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Can We offer COPD Patients better life?
ครรชิ�ต ปิ�ยะเวชิว�ร ตน์�แผน์กโรคปิอดและเวชิบำ��บำ ดว�กฤต
รพ.พระมงก�ฎเกล �24 พ.ค . 51
หั วข้ อบำรรย�ย
• สถ�น์ก�รณ์�ข้อง COPD ใน์ปิ'จจ�บำ น์
• คว�มร) พ*+น์ฐ�น์เก-.ยวก บำ COPD
• ก�รด)แลร กษ�ผ) ปิ0วย COPD ที่-.ม-อ�ก�รก��เร�บำ
• ก�รด)แลผ) ปิ0วย COPD ข้ณ์ะปิกต�
• ก�รศึ3กษ�ข้น์�ดใหัญ่5ล5�ส�ดเก-.ยวก บำผ) ปิ0วย COPD
World’s Top Ten Killers: WHOWorld’s Top Ten Killers: WHO
World’s Top Ten Killers: WHOWorld’s Top Ten Killers: WHO
6
Of the six leading causes of death in the United States, only COPD has been increasing steadily since 1970
Source: Jemal A. et al. JAMA 2005
Prevalence of COPD: geographical variation
• Global 3.9%1
• Europe 4–6%2
• United States 3.6%3,4
• Latin America ~15% of adults over 40 years5
• Asia Pacific 6.3%6
1. Murray et al. Science 1996. 2. European White Lung Book, 2003. 3. American Lung Association Report, 2005. 4. U.S Census Bureau. www.census.gov (accessed February 2006). 5. Hallal et al. Poster presented at ATS 2005. 6. Chan-Yeung et al. Int J Tuberc Lung Dis 2004.
COPDCOPD3.7%3.7%
AsthmaAsthma 10%10%
Chiangmai INNER CITY Population COPD Prevalence 2004
( n=553/66,000)
Chaicharn Pothirat et al. Chiangmai Lung Health Study 2004Chaicharn Pothirat et al. Chiangmai Lung Health Study 2004
0%
Smokers11.2%11.2%
Non-smokers
0.55%
Pack-yearsPack-years and diseasesand diseases
0.00%
9.30%12.70%
23%
0.00%
5.00%
10.00%
15.00%
20.00%
25.00%
Chaicharn P et al. WAM 2004Chaicharn P et al. WAM 2004
0 5-15 15-30 30-70 pack-yrs
Chronic smokers of Chiang Daw elderly club
0/108 7/75 14/110 47/224
Chiang Daw COPD in population
The prevalence of COPD The prevalence of COPD among at risk among at risk smokerssmokers
2121//185185 ( (11.411.4%)%)
Chaicharn P et al. WAM 2004Chaicharn P et al. WAM 2004
6.67%
3.98%
0.00%
1.00%
2.00%
3.00%
4.00%
5.00%
6.00%
7.00%
Female Male
OR=1.71OR=1.71(0.69-4.25)(0.69-4.25)
Mean pack-yrs 24.7 26.3
52.7
30.4
5.410.7
0
10
20
30
40
50
60
0 1-2/yr 3-4/yr >4 /yr
Chaicharn P et al. WAM 2004Chaicharn P et al. WAM 2004
N=209N=209
Frequency of Hospitalized Exacerbation
during the past year
Healthcare Resource Burden1 yr hospitalization May 2003-2004(n=271 episodes)
M:F 44.6%:55.4%Age 70.33 + 9.33 yr
Cause of admission AECOPD 153 (56.5%) CAP 39(14.4%) Others 29(29.3%) LOSLOS 11.7 11.7++9.57 d 9.57 d MV useMV use 218/271(80.4%) 218/271(80.4%) MV duration 7.6(1-44) dDirect hospital cost(bill)(n265) 52,229.8 (1,122-352,500)
Universal coverage 149(55%) goverment insurance 91(33.6%)Dead /expected dead 71(26.2%)Dead /expected dead 71(26.2%)
Chaicharn Pothirat et al. Economic impact study of COPD2004
N 153 39LOS 10.25+8.6 16.92+13.14 0.004Hosp charge * 41217+ 39,385 94,884 + 87,315 0.004Dead 17.7 41.0 0.002
Healthcare Resource Burden
1 yr hospitalization study May2003-2004
AECOPD COPD pneumonia AECOPD COPD pneumonia p-valuep-value
* Cost-to-Charge ratio > 0.80* Cost-to-Charge ratio > 0.80
Chaicharn Pothirat et al. Economic impact study of COPD2004
หั วข้ อบำรรย�ย
• สถ�น์ก�รณ์�ข้อง COPD ใน์ปิ'จจ�บำ น์• คว�มร) พ*+น์ฐ�น์เก-.ยวก บำ COPD
• ก�รด)แลร กษ�ผ) ปิ0วย COPD ที่-.ม-อ�ก�รก��เร�บำ• ก�รด)แลผ) ปิ0วย COPD ข้ณ์ะปิกต�• ก�รศึ3กษ�ข้น์�ดใหัญ่5ล5�ส�ดเก-.ยวก บำผ) ปิ0วย COPD
Definition of COPD COPD is a preventable and treatable
disease with some significant extrapulmonary
effects that may contribute to the severity in
individual patients. Its pulmonary component is characterized by
airflow limitation that is not fully
reversible. The airflow limitation is usually progressive
and associated with an abnormal
inflammatory response of the lung to
noxious particles or gases.
