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Title: Pulmonary Function Studies


1
Pulmonary Function Studies
  • The Role of the Therapist in COPD Diagnosis
  • S. Lande Lambert, CRT

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SPIROMETRY FOR HEALTH CARE PROVIDERSGlobal
Initiative for Chronic Obstructive Lung Disease
(GOLD)
5
CONTENTS
  • I. INTRODUCTION
  • II. BACKGROUND INFORMATION
  • A. What Is Spirometry?
  • B. Why Perform Spirometry?
  • C. Spirometry in Primary Care
  • D. Screening for Airway Obstruction in Primary
    Care
  • E. Recognizing COPD
  • III. USING SPIROMETRY IN CLINCIAL PRACTICE
  • A. Types of Spirometers
  • B. Information Provided by the Spirometer
  • C. Diagnosis of Airway Obstruction
  • Figure 1. GOLD Spirometric Criteria for COPD
    Severity

6
CONTENTS (contd)
  • IV. SPIROGRAM INTERPRETATION
  • A. Normal Lung Function
  • Figure 2. Normal Spirogram Volume-Time
    Curve
  • B. Bronchodilator Reversibility Testing in COPD
  • C. Patterns of Spirometric Curves
  • Figure 3. Volume-Time Curves (before and
    after bronchodilator)
  • Figure 4. Features of Ventilatory Abnormality
    in Spirometry
  • Figure 5. Patterns of Ventilatory
    abnormalities
  • D. Flow-Volume Measurement

7
CONTENTS (contd)
  • V. PERFORMING SPIROMETRY
  • A. Preparing the Patient
  • Figure 6A. Normal Flow-Volume Curve
  • Figures 6B, 6C, 6D. Patterns of Flow-Volume
    Curves Showing Ventilatory Abnormalities
  • B. Measuring FEV1, FVC, and Flow-Volume
    Curves
  • C. Differential Diagnosis

8
CONTENTS (contd)
  • VI. TROUBLESHOOTING
  • A. Accuracy and Quality of Readings
  • Figure 7. Examples Poorly Performed Curves
  • B. Equipment Maintenance and Calibration
  • C. Infection Control
  • D. When to Refer for Further Respiratory
    Function Testing
  • REFERENCES

9
I.INTRODUCTION
10
I. Introduction
  • Chronic Obstructive Pulmonary disease (COPD) is a
    clinical diagnosis that should be based on
    carefully history taking, the presence of
    symptoms and assessment of airway obstruction
    (also called airflow limitation). The GOLD
    international COPD guidelines1, as well as
    national guidelines2, advise spirometry as the
    gold standard for accurate and repeatable
    measurement of lung function. Evidence is
    emerging that when spirometry confirms a COPD
    diagnosis, doctors initiate more appropriate
    treatment. Spirometry is also helpful in making a
    diagnosis in patients with breathlessness and
    other respiratory symptoms and for screening in
    occupational environments.

11
I. Introduction (Contd)
  • Although the use of spirometers in primary care
    is increasing, in some countries uptake is still
    low. In those countries where spirometry is in
    more common usage, there are major concerns
    regarding the technical ability of operators to
    perform the test and interpret its results. Many
    primary care physicians, nurses, and other health
    care providers have had little formal training in
    spirometry. More accredited courses are appearing
    but these are often time consuming and fairly
    expensive. Many clinicians feel apprehensive
    about purchasing a spirometer because of
    uncertainties about performing and interpreting
    spirometry. Epidemiologic studies confirm that
    both late diagnosis and under-diagnosis of COPD
    are commonproblems that wider use of spirometry
    could help to address.

12
I. Introduction (Contd)
  • There is therefore a considerable need to
  • Encourage the use of spirometers in primary
    care
  • Explain the importance of spirometry in the
    management of COPD
  • Provide information on how to perform
    spirometry correctly
  • Explain interpretation of spirometry results

Most guidelines recommend the use of spirometers
that provide a real-time trace to help assess the
quality and repeatability of blows. Such
spirometers tend to be quite expensive and
expectations that these could be used widely in
poorer countries are unrealistic. Cheaper
substitutes are available at relatively low cost
these can provide the basic indices accurately
but give little indication as to how well
patients perform the test.
13
II.BACKGROUND INFORMATION
14
A. What Is Spirometry?
  • Spirometry is a method of assessing lung function
    by measuring the volume of air that the patient
    can expel from the lungs after a maximal
    inspiration.
  • The indices derived from this forced exhaled
    maneuver have become the most accurate and
    reliable way of supporting a diagnosis of COPD.
    When these values are compared with predicted
    normal values determined on the basis of age,
    height, sex, and ethnicity, a measure of the
    severity of airway obstruction can be determined.
    It is on these values that COPD guidelines around
    the world base the assessment of mild, moderate,
    and severe disease levels.

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A. What Is Spirometry? (contd)
  • Spirometry is however only one way of
    interpreting COPD disease severity. Other
    measures, such as the MRC dyspnea scale for
    measuring breathlessness, exacerbation
    frequency, body mass index, quality of life
    assessment, and exercise capacity all help to
    build a more complete picture2.

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B. Why Perform Spirometry?
  • Spirometry is the best way of detecting the
    presence of airway obstruction and making a
    definitive diagnosis of asthma and COPD. Its
    major uses in COPD are to
  • Confirm the presence of airway obstruction
  • Confirm an FEV1/FVC ratio lt 0.7 after
    bronchodilator
  • Provide an index of disease severity
  • Help differentiate asthma from COPD
  • Detect COPD in subjects exposed to risk
    factors, predominantly tobacco smoke,
    independently of the presence of respiratory
    symptoms
  • Enable monitoring of disease progression
  • Help assess response to therapy

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B. Why Perform Spirometry? (contd)
  • Aid in predicting prognosis and long-term
    survival
  • Exclude COPD and prevent inappropriate
    treatment if spirometry is normal

Spirometry has many other applications in
assessing and managing respiratory disease. These
include measuring the presence and severity of
restrictive lung defects, screening of the
workforce in hazardous occupational environments,
pre-employment screening for certain occupations,
and assessing fitness to dive. Some believe it
may be useful as a motivating tool to help
smokers to quit, but solid scientific evidence on
this point is lacking at present, and research
findings have been equivocal.
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C. Spirometry in Primary Care
  • The development of COPD is slow and insidious and
    symptoms tend to be noted by patients only after
    there has been a significant loss of lung
    function, often to 50-60 of predicted value.
    People with COPD often present far too late to
    their doctor because they accept cough or mild
    breathlessness as a normal result of years of
    smoking or because they do not wish to be told
    that they have to stop smoking. However, stopping
    smoking is key. It is the most important way of
    slowing disease progression, and it is most
    beneficial in the early stages of COPD.
  • COPD is markedly under-diagnosed, with recent
    estimates of between 25 and 50 of patients with
    clinically important disease being undetected or
    misdiagnosed. (contd)

