GOLD16 – MANAGEMENT AND TREATMENT OF COPD

GOLD16 – MANAGEMENT

AND TREATMENT OF COPD

Raphael Northoff-PTA (pharmaceutical & technical assistant)

Intern with Clinica Universidad de La Sabana

About GOLD

lounched in 1997

Health careprofessionalsfrom over 50

different nations

Initial virsion of guidelines in

2001

In collaborationwith NIH and

WHO

Updatesprepaered every

year

World COPD Day

Relationshipswith profit-

makingorganizations

GOLD objectives

Recommend effective COPD management and prevention strategies for use in all countries.

Increase awareness of the medical community, public health officials and the general public that COPD is a public health problem.

Decrease morbidity and mortality from COPD through implementation and evaluation of effective programs for diagnosis and management.

Promote study into reasons for increasing prevalence of COPD including relationship with environment.

Implement effective programs to prevent COPD.

The GOLD definition of COPD

Chronic Obstructive Pulmonary Disease (COPD), a common preventable and

treatable disease, is characterized by persistent airflow limitation that is

usually progressive and associated with an enhanced chronic inflammatory

response in the airways and the lung to noxious particles or gases.

Exacerbations and comorbidities contribute to the overall severity in

individual patients.

is a leading cause of morbidity and mortality worldwide and results in an

economic and social burden that is both substantial and increasing

Inhaled cigarette smoke and other noxious particles such as smoke from

biomass fuels cause lung inflammation, a normal response that appears to be

modified in patients who develop COPD

may induce parenchymal tissue destruction (resulting in emphysema), and

disrupt normal repair and defense mechanisms (resulting in small airway

fibrosis). These pathological changes lead to air trapping and progressive

airflow limitation and in turn to breathlessness and other characteristic symptoms

of COPD

COPD

FACTORS THAT INFLUENCE DISEASE

DEVELOPMENT AND PROGRESSION

COPD

GENS

AGE & GENDER

LUNG GROWTH AND

DEVELOPMENT

SOCIOECO-NOMIC

SATTUS

EXPOSURE TO

PARTICLES

ASTHMA, BRONCHIAL

HYPERACTIVITY

CHRONIC BRONCHITIS

alpha-1 antitrypsin

Men ≈ women

Duration of exposure?

Gestation, birth,

childhood

“Childhood infections”

“Childhood

disadvantages'”

Poverty inversely related to risk

of developing COPD

Smoke, organic/ inorganic

dusts, chemical agents and

fumes, (indoor) air pollution,

occupational exp.

May be risk factor,

clinically separating

may not be easy

hypersecretion of

mucus decline FEV1,

young + smoking +

chronical bronchitis ↑

developing COPD

Pathophysiology

Airflow limitation and air trapping – Gas

Exchange AbnormalitiesMucus Hypersecretion

Pathophysiology

Pulmonaryhypertension

Exacerbations

Inflammatory aspect asthma - COPD

Both are associated with chronic inflammation of respiratory tract

BUT

Differences in the involved inflammatory cells and mediators

for instance

COPD asthma

CD8+ (cytotoxic) Tc1 lymphocytes eosinophils, leukotriens, IL5

present only in smokers, neutrophilic

Differences in pathological pathway, symptoms and response to therapy

Some patients with COPD have features consistent with asthma and may have a

mixed inflammatory pattern with increased eosinophils

Pathophysiology - Comorbidities

COPD often coexists with other diseases that may havea significant impact prognosis!

Cardiovascular disease Depression Osteoporosis

Lung cancer Metabolic Syndrome & Diabetes GERD

Process of managing COPD

Diagnose & Assess

Adjust treatment

Review response

Diagnose

Identify & reduce exposure to risk

factors

Inhaler technique & adherence

COPD medications

Non-pharmacologic treatment

Symptoms

Exacerbations

Side effects

Patient satisfaction

Lung function

Hospitalization

discharge and

follow up

ICU

Palliative

care

Diagnosis and Assessment

Consider clinical diagnosis of COPD if patient has:

dyspnea, chronic cough or sputum production, and a history of exposure to risk factors for the disease

