Managing COPD --- New Standard of Care

Transcription

1 Managing COPD --- New Standard of Care

2 Introduction Pathophysiology Recent advance in treatment Pharmacology Pulmonary rehabilitation Surgical treat

3 Facts About COPD COPD is the 4 th leading cause of death in the United States (behind heart disease, cancer, and cerebrovascular disease). In 2000, the WHO estimated 2.74 million deaths worldwide from COPD. In 1990, COPD was ranked 12 th as a burden of disease; by 2020 it is projected to rank 5 th.

4 Five leading causes of death by the year 2020 Ischaemic heart disease Cerebrovascular disease COPD Lower respiratory infections Trachea, bronchus and lung cancers 0 2,000 4,000 6,000 8,000 10,000 12,000

5 Respiratory diseases in developing countries communicable tbc, pneumoina, etc. % % changes in: demographics, HCSs schooling, income, tobacco XXth non-communicable asthma, COPD, lung cancer XXIth

6 Percent Change in Age-Adjusted Death Rates, U.S., Proportion of 1965 Rate Coronary Heart Disease Stroke Other CVD COPD All Other Causes % 64% 35% +163% 7%

7 CONTRIBUTING FACTORS (1) tobacco smoke indoor pollution outdoor pollution occupation malnutrition low birth weight COPD CRD LC Asthma atopy hygiene multiple early lung infections + indoor allergens

8 Goal of the strategy to support Member States in their efforts to reduce : MORBIDITY DISABILITY MORTALITY COPD CRD LC Asthma

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10 Pathophysiology of COPD and Asthma Noxious agent COPD Asthma Sensitizing agent CD8 + lymphocyte Alveolar macrophage Mast cell CD4 + lymphocyte Cytokines (IL-8) Mediators (LTB 4 ) Neutrophil Eosinophil Histamine Cytokines (IL-4, IL-5, IL-13) Mediators (LTD 4 ) Proteases Alveolar wall destruction Mucus hypersecretion Epithelial shedding Airway hyperreactivity Inflammatory mediators Airway thickening Barnes PJ (1999; 2000)

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12 Differential Diagnosis of COPD and Asthma Age of onset Smoking history Family history COPD Usually >35-40 yrs Usually >20 pack-years Uncommon (except α 1 -antitrypsin disease) Asthma Any age (usually 40 yrs) Independent of smoking Usually Airway reversibility Not fully reversible Only partially reversible with bronchodilator use Smoking cessation can slow the decline in lung function Largely reversible Usually near-normal pulmonary function Barnes PJ (1999)

13 Differential Diagnosis (Continued) Symptom pattern Cough (most prominent) Purulent sputum Elevated IgE Eosinophils COPD Usually chronic Slowly progressive Nonspecific Early morning Typical Uncommon Uncommon Asthma Varies day by day Nocturnal/early morning Nocturnal Post-exercise Uncommon Common Common Barnes PJ (1999)

14 Severity of Disorder COPD (GOLD) FEV1 Step down? Treatment in stationary period? GINA Attack frequency Step down Treatment in stable period?

15 Overlapping Area Asthma? COPD

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23 Tidal Volume at rest Inspiration IRV V T Breathing frequency at rest: / min EILV Healthy Mild COPD Severe COPD ERV Expiration =4 sec Healthy subjects: COPD patients: EELV breathing rest time less breathing rest time

24 TLC FRC Dynamic Hyperinflation Normal Static Hyperinflation Dynamic Hyperinflation IC IRV V T ERV RV Air trapping at rest Years - Decades Air trapping from exertion Seconds - Minutes

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27 Factors Determining Severity Of COPD Severity of symptoms Severity of airflow limitation Frequency and severity of exacerbations Presence of complications of COPD Presence of respiratory insufficiency Comorbidity General health status Number of medications needed to manage the disease

28 New Classification of Severity Old 0:At Risk I:Mild II:Moderate III:Severe IIA IIB New 0:At Risk I:Mild II:Moderate III:Severe IV:Very Severe Chronic symptoms FEV1/FVC< 70% FEV1/FVC<70 % FEV1/FVC< 70% FEV1/FVC< 70% Exposure to risk factors Normal spirameter FEV1> 80% With or without symptoms 50%< FEV1< 80% With or without symptoms 30%< FEV1< 50% With or without symptoms FEV1< 30% or presence of chronic respiratory failure or right heart failure