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C. Spirometry in Primary Care (contd)
  • Although awareness has increased in the last 10
    years, the management and diagnosis of COPD in
    primary care is still poor. The wrong diagnosis
    is commonsome patients who have a clinical
    diagnosis of COPD are found to have normal lung
    function, many patients with COPD are
    undiagnosed, and there is much confusion
    regarding labeling patients with COPD or asthma.
  • Primary care physicians are in an ideal position
    to be able to detect COPD in its early stages and
    perform spirometry to confirm the diagnosis3,4.
    Management of COPD is largely carried out in
    primary care and much can now be done to improve
    symptoms and quality of life, and to reduce the
    frequency and impact of exacerbations. Such
    information is clearly set out in most national
    and international guidelines.

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D. Screening for Airway Obstruction in Primary
Care
  • The role of screening at-risk populations in
    primary care is more controversial. When
    assessing the efficacy of screening programs, a
    number of important factors need to be
    considered. These include the criteria for the
    population to be screened, the percentage of
    positive results, and the cost effectiveness of
    screening. It is crucial to assess the clinical
    outcomes of screening. Although we have some
    answers to these questions, the main issue of
    whether detecting early disease in relatively
    asymptomatic smokers significantly increases quit
    rates has still to be resolved.
  • The most cost-effective method would appear to be
    a case-finding technique, performing spirometry
    in those atrisk of COPD. In a Dutch study5, 27
    of smokers or exsmokers over 35 years of age
    who also had a persistent cough were found to
    have airway obstruction.

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E. Recognizing COPD
The GOLD guidelines1 define COPD as A
preventable and treatable disease with some
significant extrapulmonary effects that may
contribute to the severity in the individual
patient. Its pulmonary component is characterized
by airflow limitation that is not fully
reversible. The airflow limitation is usually
progressive and associated with an abnormal
inflammatory response of the lung to noxious
particles or gases.
  • The main clinical features of COPD are
  • Chronic cough, which may be daily and
    productive, but can also be intermittent and
    unproductive
  • Breathlessness on exertion, initially
    intermittent and becoming persistent

22
E. Recognizing COPD (contd)
  • Sputum production any pattern of sputum
    production may indicate COPD
  • Frequent exacerbations of bronchitis
  • A history of exposure to risk factors,
    especially tobacco smoke, occupational dusts,
    home cooking and biomass fuels.

The GOLD guidelines recommend that clinicians
should suspect COPD and perform spirometry
whenever any of these indicators are present in
an individual aged over 40 years. When these
features are present it is crucial to ask, COULD
IT BE COPD?
23
III.USING SPIROMTERYIN CLINICAL PRACTICE
24
A. Types of Spirometers
  • There are many different types of spirometer with
    costs varying from 1003,000 Euros/502,000 USD.
  • Bellows or rolling seal spirometers are large
    and not very portable, and are used predominantly
    in lung function laboratories. They require
    regular calibration with a 3-liter syringe and
    are very accurate.
  • Electronic desktop spirometers are compact,
    portable, and usually quick and easy to use. They
    have a real-time visual display and paper or
    computer printout. Some require calibration with
    the 3-liter syringe others can be checked for
    accuracy with the syringe but require any changes
    to be performed by the manufacturer. (contd)

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A. Types of Spirometers (contd)
  • Generally they need little attention other than
    cleaning. They maintain accuracy over years and
    are ideal for primary care.
  • Small, inexpensive hand-held spirometers
    provide a numerical record of blows but no
    printout. It may be necessary to look up
    predicted values in tables, but some include
    these in their built-in software. Recent models
    allow pre-programming of patient details so that
    the spirometer also gives percent predicted
    values. These are good for simple screening and
    are accurate for diagnosis if the more expensive
    desktop form is impractical or too expensive.5

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A. Types of Spirometers (contd)
  • Many spirometers provide two forms of traces. One
    is the standard plot of volume exhaled against
    time. The other is a plot of flow (L/sec) on the
    vertical axis versus volume expired (L) on the
    horizontal axis. This is a flowvolume trace and
    is most helpful in diagnosing airway obstruction.
  • In some countries a printed record of spirometry
    is essential for claiming insurance/practitioner
    reimbursement. The type of spirometer to be used
    may need to be considered in the light of this,
    as some automatically produce a printout, others
    can store data to be printed later from a PC, and
    others do not have printing capacity at all.

27
B. Information Provided by the Spirometer
The standard spirometry maneuver is a maximal
forced exhalation (greatest effort possible)
after a maximum deep inspiration (completely full
lungs). Several indices can be derived from this
blow.
  • FVC Forced Vital Capacity the total volume
    of air that the patient can forcibly exhale in
    one breath.
  • FEV1 Forced Expiratory Volume in One Second
    the volume of air that the patient is able to
    exhale in the first second of forced expiration.
  • FEV1 /FVC the ratio of FEV1 to FVC expressed
    as a fraction (previously this was expressed as a
    percentage).

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B. Information Provided by the Spirometer
(contd)
  • Values of FEV1 and FVC are measured in liters and
    are also expressed as a percentage of the
    predicted values for that individual.
  • The ratio of FEV1/FVC is normally between 0.7 and
    0.8. Values below 0.7 are a marker of airway
    obstruction, except in older adults where values
    0.650.7 may be normal. Caution particularly
    needs to be taken in patients over 70 years,
    where the use of predicted values extrapolated
    from the younger population may result in
    over-diagnosing COPD. In people over 70 years
    old, the FEV1/FVC ratio may need to be lowered to
    0.65 as a lower limit of normal. Conversely, in
    people under 45, using a ratio of 0.7 may result
    in under-diagnosis of airway obstruction. To
    avoid both of these problems, many experts
    recommend use of the lower limit of normal for
    each population.

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B. Information Provided by the Spirometer
(contd)
  • Predicted values are calculated from thousands of
    normal people and vary with sex, height, age and
    ethnicity. The standard predicted values in most
    of Europe are those established by the European
    Respiratory Society or the European Community
    Health and Respiratory Survey (ECHRS), but other
    values may be used in different countries. Those
    values most appropriate for the local population
    should be used.
  • FlowVolume Measurement - Many electronic desktop
    spirometers and spirometers used in lung function
    laboratories utilize a pneumotachograph measuring
    gauge, which measures airflow and integrates the
    signal to derive volume. This allows the
    spirometer to plot traces of flow rate against
    the volume of air exhaled, producing a
    flowvolume curve. On many spirometers such
    curves provide the main initial visual realtime
    display when patients are performing their blows.

