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CLINICAL PRACTICE GUIDELINES
Chronic Obstructive
Pulmonary Disease
Chronic Obstructive Pulmonary
Disease Association (Singapore)
Association of Aged Care
Physicians Singapore
Singapore Medical
Association
SINGAPORE THORACIC SOCIETY
College of Family Physicians
Singapore
Oct 2006
MINISTRY OF HEALTH
SINGAPORE
ISBN 981-05-6800-2
Chapter of Respiratory Physicians
College of Physicians, Singapore
Academy of Medicine
Singapore
MOH Clinical Practice Guidelines 4/2006
Levels of evidence and grades of recommendation
Levels of evidence
Level
1+ +
1+
-
1
2+ +
2+
-
2
Type of Evidence
High quality meta-analyses, systematic reviews of randomised
controlled trials (RCTs), or RCTs with a very low risk of bias.
Well conducted meta-analyses, systematic reviews of RCTs, or
RCTs with a low risk of bias.
Meta-analyses, systematic reviews of RCTs, or RCTs with a high
risk of bias
High quality systematic reviews of case control or cohort studies.
High quality case control or cohort studies with a very low risk of
confounding or bias and a high probability that the relationship is
causal
Well conducted case control or cohort studies with a low risk of
confounding or bias and a moderate probability that the relationship
is causal
Case control or cohort studies with a high risk of confounding or
bias and a significant risk that the relationship is not causal
3
Non-analytic studies, e.g. case reports, case series
4
Expert opinion
Grades of recommendation
Grade
A
B
C
D
GPP
(good practice
points)
Recommendation
At least one meta-analysis, systematic review of RCTs, or RCT
rated as 1+ + and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+,
directly applicable to the target population, and demonstrating
overall consistency of results
A body of evidence including studies rated as 2++, directly
applicable to the target population, and demonstrating overall
consistency of results; or
Extrapolated evidence from studies rated as 1+ + or 1+
A body of evidence including studies rated as 2+, directly
applicable to the target population and demonstrating overall
consistency of results; or
Extrapolated evidence from studies rated as 2+ +
Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
Recommended best practice based on the clinical experience of
the guideline development group.
1
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Published by Ministry of Health, Singapore
16 College Road,
College of Medicine Building
Singapore 169854
Printed by Oxford Graphic Printers Pte Ltd
Copyright  2006 by Ministry of Health, Singapore
ISBN 981-05-6800-2
Available on the MOH website: http://www.moh.gov.sg/cpg
Statement of Intent
These guidelines are not intended to serve as a standard of medical care.
Standards of medical care are determined on the basis of all clinical data
available for an individual case and are subject to change as scientific
knowledge advances and patterns of care evolve.
The contents of this publication are guidelines to clinical practice, based on
the best available evidence at the time of development. Adherence to these
guidelines may not ensure a successful outcome in every case. These
guidelines should neither be construed as including all proper methods of
care, nor exclude other acceptable methods of care. Each physician is
ultimately responsible for the management of his/her unique patient, in the
light of the clinical data presented by the patient and the diagnostic and
treatment options available.
3

Chronic obstructive pulmonary disease is a major cause of mortality and
morbidity worldwide: it is the fourth leading cause of death worldwide. In
terms of morbidity (as measured in disability-adjusted life years lost),
chronic obstructive pulmonary disease ranks thirteenth. According to the
WHO Global Burden of Disease Study, by 2020 it will be the fifth leading
cause of disability-adjusted life years lost.
Chronic obstructive pulmonary disease is the seventh leading cause of
death in Singapore today and morbidity due to this disease is rising. It is
timely that we develop the first national guidelines on chronic obstructive
pulmonary disease in order to deal with the disease. A multidisciplinary
expert committee has reviewed the latest evidence from the scientific
literature and used their expertise to localize the guidelines.
I hope these guidelines will assist all doctors, especially primary care
physicians, in managing their patients with chronic obstructive pulmonary
disease.
PROFESSOR K SATKU
DIRECTOR OF MEDICAL SERVICES
5
Contents
Page
Executive summary of recommendations
1
1
Introduction
15
2
Epidemiology and Risk factors
17
3
Definition, Differential Diagnosis and Classification
of Severity
18
4
Evaluation
22
5
Pharmacotherapy for Stable COPD
25
6
Non-pharmacological Management of Stable
COPD
36
7
Monitoring of patients with Stable COPD
48
8
Management of Acute Exacerbations
49
9
Air Travel
55
10
Surgery in COPD Patients
57
11
End of Life Care
59
12
Clinical Quality Improvement
61
References
62
Self-assessment (MCQs)
78
W orkgroup members
83
Executive summary of recommendations
Details of recommendations can be found in the main text at the pages indicated.
Definition, Differential Diagnosis and Classification of
Severity
D Where diagnostic doubt remains, or both COPD and asthma are
present, the following findings will help identify asthma (pg 18):
•
•
•
A large response (FEV1 greater than 400 ml) to bronchodilators.
A large response (FEV1 greater than 400 ml) to 30 mg oral
prednisolone daily for 2 weeks.
Serial peak flow measurements showing 20% or greater diurnal or
day-to-day variability.
Grade D, Level 4
D Where chronic asthma cannot be distinguished from COPD with
the current imaging or lung function testing, it is assumed that the two
diseases co-exist and their management should be similar to that of
asthma (pg 19).
Grade D, Level 4
D COPD should be differentiated from congestive heart failure,
bronchiectasis, and obliterative bronchiolitis (pg 19).
Grade D, Level 4
D A classification of disease severity into 5 stages based on
spirometry cut points is recommended (pg 20).
Grade D, Level 4
Table 3
Classification of severity*
Stage
0: At Risk
Characteristics
normal spirometry
chronic symptoms (cough, sputum production)
I: Mild COPD
FEV1/FVC < 70%
FEV1 ≥ 80% predicted
with or without chronic symptoms (cough,
sputum production)
II: Moderate COPD
FEV1/FVC < 70%
50% ≤ FEV1 < 80% predicted
with or without chronic symptoms (cough,
sputum production)
III: Severe COPD
FEV1/FVC < 70%
30% ≤ FEV1 < 50% predicted
with or without chronic symptoms (cough,
sputum production)
IV: Very Severe
FEV1/FVC < 70%
FEV1 < 30% predicted or FEV1 < 50%
COPD
predicted plus chronic respiratory failure
*Classification based on postbronchodilator FEV1
FEV1: forced expiratory volume in one second; FVC: forced vital
capacity; respiratory failure: arterial partial pressure of oxygen (PaO2)
less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of
CO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) while breathing air at sea
level.
(Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD),
2005)
Evaluation
D A diagnosis of COPD should be considered in any patient more
than 35 years old, who has chronic cough, sputum production, or
dyspnoea, and/or a history of exposure to risk factors for the disease
(see Table 4) (pg 22).
Grade D, Level 4
D Spirometry is useful for the definitive diagnosis of COPD and for
the staging of disease severity and should be performed in individuals
with symptoms suggestive of COPD (pg 23).
Grade D, Level 4
D It is also recommended that bronchodilator reversibility testing be
performed to help identify some subjects with asthma or a large
asthma component to COPD and to establish a patientʼs best attainable
lung function (pg 24).
Grade D, Level 4
D Arterial blood gases should be performed in patients with FEV1
<40% predicted or with clinical signs suggestive of respiratory failure
or right heart failure (pg 24).
Grade D, Level 4
D A chest X-ray is seldom diagnostic in COPD but it is valuable in
excluding alternative diagnoses and should be performed to look for
abnormalities that may suggest other conditions. Computed
tomography of the chest is not routinely recommended (pg 24).
Grade D, Level 4
Pharmacotherapy for stable COPD
A Inhaled short-acting bronchodilators are recommended as first-line
therapy in all stages of COPD to relieve symptoms and improve
exercise capacity (pg 26).
Grade A, Level 1+
A Regular treatment with one or both classes of the inhaled longacting bronchodilators should be considered for patients with
moderate to very severe COPD with frequent exacerbations (pg 28).
Grade A, Level 1+
D Inhaled long-acting bronchodilators may be added to the treatment
regimen when symptoms are not controlled with short-acting inhaled
bronchodilators alone (pg 28).
Grade D, Level 4
D Theophylline may be a useful addition where symptom control is
still not achieved with existing inhaled bronchodilator therapy.
Theophylline may be of value for patients who are non-adherent to or
unable to use inhaled therapy (pg 30).
Grade D, Level 4
A Inhaled corticosteroids as long-term maintenance therapy are
recommended for patients with FEV1 <50% predicted who experience
frequent exacerbations (pg 32).
Grade A, Level 1+
A Long-term oral corticosteroids are not recommended in stable
COPD (pg 32).
Grade A, Level 1+
D Combination inhaled corticosteroids and long-acting ? 2-agonists
should be considered for patients in whom both its components are
indicated (pg 33).
Grade D, Level 4
C Annual influenza vaccination should be offered to the elderly (65
years and above) in all stages of COPD (pg 33).
Grade C, Level 2++
D Pneumococcal vaccination may be considered in COPD patients
(pg 34).
Grade D, Level 4
D If considering pneumococcal vaccination for a COPD patient,
usually only one dose of the vaccine is needed. A second dose is
recommended for persons aged 65 or older who received their first
dose when they were under 65, if 5 or more years have passed since
that dose (page 34).
Grade D, Level 4
Table 7
Recommended pharmacotherapy in stable COPD
Symptoms
Exacerbations
Spirometry
Intermittent
AND
Regardless of
FEV1
Few
exacerbations
Recommended
pharmacotherapy
SABA or
Combination SABA/SAAC inhaler
as needed for symptom relief
SABA
as needed for symptom relief
Persistent*
AND/OR
Frequent
exacerbations†
AND
FEV1 > 50%
predicted
With one of the following:
1) SAAC 4 to 6 hourly or
2) Combination SABA/SAAC
inhaler 4 to 6 hourly or
3) Long-acting anticholinergic
(LAAC) once daily‡
to which may be added:
Long-acting 2
2-agonist (LABA)
12 hourly‡
AND/OR
Intermittent
or
Persistent
AND
AND
Frequent
exacerbations
FEV1 < 50%
predicted
Sustained-release theophylline
12 hourly or once daily‡
As above
AND
Inhaled corticosteroids
SABA = short-acting 2-agonist
SAAC = short-acting anti-cholinergic
*
Persistent symptoms: exertional dyspnoea, diminished exercise capacity, persistent
cough, wheeze despite SABA/combination SABA/SAAC inhaler as needed.
†
Frequent exacerbations: two or more acute exacerbations a year requiring systemic
steroids.
GPP The choice between LAAC, LABA or theophylline is dependent on the
individual patientʼs response in terms of symptom relief and side-effects, and
affordability of the medication. This should be re-evaluated if there is lack of
therapeutic response.
‡
GPP
Non-pharmacological Management for Stable COPD
Patient education
D Patient education is a vital part of COPD management and should
begin at the time of first assessment for COPD and continue with each
follow-up visit (pg 36).
Grade D, Level 4
D The intensity and content of patient educational messages should
vary depending on the severity of the patientʼs disease (see Table 8)
(pg 36).
Table 8
Recommended topics for patient education
according to severity of disease
Severity of Disease
Stage 0: At Risk
Patient Education Topic
Information and advice about reducing
risk factors.
Stage I: Mild COPD
through Stage III:
Severe COPD
Above topic, plus:
Information about the nature of COPD.
Instruction on how to use inhalers and
nebulizer.
Information on influenza vaccination and
medication.
Recognition and treatment of
exacerbation.
Strategies for minimizing dyspnea
Information on pulmonary rehabilitation.
Stage IV: Very Severe
COPD
Above topic, plus:
Information about complications.
Information about oxygen treatment.
Advance directive and end-of-life
decisions.
[Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD),2005]
Grade D, Level 4
D Patient education should be (pg 37):
•
•
•
•
•
•
Tailored to meet the needs of the individual patient
Interactive
Directed to improving quality of life
Simple to follow
Practical
Appropriate to the intellectual and social skill of the patient and
the caregivers.
Grade D, Level 4
Smoking cessation
A Smoking cessation should be emphasized as an essential first step
in management of COPD patients (pg 37).
Grade A, Level 1++
GPP Clinicians should play a prominent role in promoting attempts
to stop smoking in their patients (pg 37).
GPP
A All smokers, including those who may be at risk for COPD as well
as those who already have the disease, should be offered at least a
brief tobacco dependence counseling at every health care provider
visit (pg 37).
Grade A, Level 1++
D Pharmacotherapy for smoking cessation is recommended when
counseling is not sufficient to help patients quit smoking (pg 38).
Grade D, Level 4
A Treatment of nicotine dependence is effective and should be
offered to smokers in addition to counselling (pg 38).
Grade A, Level 1++
A These pharmacotherapies reliably increase long-term smoking
abstinence rates and at least one of these medications should be added
to counseling if necessary and in the absence of contraindications (pg
38).
Grade A, Level 1++
Nutrition in COPD
D All patients with COPD should undergo simple nutrition screening
(pg 39).
Grade D, Level 4
GPP Nutritional intervention should be considered in all COPD
patients with BMI < 18.5 kg/m2 or significant involuntary weight loss
(>10% during the last 6 months or > 5% in the past month) (pg 39).
GPP
Pulmonary rehabilitation
D Pulmonary rehabilitation may be considered for patients with the
following (pg 41):
• persistent symptoms especially dyspnoea,
• reduced exercise tolerance or experience a restriction in activities,
• recurrent admissions to hospitals over the last 6 months.
Grade D, Level 4
B The physical components of pulmonary rehabilitation should
include both lower extremity training (e.g., bicycle, ergometry,
treadmill) and upper extremity training (strength and endurance) (pg
41).
Grade B, Level 2+
D Psychosocial and behavioral interventions (health education,
smoking cessation clinic, and support groups addressing psychosocial
issues) as well as nutritional intervention should also be included as
non-physical components of the comprehensive pulmonary
rehabilitation programs (pg 41).
