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Penyakit yg ditandai :

Hambatan aliran udara Tidak reversibel/reversibel parsial

Progresif

Respons inflamasi abnormal paru

Partikel noxiuos atau gas

A leading cause of morbidity & mortality worldwide

Penyebab kematian ke 4 di USA dan Eropa

Biaya pengobatan PPOK > asma


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PenyebabFaktor risiko

Host Lingkungan

-Genetik:defisiensi 1antitripsin

-Airway hyperreactivity

- Rokok sigaret- Occupational dust

dan chemical- Polusi indoor,outdoor- Infeksi sal napas


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Future

COPD case

Future

asthmatic

Future COPD if

smoker


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LUNG INFLAMMATION

NOXIOUS

PARTICLEGASES

OXIDATIVE STRESS PROTEINASE IMBALANCE

HOST FACTORS

ANTI OXIDANTS[ environmental ]

ANTI OXIDANTS

ANTI PROTEINASES

[ genetic ]

REPAIR

MECHANISM

RE

PAIR

MECHANISM

PATHOGENESIS OF COPD

ANTI PROTEASE ENZYME1-Antitrypsin


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Bronchus

Alveoli

Bronchiole


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Diagnosis of COPD is based

on a history of exposure to risk factors

and the presence of airf low limitation

that is not fully reversible,

with or without the presence of symptoms.


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SYMPTOMS :

CoughSputumDyspnea

EXPOSURE TO RISK FACTORS :

Tobacco SmokeOccupationIndoor / outdoor pollution

1 2

DIAGNOSIS

OF COPD

SPIROMETRY

3


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Spirometry in COPD Diagnosis

0

5

1

4

2

3

Liter

1 65432

FVC

FVC

FEV1

FEV1

Normal

COPD

3.900

5.200

2.350

4.150 80 %

60 %

Normal

COPD

FVCFEV1 FVCFEV1/

Seconds


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Asia Pacific COPD Roundtable Group 2002

Where there is no access to spirometry, thediagnosis of COPD should be based on :

symptoms, physical signs, and history


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A CXRs are seldom diagnostic it can be useful for excluding other diseases


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GOLD Workshop Report

Four components of COPD management

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

Education

Pharmacologic

Non-pharmacologic

4. Manage exacerbations


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COPD management

Established diagnosis

Asses symptoms

Stop smoking

Healthy lifestyle

Immunization

Treat obstruction BRONCHODILATORS

Assess hypoxemia

Pulmonary rehabilitation program

Long-term oxygen therapy


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Acute Excacerbation of COPD : COPD Guideline Algorithm

PEFR : peak expiratory flow rate,CXR : chest X-ray,NPPV : noninvasive positive pressure ventilationCOPD : chronic obstructive pulmonary disease.AECOPD : acute excacerbation of COPD,URI : upper respiratory infection.O2 : oxygen therapyPRN : as needed

1.

Use anticholinergic bronchodilators first, once at maximum dose, thenadd b 2agonists bronchodilators.2.Dosing regimen used in the SCCOPE trial : 3 days intravenous

Methylprednisolone, 125 mg every 6 hours followed by oral Prednisone,tapper to complete the 2 week course (60mg/day on days 4-7,40 mg/day on days 8-11, and 20 mg/day on days 12-15).

3.NPPV should be administered under the supervision of the traited physician4.Use narrow spectrum antibiotics ; the agent favored in the trials were

Amoxicillin and trimethopin-sulfamethoxazole, and tetracycline.

Increase in

symptoms from baseline

Stable COPD

patients

Patient presentsat ER or hospital

Examine patient for three

Diagnostic criteria for AECOPD :

1.Increase in dyspnea

2.Increase in sputum volume

3.Increase in sputum purulence

Consider other diagnosis

Management :1.CXR2. Inhaled bronchodilators (1)

3.Systemic corticosteroids (2)

4.O2PRN

5.NPPV PRN (3)

Criteria present ?

One or more

criteria present ?

Two or more

diagnostic

criteria present ?

Three criteria :

treat for severe

excacerbation

Management :

1. CXR

2. Inhaled bronchodilators (1)

Further Considerations

for Diagnosis.There is no evidence for using

The following for diagnosis or as

Indicators of severity of AECOPD:

1. Acute spirometry

2. Acute PEFR

3. Pulse oximetry

Further Considerations

for Management.The following are not useful in

the management of AECOPD :

1.Methylxanthine bronchodilators

2.Chest physiotherapy.

3.Mucolytics.

4.Inhaled steroids.

None of 3 diagnostic criteria present

One diagnostic criterion with at least one of the following ?

