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ERS Annual Congress Vienna

15 September 2012
Postgraduate Course 9 Progress on the treatment of COPD

Saturday, 1 September 2012 09:3013:00 Room: Lehar 3-4
Nonmedical therapy for COPD

Dr. Fernando J. Martinez Division of Pulmonary and Critical Care University of Michigan Health System 1500 E. Medical Center Dr. 3916 Taubman Center 48109 MI Ann Arbor United states of America fmartine@umich.edu Aims
To define the evidence based supporting nonpharmacological therapy in COPD, including: Pulmonary rehabilitation Oxygen therapy i. In patients with resting hypoxemia ii. In patients without resting hypoxemia Vaccination i. Influenza ii. Pneumococcal Volume reduction i. Surgical ii. Bronchoscopic Lung transplantation
Summary
Nonpharmacological therapies have become an important component of the comprehensive management of COPD patients. These approaches have been recently codified by the GOLD Science Committee [1]. They include, among other approaches, pulmonary rehabilitation, long term oxygen therapy, vaccination, lung volume reduction (surgical and bronchoscopic), and lung transplantation. The evidence base for supporting each of these approaches is variably compelling.
Pulmonary rehabilitation
Pulmonary rehabilitation has been demonstrated to achieve its principal goals of reducing symptoms, improving quality of life, and increasing physical and emotional participation in everyday activities [2]. A large number of investigators have documented that pulmonary rehabilitation increases six minute walk distance and improves health status [3]. These benefits have been confirmed with rehabilitation delivered in inpatient, outpatient, and home settings [3, 4]. A recent systematic review concluded that pulmonary rehabilitation following a hospitalization for an acute exacerbation of COPD reduces subsequent hospital readmission and mortality and improves health-related quality of life [5]. Although difficult to crisply define, a longer rehabilitation course seems to result in greater improvement in health status [6]. The minimum length of an effective rehabilitation program is likely longer than 6 weeks [7]. The components of a pulmonary rehabilitation program include exercise training, smoking cessation, nutrition counselling, and education [2]. It is notable that some patients do not attend or complete pulmonary rehabilitation programs; active smokers and those with depression are more likely to be in this less compliant group [8].
Long term oxygen therapy (LTOT)

