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									Global Initiative for Chronic
Obstructive
L ung
Disease
              GOLD Website Address



     http://www.goldcopd.com


18/Oct/2005         Dr. David P. Breen   2
              Facts About COPD

    COPD is the 4th leading cause of death in the
     United States (behind heart disease, cancer,
     and cerebrovascular disease).

    In 2000, the WHO estimated 2.74 million
     deaths worldwide from COPD.

    In 1990, COPD was ranked 12th as a burden
     of disease; by 2020 it is projected to rank 5th.
18/Oct/2005             Dr. David P. Breen          3
            Leading Causes of Deaths
            U.S. 1998
       Cause of Death                                  Number
 1.       Heart Disease                                724,269
 2.       Cancer                                       538,947
 3.       Cerebrovascular disease (stroke) 158,060
 4.       Respiratory Diseases (COPD)                   114,381
 5.       Accidents                                      94,828
 6.       Pneumonia and influenza                        93,207
 7.       Diabetes                                       64,574
 8.       Suicide                                        29,264
 9.       Nephritis                                      26,295
10.       Chronic liver disease                          24,936
18/Oct/2005
          All other causes of death Dr. David P. Breen  469,314   4
                  Percent Change in Age-Adjusted
                  Death Rates, U.S., 1965-1998
  Proportion of 1965 Rate
  3.0
3.0
         Coronary           Stroke        Other CVD         COPD         All Other
  2.5
2.5       Heart                                                          Causes
         Disease
  2.0
2.0

  1.5
1.5

  1.0
1.0


  0.5
0.5

            –59%             –64%            –35%           +163%          –7%
0.0 0
          1965
   18/Oct/2005   - 1998   1965 - 1998   Dr.1965P.-Breen
                                           David   1998   1965 - 1998   1965 - 1998 5
                 Age-Adjusted Death Rates for
                 COPD, U.S., 1960-1998
 Deaths per 100,000
 60
60

                              White Male
 50
50

 40
40
                                     Black Male
 30
30
                                            White Female
 20
20
                                                           Black Female
10
 10

 00
   1960
  18/Oct/2005   1965   1970              1980
                              1975 Dr. David P. Breen   1985    1990      1995   2000
                                                                                   6
  1960          1965   1970   1975        1980          1985    1990      1995   2000
              Facts About COPD: U.S.
      Between 1985 and 1995, the number of
       physician visits for COPD increased from
       9.3 to16 million.
      The number of hospitalizations for COPD
       in 2000 was estimated to be 726,000.
      Medical expenditures in 2002 were
       estimated to be $18.0 billion.
18/Oct/2005           Dr. David P. Breen          7
        Facts About COPD
  Cigarette smoking is the primary cause of
   COPD.

  In the US 47.2 million people (28% of men and
   23% of women) smoke.

  The WHO estimates 1.1 billion smokers
        worldwide, increasing to 1.6 billion by 2025. In
        low- and middle-income countries, rates are
        increasing at an alarming rate.
18/Oct/2005                Dr. David P. Breen           8
                    Irish Figures

   Diseases of the Respiratory system are the cause of
    one in five deaths in Ireland today
   In 1999 , Respiratory disease caused 7100 deaths:
    3700 in men and 3400 in women
   26% of respiratory deaths were due to COPD
        =1846 COPD-related deaths
   Clear social gradient: Respiratory mortality in the
    lowest occupational class was 200% higher than
    the highest occupational class              Inhale survey
18/Oct/2005                Dr. David P. Breen               9
                              Clinically apparent disease




                                                           Subclinical/
                                                       undiagnosed disease




18/Oct/2005   Dr. David P. Breen                                     10
              COPD and Smoking

 95% of COPD is caused by smoking
 45% of young Irish adults are current smokers

 Prevalence of current smokers is higher in
  females (46.5% female v 44.2% male)
 30% of school-leavers smoke



