Chronic Obstructive Pulmonary Disease

Mulyadi
Pulmonology Dept.
Faculty of MedicineSyiah Kuala University
Dr. Zainoel Abidin General Hospital
Banda Aceh
 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
 Penyebab
Faktor risiko
Host Lingkungan

-Genetik: - Rokok sigaret

defisiensi α 1 antitripsin - Occupational dust
-Airway hyperreactivity dan chemical
- Polusi indoor,outdoor
- Infeksi sal napas
 Future
COPD case

Future
asthmatic

Future COPD if
smoker
 PATHOGENESIS OF COPD
PARTICLE
NOXIOUS GASES

HOST FACTORS
ANTI OXIDANTS
[ environmental ]

LUNG INFLAMMATION

ANTI OXIDANTS ANTI PROTEINASES

[ genetic ]

OXIDATIVE STRESS PROTEINASE IMBALANCE

REPAIR REPAIR
MECHANISM MECHANISM

ANTI PROTEASE ENZYME

1-Antitrypsin
Bronchus

Bronchiole

Alveoli
Diagnosis of COPD is based
on a history of exposure to risk factors
and the presence of airflow limitation
that is not fully reversible,
with or without the presence of symptoms.
 DIAGNOSIS
OF COPD

1 2

SYMPTOMS : EXPOSURE TO RISK FACTORS :

• Cough • Tobacco Smoke
• Sputum • Occupation
• Dyspnea • Indoor / outdoor pollution

SPIROMETRY
 Spirometry in COPD Diagnosis
0
FEV1 FVC FEV1/ FVC
Normal 4.150 5.200 80 %
1 COPD 2.350 3.900 60 %

2
FEV1
Liter

3
COPD
4 FVC
FEV1

5 Normal
FVC
1 2 3 4 5 6 Seconds
Asia Pacific COPD Roundtable Group 2002
 Where there is no access to spirometry, the
diagnosis of COPD should be based on :
symptoms, physical signs, and history
A CXRs are seldom diagnostic, it can be useful for excluding other diseases
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
COPD management

• Stop smoking
Established diagnosis
• Healthy lifestyle
Asses symptoms
• Immunization

Treat obstruction BRONCHODILATORS

Assess hypoxemia Long-term oxygen therapy

Pulmonary rehabilitation program

 Acute Excacerbation of COPD : COPD Guideline Algorithm
Stable COPD
patients
Increase in
symptoms from baseline
Patient presents
at 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
no
Criteria present ?
Further Considerations
for Diagnosis.
PEFR : peak expiratory flow rate, There is no evidence for using
CXR : chest X-ray, The following for diagnosis or as
NPPV : noninvasive positive pressure ventilation
COPD : chronic obstructive pulmonary disease. Indicators of severity of AECOPD:
AECOPD : acute excacerbation of COPD, 1. Acute spirometry
URI : upper respiratory infection. 2. Acute PEFR
O2 : oxygen therapy
PRN : as needed 3. Pulse oximetry
1. Use anticholinergic bronchodilators first, once at maximum dose, then
add b 2 agonists bronchodilators.
2. Dosing regimen used in the SCCOPE trial : 3 days intravenous Further Considerations
Methylprednisolone, 125 mg every 6 hours followed by oral Prednisone, for Management.
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). The following are not useful in
3. NPPV should be administered under the supervision of the traited physician the management of AECOPD :
4. Use narrow spectrum antibiotics ; the agent favored in the trials were
1.Methylxanthine bronchodilators
Amoxicillin and trimethopin-sulfamethoxazole, and tetracycline. 2.Chest physiotherapy.
3.Mucolytics.
4.Inhaled steroids.
Consider other diagnosis
None of 3 diagnostic criteria present

yes
One diagnostic criterion with at least one of the following ?
One or more one only 1. URI in the past 5 days.
criteria present ? 2. Fever without apparent cause. no Consider other diagnosis
3. Increased wheezing
two or more
4. Increased cough
5. 20 % increase in heart rate or respyratory rate over baseline
Two or more two only
diagnostic
criteria present ? yes
three
Three criteria : Two criteria only : Yes.
treat for severe treat for moderate Treat for mild excacerbation
excacerbation excacerbation of COPD