The benefits of LTOT are best established for patients with severe disease associated with resting hypoxemia [9]. The Medical Research Council proved that 15 hours/day of oxygen improved three
71
year survival compared with no oxygen in patients with severe airflow obstruction, resting hypoxemia, and mild pulmonary hypertension [10]. The National Institutes of Healths Nocturnal Oxygen Therapy Trial demonstrated improved survival with continuous LTOT compared with nocturnal LTOT in patients with severe resting hypoxemia [11]. The role of LTOT in COPD patients with moderate hypoxemia has been less certain [9]. A metaanalysis of two small randomized trials in such patients did not support a mortality benefit in this population (summary OR 1.39, 95% CI 0.74-2.59) [12]. Inconclusive data have also been reported for LTOT in COPD patients with normoxemia at rest and desaturation during exercise or at night. Despite these data LTOT is widely used to treat COPD patients without resting hypoxemia. An analysis of subjects with severe emphysema participating in the National Emphysema Treatment Trial (NETT) noted that at enrolment 33.8% of subjects who were nonhypoxemic at rest utilized LTOT [13]. When compared to similar participants in the NETT not prescribed LTOT these individuals were more likely to desaturate during exercise, exhibit more dyspnoea and experience worse quality of life. The use of oxygen as-needed or during short-term bursts has been suggested to improve symptoms or the outcome of pulmonary rehabilitation [9]. A recent, randomized controlled trial examined the role of at least 15 hours oxygen or medical air/day for 7 days in patients with refractory dyspnoea (59-68% with COPD); the primary endpoint of breathlessness recorded in the morning or evening was not different between the intervention groups [14]. Similarly, a 12 week, randomized, placebo-controlled study of breathless COPD patients without resting hypoxemia did not confirm improvement in dyspnoea, quality of life, or function with oxygen therapy compared with room air [15]. An interesting study of 22 patients who felt that short burst oxygen therapy led to functional improvements documented that only five of these patients were correctly able to identify oxygen versus room air during a blinded, exercise challenge [16]. A biologically plausible risk of LTOT in COPD patients has been demonstrated by one group that confirmed that hyperoxia increased oxidative stress and airway inflammation [17]. The National Heart, Lung and Blood Institute in collaboration with the Centers for Medicare & Medicaid Services are conducting a multicentre study in the United States, the Long Term Oxygen Therapy Trial (LOTT) [9]. The LOTT investigators will randomize 1134 COPD patients with an FEV1 < 65% predicted, an FEV1/FVC < 70%, a modified MRC > 1, and a resting oxygen saturation 89-93% or desaturation to < 90% during a six minute walk test to oxygen therapy or no oxygen therapy. LTOT will be prescribed continuously for those patients with resting O2 saturations between 89-93% or with exercise and sleep for subjects with resting saturation > 93% but exertional desaturation to < 90%.
Vaccination
Influenza vaccination can reduce serious illness including lower respiratory tract infections requiring hospitalization in COPD patients [18, 19]. The influenza strains are adjusted each year to maximize effectiveness and should be given once each year [20]. Population based studies in elderly persons with chronic lung disease and limited controlled trial data in COPD suggest that pneumococcal polysaccharide vaccine has beneficial effects in COPD patients [21, 22]. Functional response to the 23-valent pneumococcal polysaccharide vaccine may differ from the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine [23]. Although the strength of the data is not dramatic [24], their use has been advocated in international guidelines depending on local guidelines and availability [1].
Lung volume reduction/transplantation