                                        ECRHS Group
18/Oct/2005        Dr. David P. Breen                 11
                Smoking in Ireland
Adults
      43%  in 1973  29% in 1994  27% now
      highest in lowest SE groups
      declining more slowly in women than men
Children and teenagers
      1/10 6th class pupils smoke regularly, 15% boys, 5% girls
      1/2 6th class pupils have tried smoking
      smoking increases steadily in teens in both sexes
      30-35% of 17 yo Dublin schoolchildren smoke regularly,
       equal in both sexes


18/Oct/2005                 Dr. David P. Breen                12
              Lung Function decline




18/Oct/2005          Dr. David P. Breen   13
18/Oct/2005   Dr. David P. Breen   14
Global Initiative for Chronic
Obstructive
L ung
Disease
GOLD Workshop Report:
Contents
          Introduction
          Definition and classification
          Burden of COPD
          Risk factors
          Pathogenesis, pathology,
           and pathophysiology
          Management
          Future research
              Definition of COPD

Chronic obstructive pulmonary disease
(COPD) is a disease state characterized
by airflow limitation that is not fully
reversible. The airflow limitation is usually
both progressive and associated with an
abnormal inflammatory response of the
lungs to noxious particles or gases.
18/Oct/2005           Dr. David P. Breen    17
       Burden of COPD
       Key Points
   The burden of COPD is underestimated
    because it is not usually recognized and
    diagnosed until it is clinically apparent and
    moderately advanced.
   Prevalence, morbidity, and mortality vary
    appreciably across countries but in all
    countries where data are available, COPD
    is a significant health problem in both men
    and women.
    Burden of COPD
    Key Points
 The global burden of COPD will
  increase enormously over the
  foreseeable future as the toll from
  tobacco use in developing countries
  becomes apparent.
        Burden of COPD
        Key Points

   The economic costs of COPD are high
    and will continue to rise in direct relation
    to the ever-aging population, the
    increasing prevalence of the disease,
    and the cost of new and existing medical
    and public health interventions.
               Direct and Indirect Costs of
               COPD, 2002 (US $ Billions)

         Direct Medical Cost:                                $18.0

         Total Indirect Cost:                             $ 14.1
              – Mortality related IDC                              7.3
              – Morbidity related IDC                              6.8

         Total Cost                                          $32.1
18/Oct/2005                  Dr. David P. Breen   Source: NHLBI, NIH, DHHS   21
              Risk Factors for COPD
 Host Factors      Genes (e.g. alpha1-antitrypsin
                   deficiency)
                   Hyperresponsiveness
                   Lung growth

 Exposure          Tobacco smoke
                   Occupational dusts and chemicals
                   Infections
18/Oct/2005        Socioeconomic status
                        Dr. David P. Breen         22
              Pathogenesis of COPD
                 NOXIOUS AGENT
     (tobacco smoke, pollutants, occupational agent)
                                             Genetic factors
                                             Respiratory
                                             infection
                                             Other


                      COPD
18/Oct/2005             Dr. David P. Breen                     23
                    Noxious particles
                         and gases
                                                 Host factors

                    Lung inflammation
 Anti-oxidants                                   Anti-proteinases


      Oxidative stress                         Proteinases

                                               Repair mechanisms

                    COPD pathology
18/Oct/2005               Dr. David P. Breen                    24
18/Oct/2005   Dr. David P. Breen   25
18/Oct/2005   Dr. David P. Breen   26
              Causes of Airflow Limitation

   Irreversible
     Fibrosis and narrowing of the
       airways
     Loss of elastic recoil due to
       alveolar destruction
     Destruction of alveolar support
       that maintains patency of small
       airways
18/Oct/2005           Dr. David P. Breen   27
              Causes of Airflow Limitation

   Reversible
     Accumulation of inflammatory cells,
      mucus, and plasma exudate in bronchi
     Smooth muscle contraction in
      peripheral and central airways
     Dynamic hyperinflation during exercise


18/Oct/2005           Dr. David P. Breen   28
                Objectives of COPD
                Management
               Prevent disease progression
               Relieve symptoms
               Improve exercise tolerance
               Improve health status
               Prevent and treat exacerbations
               Prevent and treat complications
               Reduce mortality
18/Oct/2005                  effects
                Minimize sideDr. David P. Breen from treatment   29
              GOLD Workshop Report
              Four Components of COPD
              Management

                              1. Assess and monitor disease

                              2. Reduce risk factors

                              3. Manage stable COPD
                                       Education
                                       Pharmacologic
                                       Non-pharmacologic

                              4. Manage exacerbations
18/Oct/2005                    Dr. David P. Breen           30
              Assess and Monitor
              Disease: Key Points

   Diagnosis of COPD is based on a history of
    exposure to risk factors and the presence
    of airflow limitation that is not fully
    reversible, with or without the presence of
    symptoms.


