PULMONARY REABILITATION A. CHABBOU MD MP Journées Scientifiques: SOUSSE LE 25 FEVRIER 2006

PULMONARY REABILITATION

A. CHABBOUMD MP

Journées Scientifiques: SOUSSE LE 25 FEVRIER 2006


Rationel

The limitations of the patient with COPD- Deconditioning ) impact on skeletal muscle

- Systemic manifestations ) and cardiovscular system

muscle dysfunction EXERCISE LIMITATIONS

inability to increase oxygen delivery to the peripheral muscle

Pulmonary hypertension Constraints on lung mechanics

During exercice (dynamic hyperinflamation

and flow limitation)

gaz exchange

inefficiency in the lungs

Cardio vascular Pulmonary limitations

Limitation

Limitations are - cardiovascular - pulmonary - and skeletel muscle

PULMONARY REABILITATION Skeletal muscle dysfunction :

- déterminant factors - complementary mechanisms : 1- muscle strength exercise traning

2- muscle endurance 3- impaired muscle oxidative capacity

- activity of the enzymes : citrate synthase hydrooxy acetyl

COA deshydrogenase

4- a shift toward a glycolytic fiber type distribution (low fraction of type I fibers)*

skeletal muscle endurance fatigability exercise training Lowering of the lactate threshold ventilatory requirements during exercise

PULMONARY REABILITATIONSkeletal muscle dysfunction*

Proportion of type-IIA fibres % 29.4¡12.1 34.8¡11.9Proportion of type-IIXfibres % 27.2¡12.345.8¡18.9**CSA of type-IIX fibres mm2 4248¡1300 2566¡1137** P<0.001

Myopathological features in skeletal muscle of patients with chronic obstructive pulmonary disease H.R. Gosker*, B. Kubat#, G. Schaart}, G.J. van der Vussez, E.F.M. Wouters*, A.M.W.J. Schols*

PULMONARY REABILITATIONComplementary mecanisms

1- The sedentary life style of COPD patients skeletal muscle atrophy at 2 levels :

- The whole muscle level- The myocyte level With indirectly : the loss in fat-free mass2- Systemic inflammation **: recent studies have underlined the importance of systemic inflammation as a mechanism for

developement of muscle weakness, especially during severe exacerbations of COPD

- Circulating levels of IL8 : are significantly correlated with muscle weakness- Weight loss, especially fat-free mass has been associated with systemic

inflammation levels of skeletal muscle apoptosis were observed in patients presenting with

weight loss- Oxidative stress is another factor related to the process of muscle wasting.** - Patients with COPD are exposed to levels of oxidative stress :

- when stable- and during exacerbations

PULMONARY REABILITATION Systemic inflammation

Nitrite and nitrate levels in patients with chronic obstructive pulmonary disease ( ) and control subjects ( ). *: p<0.05; **:

p<0.01.

Skeletal muscle inflammation and nitric oxide in patients with COPD M. Montes de Oca1, S. H. Torres2, J. De Sanctis3, A. Mata1, N. Hernández2 and C. Tálamo1

Eur Respir J 2005; 26:390-397


Endothelial constitutive nitric oxide synthases (eNOS), inducible isoform nitric oxide synthases (iNOS) and

nitrotyrosine levels in patients with chronic obstructive pulmonary disease ( ) and control subjects ( ). ***: p<0.001.


Tumour necrosis factor (TNF)- levels in patients with chronic obstructive pulmonary disease ( ) and control subjects ( ). #: p<0.0001.

