2 vs. 23.3 kg/m 2 ), 동반질환으로류마티스관절염 (4.8% vs. 2.6%), 골다공증 (11.0% vs. 3.0%), 그리고우울증 (18.5%. vs. 9.1%) 의빈도가더높았다. 삶의질비교에서도비흡연 COPD 환자에서운동능력, 통증 / 불편감, 불안감 / 우울증과관련한문제가있는경우가많았고, EuroQol Five-Dimension Questionnaire (EQ5D) 점수 (0.87 vs. 0.94) 도낮았다 49. 3. 결론 비흡연 COPD 환자들에대한연구는전체 COPD 연구의일부집단의분석결과들을토대로진행되어, COPD 의흡연이외위험인자에대한연구가부족하다. COPD 질병위험부담은점점증가하고있으며, 특히개발도상국에서는높은흡연율과간접흡연문제뿐만아니라, 비흡연요인에노출이적지않다. 따라서, 다양한국가의비흡연 COPD 의질병위험부담실태를파악할필요가있다. 또한비흡연 COPD 환자가흡연 COPD 환자와유사한예후, 영상학적변화, 생리학적변화, 그리고동반질환발병을보이는지에대한연구가필요하다. 그리고, 현재까지 COPD 치료약제들의대다수임상연구가흡연력이있는 COPD 환자들을대상으로진행되었기때문에, 비흡연 COPD 환자도흡연 COPD 환자와동일한치료를받는것이효과가있는지에대해서도살펴봐야한다. References 1. Fairbairn AS, Reid DD. Air pollution and other local factors in respiratory disease. Br J Prev Soc Med 1958;12:94-103. 2. Phillips AM. The influence of environmental factors in chronic bronchitis. J Occup Med 1963;5:468-75. 3. Behrendt CE. Mild and moderate-to-severe COPD in nonsmokers: distinct demographic profiles. Chest 3
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