Grade D, Level 4
Oxygen therapy in chronic obstructive pulmonary disease
A Patients with very severe COPD and chronic respiratory failure
should be assessed for the need for long-term oxygen therapy (pg 42).
Grade A, Level 1+
A Indications for long-term oxygen therapy (at least 15 hours/day) in
patients with COPD should be based on the following indices obtained
in stable state (pg 42):
•
Without pulmonary hypertension (Cor Pulmonale), congestive
heart failure, polycythaemia (Hct >55%):
1.
PaO2 < 55 mmHg on Room Air
OR
SaO2 < 89% on Room Air
2.
•
With pulmonary hypertension (Cor Pulmonale), congestive heart
failure, polycythaemia (Hct >55%):
1.
PaO2 between 55 mmHg - 60 mmHg on Room Air
OR
SaO2 < 89% on Room Air
2.
Grade A, Level 1+
D Oxygen concentrator is the preferred mode of delivery of oxygen. It
is the most convenient and economical method of providing long-term
oxygen therapy (pg 43).
Grade D, Level 3
D Very severe COPD patients with hypercapnic respiratory failure
requiring long-term oxygen therapy should have the oxygen flow rate
titrated cautiously to maintain a SaO2 > 90% (pg 43).
Grade D, Level 4
Monitoring of patients with stable COPD
D & GPP Patients should be seen and assessed regularly (e.g. threemonthly in the stable state) (pg 48).
At each follow-up visit:
• Patients should be asked regarding onset of any new symptoms
and/or worsening of exercise capacity.
•
Current smokers should be given repeated advice to quit.
•
Adherence to medications should be assessed, and the patientʼs
inhaler technique checked and re-taught if necessary.
Grade D, Level 4/GPP
D & GPP Indications for specialist referral (pg 48)
•
Severe COPD (FEV1 < 50% predicted).
•
Frequent exacerbations (e.g. two or more a year) despite
compliance to treatment.
•
Rapidly progressive course of the disease.
•
Development of new symptoms e.g. haemoptysis, or new physical
signs e.g. cyanosis, peripheral oedema.
Grade D, Level 4/GPP
Management of Acute Exacerbations
C Chest radiography is recommended in an acute exacerbation, when
other diagnoses like pneumonia or heart failure need to be excluded
(pg 50).
Grade C, Level 2+
D Sputum culture is not recommended for routine investigation of
patients with exacerbation (pg 50).
Grade D, Level 3
D Pulse oximetry, if available, can assist doctors in identifying
patients with hypoxaemia when oxygen saturation (SaO2) is less than
90% (pg 50).
Grade D, Level 3
Pharmacological management
A Inhaled anticholinergic bronchodilators or inhaled short-acting
agonists are beneficial and should be used in the treatment of patients
presenting with acute exacerbation of COPD (pg 52).
Grade A, Level 1+
D Both nebulisers and hand-held inhalers can be used to administer
inhaled therapy during exacerbations of COPD, as they are equally
effective in achieving bronchodilation in COPD exacerbations (pg
52).
Grade D, Level 4
10
A In the absence of significant contraindications, oral corticosteroids
should be used, in conjunction with other therapies, in all patients
admitted to hospital with an exacerbation of COPD (pg 52).
Grade A, Level 1+
A In the absence of significant contraindications, oral corticosteroids
should be considered in patients managed in the community who have
an exacerbation with a significant increase in the breathlessness which
interferes with daily activities (pg 52).
Grade A, Level 1+
A Prednisolone 30 mg orally should be prescribed for 7 to 14 days to
patients with an exacerbation. It is recommended that a course of
corticosteroid treatment should not be longer than 14 days as there is
no advantage in prolonged therapy (pg 53).
Grade A, Level 1+
A Antibiotics should be used to treat exacerbations of COPD when
(pg 53):
(1) there is history of purulent sputum
(2) there are clinical signs of pneumonia
(3) there is consolidation on a chest radiograph
Grade A, Level 1+
Non-pharmacological therapy
GPP Oxygen therapy should be considered if patient is known, or
suspected, to have hypoxaemia. This can be administered via nasal
prongs, or venturi mask. One should exercise caution in the oxygen
dose for patients, such that the lowest possible oxygen concentration
to maintain oxygen saturation above 90% is provided. If pulse
oximetry is not available, the concentration of the oxygen mask
should not exceed 28%, or the nasal prong oxygen flow rate should be
kept at 2L/min (pg 53).
GPP
A Non-invasive ventilation should be used as the treatment of choice
in the hospital, for persistent hypercapnic ventilatory failure during
exacerbations despite optimal medical therapy (pg 53).
Grade A, Level 1+
11
Algorithm for the management of an acute exacerbation
Acute exacerbation
Assessment by physician
Signs of severe exacerbation (any of the following)
marked dyspnoea and tachypnoea (>30 respirations/minute)
use of accessory muscles (sternomastoid and abdominal) at rest
cyanosis
confusion
SaO2 <90%
•
•
•
•
•
No
Mild exacerbations
• Initiate, increase dose or frequency, or combine β2-agonist and/or
• Anticholinergic
• Encourage sputum clearance by coughing
• Consider chest physiotherapy
• Encourage fluid intake
• Avoid sedatives and hypnotics
• Consider antibiotics
• Consider oral corticosteriods*
Instruct patients on symptoms and signs of worsening and actions to
take: Contact primary care physician or go to emergency department.
Improved
Reassess within 48 hours
by physician
Yes
Refer to
hospital
Worsened
Not improving
Continue same
management or reduce
intensity (step down)
Stable COPD
management
Consider adding corticosteroids*
or a course of antibiotics if not
given earlier. Instruct patient on
symptoms, signs of worsening
and action to take.
*30 mg of prednisolone daily for up to 14 days
(Adapted from European Respiratory Society Consensus Statement, 1995)
12
Worsened
When to refer to the Emergency Department (ED)
GPP Any one of the following signs may indicate severe
exacerbations requiring urgent referral to the Emergency Department
(pg 54):
1.
2.
3.
4.
5.
marked dyspnoea and tachypnoea (> 30 respirations/minute)
use of accessory muscles (sternomastoid and abdominal) at
rest
cyanosis
confusion
SaO2 <90%
GPP
Air Travel
D Patients with severe COPD, history of air travel intolerance with
respiratory symptoms (dyspnoea, chest pain, confusion, syncope), comorbidity with other conditions worsened by hypoxaemia
(cerebrovascular disease, coronary artery disease, heart failure), and
recent pneumothorax should undergo assessment before flying.
The following assessment is recommended141:
•
history and examination with particular reference to cardiorespiratory disease, dyspnoea and previous flying experience
•
spirometry (in non-tuberculous patients only)
•
measurement of SpO2 by pulse oximetry. Readings should be
taken from a warm ear or finger after sufficient delay for the
oximeter to display a stable reading. Blood gases are preferred if
hypercapnia is known or suspected
(pg 55)
Grade D, Level 4
D Patients who have resting sea level oximetry between 92% and
95% and who have additional risk factors (Table 9) should be referred
for further assessment (pg 55).
Grade D, Level 4
13
Surgery in COPD patients
GPP Preoperative assessment of a COPD patient should include (pg
57):
1.
2.
3.
4.
5.
Detailed history and physical examination
Assessment of functional capacity (American Society of
Anesthesiology Physical Status Scale). See Table 10.
Preoperative Spirometry
Arterial Blood Gas especially in moderate to severe COPD
Chest Radiograph
GPP
A COPD patients being considered for surgery should be assessed for
risk of developing venous thromboembolism and also for
thromboprophylaxis during the perioperative assessment (pg 58).
Grade A, Level 1+
A Combination of bronchodilators, chest physiotherapy, antibiotics,
smoking cessation for at least 4-8 weeks and a short course of oral
corticosteroids should be given for patients with acute exacerbation so
as to reduce the risk of postoperative pulmonary complications (pg
58).
Grade A Level 1+
End of Life Care in COPD
D Patients should be educated about their disease, prognosis and
possible circumstances of death (pg 59).
Grade D, Level 3
D Physicians should discuss end of life issues and advance care
planning with patients (and their relatives) who have severe to very
severe COPD (pg 59).
Grade D, Level 3
B Physicians who look after severe to very severe COPD patients (as
with all physicians caring for the terminally ill) will need to be
prepared to discuss end of life issues with patients (pg 60).
Grade B, Level 1+
14
1
1.1
Introduction
Aim and scope of guidelines
The aim of these guidelines is to give physicians a practical approach
and guide to the care of chronic obstructive pulmonary disease
(COPD) patients. It is hoped that with the aid of the guidelines, the
clinician will be able to deliver an even higher standard of care for our
patients.
Emphasis is placed on the definition, diagnosis and evaluation of the
disease as it has been shown to be frequently under-recognised and
under-diagnosed.1
The appropriate management of the patient in the stable state as well
as in acute exacerbations with both pharmacological and nonpharmacological measures is explored in detail. A table on the use of
pharmacotherapy is created to help clinicians deal with the myriad of
drug classes and combinations available for treatment.
Finally, sections on unique aspects of care in COPD patients are also
included to ensure comprehensive coverage of the subject.
1.2
Target group
These guidelines are meant for all doctors having to care for COPD
patients; in particular, primary care doctors and doctors who are not
respiratory physicians.
1.3
Guideline development
It is timely that the nation develops her first national guidelines on
COPD with the current recognition of the importance of appropriate
management of chronic diseases. The need for these guidelines was
first mooted by the College of Family Physicians, Singapore; the
chairperson and committee were subsequently appointed by the
Ministry of Health.
This committee was carefully selected to represent a multidisciplinary group of clinicians working in different settings. Both
private and public primary care, intermediate care at community
15
hospitals as well as acute care physicians in the private and public
tertiary hospitals were involved in the development of the guidelines.
We also had representatives from the National University of
Singapore.
The workgroup reviewed literature from many of the COPD
guidelines that had already been developed by renowned bodies in the
world [e.g. Global Initiative for Chronic Obstructive Lung Disease
(GOLD), National Institute for Health and Clinical Excellence
(NICE), American Thoracic Society/European Respiratory Society
(ATS/ERS)].2,3,4 Best available current evidence and expert opinions
were also sought in areas that were not covered in other published
guidelines.
1.5
Review of guidelines
Evidence-based clinical practice guidelines are only as current as the
evidence that support them. Users must keep in mind that new
evidence could supersede recommendations in these guidelines.
The workgroup advises that these guidelines be scheduled for review
three years after publication, or if new evidence appears that requires
substantive changes to the recommendations.
16
2
2.1
Epidemiology and Risk Factors
Epidemiology
Chronic obstructive pulmonary disease (COPD) is a major cause of
mortality and disability worldwide.5 Whereas morbidity and mortality
of other major chronic diseases have been steadily declining, the
trends for COPD are continually increasing, especially among the
elderly.6 According to the WHO Global Burden of Disease Study, by
2020, COPD will be the fifth leading cause of disability-adjusted life
years (DALY) lost worldwide.7
COPD costs the US economy an estimated $23.9 billion a year, most
of it in direct costs of medical care.8 Hospitalization for acutely
exacerbated COPD accounts for a large part of the high healthcare
expenditure for COPD.8 Expenditure for inpatient hospitalizations of
COPD per patient is more than twice that for other inpatients.9
More than half of COPD patients who are hospitalized for acute
exacerbations are readmitted at least once within 6 months after
hospital discharge.10 Exacerbated COPD results in relatively longer
length of stay than most other diseases, and in poor quality of life.11,12
The prevalence of COPD in older adults after 40 years of age varies
from 8% to 20% in different countries.1,13
In Singapore, COPD is currently the seventh leading cause of death.14
About 2,000 hospitalizations for COPD per year are recorded and the
numbers are steadily increasing.15
COPD is under-recognized and under-diagnosed. Less than 50% of
individuals with COPD based on airflow limitation have a doctorʼs
diagnosis of COPD.1
2.1.1 Risk factors
The risk of COPD is highest after age 50, and is generally higher in
men than women, although this appears to be changing. Smoking is by
far the most important risk factor. Other major environmental factors
are occupational dusts and chemicals (vapors, irritants, fumes), and
indoor/outdoor air pollution.16,17 Severe hereditary deficiency of
alpha-1 antitrypsin is a well-documented host factor,18 although rare
locally.
17
3
3.1
Definition, Differential Diagnosis and
Classification of Severity
Definition
COPD is a heterogenous disorder characterised by airflow obstruction
that is not fully reversible. The airflow limitation is usually both
progressive and associated with exposure to noxious particles or
gases.2
3.2
Differential diagnosis
A major differential diagnosis of COPD is bronchial asthma. These
two conditions are frequently distinguishable on the basis of history
and examination in untreated patients presenting for the first time.2,3
Table 1 shows the features that help to differentiate between COPD
and Asthma.
Table 1
Clinical features of COPD and bronchial
asthma2,3
Smoking history
Symptoms < 35 years
Chronic productive
cough
Breathlessness
Nocturnal symptoms
Diurnal variation of
symptoms
COPD
Nearly all
Rare
Common
Asthma
Possibly
Often
Uncommon
Persistent/progressive
Uncommon
Uncommon
Variable
Common
Common
D Where diagnostic doubt remains, or both COPD and asthma are
present, the following findings will help identify asthma3:
• A large response (FEV1 greater than 400 ml) to bronchodilators.
• A large response (FEV1 greater than 400 ml) to 30 mg oral
prednisolone daily for 2 weeks.
• Serial peak flow measurements showing 20% or greater diurnal or
day-to-day variability.
