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: defisiensi 1 antitripsin -Airway hyperreactivity

- Rokok sigaret - Occupational dust dan chemical - Polusi indoor,outdoor - Infeksi sal napas

Future COPD case

Future asthmatic

Future COPD if smoker

PATHOGENESIS OF COPD

NOXIOUS
HOST FACTORS ANTI OXIDANTS [ environmental ]

PARTICLE GASES

LUNG INFLAMMATION
ANTI OXIDANTS ANTI PROTEINASES [ genetic ]

OXIDATIVE STRESS
REPAIR MECHANISM

PROTEINASE IMBALANCE
REPAIR 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

SYMPTOMS : Cough Sputum Dyspnea 3

EXPOSURE TO RISK FACTORS : Tobacco Smoke Occupation Indoor / outdoor pollution

SPIROMETRY

Spirometry in COPD Diagnosis

0 1 2 FEV1 FVC
5.200 3.900

FEV1/ FVC
80 % 60 %

Normal COPD
FEV1

4.150 2.350

Liter

COPD
4 5 1 2 FEV1 FVC

Normal
3 4

FVC 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
Established diagnosis Asses symptoms Stop smoking

Healthy lifestyle
Immunization BRONCHODILATORS

Treat obstruction

Assess hypoxemia

Long-term oxygen

therapy

Pulmonary rehabilitation program

Acute Excacerbation of COPD : COPD Guideline Algorithm

Stable COPD patients Increase in symptoms from baseline PEFR : peak expiratory flow rate, CXR : chest X-ray, NPPV : noninvasive positive pressure ventilation COPD : chronic obstructive pulmonary disease. AECOPD : acute excacerbation of COPD, URI : upper respiratory infection. O2 : oxygen therapy PRN : as needed
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

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 Criteria present ? yes One or more criteria present ? two or more Two or more diagnostic criteria present ? three Three criteria : treat for severe excacerbation Management : 1.CXR 2. Inhaled bronchodilators (1) 3.Systemic corticosteroids (2) 4.Antibiotics (4) 5.O2 PRN 6.NPPV PRN (3) two only one only no

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 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 physician 4. Use narrow spectrum antibiotics ; the agent favored in the trials were Amoxicillin and trimethopin-sulfamethoxazole, and tetracycline.

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

Consider other diagnosis

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 yes Two criteria only : treat for moderate excacerbation Management : 1.CXR 2. Inhaled bronchodilators (1) 3.Systemic corticosteroids (2) 4.O2 PRN 5.NPPV PRN (3) Yes. Treat for mild excacerbation of COPD

no

Consider other diagnosis

Management : 1. CXR 2. Inhaled bronchodilators (1)

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

Acute excacerbation of COPD : 3 cardinal symptoms: worsening of dyspnea, increase of sputum purulence, increase of sputum volume. mild 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. moderate 2 of 3 cardinal symptoms severe All 3 cardinal symptoms

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 All Chronic symptoms (cough, sputum) Exposure to risk factors Normal spirometry FEV1 / FVC < 70 % FEV1 80 % predicted With or without symptoms II A FEV1 / FVC < 70 % 50%<FEV1< 80% predict With or without symptoms II B FEV1 / FVC < 70 % 30% FEV1>50% predict With or without symptoms Short acting bronchodilator when needed Characteristic Recommended treatment Avoidance of risk factors, Infuenza vaccination, Exercise, Patient education.

O : at risk

I : mild COPD

II : moderate COPD

Regular treatment with one or more bronchodilators. Rehabilitation Regular treatment with one or more bronchodilators. Rehabilitation Regular treatment with one or more bronchodilators. Inhaled glucocortico steroids if significant symptoms and lung function response, or if repeated excacerbations. Treatment of complications. Rehabilitation Long term oxygen therapy if respiratory failure. Consider surgical treatment.

Inhaled glucocortico steroids if significant symptoms and lung function response.

Inhaled glucocortico steroids if significant symptoms and lung function response, or if repeated excacerbations.

III : severe COPD

FEV1 / FVC < 70 % FEV1<30% predicted or presence of respiratory failure or right heart failure.