16
Risk Factors for COPD
NutritionNutrition
InfectionsInfections
Socio-economic Socio-economic statusstatus
Aging PopulationsAging Populations
AgeAge 40-50 40-50 50-55 50-55 55-60 55-60 60-70 60-70
Courtesy of D. O’Donnell.Adapted from Fletcher CM, Peto R. BMJ 1977
FEV 1 (
%) R
elat
ive
to A
ge 2
5
Age (years)
Death
Disability
Symptoms
Not SusceptibleSusceptibleSmokers
Stopped smokingat 45 (mild COPD)
Stopped smokingat 55 (severe COPD)
30 40 50 60 70 80 900
20
40
60
80
20
100
Loss of connective tissue support results in dynamic
airway collapse
Mucus hyper-secretion
Increased mucus viscosity
Reduced mucociliary transport
Mucosal damage
Muco-ciliary Dysfunction
Pathophysiological features of COPD
Mucociliarydysfunction
Airwayinflammation
Systemiccomponent
Structuralchanges
Airflowlimitation
หัลอดลมข้องผ) ปิ0วยที่-.ไม5ใชิ5 COPD
หัลอดลมข้องผ) ปิ0วย COPD
Healthy H. influenzae
Mucociliary dysfunction
Increased numbers / activation:
NeutrophilsMacrophagesCD8+
Elevated: IL-8, TNF-α, LTB4
Protease/anti-protease imbalance
Mucosal edema
Airway Inflammation
Pathophysiological features of COPD
Mucociliarydysfunction
Airwayinflammation
Systemiccomponent
Structuralchanges
Airflowlimitation
Pathophysiological features of COPD
Airwayobstruction
Smooth muscle contraction
Increased cholinergic tone
Bronchial hyperreactivity?
Loss of elastic recoil
Normal COPD
Systemic Component
Pathophysiological features of COPD
Mucociliarydysfunction
Airwayinflammation
Systemiccomponent
Structuralchanges
Airflowlimitation
Respiratory system
Target organs
Systemic inflammation
Cardiac risk factors* in COPD patients
*adjusted for age, sex, BMI, smoking status, race and comorbidity*adjusted for age, sex, BMI, smoking status, race and comorbidity(Data are mean +/- SEM)(Data are mean +/- SEM)
Sin D and Man P. Circulation 2003
33
44
55
66
77
Neutrophils (10Neutrophils (1033/µL)/µL)
400400
200200
250250
300300
350350
Platelets (10Platelets (1033/µL)/µL)
400400
250250
300300
350350
Fibrinogen (mg/dL)Fibrinogen (mg/dL)
2.52.5
00
0.50.5
11
1.51.5
22
CRP (mg/dL)CRP (mg/dL)
STAGE 3- 4STAGE 3- 4STAGE 2STAGE 2STAGE 1STAGE 1NORMALNORMALCOPD severityCOPD severity
COPD patientHealthy control
Skeletal muscle apoptosis in COPD
Agustí AGN et al. Eur Respir J 2000
Prevalence of osteoporosis in COPD
Bolton. Am J Respir Crit Care Med 2004
55
3111
32
49
48
13 2041
0%
20%
40%
60%
80%
100%
No bone loss Osteopenia Osteoporosis
FEV1<50% predn=46
FEV1>50% predn=35
Healthy subjectsn=38
Pe
rce
nta
ge
of s
ubj
ect
gro
up
Osteoporosis in COPD
55
32
12
32
50
47
50
13 18
4150
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
No bone loss Osteopenia Osteoporosis
Low BMIlow FFMI
n=16
Normal BMIlow FFMI
n=17
Normal BMINormal FFMI
n=44
Healthysubjects
n=38
Pe
rce
nta
ge
of s
ubj
ect
gro
up
Bolton. Am J Respir Crit Care Med 2004
หั วข้ อบำรรย�ย
• สถ�น์ก�รณ์�ข้อง COPD ใน์ปิ'จจ�บำ น์• คว�มร) พ*+น์ฐ�น์เก-.ยวก บำ COPD
• ก�รด)แลร กษ�ผ) ปิ0วย COPD ที่-.ม-อ�ก�รก��เร�บำ• ก�รด)แลผ) ปิ0วย COPD ข้ณ์ะปิกต�• ก�รศึ3กษ�ข้น์�ดใหัญ่5ล5�ส�ดเก-.ยวก บำผ) ปิ0วย COPD
32
GOLD: Definition of COPD Exacerbations
“An event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.”
