Upload
theerasuk-kawamatawong
View
1.511
Download
9
Embed Size (px)
Citation preview
Asthma and COPD Overlap Syndrome
(ACOS)
Theerasuk Kawamatawong MD, FCCP
Division of Pulmonary and Critical Care Medicine
Department of Medicine
Ramathibodi Hospital Mahidol University
What is asthma? What is COPD?
Asthma is a chronic inflammatory
disorder of the airways in which
many cells and cellular elements
play a role and associated with
• Airway hyperresponsiveness• Recurrent episodes of symptoms
• Widespread and variable
airflow obstruction within the lung that is reversible in nature
Asthma
COPD is a preventable and treatable disease
• Exacerbations & co-morbidities
• Characterized by
• Persistent airflow limitation &progressive
• Associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases
COPD
Global Initiative for Asthma 2014Global Initiative for Chronic Obstructive Lung Disease. 2013
Inflammatory airway diseases
Obstructive airway diseases
Epithelial Cell
COPD cigarette smokes Wood smoke (Biomass)
Alveolar Macrophages
CD8 T lymphocytes(Tck) Neutrophils
Small airway fibrosis Alveolar destruction
Epithelial Cell Mast cells
Asthma (Allergen sensitization)
Bronchial construction Airway hyper-responsiveness
CD8 T lymphocytes(Th2) Eosinophils
Clinical features distinguished asthma from COPDFor General Practice
Asthma COPD
Onset at any time Onset –mid & late life
Usually non smoke Almost invariable
Cough & phlegm (less common) Productive cough common (CB type)
Dyspnea on effort variable DOE predictable and progressive (m/y)
Nocturnal (common) Nocturnal ( uncommon)
Diurnal variation Little variation in flow
Good response to bronchodilator Response to bronchodilator (15-20%)
BHR to nonspecific agent BHR in minor patients
BD: Bronchodilator BHR: Bronchial hyperresponsiveness
Spirometry in obstructive airway diseases Reversible or not reversible obstruction
FEV1
1 2 3 4 5
Normal
Asthma (after BD)
Asthma (before BD)
No plateau after 6 sec Flow
Volume
Normal
Asthma (after BD)
Asthma (before BD)
Scoop pattern(concave of expiratory limb)
Expiratory Spirogram Flow volume loop
Reversibility test with short acting bronchodilator
Volume (L)
Time (s)
12% and 200 ml of FEV1
Spirometry for COPD Diagnosis and Classification of Severity
5
4
3
2
1
1 2 3 4 5 6
Lit
ers COPD
Normal
FEV1
Seconds
FEV1
FVC
FVC
Subjects FEV1 FVC FEV1 / FVC
Normal 4.150 5.200 0.8
COPD 2.350 3.900 0.6
A post-bronchodilator FEV1/FVC < 0.70 confirms the presence of airflow limitation
GOLD 201
Dutch hypothesis
Common cause ?
Common mechanisms
Asthma COPD
British hypothesis
Different causes
Different mechanisms
Asthma COPD
COLD or CNSLD
Co-morbidities and life style factors of real world asthma
Co-morbid disease and life style factors
Prevalence/ degree of problem among patients with asthma
Rhinitis and rhinosinusitis 24-94% (as measured in range of European and American studies) 50-100% (lifetime prevalence)
Anxiety and depression 25-50% prevalence in severe and difficult -to –control asthma)
Obesity Prevalence has increases concurrently with that of asthma over the past decades
GERD Five fold high risk of GERD symptoms in individuals with asthma
Smoking 15-35% (current smokers, with wide variation) 22-43% (ex-smokers)
Device misuse 70%
Real world ICS adherence 30-40%
David Pride and Jean Bousquet et al Curr Allergy Asthma Rep 2011
Lung growth and decline (Interaction of genetic and environmental factors)
-1 0 1 5 10 15 2 0 25 30 35 40 45 50 55 60 65 70 75 80 85 Age
Environment(E) TS & Genes
EnvironmentETS & Genes
Genre leading to abnormal lung development & lung growth
Asthma COPD
Gene for (allergic) inflammation
Airway re-modeling Small airway disease
Gene for Inflammation
Airway re-modelingMucus production
Small airway diseaseEmphysema
Environment(E) TS & Genes
Environment(E) TS & Genes
Case HN 4047696
• ผปวยชายไทย อาย 64 ป อาชพ ท าธรกจสวนตว • มาดวยอาการไอ มเสมหะในปอด 2 ป เหนอยมากขน มาได 1 ป • 30 ป กอนไดรบการวนจฉยโรคหด จากแพทย ทโรงพยาบาลอน เคยท าการ
ตรวจสารกอภมแพทางผวหนง พบวาแพไรฝน • ไดรบการรกษา แตไมสม าเสมอ มอาการเหนอยเปนครงคราว ใชยาขยาย
หลอดลม ชนดรบประทาน และพนแลวอาการดขน • มประวตสบบหรกนกรอง 10 pack years เลกสบบหรไป 20 ป• มประวตมารดา เปนโรคหด • ผปวยมอาการคดจมกน ามกไหล เปนบางครงเวลาสมผสกบฝนละออง• ตรวจรางกาย พบวาม nasal mucosal swelling both noses
• AP chest diameter, expiratory wheeze both lungs
Examination patients with rhino-conjunctivitis
Allergic Rhinitis : co-morbidities
Vasomotor rhinitis: co-morbidities
Oral candidiasis :local side effect
Malampatti score (OSAHS) co-morbidities
Posterior nasal drip or cobble stone granular pharynx