Spirometry is required to make the diagnosis in this clinical context

presence of a post-bronchodilator FEV1/FVC < 0.70 confirms the presence of persistent airflow limitation and thus of COPD

Comorbidities occur frequently in COPD patients

cardiovascular disease, skeletal muscle dysfunction, metabolic syndrome, osteoporosis, depression and lung cancer

can occur in patients with mild, moderate and severe airflow limitation and influence the prognosis

comorbidities should be actively looked for and treated appropriately if present

Goals of COPD assessment:

determine the severity of the disease (including severity of airflow limitation), the impact on the patient’s health status, and the risk of future events (exacerbations, hospital admissions and death) guide therapy

Differential Diagnosis

Assessment of COPD

Symptoms

• CAT¹

• CCQ²

• mMRC³ (onlyassessment of breathlessness)

Airflowlimitation

• Based on post-bronchodilator

FEV1 (GOLD Classification 1-4)

Risk of Exacerbation

• Frequency and hospitalization

Comorbiditis

• May influaencemortlity and hospitalization

• Look for routinelyand treatappropiatly

¹ CAT COPD Assessment Test

² CCQ Clinical COPD Questionaire

³ mMRC modified British Medical Research Council

COMBINED ASSESSMENT OF COPD

Therapeutic options

Smoking cessation!

Greatest capacity to influence COPD !

if effective resources and time are dedicated to

smoking cessation, 25% long term quit rates can

be achieved

PREVENTION COUNCELING

NICOTINE

REPLEACEMENT

THERAPY

Programs with clear,

consistent and repeated

nonsmoking messages

Smoke-free schools..

Even short counseling

results quit rates of

5-10%

Nicotine gum, inhaler or

spray, transdermal patch,

sublingual tablet etc.

Varenicline ?

Bupropion ?

Nortriptiyline ?

Therapeutic options

Occupational Exposure

Elimination or reduction of exposures in the workplace

Surveillance and early detection

Indoor and Outdoor Air Pollution

Reduce or avoid burning biomass for cooking and heating in poorly ventilated dwellings

Advice patient to monitor public anouncements of air quality

Physical Activity

Remain activ!

All COPD patients benefit from regular physical activity

Pulmonary rehabilitation

Pulmonary rehabilitation

Smoking cessation

Exercise training

Nutrition counseling

education

Minimum 6 weeks

Continue at home!

Reduce anxious and

depression

Improves health related

quality of life as far as

survival

Those programs can be

costly

Encourage patient exercise

on his own !

Pharmacological therapies for stable

COPD

Improve health status and exercise tolerance

Reduce symptoms/ frequency and severity of exacerbations/ mortality

To date, none of the existing medications for COPD has been

conclusively shown to modify the long-term decline in lung function

when this is tested as a primary or secondary outcome in clinical trials

Care of the health!

It is crucial for patients with COPD to understand the nature of their disease!

education!

Explain the COPD risk factors for its progression and their role in achieving optimal health outcomes

Ongoing monitoring including continuous evaluation of exposure to risk factors and monitoring of disease progression

general advice on healthy living, including diet and the fact that physical exercise is safe and encouraged

evidence for the effectiveness of

pharmacologic treatments is not available

for patients with

FEV1 > 80% predicted

No evidence to recommend one

class of long-acting

bronchodilators over another for

initial treatment

Consider Combination of 2 long-

term bronchodilators if severe

breathlessness

Combination with PDE 4 inhibitor

may be considered if chronic

bronchitis

Unfortunately there is only one

study directly comparing ICS/ long-

acting beta agonist or long-acting

anticholinergic, which makes

differentiation difficult

First choice: inhaled corticosteroid

plus long-acting beta2-agonist or long-

acting anticholinergic, although there

are conflicting findings concerning this

treatment

second choice: combination of all

three classes of drugs (inhaled

corticosteroids/long-acting beta2-

agonist/long-acting anticholinergic)

