frailty and sarcopenia in the lung transplant candidate · frailty and sarcopenia in the lung...
TRANSCRIPT
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Frailty and Sarcopenia in the Lung Transplant Candidate
Dmitry Rozenberg, MD, FRCPC Clinical Associate
Toronto Lung Transplant Program
Pulmonary Rehabilitation
Toronto General Hospital
University Health Network
University of Toronto
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Disclosures
• Financial: Salary support from University of Toronto, Clinician Scientist Training Program
2 2
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Objectives
• Describe the evidence for frailty and sarcopenia in advanced lung disease.
• Recognize the clinical implications of frailty and sarcopenia in lung transplant patients.
• Identify various construct measures that might be helpful in assessing lung transplant candidates.
3 3
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Construct of Frailty
• Conceptual Model:1
- Dynamic state
- Several domains (physical, psychological, social).
• Operational Models:
1) Criteria Based Definition: (Fried Frailty Index)2
2) Cumulative Deficits: Multiple comorbidities (Rockwood)3
3) Clinical Frailty Scale:4
4 4
1. Gobbens RJ. J. American Medical Directors 2010
2. Fried LP. Gerontol A Biol Sci Med Sci 2001
3. Rockwood K. Rev Clin Gerontol 2002
4. Rockwood K. CMAJ 2005
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(1) Fried Frailty Index
•Most common operational model in elderly:
• ≥ 3 of 5 dichotomous elements
1) Unintentional weight loss
2) Weakness
3) Self-reported exhaustion
4) Slowness
5) Reduced physical activity
5 5
Fried LP. Gerontol A Biol Sci Med Sci 2001
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Rockwood Frailty Indeces
(2) Cumulative Frailty Index:1
•Cumulative sum of impairments (70)
•Strong Predictive Validity
•Disadvantage: Time commitment
(3) Clinical Frailty Index:2
•Clinical Judgement
•Robust Health (1) Functional Dependence (7)
6 6
1. Rockwood K. Rev Clin Gerontol 2002
2. Rockwood K. CMAJ 2005
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Prevalence of Frailty in Elderly
• Community Studies - Age > 65 years; n = 21 studies; 61,500
- Large variation in prevalence (4 - 59%)
• Operational model:
- Criteria Based Definition (9.9%)
- Encompassing Frailty Model (13.6%)
• Increases with Age
- Age 65-69 years (4 %)
- Age > 85 years (26 %)
7 7
Collard RM. J Am Geriatr Soc 2012.
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Prevalence of Frailty
• Vulnerable Social Status - Mortality increased at 5 years (32.5 % vs. 11%)
•Comorbidities - 2/3 of Frail adults have ≥ 2 comorbidities
8 8
Collard RM. J Am Geriatr Soc 2012.
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Importance of Frailty in the Elderly
Two Population Studies in the Elderly
1) Fried Frailty Index
2) Rockwood Clinical Frailty
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Fried Frailty Index
10 10
Fried LP. Gerontol A Biol Sci Med Sci 2001.
No Frailty
Intermediate
Frail
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Clinical Frailty Scale (CSHA) Risk for Institutionalization and Mortality
11 Rockwood K, et al. CMAJ 2005.
Institutionalization Mortality
(1)Very Fit (Robust) (7) Severely Frail
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Why is Frailty Important?
• Elderly Adults: - Falls, disability, institutionalization and increased mortality
- Sensitivity to air pollution1
• Post-operatively: - Increased complications after general surgery2
- Delayed graft function in renal transplant recipients3
• Cardiac patients: - ED visits, hospitalizations and mortality in CHF4
- LVAD implantation associated with mortality5
12 12
1. Eckel SP. Am J Epidemiol 2012.
2. Makary MA. J Am Coll Surg 2010.
3. Garonzik-Wang JM. Archives of surgery 2012.
4. Uchmanowicz I. Curr Heart Fail Rep 2014.
5. Dunlay SM. The Journal of Heart and Lung Transplantation 2013.
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Frailty in Respiratory Disease
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14 14
Park SK. Heart and Lung 2013.
• NHANES survey (n= 20,470); Final sample (n=211)
• Cumulative Frailty definition: Score 0-9; Frail ≥ 2
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15 15
Park SK. Heart and Lung 2013.
• Prevalence of Frailty (58 %)
• Strongest predictor of frailty was dyspnea
• Co-morbidities (arthritis, DM2, liver disease, HTN)
• Frailty associated with disability of ADL/IADLs.
• Significant relationship between Frailty and
inactive days secondary to health
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Frailty in the Lung Transplant Candidate
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Frailty in the Lung Transplant Candidate
Objectives:
1) Assess association of frailty with health
related quality of life
2) Impact of frailty on transplant outcomes
17 17
Rozenberg D. ISHLT Abstract Presentation 2014.