Allergic rhino-conjunctivitis Allergic shiners co-morbidities
Speaker received the permission from patients for presenting these picture for academic purposes
Chest film PA and lateral HN 4047696
Paranasal sinus film HN 4047696
การทดสอบสมรรถภาพปอดสไปโรเมตรย (31/3/2014)
PFT parameter
Predicted value
Pre-BD Pre-BD% predicted
Post-BD Post-BD% predicted
% change
VC 3.79 2.93 77.4% 3.76 99.2% 28.1%
FVC (L) max 3.93 2.93 74.7% 3.76 95.7% 28.1 %
FEV1 2.96 1.05 35.4% 1.31 44.4 25.5 %
FEV1 /FVC 0.36 0.34
FEF 25-75% 3.21 0.35 11% 0.41 13.2% 20.6%
PEFR (L/s) 7.82 3.52 45% 3.71 47% 5.3
Pre-BD: Pre-bronchodilator Post-BD: Post-bronchodilator
การทดสอบทางหองปฏบตการ
• CBC Hb 13.3 g/dl, Hct 41%, WBC 7000/mm3, P60% L 25% Eosinophils 10% Mono 4% Baso 1%
• Specific IgE 147.1 IU/ml (Normal <120 IU/ml)
• Specific IgE positive for D pteronyssinus (0.93 KUA/L)
• Fractional excretion exhaled nitric oxide (FeNO)
118 ppb (Normal <50 ppb in adults)
ทานจะใหการวนจฉยวาผปวยเปนโรคอะไร เพราะเหตผล • Allergic bronchial asthma
• Asthma with airway remodeling
• COPD (Emphysema)
• COPD (Chronic bronchitis)
• COPD with allergic rhinitis and sinusitis
Asthma COPD overlap syndrome (ACOS)
COPD-asthma overlap syndrome (COAS)
HX diagnosed asthma
FEV1>12% & 200 ml Eo
PFT FEV1/FVC<0.7
Cigarette smoking
CXR hyperinflation
Chronic cough
PNS film, SPT, sIgE
High resolution computed tomography of chest
High resolution computed tomography of chest
Role of lung function in asthma and COPD
Test Asthma COPD
Normal FEV1/FVC (pre or post BD)
Compatible with asthma diagnosis (controlled)
Generally not compatible COPD diagnosis
Low FEV1/FVC (<0.7 post BD)
Indicates airflow limitation but may improve on treatment
Required for COPD diagnosis
FEV1 normal Compatible with asthma diagnosis (controlled)
Rule out COPD if FEV1/FVC ratio is normal
FEV1 low A measure in assessment of current asthma controlRisk factor for asthma exacerbation
Indicator of spirometryseverity
Improvement FEV1
>12% and 200 ml post BD
Usual at some time in course of disease, but not when controlled or when on controllers
Often present but an asthmatic component should be considered
Improvement FEV1
>12% and 400 ml post BD
High probability of asthma or asthma component
Unusual
21
Role of blood test and HRCT in asthma and COPD
Test Asthma COPD
Inflammatory biomarkers and imaging finsings
Blood eosinophilia Support asthma diagnosis May increase during exacerbation
Sputum inflammatory cell analysis
Role in differential diagnosis not established in large population
FENO High level supports a diagnosis of eosinophilic asthma
Usually normal
High resolution CTscan
Normal or some bronchial wall thickening
Emphysema can be quantified
Tests for atopy(specific IgE or skin prick test)
Modestly increases in probability of asthma but not essential for diagnosis
Confirm to background prevalence Dose not rule out COPD
Role of special lung function in asthma and COPD
Test Asthma COPD
Peak Expiratory flow rate (PEFR)
Useful in assessing variability, response to treatment, identifying agents and trigger (occupational asthma)Reversibility and therapeutic response
Not useful in diagnosis and monitoring
Special tests
DLCO Normal or high Often reduced
Arterial blood gas (ABG)
Normal between exacerbation May be abnormal between exacerbation
Airway hyper-responsiveness
Not useful in distinguishing asthma and COPD
Airways inflammation and asthma severity
Djukanović Ratko. et al Am J Respir Crit Care Med 2000
Sputum ECP Sputum Eo count
74 Asthmatics 22 non-atopic control
Eosi
no
ph
ils (
10
3/g
)
10000
1000
100
10
1
4000
1000
100
10
1
ECP
(n
g/m
l)
Control Intermittent Mild moderate
severe Control Intermittent Mild moderate
severe
P< 0.001
P< 0.01
P <0.01
P <0.05
P< 0.001
P< 0.001
P< 0.001
P< 0.001
Airways Inflammation and level of treatments
Sputum NeutrophilsSputum Eosinophils
Djukanović Ratko. et al Am J Respir Crit Care Med 2000
Eosi
no
ph
ils (
10
3/g
)
20000
10000
1000
100
10
1
100000
10000
1000
100
10
Control LowICS Mild
mod
HighICS
severe
Neu
tro
ph
ils (
10
3/g
)
OCS- OCS+
severeControl Low
ICS Mild to mod
HighICS
severe
OCS- OCS+severe
P <0.01
P <0.01
P< 0.001
P< 0.001
P< 0.001
P< 0.001 P< 0.005
Numbers of inflammatory cells and mediators increase as COPD severity progresses
GOLD stage
Cell Type
Percent of Airways with Measurable Cells in small
airways (%) by GOLD Stage
I II III IV
PMNs 67 55 84 100
Macrophages 54 66 73 92
Eosinophils 25 33 29 32
CD4+ 63 87 77 94
CD8+ 85 80 88 98
B cells 7 8 45 37
Hogg JC, et al. N Engl J Med. 2004;350:2645-2653.
