Management Of Copd & Asthma
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Transcript of Management Of Copd & Asthma
Management of COPD & Asthma
COPD Guidelines
“...disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.”
COPD should be considered in any patient with: History of exposure to risk factors (especially cigarette
smoke) Cough (sputum) Dyspnea
Cough and sputum production may precede development of airflow limitation
Leading Causes of Death, US (1998)
Causes of Death
1. Heart disease
2. Cancer
3. Cerebrovascular disease (stroke)
4. COPD and allied conditions
5. Accidents
6. Pneumonia and influenza
7. Diabetes
8. Suicide
9. Nephritis
10. Chronic liver disease
All other causes of death
Number
724,269
538,947
158,060
114,381
94,828
93,307
64,574
29,264
26,295
24,936
469,314Global Obstructive Lung Disease (GOLD) Initiative website (www.goldcopd.com), accessed April 2, 2001.
0.0
0.5
1.0
1.5
2.0
2.5
3.0Coronary
HeartDisease
Stroke OtherCVD
COPD All OtherCauses
- 59% - 64% - 35% + 163% - 7%
1965–1998 1965–1998 1965–1998 1965–1998 1965–1998
Percent Increases in Adjusted Death Rates, US, 1965 – 1998
Pro
po
rtio
n o
f 19
65 R
ate
Global Obstructive Lung Disease (GOLD) Initiative website (www.goldcopd.com), accessed April 2, 2001.
Risk Factors
Risk Factors in COPD:
COPD: Risk Factors
Exposures Smoking (generally ≥90%) Passive smoking Ambient air pollution Occupational dust/chemicals Childhood infections (severe respiratory, viral) Socioeconomic status
Host factors Alpha1-antitrypsin deficiency (<1%) Hyperresponsive airways Lung growth
Differential Diagnosis
ChronicBronchitis Emphysema
Asthma
COPDCOPD
Airflow Obstruction
Asthma
Definition: Airways hyper-responsiveness, reversible airways obstruction
Pathophysiology: Inflammation
Inelastic collapsible bronchioles
Enlarged air sacs due to destruction of alveolar walls (bullae)
Emphysema
Abnormal permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls and without obvious fibrosis
Destruction of the alveolar wall damages pulmonary capillaries by tearing, fibrosis, or thrombosis
Walls of individual sacs torn (repair not possible)
Chronic Bronchitis
Presence of chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of chronic cough have been excluded
Air passage narrowed by plugged and swollen mucous membrane
Bronchiole
Mucus and pus impede action of respiratory cilia
Asthma Is A Disease Of The Large & COPD The Small Airways
Asthma
Emphysema
Bronchitis
Bronchitis
trachea
bronchi
alveoli
Reversible airflow obstruction + ++ +
Airway inflammation + + + + +
Mucus hypersecretion + + + +
Goblet cell metaplasia + + +
Impaired mucus clearance + + + +
Epithelial damage ++ —
Alveolar destruction — ++
Smooth muscle hypertrophy + + —
Basement membrane thickening +++ —
Disease Pathology Asthma COPD
Inflammation: COPD vs Asthma
Inflammation is an important component in the pathogenesis of asthma and COPD
The inflammatory response in asthma and COPD is markedly different, although some cell types are present in both diseases
The predominant inflammatory cells in asthma include Eosinophils Mast cells CD4+ T lymphocytes
The predominant inflammatory cells in COPD include Neutrophils CD8+ T lymphocytes Macrophages
The role of these cells in COPD is not fully understood
Inflammatory Cell Levels in Ex-Smokers With COPD (>1 Year of Smoking Cessation)
Rutgers et al. Thorax. 2000;55:12-18.
Values are expressed as percentages of the total number of nonsquamous cells. The role of these cells in COPD is not fully understood.
Sp
utu
m N
eutr
op
hil
s (%
)
Sp
utu
m L
ymp
ho
cyte
s an
d E
osi
no
ph
ils
(%)
NeutrophilsP=0.0001
LymphocytesP=0.0161
EosinophilsP=0.0083
100
90
80
70
60
50
40
30
20
10
0
10
8
6
4
2
0
Patients with COPDHealthy controls
AsthmaSensitizing agent
COPDNoxious agent
Asthmatic airway inflammationCD4+ T-lymphocytes
Eosinophils
COPD airway inflammationCD8+ T-lymphocytes
MacrophagesNeutrophils
Airflow limitation
Completelyreversible
Completelyirreversible
Physiologic Differences
Asthma
Normal DLCO
Normal lung volume
Normal elastic recoil
Flow dominant BD response
COPD
Abnormal DLCO
Hyperinflation
Decreased elastic recoil
Volume dominant BD response
Sciurba FC, CHEST 2004;117S-124S
Response to Bronchodilators
ASTHMA SABA
ToleranceDosed PRN
LABAMonotherapy assoc.