1. URI in the past 5 days.

2. Fever without apparent cause.

3. Increased wheezing

4. Increased cough

5. 20 % increase in heart rate or respyratory rate over baseline

Consider other diagnosis

Two criteria only :

treat for moderate

excacerbation

Yes.

Treat for mild excacerbation

of COPD

one only

yes

no

two only

two or more

three

no

yes

Management :1.CXR2. Inhaled bronchodilators (1)

3.Systemic corticosteroids (2)

4.Antibiotics (4)

5.O2PRN6.NPPV PRN (3)


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Components of management of Stable COPD (GOLD)

1. Asses and Monitor Disease Perform spirometry in patients who have chronic cough and dyspnea

with history of exposure to risk factors.Diagnose by spirometry.

COPD defined as FEV1/FVC < 70 % and a post bronchodilator FEV1 < 80 %Arterial blood gases if FEV1 < 40 % predicted or signs of respiratory

failure or right heart failure. Monitor disease progresion.

2. Reduce risk factors exposure to tobacco smoke, occupational dustsand chemicals, and indoor and outdoor pollutants.


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Components of management of Stable COPD (GOLD)

3. Therapy Bronchodilator therapy for symptom management, inhaled therapy preferred The choice between b2 agonists, anticholinergics, and theophylline therapy

depends on availability and individual response in symptom relief and sideeffects.

Prescribe on as-needed basis or on regular basis. Long-acting bronchodilators are ore convenient.Combining drugs with differents mechanisms and duration of action might

increase the degree of bronchodilation for equivalent or lesser side effects.A combination of short action b2 agonists and the anticholinergics drugipratropium in stable COPD produced greater and more sustainedimprovements in FEV1 than either alone and does not produce evidence oftachyphylaxis over 90 days treatment.

In moderately severe (IIIA) patients, inhaled glucocorticosteroids, if significant

symptoms and lung fuction response; and in II B and III, if symptoms, lungfunction response, or repeted exacerbations.

4. Manage excacerbation (see above)


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Defenition of Excacerbation of COPD

Acute excacerbation

of COPD :

3 cardinal symptoms:

worsening of

dyspnea,

increase of sputum

purulence,

increase of sputum

volume.

mild moderate severe

1 of 3 cardinal symptoms, as well as 1 of

the following :

Upper respiratory infection in past 5 days,

fever without apparent cause,

increase wheezing,

increase cough,

increase in respiratory rate or heart rate

by 20 % above baseline.

2 of 3

cardinal

symptoms

All 3

cardinal

symptoms


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Acute Exacerbations

Chronic obstructive pulmonary disease(COPD) is characterized by chronic

airflow obstruction with acuteexcacerbation (dyspnea, cough, andsputum production). Acuteexacerbation may be triggered bytracheobronchial infections orenvironmental exposure.

Nearly half of patients discharged fromhospital after acute excacerbations arereadmitted more than once within 6months.

Identifying patients at high risk for

relapse should help guide decisionsabout hospital admission and follow-upappointments.

Inhaled bronchodilators andsystemic corticosteroids arerecommended for acuteexcacerbations of COPD. Systemiccorticosteroids should not be usedfor more than 2 weeks.

Appropriate use of antibiotics in

acute excacerbations of COPD isimperative to help control theemergence of multidrug-resistantorganisms.


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Recommendations

Acute Excacerbations

1. An admission chest radiography may be useful since it hasbeen shown that up to 23 % of patients admitted had changesin management related to findings on chest radiography.

Chest radiography in patients visiting the emergencydepartment may also be useful. To date, there is no evidencefor or against the utility of chest radiography in the officesetting.

2. For patients hospitalized with an acute excacerbation ofCOPD, acute spirometry should not be used to diagnose anexcacerbation or to asses its severity.


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RecommendationsAcute Excacerbations

3. Inhaled anticholinergic bronchodilators or inhaled short acting b2agonists are beneficial in the treatment of patients presenting to thehospital with acute excacerbation of COPD. Since inhaledanticholinergic bronchodilators have fewer and more benign sideeffects, consider these agen first. Only after the initial

bronchodilator is at maximum dose is the addition of a secondinhaled bronchodilator beneficial.

4. In the treatment of patients presenting to the hospital withmoderate or severe acute excacerbation of COPD, the followingtheurapeutic option are beneficial :

(a). systemic corticosteroids given for up to 2 weeks in patientswho are not receiving long-term therapy with oral steroids,(b). NPPV administered under the supervision of a trained

physician,(c). oxygen, with caution, in hypoxemic patients.