Grade D, Level 4
18
The definition of COPD requires confirmation of persistent airflow
obstruction
after
administration
of
a
bronchodilator. 4
Bronchoreversibility, however, cannot serve as an absolute criterion
for separating asthma from COPD.19 On the other hand,
documentation of complete reversibility is useful in excluding COPD,
and a documentation of bronchoreversibility of a rise of FEV1 >400
ml has been suggested3 to indicate such a reversibility. Similarly, a
variation of 20% or greater diurnal or day-to-day variability is the
level for documenting complete bronchoreversibility.19
D Where chronic asthma cannot be distinguished from COPD with
the current imaging or lung function testing, it is assumed that the two
diseases co-exist and their management should be similar to that of
asthma.3
Grade D, Level 4
D COPD should be differentiated from congestive heart failure,
bronchiectasis, and obliterative bronchiolitis.3
Grade D, Level 4
Congestive heart failure, bronchiectasis, and obliterative bronchiolitis
may present with similar symptoms and signs as COPD. These
conditions may mimic COPD or may co-exist in a patient with COPD.
See Table 2.
Table 2
Features useful in differentiating other
conditions from COPD3
Congestive heart failure – fine basilar crepitations, chest X-ray
shows dilated heart, pulmonary oedema, and pulmonary function
tests indicate volume restriction and not airflow limitation.
Bronchiectasis – large volumes of purulent sputum, commonly
associated with bacterial infection, coarse crepitations on
auscultation, clubbing, chest X-ray shows bronchial dilatation and
bronchial wall thickening.
Obliterative bronchiolitis – Onset in younger age, non-smoker,
may have history of rheumatoid arthritis or fume exposure,
computed tomography on expiration shows hypodense areas.
[Source: National Collaborating Centre for Chronic Conditions, National
Institute for Health and Clinical Excellence (NICCCC/NICE), 2004]
19
3.3
Classification of severity
Spirometry
D A classification of disease severity into 5 stages based on
spirometry cut points is recommended. 2
Grade D, Level 4
The FEV1 and FEV1/FVC cut-points used by the Global Initiative for
Obstructive Lung Disease (GOLD) for classifying the severity of
COPD into 5 stages is shown in Table 3. These cut points are used for
the purposes of educational simplicity: they have not been clinically
validated.
Table 3
Classification of severity*
Stage
0: At Risk
Characteristics
normal spirometry
chronic symptoms (cough, sputum production)
I: Mild COPD
FEV1/FVC < 70%
FEV1 ≥ 80% predicted
with or without chronic symptoms (cough,
sputum production)
II: Moderate COPD
FEV1/FVC < 70%
50% ≤ FEV1 < 80% predicted
with or without chronic symptoms (cough,
sputum production)
III: Severe COPD
FEV1/FVC < 70%
30% ≤ FEV1 < 50% predicted
with or without chronic symptoms (cough,
sputum production)
IV: Very Severe
FEV1/FVC < 70%
COPD
FEV1 < 30% predicted or FEV1 < 50%
predicted plus chronic respiratory failure
*Classification based on postbronchodilator FEV1
FEV1: forced expiratory volume in one second; FVC: forced vital
capacity; respiratory failure: arterial partial pressure of oxygen (PaO2)
less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of
CO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) while breathing air at sea
level.
(Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD),
2005)
20
Other classification systems
Other ways of classifying disease severity have been described. Until
their usefulness is validated, the classification of disease severity
based on airway obstruction will be used.
Two of the ways of classifying disease severity are:
(1) the use of the Medical Research Council Dyspnoea Scale
described by Nishimura et al20, and
(2) the BODE index which is a multidimensional index consisting of
body mass index (B), the degree of airway obstruction (O),
dyspnoea (D), and exercise capacity (E), measured by the sixminute-walk test.21
21
4
4.1
Evaluation
Clinical assessment
D A diagnosis of COPD should be considered in any patient more
than 35 years old, who has chronic cough, sputum production, or
dyspnoea, and/or a history of exposure to risk factors for the disease22
(see Table 4).
Grade D, Level 4
Table 4
Chronic
cough
Chronic
sputum
production
Dyspnoea
History of
exposure to
risk
factors
Key indicators for considering a
diagnosis of COPD
Present intermittently or everyday. Often
present throughout the day; seldom only
nocturnal.
Any pattern of chronic sputum production may
indicate COPD.
Progressive (worsens over time). Persistent
(present every day). Described by the patient
as: “increased effort to breathe,” “heaviness,”
“air hunger,” or “gasping.”
Worse on exercise.
Worse during respiratory infections.
Tobacco smoke. Occupational dusts and
chemicals. Smoke from home cooking
especially and heating fuels.
4.1.1 Physical examination
Physical examination is rarely diagnostic in COPD. Physical signs of
airflow obstruction, e.g. hyperinflation, are rarely present until
significant lung function impairment has occurred.23,24 Hence their
detection has a low sensitivity and specificity.22
Physical signs of airflow obstruction that that may be present are3:
• Hyperinflated chest
• Purse lip breathing
22
•
•
•
•
•
Use of accessory muscle
Paradoxical movements of lower ribs
Reduced crico-sternal distance
Reduced cardiac dullness
Wheeze or quiet breath sounds
Loss of muscle mass and peripheral muscle weakness are present in
advanced disease.
4.1.2 Assessment of severity
Assessment of severity is based on the patientʼs level of symptoms,
the severity of the spirometric abnormality, and the presence of
complications such as cor pulomonale, respiratory failure and right
heart failure.22
Physical signs of cor pulmonale to look for are3:
• Central cyanosis
• Raised jugular venous pressure
• Left parasternal heave
• Loud P2 and a loud ejection click
• Pansystolic murmur or tricuspid regurgitation
• Hepatomegaly
• Peripheral oedema
Progressive impairment of consciousness, the presence of a bounding
pulse, flapping tremor and papilloedema indicate carbon dioxide
retention and impending respiratory failure.
4.2
Lung function tests
4.2.1 Spirometry
D Spirometry is useful for the definitive diagnosis of COPD and for
the staging of disease severity, and should be performed in individuals
with symptoms suggestive of COPD.22
Grade D, Level 4
Spirometry should measure the maximal volume of air forcibly
exhaled from the point of maximal inhalation (forced vital capacity,
FVC) and the volume of air exhaled during the first second of this
23
maneuvre (forced expiratory volume in one second, FEV1), and the
ratio of these two measurements (FEV1/FVC) should be calculated.22
The primary benefit of spirometry is to identify COPD patients who
may benefit from pharmacologic treatment in order to improve
symptoms and exacerbations.25
Spirometry for case finding among all adults with a history of
exposure to pulmonary risk factors, whether they have persistent
respiratory symptoms or not, is unlikely to be beneficial unless future
studies establish that spirometry improves smoking cessation rate, or
that treatments other than smoking cessation benefit individuals with
airflow obstruction who do not report respiratory symptoms.25
Spirometry for monitoring individuals or adjusting treatment is
unlikely to be beneficial unless future studies establish that relative
effectiveness between therapies varies according to an individualʼs
baseline or follow-up spirometry.25
4.2.2 Bronchodilator reversibility testing
D It is recommended that bronchodilator reversibility testing be
performed to help to identify some subjects with asthma or a large
asthma component to COPD23 and to establish a patientʼs best
attainable lung function.22
Grade D, Level 4
4.3
Arterial blood gases
D Arterial blood gases should be performed in patients with FEV1
<40% predicted or with clinical signs suggestive of respiratory failure
or right heart failure.22
Grade D, Level 4
4.4
Chest X-ray
D A chest X-ray is seldom diagnostic in COPD but it is valuable in
excluding alternative diagnoses1 and should be performed to look for
abnormalities that may suggest other conditions. Computed
tomography of the chest is not routinely recommended.22
Grade D, Level 4
24
5.1
Goals of pharmacotherapy in COPD
•
•
•
•
Relieve, reduce and abolish symptoms
Increase exercise capacity
Reduce frequency and severity of acute exacerbations
Improve health related quality of life
These goals should be achieved with minimum side-effects from the
medications.
There is currently no evidence that any pharmacotherapy influences
lung function decline or mortality in COPD. Evidence from largescale studies regarding the effect of pharmacotherapy on these
outcome measures is anticipated in the near future.
5.2
5.3
Principles of therapy
•
Treatment needs to be maintained long-term.
•
Treatment is according to stage of severity, with step-wise
increase usually required, as COPD is a progressive disease.
•
Inhaled therapy via metered dose or dry powder inhalers is
preferred. The use of a large-volume spacer is advised for patients
who have difficulty mastering the metered-dose inhaler technique.
Drugs used in the pharmacotherapy of stable COPD
I.
Bronchodilators :
A) Inhaled short-acting 2-agonists
B) Inhaled short-acting anti-cholinergic
C) Combination short-acting 2-agonists + short-acting
anticholinergic inhalers
D) Inhaled long-acting ? 2-agonists
E) Inhaled long-acting anti-cholinergic
F) Oral theophylline
II. Inhaled corticosteroids
III. Combination inhaled corticosteroids + long-acting 
? 2-agonists
25
IV. Vaccines – influenza, pneumococcal
V. Others
I.
Bronchodilators
Bronchodilator drugs are the mainstay of pharmacological therapy in
COPD. They relax bronchial smooth muscles, relieve bronchospasm
and improve symptoms. All categories of bronchodilators have been
shown to increase exercise capacity in COPD, without necessarily
producing significant changes in FEV1. Bronchodilators have however
not been shown to have any effect on the rate of lung function decline
or survival in COPD.
Bronchodilators used in the pharmacotherapy of COPD comprise
short- and long-acting anti-cholinergics (available only as inhaled
medications), and short- and long-acting 
? 22-agonists (available in the
oral and inhaled form) and oral theophylline.
Inhaled therapy via metered-dose or dry powder inhaler is preferred as
these have a more rapid onset of action, with less systemic side effects
than the oral formulations. Wet nebulizers are generally not
recommended for regular use in stable COPD – the delivery of higher
drug doses via this method may increase side effects, and these
devices are more costly and require appropriate maintenance.26
The choice of bronchodilator(s) would depend on the individual
patientʼs response in terms of symptom relief, side-effects and
affordability.
Short-acting inhaled bronchodilators
A Inhaled short-acting bronchodilators are recommended as first-line
therapy in all stages of COPD to relieve symptoms and improve
exercise capacity.
Grade A, Level 1+
A. Short-acting 22-agonists (SABA)
Examples of inhaled short-acting 22-agonists:
• salbutamol (Ventolin®, Respolin®, Salamol®, Buventol®)
• terbutaline (Bricanyl®)
• fenoterol (Berotec®)
26
22-agonists produce bronchodilation by smooth muscle relaxation
through the activation of the adenylate cyclase pathway which
increases intracellular concentrations of cyclic adenosine
monophosphate. Regular administration of inhaled short-acting 22agonists is an effective and inexpensive treatment for the management
of patients with stable COPD.27 SABAs produce bronchodilation
more rapidly than anti-cholinergic agents, acting within 15 minutes of
administration with effects lasting 4 to 5 hours. They may be used up
to a maximum of 4 to 6 times a day. They may be used as on-demand
medications for relief of acute dyspnoea and for prophylaxis prior to
exertion. The main side-effects are tremor and palpitations.
B. Short-acting anti-cholinergic (SAAC)
Example: ipratropium bromide (Atrovent®)
Anti-cholinergic agents induce bronchodilation by attenuating vagal
tone in the airways via the blockage of acetylcholineʼs effect on M3
receptors. Ipratropium bromide is either equivalent to or more potent
than 22-agonist as a bronchodilator in COPD.28 It should be taken
regularly (4 to 6 hourly) rather than on an as-needed basis because of
its relatively slow onset of action. As quaternary anti-cholinergic
agents are poorly absorbed into the circulation, they are virtually free
of systemic side effects. The main side-effect is dryness of the mouth.
Tachyphylaxis does not develop despite prolonged usage of
anticholinergics.
Combination inhaler containing SAAC and SABA
Examples of combination products are:
• fenoterol combined with ipratropium bromide (Berodual®,
Duovent® nebuliser solution)
• salbutamol combined with ipratropium bromide (Combivent®)
As 22-agonists and anticholinergics produce bronchodilation through
different pathways, combination products were introduced in the hope
of achieving greater bronchodilation than with monotherapy. The
combination product was shown to produce greater and more
sustained improvements in FEV1 than either drug alone.29
27
Long-acting inhaled bronchodilators
A Regular treatment with one or both classes of the inhaled longacting bronchodilators should be considered for patients with
moderate to very severe COPD with frequent exacerbations.
Grade A, Level 1+
D Inhaled long-acting bronchodilators may be added to the treatment
regimen when symptoms are not controlled with short-acting inhaled
bronchodilators alone.2,3
Grade D, Level 4
C. Long-acting 22-agonists (LABA)
Examples of long-acting inhaled 22-agonists
• salmeterol (Serevent®)
• formoterol (Foradil®/ Oxis®)
Salmeterol and formoterol are potent 2-agonists with 12-hour or
greater duration of action when inhaled by patients with partially
reversible COPD.30 Formoterol has a faster onset of action (one to
three minutes compared with 10 to 20 minutes for salmeterol). Peak
effects are achieved at 1 to 2 hours for both compounds.
Regular use of LABAs has been shown to improve health status and to
reduce acute exacerbation rates compared to placebo31 but evidence
for effects of LABAs on symptoms and health-related quality of life is
inconsistent.32 Despite their dosing convenience, LABAs are more
expensive and evidence for advantage over ipratropium in terms of
efficacy is inconsistent in patients with poorly reversible stable
COPD.33 LABAs should be reserved for COPD patients who report
definite improvement (in terms of better exercise capacity or reduced
symptoms) whilst on this therapy.
D. Long-acting anticholinergic
Tiotropium (Spiriva®) is the only long-acting cholinergic currently
available. It has a duration of action greater than 24 hours. Like
ipratropium, tiotropium is poorly absorbed from the gastrointestinal
tract and the lung, thus reducing systemic bioavailability and
accounting for a favorable systemic safety profile.