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B. Information Provided by the Spirometer
(contd)
  • FEV6 - This is a more recently derived value
    which measures the volume of air that can
    forcibly be expired in 6 seconds. It approximates
    the FVC and in normal people the two values would
    be identical. Using FEV6 instead of FVC may be
    helpful in patients with more severe airflow
    obstruction who make take up to 15 seconds to
    fully exhale. As they find this difficult and
    often stop before full exhalation, the FVC, and
    hence the severity of airway obstruction, may be
    underestimated. Some new hand-held spirometers
    from Vitalograph use the FEV6 instead of FVC and
    have predicted tables to match. The FEV1/FEV6 is
    well validated and is an acceptable alternative
    to FEV1/FVC6,7.

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B. Information Provided by the Spirometer
(contd)
  • Slow VC Slow Vital Capacity the patient takes
    a full breath in as before but exhales slowly in
    their own time. In patients with COPD with more
    marked airway obstruction and dynamic
    compression, the slow vital capacity may exceed
    the FVC by gt 0.5 liters. This index is not used
    routinely in primary care. However, ATS /ERS
    guidelines are increasingly suggesting FEV1/ Slow
    VC as the preferred ratio6.

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C. Diagnosis of Airway Obstruction
  • The spirometric criterion required for a
    diagnosis of COPD is an FEV1/FVC ratio below 0.7
    after bronchodilator.
  • Go to Figure 1.

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IV.SPIROGRAM INTERPRETATION
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A. Normal Lung Function
  • Interpretation of spirometry involves looking at
    the absolute values of FEV1, FVC, and FEV1/FVC,
    comparing them with predicted values, and
    examining the shape of the spirograms. Patients
    should complete three blows that are consistent
    and within 5 of each othermany electronic
    spirometers automatically provide this
    information.
  • In a patient with normal lung function, the
    volumetime curve should rise rapidly and
    smoothly and plateau within 3-4 seconds. With
    increasing degrees of airway obstruction it takes
    longer to blow out the airup to 15 secondsand
    the upward slope of the spirogram is much less
    steep.
  • Go to Figure 2.

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B. Bronchodilator Reversibility Testing in COPD
  • Assessing bronchodilator reversibility is
    important to determine whether fixed airway
    narrowing is present8. In patients with COPD,
    post-bronchodilator FEV1/FVC remains lt 0.7.
    However, the FEV1 may improve significantly after
    bronchodilator, and a change of gt 12 AND gt 200
    mL in FEV1 can occur in COPD1. In addition, the
    degree of bronchodilator reversibility can vary
    from day to day. Larger changes in FEV1 do not
    negate a diagnosis of COPD, although the greater
    these changes are the greater the likelihood that
    the patient has asthma, either instead of or in
    addition to COPD.

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B. Bronchodilator Reversibility Testing in COPD
(contd)
  • Bronchodilator reversibility testing is best done
    as a planned procedure, as it is time consuming.
    If the patient is undiagnosed and on no therapy,
    acute reversibility can be assessed on the first
    visit. Short-acting bronchodilators need to be
    withheld for at least 4 hours prior to testing,
    and long-acting bronchodilators for 12 hours.
    Recent treatment with inhaled glucocorticosteroids
    can also reduce bronchodilator reversibility
    because the pre-bronchodilator FEV1 may improve
    significantly with inhaled glucocorticosteroid
    therapy, especially if asthma is present.

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B. Bronchodilator Reversibility Testing in COPD
(contd)
Reversibility testing needs to be interpreted in
the light of the patients clinical history and
examination. Some patients with COPD can have
greater reversibility and some, especially those
with late-onset or longstanding asthma,
demonstrate very little FEV1 change in response
to bronchodilators.
  • Spirometry should be undertaken when the
    patient is clinically stable and free from a
    respiratory tract infection.
  • Short-acting bronchodilators should be
    withheld for the previous 6 hours, long-acting
    bronchodilators for 12 hours, and sustained
    release theophylline for 24 hours.

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B. Bronchodilator Reversibility Testing in COPD
(contd)
  • FEV1/FVC should be measured before and 15-20
    minutes after bronchodilator is given.
  • The bronchodilator should be given by metered
    dose inhaler, ideally through a spacer. A
    nebulizer may be used but generally larger doses
    are delivered by this route.
  • The dose administered should be high on the
    dose-response curve.
  • Possible dose protocols include 400 µg
    salbutamol, up to 160 µg ipratropium, or the two
    combined.

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B. Bronchodilator Reversibility Testing in COPD
(contd)
  • Calculating bronchodilator reversibility
  • FEV1 Reversibility Post-bronchodilator
    FEV1
  • Pre-bronchodilator FEV1 x 100
  • Pre-bronchodilator FEV1
  • In the example shown in Figure 3
  • FEV1 reversibility 2.2 2.0
    x 100 10

  • 2.0
  • As a general rule spirometry that becomes normal
    after bronchodilator is not COPD!

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C. Patterns of Spirometric Curves
  • There are 3 basic patterns to recognize
  • NORMAL FEV1 and FVC above 80 predicted
    FEV1/FVC ratio above 0.7
  • OBSTRUCTIVE FEV1 below 80 predicted
  • FVC can be normal or reduced usually to a
    lesser degree than FEV1
  • FEV1/FVC ratio below 0.7
  • RESTRICTIVE FEV1 below 80 predicted
  • FVC below 80 predicted
  • FEV1/FVC ratio normal - above 0.7.
  • Spirometry may show a restrictive pattern,
    suggesting the patient's dyspnea is due to a
    restrictive lung disease, and not COPD. In this
    case, the patient should be referred for further
    lung function testing and investigations.

