Evidence for early Pulmonary Rehabilitation following hospitalisation for exacerbation of COPD

Centre for Inflammation Research Evidence for early Pulmonary Rehabilitation following hospitalisation for exacerbation of COPD Pulmonary Rehabilitation Clinicians Day Roberto A. Rabinovich ELEGI/Colt laboratory Centre for Inflammation Research The University of Edinburgh2

Chronic Obstructive Pulmonary Disease Definition Chronic Obstructive Pulmonary Disease is a preventable and treatable state characterized by airflow limitation that is not fully reversible The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles and gases, primarily caused by cigarette smoking Although COPD affects the lungs, it also produces significant systemic consequences ATS/ERS Statement 24

Chronic Obstructive Pulmonary Disease Classification ATS/ERS Severity GOLD Post Bd FEV 1 /FVC FEV 1 % pred At risk > 7 Cough and sputum > 8 Mild I < 7 > 8 Moderate II < 7 5-8 Severe III < 7 3-5 Very severe < 7 < 3 IV < 7 < 3 o < 5 plus CRF

Chronic Obstructive Pulmonary Disease Phenotypes 1. Variable FEV 1 6MWD MRC BMI 65 35-1 >21 BODE Index Score 1 2 5-65 36-49 25-349 15-249 2 3 <21 3 35 149 4 Probability of Death.8.6.4.2 Score -2 Score 3-4 Score 5-6 Score 7-1 1 2 3 4 52 Months Celli B et al NEJM 24; 35: 15

Exercise Tolerance in COPD More than lung function Quadriceps Twitch Force (% of Baseline) 14 12 1 8 6 4 Causes for stopping: Fatigue (6%) no fatigue fatigue baseline 1 min Mador MJ, AJRCCM 2;161: 447-453

Quadriceps strength ( % of resting value) 12 1 8 6 4 Muscle Dysfunction exercise tolerance Improvement in FEV 1 12% Fatigue No-fatigue * +92% 2 Rest 1 2 3 4 5 Time (seconds) Saey D et al 23 Am J Respir Crit Care Dis;168:425

Muscle Dysfunction Endurance 3 * Endurance time (minutes) 25 2 15 1 5 Control COPD control COPD Coronell, Eur Respir J 24;24: 129-136

Muscle mass and strength 12 1 Control COPD.9.8.7 Thigh Cross Sectional Area Quadriceps strength (Kg) 8 6 4.6.5.4 2 COPD control 2 4 6 8 1 12 14 16 CSA thigh (cm 2 ) Bernard S., Am J Respir Crit Care Med 1998;158: 629-634 control COPD

Chronic Obstructive Pulmonary Disease Muscle dysfunction Functional disorders Physio-pathological Changes Strength Resistance Fatigue Bioenergetics Fiber type distribution Capillarization and O 2 delivery Muscle mass It is characterized by two different, but possibly related, phenomena: Muscle wasting Malfunction of the remaining muscle

Physiopathological changes fibre type % 7 6 5 4 3 2 1 Control COPD Type I Type II Jobin J, J Cardiopulm Rehabil, 1998;18(6): 432-437

Physiopathological changes Bionergetics and oxidative capacity mmol/min/g 5 45 4 35 3 25 2 15 1 5 CS HADH Control COPD Maltais F, AJRCCM 1996;153: 288-293

Physiopathological changes Bionergetics and oxidative capacity 6 control COPD [Pi]/[Pcr] 6 control COPD Time (sec) 4 2 4 2 Pcr recovery time 1 2 3 4 5 Watt s Sala E, Am J Respir Crot Care Med 1999;159: 1726-1734

Physiopathological changes capillarisation and O 2 transport 25 1.6 2 1.4 1.2 15 1 Controles COPD 1.8.6 Controles COPD 5.4.2 Capillaries/mm 2 Capillaries/fibre Jobin J, J Cardiopulm Rehabil 1998, 18(6), 432-437

