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CONTENTS
CONTENTS
Respiratory Medicine ELEGI, Colt Research Lab Wilkie Building, Medical School, Teviot Place, Edinburgh, UK.
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 932
Goals and objectives. . . . . . . . . . . . . . . . . . . . . 933
Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . 933
Evidence, methodology and validation . . . . . . . . 933
Concept of a "live", modular document . . . . . . . 933
Organisation of the document . . . . . . . . . . . . . . 933
Definition of COPD . . . . . . . . . . . . . . . . . . . . . . . 933
Diagnosis of COPD . . . . . . . . . . . . . . . . . . . . . . . 933
Epidemiology, risk factors and natural history
of COPD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 934
Pathology and pathophysiology in COPD . . . . . . . . 934
Clinical assessment, testing and differential diagnosis of
COPD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 934
Medical history . . . . . . . . . . . . . . . . . . . . . . . . 935
Physical signs . . . . . . . . . . . . . . . . . . . . . . . . . . 935
Smoking cessation. . . . . . . . . . . . . . . . . . . . . . . . . 935
Brief intervention . . . . . . . . . . . . . . . . . . . . . . . 935
Management of stable COPD: pharmacological therapy 936
Bronchodilators . . . . . . . . . . . . . . . . . . . . . . . . 936
Glucocorticoids . . . . . . . . . . . . . . . . . . . . . . . . 936
Outcomes of frequently used drugs . . . . . . . . . . 936
Combination therapy . . . . . . . . . . . . . . . . . . . . 937
Management of stable COPD: long-term oxygen
therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 937
Management of stable COPD: pulmonary
rehabilitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 937
Management of stable COPD: nutrition . . . . . . . . . 938
Background
The Standards for the Diagnosis and Treatment of Patients
with COPD document 2004 updates the position papers on
chronic obstructive pulmonary disease (COPD) published by
the American Thoracic Society (ATS) and the European
Respiratory Society (ERS) in 1995 [1, 2]. Both societies felt
the need to update the previous documents due to the
following. 1) The prevalence and overall importance of
COPD as a health problem is increasing. 2) There have
*Pulmonary and Critical Care Division, St Elizabeth9s Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
#
Respiratory Medicine ELEGI, Colt Research Lab Wilkie Building, Medical School, Teviot Place, Edinburgh, UK.
Correspondence: B.R. Celli, St Elizabeth9s Medical Center, 736 Cambridge St, Boston. MA 02135, USA. Fax: 1 6175627756. E-mail:
bcelli@cchcs.org
933
Participants
The committee members who were involved in the production of this document are clinicians, nurses, respiratory therapists and educators interested in the field of COPD. The current
Standards for the Diagnosis and Treatment of Patients with
COPD document is unique in that it also had input from
patients suffering from COPD. The committee members were
proposed and approved by the ATS and ERS. The members
were selected because of their expertise and willingness to
participate in the generation of the document. A unique
feature of this project was the development of a patient
document that could serve as a formal source of information
for the patients, thereby making them partners in the effort to
decrease the burden of the disease.
Definition of COPD
Chronic obstructive pulmonary disease (COPD) is a
preventable and treatable disease state characterised by
airflow limitation that is not fully reversible. The airflow
limitation is usually progressive and is associated with an
abnormal inflammatory response of the lungs to noxious
particles or gases, primarily caused by cigarette smoking.
Although COPD affects the lungs, it also produces significant
systemic consequences.
Diagnosis of COPD
The diagnosis of COPD should be considered in any
patient who has the following: symptoms of cough; sputum
production; or dyspnoea; or history of exposure to risk factors for the disease.
