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2006년도 천식강의

입력일:2007-07-31 / 수정일:2007-08-17 / 조회수:20438 / 추천수:201 / 작성자:한만용

2006년 의과대학생을 위한 천식 강의록입니다. 다른 곳에 있던 것을 나의 홈페이지에서 긴 글을 넣을 수 있게 되어서 옮기게 되었다. 앞으로 이제까지 올리지 않은 글을 다 옮기고자 한다.

  1. 기관지 천식은 알레르기 질환과 마찬가지로 최근 증가하고 있다.
  2. 기관지 천식의 정의는 다양하다. 요점은 기도 염증(Airway inflammation)이다.   
  3. 기관지 천식의 병태 생리는 기도 염증이며, 기도 개형 개념을 숙지해야 한다.    
  4. 기도 개형은 비 가역적인 구조변경을 말한다.  
  5. 기도 염증 상태를 알기 위해 다양한 방법으로 의사들은 접근하게 된다.  
  6. 위험요인을 피하는 것이 중요하다.    
  7. 기관지 천식 환자 진단 핵심은 문진이다.  
  8. 기관지 천식 환자는 폐기능 검사에서 폐쇄형 특징을 보인다.    
  9. 최대호기유속(Peak expiratory flow)은 간편하게 측정 가능하다.    
  10. 기관지 과민성(Hyperresponsiveness)은 유발검사로 확인이 가능하다.   
  11. 자극물질을 기도에 투여하는 방법에는 2분 호흡법과 Dosimeter 법이 있다.   
  12. 특이적 기도 유발검사에서 기도 반응은 초기반응과 후기반응이 있다.    
  13. 기관지 과민도의 정도는 천식을 진단하는데 유용하나, 절대적이지 않다.
  14. 비특이 유발검사를 한 후 검사결과를 해석할 수 있어야 한다.   
  15. 천식의 중등도는 증상, 폐기능과 약물 요구량으로 판단한다.    
  16. 천식 약물은 조절제(Controler)와 완화제(Relievers)가 있다.   
  17. 유지요법은 천식 단계에 따라 결정된다.
  18. 흡입치료는 네가지 방법이 있다.
  19. 흡입 되는 약물의 크기는 0.5 - 5 um 가 적절하다.
  20. 네뷸라이져에는 두가지 종류가 있다. 하나는 Jet 식, 다른 하나는 초음파식  
  21. 흡입치료는 사용연령에 따라 선택할 수 있는 기기종류가 다르다.  
  22. 흡입용 스테로이드가 천식 치료의 기본이다.   
  23. 흡입용 스테로이드는 용량을 적절하게 조절하면서 사용해야 한다.  
  24. 흡입용 스테로이드를 저용량으로 사용하면 부작용이 최소화된다.
  25. 기관지 확장제에는 속효형과 지속형이 있다. 쓰임새가 다르다.
  26. 궁극적인 천식의 치료 목적은 환자를 편하게 해주는 것이다.
  27. 영유아를 비롯한 소아 천식의 특징은 감염과 감별하기 힘들다는 점이다.
  28. 천식은 천명음이 나거나 기침이 오래가는 질병과 감별해야 한다.  
  29. 천식은 알레르기 비염, 부비동염과 연관되어 있다.
  30. 기침이 오래가면 기관지 천식, 부비동염 또는 위식도 역류를 먼저 고려해야 한다.    
  31. 운동유발기관지 수축은 운동부하검사로 확인할 수 있다.    
  32. 직업성 천식은 노출량이 증가할수록 발생이 는다.  
  33. 천식 발작은 완화제(Relievers)로 치료한다.   
  34. 기관지 천식의 학습목표는 다음과 같다.   
  35. 이곳에 사용한 약어는 다음과 같다.   
  36. 참고문헌

기관지 천식은 알레르기 질환과 마찬가지로 최근 증가하고 있다.

Lancet 1998년에 발표된 내용에 따르면, 국내 천식 유병율은 아직 유럽국가보다 적다. 이는 ISAAC(International Study of Asthma and Allergies in Children) 연구 내용이며 우리나라도 참여한 결과이다(Lancet 1998).학생들이 알아야 할 개념은 다음과 같다.

  • 기관지 천식은 소아에서 가장 흔한 만성 질환이다.
  • 기관지 천식은 최근 30여년동안 증가하고 있다. 선진국, 개발도상국 모두 증가하고 있다.
  • 국내 유병율은 5% 내외라 여겨지며 이는 진단방법에 따라 차이가 날 수 있다.
  • 왜 증가하고 있는지는 잘 알지 못한다. 생활패턴의 변화, 알레르겐 증가, 위생이론, 대기오염 등 다양한 설명을 하고 있다.

기관지 천식의 정의는 다양하다. 요점은 기도 염증(Airway inflammation)이다.

기관마다, 년도 마다 기관지 천식의 정의는 변화하여 왔다.

GINA 2005(Global Initiative for Asthma)(GINA 2005)

    Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation causes an associated increase in airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment.

GINA 2003

    Asthma is a chronic inflammatory disorder of the airways in which many cells play a role, in particular mast cells, eosinophils, and T lymphocytes. In susceptible individuals this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough particularly at night and/or in the early morning. These symptoms are usually associated with widespread but variable airflow limitation that is at least partly reversible either spontaneously or with treatment. The inflammation also causes an associated increase in airway responsiveness to a variety of stimuli.

NHLBI(National Heart Lung and Blood Institute) 1997(NHLBI 1997)

    Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli.

천식 정의 요점은 다음과 같다.

  • 기도 염증은 기도 과민성(airway hyperresponsiveness), 호흡 장애(airflow limitation)와 기관지 천식의 특징적인 증상인 기침, 가슴답답, 천명음과 같은 증상, 만성화의 주요한 요인이다.
  • 기도 염증은 급성 기관지 수축, 기관지 부종, 점액 Plug 형성과 기도 개형에 영향을 준다. 이는 기도 폐쇄를 유도한다.

기관지 천식의 병태 생리는 기도 염증이며, 기도 개형 개념을 숙지해야 한다.

