COPD

" 2006

COPD
30 ‡

90%

Wayne McLaren«Former Marlboro man ,30

,51

2001 " .

1965-1998 .." . ....

( ) COPD of all smokers«) Bad Genes (COPD affects only 15 -20% Breathe Noxious Crap Lung Inflammation COPD .

3 ‡ ‡ ‡ ‡ ‡ ‡ " * ‡ . cor <- <<.2± Blue bloater . pulmonale .

" ‡ ‡ ‡ ‡ ‡ ‡ ± ± " ± " * . . (hyperresonant) . " ± ) cor pulmonale .2 pink puffer ( .( : ± -1 ) .

COPD ‡ ‡ ‡ ‡ ‡ " .

GOLD = Guidelines ‡ Global Initiative for Chronic Obstructive Lung Disease (GOLD) Launched in 1997 .

GOLD classification of COPD ‡ ‡ ‡ ‡ ‡ Stage 0 Stage I Stage II Stage III Stage IV At Risk Mild COPD Moderate COPD Severe COPD Very Severe COPD .

‡Forced Expiratory Volume (FEV): At the start of the FVC maneuver.Stages by spirometry ‡Forced Vital Capacity (FVC): volume expelled following a maximum inhalation effort. the spirometer measures the volume at timed intervals ‡FEV1: FEV in the first second. .

FEV1/FVC 70% FEV1 " ± ± ‡ ‡ ‡ Normal Severe Obstruction .

10% .FEV1 . . 80-120% / " 50-70 COPD 50% FEV1 ‡ ‡ ‡ ‡ FEV1 1 / ± .

production) .At Risk Normal spirometry Stage 0 Chronic symptoms (cough. sputum.

Mild COPD Stage I ‡ FEV1/FVC <70% ‡ Normal FEV1 (>80% predicted) .

Moderate COPD Stage II ‡ 50% <FEV1 <80% predicted ‡With or without chronic symptoms ‡FEV1/FVC <70% .

Severe COPD Stage III ‡ 30% <FEV1 <50% predicted ‡With or without chronic symptoms ‡FEV1/FVC <70% .

Very Severe COPD Stage IV ‡ FEV1 <30% predicted or ‡ FEV1 <50% predicted plus chronic respiratory failure ‡FEV1/FVC <70% .

1 ± ± .? : . :( ) ± ± ± . ± .3 ...2 ± ± ± .

= " FEV1 . FEV1 . baseline " 50% " 25% * ‡ ‡ ‡ .

) COPD ( 1FEV) ‡ " :(50% ‡ . . ‡ :FEV1/FVC ± ) cor pulmonale ‡ . ( 3S . ± ± 6 50% . 1P .

‡ ) 3-6 FEV1 ( . .. FEV1 " " " FEV1 COPD ‡ ‡ = 70% FEV1/FVC ‡ ‡ FEV1 FEV1 ‡ -( ) ‡ .FVC .

CT ‡ .PA ± . " ) " .2 .3 . ) ± ± ‡ ± " : 2 COPD .4 ‡ " ( ) .: ( ( .1 .

‡ .: 50% . screening 92% . SaO2 FEV1 ‡ ‡ ‡ ‡ .

cor pulmonale Alpha-1 antitrypsin ‡ : COPD ± ± ..± . . ± . ‡ ‡ multifocal atrial ..RVH P pulmonale . .tachycardia COPD ‡ .

. ) COPD : . . . . .( . / ) ± ( ± ± ± ± ± ‡ ‡ ‡ ± COPD ± ± ± ± ‡ . . . .

" ±2 . ± ± " ± BNP ‡ ‡ ‡ ? ‡ restriction .

TB .2 .1 .1 .DD . ± CT/ " ± .2 .3 .

COPD .

. .. . . COPD " ‡ ‡ ‡ : ‡ ( . " . ± ) .

. ...

± ± . 5 .5 .3 ± : .1 . . - ± .COPD ) " 0. COPD .COPD .( .2 .