“other possible treatments” if recommended first -

or alternative choice are unavailable or

unaffordable

Bronchodilatorsare central to symptom management in COPD

increase the FEV1 or change other spirometric variables

usually widening of the airways (smooth muscles) rather than changes in lung

elastic recoil

improve emptying of the lungs

tend to reduce dynamic hyperinflation at rest and during exercise

The extent of these changes, especially in severe and very severe patients, is not

easily predictable from the improvement in FEV1

Dose – response : highly Increasing the dose of beta2-agonist/ anticholinergic

(especially nebulizers) subjective benefit in acute episodes but not necessarily

helpful in stable disease

Bronchodilatorsare central to symptom management in COPD

Inhaled therapy is preferred

The choice between different bronchodilators depends on availability and individual response symptoms relief and side effects?

beta2-agonists

Anticholinergics

Theophylline

Long acting bronchodilators

convenient/ more effective at producing maintained symptom relief than short acting bronchodilators

Reduce exacerbations and related hospitalizations

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

Short acting Long acting

are prescribed on as-needed or on a regular basis

beta 2-agonists (SABA/ LABA)

Selective stimulation of adrenergic receptors bronchial musculature

Effect:

Spasmolytic in bronchial tubes

Bronchodilator effect

short onset of action 1 - 5 min and relief for 3 - 6 hours

Fenoterol, Salbutamol, Terbutaline ect.

long slow onset and duration of 12 to 24 hours

Formoterol (rapid onset), Salmoterol ect.

Anticholinergics

inhibition of muscarinic Ach-receptors

Bronchodilator effect by inhaling anticholinergic

prevent wheezing, shortness of breath, coughing and chest tightness as b2-

agonist do

Tiotropium

Blocks selectively M1 and M3 for more than 24 hours

reduces exacerbations and related hospitalizations, improves symptoms and health status and improves the effectiveness of pulmonary rehabilitation

Combination of Bronchodilators

may increase the degree of bronchodilation or lesser side effects!

long-acting beta2-agonist + long-acting anticholinergic

significant increase in lung function whereas outcomes is still limited

beta2-agonist + anticholinergic or theophylline

may produce additional improvements in lung function and health status compared to either medication alone

Short-term formoterol and tiotropium has been shown to have a bigger impact on FEV1 than the single components

short-acting beta2-agonist + anticholinergic

greater and more sustained improvements in FEV1 than either drug alone

(does not produce evidence of tachyphylaxis over 90 days of treatment)

Methylxanthines

Controversy remains of the exact effect f xanthine derivatives

Unspecific adenosine-receptor agonist, antagonizing equally A1, A2, A3

A2b (A3) responsible for release of inflammatory mediators

Unspecific Inhibition of phosphodiesterase (PDE)

in so doing also bronchodilatating effect

Theophylline

metabolized by cytochrome P450/ Clearance declines with age

many other physiological variables and drugs modify theophylline

All studies that have shown efficacy of theophylline in COPD were performed with slow-release preparations

Theophylline is less effective and less well tolerated than inhaled long-acting bronchodilators

Corticosteroids

Inhaled Corticosteroids (ICS)

only as combination therapy

dose-response relationships and long-term safety of ICS in COPD are not known

their role in the management of stable COPD is limited to specific indications

if FEV1 < 60% predicted regular treatment with ICS improves symptoms, lung function, and quality of life, and reduces the frequency of exacerbations

Only moderate to high doses have been used in long-term clinical trials

Oral Corticosteroids (OCS)

Long-term treatment is not recommended (numerous side-effects)

for treating acute exacerbations improve symptoms, lung function, reduce rate of treatment failure, and shorten length of hospital stay

preventing a subsequent exacerbation

Combination ICS/ Bronchodilator

ICS + long-acting beta2-agonist

more effective than the individual components in improving lung function and health

status and reducing exacerbations in moderate to very severe COPD

addition of a long-acting beta2-agonist/ ICS combination to tiotropium

improves lung function, quality of life and may reduce exacerbations (more studies of

triple therapy are needed

is associated with an increased risk of pneumonia

Phosphodiesterase inhibitors

(PDE – inhibitors)Oral administration once daily

principal action is to reduce inflammation by inhibiting of the breakdown of

intracellular cyclic AMP

no direct bronchodilator activity

improve FEV1 in patients treated with salmeterol or tiotropium

May be helpful for patients with chronic bronchitis

should always be used in combination with at least one long-acting bronchodilator!