18/Oct/2005           Dr. David P. Breen     31
              Assess and Monitor
              Disease: Key Points

   Patients who have chronic cough
    and sputum production with a
    history of exposure to risk factors
    should be tested for airflow
    limitation, even if they do not have
    dyspnea.
18/Oct/2005           Dr. David P. Breen   32
              Assess and Monitor
              Disease: Key Points

 For the diagnosis and assessment of
  COPD, spirometry is the gold standard.
 Health care workers involved in the
  diagnosis and management of COPD
  patients should have access to
  spirometry.
18/Oct/2005           Dr. David P. Breen   33
              Assess and Monitor
              Disease: Key Points

   Measurement of arterial blood gas
    tension should be considered in all
    patients with FEV1 < 40% predicted
    or clinical signs suggestive of
    respiratory failure or right heart
    failure.
18/Oct/2005           Dr. David P. Breen   34
              Diagnosis of COPD
                                          EXPOSURE TO RISK
  SYMPTOMS                                    FACTORS
     cough                                  tobacco
    sputum                                occupation
   dyspnea                         indoor/outdoor pollution




                SPIROMETRY
18/Oct/2005          Dr. David P. Breen                      35
                Spirometry: Normal and COPD

        0
                                             FEV1       FVC     FEV1/ FVC
                                Normal       4.150      5.200       80 %
        1                       COPD         2.350      3.900       60 %


        2
                     FEV1
Liter




        3
                                                            COPD
        4                                                                  FVC
                     FEV1

        5                       Normal
                                                  FVC
                 1          2     3           4         5       6   Seconds
  18/Oct/2005                      Dr. David P. Breen                            36
              Factors Determining Severity
              Of Chronic COPD
 Severity of symptoms
 Severity of airflow limitation
 Frequency and severity of exacerbations
 Presence of complications of COPD
 Presence of respiratory insufficiency
 Comorbidity
 General health status
 Number of medications needed to manage the
  disease
18/Oct/2005             Dr. David P. Breen     37
              Classification by Severity
Stage              Characteristics
0: At risk       Normal spirometry
                 Chronic symptoms (cough, sputum)

I: Mild          FEV1/FVC < 70%; FEV1  80% predicted
                 With or without chronic symptoms (cough, sputum)

II: Moderate     FEV1/FVC < 70%; 50% FEV1 < 80% predicted
                 With or without chronic symptoms (cough, sputum, dyspnea)

III: Severe      FEV1/FVC < 70%; 30%  FEV1 < 50% predicted
                 With or without chronic symptoms (cough, sputum, dyspnea)

IV: Very Severe FEV1/FVC < 70%; FEV1 < 30% predicted or FEV1
18/Oct/2005                  Dr. David P. Breen                       38
                < 50% predicted plus chronic respiratory failure
              GOLD Workshop Report
              Four Components of COPD
              Management

                              1. Assess and monitor disease

                              2. Reduce risk factors

                              3. Manage stable COPD
                                       Education
                                       Pharmacologic
                                       Non-pharmacologic

                              4. Manage exacerbations
18/Oct/2005                    Dr. David P. Breen           39
      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 to reduce the risk of
  developing COPD and stop its progression
  (Evidence A).
      Reduce Risk Factors
      Key Points
 Brief tobacco dependence treatment is effective
  (Evidence A), and every tobacco user should be
  offered at least this treatment at every visit to a
  health care provider.