Management : Management :
1.CXR 1.CXR
2. Inhaled bronchodilators (1) 2. Inhaled bronchodilators (1) Management :
3.Systemic corticosteroids (2) 3.Systemic corticosteroids (2) 1. CXR
4.Antibiotics (4) 4.O2 PRN 2. Inhaled bronchodilators (1)
5.O2 PRN 5.NPPV PRN (3)
6.NPPV PRN (3)
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 dusts

and chemicals, and indoor and outdoor pollutants.
Components of management of Stable COPD (GOLD)
3. Therapy
● Bronchodilator therapy for symptom management, inhaled therapy preferred
● The choice between b 2 agonists, anticholinergics, and theophylline therapy
depends on availability and individual response in symptom relief and side
effects.
● 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 b 2 agonists and the anticholinergics drug
ipratropium in stable COPD produced greater and more sustained
improvements in FEV1 than either alone and does not produce evidence of
tachyphylaxis 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, lung
function response, or repeted exacerbations.

4. Manage excacerbation (see above)

 Defenition of Excacerbation of COPD

mild moderate severe

Acute excacerbation
of COPD :
3 cardinal symptoms: 1 of 3 cardinal symptoms, as well as 1 of 2 of 3 All 3
worsening of the following : cardinal cardinal
 dyspnea, • Upper respiratory infection in past 5 days, symptoms symptoms
 increase of sputum • fever without apparent cause,
purulence, • increase wheezing,
 increase of sputum • increase cough,
volume. • increase in respiratory rate or heart rate
by 20 % above baseline.
Acute Exacerbations
■ Chronic obstructive pulmonary disease ■ Inhaled bronchodilators and
(COPD) is characterized by chronic systemic corticosteroids are
airflow obstruction with acute recommended for acute
excacerbation (dyspnea, cough, and excacerbations of COPD. Systemic
sputum production). Acute corticosteroids should not be used
exacerbation may be triggered by for more than 2 weeks.
tracheobronchial infections or ■ Appropriate use of antibiotics in
environmental exposure. acute excacerbations of COPD is
■ Nearly half of patients discharged from imperative to help control the
hospital after acute excacerbations are emergence of multidrug-resistant
readmitted more than once within 6 organisms.
months.
Identifying patients at high risk for
relapse should help guide decisions
about hospital admission and follow-up
appointments.
Recommendations
Acute Excacerbations

1. An admission chest radiography may be useful since it has

been shown that up to 23 % of patients admitted had changes
in management related to findings on chest radiography.
Chest radiography in patients visiting the emergency
department may also be useful. To date, there is no evidence
for or against the utility of chest radiography in the office
setting.

2. For patients hospitalized with an acute excacerbation of

COPD, acute spirometry should not be used to diagnose an
excacerbation or to asses its severity.
 Recommendations
Acute Excacerbations

3. Inhaled anticholinergic bronchodilators or inhaled short acting b2

agonists are beneficial in the treatment of patients presenting to the
hospital with acute excacerbation of COPD. Since inhaled
anticholinergic bronchodilators have fewer and more benign side
effects, consider these agen first. Only after the initial
bronchodilator is at maximum dose is the addition of a second
inhaled bronchodilator beneficial.

4. In the treatment of patients presenting to the hospital with

moderate or severe acute excacerbation of COPD, the following
theurapeutic option are beneficial :
(a). systemic corticosteroids given for up to 2 weeks in patients
who 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.
 Recommendations
Acute Excacerbations
5. In patients with severe excacerbation of COPD, initial
narrow spectrum antibiotics are reasenable first line agents.
The superiority of newer, more broad spectrum antibiotics
has not been established.

6. In the treatment of patients with acute excacerbation of

COPD, the following therapeutic options
are not beneficial : mucolitic medications,
chest physiotherapy, and
methyl xanthine bronchodilators.
The latter 2 options may be harmful.