Representing drug: Roflumilast

Mucolytics and Antioxidant Agents

a few patients with viscous sputum may benefit from mucolytics, benefits seem to

be very small

widespread use of these agents cannot be recommended at present

In most common use:

N-acteylcystein, also an antioxidative agent

could maybe have a role in the treatment of patients with recurrent exacerbation

Cystein

Other pharmacological treatments

Vaccines

• Influenza vaccination can reduce serious illness(lower respiratory tract infections) requiring hospitalization up to death in COPD patients

• Pneumococcal polysaccharide vaccine recommended for COPD patients ≥ 65 years younger patients with significant comorbid conditions

Alpha-1 Antitrypsin Augmentation

• only young patients with severe hereditary alpha-1 antitrypsin deficiency and established emphysema may be candidates

• very expensive, is not available in most countries

Antibiotics

• Not recommended,

except for treatment of

infectious exacerbations/

other bacterial infections

Vasodilators

• nitric oxide is

contraindicated in stable

COPD

Antitussives

• Cough has a significant

protective role

Other treatments

Oxygen therapy

• increase survival in patients with severe resting hypoxemia

• Indicated for PaO2 ≤ 8.0 kPa/ SaO2 ≤ 88%, pulmonary hypertension, congestive cardiac failure, polycythemia ?

Ventilatory support

• Non-invasive ventilation (NIV) is increasingly used in patients with stable very severe COPD

• contradictory results regarding the clinical benefits of long-term NIV

NIV + long-term O2 may

be of some use in a

selected subset of

patients

It may improve survival

but does not improve

quality of life

patients with COPD and

obstructive sleep apnea

benefit from continuous

positive airway pressure

(CPAP) in survival and

risk of hospital

admission

Surgical treatments

Lung Volume Reduction Surgery (LVRS)

parts of the lung are resected

reduce hyperinflation making respiratory muscles more effective pressure generators by

improving their mechanical efficiency In addition LVRS increases the elastic recoil pressure of

the lung and thus improves expiratory flow rates and reduces exacerbations

advantage of surgery over medical therapy more significant among patients with

predominantly upper-lobe emphysema and low exercise capacity prior to treatment

Lung Transplantation

appropriately selected patients with very severe COPD improve quality of life and functional

capacity

post-operative mortality, acute rejection, fungal or bacterial infections etc.

limited by the shortage of donor organs and costs

Treatment of Exacerbations exacerbation of COPD

acute event

worsening of the patient’s respiratory symptoms beyond normal day-today variations

change in medication

most common precipitating factors

viral upper respiratory tract infections

infection of the tracheobronchial tree

diagnosis of an exacerbation

clinical presentation of the patient complaining of an acute change of symptoms (baseline dyspnea, cough and/ or sputum production), beyond day-to-day variations

goal of treatment in COPD exacerbation

minimize the impact of the current exacerbation

prevent the development of subsequent exacerbations

Exacerbation – severity assessment

Arterial blood gases measurements

Pa02 < 8.0 kPa with or without PaCO2 > 6.7 kPa respiratory failure

Chest radiographs to exclude alternative diagnoses

ECG – coexisting of cardiac problems ?

Other laboratory tests

Whole blood count polycythemia or bleeding ?

Purulent sputum empirical antibiotic treatment ?

Biochemical tests electrolyte disturbances, diabetes, poor nutrition ?

Exacerbation - Treatment options

Oxygen

key component of hospital treatment of an exacerbation.

titrated to a target saturation of 88-92%

Bronchodilators

short-acting inhaled beta2-agonists with or without short-acting anticholinergics

Intravenous methylxanthines (theophylline/ aminophylline) may be considered as

second-line therapy if insufficient response to short-acting bronchodilators

Systemic corticosteroids

shorten recovery time, improve lung function, arterial hypoxemia reduce the risk of early

relapse, treatment failure, and length of hospital stay

Exacerbation - Treatment options

Antibiotics

infectious agents in COPD exacerbations can be viral or bacterial

use remains controversial

Antibiotics should be given to patients:

with increased dyspnea, increased sputum purulence (+ sputum volume)

Who require mechanical ventilation

antibiotics for only moderately or severely ill patients with COPD exacerbations with increased cough and sputum purulence