Table. — Skeletal muscle levels of inflammatory markers in low and normal weight chronic obstructive pulmonary disease(COPD)

Variables Low weight COPD

Nitrites µmol·mg–1 protein 11.4±2.0 13.6±3.1 NS

Nitrates µmol·mg–1 protein 19.5±2.2 24.5±2.9 NS

Total µmol·mg–1 protein 30.9±3,5 34.3±2.8 NS

Nitrotyrosine ng·mg–1 protein

24.5±6.9 25.2±0.1 NS

iNOS ng·mg–1 protein 27.1±7.6 36.6±9.4 NS

eNOS ng·mg–1 protein 32.2±6.2 31.9±3.1 NS

nNOS ng·mg–1 protein 85.3±18.4 101.7±23.1 NS

TNF- pg·mg–1 protein 201±93 267±207 NS

CD163 ng·mg–1 protein 6.4±0.7 6.8±2.7 NS

CD154 ng·mg–1 protein 14.3±5.9 17.6±8.5 NS

Normal weight COPD

P-value


Transversal section of the vastus lateralis part of quadriceps muscle. Immunohistochemical reaction with anti-CD68, clone MB11.

a) Control subject, male aged 68 yrs. The black dots are muscle fibres and endothelial cell nuclei.

b) Chronic obstructive pulmonary disease patient, male aged 68 yrs. The black stain represents macrophages infiltrate. Scale bar = 50 µm.

Oblique section of vastus lateralis part of quadriceps muscle in a 70-yr old female chronic obstructive pulmonary disease (COPD) patient. b) Longitudinal section of vastus lateralis part of quadriceps

muscle in a 69-yr-old female COPD patient. Arrows show prolongations of macrophage surrounding capillary. M: macrophage; NM: nucleus of macrophage; F: muscle fibres; NF: nucleus of muscle fibre;

C: capillary; NE: nucleus of capillary endothelial cell; P: pericyte. Scale bars = 1 µm.

Skeletal muscle dusfunction*


Exercice intolerance : MultifactorialImpairment of lung mechanics Altered gaz exchange Impairment of respiratory musclesCardiac dysfuntionDeconditioning

Poor nutritional statusPsychological problems


Disease Deficiency Incapacity Handicap

COPD Aw obstruction dyspnea prostration

COPD Bronchodilatation Tolerance Move

PULMONARY REHABILITATION


Goals

- General : Improve physical and psychological or emotional functioning of patients in interaction with theire environment

- Specific :- Reduce symptoms- Improve activity and daily function QOL- Restore the highest level of independant function (in every day activities)- Enhance knowledge of the disease- Improve self-management

Non pulmonary problems Not addressed by medical therapy

PULMONARY REABILITATION Components of the rehabilitation program

1- Optimal medical treatment2- Smoking cessation3- Exercise training4- Breathing retraining5- Chest physiotherapy6- Education7- Psychological aspects and support8- Nutritional therapy9- Nursing care10- Miscellaneous

PULMONARY REABILITATION Exercise Training

Limitations inability toO2 delivery to muscles

Needs

Exercise Training inefficiency of Adapted to the gaz exchange Individual lung mechanics hyper inflation flow limitation

Training programs pulmonary that stimulates hypertention cardiovascular and during exercise skeletal muscle muscle dysfunction

PULMONARY REABILITATION Exercise training

- Lower extremity training : lower limbs exercise- Upper extremity training : arms exercise- Respiratory muscles training : respiratory muscles exercise


Exercise training

ModalitiesInpatient settingOut patient settingCommunity based settingHome based setting

Inpatient setting- transdisciplinary team- favorable environnement and climate- Patient entire disponibility- 24 houres prolonged and tight management for weak patients


Exercise training

1- Methods- Cycle ergometer- Walking (Treadmill)Better physiological benefit when exercise above a «critical level of

intensity»2- Patients selection*

Preliminary exercise test Resting respiratory function measurements (poor correlation)

3- Type of exercise : - intensity** - endurance

4- Duration : No ideal duration established 8 weeks : common duration***

5- Results : Physiological change : **** blood lactate ventilation endurance

After high work rate training programs


Exercise trainingDuration of programsKey Goal change the patient’s behavion from a sedentary

toward a more active life style

Measurable physiological changes : weeks behavioral changes months

Longer duration

Better long term effect > 8 weeks 6 months > 3 mouths


Results

- Increase in maximal exercise performance- Physiologic adaptations in peripheral muscles - Improve of cardiac function - Reduction in ventilation and lactate levels at identical

exercise work rates

length indefinite 4-12 weeks

Long term effects

12 months

Maintenance +


Upper extremity Training- Improve arm muscles function- Does not improve exercise tolerance- Does not improve QOL