28
Tiotropium has been shown to be effective in reducing acute
exacerbations, reducing symptoms and improving health-related
quality of life compared to placebo and to ipratropium bromide.31,34
One-year clinical trials suggest that it may slow FEV1 decline.35
Additional long-term studies are required to evaluate its effect on
mortality and change in FEV1, to clarify its role in comparison to, or
in combination with, long-acting ? 2-agonists and to assess its
effectiveness in mild and very severe COPD.
The effect of co-administration of other anticholinergic-containing
drugs with tiotropium has not been studied and is best avoided.
Combined use of a short or long-anticholinergic and LABA
Combining bronchodilators with different mechanisms and durations
of actions may increase the degree of bronchodilation for equivalent
or fewer side-effects. Previous studies in patients with moderate-tosevere stable COPD demonstrated that combination of ipratropium
with either formoterol or salmeterol is more effective than a
combination of the anti-cholinergic with SABAs, and shows additive
effects in improving lung function.36 Randomized controlled studies
have pointed favorably in the direction of combination of tiotropium
with a LABA.37 Findings suggest that since tiotropium ensures
prolonged bronchodilation, whereas formoterol adds fast onset and a
greater peak effect, the two drugs appear complementary.38
29
Table 5
Inhaled bronchodilators
Drug
Dosage / puff
(µg)
Inhaler delivery
device
Duration of
action
Short-acting 2-agonists (SABA)
Salbutamol (Ventolin®)
100
MDI
4-6h
Terbutaline (Bricanyl®)
500
DPI (turbuhaler)
4-6h
Fenoterol (Berotec®)
200
MDI
4-6h
20
MDI
4-6h
Short-acting Anti-Cholinergic (SAAC)
Ipratropium bromide
®
(Atrovent )
Combination SABA + SAAC
Fenoterol
/
(Berodual®)
Ipratropium
50 / 20
MDI
4-6h
Salbutamol /
(Combivent®)
Ipratropium
120 / 20
MDI
4-6h
Long-acting 2-agonists (LABA)
Formoterol (Oxis®)
4.5, 9
DPI (turbuhaler)
12+ h
Salmeterol (Serevent®)
25
MDI
12+ h
18
DPI (handihaler)
24+ h
Long-acting Anti-Cholinergic
Tiotropium (Spiriva®)
MDI = metered-dose inhaler
DPI = dry powder inhaler
E. Theophylline
D Theophylline may be a useful addition where symptom control is
still not achieved with existing inhaled bronchodilator therapy.
Theophylline may be of value for patients who are non-adherent to or
unable to use inhaled therapy.26
Grade D, Level 4
30
Oral theophylline, a non-specific phosphodiesterase inhibitor, has
been used for many years for the treatment of obstructive airway
diseases. In addition to its bronchodilator function, theophylline also
has effects on the respiratory muscles, mucociliary clearance,
ventilatory drive, and has immunomodulatory properties.
Careful monitoring for side-effects and drug interactions is needed in
view of its narrow therapeutic index. A target therapeutic range of 8 to
13 mg/dl is recommended. It is important to be aware of factors which
decrease its clearance, including potential drug interactions, and which
may precipitate drug toxicity (Table 6). Signs of toxicity include
arrhythmias and convulsions.
Table 6
Drugs and physiological variables that affect
theophylline metabolism in COPD2
Increased clearance
Decreased clearance
• Cigarette smoking
• Old age
• Anticonvulsant drugs
• Hypoxemia
• Rifampicin
• Respiratory acidosis
• Alcohol
• Congestive cardiac failure
• Liver cirrhosis
• Erythromycin, clarithromycin
• Quinolones
• Cimetidine (not ranitidine)
• Viral infections
• Some herbal remedies
[Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD),
2005]
A systematic review and meta-analysis of 20 randomised controlled
trials showed that theophylline improves lung function, ventilatory
capacity and arterial blood gas tensions compared to placebo, and that
patients preferred theophylline compared to placebo, although the risk
of nausea was increased.39
31
There are on-going trials to assess the efficacy and safety of the new,
specific (Type IV) phosphodiesterase inhibitors (oral or inhaled) in
COPD.
II.
Inhaled corticosteroids
A Inhaled corticosteroids as long-term maintenance therapy are
recommended for patients with FEV1 < 50% predicted who
experience frequent exacerbations.
Grade A, Level 1+
Examples of inhaled corticosteroids (ICSs) are beclomethasone
dipropionate (Becloforte®), budesonide (Pulmicort®) and fluticasone
propionate (Flixotide®).
Unlike asthma where ICSs play a key anti-inflammatory role and are
recommended first-line therapy, current evidence supports limiting the
use of ICSs in COPD to patients with moderate to severe disease and
who have frequent exacerbations. Six placebo-controlled trials with at
least 6 months follow-up period of inhaled corticosteroids at moderate
to high doses showed that ICS led to a 24% reduction in
exacerbations.40-45 This beneficial effect was uniformly seen in
studies with patients who had mean FEV1 < 2.0 L (or < 70%
predicted), regardless of the duration of the study or specific
formulation used.31
ICSs have only a modest effect on lung function in COPD. Individual
long-term studies have shown that they do not affect the rate of FEV1
decline in COPD of all severity grades.45-47
ICSs are associated with increased risk of oral candidiasis, dysphonia
and easy bruising, and may have a modest deleterious effect on bone
mineral density, although there was no clinically increased risk of
fractures reported in the trials.47,48
Oral corticosteroids
A Long-term oral corticosteroids are not recommended in stable
COPD.49
Grade A, Level 1+
32
Although a short course of high dose oral corticosteroid (prednisolone
30 mg/day) can improve lung function in some COPD patients, long
term use of lower doses (prednisolone at < 10 to 15 mg/day) does not
prevent worsening of the condition and is associated with increased
risk of adverse effects such as diabetes and osteoporosis.49
III.
Combination ICS + LABA
D Combination inhaled corticosteroids and long-acting 2-agonists
should be considered for patients in whom both its components are
indicated.26
Grade D, Level 4
The combination products available are Seretide® (fluticasone
propionate + salmeterol xinfonate) and Symbicort® (budesonide +
formoterol).
Three trials showed that combination therapy was associated with
lower exacerbation rates compared to monotherapy with LABA or
placebo.50-52 The effect was additive and not synergistic. Combination
therapy was also effective in improving trough FEV1 compared to
placebo, LABA and inhaled corticosteroids.
The combination formulation will be more convenient and will aid
compliance in patients for whom both an ICS and LABA are
indicated.
IV.
Vaccines
Influenza vaccination
C Annual influenza vaccination should be offered to the elderly (65
years old and above) in all stages of COPD.
Grade C, Level 2++
Influenza vaccination was associated with fewer hospitalizations for
pneumonia and influenza and with lower risk for death during the
influenza seasons in the elderly with chronic lung disease.53
33
Pneumococcal vaccination
D Pneumococcal vaccination may be considered in COPD patients.3
Grade D, Level 4
Although there is currently no firm evidence for its protective effect
against pneumococcal pneumonia and its usefulness in COPD patients
per se, the 23-valent polysaccharide pneumococcal vaccine is
advocated by some experts and national authorities for the elderly and
those with certain medical conditions including chronic heart and lung
disease. Vaccination has been shown to reduce bacteremic
pneumococcal disease in adults, and to be associated with reduced
death, complications and length of stay among hospitalized adults
with community-acquired pneumonia.54,55
D If considering pneumococcal vaccination for a COPD patient,
usually only one dose of the vaccine is needed. A second dose is
recommended for persons aged 65 or older who received their first
dose when they were under 65, if 5 or more years have passed since
that dose.55a
Grade D, Level 4
V.
Others
There is no evidence to date to support the benefit of the routine use of
maintenance antibiotic therapy, mucolytics/anti-oxidants respiratory
stimulants, vasodilators, nedocromil sodium or leukotriene modifiers
in stable COPD.
5.4
Cost-effectiveness of pharmacotherapy in COPD
A recent methodological critique of seven pharmacoeconomic studies
on maintenance therapy for COPD showed tiotropium to be
considered cost-effective relative to ipratropium, and inhaled
corticosteroids to be cost-effective for patient with moderate to severe
COPD relative to standard care.56 No conclusive information could be
reached for the cost-effectiveness of long-acting ?2-agonists.
Variations in drug costs and primary and tertiary healthcare costs
make it difficult to extrapolate the findings of cost-effectiveness
analyses in other healthcare settings to the local situation.
34
Table 7
Recommended pharmacotherapy in stable COPD
Symptoms
Exacerbations
Spirometry
Intermittent
AND
Regardless of
FEV1
Few
exacerbations
Recommended
pharmacotherapy
SABA or
Combination SABA/SAAC inhaler
as needed for symptom relief
SABA
as needed for symptom relief
Persistent*
AND/OR
AND
Frequent
†
exacerbations
FEV1 > 50%
predicted
With one of the following:
1) SAAC 4 to 6 hourly or
2) Combination SABA/ SAAC
inhaler 4 to 6 hourly or
3) Long-acting anticholinergic
(LAAC) once daily‡
to which may be added:
Long-acting 2
2-agonist (LABA)
12 hourly‡
AND/OR
Intermittent
or
Persistent
AND
AND
Frequent
exacerbations
FEV1 < 50%
predicted
Sustained-release theophylline
12 hourly or once daily‡
As above
AND
Inhaled corticosteroids
SABA = short-acting 2-agonist
SAAC = short-acting anti-cholinergic
*
Persistent symptoms: exertional dyspnoea, diminished exercise capacity, persistent
cough, wheeze despite SABA/combination SABA/SAAC inhaler as needed
†
Frequent exacerbations: two or more acute exacerbations a year requiring systemic
steroids
‡
GPP The choice between LAAC, LABA or theophylline is dependent on the
individual patientʼs response in terms of symptom relief and side-effects, and
affordability of the medication. This should be re-evaluated if there is lack of
therapeutic response.
GPP
35
6
6.1
Non-pharmacological Management for Stable
COPD
Patient education
Patient education plays a role in improving patient responses to
exacerbations, ability to cope with illness, improving health status and
smoking cessation.57-63
D Patient education is a vital part of COPD management and should
begin at the time of first assessment for COPD and continue with each
follow-up visit.64,65
Grade D, Level 4
The patient should be informed about the nature of his/her condition
and its treatment.
D The intensity and content of patient educational messages should
vary depending on the severity of the patient’s disease (see Table 8).
Table 8
Recommended topics for patient education
according to severity of disease
Severity of Disease
Stage 0: At Risk
Stage I: Mild COPD
through Stage III:
Severe COPD
Stage IV: Very
Severe COPD
Patient Education Topic
Information and advice about reducing risk
factors.
Above topic, plus:
Information about the nature of COPD.
Instruction on how to use inhalers and
nebulizer.
Information on influenza vaccination and
medication
Recognition and treatment of exacerbation.
Strategies for minimizing dyspnea
Information on pulmonary rehabilitation.
Above topic, plus:
Information about complications
Information about oxygen treatment
Advance directive and end-of-life
decisions
[Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD),2005]
Grade D, Level 4
36
D Patient education should be:64
•
•
•
•
•
•
Tailored to meet the needs of the individual patient
Interactive
Directed to improving quality of life
Simple to follow
Practical
Appropriate to the intellectual and social skill of the patient and
the caregivers.
Grade D, Level 4
Providing information and tools to enhance self-management in an
interactive session is more effective than didactic teaching.61,62
6.2
Smoking cessation
Smoking cessation is the single most effective and cost-effective way
in reducing the risk of developing COPD and stopping its
progression.66
A Smoking cessation should be emphasized as an essential first step
in management of COPD patients.66-71
Grade A, Level 1++
GPP Clinicians should play a prominent role in promoting attempts
to stop smoking in their patients.
GPP
A All smokers, including those who may be at risk for COPD as well
as those who already have the disease, should be offered at least a
brief tobacco dependence counseling at every health care provider
visit.68,72,73
Grade A, Level 1++
Brief strategies to help smokers to quit are summarized in the 5 As
approach68,74,75:
Ask: Systematically identify all tobacco users at every visit.
Implement an office-wide system that ensure that, for EVERY
patient at EVERY clinic visit, tobacco-use status is queried and
documented.
37
Advise: Strongly urge all tobacco users to quit.
In a clear, strong and personalized manner, urge every tobacco
user to quit.
Assess: Determine willingness to make a quit attempt.
Ask every tobacco user if he or she is willing to make a quit
attempt at this time (e.g. within the next 30 days)
Assist: Aid the patient in quitting.
Help the patient with a quit plan; provide practical counseling;
provide social support; recommend use of approved
pharmacotherapy; provide supplementary materials
Arrange: Schedule follow-up contact.
Schedule follow-up contact, either in person or via telephone
Pharmacotherapy
D Pharmacotherapy for smoking cessation is recommended when
counseling is not sufficient to help patients quit smoking.68
Grade D, Level 4
A Treatment of nicotine dependence is effective and should be
offered to smokers in addition to counseling.73,76-81
Grade A, Level 1++
In Singapore, there are four types of pharmacotherapies for tobacco
dependence available currently i.e. bupropion SR, nicotine gum,
nicotine inhaler, and nicotine patch.
A These pharmacotherapies reliably increase long-term smoking
abstinence rates72,73,75,76-89 and at least one of these medications should
be added to counseling if necessary and in the absence of
contraindications.68,75
Grade A, Level 1++
The choice of medication is a matter of the patient’s personal
preference, medication availability, past experience, medical history
and the presence of contraindications.76,90
38
These guidelines have been withdrawn
MOH clinical practice guidelines are considered withdrawn five years
after publication unless otherwise specified in individual guidelines.
Users should keep in mind that evidence-based guidelines are only as
current as the evidence that supports them and new evidence can
supercede recommendations made in the guidelines.