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Recommendations

Acute Excacerbations5. In patients with severe excacerbation of COPD, initial

narrow spectrum antibiotics are reasenable first line agents.The superiority of newer, more broad spectrum antibioticshas not been established.

6. In the treatment of patients with acute excacerbation ofCOPD, the following therapeutic optionsare not beneficial : mucolitic medications,

chest physiotherapy, andmethyl xanthine bronchodilators.

The latter 2 options may be harmful.

7. Currently, there are no reliable methods of riskstratification for relapse or in patient mortality.


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Therapy at each stage of COPD (GOLD)

Stage Characteristic Recommended treatment

AllAvoidance of risk factors,

Infuenza vaccination,Exercise, Patient education.

O : at riskChronic symptoms (cough, sputum)Exposure to risk factorsNormal spirometry

I : mild

COPD

FEV1 / FVC < 70 %FEV1 80 % predictedWith or without symptoms

Short acting bronchodilator when needed

II :

moderate

COPD

II AFEV1 / FVC < 70 %50%50% predictWith or without symptoms

Regular treatment with one or more

bronchodilators.

Rehabilitation

Regular treatment with one or more

bronchodilators.

Rehabilitation

Inhaled glucocortico steroids ifsignificant symptoms and lungfunction response.

Inhaled glucocortico steroids ifsignificant symptoms and lungfunction response, or ifrepeated excacerbations.

III :

severe

COPD

FEV1 / FVC < 70 %FEV1


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Sympatomimetic bronchodilators

DrugAdrenergic

Receptoractivity

Route ofadministration

Usual adult dose Maximumrecommended

daily dose

SHORT ACTING

AlbuterolTablets : 2 mg, 4 mg (Proventil, ventolin, generics)Tablets, extended release : 4 mg (proventil),8 mg (Volmax)Syrup : 2 mg / 5 ml ( Proventil, Ventolin)

MDI : 80 mg / actuation (Proventil HVA, Ventolin)Solution for inhalation : 0,083 % (0,83 mg/ml),

0,5%(5mg/ml) Ventolin,Capsules for inhalation::200 mg/ml (Ventolin rotocaps)

b < b2POPOPO

InhInh

Inh

2 or 4 mg tid or qid4 - 8 mg q 12 h2or 4 mg tid or qid 3

1 - 2 inh q 4 - 6h2.5mg tid or qid by nebulization over 5-15 minutes.Note: 0.5% solution must be diluted to total 3 ml volume withsteril normal saline before nebulization.200 mcg inh q 4 to 6h using Rotohaler device 4

32 mg in DD16 mg q 12h8 mg qid

BitolterolMDI : 0,8%. 0,37mg/actuation (Tornalate)Solution for inhalation : 0,2% (Tornalate)

b1 < b2InhInh

2 inh tid0.5 - 1 ml (1-2 mg) tid by intermittent flow nebulization

-3 inh q 6h or 2Inh q 6h.

-8 mg (intermitten flow).

-14 mg (continous flow).

EpinephrineSolution for inhalation:

1:100 and 1:1000 (Adrenalin)Solution for inhalation: 2,25 % racepinephrineHCl (equivalento 1,125% epinephrine base), (Asthma Nephrin, Micro Nephrin)

b b2Inh

Inh

8-10 drops added to nebulizer.Administer 1-3 inh 4-6 times daily(3hr intervals) (hand pump

nebulizer).Add 0.5ml (10 drops) to 3ml diluent4 or 0.2 - 0.4 ml ( 4 - 8drops) of MicroNefrin to 4.6 to 4.8 ml water.1 Administer for15 min. q 3 - 4 h.

IsoproterenolSolution for inhalation:0,5%(1:200), 1%(1:100) (Isuprel).

MDI:0.25%, 103 mcg/dose (Isuprel), 80 mcg/actuation (Medihaler)

b b2 InhInh

5 -15 deep inh using 1:200 solution in handbulb nebulizer.0.5ml of 1:200 diluted to 2-2.5ml by nebulizer or IPPB; mayrepeat 5 times daily.1-2 Inh 6-8 times daily (q 3-4h)

Levalbuterol HCl. Solution for inhalation 0.63mg/3ml and 1.25/3ml Inh 0.63 -1.25 mg tid (every 6-8h) by nebulization

MetaproterenolTablets : 10 mg, 20 mgSyrup : 10 mg / 5 ml (Alupent)MDI : 75mg and 150 mg (0,68 mg / actuation) (Alupent)

Solution for inhalation 0.4%, 0.6%, 5% (Alupen)

b1 < b2PO

Inh

Inh

20 mg tid or qid6

2-3 inh q 3-4h

0.2-0.3 ml (5% sol) diluted to 2.5ml with diluent, given byIPPB device, 3-4 time daily (4h)

12 inh

Pirbuterol.MDI: 0.2 mg / actuation (Maxair) b1 < b2 Inh 2 inh (0.4 mg) q 4-6h 12 inh

Terbutaline.Tablets: 2.5mg, 5mgMDI : O2mg / actuationInjection : 1 mg / ml

b1 < b2 POInhSC

1 tablet (5 mg) tid during waking hours (6 h intervals) 52 Inh q 4-6h0,25 mg in lateral deltoid ; may repeat every 15-30 min.If clinical improvement does not occur.