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D. FlowVolume Measurement
  • Many electronic desktop spirometers and
    spirometers used in lung function laboratories
    utilize a pneumotachograph measuring gauge, which
    measures airflow and integrates the signal to
    derive volume. This allows the spirometer to plot
    traces of flow rate against the volume of air
    exhaled, producing a flowvolume curve. On many
    spirometers such curves provide the main initial
    visual realtime display when patients are
    performing their blows.
  • The interpretation of flowvolume curves is less
    well understood in primary care as it may not be
    taught in basic spirometry courses. Nevertheless
    the curve is a most helpful addition when
    interpreting lung function results, and provides
    a quick and simple check on whether or not airway
    (contd)

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D. FlowVolume Measurement (contd)
obstruction is present. It is also a tool for
identifying the early stages of airway
obstruction and provides additional help in the
interpretation of a mixed pattern of obstruction
and restriction. In the simplest terms it is
adequate to look at the shape of the curve and
compare it with the shape of the predicted
curveusually a dotted lineconstructed by the
spirometer.
  • A normal trace (Figure 6A) will have a rapid
    rise to maximal expiratory flow and then an
    almost linear, uniform decline in flow until all
    the air is expelledthe point of intersection
    with the x axis is the FVC.

47
D. FlowVolume Measurement (contd)
  • In airflow obstruction (Figure 6B) there is a
    concave dip in the second part of the curve which
    will become more marked with increasing
    obstruction. This will be seen in COPD and asthma
    and any other disease causing airflow
    obstruction.
  • In more severe emphysema (Figure 6C) where
    loss of airway elasticity causes the airways to
    collapse when forced exhalation occurs (dynamic
    compression), there will be a characteristic
    sudden fall in flow after maximal expiratory flow
    is reachedthe steeple pattern.
  • In restrictive lung abnormalities (Figure 6D)
    the shape of the flowvolume curve is normal but
    there is a reduction in lung volume which moves
    the FVC point to the left compared with the
    predicted curve.

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V.PERFORMING SPIROMETRY
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A. Preparing The Patient
  • It is important to explain the purpose of the
    test and describe clearly what the patient will
    be asked to do. It is often helpful to
    demonstrate or mimic the procedure yourself and
    emphasize the importance of taking a full breath
    and blowing out as fast and hard as possible.
  • Before starting the patients age, sex, and
    height need to be recorded and entered into the
    spirometer so that predicted curves and values
    can be calculated by the spirometer. If the
    patient is of Asian or Afro-Caribbean origin you
    may need to adjust the normal values as these
    tend to be about 10 less in these groups than in
    Caucasians. Many spirometers do this adjustment
    for you.

50
A. Preparing The Patient (contd)
  • Inquire and record the time of last
    bronchodilator inhaler use, particularly if
    performing a reversibility test. The patient
    should be comfortable and preferably have
    recently emptied their bladder the procedure
    can cause urinary incontinence. Ideally, they
    should be seated for the procedure as there is a
    small risk of syncope, which is greater if
    standing.
  • Go to Figure 6A.
  • Go to Figure 6B.

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B. Measuring FEV1, FVC, and FlowVolume Curves
  • Attach a clean, disposable, one-way mouthpiece
    to the spirometer.
  • Instruct the patient to breathe in fully until
    the lungs feel full.
  • The patient should hold their breath long
    enough to seal their lips tightly around the
    mouthpiece.
  • Blast the air out as forcibly and fast as
    possible until there is no more air left to
    expel. The operator should verbally encourage the
    patient to keep blowing and keep blowing during
    this phase. Watch the patient to make sure a good
    mouth seal around the mouthpiece is achieved.

54
B. Measuring FEV1, FVC, and FlowVolume Curves
(contd)
  • Check that an adequate trace has been
    achieved. Sometimes with electronic spirometers
    the patient may leak a small volume of air into
    the mouthpiece while sealing the lips which will
    register as the blow.
  • Repeat the procedure at least twice until
    three acceptable and reproducible blows are
    obtained. Maximum of 8 efforts.
  • There should be three readings, of which the
    best two are within 100 mL or 5 of each other
    and best.
  • Depending on the model of spirometer, the
    numbers appear as a table of actual and predicted
    figures together with volumetime and flowvolume
    traces. The best readings of FEV1 and FVC are
    usually recorded.

55
B. Measuring FEV1, FVC, and FlowVolume Curves
(contd)
  • The use of a nose clip is uncommon in primary
    care but it can be helpful alternatively, ask
    the patient to pinch their nose if they are
    having difficulties with blowing correctly.
  • Spirometers with real-time traces and printouts
    are preferred as they provide helpful information
    about the quality and acceptability of the blows.

56
C. Differential Diagnosis
  • If spirometry confirms airway obstruction, the
    main differential diagnoses are COPD and asthma.
    These two conditions can often be differentiated
    through a careful clinical history and smoking or
    other exposure patterns. However, at times
    certainty is not possible. Although FEV1
    reversibility of more than 12 favors a diagnosis
    of asthma, reversibility of this magnitude and
    higher is seen in COPD, even if less frequently.

57
C. Differential Diagnosis (contd)
  • A history of childhood wheezing, atopic symptoms,
    and diurnal variation in peak flow gt 20 (as
    established by monitoring at home twice daily for
    2 weeks) may all favor a diagnosis of asthma.
    Similarly, a therapeutic trial of prednisolone 30
    mg daily for 2 weeks, or of inhaled
    corticosteroids for 2-4 weeks, that leads to
    marked improvement in FEV1 may help to identify
    asthma as the more likely diagnosis. The British
    NICE COPD Guidelines2 suggest a greater than 400
    mL increase in FEV1 after treatment trial
    indicates asthma. A reduced diffusing capacity in
    addition to airflow limitation is characteristic
    of emphysema.

58
VI.TROUBLESHOOTING
59
A. Accuracy and Quality of Readings
  • The most common reason for inconsistent readings
    is patient technique. Errors may be detected by
    observing the patient throughout the maneuver and
    by examining the resultant traces.
  • Spirometry becomes much easier to perform and
    interpret with practice. Despite this, some
    patients find it a difficult test, and will not
    be able to perform repeatable curves. Do not be
    discouraged this can occur even for
    professionals in respiratory function
    laboratories. However, familiarity with the
    spirometer is important, and adopting the same
    careful approach each time will help you gain
    confidence. Common problems are shown below but
    do not be discouraged by the long list it is
    simply to alert you to points you need to watch
    closely.

60
A. Accuracy and Quality of Readings (contd)
Common problems (and examples of traces where
appropriate) include
  • Inadequate or incomplete inhalation (Figure
    7C, 7E)
  • Lack of blast effort during exhalation
    sub-maximal effort (Figure 7E)
  • Delayed onset of maximal effort
    under-estimates FEV1 (Figure 7D)
  • Incomplete emptying of lungs common in COPD
    where this can take up to 15 seconds, and in more
    elderly and infirm patients (Figure 7E)
  • Additional breath during maneuver
  • Lips not tight around mouthpiece (leaks
    under-estimate FEV1 and FVC)

61
A. Accuracy and Quality of Readings (contd)
Common problems (and examples of traces where
appropriate) include (Contd)
  • A slow start to the blow - under-estimates FEV1
    (Figure 7D)
  • Exhaling in part through the nose
  • Coughing (Figure 7A)
  • Glottic closure
  • Obstruction of mouthpiece by teeth or tongue
  • Poor posturee.g., leaning forward or
    slouching
  • Poor operator knowledge and training
  • Poorly maintained and calibrated spirometer
  • Go to Figure 7A, B, C, D, E.

