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)


Stage I: Mild

Diagnosis

FEV1 >80% predicted

FEV1/FVC <70%

With/without symptoms

Treatment Avoid risk factors

Short-acting bronchodilator PRN

Stage II: Moderate


Diagnosis

50% FEV1 <80% predicted

FEV1/FVC <70%


Treatment

Avoid risk factors

Regular therapy with 1 bronchodilators

Inhaled corticosteroids if significant symptoms and lung function response

Rehabilitation

Stage III:Severe


Diagnosis 30% FEV1 < 50%

predicted

FEV1/FVC < 70%


Treatment Avoid risk factors


Rehabilitation

Inhaled corticosteroids if significant symptoms and lung function response or if repeated exacerbations

Stage IV: Very Severe


Diagnosis

FEV1 < 30% predicted

FEV1/FVC < 70%

Respiratory failure

Right-side-of-the-heart failure

Treatment

Avoid risk factors


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


FEV1 >50% increasedsputum volume/

purulence

Pathogens

H influenzaeM catarrhalis

S pneumoniae*

Suggested Therapy

Amoxicillin



* Resistance to beta-lactams common.


III. Complicatedchronicbronchitis


As for Class II +

any one of:FEV1 <50%,

advanced age,≥4 exacerbations/yr,

significant co-morbidity

Pathogens


S pneumoniae*

Suggested Therapy

Quinolone

Penicillin + -lactamase

inhibitor

2nd- or 3rd-gen. cephalosporin

2nd-gen. macrolide




IV. Chronicbronchialinfection


Class III +continuous

sputum throughout

the year

Pathogens


S pneumoniaeEnterobacteriae spp

P aeruginosa

Suggested Therapy

Quinolone


“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

Management Of Copd & Asthma

Health & Medicine

Transcript of Management Of Copd & Asthma