% a total number of airway examined
PMN = Polymorphonuclear cells
Partial reversible obstructive COPD Increased FeNO and Sputum Eosinophilia
63.8 2.7 9 26.64.1 pack-y
KCO 62.2 %
66.7 ±3.1 923.6 2.7 pack-y
KCO 58.6%
Leonardo M. Fabbri and Alberto Papi et al Am J Respir Crit Care Med 2000
FeNOSputum Eo countRev COPD >12% & 200 ml Post salbutamol 200 µg
Spu
tum
cel
l co
un
ts (
%)
Neutrophils Eosinophils
Control COPD Not Rev
COPD Rev
Control COPD Not Rev
COPD Rev
100
0COPD
Rev
COPD Not Rev
Control
Exh
aled
NO
(p
pb
)
61.7.4.5
FEV
1in
crea
se a
fter
sal
bu
tam
ol (
ml)
FENO (ppb)
250
200
150
100
50
0 10 20 30 40 50
COPD with partial bronchodilator response to SABA is associated with exhaled NO
and sputum eosinophilia
Stable COPD with partial bronchodilator response to inhaled albuterolis associated with increased exhaled NO and sputum eosinophilia
Leonardo M. Fabbri and Alberto Papi et al Am J Respir Crit Care Med 2000
Inflammatory cell patterns in sputum COPD and asthma with fixed obstruction
FEV1 56 3 %20 pack years
FEV1 56 2 %5 pack years
FEV1 56 3 % FEV1 56 2 %
Leonardo M. Fabbri and Alberto Papi et al Am J Respir Crit Care Med 2003
FeNOSputum Eo count
25%
15
10
5
0
Spu
tum
eo
sin
op
hils
%
Exh
aled
NO
(p
pb
)
60
40
20
0
COPD Asthma COPD Asthma
Bronchial biopsy EG2+ stain and R-BM Asthma with fixed obstruction COPD
Leonardo M. Fabbri and Alberto Papi et al Am J Respir Crit Care Med 2003
EG2+ stain
H&E stain
Different phenotypes of fixed chronic airway obstruction from induced sputum
Maria Laura Bartoli et al Respiration 2009
Asthma COPDFEV1 46.2 ± 6.9 % vs . 50.9 ± 12.6 % Age 58.0 ± 10.5 y vs. 71.9 ± 5.7 y
N =45
Asthma COPDFEV1 46.2 ± 6.9 % vs . 50.9 ± 12.6 % Age 58.0 ± 10.5 y vs. 71.9 ± 5.7 y
Eosi
no
ph
ils (
%)
Asthma CB Emphysema
ECP
(p
g/m
l)
Asthma CB Emphysema
Neu
tro
ph
ils (
%)
Asthma CB Emphysema
NE
(p
g/m
l)
Asthma CB Emphysema
Neutrophilic asthma vs. COPD HRCT detected bronchial wall thickness (BWT)
Neurtopilic asthma65 (10) y, atopy (90%)Smoke 20 packs FEV1 62.1% KCO 97.0%
COPD68 (7) y atopy (47%)Smoke 67.5 packsFEV1 57.6%KCO 56.5%
Smoker control62 (12) y atopy (47%)Smoke 38 packs FEV1 101 %KCO 73.1%
All participants n =35
NeutrophilicAsthma
COPD SmokerControl
Peter G. Gibson et al. Respir Med 2009
Bro
nch
ial w
all t
hic
knes
s sc
ore
10
8
6
4
2
0Bronchial wall thickness score
FEV
1p
red
icte
d (
%)
100 %
80
60
40
20
0
Variable reversibility depending on bronchodilator agent test in COPD
Donohue JF. Therapeutic responses in asthma and COPD. Bronchodilators. Chest. 2004
N=813
Ipatropium only(n =91)11.2%Salbutamol only
(n =222)27.4%
Both(n =280)34.6%
Neither (n =217)26.8%
FEV1
1 2 3 4 5
Normal
Asthma (after BD)
Asthma (before BD)
No plateau after 6 secVolume (L)
Time (s)
Reversibility test with short acting bronchodilator
12% and 200 ml of FEV1
The reproducibility of reversibility defined according
to ATS- ERS criteria
Total % notreversible
at each visit
Calverley PMA et al. Thorax 2003
Visit 0
Visit 1
Visit 2
ATS criteria FEV1 12 % and 200 ml PFT every 2 months
58%
62%
59%
664
388 276
290 98 122 154
215 75 48 50 76 46 51 103
Reversible Not reversible
Physiologic differences between asthma and COPD
Physiology Asthma COPD
Elastic recoil Normal Decreased
Diffusion capacity (DLCO)
Normal or increased Decreased
Lung volume Normal Hyperinflation
Bronchodilatorresponse
Flow-dominant (FEV1
response) Volume dependent
(FVC response)
Sciurba FC. Chest 2004; 126: 117-124
Normal Volume dependentobstruction
Obstruction withreversibility
Flow and volume responses reversibility testing in mild-severe COPD
Tjard Schermer et al Resp Med 2007
N =2210
FVC
Ch
ange
FEV1 Change
400 µg salbutamol
800
600
400
300
200
100
0
-100
-200-100 0 100 200 300 400 500 600 700 800
GOLD 1 GOLD 2 GOLD 3 GOLD 4
Mean values for ∆FEV1 0.180 Liter (SD 0.150) ∆ FVC 0.226 Liter (SD 0.227)
Volume (FVC) vs. flow (FEV1) responsiveness in COPD
Tjard Schermer et al Resp Med 2007
FVC responder FEV1responder
N =2210
GOLD stage GOLD stage
I II III IV I II III IV