 Three types of counseling are especially effective:
  practical counseling, social support as part of
  treatment, and social support arranged outside of
  treatment (Evidence A).
    Reduce Risk Factors
    Key Points
 Several effective pharmacotherapies for
  tobacco dependence are available
  (Evidence A), and at least one of these
  medications should be added to
  counseling if necessary, and in the
  absence of contraindications.
     Reduce Risk Factors
     Key Points
 Progression of many occupationally-
  induced respiratory disorders can be
  reduced or controlled through a variety
  of strategies aimed at reducing the
  burden of inhaled particles and gases
  (Evidence B).
    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.
              GOLD Workshop Report
              Four Components of COPD
              Management

                              1. Assess and monitor disease

                              2. Reduce risk factors

                              3. Manage stable COPD
                                       Education
                                       Pharmacologic
                                       Non-pharmacologic

                              4. Manage exacerbations
18/Oct/2005                    Dr. David P. Breen           45
         Manage Stable COPD
         Key Points
   The overall approach to managing stable COPD
    should be characterized by a stepwise increase in
    the treatment, depending on the severity of the
    disease.

   For patients with COPD, health education can play a
    role in improving skills, ability to cope with illness,
    and health status. It is effective in accomplishing
    certain goals, including smoking cessation
    (Evidence A).
18/Oct/2005                Dr. David P. Breen               46
              Manage Stable COPD
              Key Points

   None of the existing medications for COPD
    has 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.

18/Oct/2005            Dr. David P. Breen          47
              Manage Stable COPD
              Key Points
   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.

   The principal bronchodilator treatments are beta2-
    agonists, anticholinergics, theophylline, and a
    combination of these drugs (Evidence A).
18/Oct/2005              Dr. David P. Breen              48
              Bronchodilators in Stable
              COPD

   Bronchodilator medications are central to symptom
    management in COPD.

   Inhaled therapy is preferred.

   The choice between beta2-agonist, anticholinergic,
    theophylline, or combination therapy depends on
    availability and individual response in terms of
    symptom relief and side effects.
18/Oct/2005              Dr. David P. Breen              49
              Bronchodilators in Stable
              COPD
   Bronchodilators are prescribed on an as-needed or
    on a regular basis to prevent or reduce symptoms.

   Regular treatment with long-acting inhaled
    bronchodilators is more effective and convenient
    than treatment with short-acting bronchodilators, but
    more expensive.

   Combining bronchodilators may improve efficacy
    and decrease the risk of side effects compared to
    increasing the dose of a single bronchodilator.
18/Oct/2005              Dr. David P. Breen             50
        Manage Stable COPD
        Key Points
   Regular treatment with inhaled glucocorticosteroids
    is appropriate for symptomatic COPD patients with
    an FEV1 < 50% predicted (Stage III: Severe COPD
    and Stage IV: Very Severe COPD) and repeated
    exacerbations e.g. 3 in the last three years
    (Evidence A).
 This treatment has been shown to reduce the
    frequency of exacerbations and improve health
    status (Evidence A). Dr. David P. Breen
18/Oct/2005                                            51
              Manage Stable COPD
              Key Points
   Chronic treatment with systemic glucocortico-
    steroids should be avoided because of an
    unfavorable benefit-to-risk ratio (Evidence A).

 All COPD-patients benefit from exercise
    training programs, improving with respect to
    both exercise tolerance and symptoms of
    dyspnea and fatigue (Evidence A).
18/Oct/2005            Dr. David P. Breen          52
              Manage Stable COPD
              Key Points

   The long-term administration of oxygen
    (> 15 hours per day) to patients with
    chronic respiratory failure has been
    shown to increase survival (Evidence A).