최근까지 기관지 천식의 병리 소견은 천식 발작으로 사망한 환자의 부검결과에서 얻어졌다. 1980년대 초 기관지경 검사가 가능하면서 병태생리에 대한 이해가 넓어졌다. 이에는 다음과 같은 소견이 포함된다.

  • 기도 내 점액, 점액 과분비(Mucus plug)
  • 기도 상피세포 탈락(Desquamation of epithelium)
  • 기저막층의 비후(Subbasement membrane thickening)
  • 기관지 평활근의 비후(Hypertrophy of smooth muscle) 및 수축
  • 점막하 분비선 증식(Submucus gland hyperplasia)
  • 점막 혈관확장(Vasodilation)
  • 점막, 점막하층의 부종(Edema of mucosa and submucosa)
  • 다양한 염증세포의 조직 침윤(Infiltration with eosinophils, neutrophils, mast cells, and T cells)
  • 기관지 천식 기도 염증은 2 mm 이하의 소기도, 폐 실질(Parenchyma)를 포함한 전 기도 염증 반응이다. 또한 이는 급성, 만성 모두에서 기도 염증이 동반된다.
  • 호산구와 림프구 이외에도 호중구가 염증에 관여하며 중증의 천식천식환자, 급작스런 천식 발작환자에서 증가되어 있다. 사망한 천식 환자 기도 내 세포분포는 호중구가 주요 세포이다.
  • 구조 유지 세포(Structural cell)로서 섬유모세포(fibroblast), 내피세포(endothelial cell)과 상피세포(epithelial cell)에서 분비하는 사이토카인의 기능에 관심이 증가하고 있다.

기도 개형은 비 가역적인 구조변경을 말한다.

  • 천식을 가지고 있는 환자 중 기도 호흡이 완전히 회복되지 않기도 한다. 이는 기도에 구조적인 변화가 일어난 경우이다. 이러한 변화가 있는 환자는 증상이 지속될 수 있고 치료에 반응을 보이지 않을 수 있다. 이를 기도 개형(Airway remodeling)이라고 한다.
  • 상피하조직의 섬유화, 기도 평활근의 증식 및 비후, 신혈관 형성과 점액선의 증식으로 기도벽이 두꺼워지는 것이다.
  • 기도 개형을 예방하기 위한 치료 전략이 수립되고 있지만 아직 긍정적인 결과는 매우 한정되어 있다.

기도 염증 상태를 알기 위해 다양한 방법으로 의사들은 접근하게 된다.

이와 같이 기도 염증 상태를 확인하는 방법은 여러 가지가 있다.

1. 기도 내 염증 반응을 확인하는 것.

  • 기관지 폐포 세척액 검사 : Bronchoalveolar lavage(BAL), Bx
  • 객담 검사(객담 유도 검사)
  • Nitric oxide 또는 호기가스 분석법

2. 기도 과민반응을 평가하는 방법

  • 유발검사(Provocation Test)

3. 기도 폐쇄를 평가하는 방법

  • 폐활량검사(Spirometer)

4. 증상으로 평가하는 방법

  • 자세한 과거력 조사
  • 설문지 조사

위험요인을 피하는 것이 중요하다.

  • 기관지 천식과 관련되어 유발인자, 기여인자, 촉진인자, 악화인자 등 다양한 위험요인에 대한 설명이 있다. 이를 정확히 분별하기는 힘들다. 이곳에서는 천식의 원인이 되는 물질과 천식 증상을 악화시키는 요인으로 구분하여 설명한다. 이를 통틀어 위험요인이라고 하여 설명한다.
  • 위험요인은 다음과 같이 분류할 수 있다.
  1. 실내 항원
    1. 집먼지 진드기
    2. 애완동물 ; 고양이, 강아지, 설치류, 소와 말, 기르는 새 등)
    3. 진균(곰팡이)
    4. 바퀴벌레
    5. 내독소
    6. 실내 화분용 화초 및 화분(꽃가루)
    7. 감염원(RS 바이러스, Chlamydia sp., 마이코플라즈마 폐렴균 등)
    8. 화학물질 ; 포름알데히드, 방향제, 담배연기, NO2, Nox, 살충제, 오존, 미세입자, 가소제, VOCs(volatile organic compounds)
  2. 실외 항원
    1. 화분(꽃가루)
    2. 진균(곰팡이)
    3. 대기오염 ; 미세입자, 아황산가스, 오존, 일산화질소 등
  3. 직업 노출 항원
  4. 약물
    1. 아스피린과 NSAID 약물
    2. beta2 항진제
  5. 음식물
  • 화분과 진균은 실내, 실외 항원 모두에 포함된다. 대기오염도 실내에 영향을 줄 수 있다.
  • 위험요인을 어떻게 회피할 것인가는 알레르기 치료의 핵심 전략이며 이는 '알레르기 치료원칙'에서 거론되었다. 보통 1차 예방, 2차 예방, 3차 예방 모두에서 중요한 전략이다.
  • 약물에 의한 천식 악화는 성인에서 흔하면 음식물에 의한 악화는 드물지만 소아에서 흔하다.

기관지 천식 환자 진단 핵심은 문진이다.

  • 기관지 천식을 진단하기 위해서는 자세한 병력조사, 임상 소견 및 다양한 검사를 통해서 확인할 수 있다. 이중 문진은 진단의 핵심이다.
  • 천식을 진단하기 위한 문진 시 확인해야 할 사항들
    • 천식 의심되는 증상들
    • 가족력(가족 중 알레르기가 있는지 등)
    • 과거력(아토피 피부염을 비롯한 알레르기 증상여부, 입원여부, 호흡기 질환 여부, 등)
    • 증상을 악화시키는 의심스런 요인들, 악화 양상
    • 동반 질환여부(알레르기 비염, 부비동염, 잦은 상기도 감염, 위식도 역류 등)
  • 천식환자는 다음과 같은 증상을 호소한다.
    • 천명음이 들린다.
    • 기침을 한다.
    • 숨이 차다(호흡 곤란을 느낀다)
  • 이러한 증상이 위험요인에 노출되면 악화된다.
  • 천명음이 없이 기침만 하는 환자도 있다. 이를 어떤 연구자들은 Cough variant Asthma(기침이형천식)이라고도 한다.
  • 천명음을 일으킬 수 있는 다른 요인들을 배제시켜야 한다.
  • 기침이 오래가는 환자들에게 '알레르기성 기침' '알레르기성 기관지염' '만성 기관지염' 또는 '천명성 기관지염' 이라는 진단명이 붙기도 한다. 이러한 질환이 천식여부를 확인해 주는 것이 중요하다.