NICE: Definition of COPD Exacerbations• An exacerbation is a sustained worsening of
the patient’s symptoms from his or her usual stable state that is beyond normal day-to-day variations, and is acute in onset. Commonly reported symptoms are worsening breathlessness, cough, increased sputum production and change in sputum colour. The change in these symptoms often necessitates a change in medication
Disease progress vs Exacerbation
Progression
Exacerbation
COPD: Progressive Disease อา
การ/
lu
ng
fu
ncti
on
ระยะเวลา
Normal daily activity
Acute exacerbation
Outcome of COPD exacerbations
Seneff et al. JAMA 1995Murata et al. Ann Emerg Med 1991
Adams et al. Chest 2000Patil et al. Arch Intern Med 2003
2.5%-10%2.5%-10%(within 5 days)(within 5 days)
Hospital mortalityHospital mortalityIn hospitalized In hospitalized
patientspatients
22%-32%22%-32%(within 14 days)(within 14 days)
Relapse (repeat ER visit)Relapse (repeat ER visit)In ER patientsIn ER patients
24%24%(within 1 year)(within 1 year)
Hospital mortalityHospital mortalityIn ICU patientsIn ICU patients
13%-33%13%-33%(within 14 days)(within 14 days)
Treatment failure rateTreatment failure rateIn outpatientsIn outpatients
Percent of patients
COPD Exacerbations
• 43% of patients hospitalized for a COPD exacerbation died within one year (USA)1
• The in-hospital mortality rate of patients with a COPD exacerbation was 11% (USA)
• 25% of men and 38% of women will die within one year after having an initial recognized MI2
• The in-hospital acute MI mortality rate was 9.4% in 1999 (USA)
Myocardial Infarction
Exacerbations: Outcomes
38
ก�รด)แลร กษ�ผ) ปิ0วย COPD ที่-.ม-อ�ก�รก��เร�บำ
ส�เหัต�ส��ค ญ่ที่-.ที่��ใหั ผ) ปิ0วย COPD ม-อ�ก�รก��เร�บำค*อก�รต�ดเชิ*+อใน์ที่�งเด�น์หั�ยใจและมลภ�วะที่�งอ�ก�ศึ แต5 ผ) ปิ0วยปิระม�ณ์หัน์3.งใน์ส�มตรวจไม5พบำส�เหัต�ข้องก�รที่-.ม- อ�ก�รก��เร�บำ (Evidence B)
ผ) ปิ0วย COPD ที่-.ม-อ�ก�รก��เร�บำและอ�ก�รหัร*ออ�ก�รแสดงเข้ �ได ก บำก�รต�ดเชิ*+อที่�งเด�น์หั�ยใจเชิ5น์เสมหัะข้ น์ เข้-ยว อ�จได ปิระโยชิน์�จ�กก�รร กษ�ด วยย�ปิฏิ�ชิ-วน์ะ
(Evidence B)
ส�เหัต�ที่-.ที่��ใหั ผ) ปิ0วย COPD ม-อ�ก�รก��เร�บำ
• ก�รต�ดเชิ*+อ:– Rhinoviruses (common
cold)– Influenza– Parainfluenza– Coronavirus– Adenovirus– Respiratory Syncitial virus– C. pneumoniae– H. influenza– S. pneumoniae– M. catarrhalis– Staph. Aureus– P. aeruginosa
• มลภ�วะที่�งอ�ก�ศึ:– Nitrogen dioxide– Particulates– Sulphur dioxide– Ozone
• 30% ไม5พบำส�เหัต�
ก�รว�น์�จฉั ยแยกโรค• Pneumonia• Pneumothorax• Heart failure• Pulmonary embolism• Upper airway obstruction• Aspiration• Pleural effusion
41
ก�รด)แลร กษ�ผ) ปิ0วย COPD ที่-.ม-อ�ก�รก��เร�บำ
ย�ส)ดข้ย�ยหัลอดลมโดยเฉัพ�ะ inhaled
β2-agonists และก�รใหั steroids ชิน์�ดร บำปิระที่�น์ ม-ปิระโยชิน์�ใน์ก�รร กษ�ผ) ปิ0วย
COPD ที่-.ม-อ�ก�รก��เร�บำ(Evidence A)
ก�รด)แลร กษ�ผ) ปิ0วย COPD ที่-.ม-อ�ก�รก��เร�บำ