The diagnosis requires spirometry; a post-bronchodilator
forced expiratory volume in one second (FEV1)/forced vital
capacity (FVC) f0.7 confirms the presence of airflow
limitation that is not fully reversible (table 1). Spirometry
should be obtained in all persons with the following history:
exposure to cigarettes; and/or environmental or occupational
pollutants; and/or presence of cough, sputum production or
dyspnoea. Spirometric classification has proved useful in
predicting health status [4], utilisation of healthcare resources
[5], development of exacerbations [6, 7] and mortality [8] in
934
Postbronchodilator
FEV1/FVC
FEV1 % pred
w0.7
f0.7
f0.7
f0.7
f0.7
o80
o80
5080
3050
v30
Exposures
Genetic factors
Sex
Airway hyperreactivity,
IgE and asthma
Smoking
Socio-economic status
Occupation
Environmental pollution
Perinatal events and childhood illness
Recurrent bronchopulmonary infections
Diet
Ig: immunoglobulin.
935
of
chronic
obstructive
Diagnosis
Suggestive features
COPD
Mid-life onset
Slowly progressing symptoms
Long history of smoking
Early onset
Varying symptoms
Symptoms during the night/early
morning
Presence of allergy, rhinitis and/or
eczema
A family history
Airflow limitation that is largely
reversible
Fine basilar crackles on auscultation
Dilated heart on chest radiography
Pulmonary oedema
Volume restriction not airflow
limitation on pulmonary function
tests
Large volume of purulent sputum
Commonly associated with bacterial
infection
Coarse crackles/clubbing on
auscultation
Bronchial dilation and bronchial wall
thickening on chest radiography/CT
Onset at all ages
Lung infiltrate on chest radiography
Microbiological confirmation
High local prevalence of tuberculosis
Younger onset and in nonsmokers
History of rheumatoid arthritis/fume
exposure
Hypodense areas on expiration on
CT suggestive of bronchiolitis
Effects mostly male nonsmokers
Almost all have chronic sinusitis
Diffuse small centrilobular nodular
opacities and hyperinflation on
chest radiography and HRCT
Physical signs
Asthma
Bronchiectasis
Tuberculosis
Obliterative bronchiolitis
Diffuse panbronchiolitis
Medical history
A directed medical history should assess the following
issues: symptoms of cough, sputum production and dyspnoea;
past medical history of asthma, allergies and other respiratory
Smoking cessation
Cigarette smoking is an addiction and a chronic relapsing
disorder, and is regarded as a primary disorder by the
Department of Health and Human Services Guidelines in the
USA [26, 27] and by the World Health Organization (WHO).
Therefore, treating tobacco use and dependence should be
regarded as a primary and specific intervention. Smoking
should be routinely evaluated whenever a patient presents to a
healthcare facility and all smokers should be offered the best
chance to treat this disorder.
The most comprehensive of the guidelines prepared on
smoking cessation is "Treating Tobacco Use and Dependence", an evidence-based guideline sponsored by the US
Department of Health and Human Services and released in
2000, which updates the previous evidence-based guideline
"Smoking Cessation" released in 1996. The guideline and the
meta-analyses on which it is based are available online [28].
The key findings of this report are summarised in table 4.
Brief intervention
The key steps in brief intervention are as follows. Ask:
systematically, identify all tobacco users at every visit,
implement an office-wide system that ensures that tobacco
use is queried and documented for every patient at every clinic
visit. Advise: strongly urge all tobacco users to quit, in a clear,
strong and personalised manner. Assess: determine willingness to make a quit attempt. Assist: help the patient with
a quit plan, provide practical counselling, provide treatment
and social support, help the patient obtain extra treatment
and social support, recommend the use of approved pharmacotherapy (except in special circumstances), and provide
supplementary materials. Arrange: schedule follow-up contact,
either in person or via the telephone.
Permanent remissions can be achieved in a substantial
percentage of smokers with currently available treatments.