Mea
n F
VC
res
po
nse
Mea
n F
EV1
res
po
nse
Former smoker
Current smoker
Former smoker
Current smoker
250
200
150
100
0
250
200
150
100
0
P 0.97P 0.44
∆ FEV1 decreased as the GOLD stage became more severe whereas ∆ FVC changed in the opposite direction
Parameters Asthma COPD P value
Pre-bronchodilator
FEV1(%Pred) 63+11 62+19 NS
FVC(%Pred) 88+15 86+13 NS
FEV1/FVC 0.6+0.1 0.5+0.1 0.006
Post-bronchodilator
FEV1(%Predicted ) 67+10 66+19 NS
FVC(%Predicted ) 91+15 88+13 NS
FEV1/FVC 0.6+0.1 0.5+0.1 0.006
Body plethysmography
TLC(L) 4.0+0.8 5.0+0.9 <0.001
RV(L) 1.8+0.5 2.1+0.5 0.034
DLCO(%Predicted ) 79+16 78+23 NS
Kco(%Prediected) 109+22 82+21 <0.001
VA/TLC 0.85+0.1 0.83+0.08 NS
Older asthma with fixed obstruction and COPD (Ramathibodi hospital cohort)
Pornsuriyasak P et al Abstract Eur Respir J 2014
Median total IgE (IU/ml) 124 (24-1530)
Mean exhaled NO (ppb) 67 (16-142)
+ve specific IgE or SPT 10 (40%)
Treatment asthma with fixed airflow obstruction (Ramathibodi hospital cohort)
Clinical characteristics Asthma with fixed
obstruction(N=25)
COPD(N=22)
P value
Sex (M/F), N 4/21 21/1 <0.001
Age (years) 69±6 73±7 0.031
BMI(kg/m2) 24±4 22±4 NS
Duration of being diagnosed (y)* 14(2-60) 2(1-11) <0.001
Smoking (pack-years)* 0(0-8) 17(10-120) <0.001
ICS treatment, n (%) 25 (100) 16 (72) 0.005
ICS/LABA treatment, n (%) 24 (96) 14 (63) 0.005
Montelukast treatment, n (%) 14 (56) 1 (4.5) <0.001
LAMA treatment, n (%) 5 (20) 18 (82) <0.001
Pornsuriyasak et al Abstract Eur Respir J 2014
Comparing serum inflammatory markers between COPD with/without chronic bronchitis
Parameters COPD without chronic bronchitis(n=64)
COPD with chronic bronchitis(n=57)
P value
White blood cell counts 7035 (median) 7280 (median) 0.34
Serum fibrinogen (mg/dl) 332.73 (103.73) 351.09 (107.9) 0.34
Serum highly sensitive C-reactive protein (hsCRP) mg/ml
1.5 (median) 2.5 (median) 0.17
Eosinophil counts (cells/mm3) 228.5 (0-1780) 246.7 (0-1437) 0.87
Independent t-test for comparing meanRank sum test for nonparametric
Lueprasitsakul K et al Abstract Eur Resp J 2014
ทานจะใหการรกษาผปวยโดยการใชยาอยางไร
• Inhaled short acting bronchodilator (prn or regular)
• Inhaled corticosteroid
• Inhaled corticosteroid and long acting B2 agonist
• Inhaled long acting anti-muscarinic
• Combined inhaled long acting anti-muscarinic and long acting B2 agonist
• Inhaled corticosteroid plus LABA and LAMA
• Theophylline and leukotriene receptor antagonist
Pulmonary rehabilitation Smoking cessationVaccination
41
GOLD multidimensional assessment of COPDR
isk
(GO
LD C
lass
ific
atio
n o
f A
irfl
ow
Lim
itat
ion
)
Ris
k (E
xace
rbat
ion
his
tory
)
> 2
1
0
(C) (D)
(A) (B)
4
3
2
1
Symptoms(mMRC or CAT score or CCQ)
Patient is now in 1 of 4 categories:
A: Less symptoms, low risk
B: More symtoms, low risk
C: Less symptoms, high risk
D: More Symtoms, high riskk
Combined assessment symptoms and risk
GOLD 2013
mMRC 0-1CAT < 10CCQ <1
mMRC > 2CAT > 10CCQ ≥1
FEV
1≥
50
%
FEV
1<5
0%
CAT score =3+3+2+2+2+2+2+3 =19MMRC= 1
Step 1 Step 2 Step 3 Step 4 Step 5
Asthma education and environmental control
As need rapid acting B2A
As need rapid acting B2 agonist
Controller option Select one Select one Add 1 or more Add 1 or both
Low dose ICS Low ICS+LABA Medium or high ICS +LABA
Oral steroid
(low dose)
Anti-LT Medium or high dose ICS
Anti-LT Anti-IgE
treatment
Low dose ICS +Anti-LT
SR Theophylline
Low dose ICS + SR theophylline
Level of control Treatment action
Controlled Maintain and find lowest controlling step
Partly controlled Considered stepping up to gain control
Uncontrolled Step up until controlled
Exacerbation Treat exacerbation
Reduce Increase
Red
uce
In
crea
se
Management approach based on control GINA
Pharmacologic treatment GOLD 2013
Patient Recommended first choices Alternative choices Other possible choices
A SAMA prnor
SABA prn
LAMA orLABA or
SABA and SAMA
Theophylline
B LAMAor
LABA
LAMA and LABA SABA and/or SAMA orSAMA or
TheophyllineC ICS + LABA
orLAMA
LAMA and LABALAMA and PDE4-inh.LABA and PDE4 inh.