Lung volume reduction reduces symptoms in COPD patients. The most dramatic approaches involve the resection of the most severely diseased emphysematous tissue. The NETT confirmed that lung volume reduction surgery improved pulmonary function, exercise capacity, health status and survival in patients with severe emphysema who had upper lobe predominant emphysema on chest computed tomography and a decreased exercise capacity after pulmonary rehabilitation [25, 26]. Emphysema patients with upper lobe predominant emphysema but a high post-pulmonary rehabilitation exercise
72
capacity did not experience a survival benefit but did experience improved health status and exercise capacity. This surgical approach has potential risk; severe emphysema patients with severely decreased airflow (FEV1 < 20% predicted) and either a severely decreased DLCO (< 20% predicted) or homogenous emphysema on computed tomography experienced higher mortality with surgery than medical therapy in the NETT [27]. Numerous investigators have examined the role of nonsurgical, bronchoscopic approaches to lung volume reduction [28]. The most advanced is the placement of one-way valves in areas of severe emphysema to allow air and secretions to move from alveoli to the central airways, while preventing air from entering the distal airspaces. A large, prospective study of the Zephyr (Emphasys Medical [now Pulmonx]) demonstrated modest improvements in FEV1 and six minute walk distance six months after valve placement [29]. Alternative endobronchial valve systems are undergoing active study. Alternative approaches under investigation include the instillation of a biological sealant [3032] or thermal vapour [33]. Lung transplantation is a viable, alternate surgical approach for selected patients with advanced COPD [34].
References
1. Global Initiative for Chronic Obstructive Lung Disease. 2011 [cited 2012 July 15]; Available from: http://www.goldcopd.org/uploads/users/files/GOLD_Report_2011_Feb21.pdf. 2. Nici, L., et al., American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med, 2006. 173: p. 1390-413. 3. Lacasse, Y., et al., Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews, 2006(4. Art. No.: CD003793. DOI: 10.1002/14651858.CD003793.pub2). 4. Marciniuk, D., et al., Optimizing pulmonary rehabilitation in chronic obstructive pulmonary disease-practical issues: A Canadian Thoracic Society Clinical Practice Guideline. Can Respir J, 2010. 17(4): p. 159-68. 5. Puhan, M., et al., Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews, 2011(10. Art. No.: CD005305. DOI: 10.1002/14651858.CD005305.pub3). 6. Beauchamp, M., et al., Optimal duration of pulmonary rehabilitation for individuals with chronic obstructive pulmonary disease-a systematic review. Chronic Respir Dis, 2011. 8: p. 129-40. 7. Green, R., et al., A randomised controlled trial of four weeks versus seven weeks of pulmonary rehabilitation in chronic obstructive pulmonary disease. Thorax, 2001. 56: p. 1435. 8. Keating, A., A. Lee, and A. Holland, What prevents people with chronic obstructive pulmonary disease from attending pulmonary rehabilitation? A systematic review. Chronic Respir Dis, 2011. 8(2): p. 89-99. 9. Stoller, J., et al., Oxygen therapy for patients with COPD. Current evidence and the LongTerm Oxygen Treatment Trial. Chest, 2010. 138: p. 179-87. 10. Report of the Medical Research Council Working Party, Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet, 1981. 1 (8222): p. 681-6. 11. Nocturnal Oxygen Therapy Trial Group, Continuous or noxturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med, 1980. 93(3): p. 391-8. 12. Cranston, J., et al., Domiciliary oxygen for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews, 2005(4): p. Art. No.: CD00174. DOI: 10.1002/14651858.CD001744.pub2. 13. Drummond, M., et al., Continuous oxygen use in nonhypoxemic emphysema patients identifies a high-risk subset of patients. Retrospective analysis of the National Emphysema Treatment Trial. Chest, 2008. 134: p. 497-506.
73
14. Abernathy, A., et al., Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial. Lancet, 2010. 376: p. 784-93. 15. Moore, R., et al., A randomised trial of domiciliary, ambulatory oxygen in patients with COPD and dyspnoea but without resting hypoxemia. Thorax, 2011. 66: p. 32-7. 16. Quantrill, S., et al., Short burst oxygen therapy after activities of daily living in the home in chronic obstructive pulmonary disease. Thorax, 2007. 62: p. 702-5. 17. Carpagnano, G., et al., Supplementary oxygen in healthy subjects and those with COPD increases oxidative stress and airway inflammation. Thorax, 2004. 59: p. 1016-9. 18. Wongsurakiat, P., et al., Economic evaluation of influenza vaccination in Thai chronic obstructive pulmonary disease patients. J Med Assoc Thai, 2003. 86: p. 497-508. 19. Wongsurakiat, P., et al., Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study. Chest, 2004. 125: p. 2011-20. 20. Centers for Disease Control and Prevention, Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep, 2009. 58(RR08): p. 1-52. 21. Alfageme, I., et al., Clinical efficacy of anti-pneumococcal vaccination in patients with COPD. Thorax, 2006. 61(3): p. 189-95. 22. Nichol, K., et al., The health and economic benefits associated with pneumococcal vaccination of elderly persons with chronic lung disease. Arch Intern Med, 1999. 159: p. 2437-42. 23. Dransfield, M., et al., Long-term comparative immunogenicity of protein conjugate and free polysaccharide pneumococcal vaccines in Chronic Obstructive Pulmonary Disease. Clin Infect Dis, 2012. 24. Walters, J., et al., Injectable vaccines for preventing pneumococcal infection in patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews, 2010. 11: p. CD001390. 25. National Emphysema Treatment Trial Research Group, A randomized trial comparing lungvolume-reduction surgery with medical therapy for severe emphysema. N Engl J Med, 2003. 348: p. 2069-73. 26. Naunheim, K., et al., Long-term follow-up of patients receiving lung-volume-reduction surgery versus medical therapy for severe emphysema by the National Emphysema Treatment Trial Research Group. Ann Thorac Surg, 2006. 82: p. 431-43. 27. National Emphysema Treatment Trial Research Group, Patients at high risk of death after lung-volume-reduction surgery. N Engl J Med, 2001. 345: p. 1075-83. 28. Ingenito, E., D. Wood, and J. Utz, Bronchoscopic lung volume reduction in severe emphysema. Proc Am Thorac Soc, 2008. 5: p. 454-60. 29. Sciurba, F., et al., A randomized study of endobronchial valves for advanced emphysema. N Engl J Med, 2010. 363: p. 1233-44. 30. Criner, G., et al., Biologic lung volume reduction advanced upper lobe emphysema: phase 2 results. Am J Respir Crit Care Med, 2009. 179: p. 791-8. 31. Reilly, J., et al., Biological lung volume reduction. A new bronchoscopic therapy for advanced emphysema. Chest, 2007. 131: p. 1108-13. 32. Refaely, Y., et al., Biologic lung volume reduction therapy for advanced homogenous emphysema. Eur Respir J, 2010. 36: p. 20-7. 33. Snell, G., et al., Bronchoscopic thermal vapour ablation therapy in the management of heterogeneous emphysema. Eur Respir J, 2012. 39: p. 1326-33. 34. Todd, J. and S. Palmer, Lung transplantation in advanced COPD: is it worth it? Semin Respir Crit Care Med, 2010. 31(3): p. 365-72.
Evaluation
1. Pulmonary rehabilitation has been demonstrated to improve which of the following outcomes in COPD patients: a. Health status b. Rehospitalisation after a hospitalisation for an acute exacerbation of COPD c. Exercise capacity
74
d. All of the above 2. Long term oxygen therapy has been shown to improve mortality in COPD patients with: a. Resting hypoxemia b. Isolated exertional desaturation c. Isolated nocturnal desaturation d. None of the above 3. Lung volume reduction surgery has been demonstrated to improve mortality in COPD patients with: a. Diffuse emphysema and mild airflow obstruction b. Upper lobe predominant emphysema and low, post-rehabilitation exercise capacity c. Lower lobe predominant emphysema and high, post-rehabilitation exercise capacity d. None of the above
75
Non-pharmacological therapy for COPD