Successful treatment of this disorder can have a substantial
benefit in reducing many secondary complications of which
COPD is one. All patients willing to make a serious attempt
Table 4. Key points of the Treating Tobacco Use and Dependence guidelines
Tobacco dependence is a chronic condition that warrants repeated treatment until long-term or permanent abstinence is achieved
Effective treatments for tobacco dependence exist and all tobacco users should be offered these treatments
Clinicians and healthcare delivery systems must institutionalise the consistent identification, documentation and treatment of every tobacco
user at every visit
Brief tobacco dependence intervention is effective and every tobacco user should be offered at least brief intervention
There is a strong dose-response relationship between the intensity of tobacco dependence counselling and its effectiveness
Three types of counselling were found to be especially effective: practical counselling, social support as part of treatment and social
support arranged outside treatment
Five first-line pharmacotherapies for tobacco dependence are effective: bupropion SR, nicotine gum, nicotine inhaler, nicotine nasal
spray and nicotine patch, and at least one of these medications should be prescribed in the absence of contraindications
Tobacco-dependence treatments are cost effective relative to other medical and disease prevention interventions
936
Bronchodilators
Three types of bronchodilator are in common clinical use:
b-agonists, anticholinergic drugs and methylxanthines. Despite
substantial differences in their site of action within the cell
and some evidence for nonbronchodilator activity with some
classes of drug, the most important consequence of bronchodilator therapy appears to be airway smooth muscle relaxation and improved lung emptying during tidal breathing. The
resultant increase in FEV1 may be relatively small but is often
accompanied by larger changes in lung volumes [29], with a
Glucocorticoids
Confirm diagnosis
of COPD
Intermittent symptoms
e.g. cough, wheeze,
exertional dyspnoea
SA-BD as needed
e.g. inhaled b-agonist, anticholinergic
Persistent symptoms
e.g. dyspnoea, night
waking
Yes
Glucocorticoids act at multiple points within the inflammatory cascade, although their effects in COPD are more
modest as compared with bronchial asthma. Data from large
patient studies suggest that inhaled corticosteroids can produce a small increase in postbronchodilator FEV1 and a small
reduction in bronchial reactivity in stable COPD [3840]. In
patients with more advanced disease (usually classified as an
FEV1 v50% pred) there is evidence that the number of
exacerbations per year and the rate of deterioration in health
status can be reduced by inhaled corticosteroids in COPD
[38]. Evidence from four large prospective 3-yr studies has
shown no effect of inhaled corticosteroids on rate of change
of FEV1 in any severity of COPD [3841].
When therapy is thought to be ineffective, a trial of withdrawing treatment is reasonable. Some patients will exacerbate when this occurs, which is a reason for re-instituting this
therapy [42]. The results of forthcoming large randomised
trials with mortality as an outcome will help clarify the role of
inhaled glucocorticoids in COPD.
Yes
Add/substitue oral theophylline
Fig. 1. Algorithm for pharmacological treatment of chronic obstructive pulmonary disease (COPD). SA-BD: short-acting bronchodilator;
LA-BD: long-acting bronchodilator; ICS: inhaled corticosteroid.
Assess effectiveness by treatment response criteria. If forced expiratory volume v50% predicted and exacerbations of COPD requiring a
course of oral corticosteroid or antibiotic occurred at least once
within the last year, consider adding regular ICS. Always ensure the
patient can use an inhaled device effectively and understands its
purpose. If an ICS and a long-acting b-agonist are used, prescribe a
combination inhaler.
937
Table 5. Effect of commonly used medications on important clinical outcomes in chronic obstructive pulmonary disease
FEV1
Short-acting b-agonists
Ipratropium bromide
Long-acting b-agonists
Tiotropium
Inhaled corticosteroids
Theophylline
Yes
Yes
Yes
Yes
Yes
Yes
(A)
(A)
(A)
(A)
(A)
(A)
Lung volume
Dyspnoea
HRQoL
AE
Exercise
endurance
Disease
modifier
by FEV1
Mortality
Side-effects
Yes (B)
Yes (B)
Yes (A)
Yes (A)
NA
Yes (B)
Yes (A)
Yes (A)
Yes (A)
Yes (A)
Yes (B)
Yes (A)
NA
No (B)
Yes (A)
Yes (A)
Yes (A)
Yes (B)
NA
Yes (B)
Yes (A)
Yes (A)
Yes (A)
NA
Yes (B)
Yes (B)
Yes (B)
Yes (B)
NA
Yes (B)
NA
No
No
NA
No
NA
NA
NA
NA
NA
NA
NA
Some
Some
Minimal
Minimal
Some
Important
FEV1: forced expiratory volume in one second; HRQoL: health-related quality of life; AE: exacerbation of COPD; NA: evidence not available.