SABA and/or SAMA orSAMA or
TheophyllineD ICS + LABA
and/ orLAMA
ICS + LABA and LAMA orICS+LABA and PDE4-inh. or
LAMA and LABA orLAMA and PDE4-inh.
Carbocysteine orSABA and/or SAMA or
SAMA orTheophylline
GOLD guideline 2013
Medications for asthma and COPD
Asthma COPD
Anti-inflammatory drugs -Corticosteroids-Anti-leukotriene-Theophylline
Bronchodilators -Short and long acting β2-agonits -Short and long acting anticholinergic-Theophylline
Bronchodilator-Short acting β2-agonits -Short acting anticholinergic
Anti-inflammatory drugs -corticosteroid -PDE4 inhibitors
ICS/LABA combination ICS/LABA combination
Anti-immunoglobulin E Mucolytic drugs
Asthma aims of gaining & maintaining control in stepwise approach
Treatment of asthma is characterized by suppress inflammation
COPD aims of preventing disease progression in stepwise approach
Treatment of COPD is characterized by relief of symptoms
Different bronchodilator in asthma and COPD
Asthma COPD
Short acting β2 agonist -Dosed as needed -tolerance
Short acting β2 agonist s -Regularly dosed -No tolerance
Long acting β2 agonist -Monotherapy associated with increase frequency of exacerbation
Long acting β2 agonist s-Monotherapy associated with decrease frequency of exacerbation -Little tolerance
Anticholinergics-Efficacious in acute asthma attack
Anticholinergics-efficacious in acute and stable disease
HS Nelson et al. Chest. 2006;129(1):15-26
ICS/LABA vs. LABA Outcome: PneumoniaAnalysis broken down by ICS/LABA type
Nannini et al. Cochrane Database Syst Rev 2012; 9: CD006829
Study/ subgroupCombination
n/NLABAn/N
Odds ratioM-H, Random, 95% CI
FLU/SAL
Mahler 2002 2/165 0/160 4.91 (0.23, 103.04)SCO100470 2/518 4/532 0.51 (0.09, 2.81)Hanania 2003 0/178 1/177 0.33 (0.01, 8.15)TRISTAN 7/358 9/372 0.80 (0.30, 2.18)O’Donnell 2006 0/62 0/59 Not estimableKardos 2007 23/507 7/487 3.26 (1.39, 7.67)TORCH 303/1546 205/1542 1.59 (1.31, 1.93)Ferguson 2008 29/394 15/388 1.98 (1.04, 3.75)Anzueto 2009 26/394 10/403 2.78 (1.32, 5.84)
Subtotal (95% CI) 4122 4120 1.75 (1.25, 2.45)
Total events: 392 (Combination), 251 (LABA)Heterogeneity: Tau2 = 0.06; Chi2 = 10.03, df = 7 (P = .19); I2 =30%Test for overall effect: Z = 3.23 (P = 0.001)
BUD/FORM
Calverley 2003 8/254 7/255 1.15 (0.41, 3.23)Tashkin 2008 10/558 5/284 1.02 (0.34, 3.01)Rennard 2009 37/988 17/495 1.09 (0.61, 1.96)
Subtotal (95% CI) 1800 1034 1.09 (0.69, 1.73)
Total events: 55 (Combination), 29 (LABA)Heterogeneity: Tau2 = 0.00; Chi2 = 0.03, df = 2 (P = .99); I2 = 0%Test for overall effect: Z = 0.37 (P = .71)
Total (95% CI) 5922 5154 1.55 [ 1.20, 2.01 ]
Total events: 447 (Combination), 280 (LABA)Heterogeneity: Tau2 = 0.04; Chi2 = 12.84, df = 10 (P = 0.23); I2 = 22%Test for overall effect: Z = 3.32 (P = .0009)Test for subgroup differences: Chi2 = 2.62, df = 1 (P = .11), I2 = 62%
0.01 0.1 1 10 100
Favours combination
Favours LABA
Inhaled corticosteroid therapy is associated with an increased risk of pneumonia.
Regular treatment with inhaled corticosteroids (ICS) improves symptoms, lung function and quality of life and reduces frequency of exacerbations for COPD patients with an FEV1 < 60% predicted.
Inhaled corticosteroid therapy is associated with an increased risk of pneumonia.