ก�รใชิ เคร*.องชิ5วยหั�ยใจชิน์�ดไม5ต องใส5ที่5อชิ5วยหั�ยใจใน์ผ) ปิ0วยที่-.ม-อ�ก�รก��เร�บำ จะที่��ใหั respiratory acidosis ด-ข้3+น์,
pH ใน์เล*อดเพ�.มข้3+น์, ลดอ ตร�ก�รใส5ที่5อชิ5วยหั�ยใจ, ลดอ ตร�ก�รหั�ยใจ, ลดอ�ก�รเหัน์*.อย, ลดระยะเวล�ก�รอย)5ใน์โรงพย�บำ�ล, และอ ตร�ก�รเส-ยชิ-ว�ตลดลง
(Evidence A)
ก�รด)แลร กษ�เบำ*+องต น์ที่-.หั องฉั�กเฉั�น์• ปิระเม�น์คว�มร�น์แรง (อ�ก�ร , ABG, CXR)
• ใหั ก�รบำ��บำ ดด วยออกซิ�เจน์โดยใหั ระด บำ SpO2 อย)5ใน์ชิ5วง 90-94%
• ใหั ย�ส)ดข้ย�ยหัลอดลม– เพ�.มข้น์�ดและคว�มถ-.จ�กที่-.ผ) ปิ0วยเคยได ร บำ– ใหั β2-agonist ร5วมก บำ anticholinergics
• ใหั ย�สเต-ยรอยด�ชิน์�ดร บำปิระที่�น์หัร*อชิน์�ดฉั-ดเข้ �หัลอดเล*อดด��
• พ�จ�รณ์�ใชิ NIV• ปิระเม�น์ผ) ปิ0วยเปิ;น์ระยะ
ผ) ปิ0วยที่-.ควรร บำไว ร กษ�ใน์โรงพย�บำ�ล• ผ) ปิ0วยที่-.อ�ย�ม�ก• ผ) ปิ0วยที่-.อย)5บำ �น์ต�มล��พ งหัร*อก�รเด�น์ที่�งล��บำ�ก• ผ) ปิ0วยที่-.ม-โรคร5วมเชิ5น์ CAD, CRF, cirrhosis• ผ) ปิ0วยที่-.ม-อ�ก�รก��เร�บำบำ5อย• ผ) ปิ0วยที่-.ม-อ�ก�รร�น์แรง• ผ) ปิ0วยที่-.ม-ก�รร) ส3กต วเปิล-.ยน์แปิลง• ตรวจร5�งก�ยพบำอ�ก�รแสดงที่-.เก�ดข้3+น์ใหัม5เชิ5น์ cyanosis,
peripheral edema• ม-ก�รเต น์ข้องหั วใจผ�ดปิกต�ที่-.เก�ดข้3+น์ใหัม5• ไม5แน์5ใจใน์ก�รว�น์�จฉั ย• ผ) ปิ0วยที่-.ไม5ตอบำสน์องต5อก�รร กษ�เบำ*+องต น์
ผ) ปิ0วยร�ยใดที่-.ควรใส5เคร*.องชิ5วยหั�ยใจชิน์�ดผ5�น์ที่5อชิ5วยหั�ยใจ
• ผ) ปิ0วยหัย�ดหั�ยใจ• ผ) ปิ0วยที่-.ไม5ตอบำสน์องต5อก�รใชิ NIV• อ�ก�รหัอบำเหัน์*.อยม�ก , อ ตร�ก�รหั�ยใจ > 35,
abdominal paradox
• pH < 7.25 หัร*อ PaCO2 > 60 mmHg • ม-ระด บำออกซิ�เจน์ใน์เล*อดต�.�และไม5ตอบำสน์องต5อ
ก�รบำ��บำ ดด วยออกซิ�เจน์• ม-ภ�วะแที่รกซิ อน์อ*.น์ๆ
หั วข้ อบำรรย�ย
• สถ�น์ก�รณ์�ข้อง COPD ใน์ปิ'จจ�บำ น์• คว�มร) พ*+น์ฐ�น์เก-.ยวก บำ COPD
• ก�รด)แลร กษ�ผ) ปิ0วย COPD ที่-.ม-อ�ก�รก��เร�บำ• ก�รด)แลผ) ปิ0วย COPD ข้ณ์ะปิกต�• ก�รศึ3กษ�ข้น์�ดใหัญ่5ล5�ส�ดเก-.ยวก บำผ) ปิ0วย COPD
47
ก�รด)แลร กษ�ผ) ปิ0วย COPD ข้ณ์ะที่-.อ�ก�รคงที่-.
ก�รร กษ�ผ) ปิ0วย COPD พ�จ�รณ์�ต�มอ�ก�รเพ*.อใหั ผ) ปิ0วยม-ค�ณ์ภ�พชิ-ว�ตที่-.ด-
ก�รใหั ค��แน์ะน์��ผ) ปิ0วยรวมถ3งก�รใหั ค��ปิร3กษ�ใน์ก�รเล�กบำ�หัร-.เปิ;น์ส�.งส��ค ญ่ที่-.ส�ด (Evidence A)
ย งไม5ม-ย�ใดที่-.จะเปิล-.ยน์แปิลงก�รเส*.อมสมรรถภ�พปิอดข้องผ) ปิ0วยได ใน์ระยะย�ว (Evidence A). แต5ย�จะที่��ใหั ผ) ปิ0วยม-อ�ก�รลดลงรวมถ3งลดภ�วะแที่รกซิ อน์ต5�งๆจ�ก COPD ได
48
ย�ข้ย�ยหัลอดลมเปิ;น์ปิ'จจ ยหัล กใน์ก�รลดอ�ก�รข้องผ) ปิ0วย COPD (Evidence A). อ�จใหั ใน์เม*.อม-อ�ก�รหัร*อใหั แบำบำสม�.�เสมอข้3+น์ก บำผ) ปิ0วยแต5ละร�ย
ย�ข้ย�ยหัลอลมหัล กๆได แก5 ß2-agonists,
anticholinergics, และ methylxanthines อ�จใหั ชิน์�ดเด-ยวหัร*อหัล�ยชิน์�ด ร5วมก น์ (Evidence A).
ก�รใหั ย�ข้ย�ยหัลอดลมชิน์�ดออกฤที่ธิ์�>ย�วอย5�งสม�.�เสมอ จะ ได ผลก�รร กษ�ที่-.ด-และสะดวกกว5�ก�รใชิ ย�ข้ย�ยหัลอดลม ชิน์�ดออกฤที่ธิ์�>ส +น์ (Evidence A).
ก�รด)แลร กษ�ผ) ปิ0วย COPD ข้ณ์ะที่-.อ�ก�รคงที่-.ย�ข้ย�ยหัลอดลม
49
ก�รใหั ย�สเต-ยรอยด�ชิน์�ดส)ดร5วมก บำย�ข้ย�ยหัลอดลมม-ปิระโยชิน์�ใน์ผ) ปิ0วย COPD ที่-. FEV1 < 50% predicted (Stage III: Severe COPD หัร*อ Stage IV: Very Severe COPD) ที่-.ม-อ�ก�รก��เร�บำบำ5อย (Evidence A).