기관지 천식 환자는 폐기능 검사에서 폐쇄형 특징을 보인다.

  • - 천식 환자에서 폐기능 검사를 하면 다음과 같은 특징을 보인다.
  • 폐활량
    • RV 증가 >> FRC 증가 > TLC 증가
    • VC 감소
    • Inspiratory flow preserved, Expiratory flow rate decreased

  • Flow-Volume Curve
    • Low FEV1
    • FEV1/FVC < 0.8
    • Post bronchodilator FEV1 > 12%

  • VC 는 감소하며 Inspiratory flow는 변하지 않으나 Expiratory flow는 감소하게 된다.
  • 5세 미만의 소아에서는 폐기능 검사를 시행하기 힘들다.

최대호기유속(Peak expiratory flow)은 간편하게 측정 가능하다.

  • 최대호기유속이란 최대흡입 후 강제최대호기(Forced maximal flow)에 나타나는 유속을 말한다. 단위는 Liter/min(L/m)이다.
  • 이는 때때로 Spirometer에서 MEFR(forced expiratory flow maximum or maximum expiratory flow) 라고 불려지기도 한다.
  • 이외에도 Flow rate를 확인하는 방법
    • MEFV curve(Maximal expiratory flow-volume curve)
    • FEF25-75(Force expiratory flow 25-75%)
  • 최대호기유속기(Peak flow meter)는 아래 그림과 같고 PEF을 측정하는데 사용한다.
  • 가격이 싸기에 천식 환자를 모니터하는데 유용하게 사용될 수 있다.
  • 정상인에서는 하루 변동치가 10% 미만이나, 천식 환자에서는 중등도 평가, 폐기능 하루 변동치 측정, 기관지 천식 조절 여부 등에 활용될 수 있다.

                           

그림 1) 최대호기 유속기                 그림 2) 하루 변동치

  • 신호등은 보호자들에게 설명할 때 사용되는 것이다. 녹색등은 하루 변동치가 20% 미만일 때, 노란 등은 하루 변동치가 20-50% 일 때, 적색등은 50% 이상일 때를 말한다. 기관지 확장제를 사용했음에도 노란등이 켜진다는 것은 약물 요구량이 증가해야 한다는 것을 의미한다.
  • 모든 환자에서 이 측정이 필요한 것은 아니다. 5세 이상이며 입원을 하였거나 증상 자각을 적절히 하지 못하는 아이들에게 필요할 수 있다.
  • 노력 여하에 따라, 동기유발에 따라, 호흡근육 힘에 따라 측정치가 달라질 수 있다. 그러므로 변동치가 매우 크다. 재현성은 좋으나 대상자마다 차이가 많다는 것을 알아야 한다.
  • 또한 상품마다 수치도 차이가 많다. 그러므로 한 개 상품으로 측정해야 한다.
  • FEV1이 직경이 큰 것과 중간 크기의 기관지를 반영하지만 PEF는 큰 기관지를 반영한다. FEV1과 비교하였을 때 상관관계는 높으나 측정치의 표준편차가 넓다.
  • 일반적으로 PEF는 기도 폐쇄정도를 FEV1 보다 민감하지 않고 기관지 확장제 투여 후 회복율도 FEV1 보다 민감하지 않다.
  • 결국 PEF는 FEV1을 대신할 수 없다.

기관지 과민성(Hyperresponsiveness)은 유발검사로 확인이 가능하다.

  • 기도 과민성이란 외부 또는 내부 자극물에 대해 기관지 수축이 심해지는 것을 말한다. 여러 기전이 설명되고 있지만 중요한 요소는 역시 기도 염증이다. 기도 과민성은 천식의 중요한 요소이다. 기관지 과민도는 천식에 특이적이지는 않지만 천식을 가지고 있는 대부분의 환자에서 기도 과민성을 보인다.
  • 기도 과민성을 알레르겐을 흡입하여 유도하는 ‘특이적 유발검사’와 히스타민 또는 메타콜린, 3% 식염수와 같은 비특이 자극물질로 유발하는 ‘비특이적 유발검사’가 있다.
  • 이러한 자극 분류를 직접자극(Direct Stimuli) 방법과 간접자극(Indirect Stimuli) 방법으로 나누기도 한다. 직접 자극이란 기도평활근에 직접 자극되어 기도 수축을 야기하는 방식을 말하며, 이에는 Cholinergic agonist 인 Methacholine, acethylcholine, Carbachol 과 히스타민, 프로스타그란딘 D2, 류코트리엔으로 자극을 주는 것을 말한다. 이와달리 간접자극은 기도내 세포인 상피세포, 신경과 염증세포에 자극을 주어 반응을 유도하는 물질을 말한다. 이에는 운동, NonIsotionic aerosol(hyper-, hypo, distilled water, manitol)과 약물로 아데노신, 알레르겐과 아스피린과 같은 자극을 말한다. 직접자극보다는 간접자극 방법이 알레르겐회피에 의한 기도염증의 변화를 더 잘 반영한다.
  • 기도 유발검사는 기도에 자극을 주어 FEV1이 떨어지는 정도를 파악하는 방법이다. 20% 이상 떨어질 때의 메타콜린 농도를 계산하여 PC20(Provocative concentration) 또는 PD20를 정하게 된다.
  • 흡입 후 폐기능 측정은 30초에서 3분이내에 시행하는데 이때 기도 저항을 측정하는 도구로는 FEV1, Raw, sRaw, PEFR 과 유속 측정이 있다. 이중 FEV1이 검사비용, 단순성, 재현성을 고려하여 가장 많이 사용된다.