GOLD grade levels are indicated in brackets (see text for explanation).
Combination therapy
Combining medications of different classes seems a convenient way of delivering treatment and obtaining better
results. This includes better lung function and improved
symptoms [4345].
Data from trials combining long-acting inhaled b-agonists
and inhaled corticosteroids show a significant additional
effect on pulmonary function and a reduction in symptoms in
those receiving combination therapy compared with its components [45]. The largest effects in terms of exacerbations and
health status are seen in patients with an FEV1 v50% pred,
where combining treatment is clearly better than either
component drug used alone.
No
Continue LTOT
Pa,O2 <7.3 or 7.37.8 kPa
+ cor pulmonale, polycythemia
during rest, sleep and exertion?
Yes
Continue LTOT
No
Discontinue
LTOT
938
Spirometry, DL,CO
FEV1 <60% pred or
DL,CO <60% pred
Unusually
decreased
exercise
capacity
Quantitative lung
scan to predict
postoperative lung
function
ppo FEV1 <40% pred or
ppo DL,CO <40% pred
Measure aerobic
capacity (stair climb
as alternate)
Consider
surgery
939
Favourable
Unfavourable
Clinical
Physiological
Older age
Co-morbid illness
Cardiac disease
Pulmonary hypertension
w10% weight loss
Frequent respiratory infections
Chronic bronchitis
FEV1 v35% pred
Low trapped gas volume
Decreased DL,CO
Imaging
CXR
CT
Angiography
Isotope scan
CXR: chest radiography; CT: computed tomography; FVC: forced vital capacity; FEV1: forced expiratory volume in one second; DL,CO: carbon
monoxide diffusing capacity of the lung; Pa,O2; arterial oxygen tension; Pa,CO2; arterial carbon dioxide tension. Table modified from [68].
Candidate
for LVRS
Yes
DL,CO 20%
pred?
FEV1 20%
pred?
No
Yes
No
No
Homogenous
emphysema?
Upper lobe
predominant
emphysema?
Yes
Yes
Group A
Definition
No
Low postrehabilitation
exercise
capacity?
Yes
Yes
Group B
Group C
Low postrehabilitation
exercise
capacity?
No
Group D
No
Group E
940
Assessment
Several clinical elements must be considered when evaluating patients with exacerbations. These include the severity of
the underlying COPD, the presence of co-morbidity and the
history of previous exacerbations. The physical examination
should evaluate the effect of the episode on the haemodynamic and respiratory systems. The diagnostic procedures to
be performed depend on the setting of the evaluation [82, 83].
The pharmacological treatment of patients with an exacerbation of COPD is based on the same medications utilised in
the management of the stable patient [13]. However, the
evidence supports the use of systemic glucocorticosteroids
[8488].
Table 8 shows the elements of the clinical evaluation and
diagnostic procedures that are usually informative in patients
with exacerbations according to the severity of the episode.
Treatment of exacerbations
The treatment of exacerbations has to be based on the
clinical presentation of the patient, as shown in tables 10, 11
and 12.
Table 8. Clinical history, physical findings and diagnostic procedures in patients with exacerbation of chronic obstructive
pulmonary disease (COPD)
Clinical history
Co-morbid conditions#
History of frequent exacerbations
Severity of COPD
Physical findings
Haemodynamic evaluation
Use accessory respiratory muscles, tachypnoea
Persistent symptoms after initial therapy
Diagnostic procedures
Oxygen saturation
Arterial blood gases
Chest radiograph
Blood tests}
Serum drug concentrationsz
Sputum gram stain and culture
Electrocardiogram
Level I
Level II
Level III
z
z
Mild/moderate
zzz
zzz
Moderate/severe
zzz
zzz
Severe
Stable
Not present
No
Stable
zz
zz
Stable/unstable
zzz
zzz
Yes
No
No
No
If applicable
No
No
Yes
Yes
Yes
Yes
If applicable
Yes
Yes
Yes
Yes
Yes
Yes
If applicable
Yes
Yes
z: unlikely to be present; zz: likely to be present; zzz: very likely to be present. #: the more common co-morbid conditions associated with poor
prognosis in exacerbations are congestive heart failure, coronary artery disease, diabetes mellitus, renal and liver failure; }: blood tests include cell
blood count, serum electrolytes, renal and liver function; z: serum drug concentrations, consider if patients are using theophylline, warfarin,
carbamezepine, digoxin; : consider if patient has recently been on antibiotics.