with increased frequency of exacerbations
Little tolerance Anticholinergic
Efficacious in acute attack
COPD SABA
No toleranceRegularly dosed
LABAMonotherapy assoc.
with decreased frequency of exacerbations
Little tolerance Anticholinergic
Efficacious in stable disease
Donohue JF, CHEST 2004;125S-137S
Similarities
Bronchial hyper-reactivity
Bronchodilator response
Peripheral blood eosinophilia
Elevated IgE
Eosinophils in the BAL and airways
Lung Health StudyMethacholine Bronchial Responsiveness
Dose Cumulative Percent
(mg) Men Women
1 4 9
5 26 48
10 46 74
25 63 87
Tashkin et al AJRCCM 1996; 153:1802-11
Relationship Between Initial Histamine Threshold and Annual Rate of Decline in FEV1
16127 ± 59 < 2
5077 ± 42 2-3
1547 ± 22 > 4
Patients (n) Decline in FEV1 (ml/yr)
Log Histamine Threshold
Postma, Am Rev Respir Dis 1986: 134:276-280
Level Of BHR And Mortality From COPD During 30 Years of Follow Up
RR (95% CI) COPD mortality
Threshold histamine dose n (n=60)
> 32 mg/ml 998 1
32 mg/ml 391 3.83 (0.97 - 15.10)
16 mg/ml 286 4.40* (1.16 - 16.67)
8 mg/ml 191 4.78* (1.27 - 18.00)
4 mg/ml 103 6.69* (1.71 - 26.13)
1 mg/ml 39 15.8* (3.72 - 67.13)
* p0.05Hospers, et al. Lancet 2000; 356:1313-1317
Changes in Responder Classification After Albuterol and Ipatroprium Bromide
Bronchodilator Response: COPD vs. Asthma
Higgins BG, Eur Resp J; 1991 p415
Assessment/Diagnosis
Why Do We Need Spirometry?Why Do We Need Spirometry?
Objective Vital Sign for the Lungs (“Poor Perceiver”)
More Accurate Assessment of Severity Early recognition of disease Improves choice of therapy Leads to greater patient satisfaction
Determine Reversibility (Asthma) Vs. fixed obstruction (COPD) or Restriction
Differential Diagnosis (Pulmonary & Cardiac Abnormalities)
Identify and Quantify Defects in Lung Function
Reinforces therapeutic decisions to patients
Potential Source of Revenue
Adapted from Crapo RA.: Current Concepts - Pulmonary-Function Testing. N Engl J Med 2001; Vol 331:61-67 and
(http://www.nlhep.org/resources/PreventEmphysemaNow.html -page 1) Prevent Emphysema Now! by: Thomas L. Petty, M.D. and Dennis E.
Doherty, M.D.
FE
V1 (
% o
f va
lue
at
age
25
)
Age (years)Adapted from Fletcher C et al. Br Med J. 1977;1:1645–1648.
COPD Risk and Smoking Cessation
0
25
50
75
100
25 50 75
Death
Disability
Never smoked or not susceptible to smoke
Smoked regularlyand susceptible toeffects of smoke
Stopped smoking at 45 (mild COPD)
Stopped smoking at 65 (severe COPD)
Laboratory Testing
Spirometry (pre- and post-bronchodilator
Chest radiography
Lung volumes
Carbon monoxide diffusing capacity
Arterial blood gases
Stage 0: At Risk
GOLD Guidelines for COPD
Diagnosis Chronic cough/sputum
PFTs within normal limits
No symptoms
Treatment
Avoid risk factors(smoking cessation)
GOLD Guidelines for COPD
Stage I: Mild
Diagnosis
FEV1 >80% predicted
FEV1/FVC <70%
With/without symptoms
Treatment Avoid risk factors
Short-acting bronchodilator PRN
Stage II: Moderate
GOLD Guidelines for COPD
Diagnosis
50% FEV1 <80% predicted
FEV1/FVC <70%
With/without symptoms
Treatment
Avoid risk factors
Regular therapy with 1 bronchodilators
Inhaled corticosteroids if significant symptoms and lung function response
Rehabilitation
Stage III:Severe
GOLD Guidelines for COPD
Diagnosis 30% FEV1 < 50%
predicted
FEV1/FVC < 70%
With/without symptoms
Treatment Avoid risk factors
Regular therapy with 1 bronchodilators
Rehabilitation
Inhaled corticosteroids if significant symptoms and lung function response or if repeated exacerbations
Stage IV: Very Severe
GOLD Guidelines for COPD
Diagnosis
FEV1 < 30% predicted
FEV1/FVC < 70%
Respiratory failure
Right-side-of-the-heart failure
Treatment
Avoid risk factors
Regular therapy with 1 bronchodilators
Inhaled corticosteroids if significant symptoms and lung function response or repeated exacerbations
Rehabilitation
Treatment of complications
Long-term O2 therapy for hypoxic respiratory failure
Evaluate for surgical treatment
1–Antitrypsin Deficiency
Hereditary disorder
Reduced protection vs. neutrophil elastase
Destruction of lung parenchyma
Increased risk of emphysema and liver disease
IV infusions of human 1–antitrypsin(augmentation therapy)
Only currently approved therapy
Once-weekly (60 mg/kg)
2% of COPD population
0 6 12 18 24 30 36 42 48 54 60
Never (n = 162)Partially (n = 285)Always (n = 316)
Time (months)
FEV1 < 50% Predicted
50
40
30
20
10
0
Augmentation Therapy: Impact on Mortality
Alpha-1-Antitrypsin Deficiency Registry Study Group. Am J Respir Crit Care Med. 1998;158:49–59.