62
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63
B. Equipment Maintenance and Calibration
  • In order to provide accurate and repeatable
    results, spirometers must be regularly cleaned
    and maintained as directed in the manufacturers
    instructions. The correct functioning must be
    frequently checked with some form of calibration.
  • Ideally, calibration should be performed with a
    3-liter syringe which will allow validation of
    spirometer accuracy. Some electronic spirometers
    can be recalibrated by the user but others only
    by returning them to the manufacturer. Most
    modern electronic spirometers, however, drift
    very little from the set calibration levels so
    use of the 3-liter syringe helps to check that
    levels are unchanged.

64
B. Equipment Maintenanceand Calibration (contd)
  • An alternative is to assess overall performance
    of the spirometer by regularly testing of a
    healthy individual every weeka biological
    control. Generally a variation of more than 5
    in FEV1 or FVC should alert you to a problem
    which may necessitate further testing and
    possible return to the manufacturer.

65
C. Infection Control
  • Precautions must be taken to minimize any cross
    infection via the spirometer. The use of
    low-resistance barrier filters and disposable
    mouthpieces significantly reduces the risk of
    infection and also helps to protect the equipment
    from exhaled secretions. A new filter must be
    used for each patient.

66
D. When To Refer For Further Respiratory
Function Testing
  • Many physicians do not have the time to perform
    their own spirometry, and their practice nurse or
    assistant physician may undertake spirometry.
    Some studies suggest that superior results
    (reliability and validity) are obtained this way.
    When spirometry is abnormal but not diagnostic,
    or if the test cannot be performed reproducibly,
    it is preferable for patients to be referred to a
    lung function laboratory or a specialist, for
    optimal performance and interpretation of
    spirometry. In addition, further lung function
    testing that includes more comprehensive tests
    will assist in making a definitive diagnosis.
    These tests may include full lung volumes,
    diffusing capacity, bronchial provocation
    testing, skin-prick testing, exhaled breath
    testing, and arterial blood gas measurements. A
    restrictive or mixed obstructive-restrictive
    spirometric pattern almost always requires more
    complete lung function testing before a final
    diagnosis can be made.

67
REFERENCES
68
  • 1. Global Initiative for Chronic Obstructive
    Lung Disease. Global strategy for the diagnosis,
    management, and prevention of chronic obstructive
    pulmonary disease. (Updated 2007).
    http//www.goldcopd.org.
  • 2. National Collaborating Centre for Chronic
    Conditions. Chronic obstructive pulmonary
    disease national clinical guideline on
    management of chronic obstructive pulmonary
    disease in adults in primary and secondary care.
    Thorax 2003, 59 (Suppl 1) 1-232.
  • 3. Dales RE, Vandemheen KL, Clinch J, et al.
    Spirometry in the primary care setting. Influence
    on clinical diagnosis and management of airflow
    obstruction. Chest 2005, 128 2443 7.
  • 4. Enright P. Does screening for COPD by Primary
    Care Physicians have the potential to cause more
    harm than good? Chest 2006, 129 833-4.
  • 5. van Schayck CP,Loozen JM, Wagena et al.
    Detecting patients at high risk of developing
    chronic obstructive pulmonary disease in general
    practice cross-sectional case-finding study. BMJ
    2002, 324 1370-4.
  • 6. Miller MR, Hankinson J, Brusasco V, et al.
    ATS-ERS taskforce Standardisation of Lung
    Function Testing. Standardisation of spirometry.
    Eur Respir J 20052631938
  • 7. Vandevoorde J, Verbanck S, Schuermans D,
    Kartounian J, Vincken W. FEV1/FEV6 and FEV6 as
    alternative for FEV1/FTC and FVC in the
    spirometric detection of airway obstruction and
    restriction. Chest 20051271560-64.
  • 8. Johannsen A, Lehmann S, Omenaas E R, et al.
    Post bronchodilator spirometry reference values
    in adults and implications for disease
    management. Am J Respir Crit Care Med 2006, 73
    1316 -257.

69
lobal Initiative for Chronicbstructiveungisease
G OLD
70
GOLD Structure
  • GOLD Executive Committee
  • Roberto Rodriguez-Roisin, MD Chair
  • Klaus Rabe, MD, PhD Co-Chair

Dissemination/Implementation Task Group
Christine Jenkins, MD - Chair
Science Committee Peter Calverley - Chair
71
GOLD Executive Committee
Y. Fukuchi, Japan, APSR C. Jenkins, Australia A.
Kocabas, Turkey E. Nizankowska, Poland T. van der
Molen, Netherlands C. Van Weel, Netherlands ,WONCA
  • R. Rodriguez-Roisin, Chair, Spain
  • K. Rabe, Co-Chair, Netherlands
  • A. Anzueto, US, ATS
  • P. Calverley, UK
  • A. Casas, Columbia, ALAT
  • A. Cruz, Switzerland, WHO
  • T. DeGuia, Philippines

72
GOLD Science Committee
P. Jones K. Rabe R. Rodriguez-Roisin J.
Vestbo J. Zielinski
  • P. Calverley, Chair
  • A. Agusti
  • A. Anzueto
  • P. Barnes
  • M. Decramer
  • Y. Fukuchi

73
Description of Levels of Evidence
74
Bangladesh
Saudi Arabia
Slovenia
Germany
Ireland
Brazil
Yugoslavia
Croatia
United States
Australia
Canada
Austria
Taiwan ROC
Portugal
Philippines
Thailand
Malta
Norway
Greece
Moldova
China
Syria
South Africa
United Kingdom
Hong Kong ROC
Italy
New Zealand
Israel
Chile
Nepal
Argentina
Mexico
Russia
Pakistan
United Arab Emirates
Japan
Peru
GOLD National Leaders
Korea
Poland
Netherlands
Egypt
Venezuela
Switzerland
India
Georgia
France
Macedonia
Iceland
Denmark
Czech Republic
Turkey
Belgium
Slovakia
Singapore
Spain
Ukraine
Columbia
Romania
Uruguay
Sweden
Vietnam
Kyrgyzstan
Albania
75
GOLD Structure
  • GOLD Executive Committee
  • Roberto Rodriguez-Roisin, MD Chair
  • Klaus Rabe, MD, PhD Co-Chair

Dissemination/Implementation Task Group
Christine Jenkins, MD - Chair
Science Committee P. Calverley - Chair
76
GOLD Website Address
http//www.goldcopd.org
77
lobal Initiative for Chronicbstructiveungisease
G OLD
78
GOLD Objectives
  • Increase awareness of COPD among health
    professionals, health authorities, and the
    general public.
  • Improve diagnosis, management and prevention of
    COPD.
  • Stimulate research in COPD.