Outcome measures : exercise testing- COPD patients mean age : 60 years- Most COPD patients are past smokers- COPD patients are at risk of other tobaco-related

diseases : - ischemic cardiac diseases, arteriel HT, cardiac arrhythmias

- Stress test for coronary disease : - 1 death/5000- 1 major complication/1000

- Exercise testing in COPD patients : 1/3 arterial blood desaturation (SaO2 < 89 %) not predicted by rest spirometry nor CO diffusing capacity

- Need of a preliminary exercise test


Outcome measures : exercise testingsTypes of exercise tests

1- Submaximal exercise tests- cycle or treadmill- at a constant fraction of maximal work rate >

60 % of the peak V 02- at low intensity, below to the lactic acidosis

threshold- Measures exercise endurance- Measurements : endurance time, heart rate,

respiratory rate, blood pressure, ECG, SaO2, exhaled gazes, inspiratory capacity

Exercise trainingOut come measures : exercise testing

2- Six minute walk test- Walks at his own pace- Simple, well tolerated and relevant to daily activites- But varies upon encouragement and coaching and

should be standardized 3- Shuttle walk test

- Walk up and down a 10 m distance with increasing speeds dictated by a beep

- Measures more exercise capacity than endurance- But self pacing is eliminated- Reproductible and correlates well with VO2 peak

during increamental treadmill exercise ( r = 0,88)

Exercise trainingOutcome measures : exercise testing

Type of exercise tests 4- Incremental exercise tests

- bicycle or treadmill- Measurements : Heart rate, respiratory rate,

blood pressure, ECG, SaO2, dyspnea, leg fatigue, minute ventilation, oxygen consumption, CO2 production, anaerobic threshold and dead space

- Equipment problems : - Cost of the test : 30- Cost of equipement/test : 10

Level of Handicap Assessement MeasuresDeficiencies

Respiration FEV1- A Obstruction FRC- P.Elasticity IC- Gaz exchange DLCO PaO2, PaCO2, SaO2

Muscle

- Respiratory MIP- Limbs and arms MEP

Incapacity

Dyspnea - Questionaires - Walk test 6 min

Exercise - Endurance test - Exercise fonctional tests

Disadvantage(handicap) QOL questionairesLife socio-professional



Specific strategies to increase training intensityNeuromuscular electrical stimulation (NES)Specific muscle groups of lower limbs are activated with low-intensity

electrical current2 trials of transcutaneous neuromuscular electrical stimulation of

lower limbs in severe muscle weakness in stable patients - significant - muscle strength

- exercise capacity

1 study : faster functionnal recovery in patients with respiratory failure under mechanical ventilation, bed bound for > 30 days.

Zanotti E, Felicetti G, Maini M, Fracchia C. Peripheral musclestrength training in bed-bound patients with COPD receiving mechanicalventilation : effect of electrical stimulaiton. Chest 2003;124 : 292-296

NES is safe and can be conducted at home

Neder JA, Sword D, Ward SA, Mackay E, Cochrane LM, Clark CJ. Homebased neuromuacular electrial stimulation as pulmonary rehabilitation in chronic obstructuve pulmonary disease. Troosters et al


Specific strategies to increase training intensityBreathing exercises- Diaphragmatic breathing : Decreases breathing efficiency- pursed lip breathingIncreases gaz exchange, increases tidalvolume, reduces inspiratory time, reduces dyspnea, reduces

end expiratory volumes

Effectineness assessed by SaO2

Bianchi R, Gigliotti F, Romagnoli I. Chest wall kinematics and breathlessness during pursed-lip breathing in patients with COPD. Chest 2004 ; 125 : 459465.