Cost-effectiveness of smoking interventions
Studies done in the United States on the cost effectiveness of the
clinical practice recommendation in the AHCPR guideline for
smoking cessation showed: the average cost per quitter was
US$3,779; the average cost per life-year saved, US$2,587; and the
average cost per QALY (quality-adjusted life-year) saved,
US$1,915.91
6.3
Nutrition in COPD
Prospective studies have shown that both weight loss and muscle
wasting are associated with an increased risk of mortality, morbidity,
and disability in COPD patients.92 At the same time, significant loss
in FFM (fat-free mass) has also been shown to be related to impaired
skeletal muscle strength, exercise capacity as well as decreased health
status.93 Prevalence studies have shown that malnutrition is found in
25% of patients with moderate to severe COPD patients and up to
35% of cases with very severe disease.94
The goal of nutritional intervention is to maintain reasonable body
weight (BMI 18.5 to 23).95 Nutritional intervention can be extended to
prevention and early treatment of weight loss in COPD patients. It
can also be combined with exercise and other components of a
comprehensive pulmonary rehabilitation programme.
D All patients with COPD should undergo simple nutrition screening.
Grade D, Level 4
This can be done by the following ways96:
• Measurement of body-mass index
• Evaluation of food, nutrient and fluid intake
• Other anthropometric measurements e.g. skin fold thickness
• Evaluation of biochemical markers e.g. serum albumin
GPP Nutritional intervention should be considered in all COPD
patients with BMI < 18.5 kg/m2 or significant involuntary weight loss
(>10% during the last 6 months or > 5% in the past month).
GPP
39
This can be done by the following ways97:
• Modification of patients’ dietary habits and administration of
energy dense nutritional supplement
• Maintenance of adequate dietary intake of vitamins and minerals
• Adoption of healthy lifestyle e.g., stop smoking, encourage
moderate physical activity
• Patients who become breathless while eating should be advised to
take small, frequent meals (to avoid post-prandial dyspnoea and
satiety and to improve compliance)
• Referral to dietician for further nutritional optimization
There is limited evidence that COPD patients benefit from nutritional
intervention per se. However, nutritional assessment in combination
with pulmonary rehabilitation and nutritional intervention has been
shown to improve the functional status of COPD patients.98,99
6.4
Pulmonary rehabilitation
Pulmonary rehabilitation is a structured multidisciplinary program of
care for patients with chronic respiratory impairment that is
individually tailored and designed to optimize physical and social
performance and autonomy.100 Team members include respiratory
physicians, family physicians, nurses, physiotherapists, occupational
therapists, dieticians, and medical social workers.100 Pulmonary
rehabilitation can be conducted as inpatient, outpatient or home
programs. Consideration of cost, availability and accessibility will
determine the patient’s choice.101-103
Studies have shown that COPD patients undergoing pulmonary
rehabilitation have experienced the following benefits:
• Improvement in exercise capacity and functional walking
distance.104-106
• Relief of dyspnoea and fatigue as well as enhancement of mastery
(sense of control over condition).104,106,107
• Improvement in health related quality of life.104-107
• Reduction in the number of hospitalizations and days in
hospital.101,105,108,109
• Reduction in anxiety and depression.101
40
D Pulmonary rehabilitation may be considered for patients with the
following:100,105,106
•
•
•
persistent symptoms especially dyspnoea,
reduced exercise tolerance or experience a restriction in activities,
recurrent admissions to hospital over the last 6 months.
Grade D, Level 4
The following conditions may adversely affect the outcome of
pulmonary rehabilitation:100
1.
2.
3.
Conditions that may interfere with the patient undergoing the
rehabilitation programme e.g. advanced arthritis, inability to learn
or disruptive behavior.
Conditions that may place the patient at undue risk during
exercise training e.g. severe pulmonary hypertension, unstable
angina or recent myocardial infarction.
Poorly motivated patients who are unable to complete the entire
rehabilitation programme.
B The physical components of pulmonary rehabilitation should
include both lower extremity training (e.g. bicycle, ergometry,
treadmill) and upper extremity training (strength and endurance).110
Grade B, Level 2+
D Psychosocial and behavioural interventions (health education,
smoking cessation clinic, and support groups addressing psychosocial
issues) as well as nutritional intervention should also be included as
non-physical components of the comprehensive pulmonary
rehabilitation programmes.100
Grade D, Level 4
6.5
Oxygen therapy in chronic obstructive pulmonary
disease
Long-term oxygen therapy (LTOT) has been shown to improve
survival in COPD patients with severe chronic respiratory
failure.111,112 The precise mechanism of this improvement in survival
is unknown.
41
Long-term oxygen therapy may also have a beneficial impact on
sleep, cognitive function and exercise tolerance in COPD patients with
chronic hypoxaemia.111,113
Domiciliary oxygen therapy has not been shown to improve survival
in COPD patients with mild to moderate hypoxaemia
(i.e. PaO2 > 55 mmHg) or with only nocturnal arterial
desaturation.114,115
The goal of long-term oxygen therapy is to maintain a baseline PaO2 >
60 mmHg and SaO2 > 90%. This is to ensure adequate oxygen
delivery to vital organs.
Inappropriate prescription for long-term oxygen therapy in patients
with COPD can result in respiratory depression.
A Patients with very severe COPD and chronic respiratory failure
should be assessed for the need for long-term oxygen therapy.
Grade A, Level 1+
A Indications for long-term oxygen therapy (at least 15 hours/day) in
patients with COPD should be based on the following indices obtained
in stable state111,112:
•
Without pulmonary hypertension (Cor Pulmonale), congestive
heart failure, polycythaemia (Hct >55%)
1.
PaO2 < 55 mmHg on Room Air
OR
SaO2 < 89% on Room Air
2.
•
With pulmonary hypertension (Cor Pulmonale), congestive heart
failure, polycythaemia (Hct >55%):
1.
PaO2 between 55 mmHg - 60 mmHg on Room Air
OR
SaO2 < 89% on Room Air
2.
42
Grade A, Level 1+
D Oxygen concentrator is the preferred mode of delivery of oxygen. It
is the most convenient and economical method of providing long-term
oxygen therapy.116
Grade D, Level 3
Prescription for oxygen therapy usually includes the following117:
1.
Source of supplemental oxygen (liquid oxygen, gas cylinders
or oxygen concentrators)
2.
Method of delivery (e.g. intranasal prongs, demand nasal
prongs, reservoir cannula, etc.)
3.
Duration of use.
4.
Oxygen flow rate at rest, during exercise or sleep.
Ambulatory COPD patients who need supplemental oxygen outside
the home are usually prescribed oxygen sources e.g. portable gas
cylinders or liquid oxygen.117
As there is a risk of fire and explosion, very severe COPD patients
requiring long-term oxygen therapy should be advised against
smoking cigarettes.117
D Very severe COPD patients with hypercapnoiec respiratory failure
requiring long-term oxygen therapy should have the oxygen flow rate
titrated cautiously to maintain a SaO2 > 90%.117
Grade D, Level 4
6.6
Surgical options for COPD patients
There are a variety of surgical options available for patients with
COPD. These options are primarily focused at improving symptoms
and restoring function in a select group of COPD patients.118
The surgical options available are:
1.
2.
3.
Bullectomy
Lung Volume Reduction Surgery
Lung Transplantation
43
6.6.1 Bullectomy
Surgical removal of large bullae in COPD patients may improve
symptoms, exercise tolerance and pulmonary function.119,120
Bullectomy can be performed via standard lateral thoracotomy,
midline sternotomy or via Video-Assisted Thoracoscopy with stapling
of the bullae.118 Removal of the giant bulla is thought to improve the
function of the adjacent compressed lung tissue and improve
symptoms of dyspnoea and exercise tolerance.
Surgical mortality for bullectomy rages from 0-22.5%.121
D Selection of patients with giant bullae who will benefit from
bullectomy should be based on clinical, radiological and pulmonary
physiological parameters as indicated below.122
Indications
1. Severe functional limitation
despite maximal medical therapy
Contraindications
1. Substantial emphysema
elsewhere in the lung
2. Ex-smoker
2. Pulmonary hypertension
3. Bulla occupying > 1/3 of the
hermithorax noted on CT thorax
with crowding of pulmonary
vascular and parenchyma around
the bulla
4. FEV1 > 40%
FVC is normal
Elevated RV
Normal DLCo
Normal PaO2 & PaCO2
3. Co-morbid illness e.g. heart
failure
4. Old age
FEV1 < 35%
Reduced DLCo
5. Absence of target zones, poor
washout in remaining lung
regions
5. Ventilation / Perfusion scan
showing localized matched
defect with normal
uptake/washout from
surrounding normal lung
CT
FEV1
FVC
DLCo
RV
=
=
=
=
=
Computed Tomography
Forced Expiratory Volume in the 1st second
Forced Vital Capacity
Diffusing Capacity for Carbon Monoxide
Residual Volume
Grade D, Level 3
44
6.6.2 Lung Volume Reduction Surgery (LVRS)
LVRS in COPD patients involves the resection of approximately 2030% of poorly functioning lung tissue in each lung thereby reducing
the intra-thoracic volume and also the mechanical disadvantage faced
by the diaphragm and other respiratory muscles.123
Overall LVRS has been shown to improve FEV1, exercise tolerance,
quality of life and may be long-term survival.124,125 The effect of
LVRS seems to be maximal at 6 months post surgery.124
A Selection of patients that will benefit from LVRS is based on the
following indications and contraindications:122,126
Indications
1. Severe functional limitation
2. Post-bronchodilator:
20% > FEV1 < 45% predicted
RV > 150% predicted
TLC > 100% predicted
DLCo > 20% predicted
Contraindications
1. Co-morbid illness e.g. heart
failure, cancer
2. Post-bronchodilator:
FEV1 < 20% predicted
DLCo < 20% predicted
3. High dose steroids
(Prednisolone >20 mg/day)
3. PaO2 > 45 mmHg
PaO2 < 60 mmHg
4. Upper lobe predominance of
heterogeneous pulmonary
emphysema noted on HRCT
thorax
5. Pulmonary Artery Systolic
Pressure < 45 mmHg
or mean Pulmonary Artery
Pressure < 35 mmHg
4. Homogenous distribution of
emphysema on HRCT thorax
5. Pulmonary arterial
hypertension
6. Obesity
6. Post-pulmonary rehabilitation
cycle ergometry exercise
capacity:
Female: < 25 Watts
Male: < 40 Watts
Note: LVRS has an unacceptably high mortality in patients with the following preoperative pulmonary physiological and radiological parameters:126
FEV1 < 20% predicted
Non-upper lobe predominant emphysema on HRCT thorax
DLCo < 20% predicted
Grade A, Level 1+
45
Investigations for patients being considered for LVRS include the
following:
1.
2.
3.
4.
5.
High resolution computed tomography thorax
Pulmonary Function Test including Diffusion Capacity
Arterial Blood gas
Cycle ergometry to determine exercise capacity post-pulmonary
rehabilitation
2D-echocardiogram or right heart catheter study to determine
pulmonary arterial pressure.
GPP LVRS and lung transplantation are surgical options, which are
usually considered in selected patients with advanced COPD
unresponsive to medical therapy. These patients should be referred to
specialty centres where these procedures are done for further
evaluation.
GPP
The National Emphysema Treatment Trial showed significant benefit
of LVRS on mortality, exercise capacity and quality of life in COPD
patients with upper lobe emphysema and low exercise capacity.124
In patients with non-upper lobe emphysema and high exercise
capacity, LVRS led to increased mortality and a reduction in exercise
tolerance.124 Overall 90-day surgical mortality in the non-high risk
group was 5.2% compared to 1.5% in the medically treated arm.124
6.6.3 Lung transplantation
COPD is the most common indication for lung transplantation.
The choice of bilateral lung transplantation (BLT) or single lung
transplantation (SLT) for COPD remains controversial.127,128 Bilateral
lung transplantation results in greater improvement in FEV1, but
improvements in exercise capacity are not always significantly greater
than SLT.129
Overall (both BLT and SLT) 5-year survival is approximately 59%.
However, COPD patients who have undergone BLT have a better 5year survival rate of 67% compared to 45% for SLT.130
46
Lung transplantation leads to improvement in FEV1, exercise capacity
and quality of life.129
D Lung transplantation should be considered in selected patients with
end-stage COPD.129 Selection criteria are as follows130,131:
Indications
1. Age of patient: BLT <55 years
SLT <60 years
2. FEV1 <25% predicted
3. PaCO2 >55 mmHg on Room
Air
4. PaO2 >55 mmHg on Room
Air requiring long-term
oxygen therapy
5. Pulmonary Hypertension
6. Rapid decline in FEV1 +/- life
threatening exacerbations
Contraindications
1. Age >60 years
2. Symptomatic Osteoporosis
3. Prednisolone >20 mg/day
4. Unresolved psychosocial
and substance abuse (cig.
Smoking)
5. Infections (HIV, Hep. B, C,
etc.)
6. Active malignancy
7. Renal, Heart or Liver
Dysfunction
8. Poor rehabilitative potential
Severe Musculskeletal
Disorder
(Adapted from Cassivi SD et al, 2002; American Thoracic Society, 1998.)
Grade D, Level 3 & 4
Compared to patients with other cardiopulmonary disease, patients
with COPD exhibit the best overall survival after lung
transplantation.132
47
7
Monitoring of Patients with Stable COPD
D & GPP Patients should be seen and assessed regularly (e.g. threemonthly in the stable state).3
At each follow-up visit:
• Patients should be asked regarding onset of any new symptoms
and/or worsening of exercise capacity.
•
Current smokers should be given repeated advice to quit.
•
Adherence to medications should be assessed, and the patient’s
inhaler technique checked and re-taught if necessary.
Grade D, Level 4/GPP
D & GPP Indications for specialist referral3
•
Severe COPD (FEV1 < 50% predicted).
•
Frequent exacerbations (e.g. two or more a year) despite
compliance to treatment.