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Establishing Operational Frailty Index
• 194 patients (46%) HRQL & Rehab (Jan/04- June/09)
• Fried Frailty Phenotype ( ≥ 3 out of 5)
- Shrinking (BMI < 18.5 kg/m2)
- Quadriceps Training Volume
- Exhaustion (SF-36 Vitality Score)
- Slowness (6 Minute Walk Distance)
- Low Activity (SF- 36 Physical Function)
• Reference Standard (SGRQ):
“I have become frail or invalid because of my lung respiratory/problem”.
18 18
Rozenberg D. ISHLT Abstract Presentation 2014.
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44 % Categorized as Frail
Characteristics Frail (n=86) Not Frail
(n=108)
p value
Age (years) 57 IQR [50-62] 52 [36-62] 0.03
Male (%) 45 (52 %) 60 (56 %) 0.67
COPD 37 (43 %) 29 (27 %) 0.02
ILD 32 (37 %) 36 (33 %) 0.65
CF 11 (13 %) 32 (30 %) 0.01
Other 6 (7 %) 11 (10 %) 0.61
Days on
Transplant List
157 [75-264] 131 [65-261] 0.59
Rozenberg D. ISHLT Abstract Presentation 2014.
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Frailty Associated with Lower HRQL
HRQL Frail (n=86) Not Frail
(n=108)
p value
SGRQ
Total Score 73.2 ± 10.5 58.6 ± 13.2 < 0.001
EQ-5D 0.49 [0.19-0.62] 0.66 [0.52-0.81] < 0.001
* Frailty was the only significant predictor: • SGRQ Total Score (+ 13.6 95% CI 10.1 to 17.2)
• EQ-5D (- 0.23 95% CI -0.30 to -0.15)
Rozenberg D. ISHLT Abstract Presentation 2014.
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Frailty Associated with Increased
Duration of Hospitalization and Lower 6MWD
Post-transplant Frail (n=86) Not Frail
(n=108)
p value
ICU Days 3 [2-10] 3 [2-6] 0.10
Length of Stay (Days) 22 [16-36] 17.5 [13-28] 0.02
Inpatient Rehab 15 (17%) 11 (10%) 0.20
6 MWD (m) 3 months 424 ± 88 475 ± 115 0.002
Frailty and Diagnostic Category were significant:
• Median Length of Stay (2.1 days 95% CI 0.6 to 7.1)
• 6MWD Change from Pre-Tx (53 m 95% CI 23 to 84)
Rozenberg D. ISHLT Abstract Presentation 2014.
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No Survival Difference Observed
Proportional Hazards Ratios: Unadjusted: 0.71 [95% CI 0.46 – 1.09]
Adjusted: 0.94 [95% CI 0.61 – 1.47]
Hospital Mortality: Frail 3 (4%) vs. Not Frail 8 (7%), p=0.35
Rozenberg D. ISHLT Abstract Presentation 2014.
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Study Conclusion
•Frailty associated with decreased HRQL scores
• Increased length of stay and reduced 6MWD
•Frailty phenotype warrants additional study into its prognostic potential on survival
23 23
Rozenberg D. ISHLT Abstract Presentation 2014.
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Frailty in Advanced Lung Disease
•High prevalence not surprising (~ 50%)
•Number of co-morbidities, psycho-social and physical limitations include many of the constructs of frailty
24 24
Figure Adapted from Fried LP. Journal of Gerontology 2001
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Frailty in Lung Transplant Candidates
25 25
1. Gutierrez C, American Journal of Transplantation 2007
Physical:
• Older age1
• Body Mass Index
• Low physical activity
• Reduced muscle mass & strength
Psycho-social:
Co-morbidities: • Osteoporosis, Hypertension, Metabolic Syndrome
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Older Lung Transplant Candidates
26 26
Hook JL. Expert Rev Respir Med. 2012
Recipient’s Age at the time of Lung Transplant in USA
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BMI in Lung Transplant Candidates
27 27
Hook JL. Expert Rev Respir Med. 2012
1 year 5 years
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Low Physical Activity Levels
28 28
1. Wickerson L. Journal of Cardiopulmonary Rehabilitation and Prevention 2013.
2. Langer D. Respiratory Medicine 2012.
Lung Transplant Candidates:
Inactive compared to general
Canadian population1
• 6MWD was one of the main determinants of low
physical activity2
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Lung Transplant Candidates: Psycho-social Domain
29 29
1. Singer HK. Chest 2001.
• Advanced Lung Disease associated with reduced
HRQL and psychological impairment
• One study (n=243, Two centres)1
- Majority had mild somatic/depressive symptoms
- 25% had significant anxiety/depression
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Comorbidities: Lung Transplant Candidates
30 30
1. Lakey WC. Clin Transplant 2011.
2. Savioli G. Clin Transplant 2013.
• High prevalence of osteoporosis (37%) and
combined osteoporosis/osteopenia (86)1
• Cohort of 67 lung transplant patients (48 ±14 years)
• Prevalence of Metabolic Syndrome (3% to 24%)2
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Role of Sarcopenia in Frailty
• Body text 28pt
• Indented txt 28pt or 24pt
31 31
Fried LP. Journal of Gerontology: Medical Sciences 2001.
