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The World Health Organization (WHO) projected that, in 2005, chronic respiratory disease would be the third-leading cause of deaths from chronic disease worldwide
Adapted from: World Health Organization. Preventing chronic diseases: a vital investment. (2005) Available at: http://www.who.int/chp/chronic_disease_report/contents/en/index.html (accessed June 2009).
Definition
COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases
REVISED 2011
GOLD. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Revised 2011. Available from: http://www.goldcopd.org
additional decline
1. Celli BR, MacNee W. Eur Respir J. 2004; 23: 932946; 2. GOLD. Global Initiative for Chronic Obstructive Lung Disease. Updated 2010. Available: www.goldcopd.com
Cholinergic tone
ACh
Cholinergic receptors
ACh
Submucosal gland
Airway epithelium
Mucus Hypersecretion
Post-ganglionic nerve
M3 receptors (+)
COPD Stages
75%
Diagnosis
Moderate
50%
Treatment
Severe
25%
Very Severe
0% 25 50 Age (years)
75
Adapted from Fletcher C and Peto R, BMJ 1977; 1:1645-1648. Imagery courtesy ODonnell D
Significant lung function improvement with tiotropium in total, Asian and Japanese cohort
Tiotropium
Control 1.50 1.40 1.30 1.20 1.50 1.40 1.30 Tiotropium Control
Total cohort2
* *
* *
* *
*
*
* *
* *
* *
* * * * *
* *
* *
1.10
* *
* *
* *
* *
* *
* *
* *
* *
Post-BD
Post-BD * Tiotropium (n=46) Control (n=43) Pre-BD * Tiotropium (n=45) Control (n=43)
* *
* Control (n=2374)
Pre-BD
* Tiotropium (n=2494)
Control (n=2363)
* Tiotropium (n=156)
Control (n=147) Tiotropium (n=152) Control (n=145)
* * Pre-BD
01 6 12 18 24 30 36 42 48 Day 30 Month
01 6 12 18 24 30 36 42 48 Day 30 Month
Day 30
Y, et al. Respirology 2011; 16: 825-835; 2Adapted from Tashkin DP, et al. N Engl J Med 2008;359:1543-1554.
Japanese Cohort1
= 1.1-6.2 units
Tiotropium (n=48) Control (n=43)
Total Cohort2
= 2.3-3.3 units
Tiotropium (n=2478) Control (n=2337)
Improvement
Significant SGRQ improvement with tiotropium in total, Asian and Japanese cohort
50
50
50
45
45
45
40
40
40
35
* * * *
0 6 12 18 24 30 36 42 48
35
*
0 6
* *
35
* * * * * * * *
0 6 12 18 24 30 36 42 48
12 18 24 30 36 42 48
Month
Month
Month
*P<0.05 vs. control. Repeated measure ANOVA was used to estimate means. Estimated means are adjusted for baseline measurements. Patients with 2 acceptable SGRQ Total Scores after Month 6 were included in the analysis.
1Fukuchi
Y, et al. Respirology 2011; 16: 825-835; 2Adapted from Tashkin DP, et al. N Engl J Med 2008;359:1543-1554.
1Fukuchi
Exacerbations
Systemic inflammation increases during ECOPD potential mechanism to explain the increased risk of vascular events Plasma levels of the cardiac biomarkers NT-proBNP and troponin T were abnormal in a significant number of ECOPD patients hospitalized both markers predicted mortality
Patients with COPD had increased circulating platelete-monocyte aggregates further increased during ECOPD
Fabbri LM, et al. Thorax. 2011; 66(9): 745-747
40
35 30 25 20 15 10 5 0 0 30 60 90 120 150 180 210 240 270 300 330 360 Time to event (days)
Hazard ratio = 0.83* (95% CI, 0.77, 0.90) P<0.001 (log-rank test)
No. of patients at risk: Tiotropium Salmeterol 3707 3369 3136 2955 2787 2647 2561 2455 2343 2242 2169 2107 1869 3669 3328 3028 2802 2605 2457 2351 2251 2137 2050 1982 1915 1657 Vogelmeier C et al. N Engl J Med 2011;364:1093-1103.
Tiotropium Salmeterol
15
10
0 30 60 90 120 150 180 210 240 270 300 330 360 Time to event (days) No. of patients at risk:
Tiotropium Salmeterol 3707 3564 3453 3359 3285 3217 3177 3125 3066 3017 2977 2984 2663 3669 3502 3362 3244 3172 3080 3032 2982 2921 2870 2834 2806 2489 Vogelmeier C et al. N Engl J Med 2011;364:1093-1103.
1 (95% CI 0.83, 0.96) RR 0.93* P=0.002 0.9 (95% CI 0.86, 1.00) P=0.048 0.8
0.72
Tiotropium Salmeterol
0.09
All exacerbations
Moderate exacerbations
Severe exacerbations
RR=rate ratio. *Poisson regression correcting for overdispersion and adjusted for treatment exposure. Vogelmeier C et al. N Engl J Med 2011;364:1093-1103.
0.83
0.86 (0.78, 0.94) 0.84 (0.73, 0.97)
Tiotropium was significantly more effective across 0.05 635/1833 0.88 (0.79, 0.99) 561/1781 almost all subgroup 589/1597 627/1545 0.86 (0.77, 0.97)compared to salmeterol
127/329 152/291 746/1896 668/1773 134/271 501/1254 468/1284 311/860 839/1955 575/1714 0.64 (0.50, 0.81) 0.64 0.84 (0.75, 0.93) 0.87 (0.78, 0.97) 0.66 (0.51, 0.85) 0.89 (0.79, 1.02) 0.87 (0.76, 0.99) 0.85 (0.72, 1.00) 0.87 (0.79, 0.96) 0.82 (0.73, 0.92) 0.17
Smoking status Noncurrent 678/1929 Current 599/1778 BMI group <20 20 to <25 25 to <30 30 105/286 455/1230 424/1276 293/915
0.41
*n=no. patients with event; N=total no. patients. 0.4 0.6 *Subgroup by treatment interaction. GOLD=Global Initiative for Chronic Obstructive Lung Disease; BMI=body-mass index; ICS=inhaled corticosteroid.
1452
1401
395
416
*Analysis in subset of patients who were receiving ICS at baseline. ICS=inhaled corticosteroid.
Vogelmeier C et al. N Engl J Med 2011;364:1093-1103.
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