TreatmentEffect on
Treatment Randomized ExacerbationsStudy (mcg/day) Patients Placebo ICS vs Placebo
ISOLDE FP 1000 751 – 59 – 50 TE 25% (P = .026)
Paggiaro FP 1000 281 – 40 + 110 ME/SE 60% vs 86% (P .001)
Copenhagen LS BUD 800 290 – 42 – 42 TE 4% (NS)
EUROSCOP BUD 800 912 – 69 – 57 Not Available
Lung Health II TAA 1200 1,100 – 47 – 44 TE †
Mean FEV1
(mL/year) *
ICS: Effect on FEV1 and Exacerbations
*Paggiaro Mean FEV1 was mL per 6 months.† P values not reported.BUD = budesonide; FP = fluticasone propionate; TAA = triamcinolone acetonide.TE = total exacerbations; SE = severe exacerbations; ME = moderate exacerbations.
Complications of COPD
Hypoxemia
Cor pulmonale
Hypercapnia
Dyspnea
Hypoxemia
Adversely affects cellular metabolism; may lead to Hypoxia Pulmonary hypertension Cor pulmonale
Nonspecific signs/symptoms Accurate identification requires arterial blood gas
measurements Nocturnal symptoms present in 25%– 45% of patients with
severe COPD Oxygen supplementation mainstay treatment
Hypercapnia
Usually well tolerated in COPD patients
Treatment goals
Improve airflow
Reduce breathing effort
Improve abnormalities affecting respiratory muscle function
Noninvasive ventilation suggested therapy
Long-term data conflicting
Cor Pulmonale
Primary cause – hypoxemia
Poor prognosis
Oxygen therapy and treating underlying disease are key
Pulmonary vasodilators offer no clear benefits; may worsen hypoxemia
Diuretics may improve ventricular function
Closely monitor for side effects
Digoxin contraindicated unless left-sided congestive heart failure present
Indications
AbsolutePa O2 ≤55 mm Hg or Sa O2 ≤88%
In patients with cor pulmonale Pa O2 55–59 mm Hg or Sa O2 ≥89%
ECG evidence of P pulmonale, hematocrit >55%, and CHD
Specific IndicationsNocturnal hypoxemia
Sleep apnea with nocturnal desaturation not corrected by constant positive airway pressure or bilevel positive airway pressureNo hypoxemia at rest, but desaturation during exercise or sleep (PaO2 <55 mm Hg)
Treatment Goals
Pa O2 ≥60 mm Hg or Sa O2 ≥90%; Appropriately adjusted O2 dose during sleep and exercise
Same as above
Appropriately adjusted O2 dose during sleep
Long-Term Oxygen Therapy: Guidelines
Appropriately adjusted O2 dose during sleep
Same as above
Effects of Tiotropium Day 1 and Day 92
0.85
0.90
0.95
1.00
1.05
1.10
1.15
1.20
1.25
1.30
1.35
-1 -0.5 0 0.5 1 1.5 2 2.5 3
Day 1Day 92 Tiotropium (N = 276)
Placebo (N = 188)FE
V1 (
L)
Hours following drug administration
Casaburi R, et al. Chest. 2000;118:1294–1302.