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Sarcopenia Consensus Definition
32 32
Cruz-Jentoft AJ. Age Ageing 2010.
Sarcopenia defined:
Decreased muscle mass AND reduced
muscle strength or function
Muscle Mass
Muscle Strength Functional Test
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Importance of Sarcopenia in Advanced Lung Disease
• Individual elements of Sarcopenia studied
• In COPD patients; Increased Mortality
- Low muscle mass 1
- Mid-thigh cross- sectional area 2
- Low Strength 3
33 33
1.Slinde F. Respir Med 2005
2.Marquis K. Am J Respir Crit Care Med 2002.
3.Swallow EB. Thorax 2007.
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Sarcopenia in Lung Transplant Patients
•Despite alleviation of cardio-respiratory limitations, improved HRQL,1 and survival;2 recipients have ++ VO2 impairments3
•Majority of patients have impairments in muscle mass and strength pre- and post-transplant
34 34
1. Singer JP. Seminars in respiratory & critical care medicine 2013.
2. Orens JB. The Journal of Heart and Lung Transplantation 2006.
3. Wickerson L. The Journal of Heart and Lung Transplantation 2010.
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Low Muscle Mass (Fat Free Mass)
• Fat-free mass observed to be decreased pre- and post-transplant (using BIA)
(1) Low FFMI in 2/3 in the pre-transplant period and 1/3 of patients at 2 years post-transplant.
(2) Lower FFM in 12 recipients (~ 3 years post) compared to healthy age-matched controls
35 35
1. Kyle UG. Acta diabetologica 2003
2. Vivodtzev I. Respiratory physiology & Neurobiology 2011.
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Muscle Strength in Lung Transplant
Systematic Review:
• Quadriceps strength (QS) most common measure
• 14 out of 18 studies
- Computerized Dynamometer (n = 10)
- Hand-held Device (n = 4)
• Pre - Tx: Mean Range 49-86% (n=455)
• Post -Tx (< 3 months): 51- 72% (n=126)
• Post -Tx (> 3 months); 58-101% (n=164)
36 36 Rozenberg D. Under review. Journal of Heart and Lung Transplantation
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Muscular Function
•Lower body function: Sit-to-stand test (n=2)1,2
•No studies assessed upper extremity function
37 37
1. Bossenbroek L. Respiration 2011
2. Bossenbroek L. Journal of Heart and Lung Transplantation 2009
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Sarcopenia Measure Correlates
• QS correlates with ICU stay
post transplant1
• QS correlates with PA Measures:
- Daily steps 2
- Peak VO2 3
• Lower body function (sit-to-stand)
- Daily steps 4
38 38
1. Maury G. American Journal of Transplantation 2008.
2. Langer D. Journal of Heart and Lung Transplant 2009.
3. Pinet C. Thorax 2004.
4. Bossenbroek L. Journal of Heart and Lung Transplant 2009.
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Sarcopenia in Lung Transplant
• No lung transplant studies to date have used sarcopenia consensus definition
• Studies on clinical outcomes needed
• Patients with complex co-morbidities, myopathies, and hospitalizations excluded from many studies
39 39
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Lung Transplant Candidates
40 40
Selection Process in 2014
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Absolute Contraindications
• Malignancy in the last 2 years
• Advanced dysfunction of another organ
• Chronic extra-pulmonary infection
• Significant chest wall/spinal deformity
• Psychological/Non-adherence concerns
• Absence of Social support
• Substance Abuse
41 41 Orens JB, et al. J Heart Lung Transplant. 2006
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Relative Contraindications
•Age > 65 years old
•Unstable clinically (shock, ECMO)
•Limited functional status with poor rehab potential
•Colonization with virulent organisms
•Severe obesity
•Chronic Mechanical Ventilation
42 42 Orens JB, et al. J Heart Lung Transplant. 2006
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Lung Allocation Score
43 43
Doesn’t include: • Psycho-social
• Sarcopenia
Figure: Hook JL. Expert Rev Respir Med. 2012
Data: Organ Procurement and Transplantation Network
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Lung Allocation Score and Outcomes
44 44
• High LAS associated with decreased survival and
prolonged hospitalization
• Improved mortality in the pre-transplant period but
potentially selecting more frail candidates
Russo MJ. Chest 2010
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Importance of Frailty and Sarcopenia
45
• Many of the listing criteria don’t
necessarily capture the entire spectrum
• Frailty, Sarcopenia and Psycho-social
aspects in advanced lung disease may
prove to be important
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Frailty as a Dynamic State
46
Lung Tx Listing
Clinical Worsening
(i.e. Resp exacerbation)
Potential Modifiable Factors
• BMI, Nutrition
• Muscle Mass, Strength
• Physical Activity
• Psycho-social Factors
Post-Tx
Diagram Adapted from Fried LP. 1998
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Summary
47
• Frailty and sarcopenia are prevalent in advanced
lung disease
• Further study into the clinical implications of frailty
and sarcopenia is needed in lung transplant
candidates
• Rehabilitation strategies may play an important role
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