 

그림 설명) 비특이 자극물질의 농도를 올리게 되면 정상인은 FEV1 값이 기저치의 20%이상 떨어지지 않는다. 그러나 과민도가 있는 사람에서는 FEV1이 20%이상 떨어지며 이때의 자극물질의 농도 또는 흡입된 총량의 값을 구하여 각각 PC20 또는 PD20 라고 한다.

  • PD20(Provocative dose)는 메타콜린(히스타민) 흡입 시작부터 흡입되어 축적된 용량을 표현한 것이다.
  • 유발검사는 원인항원을 찾거나 증상정도를 파악하고 치료 반응여부를 확인하는데 유용하다.

자극물질을 기도에 투여하는 방법에는 2분 호흡법과 Dosimeter 법이 있다.

  •  흡입 약을 투여하는 방법은 2분 동안 평상 호흡으로 연속적으로 흡입하는 방법인 '2분 호흡법'(tidal breathing method)과 20 psi 압력의 압축공기로 연결된 분무기에서 발생하는 흡입체를 선량계(Dosimeter)를 이용하여 0.6초 동안 개폐함으로 일정한 용량을 5회 흡입하도록 하는 '선량계 흡입법'(Dosimeter method)이 있다

.

  • 두 방법 모두 흡입되는 용량에 차이가 없는 것으로 알려져 있다.
  • 오른쪽 그림 검사 방법은 선량계를 활용한 흡입방법이다.

특이적 기도 유발검사에서 기도 반응은 초기반응과 후기반응이 있다.

  • 항원을 흡입 후 몇 분내에 즉시 나타나는 반응을 초기반응(early asthmatic response, EAR) 이라고 하고 수 시간 후에 나타나는 반응을 후기반응(late asthmatic response, LAR) 이라고 한다.
  • 모든 환자에서 초기반응, 후기반응이 나타나는 것이 아니라, 두 반응을 보이는 환자가 있고 초기 반응만 보이는 환자와 후기반응만 보이는 환자가 있다.

.

  • 초기 반응은 기관지내 비만세포에서 유리되는 화학물질에 의해서 일어나는 것이고, 후기반응은 호산구로 대표되는 염증세포들이 침착하여 나타나는 기도염증반응이다. 이를 표로 보여주면 다음과 같다.

기관지 과민도의 정도는 천식을 진단하는데 유용하나, 절대적이지 않다.

  • 몇 개의 참고문헌에서는 PC20 농도가 25 mg/dL 이하이면 과민도가 있고 8 mg/dL 이면 천식으로 진단할 수 있다고 하지만 이는 절대적이지 않다. 유발검사에서 현재 증상이 나타나는 천식환자(현증 천식환자)는 거의 100% 양성 반응을 보인다. 그러나 PC20 를 8 mg/mL로 잡았을 때 양성예측도는 50%도 안된다. 만일 Cutoff value를 낮추면 특이도와 양성예측률이 거의 100%로 올라가나 민감도와 음성예측률은 매우 낮아진다. 그러므로 8-16 mg/mL로 잡는 수치는 매우 민감하기에 음성이 나오면 천식이 아니라고 진단할 수 있고 매우 낮은 수치에서 PC20 값이 나오면 천식이라고 진단 접근이 가능하다.
  • 만성기도폐쇄(COPD)환자에서도 기도 과민도가 보인다. 결국 메타콜린(히스타민)에 의한 기도 유발검사는 현증 천식을 찾아내는데 매우 민감하지만 다른 호흡기 질환과 감별하는데에는 한계가 있다.
  • 기관지 과민도는 다음과 같은 기준으로 정하는 것이 적절하다. 그러나 시험에서는 책 내용을 참조해서 해석해야 할 것이다.

  • 기도유발검사의 유용성은 특이도가 높다는데 있다. 천식이 아니면서 기도 과민증이 나타날 수 있다. 이러한 경우로는 알레르기 비염, 호흡기 감염, 유전적인 소인, 직접 흡연, 간접흡연 등 여러가지가 있다.
  • PC20의 유용성은 천식 진단에 도움이 된다는데 있다.  

그림 설명) 기도유발검사를 시행하기 전 여러 접근 방법으로 기관지 천식일 가능성을 10%(가로축에서 0.1) 이라고 보았는데 유발검사에서 PC20 값이 1 mg/dL 가 나왔다면 천식일 가능성이 83% 정도 된다. 즉 가로축은 검사 전 가능성을 말해주고 세로축은 검사 후 가능성을 말해준다.

  • 이러한 차이를 보이는 이유는 기도 염증이 있으면 기도 과민증이 있으나 과민증이 있다고 하여 기도 염증이 있다는 것을 의미하지 않기 때문이다.

비특이 유발검사를 한 후 검사결과를 해석할 수 있어야 한다.

- 본원에서 시행한 환자의 결과이다. 이를 보고 결과를 해석할 수 있어야 한다. 환자는 9세된 남자로 키는 148 cm, 체중은 39 kg 이었다.

  • 이 검사 결과에서 확인 가능한 것은
    • 기도 폐쇄 여부 ; FEV1 % pred., FEV1/FVC, FEF25-75
    • 기도 과민성 여부 : PC20이다.
  • FEF25-75와 MFEF는 소기도 염증에 민감하나 재현성이 부족하다는 단점이 있다.
  • 기관지 확장제 투여 후 FEV1 회복율이 12 ~ 15% 이상 되면 기관지 과민성이 있다.

천식의 중등도는 증상, 폐기능과 약물 요구량으로 판단한다.

  • 천식 유지요법으로 치료하기 위해서는 천식의 중등도를 파악하게 된다. 이때 중등도를 파악하는 방법은 기관마다 조금씩 다를 수 있다. 이곳에서는 NAEPP 가이드라인에 따라 분류한다.
  • 천식의 중등도는 ‘경증 간헐성(mild intermittent)’ ‘경증 지속성(mild persistent)’ ‘중등증 지속성(moderate persistent)’과 ‘중증 지속성(severe persistent)’으로 나눈다.
  • 중등도를 판단하는 기준은 낮 동안 증상 정도, 밤 동안 증상 정도, FEV1 또는 PEFR 예측치의 %, FEV1 또는 PEFR의 변동율, 이 네 가지로 대부분 분류하게 된다. 이는 아래 표로 나타냈다.