15 mg

0.5 mg in 4 h

LONG ACTING

Salmeterol.MDI 21 mcg/actuation (Serevent)Inhalation powder : 50 mcg (Serevent diskus)

b1 < b2 InhInh

2 Inh (42 mcg) twice daily (q 12 h)1 Inh (50 mcg) twice daily (q 12 h)

DD= devided dose Inh= inhalation IPPB= inntermittent positive pressure breathing MDI= metered dose inhalaler1.Dose for adult and children 12 years unless otherwise noted. 2.Dose for asthma/bronchospasm listed when spesific dosing recommendations for bronchoospasm associated with COPDnot available. 3Adults and children >14 years. 4Adults and children > 14 years. 5Adult and children > 15 years. 6Adult and children > 9 years or > 60 lb.


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Anticholinergic and anticholinergic combination bronchodilator

DrugRoute of

administration

Usual

adult dosage

Maximum

daily dose

Ipratropium bromide

MDI : 18 mcg / actuation (Atroven).

Solution for inhalation : 0,02 % (Atroven, various)

Inh

- 2 Inh qid.

- 500 mcg tid

to qid by

nebulizer.

12 Inh.

Ipratropium bromide and albuterolsulfate

MDI : 18 mcg / Ipratropium.

103 mcg albuterol / actuation (Combivent).

inh 2 Inh qid. 12 Inh.

MDI = metered dose inhaler,

Inh = inhalation.


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INHALED CORTICOSTEROID

DrugAdult dosing

Starting Maximum

Beclomethasone(Beclovent, Vanceril)

MDI:42 mcg/actuation84 mcg/actuation

(Vanceril Double Strength)

84mcg 3-4 times daily

or168 mcg twice daily

840 mcg

in divided doses

Budesonide(Pulmicort Turbohaler)DPI: 200mcg/actuation

200-400 mcg twice daily1

200-400 mcg twice daily2400-800 mcg twice daily3

400 mcg twice daily1

800 mcg twice daily2,3

Flunisolide(AeroBid, AeroBid-M)

MDI : 250 mcg/actuation

500 mcg (2 inhalations)

twice daily.

1 mcg (4 inhalations)

twice daily.

FluticasoneMDI (Flovent): 44, 110, and

220 mcg/actuationDPI (Flovent Rotadisk): 50, 100, and

250 mcg/actuation.

MDI: 88 mcg twice daily1

: 88-220 mcg twice daily2

: 880 mcg twice daily3

DPI: 100 mcg twice daily1

:100-200 mcg twice daily2


MDI: 440 mcg twice daily1,2


DPI: 500 mcg twice daily1,2

:1000 mcg twice daily3

Triamcinolone acetonide(Azmacort)MDI : 100 mcg/actuation

(60 mg as acetonide)

200 mcg 3-4 times dailyor

400 mcg twice daily

1600 mcgin divided doses

DPI = dry powder inhaler MDI = metered dose inhaler.1Used with inhaled bronchodilators only. 2Used with inhaled corticosteroids.3For patients currently receiving chronic oral corticosteroid therapy.


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Current best available pharmacologic therapy for COPD

Long-acting beta-2+ Inhaled corticosteroidcombination (LABACS)

New anticholinergic Tiotropium bromide.

bring new hope for patients with COPD, for whom?


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Management (GOLD)

1. Bronchodilator medications are central to the

symptomatic management of COPD. They are given onan as-needed basis or on a regular basis to prevent orreduce symptoms.

2. The principal bronchodilator treatment are b2 agonists,anti cholinergics theophylline, and a combination of oneor more of these drugs. Long- acting inhaledbronchodilators are more convinient.

3. Combining bronchodilators may improve efficacy and

decrease the risk of side effects compared to increasingthe dose of a single bronchodilator.


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Why doctors are reluctant to treat COPD?

Stop smoking is difficult

No currently available drugs slow progression

Corticosteroids are in effective

Slow progressive destruction process

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