79
Global Strategy for Diagnosis, Management and
Prevention of COPD
  • Definition, Classification
  • Burden of COPD
  • Risk Factors
  • Pathogenesis, Pathology, Pathophysiology
  • Management
  • Practical Considerations

80
Definition of COPD
  • COPD is a preventable and treatable disease with
    some significant extrapulmonary effects that may
    contribute to the severity in individual
    patients.
  • Its pulmonary component is characterized by
    airflow limitation that is not fully reversible.
  • The airflow limitation is usually progressive and
    associated with an abnormal inflammatory response
    of the lung to noxious particles or gases.

81
Classification of COPD Severity by Spirometry
Stage I Mild FEV1/FVC lt 0.70
FEV1 gt 80 predicted Stage II Moderate
FEV1/FVC lt 0.70
50 lt FEV1 lt 80 predicted Stage III Severe
FEV1/FVC lt 0.70
30 lt FEV1 lt 50 predicted Stage IV Very
Severe FEV1/FVC lt 0.70 FEV1
lt 30 predicted or FEV1 lt 50 predicted
plus chronic respiratory failure
82
At Risk for COPD
  • COPD includes four stages of severity classified
    by spirometry.
  • A fifth category--Stage 0 At Risk--that appeared
    in the 2001 report is no longer included as a
    stage of COPD, as there is incomplete evidence
    that the individuals who meet the definition of
    At Risk (chronic cough and sputum production,
    normal spirometry) necessarily progress on to
    Stage I Mild COPD.
  • The public health message is that chronic cough
    and sputum are not normal remains important -
    their presence should trigger a search for
    underlying cause(s).

83
Global Strategy for Diagnosis, Management and
Prevention of COPD
  • Definition, Classification
  • Burden of COPD
  • Risk Factors
  • Pathogenesis, Pathology, Pathophysiology
  • Management
  • Practical Considerations

84
Burden of COPD Key Points
  • COPD is a leading cause of morbidity and
    mortality worldwide and results in an economic
    and social burden that is both substantial and
    increasing.
  • COPD prevalence, morbidity, and mortality vary
    across countries and across different groups
    within countries.
  • The burden of COPD is projected to increase in
    the coming decades due to continued exposure to
    COPD risk factors and the changing age structure
    of the worlds population.

85
Burden of COPD Prevalence
  • Many sources of variation can affect estimates of
    COPD prevalence, including e.g., sampling
    methods, response rates and quality of
    spirometry.
  • Data are emerging to provide evidence that
    prevalence of Stage I Mild COPD and higher is
    appreciably higher in
  • - smokers and ex-smokers
  • - people over 40 years of age
  • - males

86
COPD Prevalence Study in Latin America
The prevalence of post-bronchodilator FEV1/FVC lt
0.70 increases steeply with age in 5 Latin
American Cities
Source Menezes AM et al. Lancet 2005
87
Burden of COPD Mortality
  • COPD is a leading cause of mortality worldwide
    and projected to increase in the next several
    decades.
  • COPD mortality trends generally track several
    decades behind smoking trends.
  • In the US and Canada, COPD mortality for both men
    and women have been increasing.
  • In the US in 2000, the number of COPD deaths was
    greater among women than men.

88
Percent Change in Age-Adjusted Death Rates, U.S.,
1965-1998
Proportion of 1965 Rate
3.0
Coronary Heart Disease
Stroke
Other CVD
COPD
All Other Causes
2.5
2.0
1.5
1.0
0.5
59
64
35
163
7
0
1965 - 1998
1965 - 1998
1965 - 1998
1965 - 1998
1965 - 1998
Source NHLBI/NIH/DHHS
89
Of the six leading causes of death in the United
States, only COPD has been increasing steadily
since 1970
Source Jemal A. et al. JAMA 2005
90
COPD Mortality by Gender,U.S., 1980-2000
Number Deaths x 1000
Source US Centers for Disease Control and
Prevention, 2002
91
Global Strategy for Diagnosis, Management and
Prevention of COPD
  • Definition, Classification
  • Burden of COPD
  • Risk Factors
  • Pathogenesis, Pathology, Pathophysiology
  • Management
  • Practical Considerations

92
Risk Factors for COPD
  • Genes
  • Exposure to particles
  • Tobacco smoke
  • Occupational dusts, organic and inorganic
  • Indoor air pollution from heating and cooking
    with biomass in poorly ventilated dwellings
  • Outdoor air pollution

Lung growth and development Oxidative
stress Gender Age Respiratory infections Socioecon
omic status Nutrition Comorbidities
93
Risk Factors for COPD
Nutrition
Infections
Socio-economic status
Aging Populations
94
Global Strategy for Diagnosis, Management and
Prevention of COPD
  • Definition, Classification
  • Burden of COPD
  • Risk Factors
  • Pathogenesis, Pathology, Pathophysiology
  • Management
  • Practical Considerations

95
(No Transcript)
96
Pathogenesis of COPD
Cigarette smoke Biomass particles Particulates
Host factors Amplifying mechanisms
LUNG INFLAMMATION
Anti-oxidants
Anti-proteinases
Oxidative stress
Proteinases
Repair mechanisms
COPD PATHOLOGY
Source Peter J. Barnes, MD
97
Changes in Lung Parenchyma in COPD
Alveolar wall destruction
Loss of elasticity
Destruction of pulmonary capillary bed
? Inflammatory cells macrophages, CD8
lymphocytes
Source Peter J. Barnes, MD
98
Pulmonary Hypertension in COPD
Chronic hypoxia
Pulmonary vasoconstriction
Muscularization Intimal hyperplasia Fibrosis Obli
teration
Pulmonary hypertension
Cor pulmonale
Edema
Death
Source Peter J. Barnes, MD
99
ASTHMA
Allergens
Mast cell
Ep cells
CD4 cell (Th2)
Eosinophil
Bronchoconstriction AHR
Airflow Limitation
Reversible
Irreversible
Source Peter J. Barnes, MD
100
Global Strategy for Diagnosis, Management and
Prevention of COPD
  • Definition, Classification
  • Burden of COPD
  • Risk Factors
  • Pathogenesis, Pathology, Pathophysiology
  • Management
  • Practical Considerations