  • 만일 환자가 약물 치료 중이라면 약물 치료 정도로서 천식 중등도를 평가하게 된다.

천식 약물은 조절제(Controler)와 완화제(Relievers)가 있다.

  • 천식치료를 위해 사용되는 약물에는,
    • 베타2 항진제(beta2 agonist) ; Salbutamol(albutamol), Terbutaline, Formoterol, Salmeterol, Procaterol, Clenbuterol 등이 있다.
    • 메틸산틴제(Methylxanthine) ; 쎄오필린(Theophylline, 테오필린), 아미노필린(aminophylline)
    • 항콜린제(anti-cholinergic) ; Ipratropium bromide
    • 부신피질 스테로이드제(Corticosteroid)
    • 크로몰린과 네도크로밀(Cromolyn, Nedocromyl)
    • 항류코트리엔제(Anti leukotriene) ; Pranlukast, Montelukast, Zafirlukast와 5-LP(Lipoxygenase) 억제제인 Zileuton
    • 면역억제제 : Methotrexate, Cyclosporin, Gold 등이있다.
  • 이를 천식 치료에서 두가지 약물 군으로 나눈다. 하나는 급성 발작이 있을 때 기관지 확장을 위해 사용할 수 있는 약물인 완화제와 다른 하나는 기도 염증을 조절하기 위한 조절제이다.
  • 조절제에는,
    • 스테로이드제(흡입용, 전신투약용),
    • 크로몰린과 네도크로밀,
    • 서방형 쎄오필린,
    • 지속형 기관지확장제(흡입용, 경구용)
    • 항류코트리엔제 가 포함된다. 이중 흡입용 스테로이드제가 가장 효과적이며 중요한 치료제이다.
  • 완화제에는,
    • 속효형 베타2 항진제(rapid acting beta2 agonist, 경구용, 흡입용),
    • 속효형 쎄오필린,
    • 흡입용 항콜린제,
    • 전신투여 스테로이드제(Systemic glucocorticosteroid) 가 있다.
  • 예를들어 기관지 발작이 왔을 때 조절제로만 사용하면 안되고 지속적인 천식 유지요법에서 완화제만 사용해서는 안된다.

유지요법은 천식 단계에 따라 결정된다.

  • 천식은 기도염증이므로 염증을 가라앉히는 흡입용 스테로이드가 가장 기본적인 치료이다.
  • 증상이 발현되면 완화제로 증상을 치료하며 지속적인 치료는 천식 단계에 따라 아래와 같은 방법을 사용하게 된다.

  • 위 표는 5세 이상의 소아 및 성인에 대한 치료 원칙이다.
  • 치료 중에 증상이 발현되면 완화제(기관지 확장제) 치료를 해주어야 한다.
  • 경증 간헐성 천식환자이지만 심한 천식 발작이 있는 환자는 중등증 지속성 천식환자와 같은 정도로 치료를 할 수 있다.
  • 항 IgE 치료는 12세 이상에서 인정을 받고 있다.
  • 5세 미만에서 치료 방침은 몇가지 점에서 다르다.
  • 5세 미만에서 지속형 흡입용 베타2 항진제를 사용할 수 없다. 그러나 중증에서는 대상이 안되지만 사용하게 된다.
  • 항 IgE 치료는 사용하지 않는다.
  • 투여 용량은 3개월 단위로 증상과 폐기능 검사 결과를 보면서 Step Up/Down을 할 수 있다.

흡입치료는 네가지 방법이 있다.

  • 정량 분무식 흡입 방법(Metered dose inhaler, MDI)
  • 스페이서와 정량분무식 흡입 방법(MDI with Spacer)
  • 건조 분말식 흡입 방법(Dry powder inhaler, DPI)
  • 네뷸라이져 방법(Nebulizer)

흡입 치료를 기관지 천식에 사용하는 것은 기도 염증 부위로 약물을 효과적으로 전달하는 것을 목적으로 하고 있다. 이 네가지 방법을 어떻게 사용하는지 알고 있어야 한다.

       

- 국내에서 사용되고 있는 MDI              - 스페이서와 MDI                              

                            

- 국내에서 사용되고 있는 DPI                     - 네뷸라이져              - MDI 분사 방식

흡입 되는 약물의 크기는 0.5 - 5 um 가 적절하다.

  • 흡입된 약물은 충돌(Impaction), 침강(Sedimentation)과 확산(Diffusion)에 의해서 폐포로 전달된다.

네뷸라이져에는 두가지 종류가 있다. 하나는 Jet 식, 다른 하나는 초음파식

  • 초음파식은 스테로이드가 전달되지 않는다. 그러므로 Jet 식으로 사용되어야 한다.

  • 초음파식 연무기

흡입치료는 사용연령에 따라 선택할 수 있는 기기종류가 다르다.

  • 어떤 흡입치료 기구를 사용할 것인가는 나이에 따라 환자 기호나 생활 패턴에 따라 선택을 달리 하여야 한다.

  • MDI with spacer
    • 5-10초 정도 흡입하도록 한다.
    • 천천히 그리고 깊게 흡입한다.
    • 분무 사이가 30초 정도 되게 한다.
    • 18개월 보다 어린아이들은 코로 숨을 쉬므로 하부기관지 흡입량이 50% 감소한다.
    • 울면 거의 약물이 흡입되지 않는다.
    • 가장 중요한 것은 마스크를 얼굴에 꼭 대는 것이다.
  • MDI
    • 흡입기 뚜껑을 열고 3회 흔든다
    • 천천히 숨을 끝까지 내 쉰다.
    • 천천히 숨을 들어 마시면서 흡입기를 물고 누르면서 숨을 깊게 들어 마신다.
    • 흡입기를 입에서 떼고 10초 숨을 참는다.
    • - 영,유아 흡입치료의 특징 ; 코로 숨을 쉬고, 기도가 좁고, Tidal volume 이 작고 호흡수가 빠르다.
  • 스페이서로 사용 좋은 점 ; 사용이 힘들지 않고, 약물 전달이 효과적이며, 흡입약물 부작용이 최소화 한다.