•
Rapidly progressive course of the disease.
•
Development of new symptoms e.g. haemoptysis, or new physical
signs e.g. cyanosis, peripheral oedema.
Grade D, Level 4/GPP
48
8
8.1
Management of Acute Exacerbations
Principles of management
Ideally, the frequency of exacerbation should be reduced by
appropriate use of inhaled corticosteroids and bronchodilators, and
vaccinations.
The impact of exacerbations should be minimised by:
–
8.2
–
giving self-management advice on responding promptly to the
symptoms of an exacerbation
starting appropriate treatment with oral steroids and/or antibiotics
–
using non-invasive ventilation when indicated.
Definition of an acute exacerbation
There is no widely accepted definition of acute exacerbation of
COPD. Most published definitions describe an exacerbation as an
acute event with worsening of the patient’s symptoms from their usual
stable state, which is beyond normal day-to-day variations. Commonly
reported symptoms are worsening breathlessness, cough, increased
sputum volume and sputum purulence.
An acute exacerbation of COPD is a clinical diagnosis.
8.3
Differential diagnoses of acute exacerbations:
•
•
•
•
•
•
•
•
pneumonia
pneumothorax
left ventricular failure/pulmonary oedema
pulmonary embolism
lung cancer
upper airway obstruction
pleural effusion
recurrent aspiration.
49
8.4
Causes of acute exacerbation of COPD
The most common causes of an exacerbation are infection of the
tracheo-bronchial tree (often viral), and air pollution.
Other contributing factors may be co-existing diseases like:
•
•
•
•
•
•
•
•
•
•
8.5
Pneumonia
Right or left heart failure or arrhythmias
Pulmonary embolism
Spontaneous pneumothorax
Inappropriate oxygen administration
Drugs (hypnotics, tranquillisers, diuretics, etc.)
Metabolic diseases (diabetes, electrolyte disturbances, etc.)
Poor nutritional state
Other diseases (gastrointestinal bleeding, etc.)
End-stage respiratory disease (fatigue of respiratory muscles,
etc.)
Investigations for patients with exacerbation
C Chest radiography is recommended in an acute exacerbation, when
other diagnoses like pneumonia or heart failure need to be excluded.133
Grade C, Level 2+
D Sputum culture is not recommended for routine investigation of
patients with exacerbation.3
Grade D, Level 3
D Pulse oximetry, if available, can assist doctors in identifying
patients with hypoxaemia when oxygen saturation (SaO2) is less than
90%.3
Grade D, Level 3
50
Algorithm for the management of an acute exacerbation
Acute exacerbation
Assessment by physician
Signs of severe exacerbation (any of the following)
marked dyspnoea and tachypnoea (>30 respirations/minute)
use of accessory muscles (sternomastoid and abdominal) at rest
cyanosis
confusion
SaO2 <90%
•
•
•
•
•
No
Mild exacerbations
• Initiate, increase dose or frequency, or combine β 2-agonist and/or
• Anticholinergic
• Encourage sputum clearance by coughing
• Consider chest physiotherapy
• Encourage fluid intake
• Avoid sedatives and hypnotics
• Consider antibiotics
• Consider oral corticosteriods*
Instruct patients on symptoms and signs of worsening and actions to
take: Contact primary care physician or go to emergency department.
Improved
Reassess within 48 hours
by physician
Yes
Refer to
hospital
Worsened
Not improving
Continue same
management or reduce
intensity (step down)
Stable COPD
management
Consider adding corticosteroids*
or a course of antibiotics if not
given earlier. Instruct patient on
symptoms, signs of worsening
and action to take.
*30 mg of prednisolone daily for up to 14 days
(Adapted from European Respiratory Society Consensus Statement, 1995)
51
Worsened
8.6
Pharmacological management
8.6.1 Bronchodilators
A Inhaled anticholinergic bronchodilators or inhaled short-acting 2agonists are beneficial and should be used in the treatment of patients
presenting with acute exacerbation of COPD.135
Grade A, Level 1+
Since the inhaled anticholinergic bronchodilators have fewer and more
benign side effects, consider these agents first. Only after the initial
bronchodilator is at maximum dose is the addition of a second inhaled
bronchodilator beneficial.135
Delivery systems for inhaled therapy during
exacerbations
D Both nebulisers and hand-held inhalers can be used to administer
inhaled therapy during exacerbations of COPD, as they are equally
effective in achieving bronchodilation in COPD exacerbations.136
Grade D, Level 4
The choice of delivery system should depend on the dose of drug
required, the ability of the patient to use the device and the resources
available to supervise the administration of the therapy.
8.6.2
Systemic corticosteroids
A In the absence of significant contraindications, oral corticosteroids
should be used, in conjunction with other therapies, in all patients
admitted to hospital with an exacerbation of COPD.137
Grade A, Level 1+
A In the absence of significant contraindications, oral corticosteroids
should be considered in patients managed in the community who have
an exacerbation with a significant increase in the breathlessness which
interferes with daily activities.137
Grade A, Level 1+
52
A Prednisolone 30 mg orally should be prescribed for 7 to 14 days to
patients with an exacerbation. It is recommended that a course of
corticosteroid treatment should not be longer than 14 days as there is
no advantage in prolonged therapy.137
Grade A, Level 1+
8.6.3
Antibiotics
A Antibiotics should be used to treat exacerbations of COPD when 138:
(1)
(2)
(3)
there is history of purulent sputum
there are clinical signs of pneumonia
there is consolidation on a chest radiograph
Grade A, Level 1+
Initial empirical treatment can be a beta lactam-beta lactamase
inhibitor combination, a 2nd generation macrolide, a 2nd generation
cephalosporin139, or a quinolone. When initiating empirical antibiotic
treatment, prescribers should always take account of any guidance
issued by their local microbiologists.
8.7
Non-pharmacological therapy
8.7.1 Oxygen therapy
GPP Oxygen therapy should be considered if patient is known, or
suspected, to have hypoxaemia. This can be administered via nasal
prongs, or venturi mask. One should exercise caution in the oxygen
dose for patients, such that the lowest possible oxygen concentration
to maintain oxygen saturation above 90% is provided. If pulse
oximetry is not available, the concentration of the oxygen mask
should not exceed 28%, or the nasal prong oxygen flow rate should be
kept at 2L/min.
GPP
8.7.2 Non-invasive ventilation (NIV)
A Non-invasive ventilation should be used as the treatment of choice
in the hospital, for persistent hypercapnic ventilatory failure during
exacerbations despite optimal medical therapy.140
Grade A, Level 1+
53
8.8
When to refer to the Emergency Department (ED)
Severe exacerbation
GPP Any one of the following signs may indicate severe
exacerbations requiring urgent referral to the Emergency Department:
1.
2.
3.
4.
5.
marked dyspnoea and tachypnoea (> 30 respirations/minute)
use of accessory muscles (sternomastoid and abdominal) at
rest
cyanosis
confusion
SaO2 < 90%
GPP
54
9
Air Travel
In spite of commercial aircraft cabin being pressurized to cabin
altitudes up to 2438 m, altitude exposure may exacerbate hypoxaemia
in patients with COPD. At 2438 m, the partial pressure of oxygen
falls to the equivalent of breathing 15% oxygen at sea level.
Therefore, particular caution should be paid to those who are
hypoxaemic at sea level.
COPD patients with large bullae are also at risk of pneumothorax as a
result of volume expansion at reduced cabin pressures. The volume of
gas in a non-communicating bulla will increase by nearly 38% on
ascent from sea level to 2438 m. However, there are no data to state
with any confidence what the maximum volume of a bulla should be
before it entails an unacceptable level of risk of rupture leading to
tension pneumothorax, pneumomediastinum or air embolism.
D Patients with severe COPD, history of air travel intolerance with
respiratory symptoms (dyspnoea, chest pain, confusion, syncope), comorbidity with other conditions worsened by hypoxaemia
(cerebrovascular disease, coronary artery disease, heart failure), and
recent pneumothorax should undergo assessment before flying.141
The following assessment is recommended141:
•
history and examination with particular reference to cardiorespiratory disease, dyspnoea and previous flying experience
•
spirometry (in non-tuberculous patients only)
•
measurement of SpO2 by pulse oximetry. Readings should be
taken from a warm ear or finger after sufficient delay for the
oximeter to display a stable reading. Blood gases are preferred if
hypercapnia is known or suspected
Grade D, Level 4
D Patients who have resting sea level oximetry between 92% and
95% and who have additional risk factors (Table 9) should be referred
for further assessment.
Grade D, Level 4
55
Table 9
Results of initial assessment141
Screening result
Recommendation
•
Sea level SpO2 > 95%
Oxygen not required
•
Oxygen not required
•
Sea level SpO2 92-95%
and no risk*
Sea level SpO2 92-95%
and additional risk factor*
•
Sea level SpO2 < 92%
Refer for hypoxic challenge
test with arterial or capillary
measurements
In-flight oxygen
•
Receiving supplemental
oxygen at sea level
Increase the flow while at
cruising altitude
(Adapted from British Thoracic Society Standards of Care Committee, 2002)
SpO2 = Spot oxygen saturation
*
Additional risk factors: hypercapnia, FEV1 < 50% predicted, lung
cancer, restrictive lung disease involving the parenchyma
(fibrosis,) chest wall (kyphoscoliosis) or respiratory muscles,
ventilator support, cerebrovascular or cardiac disease, within six
weeks of discharge for exacerbation of chronic lung or cardiac
disease.
56
10
Surgery in COPD Patients
Perioperative pulmonary complications are increased in COPD
patients by approximately 2.7 to 4.7 fold depending on the anatomical
site of the surgery and severity of lung disease.142
Patients with COPD undergoing upper abdominal or abdominal
vascular, cardiac, orthopaedic and head/neck surgery are at increased
risk of postoperative pulmonary complications e.g. atelectasis,
pneumonia, exacerbation of COPD, prolonged mechanical ventilation
and venous thromboembolism.142-144
GPP Preoperative assessment of a COPD patient should include:
1.
2.
3.
4.
5.
Detailed history and physical examination
Assessment of functional capacity (American Society of
Anesthesiology Physical Status Scale). See Table 10.
Preoperative Spirometry
Arterial Blood Gas especially in moderate to severe COPD
Chest Radiograph
GPP
Table 10 American Society of Anesthesiology (ASA)
Physical Status Scale
Class
Physical Status
I
Normal, Healthy <80 years old
II
Mild systemic disease or healthy individual > 80 years
III
Severe but not incapacitating systemic disease
IV
Incapacitating systemic disease that is a constant threat
to life
V
Moribund patient not expected to survive 24 hours
despite surgery
Note: ASA class >II is associated with a 1.7-fold increased risk of
postoperative pulmonary complication.145
57
A COPD patients being considered for surgery should be assessed for
risk of developing venous thromboembolism and also for
thromboprophylaxis during the perioperative assessment.146
Grade A, Level 1+
A Combination of bronchodilators, chest physiotherapy, antibiotics,
smoking cessation for at least 4-8 weeks and a short course of oral
corticosteroids should be given to patients with acute exacerbation so
as
to
reduce
the
risk
of
postoperative
pulmonary
complications.135,137,138
Grade A, Level 1+
COPD patients who have symptoms and signs of airflow obstruction
should be treated aggressively. Elective surgery in these patients
should be deferred especially if the patient has an acute exacerbation.
58
11
End of Life Care
It has been shown that the quality of end of life care in COPD patients
is likely to be worse than that for patients with other diseases.147,148
COPD patients have poorer symptom control, spend progressively
more time in hospital towards the end of life and are more likely to die
in hospitals.148,149
A major area of end of life care of COPD patients relates to the
patientsʼ and their relativesʼ preparedness concerning the dying
process, as well as their choice of interventions during the terminal
phase.
•
D Patients should be educated about their disease, prognosis and
possible circumstances of death.
Grade D, Level 3
Patients with COPD desire more information on diagnosis,
disease process, treatment, prognosis and what dying might be
like. It has been shown that patients feel unprepared to cope with
their poor state of health due to a lack of information about their
condition.147,150
•
D Physicians should discuss end of life issues and advance care
planning with patients (and their relatives) who have severe to
very severe COPD.
Grade D, Level 3
Studies suggest that physicians caring for patients with severe
COPD frequently do not initiate discussions about end of life care
and patients usually do not ask about them. Patients generally
expect their physicians to raise these issues with them.151-153 In
addition, many patients would like to contribute to the decision
making process regarding their end of life care.151,154
Patients with severe to very severe COPD disease are most likely
to benefit from end of life discussions because of their risk of
respiratory failure and the potential need for mechanical
ventilation. Discussions about end of life should ideally take place
when the patient is stable.150,152,154
59
•
B Physicians who look after severe to very severe COPD patients
(as with all physicians caring for the terminally ill) will need to be
prepared to discuss end of life issues with patients.
Grade B, Level 1+
Physicians can improve their communication with patients on end
of life issues with appropriate training.153,155
60
12
Clinical Quality Improvement
The workgroup proposes some possible clinical quality indicators, based on
recommendations in these guidelines, that healthcare providers may use in
monitoring their practice and to better gauge their quality of care.
Quality
indicators
Smoking
Inhaler
technique
Weight or
BMI
Influenza
vaccination
Recommended
Examples of suggested measurable
minimum
indicators
frequency*
Percentage of COPD patients whose
smoking habits and desire to quit were
assessed on ≥ 1 occasions in the past one
Annual
year (except for those who have never
smoked where smoking habits should be
recorded once)
Percentage of COPD patients who have a
Annual
record of inhaler technique assessment in
the past one year
Percentage of COPD patients who have a
Annual
record of weight or BMI assessment in the
past one year
Percentage of COPD patients who have a
Annual
record of influenza vaccination being
offered in the past one year
*Users may consider allowing an added margin of time (e.g. +3 months) when
assessing adherence to recommended annual frequencies.