Breslin EH. The pattern of respiratory muscle recruitment during pursed-lip breathing. Chest 1992 ; 101 : 75-78


Specific strategries to increase training intensityO2 supplementationControversialO2 supplementation - Reduces the ventilatory requirement for a given work

rate- increases maximal exercises tolerance- Reduces exercise – ruduced pulmonary hypertension- Studies did not show additional benefitO2 could enhance training intensity in patients with

COPDFunther studies


Specific strategies to increase training intensity Non invasive Mechanical Ventilation(NIMV) - reduces the inspiratory muscles load.- Usefulness only in severily impaired patients Hawkins P, Johnson LC. Proportional assist ventilation as an aid to exercise training in severe chronic obstructive pulmonary

disease. Thorax 2002;57:853-859Costes F, Agresti A, Noninvasive ventilation during exercise training improves exercisetolerance in patients with chronic obstructive pulmonary disease. J cardiopulm Rehabil 2003;23:307-313

- NIMV at home associated to out patient exercise training additional increase in the shuttle walk distance

QOL compared to training alone

Garrod R, Mikelsons C Paul EA. Randomized controlled trial of domiciliary noninvasive positive pressure ventilation and physical training in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 162:1335-1341


Specific strategies to increase training intensityErgogenic drugs Anabolic steroïds (AS)- Studies included only men- Drugs studied are oxandrolone, nandrolone, stanozolol and testosterone - All studies report an increase in body weight through a gain in lean body mass4 studies : AS + PRH program

Muscle strength Effects of strength training - does not improve exercise endurance (muscle hypertrophy without capillary

and aerobic enzymes increase)

Protection against side effects of corticosteroïdsNI prostate hypertrophy, aProstate cancer, Hb > 16g. Dl-1, Renal disease, Congestive heart failure

Growth hormone/Insulin like growth hormone- Disturbed anabolic/catabolic balance in COPD- Lack of evidence of benefits – high cost

- Schols AM, Soeters PB, Mostert R, Pluymers RJ. Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease : a placebo controlled randomized trial. Am J Respir Crit Care Med 1995;152 : 1268-1274

PULMONARY REABILITATION Components of the rehabilitation

program

- Smoking cessation the key to the prevention and treatment of COPD

- Give up- early stages interventions Reduced rate of FEV1 decline- Function lost is however not regained- Advanced disease, still valuable

- Maintenance of abstinence : beyond the phase of acute withdrawal for extended periods thereafter


Smoking cessationAddiction

- Nicotine substitutes- Psychological- Behavioral- Physiological

Hard to accomodate the needs of every smoker

Strategies Individual adapted programs Rather than group programs

Pharmacological interventions Behavioral interventions


Education and self-management : Optimally control the disease Achive behavioral change Improve coping with the disease

Up to 75 % of patients have difficulties in understanding how and when to take their

inhalation medication

Goodman DE, Israel E, Rosenberg M, Johnston R, Weiss ST, Drazen JM. The influence of age, diagnosis, and gender on proper use metered-dose inhalers. Am J Respir Crit Care Med 1994;150:1256-1261

Educational sessions - Improve adherence to medication- Help patients to deal with exacerbations- Reduce hospital days - Cost effective- QOL

Helpful for patients with severe disease, Small groups-or individual

Gallefoss F, Bakke PS. Cost-benefit and cost-effectiveness analysis of self-management in patients with COPD : a 1-year follow-up randomized, controlled trial. Respir Med 2002;96:424-431

PULMONARY REABILITATION Psychosocial support

Rationale : - Depression in COPD 2.5 fold higher/general population- 20-40 % of COPD present with anxiety and depression- Spouses of COPD suffer from depression and stress- Smoking cessation result in mood disturbance.Psychological interventions improve mood distrubances > exercise training only.Can be associated to smoking cessation counselling, support and to education. Enhance the chances for sustained smoking cessation