7. Currently, there are no reliable methods of risk

stratification for relapse or in patient mortality.
 Therapy at each stage of COPD (GOLD)
Stage Characteristic Recommended treatment

Avoidance of risk factors,

All Infuenza vaccination,
Exercise, Patient education.
Chronic symptoms (cough, sputum)
O : at risk Exposure to risk factors
Normal spirometry

I : mild FEV1 / FVC < 70 % Short acting bronchodilator when needed

FEV1 ≥ 80 % predicted
COPD
With or without symptoms
II A Regular treatment with one or more Inhaled glucocortico steroids if
FEV1 / FVC < 70 % significant symptoms and lung
bronchodilators. function response.
50%<FEV1< 80% predict
II : With or without symptoms Rehabilitation
moderate II B
COPD FEV1 / FVC < 70 % Regular treatment with one or more Inhaled glucocortico steroids if
significant symptoms and lung
30% ≤FEV1>50% predict bronchodilators. function response, or if
With or without symptoms repeated excacerbations.
Rehabilitation

Regular treatment with one or more

bronchodilators.
FEV1 / FVC < 70 % Inhaled glucocortico steroids if
III : FEV1<30% predicted or significant symptoms and lung function
response, or if repeated excacerbations.
severe presence of respiratory Treatment of complications.
COPD failure or right heart failure. Rehabilitation
Long term oxygen therapy if respiratory
failure.
Consider surgical treatment.
 Sympatomimetic bronchodilators
Adrenergic Route of Usual adult dose Maximum
Drug Receptor adminis recommended
activity tration daily dose

SHORT ACTING
Albuterol b1 < b2
Tablets : 2 mg, 4 mg (Proventil, ventolin, generics) PO 2 or 4 mg tid or qid 32 mg in DD
Tablets, extended release : 4 mg (proventil), 8 mg (Volmax) PO 4 - 8 mg q 12 h 16 mg q 12h
Syrup : 2 mg / 5 ml ( Proventil, Ventolin) PO 2or 4 mg tid or qid 3 8 mg qid
MDI : 80 mg / actuation (Proventil HVA, Ventolin) Inh 1 - 2 inh q 4 - 6h
Solution for inhalation : 0,083 % (0,83 mg/ml), Inh 2.5mg tid or qid by nebulization over 5-15 minutes.
0,5%(5mg/ml) Ventolin, Note: 0.5% solution must be diluted to total 3 ml volume with
Capsules for inhalation::200 mg/ml (Ventolin rotocaps) Inh steril normal saline before nebulization.
200 mcg inh q 4 to 6h using Rotohaler device 4
Bitolterol b1 < b2 -3 inh q 6h or 2
MDI : 0,8%. 0,37mg/actuation (Tornalate) Inh 2 inh tid Inh q 6h.
Solution for inhalation : 0,2% (Tornalate) Inh 0.5 - 1 ml (1-2 mg) tid by intermittent flow nebulization -8 mg (intermit
ten flow).
-14 mg (contino
us flow).
Epinephrine  b1b2 8-10 drops added to nebulizer.
Solution for inhalation: Inh Administer 1-3 inh 4-6 times daily(≥3hr intervals) (hand pump
1:100 and 1:1000 (Adrenalin) nebulizer).
Solution for inhalation: 2,25 % racepinephrineHCl (equivalen Inh Add 0.5ml (≈10 drops) to 3ml diluent4 or 0.2 - 0.4 ml (≈ 4 - 8
to 1,125% epinephrine base), (Asthma Nephrin, Micro Nephrin) drops) of MicroNefrin to 4.6 to 4.8 ml water.1 Administer for
15 min. q 3 - 4 h.
Isoproterenol b1b2 Inh 5 -15 deep inh using 1:200 solution in handbulb nebulizer.
Solution for inhalation:0,5%(1:200), 1%(1:100) (Isuprel). 0.5ml of 1:200 diluted to 2-2.5ml by nebulizer or IPPB; may
repeat ≤ 5 times daily.
MDI:0.25%, 103 mcg/dose (Isuprel), 80 mcg/actuation (Medihaler) Inh 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