흡입용 스테로이드가 천식 치료의 기본이다.

흡입용 스테로이드는 용량을 적절하게 조절하면서 사용해야 한다.

  • 흡입용 스테로이드의 원료명과 용량은 아래와 같다. 이중 빨간 색으로 표시된 것은 국내 수입 안되고 있는 것이다.

  • 기관마다 용량 기준 발표가 조금씩 다르다.
  • 흡입용으로는 DPI, MDI, Nebulizer 용이 있다.
  • 성인 용량과 소아 용량에 차이가 있다.
  • 천식 중등도에 따라 흡입하는 용량에 차이를 두어야 한다.

흡입용 스테로이드를 저용량으로 사용하면 부작용이 최소화된다.

  • 흡입용 스테로이드의 장기 사용에 따른 부작용으로 거론되는 것은 다음과 같다.
  • Local side effects
    • 목소리가 허스키해진다.(Hoarseness, dysphonia)
    • 아구창이 생긴다.(Oral candidiasis)
    • 예방책) 용량을 줄이면서 대체 약물을 사용하거나, 스페이서를 활용하거나, 사용 후 입을 헹군다.
  • Systemic side effects
    • 성장 억제
    • 골밀도 감소
    • HPA 축 억제
    • 백내장
  • 저용량의 흡입용 스테로이드를 지속적으로(몇 년을 두고)사용하였을 경우
    • 초기 1년간 성장지연이 일어나나 일시적이며 Catch Up 이 생긴다. 최종 키에서는 차이가 없거나 무시할 정도이다.
    • 골밀도 감소가 일어나지 않는다. 또는 무시할 정도(minimal) 이다.
    • HPA 억제는 일어나지 않는다. 또는 무시할 정도(minimal) 이다.
    • 백내장은 증거가 부족하다.
  • 고용량의 흡입용 스테로이드를 지속적으로 사용하면 systemic side effects 가 일어날 수 있다.

기관지 확장제에는 속효형과 지속형이 있다. 쓰임새가 다르다.

  • 속효형(Short acting beta2 agonist)는 완화제로 사용된다.
    • Salbutamol(Albuterol) ; VentolinTM
    • Terbutaline ; BrycanylTM (국내 시판 안됨)
    • Pirbuterol
    • Bitolterol
  • 지속형(Long acting beta2 agonist)는 조절제로 사용된다.
    • Salmeterol ; SereventTM (시판 안됨)
    • Formoterol ; OxisTM
  • 흡입용 스테로이드없이 지속형 기관지 확장제로만 기관지 천식을 유지치료하면 안된다.
  • 복합제제로 두가지가 나와있다.
    • Seretide evohalerTM ; Fluticasone + Salmeterol
    • Seretide diskusTM ; Fluticasone + Salmeterol
    • SymbicortTM ; Budesonide + Formoterol

궁극적인 천식의 치료 목적은 환자를 편하게 해주는 것이다.

  • 기관지 천식을 치료하였을 때 완치라는 개념의 증거는 아직 부족하지만 환자들에게 천식을 경제적이고, 부작용이 적고, 편리한 방법으로 천식을 조절하여 정상적인 삶을 유지하도록 하는 것이 치료 목표이다.
  • 이를 구체적으로 천식 치료 목표를 기술하면,
    • 밤 중 증상을 비롯한 지속적인 증상의 최소화
    • 천식 발작의 최소화
    • 응급실에 내원하지 않도록 한다.
    • beta2 작용제와 같은 기관지 확장제 사용의 최소화
    • 운동을 포함한 일상생활에 제한이 없도록
    • PEF 하루 변동치를 20% 이내가 되도록
    • 정상 폐기능
    • 약물 부작용의 최소화
  • 교육은 환자 치료의 핵심이다.
  • 알레르기 치료방법은 회피요법, 약물요법, 면역요법과 교육이 있으며 교육은 치료의 핵심전략이다.

영유아를 비롯한 소아 천식의 특징은 감염과 감별하기 힘들다는 점이다.

  • 영유아시기에 천명음이 들리면 세기관지염과 천식을 의심하게 된다. 이를 감별하기는 힘들다. 영유아 천식에서 기관지 확장제가 도움이 안되는 경우가 많으며 이는 감염과 관련된 세기관지염이기 때문이다.
  • 영유아시기에 천명음이 들렸던 아이들을 추적하였더니 세 군으로 나뉘어 지었다.
    • A. 영유아 시기에만 천명음이 들리고 나이가 차며 없어진 군(Transient Wheezer 군)
    • B. 영유아 시기 천명음이 나이가 들며 계속된 군(Persistent Wheezer 군)
    • C. 영유아 시기에는 천명음이 없었지만 나이가 들며 나타난 군(Late Wheezer 군)

  • 지속적으로 천명음이 들릴 수 있는 위험요인으로는 다음과 같다.
    • 천식의 가족력
    • 2번 이상의 재발
    • 선행감염이 없는 급작스런 발병
    • 말초혈액 호산구 증가
    • 기관지 확장제에 반응
  • 한 연구자 군에서 이를 예측하는 표로 만들어서 이를 Asthma Predictive Index(API)를 만들어서 소아 천식으로 가는 아이들에게 적극적인 치료를 권하고 있다.
  • 지속적인 천명음 군에서 폐기능이 다른 군보다 떨어짐을 보였다. 그러므로 흡입치료를 조기에 적절하게 시도되는 것이 권장된다.

천식은 천명음이 나거나 기침이 오래가는 질병과 감별해야 한다.

