Dr. Syamsudin, M. BiomedFakultas Farmasi

Universitas Pancasila Jakarta

Definitions:

Asthma: It's a chronic respiratory condition that causes the airways to constrict become inflamed and collect mucus. It can be triggered by natural allergens, cigarette smoke, pets, exercise or emotional stress.

COPD: is characterized by air flow obstruction. The airflow obstruction is usually progressive, not fully reversible and doesn't change markedly over several months. The disease is predominantly caused by smoking.

Diagnosis of COPDIt should be considered in patients over the

age of 35 who have a risk factor, generally smoking, and who present with exertional dyspnoea, chronic cough, regular sputum production, frequent winter bronchitis or wheeze. The presence of airflow obstruction should be confirmed by performing spirometry.

All health professionals should be competent in the interpretation of the

results

Faktor – faktor resikoKebiasaan merokok merupakan satu - satunya penyebab kausal yang terpenting, jauh

lebih pentingdari faktor penyebab lainnya.

• a. Riwayat merokok• - Perokok aktif• - Perokok pasif• - Bekas perokok

• b. Derajat berat merokok dengan Indeks Brinkman (IB), yaitu perkalian jumlah rata-rata batang rokok dihisap sehari dikalikan lama merokok dalam tahun :

- Ringan : 0-200 - Sedang : 200-600 - Berat : >600

• 2. Riwayat terpajan polusi udara di lingkungan dan tempat kerja• 3. Hipereaktiviti bronkus• 4. Riwayat infeksi saluran napas bawah berulang• 5. Defisiensi antitripsin alfa - 1, umumnya jarang terdapat di Indonesia

PathogenesisThree processes:

Chronic inflammationImbalance of proteinases and anti-proteinasesOxidative stress

Chronic InflammationChronic inflammation in airways,

parenchyma, pulmonary vasculatureInflammatory cells involved are:

Macrophages leukotriene B4

T-lymphocytes (CD8) interleukin 8Neutrophils TNF-α

PathologyCentral Airways:

Enlarged mucus secreting glands

Increase in goblet cells

Mucus hypersecretionPeripheral Airways

Repeated cycles of injury and repair

Increased collagen/scarring in airway wall

PathologyPulmonary vascular changes

Thickening of vessel wall (intima)

Increase in smooth muscle

Infiltration of vessel wall by inflammatory cellsAs COPD worsens, more smooth muscle,

proteoglycans and collagen further thicken the vessel wall

Pathophysiology Mucus hypersecretion

Ciliary dysfunction

Airflow limitation

Pulmonary hyperinflation

Gas exchange abnormalities

Pulmonary hypertension

Cor pulmonale

Mucus hyperserection & ciliary dysfunction → cough, sputum production

Diagnosis• A. Gambaran klinisa. Anamnesis• - Keluhan• - Riwayat penyakit• - Faktor predisposisib. Pemeriksaan fisis

B. Pemeriksaan penunjang a. Pemeriksaan rutin b. Pemeriksaan khusus

Physical ExaminationThorax:

Barrel chestLungs

Decreased breath soundsWheezing

CardiacRight-sided heart failure

Edema, tender liver, distended abdomen

Physical signs are rarely apparent until significant

impairment of lung function has occurred

Diagnostic Tests Chest X-ray

Flattened diaphragms Use to exclude other diagnoses

High resolution CT Not routinely recommended If in doubt about diagnosis of

COPD If considering bullectomy or

lung volume reduction surgery CBC

May see increased hemoglobin/hematocrit secondary to hemoconcentration

ABG Spirometry

SpirometryMeasure of FVC and FEV1

FVC = forced vital capacity Maximum volume of air forcibly exhaled from the point of

maximal inhalationFEV1 = forced expiratory volume in 1 second

Volume of air exhaled in the 1st second of the FVC maneuverCalculate the FVC/FEV1 ratio

Normal ratio = 70/80%COPD ratio = <70% pre-bronchodilator FVC & FEV areCOPD ratio = <80% post-bronchodilator both decreased

Essential to making the diagnosis of COPD

SpirometryBronchodilator Reversibility Testing

Perform in the initial assessment of COPD in order to: Exclude asthma Establish best attainable lung function Gauge patient prognosis Guide treatment decisions

Arterial Blood Gas (ABG)Obtain in patients with FEV1 < 40%

predicted OR Clinical signs of respiratory or right heart

failureCentral cyanosis, ankle swelling, increase in

jugular venous pressure (JVP) ORRespiratory Failure:

PaO2 < 60 mm Hg with or without PaCO2 > 45 mm Hg while breathing air at sea level