± : : .COPD COPD .2 .1 .3 ‡ ‡ ‡ .

..1 . ± ± ) ± ± .( ± . 2 ) .( .

serevent ‡ 20% .Bronchodilators Beta2-agonists ‡ Short-acting (2-4 hrs) ± During Day ± Salbutamol (albuterol) . Oxis ± Salmeterol ± Seretide.Ventolin ± Terbutaline ± Bricalin ‡ Long-acting (12 Hrs) ± Formoterol ± Foradil.

Apovent.Bronchodilators Anticholinergics ‡ Short-acting (>6 Hrs) ± good for night symptomstake before sleep ± Ipratropium bromide ± Aerovent. Atrovent ± Oxitropium bromide ‡ Long-acting ± Tiotropium ± Spiriva ipratropium ± 4%) ( . tiotropium 14% COPD .

Methylxanthines ‡ ‡ ‡ ‡ Aminophylline (slow release= 12-24 Hrs) Theophylline (slow release) ± Theotard. . ) ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ . " . . Theotrim RARELY OF SIGNIFICNAT BENEFIT LEVEL 8-12 mcg/ml COPD . . " . ±) " .

.2
(FEV1<50% ) COPD .( IV III ) ‡ ‡

.3
" ‡ ‡ 88-90%

COPD "

‡ ‡

- .

>1 : .Stepwise Approach to Asthma Control Reliever: Rapid-acting inhaled 2-agonist prn inhaled corticosteroid Low-dose Low to mediumdose High-dose  When asthma is controlled.agonist -Oral corticosteroid STEP 2: Mild Persistent STEP 3: Moderate Persistent STEP Down STEP 4: Severe Persistent STEP 1: Intermittent <2 <2 ± >2 : >2 . reduce therapy Monitor + long-acting inhaled 2-agonist plus (if needed) Controller: None  Theophylline-SR -Leukotriene -Long-acting inhaled 2.

FEV1 CT 50% ) FEV1 . ‡ ‡ ‡ . ‡ . ( .‡ ‡ . CT . ‡ 20% .

± ‡ * / ) ± ‡ .. . . ‡ ±) . . .

.

) ± ‡ . baseline : ± ± ± 1/3 ± : ‡ ‡ ±) ." .

. .± 6-8 ) . ± ± ± ‡ ‡ ± ± ± ± ± .( . 6 . 3 " 500 . + (new onset) . " 100 -( ) 4 2 30-60 ± " " .

± ± ± ± COPD 4 ‡ . ± . .( : (severe) " ± .(2) ) . " 40 ± ‡ ‡ . 7-10 . ( / ) . .

± SPIRIVA (Tiotropium ) .

2005.Daily Tiotropium May Reduce COPD Exacerbations.18 µg by Inhalation Indications: moderate to severe COPD Mechanism include: ± Bronchodilation ± Improved bronchociliary clearance ± Reduced hyperinflation -> more effective cough Less Inflammation ‡ Long term effect: ± fewer exacerbations ± lower healthcare utilization. Ann Intern Med. 386-387 ‡ ‡ ‡ ‡ Tiotropium is: long-acting anticholinergic Dose: Once daily .143:317-326. .

utility in preventing flares has not been demonstrated ‡ Can a long acting Bronchodilation reduce frequency of flares? .The Clinical Question: ‡ Increased cholinergic tone contributes to COPD flares ‡ Short-acting anticholinergic .

432 patients ‡ almost all men and nearly 90% white ‡ Mean FVC: 1.04 liters (35.6% of predicted for age). . placebo-controlled. ‡ duration of follow-up: 6 months.Methods ‡ Randomized. multicenter ‡ 1.