Fernando J. Martinez, M.D., M.S. University of Michigan Health System
Non-pharmacological therapy of stable COPD: GOLD 2011
www.goldcopd.org
Nonpharmacological therapy in COPD
Pulmonary rehabilitation Oxygen therapy Vaccination Lung volume reduction

Surgical Bronchoscopic
76
Benefits of Pulmonary Rehabilitation on QOL: Meta-analysis

Study Rehab N Boxall 2005 Chlumsky 2001 Engstrm 1999 Finnerty 2001 Griffiths 2000 Ringbaek 2000 Total (95% Cl) 23 13 26 24 93 17 196 Mean (SD) -5.80 (11.80) -4.07 (19.76) 0.30 (17.30) -9.30 (12.20) -7.10 (15.50) -2.10 (19.00) Usual care N 23 6 24 25 91 19 188 I2=0.0% Mean(SD) -1.40 (13.30) -4.22 (19.20) 0.50 (16.20) -2.20 (15.00) 1.30 (11.70) -2.20 (17.00) Weighted Mean Difference (Random) 95% Cl Weight (%) 15.6 2.3 9.6 14.1 52.5 5.9 Weighted Mean Difference (Random) 95% Cl -4.40 [-11.67, 2.87] 0.15 [-18.60, 18.90] -0.20 [-9.49, 9.09] -7.10 [-14.74, 0.54] -8.40 [-12.36, -4.44] 0.10 [-11.73, 11.93] -6.11 [-8.98, -3.24]
100.0
Test for heterogeneity chi-square=4.60 df=5 (P=0.47) Test for overall effect Z=4.17 (P=0.000031)
-100
-50
50
100
Favours treatment
Favours control
Lacasse Y, et al. Cochrane Database Syst Rev. 2006;4:CD003793. Permission requested.
Pulmonary Rehabilitation Significantly Improves Exercise Capacity: Meta-analysis