Metaproterenol b1 < b2
Tablets : 10 mg, 20 mg PO 20 mg tid or qid 6
Syrup : 10 mg / 5 ml (Alupent)
MDI : 75mg and 150 mg (0,68 mg / actuation) (Alupent) Inh 2-3 inh q 3-4h 12 inh
Solution for inhalation 0.4%, 0.6%, 5% (Alupen) Inh 0.2-0.3 ml (5% sol) diluted to 2.5ml with diluent, given by
IPPB device, 3-4 time daily (≥4h)
Pirbuterol. MDI: 0.2 mg / actuation (Maxair) b1 < b2 Inh 2 inh (0.4 mg) q 4-6h 12 inh
Terbutaline. Tablets: 2.5mg, 5mg PO 1 tablet (5 mg) tid during waking hours (6 h intervals) 5 15 mg
b1 < b2
MDI : O2mg / actuation Inh 2 Inh q 4-6h
Injection : 1 mg / ml SC 0,25 mg in lateral deltoid ; may repeat every 15-30 min. 0.5 mg in 4 h
If clinical improvement does not occur.

LONG ACTING
Salmeterol. MDI 21 mcg/actuation (Serevent) b1 < b2 Inh 2 Inh (42 mcg) twice daily (q 12 h)
Inhalation powder : 50 mcg (Serevent diskus) Inh 1 Inh (50 mcg) twice daily (q 12 h)

DD = devided dose Inh = inhalation IPPB = inntermittent positive pressure breathing MDI = metered dose inhalaler
1.Dose for adult and children ≥12 years unless otherwise noted. 2. Dose for asthma/bronchospasm listed when spesific dosing recommendations for bronchoospasm associated with COPD
not available. 3 Adults and children >14 years. 4 Adults and children > 14 years. 5 Adult and children > 15 years. 6 Adult and children > 9 years or > 60 lb.
 Anticholinergic and anticholinergic combination bronchodilator

Route of Usual Maximum

Drug
administration adult dosage daily dose

Ipratropium bromide - 2 Inh qid.

MDI : 18 mcg / actuation (Atroven). Inh - 500 mcg tid 12 Inh.
Solution for inhalation : 0,02 % (Atroven, various) to qid by
nebulizer.

Ipratropium bromide and albuterolsulfate

inh 2 Inh qid. 12 Inh.
MDI : 18 mcg / Ipratropium.
103 mcg albuterol / actuation (Combivent).

MDI = metered dose inhaler,

Inh = inhalation.
 INHALED CORTICOSTEROID
Adult dosing
Drug
Starting Maximum
Beclomethasone (Beclovent, Vanceril) 84mcg 3-4 times daily 840 mcg
MDI:42 mcg/actuation or in divided doses
84 mcg/actuation 168 mcg twice daily
(Vanceril Double Strength)
Budesonide (Pulmicort Turbohaler) 200-400 mcg twice daily1 400 mcg twice daily1
DPI: 200mcg/actuation 200-400 mcg twice daily2 800 mcg twice daily2,3
400-800 mcg twice daily3
Flunisolide (AeroBid, AeroBid-M) 500 mcg (2 inhalations) 1 mcg (4 inhalations)
MDI : ≈ 250 mcg/actuation twice daily. twice daily.
Fluticasone MDI: 88 mcg twice daily1 MDI: 440 mcg twice daily1,2
: 88-220 mcg twice daily2 : 880 mcg twice daily3
MDI (Flovent) : 44, 110, and
220 mcg/actuation : 880 mcg twice daily3
DPI: 100 mcg twice daily1 DPI: 500 mcg twice daily1,2
DPI (Flovent Rotadisk) : 50, 100, and :100-200 mcg twice daily2 :1000 mcg twice daily3
250 mcg/actuation. : 1000 mcg twice daily3
Triamcinolone acetonide (Azmacort) 200 mcg 3-4 times daily 1600 mcg
MDI : ≈ 100 mcg/actuation or in divided doses
(60 mg as acetonide) 400 mcg twice daily
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.
Current best available pharmacologic therapy for COPD

 Long-acting beta-2+ Inhaled corticosteroid

combination (LABACS)
 New anticholinergic Tiotropium bromide.

…bring new hope for patients with COPD, for whom?

Management (GOLD)
1. Bronchodilator medications are central to the
symptomatic management of COPD. They are given on
an as-needed basis or on a regular basis to prevent or
reduce symptoms.

2. The principal bronchodilator treatment are b2 agonists,

anti cholinergics theophylline, and a combination of one
or more of these drugs. Long- acting inhaled
bronchodilators are more convinient.

3. Combining bronchodilators may improve efficacy and

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