I Update GOLD 2017 - 평가및안정시치료 이진국 가톨릭대학교서울성모병원호흡기내과 New GOLD document has been revised in 2017. Pulmonary function is removed in the risk assessment. Escalation of treatment is introduced in GOLD 2017. Treatment algorithms are proposed in each ABCD groups. Key Words: GOLD, Guideline, Assessment, Treatment Corresponding author: Chin Kook Rhee, M.D., Ph.D. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: +82-2-2258-6067, Fax: +82-2-599-3589, E-mail: chinkook@catholic.ac.kr 1. 평가 GOLD 2017 1 에서지난 version 과변경된주요한평가부분은다음과같다. 1) ABCD 평가기준의변화 2011 GOLD부터환자를 ABCD 로평가하도록권고하고있다. GOLD 2017에서는저위험군과고위험군을구분하는기준에서폐기능을제외하였다. 단순히지난해악화력만으로환자를저위험군과고위험군으로구분하도록지침을개정하였다. 하지만그렇다고해서 spriometry 의역할이없어진것은아니다. 여전히 COPD 를진단하는데있어 spirometry 결과는절대적이며, GOLD ABCD 를평가하기전에 spirometry 결과에따른 airflow limitation 을평가하도록권고하고있다 (Figure 1). GOLD에서는 spirometry 의역할을다음과같이제시하고있다 (Table 1). 2) Blood eosinophil 이전 GOLD 에서는기술되지않았던 blood eosinophil 이평가에서추가되었다. 일부 post hoc 분석 2,3 에따르면급성악화력이있으면서 blood eosinophil 이높은환자는 ICSLABA 치료에비해 LABA 치료시악화위험도가증가되었다. 또한일부 cohort연구 4 에서는높은 blood eosinophil 을가진환자에서악화가더많이발생되었다. 따라서 GOLD 2017에서는 blood eosinophil이악화의예측하는 biomarker가될수있고 ICS의악화예방효과를예측할수도있다고기술하고있다. 하지만현재까지 blood eosinophil의역할에대해서는논란이많이있으며, 여러연구에서상반된결과들이발표되고있고, cut-off 값이정해지지않았다. GOLD 2017에서도이런점에대해잘기술하고있으며, blood eosinophil 의역할에대해신중한입장을보이고있다. 53
Figure 1. The refined ABCD assessment tool. Table 1. Role of spirometry Diagnosis Assessment of severity of airflow obstruction (for prognosis) Follow-up assessment Therapeutic decisions Pharmacologic in selected circumstances (e.g. discrepancy between spirometry and level of symptoms) Consider alternative diagnosis when symptoms are disproportionate to degree of airflow obstruction Nonpharmacologic (e.g. interventional procedures) Identification of rapid decline Table 2. Vaccination for stable COPD Influenza vaccination reduces serious illness and death in COPD patients (Evidence B). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been shown to reduce the incidence of community-acquired pneumonia in COPD patients aged <65 years with an FEV 1<40% predicted and in those with comorbidities (Evidence B). In the general population of adults 65 years the 13-vlanet conjugated pneumococcal vaccine (PPV13) has demonstrated significant efficacy in reducing bacteremia and serious invasive pneumococcal disease (Evidence B). 2. 안정시치료 1) Vaccination 이전 GOLD에서는 COPD환자에게 vaccination이필요하다고간단히기술되어있다. GOLD 2017에서는 pneumococcal vaccination 에대해좀더구체적으로기술되어있다. 특히 13가 conjugated vaccine 에대한역할이새롭게기술되어있다 (Table 2). 2) LABALAMA의역할 GOLD 2017에서는이전에비해 LABALAMA의역할이강조되고있다. 과거 LABALAMA 제제의연구는악화력이없는환자를대상으로 single bronchodilator 와비교하여폐기능개선효과가우수함을보여주었다. 하지만최근에발표된연구에서악화력이있는고위험군대상으로 LAMA 5 나 ICSLABA 6 와비교시악화면에서우월한효과를보였다 54