Study Behnke 2000a Booker 1984 Boxall 2005 Cambach 1997 Chlumsky 2001 Engsrtm 1999 Finnerty 2001 Goldstein 1994 Gosselink 2000 Gell 1995 Gell 1998 Lake 1990 Ringbaek 2000 Simpson 1992 Singh 2003 Wijkstra 1994 Total (95% Cl) Rehab N 15 32 23 12 13 26 22 36 34 29 18 7 17 14 20 28 346 Mean (SD) 0.0 (103.40) 21.00 (85.00) 39.00 (69.60) 51.00 (89.00) 54.07 (114.22) 38.00 (90.00) 75.00 (131.30) 32.00 (102.00) 58.00 (125.00) 91.00 (67.00) 63.00 (92.00) 108.60 (79.00) 10.47 (85.09) 36.00 (102.00) 54.00 (118.00) 9.00 (87.00) Usual care Weighted Mean Difference (Random) N Mean(SD) 95% Cl 15 37 23 7 6 24 23 41 28 27 17 7 19 14 20 15 323 0.0 (65.10) 5.00 (90.00) 4.20 (75.10) 46.00 (79.00) -5.67 (131.68) -2.00 (102.00) 8.00 (107.00) -11.00 (99.00) 3.00 (104.00) 8.00 (67.00) -22.00 (72.00) -35.00 (50.00) -18.52 (77.50) 7.00 (120.00) 6.30 (157.00) -28.00 (141.00) Weight (%) 5.7 10.0 9.8 4.0 1.8 7.1 4.8 8.9 6.5 11.9 6.9 4.8 7.1 3.6 3.3 3.9 100.0 Weighted Mean Difference (Random) 95% Cl 0.0 [-61.83, 61.83] 16.00 [-25.33, 57.33] 34.80 [-7.05, 76.65] 5.00 [-72.21, 82.21] 59.74 [-62.56, 182.04] 40.00 [-13.50, 93.50] 67.00 [-159.00, 135.59] 43.00 [-2.04, 88.04] 55.00 [-2.00, 112.00] 83.00 [47.88, 118.12] 85.00 [30.43, 139.57] 143.60 [74.34, 212.86] 28.99 [-24.40, 82.38] 29.00 [-53.50, 111.50] 47.70 [-38.37, 133.77] 37.00 [-41.29, 115.29] 48.46 [31.64, 65.28]
Test for heterogeneity chi-square=22.36, df=15 (P=0.16): I2=26% Test for overall effect Z=5.65 (P<0.00001)
-100 -50 Favours control
50 100 Favours treatment
Lacasse Y, et al. Cochrane Database Syst Rev. 2006;4:CD003793. Permission requested.
Pulmonary Rehabilitation: Effect on Hospitalization
Griffiths TL, et al. Lancet. 2000;355:362-368.
77
Treadmill Endurance Time Improves With Combination Tiotropium and Pulmonary Rehabilitation Randomized to Tiotropium or Placebo
Endurance Time (minutes) * Tiotropium *
Placebo Randomization Pulmonary rehabilitation Weeks of Treatment
*P<.05.
Casaburi et al. Chest. 2005;127:809-817 (A).
Study
Rehabilitation following hospitalization for an acute exacerbation of COPD decreases Peto Odds Ratio re-hospitalization
Patients, n (95% CI)
26 97 41 26 60 250 0.09 (0.001, 0.056) 0.71 (0.29, 1.77) 0.08 (0.02, 0.45) 0.29 (0.04, 1.90) 0.14 (0.03, 0.72) 0.22 (0.08, 0.58)
Behnke 2000 Eaton, 2009 Man 2004 Murphy, 2005 Seymour, 2010 Total (95%CI)
0.002
0.1
10
500
Favors control
Favors rehabilitation
Cranston et al. Cochrane Syst Rev. 2008; Vol 4
What is optimal duration of rehabilitation in COPD?
Meta-analysis not possible due to

heterogeneity and limited data HRQoL
Longer duration had more favorable effect on