ก�รใหั ย�สเต-ยรอยด�ส)ดร5วมก บำ long acting β2-
agonist ชิน์�ดออกฤที่ธิ์�>ย�วที่-.อย)5ใน์หัลอดเด-ยวก น์ได ผลด-กว5�ก�รใหั ย�สองชิน์�ดแยกหัลอดก น์ (Evidence A).
ควรหัล-กเล-.ยงก�รใหั สเต-ยรอยด�ชิน์�ดร บำปิระที่�น์ใน์ระยะย�วเน์*.อง (Evidence A).
ก�รด)แลร กษ�ผ) ปิ0วย COPD ข้ณ์ะที่-.อ�ก�รคงที่-.ย�สเต-ยรอยด�ชิน์�ดส)ด
50
แน์ะน์��ใหั influenza ว คซิ-น์ใน์ผ) ปิ0วย COPD ที่�กร�ยเน์*.องจ�กส�ม�รถลดคว�มร�น์แรงข้องโรคได
(Evidence A)
แน์ะน์��ใหั Pneumococcal polysaccharide vaccine ใน์ผ) ปิ0วย COPD ที่-.ม-อ�ย�ต +งแต5 65 ปิ?ข้3+น์ไปิ หัร*อผ) ปิ0วย COPD ที่-.ม-อ�ย�น์ อยกว5� 65 ที่-.ม-ค5� FEV1 < 40% predicted (Evidence B)
ก�รด)แลร กษ�ผ) ปิ0วย COPD ข้ณ์ะที่-.อ�ก�รคงที่-.ว คซิ-น์
Influenza Vaccination in Thailand Phunsup Wongsurakiat et al. Economic Evaluation of Phunsup Wongsurakiat et al. Economic Evaluation of Influenza Vaccination in Thai COPD patients. J Med Influenza Vaccination in Thai COPD patients. J Med Assoc Thai 2003;86:497-508Assoc Thai 2003;86:497-508
• RCT, 125 COPD patients, 62 received RCT, 125 COPD patients, 62 received vaccination, 63 received placebo ( mild, vaccination, 63 received placebo ( mild, moderate, severe)moderate, severe)
• Influenza-related ARI was 27% in placebo and Influenza-related ARI was 27% in placebo and 6.4% in treatment group (RR=0.24, vaccination 6.4% in treatment group (RR=0.24, vaccination effectiveness=76%)effectiveness=76%)
• More effective in patients with severe More effective in patients with severe diseasedisease
• Cost effectiveness in all group of COPD patientsCost effectiveness in all group of COPD patients
52
Antibiotics: ใชิ เฉัพ�ะผ) ปิ0วย COPD ที่-.ม-อ�ก�รก��เร�บำจ�กก�รต�ดเชิ*+อ
Antioxidant agents: ก�รใหั n-acetylcysteine ไม5ลดคว�มถ-.ใน์ก�รก��เร�บำข้อง COPD ยกเว น์ใน์ผ) ปิ0วยที่-.ไม5ได ร บำย�สเต-ยรอยด�ชิน์�ดส)ด
Mucolytic agents, Antitussives, Vasodilators: ไม5แน์ะน์��ใหั ใน์ผ) ปิ0วยที่-.ม-อ�ก�รคงที่-.
ก�รด)แลร กษ�ผ) ปิ0วย COPD ข้ณ์ะที่-.อ�ก�รคงที่-.ย�อ*.น์ๆ
53
Rehabilitation: ผ) ปิ0วย COPD ที่�กร�ยได ปิระโยชิน์�จ�กก�รออกก��ล ง จะที่��ใหั ผ) ปิ0วยม-อ�ก�รน์ อยลงและค�ณ์ภ�พชิ-ว�ตโดยรวมด-ข้3+น์(Evidence A)
Oxygen Therapy: ก�รใหั ก�รบำ��บำ ดด วยออกซิ�เจน์ระยะย�ว (> 15 ชิ .วโมงต5อว น์) ใน์ผ) ปิ0วยที่-.ม-ข้ อบำ5งชิ-+ส�ม�รถลดอ ตร�ก�รเส-ยชิ-ว�ตได (Evidence A)
ก�รด)แลร กษ�ผ) ปิ0วย COPD ข้ณ์ะที่-.อ�ก�รคงที่-.ก�รร กษ�อ*.น์น์อกเหัน์*อจ�กก�รใชิ ย�
IV: Very Severe III: Severe II: Moderate I: Mild
Therapy at Each Stage of COPD
FEV1/FVC < 70%
FEV1 > 80% predicted
FEV1/FVC < 70%
50% < FEV1 < 80% predicted
FEV1/FVC < 70%
30% < FEV1 < 50% predicted
FEV1/FVC < 70%
FEV1 < 30% predicted
or FEV1 < 50% predicted plus chronic respiratory failure
Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if repeated exacerbations
Active reduction of risk factor(s); influenza vaccinationAdd short-acting bronchodilator (when needed)
Add long term oxygen if chronic respiratory failure. Consider surgical treatments
หั วข้ อบำรรย�ย
• สถ�น์ก�รณ์�ข้อง COPD ใน์ปิ'จจ�บำ น์• คว�มร) พ*+น์ฐ�น์เก-.ยวก บำ COPD
• ก�รด)แลร กษ�ผ) ปิ0วย COPD ที่-.ม-อ�ก�รก��เร�บำ• ก�รด)แลผ) ปิ0วย COPD ข้ณ์ะปิกต�• ก�รศึ3กษ�ข้น์�ดใหัญ่5ล5�ส�ดเก-.ยวก บำผ) ปิ0วย COPD
TOwards a Revolution in COPD Health-
the TORCH trial
SFC 50/500 µg bd (N=1533)
TORCH: study design
SAL 50 µg bd (N=1521)
Placebo (N= 1524)3-year study duration
2 week run-in
FP 500 µg bd (N=1534)
Calverley et al. NEJM 2007
Worldwide participation in TORCH
42 countries
TORCH: main objectives
• Primary objective
– The effect of SFC 50/500 μg vs placebo on all-cause mortality over 3 years in patients with moderate-to-severe COPD
• Secondary objectives
– The effect of SFC 50/500 μg on the rate of moderate and severe exacerbations
– The effect of SFC 50/500 μg on health status (SGRQ)
Calverley et al. NEJM 2007SGRQ = St. George’s Respiratory Questionnaire
Study population: inclusion criteria
• Established history of COPD (ERS definition)