101
Four Components of COPD Management
  • Assess and monitor disease
  • Reduce risk factors
  • Manage stable COPD
  • Education
  • Pharmacologic
  • Non-pharmacologic
  • Manage exacerbations

102
GOALS of COPD MANAGEMENT VARYING EMPHASIS WITH
DIFFERING SEVERITY
  • Relieve symptoms
  • Prevent disease progression
  • Improve exercise tolerance
  • Improve health status
  • Prevent and treat complications
  • Prevent and treat exacerbations
  • Reduce mortality

103
Four Components of COPD Management
  • Assess and monitor disease
  • Reduce risk factors
  • Manage stable COPD
  • Education
  • Pharmacologic
  • Non-pharmacologic
  • Manage exacerbations

104
Management of Stable COPD Assess and Monitor
COPD Key Points
  • A clinical diagnosis of COPD should be considered
    in any patient who has dyspnea, chronic cough
    or sputum production, and/or a history of
    exposure to risk factors for the disease.
  • The diagnosis should be confirmed by spirometry.
    A post-bronchodilator FEV1/FVC lt 0.70 confirms
    the presence of airflow limitation that is not
    fully reversible.
  • Comorbidities are common in COPD and should be
    actively identified.

105
Diagnosis of COPD
EXPOSURE TO RISK FACTORS
SYMPTOMS
cough
tobacco
sputum
occupation
shortness of breath
indoor/outdoor pollution
è
è
è
SPIROMETRY
106
Management of Stable COPD Assess and Monitor
COPD Spirometry
  • Spirometry should be performed after the
    administration of an adequate dose of a
    short- acting inhaled bronchodilator to minimize
    variability.
  • A post-bronchodilator FEV1/FVC lt 0.70 confirms
    the presence of airflow limitation that is not
    fully reversible.
  • Where possible, values should be compared to
    age-related normal values to avoid overdiagnosis
    of COPD in the elderly.

107
Spirometry Normal and Patients with COPD
108
Differential Diagnosis COPD and Asthma
COPD
ASTHMA
  • Onset early in life (often childhood)
  • Symptoms vary from day to day
  • Symptoms at night/early morning
  • Allergy, rhinitis, and/or eczema also present
  • Family history of asthma
  • Largely reversible airflow limitation
  • Onset in mid-life
  • Symptoms slowly progressive
  • Long smoking history
  • Dyspnea during exercise
  • Largely irreversible airflow
  • limitation

109
COPD and Co-Morbidities
  • COPD patients are at increased risk for
  • Myocardial infarction, angina
  • Osteoporosis
  • Respiratory infection
  • Depression
  • Diabetes
  • Lung cancer

110
COPD and Co-Morbidities
  • COPD has significant extrapulmonary
  • (systemic) effects including
  • Weight loss
  • Nutritional abnormalities
  • Skeletal muscle dysfunction

111
Four Components of COPD Management
  • Assess and monitor disease
  • Reduce risk factors
  • Manage stable COPD
  • Education
  • Pharmacologic
  • Non-pharmacologic
  • Manage exacerbations

112
Management of Stable COPD Reduce Risk Factors
Key Points
  • Reduction of total personal exposure to tobacco
    smoke, occupational dusts and chemicals, and
    indoor and outdoor air pollutants are important
    goals to prevent the onset and progression of
    COPD.
  • Smoking cessation is the single most effective
    and cost effective intervention in most people
    to reduce the risk of developing COPD and stop
    its progression (Evidence A).

113
Brief Strategies to Help the Patient Willing to
Quit Smoking
  • ASK Systematically identify all tobacco
    users at every visit.
  • ADVISE Strongly urge all tobacco users to
    quit.
  • ASSESS Determine willingness to make a
    quit attempt.
  • ASSIST Aid the patient in quitting.
  • ARRANGE Schedule follow-up contact.

114
Management of Stable COPD Reduce Risk Factors
Smoking Cessation
  • Counseling delivered by physicians and other
    health professionals significantly increases quit
    rates over self-initiated strategies. Even a
    brief
  • (3-minute) period of counseling to urge a
    smoker to quit results in smoking cessation rates
    of 5-10.
  • Numerous effective pharmacotherapies for smoking
    cessation are available and pharmacotherapy is
    recommended when counseling is not sufficient to
    help patients quit smoking.

115
Management of Stable COPD Reduce Risk Factors
Indoor/Outdoor Air Pollution
  • Reducing the risk from indoor and outdoor air
    pollution is feasible and requires a combination
    of public policy and protective steps taken by
    individual patients.
  • Reduction of exposure to smoke from biomass fuel,
    particularly among women and children, is a
    crucial goal to reduce the prevalence of COPD
    worldwide.

116
Four Components of COPD Management
  • Assess and monitor disease
  • Reduce risk factors
  • Manage stable COPD
  • Education
  • Pharmacologic
  • Non-pharmacologic
  • Manage exacerbations

117
Management of Stable COPD Manage Stable COPD
Key Points
  • The overall approach to managing stable COPD
    should be individualized to address symptoms and
    improve quality of life.
  • For patients with COPD, health education plays an
    important role in smoking cessation (Evidence A)
    and can also play a role in improving skills,
    ability to cope with illness and health status.
  • None of the existing medications for COPD have
    been shown to modify the long-term decline in
    lung function that is the hallmark of this
    disease (Evidence A). Therefore, pharmacotherapy
    for COPD is used to decrease symptoms and/or
    complications.

118
Management of Stable COPD Pharmacotherapy
Bronchodilators
  • Bronchodilator medications are central to the
    symptomatic management of COPD (Evidence A).
    They are given on an as-needed basis or on a
    regular basis to prevent or reduce symptoms and
    exacerbations.
  • The principal bronchodilator treatments are
    ß2- agonists, anticholinergics, and
    methylxanthines used singly or in combination
    (Evidence A).
  • Regular treatment with long-acting
    bronchodilators is more effective and convenient
    than treatment with short-acting bronchodilators
    (Evidence A).

119
Management of Stable COPD Pharmacotherapy
Glucocorticosteroids
  • The addition of regular treatment with inhaled
  • glucocorticosteroids to bronchodilator
    treatment is appropriate for symptomatic COPD
    patients with an FEV1 lt 50 predicted (Stage III
    Severe COPD and Stage IV Very Severe COPD) and
    repeated exacerbations (Evidence A).
  • An inhaled glucocorticosteroid combined with a
    long-acting ß2-agonist is more effective than the
    individual components (Evidence A).