4 wks < 7 wks 3 mo < 18 mo
Beauchamp MK, et al. Chronic Respir Dis 2011; 8: 129-40.
78

Effect of LTOT in patients with severe hypoxemia
Oxygen supplementation in the NETT: Utilization and impact on survival

At enrollment 260/1215 participants used LTOT but were nonhypoxemic at rest
Characteristic PaO2 > 60 and LTOT 25.8% 1143 81% 68.2 55.9 PaO2 > 60 and no O2 29.8% 1363 35% 55.6 50.4 P value
FEV1 6MWD Desaturation SOBQ SGRQ
< 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001
Drummond et al. Chest. 2008; 134: 497-506
79
Effect of LTOT in patients with mild to moderate hypoxemia
15 hours/day O2 does not improve dyspnea in refractory dyspnea (~60% with COPD)
Abernethy et al. Lancet. 2010; 376: 784-93
Nor does it improve health status
Abernethy et al. Lancet. 2010; 376: 784-93
80
Oxygen therapy does not improve dyspnea in COPD patients without hypoxemia
Moore RP et al. Thorax. 2011; 66: 32-7
Effect of O2 therapy on recovery time in COPD patients who felt O2 improved activity
Quantrillet al. Thorax. 2007; 62: 702-5
O2 administration for one hour increases oxidative stress and inflammation

Healthy subjects COPD patients
Carpagnano et al. Thorax. 2004; 59: 1016-9
81
Long Term Oxygen Therapy Trial Clinical Sites

1. 2.
Ann Arbor (U Michigan) Birmingham (U Alabama) Boston (Brigham/UV/D) Cleveland (CCF/CW)
13 11 3 3 1 5 14 5 4 10 5 7
3. 4. 5. 6. 7. 8. 9.
Columbus (Ohio State/UK/UC) Denver (U Colorado) Durham (Duke) Los Angeles (Harbor) Philadelphia (Temple/UP/D)
12
8 2
10. Pittsburgh (U. Pitt) 11. Portland (Kaiser)
12. Salt Lake City (Utah) 13. Seattle (U Wash) 14. St. Louis (Wash U)
LTOT Study Design
Eligible Patient LTOT No LTOT
Primary hypothesis: COPD patients with moderate hypoxemia will have improved hospitalization free survival if they are treated with supplemental O2

82
Prevention of Hospitalizations Pneumococcal and Influenza Vaccination
Nichol, et al. Arch Intern Med 1999; 159: 2437
Influenza Vaccine Reduces InfluenzaRelated Acute Respiratory Illness in COPD

Favors Vaccination Overall FEV1 70% pred FEV1 50-69% pred FEV1 <50% pred Favors Placebo
0.2 0.4 0.6 0.8
1.2 1.4 1.6 1.8 4
Odds Ratio (95% CI)
Wongsurakiat et al. Chest. 2004;125:2011-2020 (A).

