New Era of COPD New Era of COPD Treatment Treatment - Focusing on Treatment- - Focusing on Treatment- Shih Wei Lee, MD Shih Wei Lee, MD Department of Chest Medicine Department of Chest Medicine Tao-Yuan General Hospital Department of Tao-Yuan General Hospital Department of Health Health
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New Era of COPD Treatment - Focusing on Treatment- Shih Wei Lee, MD Department of Chest Medicine Tao-Yuan General Hospital Department of Health.
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New Era of COPD TreatmentNew Era of COPD Treatment- Focusing on Treatment-- Focusing on Treatment-
Shih Wei Lee, MDShih Wei Lee, MD
Department of Chest Medicine Department of Chest Medicine
Tao-Yuan General Hospital Department of HealthTao-Yuan General Hospital Department of Health
BackgroundBackground
Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998
Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998
Definition of COPD Chronic Obstructive Pulmonary Disease (COPD)
is a preventable and treatable disease state characterised by airflow limitation that is not fully reversible.
The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking.
Ipratropium MDI with spacer or hand-held nebuliser as needed
Supplemental oxygen (if saturation <90% )
CorticosteroidsIf patient tolerates, prednisone 30–40 mg per os q day for 10 days
If patient can not tolerate oral intake, equivalent dose i.v. for up to 14 days
Consider use inhaled corticosteroids by MDI or hand-held nebuliser
Antibiotics (based on local bacteria resistance patterns) May be initiated in patients that have a change in their sputum characteristics (purulence and/or volume)
Choice should be based on local bacteria resistance patterns
Short-acting β-agonist NA Yes (B) NA Na SomeIpratropium bromide Yes (B) Yes (B) No NA SomeLong acting β-agonists Yes (A) Yes (B) No NA MinimalTiotropium Yes (A) Yes (B) NA NA MinimalInhaled corticosteroids Yes (A) NA No NA SomeTheophylline NA Yes (B) NA NA Important
Effects on commonly used medications on important clinical outcomes in COPD
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).
Inhaled glucocorticosteroid combined with a long-acting B2-agonist is more effective than the individual components (Evidence A).
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).
Inhaled glucocorticosteroid combined with a long-acting B2-agonist is more effective than the individual components (Evidence A).
Adapt from 2005 GOLD teaching slide
ICS and LABAs improve symptoms and lung function via different mechanisms in COPD
p=0.003 Symbicort vs budesonide; p=0.019 Symbicort vs formoterol
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(Adapted from Szafranski et al. ERS 2002)(Adapted from Szafranski et al. ERS 2002)
Combination Therapy
Treat Respir Med. 2004;3:173–181
ERS-ATS COPD Guidelines
Pharmacological therapy (4) Bronchodilators Short-acting bronchodilators can increase exercise tolerance acutely in
COPD.
Anticholinergics given q.i.d. can improve health status over a 3-month period.
Long-acting inhaled β-agonists improve health status, possibly more than regular ipratropium. Additionally, these drugs reduce symptoms, rescue medication use and increase the time between exacerbations.
Combining short-acting agents (salbutamol/ipratropium) produces a greater change in spirometry over 3 months than either agent alone.
Combining long-acting inhaled β-agonists and ipratropium leads to fewer exacerbations than either drug alone.
Combining long-acting β-agonists and theophylline produces a greater spirometric change than either drug alone.
Tiotropium improves health status and reduces exacerbations and hospitalisations compared with both placebo and regular ipratropium.
Phosphodiesterase-4 inhibtors• PDE type 4 is expressed predominately in inflammatory
cells, such as neutrophils, CD8+ lymphocytes, and macrophages, makes this enzyme an attractive target for the development of new drugs to treat pulmonary inflammation that is characterisitic of COPD.
• Cilomilast, Roflumilast• Postive effect on lung function but also on the frequency
of exacerbations, may also slow disease preogression• Side effect: headache, sleep distubrance, and nausea,
vascular inflammatory( arteritis ) in the messentery and organ organs.
Roland Buhl and stephen G. Farmer 2005 ATS
Antileukotriene drugs
• LTB4: endogeneous chemoattaractants for peripheral blood neutrophils to bronchial tissues
• LTB-109: an oral LTB4 receptor antagonist, clinical trial results have been disappointing.