120
Management of Stable COPD Pharmacotherapy
Glucocorticosteroids
  • The dose-response relationships and long-term
    safety of inhaled glucocorticosteroids in COPD
    are not known.
  • Chronic treatment with systemic
    glucocorticosteroids should be avoided because of
    an unfavorable benefit-to-risk ratio (Evidence A).

121
Management of Stable COPD Pharmacotherapy
Vaccines
  • In COPD patients influenza vaccines can reduce
    serious illness (Evidence A).
  • Pneumococcal polysaccharide vaccine is
    recommended for COPD patients 65 years and older
    and for COPD patients younger than age 65 with an
    FEV1 lt 40 predicted (Evidence B).

122
Management of Stable COPDAll Stages of Disease
Severity
  • Avoidance of risk factors
  • - smoking cessation
  • - reduction of indoor pollution
  • - reduction of occupational exposure
  • Influenza vaccination

123
IV Very Severe
III Severe
II Moderate
I Mild
Add regular treatment with one or more
long-acting bronchodilators (when needed) Add
rehabilitation
Add inhaled glucocorticosteroids if repeated
exacerbations
Add long term oxygen if chronic respiratory
failure. Consider surgical treatments
124
Management of Stable COPD Other Pharmacologic
Treatments
  • Antibiotics Only used to treat infectious
    exacerbations of COPD
  • Antioxidant agents No effect of
    n-acetylcysteine on frequency of exacerbations,
    except in patients not treated with inhaled
    glucocorticosteroids
  • Mucolytic agents, Antitussives, Vasodilators
    Not recommended in stable COPD

125
Management of Stable COPD Non-Pharmacologic
Treatments
  • Rehabilitation All COPD patients benefit from
    exercise training programs, improving with
    respect to both exercise tolerance and symptoms
    of dyspnea and fatigue (Evidence A).
  • Oxygen Therapy The long-term administration of
    oxygen (gt 15 hours per day) to patients with
    chronic respiratory failure has been shown to
    increase survival (Evidence A).

126
Four Components of COPD Management
  • Assess and monitor disease
  • Reduce risk factors
  • Manage stable COPD
  • Education
  • Pharmacologic
  • Non-pharmacologic
  • Manage exacerbations

127
Management COPD Exacerbations Key Points
An exacerbation of COPD is defined as An
event in the natural course of the disease
characterized by a change in the patients
baseline dyspnea, cough, and/or sputum that is
beyond normal day-to-day variations, is acute in
onset, and may warrant a change in regular
medication in a patient with underlying COPD.
128
Management COPD Exacerbations Key Points
  • The most common causes of an exacerbation are
    infection of the tracheobronchial tree and air
    pollution, but the cause of about one-third of
    severe exacerbations cannot be identified
    (Evidence B).
  • Patients experiencing COPD exacerbations with
    clinical signs of airway infection (e.g.,
    increased sputum purulence) may benefit from
    antibiotic treatment (Evidence B).

129
Manage COPD Exacerbations Key Points
  • Inhaled bronchodilators (particularly inhaled
    ß2-agonists with or without anticholinergics)
    and oral glucocortico- steroids are effective
    treatments for exacerbations of COPD (Evidence
    A).

130
Management COPD Exacerbations Key Points
  • Noninvasive mechanical ventilation in
    exacerbations improves respiratory acidosis,
    increases pH, decreases the need for endotracheal
    intubation, and reduces PaCO2, respiratory rate,
    severity of breathlessness, the length of
    hospital stay, and mortality (Evidence A).
  • Medications and education to help prevent future
    exacerbations should be considered as part of
    follow-up, as exacerbations affect the quality of
    life and prognosis of patients with COPD.

131
Global Strategy for Diagnosis, Management and
Prevention of COPD
  • Definition, Classification
  • Burden of COPD
  • Risk Factors
  • Pathogenesis, Pathology, Pathophysiology
  • Management
  • Practical Considerations

132
Translating COPD Guidelines into Primary CareKEY
POINTS
  • Better dissemination of COPD guidelines and their
    effective implementation in a variety of health
    care settings is urgently required.
  • In many countries, primary care practitioners
    treat the vast majority of patients with COPD and
    may be actively involved in public health
    campaigns and in bringing messages about reducing
    exposure to risk factors to both patients and the
    public.

133
Global Strategy for Diagnosis, Management and
Prevention of COPDSUMMARY
  • Definition, Classification
  • Burden of COPD
  • Risk Factors
  • Pathogenesis, Pathology, Pathophysiology
  • Management
  • Practical Considerations

134
Global Strategy for Diagnosis, Management and
Prevention of COPD Summary
  • COPD is increasing in prevalence in many
    countries of the world.
  • COPD is treatable and preventable.
  • The GOLD program offers a strategy to identify
    patients and to treat them according to the best
    medications available.

135
Global Strategy for Diagnosis, Management and
Prevention of COPD Summary
  • COPD can be prevented by avoidance of risk
    factors, the most notable being tobacco smoke.
  • Patients with COPD have multiple other conditions
    (comorbidities) that must be taken into
    consideration.
  • GOLD has developed a global network to raise
    awareness of COPD and disseminate information on
    diagnosis and treatment.

136
Bangladesh
Saudi Arabia
Slovenia
Germany
Ireland
Brazil
Yugoslavia
Croatia
United States
Australia
Canada
Austria
Taiwan ROC
Portugal
Philippines
Thailand
Malta
Norway
Greece
Moldova
China
Syria
South Africa
United Kingdom
Hong Kong ROC
Italy
New Zealand
Israel
Chile
Nepal
Argentina
Mexico
Russia
Pakistan
United Arab Emirates
Japan
Peru
GOLD National Leaders
Korea
Poland
Netherlands
Egypt
Venezuela
Switzerland
India
Georgia
France
Macedonia
Iceland
Denmark
Czech Republic
Turkey
Belgium
Slovakia
Singapore
Spain
Ukraine
Columbia
Romania
Uruguay
Sweden
Vietnam
Kyrgyzstan
Albania
137
GOLD Website Address
http//www.goldcopd.org
138
ADDITIONAL SLIDES WITH NOTES PREPARED
BY PROFESSOR PETER J. BARNES, MD NATIONAL HEART
AND LUNG INSTITUTE LONDON, ENGLAND
139
Changes in Large Airways of COPD Patients
Mucus hypersecretion
Neutrophils in sputum
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