83
Severe COPD Symptomatic despite maximal medical Rx and pulmonary rehabilitation
FEV1 < 15% pred
FEV1 15-45% pred
FEV1 < 20% pred & DLCO < 20% pred or Homogeneous emphysema
Naunheim et al. Ann Thorac Surg; 2006; 82:431-43
Adapted from Nathan; Chest 2005; 127: 1006-16
FEV1 < 15% pred
FEV1 15-45% pred
Yes
Consider Lung transplantation
No
Meets NETT Criteria?
Inclusion: Emphysema BMI, Pred < 20 mg, TLC > 100, RV > 150 pCO2 < 60; paO2 > 45; 6MWD > 140 m No cardiac contraindication Nonsmoking
FEV1 < 15% pred
FEV1 15-45% pred
Yes
No
Inclusion: Exclusion: Emphysema Previous thoracic surgery BMI, Pred < 20 mg, TLC > 100, RV > 150 Recurrent infections/sputum pCO2 < 60; paO2 > 45; 6MWD > 140 m Bronchiectasis, giant bulla, suspected No cardiac contraindication cancer, pulmonary hypertension, > 6 Nonsmoking liters O2 with exercise
84
FEV1 < 15% pred
FEV1 15-45% pred
Yes
Consider Lung transplantation BODE > 7 and other criteria?
No No
FEV1 < 15% pred
FEV1 15-45% pred
Yes
Consider Lung transplantation BODE > 7 and other criteria?
No No
Martinez et al, AJRCCM 2006; 173: 1326-34
FEV1 < 15% pred
FEV1 15-45% pred
Yes
No Yes
BODE > 7 and other criteria?
No
Yes
Non-upper lobe emphysema and low exercise capacity Non-upper lobe emphysema and high exercise capacity Upper lobe emphysema and low exercise capacity Upper lobe emphysema and high exercise capacity
85
FEV1 < 15% pred
FEV1 15-45% pred
Yes
No Yes
No
Yes
FEV1 < 15% pred
FEV1 15-45% pred
Yes
No Yes
No
Yes
SGRQ in upper lobe predominant emphysema

Naunheim et al. Ann Thorac Surg 2006; 82: 431-43
86
Severe COPD Symptomatic despite maximal medical Rx and pulmonary rehabilitation FEV1 < 15% pred FEV1 15-45% pred FEV1 < 20% pred & DLCO < 20% pred or Homogeneous emphysema
Yes
No Yes BODE > 7 and

other criteria?
No
Yes
Upper lobe Non-upper lobe Upper lobe Non-upper lobe emphysema and lowemphysema and high emphysema and lowemphysema and high exercise capacity exercise capacity exercise capacity exercise capacity
Bronchoscopi c approach?
Consider LVRS
Bronchoscopic approaches to LVR

Flow regulation
ZephyrEndobronchial Valves (EBV) PulmonX
One-way valve leads to atelectasis.
Intrabronchial Valves (IBV) Spiration
One-way valve leads to atelectasis.
Tissue compression
RePneu - Lung volume reduction coil (LVRC) PneumRx AeriSeal Polymeric Lung Sealant Aeris InterVapor Bronchoscopic Thermal Vapor Ablation (BTVA) Uptake
Coil reduces lung volume by coiling and compressing disease tissue. Tissue sealant flows into alveolar compartment, polymerizes and seals target area. Heated water vapor produces thermal reaction with localized inflammation followed by fibrosis.
Change in FEV1 and 6MWT at 6 Months in VENT study

FEV1 Change = 6.8%, p = 0.005 6MWT Change = 5.8%, p = 0.04
Sciurba FC et al; NEJM 2010; 363: 1233-44
87
Bronchoscopic thermal vapor ablation improves lung function in severe COPD (FEV1 15-45%) and heterogeneous upper lobe predominant emphysema
Snell G et al; ERJ 2012; 39: 1326-33
FEV1 < 15% pred
FEV1 15-45% pred
Yes
No Yes
No
Yes
Consider LVRS
FEV1 < 15% pred
FEV1 15-45% pred
Yes
No Yes
No
Yes
Consider LVRS
88
FEV1 < 15% pred
FEV1 15-45% pred
Yes
No Yes
No
Yes
Consider LVRS
FEV1 < 15% pred
FEV1 15-45% pred
Yes
No Yes
No
Yes
BODE > 7 & other risk factors
?
Consider LVRS
Martinez et al; AJRCCM 2006; 173: 1326-34

89
GOLD Assessment of COPD Comorbidities

COPD patients are at increased risk for: Cardiovascular diseases Osteoporosis Respiratory infections Anxiety and Depression Diabetes Lung cancer
These comorbid conditions may influence mortality and hospitalizations and should be looked for routinely, and treated appropriately.
www.goldcopd.org
90