PULMONARY REABILITATION Improving activities of daily living

Occupational therapyOccupational therapists interventionsaim to increase the patient functionalautonomyMethods consist of exercise trainingoriented toward daily living activities(walking efficiency, ventilatory capacity..)Wheeled devices (rollators) are useful butexpensiveThey could be useful in severe diseases


Nutritional Programs

- In COPD,- of body weight- Loss of fat-free mass is related to morbidity and

mortality - > 2 kg of body weight improve survival

- resting energy expenditure Exercise traing may induce a negative protein balance

But – it is no sure that patients receiving nutritional supplements would not distrub their regular nutritional habits with a consecutive reduced calorie intake and risk of paradoxal undernourishment.- At the opposite, obese patients should undergo weight loss through a dietary intervention without loosing fat-free mass.


Miscellaneous- Erythropoietin therapy- antioxidant therapy (Vit E, Nacetyl cysteine)- Brondilators associated to PRH improvements in QOL- In selected subpopulations individualized programs- Does not concern all patients

- Physiotherapy - sputum drainage

PULMONARY REABILITATIONUse of health care resources

Benefit of PRH is due to improved knowledge of the disease and enhanced self-management rather to physiological improvements

Admissions are reduced by 40 % when a self management program is followed despite significant physiological effects

No decrease in hospital days for long term exercise training without individualized education sessions and self management strategies.

Engström CP. Long-term effects of a pulmonary rehabilitation programme in outpatients withchronic obstructive pulmonary disease : a randomized controlled study. Scand J Rehabil Med1999;31:207-213.

Reduction in mild exacerbations may lead to stop disease progression

Exacerbation frequency linked FEV1 decline

Donaldson GC. Relationship between exacerbation frequency and lung functiondecline in chronic obstructive pulmonary disease. Thorax 2002;57:847-852

PULMONARY REABILITATIONUse of health care resources ( cost-effectineness)

- necessity of long – term followingReduction of hospitalization Griffithsetal patients with COPD spent fewer days

hospitalized during a 1 year follow-up period.

Griffiths TL, Burr ML, Campbell IA. Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation : a randomised controlled trial. Lancet2000 ; 355 : 362 - 368

Out patients PRH reduces hospital days but studies lacked statistical power

Hospital days are the primary cost driver of COPD care

Croxton TL, Weinmann GG, Senior RM. Clinical research in chronic obstructive pulmonary disease :

needs and opportunities. Am J Respir Crit Care Med 2003 ; 167 : 1142 - 1149


Maintenance strategiesSeveral strategies have been tried tomaintain the benefits as long as possibleafter graduation from PRH programs

- Continued 3 times weekly out patient 15 months - Once week high – intensity exercise training sessions - Exercise advise during the follow-up- Repeated short programs- Telephone support- Once monthly follow-up visits

Maintenance programs seem to benecessary after 6 weeks out patients or 6weeks in patients.After longer programs (6 months), benefitscould be prolonged for > 1 year.


SurvivalNo study has convincingly shown evidence of improved survival after PRH In 7 studies

Best estimate : Rehabilitation reduces short-term risk of dying by 31 %. Not statistically significant ( nb of patients insufficient, patients on PRH are in a stable state)Further studies

PRH group Control group

12 – 18 months mortality risk

7.8 % 9.9 %

Nb death 23/315 28/283

Odds of dying in PRH groupRelative risk,

0.69

0.38 – 1.25 ; p =0.395

Conclusion In COPD muscle deficiency and flow

limitation lead to deficiency and handicap PR enhances exercise capacity, improves

daily life activities and ameliorate QOL A successful PR is scientific,

transdisciplinary, individualised and sustained for at least 8 weeks

PR is cost effective Further studies are needed for specific

added stategies

Documents

PULMONARY REABILITATION A. CHABBOU MD MP Journées Scientifiques: SOUSSE LE 25 FEVRIER 2006