(Table 3). GOLD 2017 에서는이들연구결과를반영하여 D 군에서 LABALAMA 를 1 차약제로권고하고있다. 3) Triple therapy의역할 ICSLABA에 LAMA를병합한 triple therapy의역할이 GOLD 2017에서구체적으로기술되어있다 (Table 4). 이는최근발표된 triple therapy 가 ICSLABA 7 나 LAMA 8 에비해폐기능을유의하게개선시키고악화를줄여주었다는연구결과를반영한것이다. 4) PDE4 inhibitor의역할최근발표된연구결과에따르면 fixed-dose ICSLABA 를사용하고있는환자에게 PDE4 inhibitor 를추가했을때악화를줄이는효과가보고되었다. GOLD 2017에서이러한 PDE4 inhibitor 의역할이기술되어있고 (Table 5), 더나아가 D군환자에서 triple therapy 에도불구하고악화가지속될경우 PDE4 inhibitor 를추가해보는것을하나의 option으로제시하고있다. 5) 치료알고리즘위에기술된내용을바탕으로 GOLD 2017에서는아래와같은치료알고리즘을제시하고있다 (Figure 2). 이전 GOLD 와바뀐내용이상당부분있다. GOLD A에서기존의 short acting bronchodilator에서 2017에서는 bronchodilator로변경되어기술되어있다. 그이유는 GOLD 2017 에서폐기능이더이상고위험군기준에포함되지않아기존의 C군중상당부분환자가 A군으로변경될것이기때문이다. 폐기능이 50% 미만인환자에게 short acting bronchodilator 만을주는것은바람직하지않기때문에 GOLD 2017 에서는이들환자에게 short acting 이나 long acting 을따로구분하지않고 bronchodilator를처방하도록권고하고있다. GOLD B군환자에게는일단 LABA 또는 LAMA를처방한후 symptom 이지속될경우 LABALAMA로 step up하도록 Table 3. Bronchodilator in stable COPD Inhaled bronchodilator sin COPD are central to symptom management and commonly given on a regular basis to prevent or reduce symptoms (Evidence A). LABAs and LAMAs significantly improve lung function, dyspnea, and health status and reduce exacerbation rates (Evidence A). LAMAs have a greater effect on exacerbation reduction compared with LABAs (Evidence A) and decrease hospitalizations (Evidence B). Combination treatment with LABA and LAMA increases FEV 1 and reduces symptoms compared with monotherapy (Evidence A). Combination treatment with LABA and LAMA reduces exacerbations compared with monotherapy (Evidence B) or ICS/LABA (Evidence B). Tiotropium improves the effectiveness of pulmonary rehabilitation in increasing exercise performance (Evidence B). Table 4. Anti-inflammatory therapy in stable COPD (Inhaled corticosteroid) An ICS combined with an LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbators and moderate to very severe COPD (Evidence A). Regular treatment with ICSs increases the risk of pneumonia, especially in those with severe disease (Evidence A). Triple inhaled therapy of ICS/LAMA/LABA improves lung function, symptoms, and health status (Evidence A) and reduces exacerbations (Evidence B) compared with ICS/LABA or LAMA monotherapy. Table 5. Anti-inflammatory therapy in stable COPD (PDE4 inhibitor) In patients with chronic bronchitis, severe to very severe COPD, and a history of exacerbations: A PDE4 inhibitor improves lung function and reduces moderate and severe exacerbations (Evidence A). A PDE4 inhibitor improves lung function and decreases exacerbations in patients who are on fixed-dose LABA/ICS combinations (Evidence B). 55
Figure 2. Pharmacologic treatment algorithms. Green boxes and arrows indicate preferred. 권고하고있다. GOLD C군환자는악화위험성이있기때문에 1차약으로 LAMA를권고하였다. 이는기존의연구에서 LAMA가 LABA와비교시급성악화예방효과가우월함이증명되었기때문이다. LAMA에도불구하고악화가지속되면 LABALAMA 로 step up하도록권고하고있다. GOLD D군환자에게는 LABALAMA를 1차약으로권고하고있다. ICSLABA가 1차약으로권고되는경우는 asthma component 를가지고있거나 blood eosinophil 이높은경우로제한하고있다. LABALAMA 치료에도불구하고악화가지속시 triple therapy 로 step up 하도록권고하고있다. Triple 치료에도악화지속시 roflumilast나 macrolide를추가해볼수있다. 3. 결론 새롭게개정된 GOLD 2017 에서고위험군평가기준에폐기능이제외되었다. 치료에서는처음으로 escalation 개념이도입되었으며, 일부 de-escalation 도가능하도록권고하고있다. ABCD 군별로치료알고리즘을제시하였고, 추천되는치료를구분하여표시하였다. 이전 GOLD 에비해 2017년 version은 D군에서 LABALAMA의역할을강조하였다. ICSLABA의경우일부환자 ( 천식 component 가있거나 blood eosinophil이높음 ) 에서만 1차약으로권고하였다. References 1. Global Strategy for the Diagnosis, Management and Prevention of COPD. Global initiative for chronic obstructive 56
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