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ERS Annual Congress Vienna

Postgraduate Course 9 Progress on the treatment of COPD

Nonmedical therapy for COPD

Long term oxygen therapy (LTOT)

Lung volume reduction/transplantation

Non-pharmacological therapy for COPD

Non-pharmacological therapy of stable COPD: GOLD 2011

Nonpharmacological therapy in COPD

Pulmonary rehabilitation Oxygen therapy Vaccination Lung volume reduction

Benefits of Pulmonary Rehabilitation on QOL: Meta-analysis

Lacasse Y, et al. Cochrane Database Syst Rev. 2006;4:CD003793. Permission requested.

Pulmonary Rehabilitation Significantly Improves Exercise Capacity: Meta-analysis

-100 -50 Favours control

50 100 Favours treatment

Lacasse Y, et al. Cochrane Database Syst Rev. 2006;4:CD003793. Permission requested.

Pulmonary Rehabilitation: Effect on Hospitalization

Griffiths TL, et al. Lancet. 2000;355:362-368.

Placebo Randomization Pulmonary rehabilitation Weeks of Treatment

Casaburi et al. Chest. 2005;127:809-817 (A).

Cranston et al. Cochrane Syst Rev. 2008; Vol 4

What is optimal duration of rehabilitation in COPD?

Meta-analysis not possible due to

Longer duration had more favorable effect on

Beauchamp MK, et al. Chronic Respir Dis 2011; 8: 129-40.

Nonpharmacological therapy in COPD

Pulmonary rehabilitation Oxygen therapy Vaccination Lung volume reduction

Effect of LTOT in patients with severe hypoxemia

Cranston et al. Cochrane Syst Rev. 2008; Vol 4

Oxygen supplementation in the NETT: Utilization and impact on survival

FEV1 6MWD Desaturation SOBQ SGRQ

Drummond et al. Chest. 2008; 134: 497-506

Effect of LTOT in patients with mild to moderate hypoxemia

Cranston et al. Cochrane Syst Rev. 2008; Vol 4

Abernethy et al. Lancet. 2010; 376: 784-93

Nor does it improve health status

Abernethy et al. Lancet. 2010; 376: 784-93

Quantrillet al. Thorax. 2007; 62: 702-5

O2 administration for one hour increases oxidative stress and inflammation

Carpagnano et al. Thorax. 2004; 59: 1016-9

Long Term Oxygen Therapy Trial Clinical Sites

Ann Arbor (U Michigan) Birmingham (U Alabama) Boston (Brigham/UV/D) Cleveland (CCF/CW)

10. Pittsburgh (U. Pitt) 11. Portland (Kaiser)

LTOT Study Design

Eligible Patient LTOT No LTOT

Nonpharmacological therapy in COPD

Pulmonary rehabilitation Oxygen therapy Vaccination Lung volume reduction

Prevention of Hospitalizations Pneumococcal and Influenza Vaccination

Nichol, et al. Arch Intern Med 1999; 159: 2437

Influenza Vaccine Reduces InfluenzaRelated Acute Respiratory Illness in COPD

0.2 0.4 0.6 0.8

1.2 1.4 1.6 1.8 4

Odds Ratio (95% CI)

Wongsurakiat et al. Chest. 2004;125:2011-2020 (A).

Nonpharmacological therapy in COPD

Pulmonary rehabilitation Oxygen therapy Vaccination Lung volume reduction

Severe COPD Symptomatic despite maximal medical Rx and pulmonary rehabilitation

FEV1 < 15% pred

FEV1 15-45% pred

Naunheim et al. Ann Thorac Surg; 2006; 82:431-43

Adapted from Nathan; Chest 2005; 127: 1006-16

Severe COPD Symptomatic despite maximal medical Rx and pulmonary rehabilitation

FEV1 < 15% pred