• Aged 40–80 years inclusive
• Smoking history ≥ 10 pack years
• Reversibility < 10% in predicted FEV1
• FEV1 < 60% predicted (pre-bronchodilator)
• FEV1/FVC ratio ≤ 70%
• Able to use Diskus/AccuhalerERS = European Respiratory SocietyFVC = Forced Vital Capacity
Vestbo et al. Eur Respir J 2004Calverley et al. NEJM 2007
Demographics
Age 65 (8)Males 76%Current smokers
43%Pack years 49 (27)% pred baseline FEV1 (post bronc) 44 (13)
% pred reversibility 3.7 (3.7)≥1 exacerbations in previous year 57%
ITT N=6112
Mean (sd)
Calverley et al. NEJM 2007
Premature study drug discontinuation
SALM FP048
12162024283236404448
0 12 24 36 48 60 72 84 96 108 120 132 144 156
Probability of withdrawal (%)
Placebo
1524152115341533
Numberat risk
1141124012471296
1005109311121164
884986971
1042
Time to withdrawal from study medication (weeks)
SFC
Statistical comparisons: SALM/FP, SAL & FP vs placebo p < 0.001; SALM/FP vs SAL p = 0.048; SALM/FP vs FP p = 0.01Vertical bars are standard errors Calverley et al. NEJM 2007
Primary analysis: all-cause mortality at 3 years
Vertical bars are standard errors
15241533
14641487
13991426
12931339
Numberalive
0
2
4
6
8
10
12
14
16
18
0 12 24 36 48 60 72 84 96 108 120 132 144 156Time to death (weeks)
Probability of death (%)
SFC 12.6%Placebo 15.2%
HR 0.825, p=0.05217.5% risk reduction
2.6% absolute reduction
Calverley et al. NEJM 2007
TORCH in context
• What are the implications of the primary result?
– Statisticians agree that p < 0.05 is an arbitrary cut off and similar conclusions should be drawn from p values of 0.055 and 0.0451
• How does the reduction in mortality in TORCH compare with other studies?
– Smoking cessation in COPD2
– Non-invasive ventilation in respiratory failure3
– Statins in cardiovascular disease4
– ACE inhibitors in vascular disease5
1. Altman 1991; 2. Anthonisen et al. Ann Intern Med 2005 3. Peter et al. Crit Care Med 2002; 4. Wilt et al. Arch Intern Med 2004
5. Flather et al. Lancet 2000
Impact of smoking cessation programme on mortality
All-cause 14.5 year survival from the Lung Health Study (LHS)
Anthonisen et al. Ann Intern Med 2005
1.00
0.95
0.90
0.85
0.80
Proportion of patients with no event
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time since LHS baseline (years)
Special intervention group
Usual care group
15%15%
Effect of statins on all-cause mortality in patients with coronary heart disease
• Meta-analysis of 17 trials
• N = 40974
• Mean/median follow up 0.3–6.1 years
• Relative Risk Reduction = 16%
• Absolute Risk Reduction = 1.8%
Wilt et al. Arch Intern Med 2004
Effect of ACE inhibitors in patients with left-ventricular dysfunction
• Analysis of 2 trials: SOLVD treatment and prevention
• Enalapril compared with placebo
• N = 6797
• Mean follow up 39 months
• 22.5% deaths on ACE-I vs 24.8% placebo
• Odd ratio 0.87
• Absolute Risk Reduction = 2.3%Flather et al. Lancet 2000
Secondary and other efficacy endpoints
Efficacy endpoints
• Mortality benefits are important, but may be of less relevance if other endpoints are not met
• Key goals of COPD management include:
– Exacerbations
– Quality of Life
– Lung function
Rate of moderate and severe exacerbations over three
years
*p < 0.001 vs placebo; †p = 0.002 vs SALM; ‡p = 0.024 vs FP
Mean number of exacerbations/year
1.13
0.97*0.93*
0.85*†‡
25% reduction
0
0.2
0.4
0.6
0.8
1
1.2
Placebo SALM FP SFC
Treatment
Calverley et al. NEJM 2007
Rate of exacerbations requiring systemic corticosteroids over three
years
*p < 0.001 vs placebo; †p < 0.001 vs SALM; ‡p = 0.017 vs FP
0.64*0.52*
Mean number of exacerbations/year
0.46*†‡
43% reduction0.80
0
0.2
0.4
0.6
0.8
1
1.2
Placebo SALM FP SFC
Treatment
Calverley et al. NEJM 2007
Exacerbations requiring hospitalisation over three years
*p = 0.016 vs placebo; †p = 0.028 vs placebo
Mean number of exacerbations/year