Withdrawal from treatment with inhaled corticosteroids may lead to exacerbations in some patients.
COPD therapeutic Options : Inhaled Corticosteroids
© 2013 Global Initiative for Chronic Obstructive Lung Disease
Rationalized Medication Prescribing for COPD following GOLD in Ramathibodi Hospital
COPD Medications
COPD with post BD
FEV1<50%
(n=25)
COPD with post BD
FEV1≥50%
(n=84)
P value
Age (years) 70.4 (11.2) 71.2 (9.8) 0.71
AECOPD post index
date 20 (80%) 22 (26.1%) <0.05*
Female gender 5 (20) 15 (17.9%) 0.8
SABA-SAMA 25 (100%) 82 (97%) 0.59
ICS-LABA (FSC) 23 (92%) 45 (53.6%) <0.05*
ICS-LABA (BFC) 1( 4%) 6 (7.1%) 0.49
LAMA (Tiotropium) 14 (56%) 26 (31%) 0.03*
Oral xanthine SR 10 (40%) 27 (32.1%) 0.46
Oral B2 agonist 1 (4%) 3 (3.6%) 0.65
Inappropriate
medications1 (4.0%) 55 (65.5%) <0.05*
Panumatrassamee C at al. Respirology 2014
การทดสอบสมรรถภาพปอดสไปโรเมตรย (13/10/2014)
PFT parameter
Predicted value
Pre-BD Pre-BD% predicted
Post-BD Post-BD% predicted
% change
FVC 3.73 2.89 77.4% 2.92 78.3% 1.2%
FVC (L) max 3.87 2.93 74.7% 3.76 75.6% 1.2 %
FEV1 2.90 1.27 35.4% 1.29 44.4 1.6%
FEV1 /FVC 0.43 0.44
FEF 25-75% 3.16 0.49 15% 0.41 15.8% 1.6%
PEFR (L/s) 7.74 3.48 45% 3.28 42% -5%
Pre-BD: Pre-bronchodilator Post-BD: Post-bronchodilator
หลงรกษาดวย ICS-LABA-LAMA 6 เดอน (13/10/2014)
PFT parameter
Predicted value
Pre-BD Pre-BD% predicted
Post-BD Post-BD% predicted
% change
FVC 3.73 2.89 77.4% 2.92 78.3% 1.2%
FVC (L) max 3.87 2.93 74.7% 3.76 75.6% 1.2 %
FEV1 2.90 1.27 35.4% 1.29 44.4 1.6%
FEV1 /FVC 0.43 0.44
PFT parameter
Predicted value
Pre-BD Pre-BD% predicted
Post-BD Post-BD% predicted
% change
VC 3.79 2.93 77.4% 3.76 99.2% 28.1%
FVC (L) max 3.93 2.93 74.7% 3.76 95.7% 28.1 %
FEV1 2.96 1.05 35.4% 1.31 44.4 25.5 %
FEV1 /FVC 0.36 0.34
การทดสอบสมรรถภาพปอดสไปโรเมตรย 31/3/2014
CAT score =3+3+2+2+2+2+2+3 =19 MMRC= 1
CAT score =1+1+1+1+1+1+1+1 =8 MMRC= 1
Cluster analysis of asthma(Severe Asthma Research Project: SARP)
Eugene R. Bleecker at al NHBLI SARP program Am J Respir Crit Care Med 2010
Asthma with fixed airflow obstruction
33%
40% 94%
Baseline FEV1
≥68% < 68%
Max FEV1 Max FEV1<108%
≥65%<108%
<65%
Age of onset
<40 y ≥ 40 y
Cluster 1 Cluster 2 Cluster 3 Cluster 4 Cluster 5
ACOS definition
Asthma with partially reversible airflow obstruction that is, based on change in FEV1 with bronchodilators with or without emphysema or reduced carbon monoxide diffusing capacity (DLco) to <80% predicted
Zeki AA, Schivo M, Chan A, Albertson TE, Louie S. The Asthma–COPD overlap syndrome: a common clinical problem in the elderly. J. Allergy 2011,
COPD with emphysema accompanied by reversible or partially reversible airflow obstruction, with or without environmental allergies or reduced DLCO
Definition of ACOS syndrome
Major criteria• A physician diagnosis of asthma and COPD in the same patient• History or evidence of atopy (hay fever, elevated total IgE)• Age ≥40 years• Smoking >10 pack-years• Postbronchodilator FEV1 < 80% predicted and FEV1/FVC < 70%
Minor criteria• ≥15% increase in FEV1 or ≥12% and ≥200 ml increase in FEV1
postbronchodilator treatment with salbutmol
Samuel Louie, and Amir A Zeki et al Expert Rev. Clin. Pharmacol.2013
Diagnostic Criteria of the ACOS That Had Been Agreed Upon
% agreement in order to beconsider a major criteria
Type of criterion
Very positive bronchodilator test (increase in FEV1 ≥15% and ≥400 ml over baseline)
83 Major
Eosinophilia in sputum 78 Major
Personal history of asthma (history before the age of 40)
78 Major
Personal history of atopy 50 Minor
High total IgE 50 Minor
Positive bronchodilator test (increase in FEV1 ≥12% and ≥200 mlover baseline) on 2 or more occasions
39 Minor
Consensus Document on ACOS in COPD
Juan José Soler-Cataluna, Joan B. Soriano et al. Arch Bronconeumol. 2012
โรคหด Asthma Syndrome
โรคปอดอดกนเรอรง COPD Syndrome
โรคหดผสมโรคปอดอดกนเรอรงAsthma COPD Overlap Syndrome (ACOS)