61
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77
Self-assessment (MCQs)
After reading the Clinical Practice Guidelines, you can claim one CME
point under Category III (Self-Study) of the SMC Online CME System.
Before you login to claim the CME point, we encourage you to evaluate
whether you have mastered the key points in the Guidelines by completing
this set of MCQs. This is an extension of the learning process and is not
intended to “judge” your knowledge and is not compulsory. The answers
can be found at the end of the questionnaire.
Instruction: Choose the best answer
1.
In the assessment of a 40 year old smoker with chronic cough,
breathlessness and sputum production, which of the following is most
correct concerning COPD?
A)
B)
C)
D)
Physical examination is crucial to the diagnosis
Chest x-ray is diagnostic
Hemoptysis is a typical presentation
Brochiectasis and congestive heart failure are possible differential
diagnoses
E) Alpha-1 anti-trypsin deficiency is a common cause
2.
The severity of COPD is determined by:
A)
B)
C)
D)
E)
3.
Duration of the disease
The presence of cough
The amount of sputum production
Number of hospital admissions
Post bronchodilator FEV1 reading
Evidence of airway obstruction using spirometry is best based on
which of the following:
A)
B)
C)
D)
FEV1 < 80 percent predicted
FVC > 80 percent predicted
FEV1/FVC < 70%
Post-bronchodilator FEV1 > 80 percent predicted
78
4.
Which of the following is not a key indicator for considering a
diagnosis of COPD?
A)
B)
C)
D)
E)
5.
Chronic cough
Dyspnoea
History of exposure to risk factors
Chest discomfort
Sputum production
Spirometry is least useful for which of the following:
A) To establish the diagnosis of COPD
B) To determine the severity of COPD
C) To help differentiate between COPD and bronchial asthma by
bronchodilator reversibility testing
D) To determine the severity of an exacerbation of COPD
E) To evaluate changes in lung function over time or with therapy
6.
Which of the following statements is TRUE:
A) Inhaled short-acting bronchodilators have been shown to slow the
rate of FEV1 in COPD
B) Bronchodilators improve exercise tolerance in COPD despite
having little or modest effect on increasing FEV1
C) Tiotropium has a duration of action of 12 hours
D) Salmeterol and Formoterol have similar time to peak effect
E) Ipratropium bromide is best used on an as-needed basis for quick
symptom relief
7.
Which of the following statements is FALSE:
A) Inhaled corticosteroids (ICS) have been shown to reduce acute
exacerbations in COPD patients with moderate to severe COPD
B) ICS have been shown to slow the rate of FEV1 decline in COPD
C) Theophylline clearance is decreased by quinolones
D) Combination ICS and long-acting 2-agonists (LABA) have been
shown to reduce acute exacerbations compared to monotherapy
with LABA
E) Inhaled corticosteroids are not indicated for patients with Stage I
COPD
79
79
8.
Patient education is vital to COPD management and should be
provided at
A)
B)
C)
D)
9.
Stage 0
Stage 1 and 2
Stage 3 and 4
All stages
The 5 As of smoking cessation are
A)
B)
C)
D)
E)
Ask, assess, assist, advise, arrange follow-up
Assess, advocate, ask, advise, arrange follow-up
Advocate, ask, assess, advise, arrange follow-up
Ask, advise, assess, assist, arrange follow-up
Ask, admonish, advocate, assess, arrange follow-up
10. Pulmonary rehabilitation has been shown to have the following
benefits except:
A) Improvement of exercise capacity
B) Improvement of lung function
C) Reducing number of hospitalizations
D) Improvement in health-related quality of life
11. Components of pulmonary rehabilitation include the following except:
A) Physical training
B) Nutritional intervention
C) Psychosocial and behavioral intervention
D) Optimizing pharmacotherapy (inhaler)
12. Which of the following statements about long-term oxygen therapy
(LTOT) is false:
A) Long-term oxygen therapy has been shown to improve survival in
COPD patients with mild to moderate hypoxaemia.
B) Goal of long-term oxygen therapy is to maintain baseline PaO2 >
60 mmHg.
C) Long-term oxygen therapy has a beneficial impact on sleep,
exercise tolerance and cognitive function.
D) Long-term oxygen therapy should be cautiously titrated to
maintain SaO2 > 90% in COPD patients with chronic hypercapnic
respiratory failure.
80
13. The most common cause of an acute exacerbation of COPD is
A)
B)
C)
D)
E)
Pneumonia
Poor nutritional state
Infection of tracheobronchial tree
Heart failure
Arrhythmia
14. Which of the following is beneficial in the relief of an acute
exacerbation of COPD?
A)
B)
C)
D)
Inhaled short-acting 2-agonist
Inhaled steroids
Oral theophylline
Oral antibiotics
15. Which of the following statements is correct?
A) Patients often do not want to know too much about their
prognosis
B) Patients with mild disease benefit most from advanced care
planning
C) Physicians are generally adequate in their end of life discussions
with patients.
D) Physicians can improve their communication on end of life issues
with training
E) All of the above
81
81
Answer
1.
D
(pg 19)
2.
E
(pg 20)
3.
C
(pg 20)
4.
D
(pg 22)
5.
D
(pg 24)
6.
B
(pg 26, 28)
7.
B
(pg 31-33)
8.
D
(pg 36)
9.
D
(pg 37)
10.
B
(pg 40)
11.
D
(pgs 40-41)
12.
A
(pgs 41-43)
13.
C
(pg 50)
14.
A
(pg 52)
15.
D
(pgs 59-60)
82
82
Workgroup members
The members of the workgroup, who were appointed in their personal
professional capacity, are:
Chairperson
Dr Tan Boon Yeow
Consultant Family Physician
Head, Medical Services
St Lukeʼs Hospital
Vice Chairperson
Dr Ong Kian Chung
Consultant Respiratory Physician
KC Ong Chest & Medical Clinic
Mt Elizabeth Medical Centre
Members
Prof Ong Yong Yau
Emeritus Consultant
Dept of Internal Medicine
Singapore General Hospital
A/Prof Goh Lee Gan
Dept of COFM
Yong Loo Lin School of Medicine
National University of Singapore
A/Prof Ng Tze Pin
Dept of Psychological Medicine
Yong Loo Lin School of Medicine
National University Hospital
Dr Cynthia Chee Bin Eng
Senior Consultant
Dept of Respiratory Medicine
Tan Tock Seng Hospital
Dr Lew Yii Jen
Senior Family Physician
Deputy Director
Dept of Clinical Services
NHG Polyclinics
Dr Chia Tee Hien
Family physician
Registrar
St Lukeʼs Hospital
Dr Ng Chung Wai
Family Physician
Associate Consultant
Singhealth Polyclinics-Outram
Dr Seow Hoong Wei Gabriel
Consultant Family Physician
Private Practice
Dr Jagadesan Raghuram
Senior Consultant
Dept of Respiratory Medicine &
Critical Care
Singapore General Hospital
83
Ms Lathy D/O Prabhakaran
Senior Nurse Clinician
Dept of Nursing Services
Tan Tock Seng Hospital
Acknowledgement to:
A/Prof Pang Weng Sun, Senior Consultant Geriatrician, Alexandra
Hospital for his comments on the end of life care section.
Subsidiary editors
Dr Pwee Keng Ho
Assistant Director (Clinical Guidelines & Technology Assessment)
Clinical Quality Division
Ministry of Health
Dr Rajni Gupta
Clinical Guidelines & Technology Assessment Executive
Clinical Quality Division
Ministry of Health
84
84
CLINICAL PRACTICE GUIDELINES
Chronic Obstructive
Pulmonary Disease
Chronic Obstructive Pulmonary
Disease Association (Singapore)
Association of Aged Care
Physicians Singapore
Singapore Medical
Association
SINGAPORE THORACIC SOCIETY
College of Family Physicians
Singapore
Oct 2006
MINISTRY OF HEALTH
SINGAPORE
ISBN 981-05-6800-2
Chapter of Respiratory Physicians
College of Physicians, Singapore
Academy of Medicine
Singapore
MOH Clinical Practice Guidelines 4/2006
MOH CLINICAL PRACTICE GUIDELINES
4/2006
Chronic Obstructive Pulmonary Disease
Executive summary of recommendations
MINISTRY OF HEALTH
SINGAPORE
Singapore Medical
Association
Chapter of Respiratory Physicians
College of Physicians, Singapore
Association of Aged Care
Physicians Singapore
Academy of Medicine
Singapore
College of Family Physicians
Singapore
SINGAPORE THORACIC SOCIETY
Chronic Obstructive Pulmonary
Disease Association (Singapore)
Executive summary of recommendations
Details of recommendations can be found in the main text at the pages indicated.
Definition, Differential Diagnosis and Classification of
Severity
D Where diagnostic doubt remains, or both COPD and asthma are present, the
following findings will help identify asthma (pg 18):
•
•
•
A large response (FEV1 greater than 400 ml) to bronchodilators.
A large response (FEV1 greater than 400 ml) to 30 mg oral prednisolone
daily for 2 weeks.
Serial peak flow measurements showing 20% or greater diurnal or dayto-day variability.
Grade D, Level 4
D Where chronic asthma cannot be distinguished from COPD with the current
imaging or lung function testing, it is assumed that the two diseases co-exist
and their management should be similar to that of asthma (pg 19).
Grade D, Level 4
D COPD should be differentiated from congestive heart failure,
bronchiectasis, and obliterative bronchiolitis (pg 19).
Grade D, Level 4
D A classification of disease severity into 5 stages based on spirometry cut
points is recommended (pg 20).
Grade D, Level 4
Table 3
Classification of severity*
Stage
0: At Risk
Characteristics
normal spirometry
chronic symptoms (cough, sputum production)
I: Mild COPD
FEV1/FVC < 70%
FEV1 ≥ 80% predicted
with or without chronic symptoms (cough,
sputum production)
II: Moderate COPD
FEV1/FVC < 70%
50% ≤ FEV1 < 80% predicted
with or without chronic symptoms (cough,
sputum production)
III: Severe COPD
FEV1/FVC < 70%
30% ≤ FEV1 < 50% predicted
with or without chronic symptoms (cough,
sputum production)
IV: Very Severe
FEV1/FVC < 70%
FEV1 < 30% predicted or FEV1 < 50%
COPD
predicted plus chronic respiratory failure
*Classification based on postbronchodilator FEV1
FEV1: forced expiratory volume in one second; FVC: forced vital
capacity; respiratory failure: arterial partial pressure of oxygen (PaO2)
less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of
CO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) while breathing air at sea
level.
(Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2005)
Evaluation
D A diagnosis of COPD should be considered in any patient more than 35
years old, who has chronic cough, sputum production, or dyspnoea, and/or a
history of exposure to risk factors for the disease (see Table 4) (pg 22).
Grade D, Level 4
D Spirometry is useful for the definitive diagnosis of COPD and for the
staging of disease severity, and should be performed in individuals with
symptoms suggestive of COPD (pg 23).
Grade D, Level 4
D It is also recommended that bronchodilator reversibility testing be
performed to help identify some subjects with asthma or a large asthma
component to COPD and to establish a patientʼs best attainable lung function
(pg 24).
Grade D, Level 4
D Arterial blood gases should be performed in patients with FEV1 <40%
predicted or with clinical signs suggestive of respiratory failure or right heart
failure (pg 24).
Grade D, Level 4
D A chest X-ray is seldom diagnostic in COPD but it is valuable in excluding
alternative diagnoses and should be performed to look for abnormalities that
may suggest other conditions. Computed tomography of the chest is not
routinely recommended (pg 24).
Grade D, Level 4
Pharmacotherapy for stable COPD
A Inhaled short-acting bronchodilators are recommended as first-line therapy
in all stages of COPD to relieve symptoms and improve exercise capacity (pg
26).
Grade A, Level 1+
A Regular treatment with one or both classes of the inhaled long-acting
bronchodilators should be considered for patients with moderate to very severe
COPD with frequent exacerbations (pg 28).
Grade A, Level 1
D Inhaled long-acting bronchodilators may be added to the treatment regimen
when symptoms are not controlled with short-acting inhaled bronchodilators
alone (pg 28).
Grade D, Level 4
D Theophylline may be a useful addition where symptom control is still not
achieved with existing inhaled bronchodilator therapy. Theophylline may be of
value for patients who are non-adherent to or unable to use inhaled therapy
(pg 30).
Grade D, Level 4
A Inhaled corticosteroids as long-term maintenance therapy are recommended
for patients with FEV1 <50% predicted who experience frequent exacerbations
(pg 32).
Grade A, Level 1+
A Long-term oral corticosteroids are not recommended in stable COPD (pg
32).
Grade A, Level 1+
D Combination inhaled corticosteroids and long-acting 2-agonists should be
considered for patients in whom both its components are indicated (pg 33).
Grade D, Level 4
C Annual influenza vaccination should be offered to the elderly (65 years old
and above) in all stages of COPD (pg 33).
Grade C, Level 2++
D Pneumococcal vaccination may be considered in COPD patients (pg 34).
Grade D, Level 4
D If considering pneumococcal vaccination for a COPD patient, usually only
one dose of the vaccine is needed. A second dose is recommended for persons
aged 65 or older who received their first dose when they were under 65, if 5 or
more years have passed since that dose (page 34).
Grade D, Level 4
Table 7
Recommended pharmacotherapy in stable COPD
Symptoms
Exacerbations
Spirometry
Intermittent
AND
Regardless of
FEV1
Few
exacerbations
Persistent*
AND/OR
Frequent
exacerbations†
AND
FEV1 > 50%
predicted
Recommended
pharmacotherapy
SABA or
Combination SABA/SAAC
inhaler as needed for symptom
relief
SABA
as needed for symptom relief
With one of the following:
1) SAAC 4 to 6 hourly or
2) Combination SABA/SAAC
inhaler 4 to 6 hourly or
3) Long-acting anticholinergic
(LAAC) once daily‡
to which may be added:
Long-acting 22-agonist (LABA)
12 hourly‡
AND/OR
Intermittent
or
Persistent
Sustained-release theophylline
12 hourly or once daily‡
As above
AND
AND
Frequent
exacerbations
FEV1 < 50%
predicted
AND
Inhaled corticosteroids
SABA = short-acting 2-agonist
SAAC = short-acting anti-cholinergic
*
Persistent symptoms: exertional dyspnoea, diminished exercise capacity, persistent
cough, wheeze despite SABA/combination SABA/SAAC inhaler as needed.