18/Oct/2005          Dr. David P. Breen    53
              Management of COPD by
              Severity of Disease
                Stage 0: At risk

                Stage I:      Mild COPD

                Stage II: Moderate COPD

                Stage III: Severe COPD

18/Oct/2005
                Stage IV: Very Severe COPD
                           Dr. David P. Breen   54
               Management of COPD:
               All stages
             Avoidance of risk factors

              - smoking cessation
              - reduction of indoor pollution
              - reduction of occupational exposure

             Influenza vaccination
18/Oct/2005                 Dr. David P. Breen       55
               Management of COPD
               Stage 0: At Risk
              Characteristics               Recommended Treatment

    • Chronic symptoms
      - cough
      - sputum
    • No spirometric
      abnormalities


18/Oct/2005                     Dr. David P. Breen             56
               Management of COPD
               Stage I: Mild COPD
              Characteristics               Recommended Treatment

 • FEV1/FVC < 70 %                              • Short-acting
 • FEV1 > 80 % predicted                             bronchodilator as
 • With or without chronic                           needed
   symptoms



18/Oct/2005                     Dr. David P. Breen                       57
                 Management of COPD
                 Stage II: Moderate COPD
                Characteristics             Recommended Treatment

• FEV1/FVC < 70%                                  • Short-acting broncho-
• 50% < FEV1< 80% predicted                         dilator as needed
• With or without chronic                         • Regular treatment with
  symptoms                                          one or more long-acting
                                                    bronchodilators
                                                  • Rehabilitation

  18/Oct/2005                     Dr. David P. Breen                     58
                Management of COPD
                Stage III: Severe COPD
               Characteristics          Recommended Treatment
• FEV1/FVC < 70%                           • Short-acting broncho-
• 30% < FEV1 < 50% predicted                        dilator as needed
• With or without chronic                         • Regular treatment
                                                    with one or more
  symptoms
                                                    long-acting
                                                    bronchodilators
                                                  • Inhaled glucocortico-
                                                    steroids if repeated
                                                    exacerbations
 18/Oct/2005
                                                  • Rehabilitation
                                 Dr. David P. Breen                         59
               Management of COPD
               Stage IV: Very Severe COPD
              Characteristics          Recommended Treatment
• FEV1/FVC < 70%                        • Short-acting bronchodilator as
                                            needed
• FEV1 < 30% predicted or               • Regular treatment with one or
  FEV1 < 50% predicted                      more long-acting bronchodilators
  plus chronic respiratory              • Inhaled glucocorticosteroids if
  failure                                   repeated exacerbations
                                        • Treat complications
                                        • Rehabilitation
                                        • Long-term oxygen therapy if
                                            respiratory failure
18/Oct/2005                             • Consider surgical options
                                Dr. David P. Breen                        60
                                     Therapy at Each Stage of COPD
Old (2001)           0: At Risk I: Mild                              II: Moderate                        III: Severe
                                                                   IIA            IIB
New                  0: At Risk I: Mild                        II: Moderate III: Severe                  IV: Very Severe
(2003)
Characteristics       Chronic             FEV1/FVC < 70%      FEV1/FVC < 70%      FEV1/FVC < 70%      FEV1/FVC < 70%
                     Symptoms              FEV1  80%          50% < FEV1 < 80%    30% < FEV1 < 50%    FEV1 < 30% or FEV1 < 50%

                      Exposure to risk    With or without     With or without     With or without    predicted plus chronic
                     factors              symptoms             symptoms             symptoms             respiratory failure
                      Normal
                     spirometry           Avoidance of risk factor(s); influenza vaccination
                                                     Add short-acting bronchodilator when needed
                                                                   Add regular treatment with one or more long-
                                                                   acting bronchodilators
                                                                   Add rehabilitation
                                                                                 Add inhaled glucocorticosteroids
                                                                                 if repeated exacerbations
                                                                                                         Add long-term
                                                                                                         oxygen if chronic
                                                                                                         respiratory failure
       18/Oct/2005                                            Dr. David P. Breen                         Consider surgical
                                                                                                                       61
                                                                                                         treatments
              GOLD Workshop Report
              Four Components of COPD
              Management

                              1. Assess and monitor disease

                              2. Reduce risk factors

                              3. Manage stable COPD
                                       Education
                                       Pharmacologic
                                       Non-pharmacologic

                              4. Manage exacerbations
18/Oct/2005                    Dr. David P. Breen           62
         Manage Exacerbations
         Key Points
   Exacerbations of respiratory symptoms
    requiring medical intervention are important
    clinical events in COPD.