0.19
0.16* 0.170.16†
0
0.05
0.1
0.15
0.2
0.25
Placebo SALM FP SFC
Treatment
HO Pop Source Figure: 7.3.004
73
SGRQ total score
–5
–4
–3
–2
–1
0
1
2
3
0 24 48 72 96 120 156
Adjusted mean change SGRQ total score (units)
Time (weeks)
Placebo
SALM*
FP†
*p = 0.057 vs placebo; †p < 0.001 vs placebo; ††p < 0.001 vs placebo, SALM and FP; vertical bars are standard errors
Number ofsubjects
1149114811551133
854906942941
781844848873
726807807814
675723751773
635701686731
569634629681
SFC††
Calverley et al. NEJM 2007
Post-bronchodilator FEV1
Adjusted mean change FEV1 (mL)
0 24 48 72 96 120 156Time (weeks)
–150
–100
–50
0
50
100
Placebo SALM FP
**
*†
SFC
1524152115341533
1248131713461375
Number ofsubjects
1128121812301281
1049112711571180
979105410781139
906101210061073
819934908975
*p < 0.001 vs placebo; †p < 0.001 vs SALM and FPCalverley et al. NEJM 2007
Summary of efficacy results
• SFC improved survival in COPD
• This was supported by
– Significantly fewer exacerbations compared with components or placebo
– Significantly fewer hospitalisations compared with placebo
– Significant improvements in health status superior to components and placebo
– Significant improvements in lung function superior to components and placebo
1. Calverley et al. NEJM 2007
2. Jones et al. Chest 2006
INSPIRE
Wedzicha JA, et al. AJRCCM 2008;177:19-26
Methods• Inclusion criteria
– Aged 40-80 years
– Smoking history of ≥10 pack-years
– Clinical history of COPD exacerbations
– Post bronchodilator FEV1 <50% predicted
– Reversibility to 400μg salbutamol ≤10% of predicted FEV1
– MMRC score ≥ 2
• Exclusion – Any respiratory disorders other than COPD
– Requirement for long-term oxygen therapy (≥ 12 hours/
day)
MMRC = Modified medical research council dyspnoea scale
Wedzicha JA, et al. AJRCCM 2008;177:19-26
2 week
Run-in
2-years treatment
Oral prednisolone 30mg/day +
inhaled salmeterol
50μg b.d.
Tiotropium bromide 18μg o.d. via Handihaler (n=665)
SFC 50/500μg b.d. via Accuhaler (n=658)
A 2 year multicenter, randomized, double-
blind, double dummy controlled trial
Study design
Discontinued all existing
COPD maintenance medications Wedzicha JA, et al. AJRCCM 2008;177:19-
26
Outcome Measurements
•Primary efficacy endpoint– The rate of health care utilization (HCU)
exacerbations
•Secondary Endpoints– Health status (SGRQ)
– Post-dose FEV1
– Study withdrawal rate
– All cause mortality (efficacy & safety endpoint)
Wedzicha JA, et al. AJRCCM 2008;177:19-26
SGRQ = St. George’s Respiratory Questionnaire
Patient characteristics
Wedzicha JA, et al. AJRCCM 2008;177:19-26 * Baseline following treatment intensification period
Time to withdrawal on treatment in SFC and TIO
Cox Hazard Ratio 95% CI p-valueTIO vs SFC 1.29 (1.08 – 1.54) 0.005
Probability of withdrawal prior to wk 104 SFC 34.5% TIO 41.7%
Numberat Risk
0 13 26 39 52 65 78 91 104
0
4
8
12
16
20
24
28
32
36
40
44P
rob
abili
ty o
f w
ithd
raw
ing
(%)
Time to withdrawal (weeks)
Treatment
SFC 50/500
TIO 18
More subjects withdrew from the TIO arm
Wedzicha JA, et al. AJRCCM 2008;177:19-26
Rate of exacerbations (mean no./year)
VariableSFC
50/500(n=658)
TIO 18(n=665)
Rate Ratio (95% CI)
P value
HCU 1.28 1.32 0.97 (0.84 to
1.12)
0.656
Requiring oral corticosteroids
0.69 0.85 0.81 (0.67 to
0.99)
0.039
Requiring antibiotics
0.97 0.82 1.19 (1.02 to
1.38)
0.028
Wedzicha JA, et al. AJRCCM 2008;177:19-26HCU = Health care utilization
Quality of Life (Total SGRQ score over 2 years)
Wedzicha JA, et al. AJRCCM 2008;177:19-26
The total SGRQ was significantly lower in the SFC group compared with the tiotropium group, although this difference did not reach the minimum clinically importance difference
SGRQ = St. George’s Respiratory Questionnaire
Health status: Total SGRQ score
SGRQ – number of patients (%) with a change from baseline ≥ 4 units