†
Frequent exacerbations: two or more acute exacerbations a year requiring systemic
steroids.
GPP The choice between LAAC, LABA or theophylline is dependent on the
individual patientʼs response in terms of symptom relief and side-effects, and
affordability of the medication. This should be re-evaluated if there is lack of
therapeutic response.
‡
GPP
Non-pharmacological Management for Stable COPD
Patient education
D Patient education is a vital part of COPD management and should begin at
the time of first assessment for COPD and continue with each follow-up visit
(pg 36).
Grade D, Level 4
D The intensity and content of patient educational messages should vary
depending on the severity of the patientʼs disease (see Table 8) (pg 36).
Table 8 Recommended topics for patient education
according to severity of disease
Severity of Disease
Stage 0: At Risk
Patient Education Topic
Information and advice about reducing
risk factors.
Stage I: Mild COPD
through Stage III: Severe
COPD
Above topic, plus:
Information about the nature of COPD.
Instruction on how to use inhalers and
nebulizer.
Information on influenza vaccination
and medication.
Recognition and treatment of
exacerbation.
Strategies for minimizing dyspnea
Information on pulmonary
rehabilitation.
Stage IV: Very Severe
COPD
Above topic, plus:
Information about complications.
Information about oxygen treatment.
Advance directive and end-of-life
decisions.
[Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2005]
Grade D, Level 4
D Patient education should be (pg 37):
•
•
•
•
•
•
Tailored to meet the needs of the individual patient
Interactive
Directed to improving quality of life
Simple to follow
Practical
Appropriate to the intellectual and social skill of the patient and the
caregivers.
Grade D, Level 4
Smoking cessation
A Smoking cessation should be emphasized as an essential first step in
management of COPD patients (pg 37).
Grade A, Level 1++
GPP Clinicians should play a prominent role in promoting attempts to stop
smoking in their patients (pg 37).
GPP
A All smokers, including those who may be at risk for COPD as well as those
who already have the disease, should be offered at least a brief tobacco
dependence counseling at every health care provider visit (pg 37).
Grade A, Level 1++
D Pharmacotherapy for smoking cessation is recommended when counseling is
not sufficient to help patients quit smoking (pg 38).
Grade D, Level 4
A Treatment of nicotine dependence is effective and should be offered to
smokers in addition to counselling (pg 38).
Grade A, Level 1++
A These pharmacotherapies reliably increase long-term smoking abstinence
rates and at least one of these medications should be added to counseling if
necessary and in the absence of contraindications (pg 38).
Grade A, Level 1++
Nutrition in COPD
D All patients with COPD should undergo simple nutrition screening (pg 39).
Grade D, Level 4
GPP Nutritional intervention should be considered in all COPD patients with
BMI < 18.5 kg/m2 or significant involuntary weight loss (>10% during the last
6 months or > 5% in the past month) (pg 39).
GPP
Pulmonary rehabilitation
D Pulmonary rehabilitation may be considered for patients with the following
(pg 41):
• persistent symptoms especially dyspnoea,
• reduced exercise tolerance or experience a restriction in activities,
• recurrent admissions to hospitals over the last 6 months.
Grade D, Level 4
B The physical components of pulmonary rehabilitation should include both
lower extremity training (e.g. bicycle, ergometry, treadmill) and upper
extremity training (strength and endurance) (pg 41).
Grade B, Level 2+
D Psychosocial and behavioral interventions (health education, smoking
cessation clinic, and support groups addressing psychosocial issues) as well as
nutritional intervention should also be included as non-physical components of
the comprehensive pulmonary rehabilitation programs (pg 41).
Grade D, Level 4
Oxygen therapy in chronic obstructive pulmonary disease
A Patients with very severe COPD and chronic respiratory failure should be
assessed for the need for long-term oxygen therapy (pg 42).
Grade A, Level 1+
A Indications for long-term oxygen therapy (at least 15 hours/day) in patients
with COPD should be based on the following indices obtained in stable state
(pg 42):
•
Without pulmonary hypertension (Cor Pulmonale), congestive heart
failure, polycythaemia (Hct >55%):
1.
2.
PaO2 < 55 mmHg on Room Air
OR
SaO2 < 89% on Room Air
•
With pulmonary hypertension (Cor Pulmonale), congestive heart failure,
polycythaemia (Hct >55%):
1.
PaO2 between 55 mmHg - 60 mmHg on Room Air
OR
SaO2 < 89% on Room Air
2.
Grade A, Level 1+
D Oxygen concentrator is the preferred mode of delivery of oxygen. It is the
most convenient and economical method of providing long-term oxygen
therapy (pg 43).
Grade D, Level 3
D Very severe COPD patients with hypercapnoiec respiratory failure requiring
long-term oxygen therapy should have the oxygen flow rate titrated cautiously
to maintain a SaO2 > 90% (pg 43).
Grade D, Level 4
Monitoring of patients with stable COPD
D & GPP Patients should be seen and assessed regularly (e.g. three-monthly
in the stable state) (pg 48).
At each follow-up visit:
• Patients should be asked regarding onset of any new symptoms and/or
worsening of exercise capacity.
•
Current smokers should be given repeated advice to quit.
•
Adherence to medications should be assessed, and the patientʼs inhaler
technique checked and re-taught if necessary.
Grade D, Level 4/GPP
D & GPP Indications for specialist referral (pg 48)
•
Severe COPD (FEV1 < 50% predicted).
•
Frequent exacerbations (e.g. two or more a year) despite compliance to
treatment.
•
Rapidly progressive course of the disease.
10
•
Development of new symptoms e.g. haemoptysis, or new physical signs
e.g. cyanosis, peripheral oedema.
Grade D, Level 4/GPP
Management of Acute Exacerbations
C Chest radiography is recommended in an acute exacerbation, when other
diagnoses like pneumonia or heart failure need to be excluded (pg 50).
Grade C, Level 2+
D Sputum culture is not recommended for routine investigation of patients
with exacerbation (pg 50).
Grade D, Level 3
D Pulse oximetry, if available, can assist doctors in identifying patients with
hypoxaemia when oxygen saturation (SaO2) is less th an 90% (pg 50).
Grade D, Level 3
Pharmacological management
A Inhaled anticholinergic bronchodilators or inhaled short-acting β2-agonists
are beneficial and should be used in the treatment of patients presenting with
acute exacerbation of COPD (pg 52).
Grade A, Level 1+
D Both nebulisers and hand-held inhalers can be used to administer inhaled
therapy during exacerbations of COPD, as they are equally effective in
achieving bronchodilation in COPD exacerbations (pg 52).
Grade D, Level 4
A In the absence of significant contraindications, oral corticosteroids should be
used, in conjunction with other therapies, in all patients admitted to hospital
with an exacerbation of COPD (pg 52).
Grade A, Level 1+
A In the absence of significant contraindications, oral corticosteroids should be
considered in patients managed in the community who have an exacerbation
with a significant increase in the breathlessness which interferes with daily
activities (pg 52).
Grade A, Level 1+
11
A Prednisolone 30 mg orally should be prescribed for 7 to 14 days to patients
with an exacerbation. It is recommended that a course of corticosteroid
treatment should not be longer than 14 days as there is no advantage in
prolonged therapy (pg 53).
Grade A, Level 1+
A Antibiotics should be used to treat exacerbations of COPD when (pg 53):
(1) there is history of purulent sputum
(2) there are clinical signs of pneumonia
(3) there is consolidation on a chest radiograph
Grade A, Level 1+
Non-pharmacological therapy
GPP Oxygen therapy should be considered if patient is known, or suspected,
to have hypoxaemia. This can be administered via nasal prongs, or venturi
mask. One should exercise caution in the oxygen dose for patients, such that
the lowest possible oxygen concentration to maintain oxygen saturation above
90% is provided. If pulse oxymeter is not available, the concentration of the
oxygen mask should not exceed 28%, or the nasal prong oxygen flow rate
should be kept at 2L/min (pg 53).
GPP
A Non-invasive ventilation should be used as the treatment of choice in the
hospital, for persistent hypercapnic ventilatory failure during exacerbations
despite optimal medical therapy (pg 53).
Grade A, Level 1+
12
Algorithm for the management of an acute exacerbation
Acute exacerbation
Assessment by physician
Signs of severe exacerbation (any of the following)
marked dyspnoea and tachypnoea (>30 respirations/minute)
use of accessory muscles (sternomastoid and abdominal) at rest
cyanosis
confusion
SaO2 <90%
•
•
•
•
•
No
Mild exacerbations
• Initiate, increase dose or frequency, or combine β 2-agonist and/or
• Anticholinergic
• Encourage sputum clearance by coughing
• Consider chest physiotherapy
• Encourage fluid intake
• Avoid sedatives and hypnotics
• Consider antibiotics
• Consider oral corticosteriods
Instruct patients on symptoms and signs of worsening and actions to
take: Contact primary care physician or go to emergency department.
Improved
Continue same
management or reduce
intensity (step down)
Stable COPD
management
Reassess within 48 hours
by physician
Yes
Refer to
hospital
Worsened
Not improving
Consider adding corticosteroids*
or a course of antibiotics if not
given earlier. Instruct patient on
symptoms, signs of worsening
and action to take.
*30 mg of prednisolone daily for up to 14 days
(Adapted from European Respiratory Society Consensus Statement,1995)
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Worsened
When to refer to the Emergency Department (ED)
GPP Any one of the following signs may indicate severe exacerbations
requiring urgent referral to the Emergency Department (pg 54):
1.
2.
3.
4.
5.
marked dyspnoea and tachypnoea (> 30 respirations/minute)
use of accessory muscles (sternomastoid and abdominal) at rest
cyanosis
confusion
SaO2 <90%
GPP
Air Travel
D Patients with severe COPD, history of air travel intolerance with respiratory
symptoms (dyspnoea, chest pain, confusion, syncope), co-morbidity with other
conditions worsened by hypoxaemia (cerebrovascular disease, coronary artery
disease, heart failure), and recent pneumothorax should undergo assessment
before flying.
The following assessment is recommended141:
•
history and examination with particular reference to cardio-respiratory
disease, dyspnoea and previous flying experience
•
spirometry (in non-tuberculous patients only)
•
measurement of SpO2 by pulse oximetry. Readings should be taken from a
warm ear or finger after sufficient delay for the oximeter to display a
stable reading. Blood gases are preferred if hypercapnia is known or
suspected
(pg 55)
Grade D, Level 4
D Patients who have resting sea level oximetry between 92% and 95% and
who have additional risk factors (Table 9) should be referred for further
assessment (pg 55).
Grade D, Level 4
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Surgery in COPD patients
GPP Preoperative assessment of a COPD patient should include (pg 57):
1.
2.
3.
4.
5.
Detailed history and physical examination
Assessment of functional capacity (American Society
Anesthesiology Physical Status Scale). See Table 10.
Preoperative Spirometry
Arterial Blood Gas especially in moderate to severe COPD
Chest Radiograph
of
GPP
A COPD patients being considered for surgery should be assessed for risk of
developing venous thromboembolism and also for thromboprophylaxis during
the perioperative assessment (pg 58).
Grade A, Level 1+
A Combination of bronchodilators, chest physiotherapy, antibiotics, smoking
cessation for at least 4-8 weeks and a short course of oral corticosteroids
should be given to patients with acute exacerbation so as to reduce the risk of
postoperative pulmonary complications (pg 58).
Grade A Level 1+
End of Life Care in COPD
D Patients should be educated about their disease, prognosis and possible
circumstances of death (pg 59).
Grade D, Level 3
D Physicians should discuss end of life issues and advance care planning with
patients (and their relatives) who have severe to very severe COPD (pg 59).
Grade D, Level 3
B Physicians who look after severe to very severe COPD patients (as with all
physicians caring for the terminally ill) will need to be prepared to discuss end
of life issues with patients (pg 60).
Grade B, Level 1+
15
Levels of evidence and grades of recommendation
Levels of evidence
Level
++
Type of Evidence
3
High quality meta-analyses, systematic reviews of randomised
controlled trials (RCTs), or RCTs with a very low risk of bias.
Well conducted meta-analyses, systematic reviews of RCTs, or
RCTs with a low risk of bias.
Meta-analyses, systematic reviews of RCTs, or RCTs with a high
risk of bias
High quality systematic reviews of case control or cohort studies.
High quality case control or cohort studies with a very low risk of
confounding or bias and a high probability that the relationship is
causal
Well conducted case control or cohort studies with a low risk of
confounding or bias and a moderate probability that the relationship
is causal
Case control or cohort studies with a high risk of confounding or
bias and a significant risk that the relationship is not causal
Non-analytic studies, e.g. case reports, case series
4
Expert opinion
1
1+
-
1
2+ +
2+
-
2
Grades of recommendation
Grade
A
B
C
D
GPP
(good practice
points)
Recommendation
At least one meta-analysis, systematic review of RCTs, or RCT
rated as 1+ + and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+,
directly applicable to the target population, and demonstrating
overall consistency of results
A body of evidence including studies rated as 2++, directly
applicable to the target population, and demonstrating overall
consistency of results; or
Extrapolated evidence from studies rated as 1+ + or 1+
A body of evidence including studies rated as 2+, directly
applicable to the target population and demonstrating overall
consistency of results; or
Extrapolated evidence from studies rated as 2+ +
Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
Recommended best practice based on the clinical experience of
the guideline development group.
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