Salmeterol/Fluticasone Combination Change From Baseline Pre-Dose FEV1
Time (weeks)* P <0.05 vs. placebo; † P <0.05 vs. SAL; ‡ P <0.05 vs. FPData on file, GlaxoSmithKline.
350
300
250
200
150
100
50
0
-500 2 4 6 8 12 16 20 24 EP
FE
V1 (
mL
)
*†‡
*†‡
***
PBO SAL50 FP250 SAL50/FP250 FP500 SAL50/FP500
Serial FEV1
Day 1 Baseline FEV1
FSC- 1.31L IP/ALB- 1.26L
050
100150200250300
1 2 3 4 5 6
Time (hrs)
Cha
nge
in F
EV
1 (m
L)
-500
50100150200250300
1 2 3 4 5 6
Time (hrs)C
hang
e in
FE
V1
(mL)
FSC
IP/ALB
1 2 3 4 5 6
Day 1 Week 8
††*
* *
†
†FSC vs. IP/ALB: p<0.001
* IP/ALB vs FSC p 0.002
110
- 4
Predose FEV1
-20
0
20
40
60
80
100
120
140
160
Ch
ang
e in
Pre
do
se F
EV
1 (m
L)
FSC
IP/ALB
Endpoint
* p<0.001 vs. IP/ALB
*
0
* *
Week 8Week 1
*
Week 4
Acute Exacerbations of COPD (AECOPD)
Common during winter months
Symptoms Breathlessness Wheeze Cough Increased sputum production
Causes Viral infection (e.g., rhinovirus) Environmental causes (including smoking) Allergy Bacterial infection
Most Commonly IsolatedBacterial Pathogens
Haemophilus parainfluenzae
H influenzae
Streptococcus pneumoniae
Moraxella catarrhalis
Pseudomonas aeruginosa
Other gram-negative bacilli
Alpha-hemolytic streptococci
Adapted from Wilson R. Chest. 1995;108:53S–57S.
BaselineClinicalStatus
I. Acutetracheo-bronchitis
Criteria/Risk Factors
No underlying structuraldisease
Pathogens
Usuallyviral
Suggested Therapy
None; consider
macrolide or
tetracycline
AECOPD Proposed Classification of Patients
Viral Pathogens Associated With Acute COPD Exacerbations
RSV = respiratory syncytial virus.Sethi S. Infect Dis Clin Pract. 1998;7:S300–S308.
10%10%
18%20%
25%
35%
0
10
20
30
40
Influenza Parainfluenza Rhinovirus Coronavirus Adenovirus RSV
Pro
po
rtio
n o
f A
cute
V
ira
l Ex
ace
rbat
ion
s
AECOPDProposed Classification of Patients (cont’d)
* Possible beta-lactam resistance.
BaselineClinical Status
II. Simplechronicbronchitis
Criteria/Risk Factors
FEV1 >50% increasedsputum volume/
purulence
Pathogens
H influenzaeM catarrhalis
S pneumoniae*
Suggested Therapy
Amoxicillin
Adapted from Wilson R. Chest. 1995;108:53S–57S.
AECOPDProposed Classification of Patients (cont’d)
* Resistance to beta-lactams common.
BaselineClinical Status
III. Complicatedchronicbronchitis
Criteria/Risk Factors
As for Class II +
any one of:FEV1 <50%,
advanced age,≥4 exacerbations/yr,
significant co-morbidity
Pathogens
H influenzaeM catarrhalis
S pneumoniae*
Suggested Therapy
Quinolone
Penicillin + -lactamase
inhibitor
2nd- or 3rd-gen. cephalosporin
2nd-gen. macrolide
Adapted from Wilson R. Chest. 1995;108:53S–57S.
AECOPDProposed Classification of Patients (cont’d)
BaselineClinical Status
IV. Chronicbronchialinfection
Criteria/Risk Factors
Class III +continuous
sputum throughout
the year
Pathogens
H influenzaeM catarrhalis
S pneumoniaeEnterobacteriae spp
P aeruginosa
Suggested Therapy
Quinolone
Adapted from Wilson R. Chest. 1995;108:53S–57S.