AtopyCigarette smoking Biomass exposure
Smooth Muscle dysfunction Small Airway inflammation and repair
ปจจยกระตน Triggers
BronchoconstrictionAbnormal bronchial hyper-reactivity Smooth muscle hyperplasia & hypertrophy Inflammatory mediator release
Inflammatory cell infiltration Mucosal edema Epithelial damage and mucus hyper-secretion Basement membrane thickening Inflammatory mediator release
อาการ และการก าเรบฉบพลน Symptoms and Exacerbation
ACOS prevalence in obstructive airway diseases treated in different sites
Amir A. Zeki et al. J of Allergy 2011
Asthma COPD Emphysema
OverlapSyndrome
Other
43.1
23.3 19.913.7
50%
40%
30%
20%
10%
0
NS
**
*
Asthma COPD Emphysema
OverlapSyndrome
Other
34.243.4
15.8
6.6
50%
40%
30%
20%
10%
0
**
*
Types of obstructive airway diseases in general pulmonary clinic
Asthma COPD Emphysema
OverlapSyndrome
Other
52.9
23.421.4
50%
40%
30%
20%
10%
0
**
*
1.4
**
Types of obstructive airway diseases in severe asthma clinic
Amir A. Zeki et al. J of Allergy 2011
Age and gender distribution of ACOS
Amir A. Zeki et al. J of Allergy 2011
% with overlap syndrome
40
35
30
25
20
15
10
5
30-39 40-49 50-59 60-69 >70
Age (years)
3.4% 3.4%
17.2%
37.9% 37.9% 70
60
50
40
30
20
10
0
40-49 50-59 60-69 70-79 >80
Age (years)
Male Female
Sariano JB et al Chest 2013
% with overlap syndrome
Exacerbation of ACOS vs. isolated COPD
Hardin M. et al. The clinical features of the overlap between COPD and asthma. Respir. Res. 2011
Frequent exacerbation Severe exacerbation
% s
ub
ject
s
50%
40%
30%
20%
10%
0
% s
ub
ject
s
50%
40%
30%
20%
10%
0
COPD and asthma42.7
COPD and asthma32.8%
COPD 17.6%
COPD 18%
Impact of ACOS syndrome
A C
OS
61
Sputum Eo predict ICS responsiveness in asthma COPD overlap syndrome
PFT values COPD without asthma (n = 46)
COPD with asthma (n = 17)
VC (% pred) 92.3 ± 3.1 96.6 ± 3.6
FEV1 (% pred) 47.5 ± 2.8 51.3 ± 3.5
FEV1/FVC (%) 46.1 ± 1.7 50.9 ± 2.9
TLC (% pred) 132.0 ± 3.3 120.6 ± 4.9
RV (% pred) 228.5 ± 9.9 192.8 ± 13.9
RV/TLC (%) 57.0 ± 1.5 51.7 ± 1.9
DLCO (% pred) 56.2 ± 3.5 72.2 ± 5.4**
PaO2 (Torr) 67.7 ± 1.8 75.9 ± 2.7
PaCO2 (Torr) 42.0 ± 0.8 40.4 ± 1.0
Serum total IgE (IU/mL)‡ 249.0 ± 99.4 693.1 ± 309.4
Peripheral eosinophil count (/mm3) 207.9 ± 31.7 407.5 ± 81.8*
Spu
tum
eo
sin
op
hils
%
∆ FEV1 Change (ml)-200 -100 0 100 200 300 400
N =63
Yoshiaki Kitaguchi et al Int J of COPD 2012
COPD with asthma
COPD without asthma
กลมอาการ Asthma
(severe)
Asthma and COPD
Overlap Syndrome
COPD
ลกษณะประชากร อาย > 40 ป อาย > 40 ป (50-65 ป) อาย > 65 ป
ผหญง > ผชาย Varied ผชาย > ผหญง Nonsmoker
smoke< 5 pack y
Past or current smoker
smoke > 10 pack y
Past or current smoker
smoke > 10 pack y
Atopic present Atopy present No atopy
โรครวม (co-morbidities)
Rhino-sinusitis
Obesity
GERD
Rhinosinusitis
GERD
GERD
CAD
Metabolic syndrome
ปญหาทส าคญ Frequent
exacerbation
Very frequent
exacerbation> COPD
Exacerbation and exercise
intolerance
ลกษณณะทางพยาธ
สรรวทยา
FEV1/FVC <0.7
DLCO normal
FENO > 50 ppb
Sputum eosinophils
≥3%
Exacerbation >3/y
FEV1/FVC <0.7
DLCO normal or low
FENO > 25-50 ppb
Static hyperinflation
Exacerbation >3-5/y
Frequent nocturnal
awakening ≥4 /week
FEV1/FVC <0.7
DLCO <80% predicted
FENO < 25 ppb
Less nocturnal wakening
Exacerbation >2/y when
FEV1< 50% predict
Pulmonary hypertension
Positions for COPD treatmentPhenotypic approach
C DB
AExac
erb
atio
n f
req
uen
cy
0-1
/yea
r>2
/yea
r
Emphysematousphenotype
Asthma/COPD Phenotype
Chronic bronchiticphenotype
Treatment of COPD by Clinical Phenotypes
C D
A BA
irfl
ow
lim
itat
ion
by
GO
LD s
tage
4
3
2
1
Exacerbatio
n freq
uen
cy
>2
1
0
Symptoms (Questionnaire)
M. Miravitlles et al. Eur Respir J. 2013; 41(6)1252-6 2013 Global Initiative for Chronic Obstructive Lung Disease
LABA or LAMA ICS-LABA
LABA or LAMA
LABA or LAMA
Treatment of COPD by Clinical Phenotypes
Step 1 Diagnosis Chronic Airway Disease
Do symptoms suggest chronic airway disease?