  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).
18/Oct/2005             Dr. David P. Breen         63
              Manage Exacerbations
              Key Points

   Inhaled bronchodilators (beta2-agonists
    and/or anticholinergics), theophylline, and
    systemic, preferably oral, glucocortico-
    steroids are effective for the treatment of
    COPD exacerbations (Evidence A).


18/Oct/2005           Dr. David P. Breen          64
              Manage Exacerbations
              Key Points
   Patients experiencing COPD
    exacerbations with clinical signs of
    airway infection (e.g., increased volume
    and change of color of sputum, and/or
    fever) may benefit from antibiotic
    treatment (Evidence B).

18/Oct/2005           Dr. David P. Breen       65
              Manage Exacerbations
              Key Points
   Noninvasive intermittent positive pressure
    ventilation (NIPPV) in exacerbations improves
    blood gases and pH, reduces in-hospital
    mortality, decreases the need for invasive
    mechanical ventilation and intubation, and
    decreases the length of hospital stay
    (Evidence A).

18/Oct/2005           Dr. David P. Breen        66
              Management of COPD

      In selecting a treatment plan, the
       benefits and risks to the individual,
       and the direct and indirect costs to
       the individual, his or her family, and
       the community must be considered.

18/Oct/2005          Dr. David P. Breen     67
                           Could it be COPD?

Do you know what COPD is? This chronic lung disease is a major cause of illness,
yet many people have it and don’t know it.
If you answer these questions, it will help you find out if you could have COPD.
1. Do you cough several times most days?                        Yes ___ No ___
2. Do you bring up phlegm or mucus most days?                   Yes ___ No ___
3. Do you get out of breath more easily than others your age? Yes ___ No ___
4. Are you older than 40 years?                                 Yes ___ No ___
5. Are you a current smoker or an ex-smoker?                    Yes ___ No ___
If you answered yes to three or more of these questions, ask your doctor if you
might have COPD and should have a simple breathing test. If COPD is found early,
there are steps you can take to prevent further lung damage and make you feel
better.
 18/Oct/2005                            your P. Breen
               Take time to think aboutDr. David lungs……Learn about COPD!          68
              GOLD Website Address



     http://www.goldcopd.com


18/Oct/2005         Dr. David P. Breen   69
18/Oct/2005   Dr. David P. Breen   70
         Spirometry is the GOLD Standard for the
          diagnosis of COPD




18/Oct/2005              Dr. David P. Breen         71
                   Smoking Cessation


                          Pre-contemplator

                Relapse




                                                 contemplation
       Action


18/Oct/2005                 Dr. David P. Breen                   72





18/Oct/2005   Dr. David P. Breen   73
              Pharmacological treatment
        1st line treatment
           Nicotine      replacement
                  Nicotine polacrilex (gum)
                  Transdermal nicotine
                  Nicotine inhaler
                  Nicotine nasal spray
                  Nicotine lozenges
                  Combined modality
           Bupropion

        2nd line treatment
           Clonidine
           Nortripyline
18/Oct/2005                          Dr. David P. Breen   74
              Management of Stable Disease

     Smoking cessation
     Pharmacological treatment
     LTOT
     Pulmonary rehabilitation
     Surgery


18/Oct/2005            Dr. David P. Breen    75
              Pharmacological therapy


   Medications can reduce or abolish symptoms,increase
    exercise tolerance,reduce no and severity of symptoms and
    improve health status
   No treatment alters the rate of decline of lung function
   Inhaled route is preferable – smaller doses and therefore
    reduced side effects by inhalation
   Combining agents have a greater effect on symptoms than
    single agents
18/Oct/2005                Dr. David P. Breen               76
                 General principles
   Patients must be educated in the device
   Choose right device for patient – MDI v DPI v
    Spacer device
   Spacer good for delivery and reduce oral s/e
   Compliance is variable – studies show at east 85%
    of patients take 70% of the prescribed doses - ?
    Reflect the constant symptoms
   Education is essential for good adherence and
    proper use
   Spirometry essential for diagnosis but not for
    monitoring
18/Oct/2005                    Dr. David P. Breen       77
              Bronchodilators
   Β2 agonist
   Anticholinergic agents
   Methylxanthines