Muscle Dysfunction Health resources Health Resources High Low Patients (N) 23 34 Admissions Hospitalisations GP appointments DDM of CTC (N) (dias) (N) (mg/d) 2.3 3 4.4 4.6 ± ± ± ±.5 16 2.4 3.2 2.7.5 ± ± 1.5 1.2 Decramer et al ERJ, 1997, 1, 417-423

Muscle Dysfunction Health resources 9 8 High Low * # % pred 7 6 5 4 3 Age FEV1 DLCO QF PImax PEmax Decramer et al ERJ, 1997, 1, 417-423

Pulmonary Rehabilitation Rationale for exercise training COPD : is a systemic condition affecting the peripheral muscles EXERCISE TRAINING : is an intervention directed to re-establish normal muscle function

Benefits of Exercise Training HRQoL Meta-analysis n=277 TR, n=242 CO 1.2 Δ CRDQ (points) 1..8.6.4.2 MCID. DYS FAT EMO MAS Lacasse et al., Cochrane database, 22

Benefits of Exercise Training Exercise tolerance 6 minutes walking test Cambach Booker Ringbaeck O Donnell Wijkstra Cockroft Engström Goldstein Finnerty Troosters Bendstrup Guell MCID Troosters et al., Am J Respir Crit Care Dis 25; 172: 19 25 5 75 1

Benefits of Exercise Training Exercise tolerance 1 1 Porcentaje 75 5 25 75 5 25 6MWT EST Watt VO 2 Const. Crítico Eaton T et al., Chron Respir Dis 26; 3: 1-2 Troosters et al., Am J Respir Crit Care Dis 25; 172: 19

Benefits of Exercise Training effect on exacerbations 25 Rehab Control 8 2 7 n 15 1 5 n 5 2 Group Per patient LTOT Guell R et al. ERJ 23; 21: 789-94

Benefits of Exercise Training effect on exacerbations 3 Rehab Control 4 2 3 n 1 2 1 n Griffiths TL et al. Lancet 2; 355: 362-368 Days of hospitalisation appointments

Benefits of Pulmonary Rehabilitation early rehabilitation programmes after exacerbations Risk of hospitalisation Risk of death Bahnke (14/12) Man (2/21) 18 m 3 m Murphy (13/13) 6 m Global.25.5.75 1 1.5.5.1.2.5 1. 2. 5. Puhan M et al. Respir Research 25; 6: 54

COPD Exacerbations Impact on the muscle 2 175 Quadriceps strength (Nm) 15 1 5 * 15 125 1 75 5 25 Day 3 Day 8 3 8 No exercise training 9 Teme (Days) Pitta, F. Chest, 26 Spruit, M. A. Thorax, 23

Exacerbations of COPD Effect on Physical Activity Patients with COPD complain about feeling tired and not being able to cope with daily life activities early during exacerbations Hospitalisation Probablity 1..75.5.25. Time Walking (min) 175 15 125 1 75 5 25 5 1 15 2 years High Moderate Low Very Low * Risk of death Day 2 Day 7 1. *.75.5.25. 1 Month Stable COPD 5 1 15 2 years High Moderate Low Very low Pitta, Kessler, Garcia-Aymerich F. Chest, R. Chest 26 Thorax 13:133-142 26; 61: 772

Physical Activity Effect of exacerbations of COPD Dyspnoea Weakness Hypoxemia Acidosis Corticosteroids Psychology Not a good time for a walk

Pulmonary Rehabilitation During exacerbations Control Rehab 6 6 6MWD (m) 5 4 3 2 1 Visits to ER (%) 5 4 3 2 1 * Hospital Home Day 1 Day 1 Month 1 Month 2 Month 3 Month 6 Behnke M et al 2 Res Med; 94: 1184 Man W et al 24 BMJ; 329: 129

Pulmonary Rehabilitation During exacerbations Symtoms (-1) 6 5 4 3 2 Strength Training Dyspnoea Fatigue Weight (%1RM) 1 75 5 25 Troosters T et al. Am J Respir Crit Care Med, 21 D2 D3 D4 D5 D6 D7 D8