Technique:Obtain by arterial puncture; DO NOT USE

finger or ear oximeters

Other TestsAlpha-1 antitrypsin

Consider in patients with COPD < age 45Strong family hx of early COPD or with alpha-1

antitrypsin deficiency

Differential Diagnosis of COPD Asthma

Reversible airflow limitation Early onset (childhood) Symptoms vary day to day

Congestive heart failure Volume restriction, NOT

airflow limitation CXR with dilated heart,

pulmonary edema Bronchiectasis

Large volumes of purulent sputum

Commonly associated with bacterial infection

Bronchial dilation and bronchial wall thickening on CXR or CT

Tuberculosis Onset at all ages Chest x-ray with infiltrate or

nodular lesions Obliterative bronchiolitis

Younger patients/non-smokers May have a hx of rheumatoid

arthritis or fume exposure CT shows hypodense areas

with expiration Diffuse panbronchiolitis

Male/non-smokers Chronic sinusitis CXR and high resolution CT

show diffuse small centrilobular nodular opacities and hyperinflation

MedicationsGoals

Prevent and control symptomsReduce frequency and severity of exacerbations Improve health status Improve exercise tolerance

No existing medications can modify the long-term decline in lung function

Reduction of therapy once symptom control occurs is not normally possible

COPD is progressive and over time will require progressive introduction of more treatments to attempt to limit the impact of these changes

BronchodilatorsCentral to symptom management

Used in all stages of COPD severity Inhaled forms are preferredCan be prescribed as needed OR regularly to prevent or

reduce symptomsLong-acting inhaled bronchodilators are more effective and

convenient (but are more expensive)Combining drugs with different mechanisms and durations

of action may increase the degree of bronchodilation for equivalent or lesser side effects

All categories of bronchodilators have been show to increase exercise capacity without necessarily producing significant changes in FEV1

BronchodilatorsBeta2-agonists

Short-acting: albuterolLong-acting: salmeterol (Serevent™), formoterol

(Foradil™)Anticholinergics

Short acting: ipratropium bromide (Atrovent™)Long acting: tiotropium bromide (Spiriva™)

Methylxanthines (Theophylline™)Combination bronchodilators

Fenoterol/ipratropium (Duovent™)Salbutamol/ipratropium (Combivent™)

GOLD Pocket Guide to COPD Diagnosis, Management, and Prevention

GlucocorticosteroidsUse if FEV1 < 50% predicted and repeated exacerbations,

e.g. three in the last three years Severe COPD and Very Severe COPD

Does not modify the long-term decline in FEV1 BUT does reduce the frequency of excacerbations and improves health status

The combination of a long-acting beta2-agonist and an inhaled glucocorticosteroid is more effective than the individual components

Long-term treatment with oral glucocorticoids is NOT recommended

Glucocorticosteroid (inhaled) reversibility testing Treatment trial of inhaled glucocorticosteroids for 6 to 12 weeks

then repeat spirometry with and without bronchodilators Patients most likely to respond to inhaled steroids have an FEV1

increase of 200 mL and 15% above baseline post-bronchodilator

GOLD Pocket Guide to COPD Diagnosis, Management, and Prevention

Inhaled GlucocorticoidsBeclomethasone (Vanceril™)Budesonide (Pulmicort™)Fluticasone (Flovent™)Triamcinolone (Azmacort™)

GOLD Pocket Guide to COPD Diagnosis, Management, and Prevention

ImmunizationsVaccines

Influenza yearly Reduces serious illness and death in COPD patients

by approximately 50% Give once yearly: autumn OR twice yearly: autumn

and winterPneumovax

Sufficient data to support its general use in COPD is lacking, but it is commonly used

Other Medications?Alpha-1 Antitrypsin Augmentation Therapy

Only if this deficiency is present in an individual should they undergo treatment

Antibiotics Prophylactic use is NOT recommended Can be used in the treatment of infectious exacerbations of

COPDMucolytic agents

Overall benefits are small, so currently not recommended for widespread use

Types: Ambroxol Erdosteine (Erdostin, Mucotec) Carbocysteine (Mucodyne) Iodinated gylerol (Expigen)

GOLD Pocket Guide to COPD Diagnosis, Management, and Prevention

Other Medications? Antioxidant agents

N-acetylcysteine (Bronkyl, Fluimucil, Mucomyst) Have been shown to reduce the frequency of exacerbations and could

have a role in the treatment of patients with recurrent exacerbations More studies are needed

Immunoregulators Not recommended at this time No reproducible studies are available

Antitussives Regular use is contraindicated in stable COPD since cough has a

significant protective role Vasodilators

Inhaled nitric oxide Can worsen gas exchange because of altered hypoxic regulation of ventilation-

perfusion balance and is contraindicated in stable COPD

GOLD Pocket Guide to COPD Diagnosis, Management, and Prevention

Other Medications?Respiratory stimulants

Doxapram (IV) Almitrine bismesylate

Not recommended in stable COPDNarcotics

Oral and parenteral opioids are effective for treating dyspnea in patients with advanced COPD Use this with caution; benefits may be limited to a few sensitive

subjects nebulized opioids: insufficient evidence re: efficacy

Miscellaenous: Nedocromil Leukotriene modifiers Alternative healing methods

None have been adequately studied in COPD patients at this time

GOLD Pocket Guide to COPD Diagnosis, Management, and Prevention