Mode of action is smooth muscle relaxation –
 small changes in FEV but decreases in lung
 volumes resulting in better emptying and less
 hyperinflation
18/Oct/2005           Dr. David P. Breen     78
                            Β2 agonist
   Inhaled (short , long acting), oral
   Mode of action
       Increase in c-amp within cells and promote smooth
        muscle relaxation
       ?other non bronchodilator effects
   S/E
         Palpitations, PVC
      Tremor

      Sleep disturbance

      Metabolic - hypokalaemia
18/Oct/2005                 Dr. David P. Breen              79
                Anticholinergic drugs
   Only available via inhaled route
        Ipratropium
        Oxitropium
        Tiotropium
   Inhibit muscarinic receptors
   Tiotropium remains bound to receptors for up to 36 hours
   Onset of bronchodilatation in 30 mins
   S/E
        Not associated with significant incidence of prostatism or cardiac S/E
        Commonest – dry mouth(tiotropium), metallic taste (ipratropium),
         closed angle glaucoma

18/Oct/2005                        Dr. David P. Breen                             80
                   Methylxanthines
   Oral or I.V prn preparations
   Non specific PDE inhibitors and increase c-amp
   Bronchodilatation only occurs at high dose and
    narrow therapeutic/toxic window
   Keep at level of 8-14 ug.dl
   Can be bd or od drugs
   S/E
        Major – ventricular and atrial rhythm disturbance,
         convulsions
        Minor – headache, nausea, vomiting, diarrhoea and
         heartburn
18/Oct/2005                  Dr. David P. Breen               81
         Levels increased                        Levels decreased

Respiratory acidosis                  Cigarette smoke
CCF                                   Anti-convulsant drugs
Liver cirrhosis                       rifampicin
Erthyromycin
ciprofloxacin

18/Oct/2005                 Dr. David P. Breen                      82
                    Glucocorticoids
   Inhalation
      Beclomethasone

      Budesonide

      Triamcinolone

      Fluticasone

      Flunisolide

   Oral
      Not    indicated in stable – excessive S/E profile
18/Oct/2005                 Dr. David P. Breen              83
   Pharmacology
        Effect transcription processes – slow action
        High dose can be absorbed via the pulmonary circulation
   S/E
        Oral – osteoporosis, cataracts, peripheral myopathy
        Topical/local S/E can be significant
        Skin bruising
   Clinical outcomes
        If FEV<50% and a number of exacerbations/year rate of
         deterioration in health status can be reduced
        3 year prospective studies revealed no effect on rate of
         decline of FEV1
18/Oct/2005                   Dr. David P. Breen                84
              Combination therapy
   Combination treatment is a convenient, safe
    and improves compliance
   Initial data show a significant effect on
    pulmonary function and a reduction in
    symptoms
   Largest effects in most severe – FEV<50%
    and a number of exacerbations

18/Oct/2005           Dr. David P. Breen          85
                 Other agents
   Mucolytic agents – carbocysteine, iodinated
    glycerol
   Little evidence of any effect on lung function
   Cochrane review – supports a role for
    reducing no of exacerbations in chronic
    bronchitis
   N-acetylcysteine – at present prospective
    study ongoing
18/Oct/2005            Dr. David P. Breen            86
   Leukotreine receptor antagonist -No data to support role
   Maintenance antibiotic –no data to suggest that these drugs are
    effective in modifying symptoms, exacerbations or lung function

   Respiratory stimulants – oral peripheral chemoreceptor stimulant
    – improves V/Q matching and improves oxygenation – can result in peripheral
    neuropathy

   Vaccination
      Influenza – can reduce serious illness and death by
       50%
      Pneumococcal – reduces bacteraemia
18/Oct/2005                        Dr. David P. Breen                        87
        Alpha1-antitrypsin deficiency

   Augmentation therapy
   Licensed for i.v. use twice a week
   Expensive
   No RCT showing benefit
   Suggestio that rate of decline in those
    receiving drug is less than historical controls.

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