‡ Hospitalizations 7.5% for placebo patients (P=0. 0. 0.83.9% vs 32.Results ‡ Rate of flares 27.056).055).028) ‡ Trend toward time extended to first hospitalization (hazard ratio. P=0. P=0.4% for tiotropium vs 2.3% for the placebo group (P=0. Atrial Fibrillation (2. ‡ No significant difference in serious adverse events ± CHF. ‡ Time to first exacerbation was extended (hazard ratio.73.0% for tiotropium and 9.1% for placebo).037). .

most of whom were white ‡ relatively short follow-up period (6 months).Study Limitations: ‡ Limited to males. ‡ no comparison with ipratropium ‡ strong role of sponsoring pharmaceutical company .

given the large number of patients.Goroll Conclusions: ‡ The benefits are modest (4% in absolute terms and about 14% in relative terms) ‡ but promising. ‡ However: ± the data on adverse effects are limited to 6 months of follow-up ‡ Long-acting inhaled -agonists and corticosteroids remain the treatments of choice for prevention of flares ‡ Inhaled tiotropium is worth considering in patients whose exacerbations continue .

. no studies have been performed to determine adequately whether the rate of death in patients with COPD is increased by use of long-acting beta-2 agonists. low. ‡ salmeterol should be used only as add-on therapy in asthma patients not adequately controlled on other asthma-controller medications (eg.to medium-dose inhaled corticosteroids) ‡ The warning was based on data from a 28-week clinical trial (Salmeterol Multi-center Asthma Research Trial [SMART]) in 26.355 patients ‡ The FDA notes that the SMART were conducted in asthma patients.Importance ± Long Acting Beta Agonists may be problematic ‡ On March 2. 2006 the FDA approved safety labeling changes for salmeterol inhalation powder (Serevent Diskus. made by GlaxoSmithKline) to warn that use of this and other long-acting beta2 agonists may increase the risk for severe asthma exacerbations and asthma-related death.

increased from baseline with tiotropium alone.2-week courses of Morning tiotropium : ‡ alone (once daily in the morning). ‡ Methods: ± 95 COPD Pts . 129:509-17 . ‡ + formoterol (in morning) ‡ + formoterol (morn+ evening). Chest 2006 Mar.funded by Spiriva. ‡ Two remaining questions are: ± Are these changes in pulmonary function sustained during long-term treatment? ± Do they translate into improved symptoms? Effects of tiotropium with and without formoterol on airflow obstruction and resting hyperinflation in patients with COPD. ‡ Results: ± Mean FVC. FEV1. ± Twice daily formoterol added benefit overnight. placebo-controlled .Combined 2 long-acting bronchodilators confers a short-term improvement in pulmonary function ‡ Randomized. ± Morning formoterol added improvements mostly during daytime.

Dependent Abdominal Pain Constipation Dry Mouth Dyspepsia Vomiting Myalgia Infection Moniliasis Epistaxis Pharyngitis Rhinitis Sinusitis Resp Tract Infection Rash UrinaryTract Infection Placebo -Controlled Trials SPIRIVA ]n=550 [ Ipratropium-Controlled Trials SPIRIVA ]n=356 [ Placebo ]n=371 [ Ipratropium ]n=179 [ 13 7 5 5 4 16 6 4 4 4 4 4 9 6 11 41 4 7 11 5 4 3 2 3 5 2 3 3 2 2 7 5 9 37 2 5 5 5 3 6 1 12 1 1 4 1 3 1 7 3 3 43 2 4 8 2 5 6 1 6 1 2 3 3 2 1 3 2 2 35 2 2 .Adverse Reactions Accidents Chest Pain Edema.

Roflumilast Improves Lung Function in COPD Lancet 2005 Aug 13 .4 ! " ± ‡ ‡ ‡ .

Regular use of antitussives contraindicated (Evidence D) .‡ Antibiotics: other than treating infectious exacerbations.not recommended (Evidence A) ‡ Mucolytic Agents: a few patients with viscous sputum may benefit but the widespread use cannot be recommended (Evidence D) ‡ Antitussives: Cough. has a protective role. a troublesome symptom in COPD.

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