  • 소아에서는 다음과 같은 질환과 감별해야 한다.
    • Bronchiolitis obliterans ; 이 질병은 감염에 의해서 소기도에 Scarring 이 생긴 것을 말한다. 치료에 잘 반응을 안하는 것이 특징이다.
    • Interstitial lung disease ; 간질에 염증이 생긴 것으로 FEV1이 감소하지만 FEV1/FVC는 정상이다.
    • Vocal cord dysfunction(VCD) ; 흡기 중에 성대가 paradoxic 하게 닫히는 현상을 말한다. 폐기능검사로 의심할 수 있고 laryngoscopy로 확진한다.
    • Foreign bodies
    • 이외에도 위식도역류와 만성 부비동염은 감별되어야 한다.

  • 성인에서는 소아과 비슷하지만 몇가지 더 감별해야 할 질환이 있다.
    • Localized carcinoma ; laryngeal carcinoma, Tracheal carcinoma, Bronchial carcinoma
    • Generalized obstructive disease ; COPD, Bronchiectasis
    • 항시 감염과 관련된 호흡기 증상과 감별해야 한다. Common colds, Bronchiolitis, Pneumonia, Tuberculosis, HIV/AIDS infection….

천식은 알레르기 비염, 부비동염과 연관되어 있다.

  • 코와 부비동의 관계는 매우 밀접한 연관이 있다. 첫째 코와 부비동은 같은 조직으로 연결되어 있다. 둘째, 코와 부비동염 증상은 매우 유사하여 분간하기 어렵다. 셋째, 비염 증상이 있은 후 부비동염 증상이 나타난다. 넷째, 부비동염 증상이 있으면 코 증상은 거의 다 있다. 이러한 이유로 코와 부비동 증상을 나누지 않고 ‘Rhinosinusitis’ 라고 한다.- 코와 천식과의 관계도 연관이 있다. 역학조사에서, 천식을 가지고 있는 사람의 80-90%는 비염을 가지고 있는 것으로 알려져 있다. 또한 비염을 가지고 있는 사람은 정상인보다 많은 15% 정도에서 천식을 가지고 있는 것으로 알려져 있다. 비염은 이물질을 flitering 을 하는 역할을 하게 되는데 비염으로 이러한 역할을 못하면 알레르겐은 직접적으로 기관지를 자극할 수 있다.
  • 이렇게 비염과 천식과의 관계를 해석하는 방법은 세가지 가설이 있습니다.
    • 감염된 물질이 기도로 넘어간다.
    • reflex 가설. Naso-sino-bronchia reflex
    • Cell migration
  • 부비동염과 천식도 관련이 있다. 부비동염을 치료하면 천식 증상이 완화되며 만성 부비동염을 가지고 있는 환자의 50%에서 천식을 가지고 있다.
  • 그러므로 이렇게 코, 호흡기, 부비동이 연결되어 있고 치료 전략도 비슷하기에 'One airway One disease' 또는 'United airway disease' 라고도 한다.

기침이 오래가면 기관지 천식, 부비동염 또는 위식도 역류를 먼저 고려해야 한다.

- 소아에서 기침이 오래가면 아래 세가지 질병을 먼저 의심해야 한다.

- 성인에서 기침이 오래가면 천식, 부비동염, 위식도역류 세가지 질병을 먼저 의심해야 한다.

운동유발기관지 수축은 운동부하검사로 확인할 수 있다.

  • 운동부하검사는 특이적 자극방법이며 또한 간접자극 방법이기도 하다. 운동부하검사로 천식 진단 접근이 가능한데 메타콜린과 비교하여 항시 일치한 결과를 얻지는 못했다. 운동부하검사는 정상과 천식을 진단하는데 메타콜린 유발검사보다 민감도는 떨어지나 특이도는 높다. 소아에서 천식과 기관지 확장증, PCD와 BO를 감별하는데 메타콜린 보다 운동부하검사가 더 낫다. 보통 민감도/특이도로 보았을 때 운동부하검사는 메타콜린(히스타민) PC20의 1 - 2 mg/ML 와 비슷한 결과를 얻는다. 특이도가 높은 것은 이러한 물리적인 자극이 천식과 관련이 있는 다양한 염증세포에 영향을 주어 반응이 나타나기 때문이며, 민감도가 떨어지는 것은 자극이 적절한 강도로 이루는데 실패했기 때문이라 추정한다.
  • 운동부하검사는 12세이하의 소아는 6분동안, 성인은 8분동안 건조한 공기(25도 이하, 상대습도 50% 이하)에서 최대 호흡량의 60%를 4분동안 유지하는 운동을 시행해야 한다. 이는 분당 호흡량의 14배에서 21배에 이른다. 만일 호흡량을 측정할 수 있는 기구가 없다면 맥박수로 측정한다. 예상되는 최대 맥박수의 90%에 이르는 운동량을 4분까지 유지되도록 해야 한다. 보통 검사 전 FEV1 보다 10% 이하(10~20%)로 떨어졌다면 양성이라고 판정한다.
  • 운동유발성 천식(Exercise induced asthma, EIA) 또는 운동유발성 기관지수축(Exercise induced bronchospasm, EIB)라고 하며 이는 운동을 하고 나서 기관지 수축이 일어나 천식 증상이 나타나는 것을 말한다.
  • 운동부하검사로 진단하게 되며 운동 후 15 분 후에 기관지 수축이 일어난다.
  • 운동 후 FEV1이 15% 이상 감소하면 진단할 수 있다.
  • 운동 유발성 천식은 기관지 천식을 항시 가지고 있지는 않다.
  • 운동유발성 천식을 치료하기 위해서는 운동을 규칙적으로 해야 한다.

직업성 천식은 노출량이 증가할수록 발생이 는다.

  • 어떤 특정한 직업에 종사하여 분진이나 가스, 증기, 연무 등에 노출되어 기침과 가래, 호흡곤란과 같은 천식 증상이 발생 혹은 악화되다가 직장을 쉬거나 그만두면 증상이 소실되거나 현저한 개선을 보이는 경우이다.
  • 노출되는 양이 증가할수록 발생이 증가한다.
  • 노출된 물질의 Sensitizing potency 도 중요하다.
  • 원인물질은 300여가지 보고 되었다. 국내에서 흔한 것은 다음과 같다.
    • 고분자 물질(예제임)

        귤 응애(귤 과수원 농부), 점박이 응애(과수원 농부), 밀가루(제빵공), 소털(축산농가 농부), 한약재(한약 취급자), 카레가루(카레공장근로자), 라텍스(의료종사자), 미더덕(식품가공공장), 쌀겨(쌀가게) 등.