Pulmonary Rehabilitation Strength training during exacerbations Quadriceps strength (% day 2) 12 11 1 9 Control Training Myogenin / MyoD.75.5.25 1 2 3 4 Training Control Troosters T et al. Am J Respir Crit Care Med, 21

NMES: Pulmonary Rehabilitation NMES during exacerbations Frequency 5Hz 8 s On Pulse duration 4 μs Cycle duty 8/2s On/Off 2 s Off 5 Hz 4 μs Amplitud Selected By patient Session duration 3 min Amplitud (ma) (on tolerance) Sessions: 14 Neder, J. A. Thorax, 22

Pulmonary Rehabilitation NMES during exacerbations NMES

Pulmonary Rehabilitation NMES during exacerbations 14 days of stimulation Stimulated leg Ward Screening Hospital Home Control leg Strength Strength Giavedoni S et al. ERS 21

Pulmonary Rehabilitation NMES during exacerbations 2 * Δ Fuerza (%) 1-1 -2 7.8 % -5.8 % -3 Stimulated leg Control leg Giavedoni S et al. ERS 21

Pulmonary Rehabilitation NMES during exacerbations 5 Δ Fuerza (N) R=.94 P <.5-5 3 55 8 15 13 Σ ma Giavedoni S et al. ERS 21

Pulmonary Rehabilitation NMES during exacerbations ΔStrength Stimulated leg (% Basal) 5 25-25 Favours NMES Favours Control -2-1 1 2 3 4 5 Giavedoni S et al. ERS 21 Δ Strength Control leg (% Basal)

Pulmonary Rehabilitation Themore, Intensity thebest High Intensity Training Low Intensity Training -5-1 -15-2 -25-3 -5-1 -15-2 -25-3 -35-35 Lactate VE VO2 VCO2 VE/VO2 HR Lactate VE VO2 VCO2 VE/VO2 HR % change post-training Casaburi Am Rev Respir Dis. 1981;144:122

6MWD (% Pred) Pulmonary Rehabilitation Duration Short programmes (6-8 weeks) are effective in improving outcomes However a key goal of pulmonary rehabilitation 6 is to change patient s behavior 1 8 6 4 2 % Time Walking 5 4 3 2 1 * 3 Months 6 Months 3 Months 6 Months Pitta F et al. CHEST 28; 134: 273

Pulmonary Rehabilitation Duration 7 weeks 4 weeks -.2 -.4 -.6 -.8-1 -1.2-1.4-1.6 ESWT CRQt CRQd CRQf CRQe CRQm Green et al. Thorax 21; 56:143-5

meters 555 55 545 54 535 53 525 52 515 51 55 Pulmonary Rehabilitation Duration * seconds 6 5 4 3 2 1 6MWT Steps Overhead * * Berry et al. J Cardiop Rehab 23; 23:6-8

Training control Pulmonary Rehabilitation Effect of 6 month (6sessions) 3 15 Δ CRDQ (points) 2 1-1 -2 Δ 6MWD (m) 1 5-5 -1-3 -15 start 6 months 18 months start 6 months 18 months Longer pulmonary rehabilitation programs (beyond 12 weeks) produce greater sustained benefits than shorter programs (ACCP/AACVPR) Troosters et al. AJM 2; 19(3):27-12

Conclusions COPD is a complex disease affecting the lungs but incurring in several systemic effects such as muscle dysfunction Muscle dysfunction, together with lung function impairment, causes exercise intolerance Pulmonary rehabilitation, particularly exercise training, is an intervention aimed at restoring normal muscl function PR improves exercise tolerance, HRQoL and improves rate of exacerbations and hospitalisation days Early PR has the same beneficial effects that PR for stable COPD patients and may have an impact on survival

Conclusions Strength training and NMES may help preventing muscle dysfunction during exacerbations and incur beneficial effects for the patients High intensity programmes are preferable to low intensity programmes since achieve greater effects Longer programmes seems to achieve greater effect than shorter programmes It is generally believed that longer programes yield more endurable training effects