Yes No
Step 2 Syndromic Diagnosis in Adults i) Assemble the features for asthma and COPD that best describe the patientii) Compare number of features in favor of each diagnosis and selected diagnosis
Feature if present Favors asthma Favors COPD
Age of onset □ Before age 20 years □ After age 40 years
Pattern of symptom □ Variation over minutes, hrs of d
□ Worse during night or early
morning
□ Triggered by exercise, emotions,
dust or exposure to allergens
□ Persistent despite treatment
□ Good and bad days but always
daily symptoms and exertional
dyspnea
□ Chronic cough and sputum
preceded onset of dyspnea,
unrelated to triggers
Lung function □ Record of variable airflow
limitation (spirometry, peak flow)
□ Record of persistent airflow
limitation (post-bronchodilator
FEV1/FVC < 0.7)
consider other diagnosis
Step 2 Syndromic Diagnosis in Adults i) Assemble the features for asthma and COPD that best describe the patientii) Compare number of features in favor of each diagnosis and selected diagnosis
Feature if present Favors asthma Favors COPD
PFT b/w symptom □ Normal □ Abnormal
Past history or
family history
□ Previous doctor DX of asthma
□ Family history of asthma, and
other allergic rhinitis or eczema
□ Previous doctor DX of COPD,
chronic bronchitis or emphysema
□ Heavy exposure to a risk factor :
tobacco smoke, biomass fuels
Time course □ No worsening of symptoms over
time. Symptoms vary either
seasonally, or from year to year
□ May improve spontaneously or
have an immediate response to
BD or ICS over wks
□ Symptoms slowly worsening
over time (progressive course
over years)
□ Rapid-acting bronchodilator
treatment provides only
limited relief
Chest X-ray □ Normal □ Severe hyperinflation
Note: these feature best distinguish B/W asthma and COPD. Several feature (3 or more) for either asthma or COPD suggest that diagnosis . If there is similar numbers for both asthma and COPD , consider diagnosis of ACOS
Step 1 Diagnosis Chronic Airway Disease
Do symptoms suggest chronic airway disease?
Yes
Step 2 Syndromic Diagnosis in Adults i) Assemble the features for asthma and COPD that best describe the patientii) Compare number of features in favor of each diagnosis and selected diagnosis
Diagnosis Asthma Some feature of asthma
Feature of both
Some feature ofCOPD
COPD
Confidence in diagnosis
Asthma Possible asthma
Could be ACOS Possible COPD COPD
Step 3Perform spirometry
Post BD FEV1/FVC <0.7 Marked reversible airflow limitation (pre post DB)or other proof of variable airflow limitation
Step 4 Initial treatment
Asthma drugno LABA mono-Rx
Asthma drugsno LABA mono-Rx
ICS and LABA +/-LAMA
COPD drugs COPD drugs
Conclusions
• Whether the asthma-COPD overlap syndrome (ACOS) is a separate entity or a hybrid point within a spectrum of related diseases remains to be determined
• Overlap syndrome is clinically relevant with a 20% prevalence in populations with airway diseases
• ACOS is important in current or former smokers in 5th decade of life who have partially reversible obstruction &progressive exercise intolerance not response to asthma treatments
• Treatment of ACOS is extrapolated from guidelines for asthma or COPD management.
Risk factors
Gender Age BMI Infectious (Rhinovirus, influenza, mycoplasma, chlamydia)AHR Smoking Allergies Acute exacerbation Pollution/environmental toxin
In utero orEarly insults
Smoke exposure Infections Genetic susceptibility Incompatible lung growth Low birth weight Nutritional deficiency
Obstructive airway disease
Asthma-COPD Overlap Syndrome (Novel clinical phenotype? Genotype?
Asthma COPD± emphysema
Specific treatment (s) beyond that used for COPD or asthma
Know treatments Allergen avoidance ICS, LABA, LAMA CS, LTRA, 5-LO inhibitorMast cell stabilizer TheophyllineOmalizumabBronchial thermoplasty
Know treatments Smoking cessation Pulmonary rehabilitation ICS, LABA, LAMA CS, TheophyllineOxygen therapyPulmonary rehabilitationLung volume reduction surgery (RVRS) Endoscopic LVRS
Obstructive airway diseases in practicePhenotypic approach: No one size fit all
C DB
AExac
erb
atio
n f
req
ue
ncy
0-1
/ye
ar>2
/ye
ar
Emphysematousphenotype
Asthma/COPD (ACOS) Phenotype
Chronic bronchiticphenotype
Treatment of COPD by Clinical and Imaging Phenotypes
M. Miravitlles et al. Eur Respir J. 2013; 41(6)1252-6