    • 저분자 물질(예제임)

      TDI(가구, 피아노 악기), MDI(페인트 사용), 목제분진(제제소), 염료(염료 공장), 용접(용접소), 약제(제약회사, 의료종사자), 니켈등 금속(도금공장) 등.

  • 치료는 진단 후 완전한 격리이다.
  • 직업성 천식은 기도 과민도와 관련된 질병이며 과민성 폐장염은 폐실질내 염증반응이다.

천식 발작은 완화제(Relievers)로 치료한다.

  • - Critically ill asthma attack Tx
    • Oxygen
    • Short acting beta agonist every 20 min for 1 hr
    • Ipratropium bromide
    • Systemic corticosteroid(PO or IV)
    • SQ epinephrine, beta 2 agonist.
    • Continuous nebulization with monitoring of EKG and oxymetry
      • tremor, irritability, tachycardia, hypokalemia
      • Hypoxia, V/Q mismatch
    • Slightly below maintenance fluid d/t ADH secretion
    • Theophylline IV
    • Heliox(70:30 helium:oxygen mixture)
    • Magnesium sulfate IV
    • Mechanical ventilation
      • Low barotrauma
      • Short inspiratory long expiratory times
      • 10-15 ml/kg tidal volume
      • 8-15 breaths/min
      • <60 cmH20 peak pressure
      • Without PEEP
    • Rarely occur in medical center, asthma death

기관지 천식의 학습목표는 다음과 같다

  • 기관지 천식의 정의와 기본적인 병태생리를 설명한다.
  • 기관지 천식의 특징적인 임상 소견과 진찰소견을 기술한다.
  • 기관지천식 환자를 문진한다.
  • 기관지 천식의 유발 또는 악화요인을 열거한다.
  • 중증 천식을 시사하는 진찰 및 검사소견을 설명한다.
  • 크산틴(xanthine)계 약물 투여에서 주의 사항과 부작용을 설명한다.
  • 흡입 약제의 특성을 설명한다.
  • 부신피질호르몬의 적응증 및 그 사용법을 설명한다.
  • 예방적으로 사용하는 약제를 나열하고 그 기전을 설명한다.
  • 천식 환자에서 사용하지 말아야 할 약제와 그 이유를 설명한다.
  • 기관지 천식과 감별해야되는 질환들을 열거한다.
  • 기관지천식의 진단 방법을 설명한다.
  • 천식 치료에 사용되는 약물을 사용 목적에 따라 분류하고 작용기전과 부작용을 설명한다.
  • 기도과민증의 검사 방법을 기술한다.
  • 기관지천식 환자의 폐기능 검사 소견을 해석한다.
  • 기관지천식 환자의 동맥혈가스분압 소견을 해석한다.
  • 기관지 천식의 중증도를 분류한다.
  • 기관지 천식의 치료 목표를 기술한다.
  • 기관지 천식의 중증도에 따른 장기적 치료 원칙을 기술한다.
  • 급성 천식 발작의 응급치료 원칙을 기술한다.
  • 기관지천식 치료제의 작용과 부작용을 기술한다.
  • 흡입 약제의 사용법을 설명한다.
  • 기관지천식 환자에게 교육해야 할 내용을 기술한다.
  • 운동 유발성 천식의 진단과 예방법을 설명한다.
  • 직업성 천식을 정의한다.

- 학습목표의 중요성은 질병의 중요한 점을 지적한다는 것 이외에도 이를 중심으로 공식적인 시험에서 문제로 출제된다는 점이다. 그러므로 중요한 점을 먼저 공부를 하고 시작해야 한다.

- 이곳에서는,

  • – 크산틴(xanthine)계 약물 투여에서 주의 사항과 부작용을 설명한다.
  • – 부신피질호르몬의 적응증 및 그 사용법을 설명한다.
  • – 예방적으로 사용하는 약제를 나열하고 그 기전을 설명한다.

- 항목은 ‘알레르기 약물치료 원칙’과 중복되기에 강의 내용은 기본적인 것만 언급한다.

이곳에 사용한 약어는 다음과 같다.

  • AIDS; acquired immune deficiency syndrome
  • BAL ; Bronchoalveolar lavage
  • Bx ; Biopsy
  • COPD ; Chronic obstructive pulmonary disease
  • DPI ; Dry powder inhaler
  • EAR ; early asthmatic response
  • EIA ; Exercise induced asthma
  • EIB ; Exercise induced bronchospasm
  • ERV ; Expiratory residual volume
  • FEV1 : Forced expiratory volume
  • FRC ; Functional residual capacity
  • FVC ; Forced vital capacity
  • GINA : Global Initiative for Asthma
  • HPA ; Hypothalamic-pituitary-adrenal
  • IRV ; Inspiratory residual volume
  • ISAAC ; International Study of Asthma and Allergies in Children
  • LAR ; late asthmatic response
  • MDI : Metered dose inhaler
  • MEF ; Maximal expiratory flow-volume
  • NHLBI : National Heart Lung and Blood Institute
  • NSAID ; non steroidal anti inflammatory drugs
  • PC ; Provocative concentration
  • PD ; Provocative dose
  • PEFR ; Peak expiratory flow rate
  • Raw ; Resistance of airway
  • RS ; Respiratory syncytial
  • RV ; Residual volume
  • sRaw ; specific airway resistance
  • TLC ; Total lung capacity
  • VC ; Vital capacity
  • VOCs ; Volatile organic compounds
  • VCD ; Vocal cord dysfunction
  • HIV; Human immunodeficiency virus

참고문헌

  • Lancet. 1998 Apr 25;351(9111):1225-32. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. (Medline)
  • GINA 2005 Pocket Guide for Asthma Management and Prevention(Site)
  • NHLBI 1997 Guidelines for the Diagnosis and Management of Asthma(Site)

 

 

 
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