SFC(N=658)
TIO(N=665)
Odds ratio(SFC vs
TIO)
95% CI p-value
Week 32 211 (35%) 190 (30%)
1.24 1.01, 1.54
0.045
Week 56 194 (32%) 180 (29%)
1.29 1.04, 1.60
0.021
Week 80 198 (33%) 171 (27%)
1.34 1.08, 1.67
0.008
Week 104 193 (32%) 169 (27%)
1.29 1.04, 1.60
0.021
Wedzicha JA, et al. AJRCCM 2008;177:19-26
The proportion of patients achieving a clinically significant improvement
in SGRQ was greater in the SFC group than in the Tio group
SGRQ = St. George’s Respiratory Questionnaire
All Cause Mortality
SFC 50/500
TIO 18
Number of deaths*p-value
21 (3%) 38 (6%)
0.032
Hazard Ratio 95% CI p-value
SFC vs TIO
0.48 (0.27 to 0.85)
0.012
Time to death on treatment from Cox’s proportional hazards model**
* Includes all patients for whom mortality was known during the study
** Time to death on treatment excludes 7 deaths (3 SFC, 4 TIO) which occurred > 2 weeks after treatment cessation
Wedzicha JA, et al. AJRCCM 2008;177:19-26
Time to death on treatment in SFC and TIO
Numberat Risk
0 13 26 39 52 65 78 91 104
0
1
2
3
4
5
6
7
Pro
bab
ility
of
deat
h (%
)
Time to death (Weeks)
Treatment
SFC
TIO
52% risk reductionp=0.012
Wedzicha JA, et al. AJRCCM 2008;177:19-26
Hazard Ratio 95% CI p-value
SFC vs TIO 0.48 (0.27, 0.85) 0.012
Summary of events associated with death*, n (%)
Events (grouped by body system)
SFC 50/500 (n = 658)
TIO 18 (n = 665)
Cardiac disorders
Respiratory, thoracic and mediastinal
disorders
Neoplasms benign, malignant and
unspecified
General disorders & administration site
conditions
Infections and infestations
Nervous system disorders
Vascular disorders
Gastrointestinal disorders
Hepatobiliary disorders
9 (1)
5 (<1)
2 (<1)
5 (<1)
4 (<1)
1 (<1)
2 (<1)
0
1 (<1)
19 (3)
6 (<1)
7 (1)
2 (<1)
0
2 (<1)
0
1 (<1)
0Wedzicha JA, et al. AJRCCM 2008;177:19-26* Deaths can be associated with more than one adverse event
Top 5 most commonly reported AEs that began during
treatment, n (%) SFC 50/500
(n = 658)
TIO 18
(n = 665)
All events
COPD
Nasopharyngitis
Headache
Pneumonia*
Pharyngolaryngeal pain
435 (66)
122 (19)
115 (17)
48 (7)
50 (8)
34 (5)
414 (62)
104 (16)
98 (15)
60 (9)
24 (4)
26 (4)
*Includes events of pneumonia, lobar pneumonia and bronchopneumonia
Wedzicha JA, et al. AJRCCM 2008;177:19-26
Pneumonia
• The diagnosis of pneumonia was based on
clinical judgement, with radiologic confirmation
not necessarily obtained even in episodes
reported as lobar or bronchopneumonia
• The number of reported pneumonias that
overlapped with an exacerbation treated with
antiobiotics was
– 55% in the SFC group
– 48% in the TIO group
Wedzicha JA, et al. AJRCCM 2008;177:19-26
The other episodes were not given antibiotic treatment despite the report of pneumonia
Overall Study Conclusions• INSPIRE is the first large-scale trial to evaluate the impact
of two different treatment approaches-bronchodilation with
a long-acting inhaled anticholinergic agent or the
combination of bronchodilation using an LABA and
antiinflammatory therapy with an ICS-on COPD
eaxcerbations over 2-year period
• We found We found no differences in the overall rate of no differences in the overall rate of
exacerbationsexacerbations between treatment group between treatment group
• SFC treatment was associated with better health status,
fewer patient withdrawals, and a lower mortality rate than
occurred during tiotropium therapyWedzicha JA, et al. AJRCCM 2008;177:19-26
Summary
• COPD เปิ;น์โรคที่-.ย งไม5ม-ย�ใดๆร กษ�ใหั หั�ยข้�ดหัร*อชิะลอก�รด��เน์�น์ข้องโรคได น์อกจ�กก�รเล�กบำ�หัร-.
• ก�รร กษ�ปิระกอบำไปิด วยก�รใหั คว�มร) แก5ผ) ปิ0วย ก�รใหั ย� ว คซิ-น์และก�รบำ��บำ ดต5�งๆ
• ก�รก��เร�บำข้องโรคที่��ใหั ค�ณ์ภ�พชิ-ว�ตแย5ลง สมรรถภ�พปิอดลดลงและอ�ย�ข้ ยข้องผ) ปิ0วยส +น์ลง
• ก�รใหั long acting β2-agonist ร5วมก บำย�สเต-ยรอยด�ชิน์�ดส)ดส�ม�รถลดอ�ก�ร ลดก�รก��เร�บำ ลดก�รเส*.อมข้องสมรรถภ�พปิอด และอ�จก�รเส-ยชิ-ว�ตข้องผ) ปิ0วย COPD ได