Sympatomimetic bronchodilators

Drug

Adrenergic Receptor activity

Route of adminis tration

Usual adult dose

Maximum recommended daily dose

SHORT ACTING Albuterol Tablets : 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) Bitolterol MDI : 0,8%. 0,37mg/actuation (Tornalate) Solution for inhalation : 0,2% (Tornalate) b1 < b2 PO PO PO Inh Inh Inh b1 < b2 2 or 4 mg tid or qid 4 - 8 mg q 12 h 2or 4 mg tid or qid 3 1 - 2 inh q 4 - 6h 2.5mg tid or qid by nebulization over 5-15 minutes. Note: 0.5% solution must be diluted to total 3 ml volume with steril normal saline before nebulization. 200 mcg inh q 4 to 6h using Rotohaler device 4 2 inh tid 0.5 - 1 ml (1-2 mg) tid by intermittent flow nebulization 32 mg in DD 16 mg q 12h 8 mg qid

Inh Inh

-3 inh q 6h or 2 Inh q 6h. -8 mg (intermit ten flow). -14 mg (contino us flow).

Epinephrine Solution for inhalation: 1:100 and 1:1000 (Adrenalin) Solution for inhalation: 2,25 % racepinephrineHCl (equivalen to 1,125% epinephrine base), (Asthma Nephrin, Micro Nephrin) Isoproterenol Solution for inhalation:0,5%(1:200), 1%(1:100) (Isuprel). MDI:0.25%, 103 mcg/dose (Isuprel), 80 mcg/actuation (Medihaler) Levalbuterol HCl. Solution for inhalation 0.63mg/3ml and 1.25/3ml Metaproterenol Tablets : 10 mg, 20 mg Syrup : 10 mg / 5 ml (Alupent) MDI : 75mg and 150 mg (0,68 mg / actuation) (Alupent) Solution for inhalation 0.4%, 0.6%, 5% (Alupen)

b1b2

Inh 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 - 8 drops) of MicroNefrin to 4.6 to 4.8 ml water.1 Administer for 15 min. q 3 - 4 h. 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; may repeat 5 times daily. 1-2 Inh 6-8 times daily (q 3-4h) 0.63 -1.25 mg tid (every 6-8h) by nebulization 20 mg tid or qid 6 2-3 inh q 3-4h 0.2-0.3 ml (5% sol) diluted to 2.5ml with diluent, given by IPPB device, 3-4 time daily (4h) 12 inh

b1b2

Inh Inh Inh

b1 < b2

PO Inh Inh

Pirbuterol. MDI: 0.2 mg / actuation (Maxair)

Terbutaline. Tablets: 2.5mg, 5mg MDI : O2mg / actuation Injection : 1 mg / ml LONG ACTING Salmeterol. MDI 21 mcg/actuation (Serevent) Inhalation powder : 50 mcg (Serevent diskus)
1.

b1 < b2
b1 < b2

Inh
PO Inh SC

2 inh (0.4 mg) q 4-6h

1 tablet (5 mg) tid during waking hours (6 h intervals) 2 Inh q 4-6h 0,25 mg in lateral deltoid ; may repeat every 15-30 min. If clinical improvement does not occur.
5

12 inh
15 mg 0.5 mg in 4 h

b1 < b2

Inh Inh

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 inhalaler 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

Drug Route 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.

2 Inh qid.

12 Inh.

Ipratropium bromide and albuterolsulfate MDI : 18 mcg / Ipratropium. 103 mcg albuterol / actuation (Combivent).

inh

12 Inh.

MDI = metered dose inhaler, Inh = inhalation.

INHALED CORTICOSTEROID
Drug
Beclomethasone (Beclovent, Vanceril) MDI:42 mcg/actuation 84 mcg/actuation
(Vanceril Double Strength)

Adult dosing
Starting 84mcg 3-4 times daily or 168 mcg twice daily Maximum 840 mcg in divided doses

Budesonide (Pulmicort Turbohaler) DPI: 200mcg/actuation

Flunisolide (AeroBid, AeroBid-M) MDI : 250 mcg/actuation Fluticasone MDI (Flovent) : 44, 110, and 220 mcg/actuation DPI (Flovent Rotadisk) : 50, 100, and 250 mcg/actuation.

200-400 mcg twice daily1 200-400 mcg twice daily2 400-800 mcg twice daily3 500 mcg (2 inhalations) twice daily.
MDI: 88 mcg twice daily1 : 88-220 mcg twice daily2 : 880 mcg twice daily3 DPI: 100 mcg twice daily1 :100-200 mcg twice daily2 : 1000 mcg twice daily3

400 mcg twice daily1 800 mcg twice daily2,3

1 mcg (4 inhalations) twice daily.
MDI: 440 mcg twice daily1,2 : 880 mcg twice daily3 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 daily or 400 mcg twice daily

1600 mcg in 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.

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. Combining bronchodilators may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator.

3.

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