941
[89, 90]. The main delivery devices include nasal cannula and
venturi masks. Alternative delivery devices include nonrebreather masks, reservoir cannulae, nasal cannulae or transtracheal catheters.
As a general principle, prevention of tissue hypoxia
supercedes CO2 retention concerns. If CO2 retention occurs,
monitor for acidemia. If acidemia occurs, consider noninvasive or invasive mechanical ventilation.
Assess patient
Obtain ABG
Begin O2
Assure Pa,O2 >8 kPa
Adjust O2 to Sa,O2 90%
Hypercapnia?
(Pa,CO2 >6.7 kPa)
No
Yes
No change in
oxygen setting
pH <7.35?
(with Pa,O2
>8 kPa)
Reassess ABG in
12 h
Maintain O2
Sa,O2 90%
Yes
No
Hypercapnia?
Pa,CO2 >6.7 kPa
No
Maintain O2
Sa,O2 90%
Yes
Reassess ABG
in 2 h
pH <7.35?
(with Pa,O2
>8 kPa)
Yes
Consider
mechanical ventilation
NPPV or intubation
No
No change in
oxygen setting
942
Contraindication
for NPPV?
Yes
No
Intubate
MV
NPPV with
monitoring
Weaning
Improvement in
pH, Pa,CO2
clinical status
Yes
No
Continue NPPV
Intubate
MV 48 h
2-h T-tube trial
Wean to complete
disconnection
Success
Failure
Discontinue MV
NPPV
943
Follow-up evaluation
Once discharged, the patient should be followed. There are
no studies that have addressed the specific schedules more
likely to result in a positive outcome, but patients with
frequent exacerbations are more likely to relapse. Likewise,
patients who have developed respiratory failure requiring
admission to an ICU carry a very high mortality risk. Based
on this, the guidelines for the re-evaluation of patients
admitted for exacerbation of COPD should include: reassessment within 4 weeks; evaluation of improvement in symptoms
and physical exam; assessment of need for supplemental
oxygen; repeat examination if previous abnormalities were
present; assessment of ability of the patient to cope with the
environment; an understanding and re-adjustment of the
treatment regimen.
Referral indications
Referral to specialist care is indicated for COPD patients
with the following: disease onset at age v40 yrs; frequent
exacerbations (two or more per year) despite adequate
treatment; rapidly progressive course of disease (decline in
FEV1, progressive dyspnoea, decreased exercise tolerance,
unintentional weight loss; severe COPD (FEV1v50% pred)
despite optimal treatment; need for LTOT; onset of comorbid illness (osteoporosis, heart failure, bronchiectasis,
lung cancer); evaluation for surgery.
Clinical presentation
At risk
Symptomatic
Exacerbations
Respiratory
failure
Interventions
Smoking cessation
Disease management
Pulmonary rehabilitation
Other options
Disease progression
FEV1
Symptoms
944
Conclusions
This summary presents an overview of the entire document
for the health practitioner, which is readily available online
(www.copd-ats-ers, www.ersnet.org and www.thoracic.org).
This summary does not include any reference to the patient
document, which, due to its inherent characteristics, cannot
be presented in a conventional format. The readers are
encouraged to visit the website to access both full documents.
The committee that developed this document fully understands that the field is rapidly changing and that individual
components of this document need to be updated periodically
as the need arises. However, the modular and flexible design
allows for this to occur easier than ever before. The challenge
for the future is to develop mechanisms to permit the updated
flow of valid scientific information to reach all who need it.
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