“The Downward Spiral”
COPD
Airwayobstruction
Exacerbation
Mucushypersecretion
Continuedsmoking
Lunginflammation
Alveolardestruction
Impairedmucus clearance
Submucosal glandhypertrophy
Exacerbation
Exacerbation
Hypoxemia
DEATH
Asthma Management
4
Severe
Continual daytime/frequent nocturnal symptoms
60%
30%
LABA + high-dose ICS
Consider LTM
corticosteroids as needed (taper to lowest dose)
3
Moderate
Daily/Nocturnal symptoms 1 per week
60% 80%
>30%
LABA + low to moderate dose ICS
2
Mild
Persistent
>2 x per week but <1 time day/Nocturnal symptoms
>2 nights/month
≥ 80%
20-30%
Low-dose ICS
1
Mild
Intermittent
< 2 days per week/Nocturnal symptoms < 2 nights per month
≥ 80%
<20%
PRN SABA
Step SymptomsDay/Night
FEV1 & PEF (% predicted)PEF variability
Medication
Importance of early treatment with inhaled corticosteroids in asthma
0
2
4
6
8
10
12
<2 2-3 3-5 >5 An
nu
al c
han
ge in
FE
V1%
pre
d
Agertoft & Pedersen. Respir Med 1994; 88:373-81
Years that symptoms started before treatment
Relative Risk of Hospitalization in the United States
Donahue et al. JAMA. 1997;277:887-891.
Prescriptions per Person-Year
RelativeRisk
None 1-2 2-3 3-5 5-8 8+0-1
2-Agonists
Total
ICS
0
1
2
3
4
5
6
7
8
Age 0-17
Age 18-44
Age 45+
TotalAge 0-17
Age 18-44
Age 45+
No. of Canisters of Inhaled Corticosteroids per Yr.
Rat
e R
atio
fo
r D
eath
fr
om
Ast
hm
a
Low-dose ICS and the Prevention of Death from Asthma
Suissa S et al. N Engl J Med. 2000;343:332-336.
2.5
2.0
1.5
1.0
0.5
0.0 1 2 3 4 5 6 7 8 9 1011 12
•ICS protects patients from asthma-related deaths•Users of > 6 canisters/yr. Had a death rate ~ 50% lower than non-users of ICS•Death rate decreased by 21% for each additional ICS canister used during the previous year.
Placebo Montelukast sodium Beclomethasone
Weeks in active treatment
0 3 6 9 12 15
0
5
10
15
Mea
n c
han
ge
in F
EV
1 (%
)
Washout
*P < 0.01 beclomethasone vs montelukast and placebo.†P < 0.001 vs placebo.
*
†
Beclomethasone Comparison Study: FEV1
Malmstrom K, et al. Ann Intern Med. 1999;130:487-495.
Wolfe et al.ClinTher. 1996; 18: 635-646.
PlaceboFP 88 mcg b.i.d. FP 220 mcg b.i.d. FP 440 mcg b.i.d.
30
25
20
15
10
5
0
-5
-10
-15
-200 2 4 6 8 10 12 Endpoint
Week
*p<0.001 vs placebo
***
Mea
n %
Chan
ge
in F
EV
1
Patients Previously Receiving Daily Inhaled Corticosteroids-Mean Percentage Change From
Baseline in FEV1 Prior to AM Dose
Patients Treated With ADVAIR™ Diskus® 250/50 Had a Significantly Greater Improvement in FEV1
Me
an
i
n F
EV
1 fr
om
Ba
se
lin
e (
%)
*Differs from FP 250, salmeterol 50, placebo at endpoint; P 0.003Doses in mcg b.i.d.
Shapiro G, et al. Am J Respir Crit Care Med. 2000;161:527-534.
30
25
20
15
10
5
0
-5
EndpointWeek
-5% [-0.11L]
ADVAIR 250/50FP 250Salmeterol 50Placebo
23% [0.48L]
*13% [0.25L]
4% [0.05L]
2 4 6 8 10 12
Patients Treated With ADVAIR™ Diskus® 250/50 Were Less Likely to be Withdrawn for Worsening Asthma
*Differs from FP 250, salmeterol 50, placebo; P 0.002 Doses in mcg b.i.d.
Shapiro G, et al. Am J Respir Crit Care Med. 2000;161:527-534.
1.0
0.8
0.6
0.4
0.2
00 7 14 21 28 35 42 49 56 63 70 77 84
Study Day
Placebo
FP 250ADVAIR 250/50
Salmeterol 50
Pro
bab
ility
of
Rem
ain
ing
in S
tud
y
4%4%* *
22%22%
38%38%
62%62%
Anti-IgE
Monoclonal Ab to IgE
Reduces circ. IgE, # of IgE receptors on basophils & Reduces early & late phase response
Ag stimulated histamine release, bronchial rxt, & sputum eosinophilia
Reduces exacerbation rate while allowing steroid withdrawal
Asthma & COPD Summary
Both disorders of airways obstruction
Both inflammatory
COPD is progressive
1st line therapy for asthma are ICS
1st line therapy for COPD are BD
Attend to comorbidities