29 0:At Risk I:Mild II:Moderate regular treatment with one or more long-acting bronchodilators rehabilitation III:Severe Avoidance of risk factor(s); influenza vaccination IV:Very Severe short-acting bronchodilator when needed inhaled glucocorticosteroids if repeated exacerbations long-term oxygen if chronic respiratory failure surgical treatments

30 New Recommendations Long acting bronchodilators Inhalation steroid and/or long-acting B 2 -agonist Pulmonary rehabilitation Surgical treatment

31 Bronchodilators in Stable COPD Bronchodilator medications are central to symptom management in COPD. Inhaled therapy is preferred. The choice between Beta 2 -agonist, anticholinergic, theophylline or combination therapy depends on availability and individual response in terms of symptoms relief and side effects.

32 Long Acting Bronchodilator Regular use of long acting bronchodilator rather than short acting one in moderate to very severe COPD Tiotropium Evidence A

33 Long Acting Anti-cholinergic Drug Most promising medication for COPD

34 Patient Characteristics at Screening: 1-Year and 6-Month 6 Trials Number Male (%) Tio Pbo Tio Ipra Tio Sal Pbo Age (yrs) Duration of COPD (yrs) Baseline FEV 1 (L) FEV 1 % pred (L) FEV 1 /FVC (%) Placebo-controlled controlled trials Ipratropium-controlled trials Salmeterol- and placebo-controlled controlled trials Casaburi R et al. Eur Respir J (2002) Vincken W et al. Eur Respir J (2002) Brusasco V et al. Thorax (2003)

35 Mean FEV 1 Over 6 Months in Combined Salmeterol Trials 1.35 Day 1 Day 169 Tiotropium (n=386) FEV 1 (L) Salmeterol (n=388) Placebo (n=362) T-S= 70 ml T-P= 210 ml* Time after administration (minutes) *P<0.0001; P<0.001 Brusasco V et al. Thorax (2003)

36 Change from Baseline in Trough FEV 1 Over 1 Year (Versus Ipratropium) 200 Trough FEV 1 (ml) Tiotropium (n=329) T-I= 160 ml -50 Ipratropium (n=161) Test day P< at all timepoints Vincken W et al. Eur Respir J (2002)

37 Steroid Inhalation Regular use of steroid only in moderate to severe COPD Response to short tem course of steroid FEV < 50% of predict with frequent exacerbation 2001 evidence B Inhaled steroid in severe to very severe COPD with frequent exacerbation 2003 evidence A

38 Fluticasone in COPD Eur Respir J 2003; 21:68

39 ICS reduce the rate of decline in FEV 1 in COPD The highly potent steroids budesonide, fluticasone and beclomethasone reduce the annual decline in FEV 1 by 9.87 ml/y [p=0.01] Weir et al Pauwels et al Vestbo et al Burge et al All studies combined Annual change in FEV 1 (ml/y) ICS worse ICS better Sutherland et al poster presentation at ATS 2002

40 Manage Stable COPD Regular treatment with inhaled glucocorticosteroids should only be prescribed for symptomatic COPD patients with a documented spirometric response to glucocorticosteroids or in those with an FEV 1 < 50% predicted and repeated exacerbations requiring treatment with antibiotics and/or oral glucocorticosteroids (Evidence B).

41 Combination Therapy Steroid and long acting beta agonist

42 Lung function Patient demographics (2) Mean FEV 1, L Mean FEV 1, % predicted Mean reversibility, % predicted Szafranski 0.99 Calverley Patients with reversibility >15% and >200 ml, % Mean FEV 1 /VC Szafranski W, et al. Eur Respir J 2003;21:74 81 Calverley PM, et al. Eur Respir J 2003; 22:

43 FEV 1 measured at clinic visits Mean ratio in FEV 1 of baseline (%) Szafranski Time from randomisation (months) p<0.001 Symbicort vs placebo and budesonide; p<0.001 formoterol vs placebo; p=0.005 budesonide vs placebo Szafranski W, et al. Eur Respir J 2003;21:74 81 Calverley PM, et al. Eur Respir J 2003; 22: Calverley Time from randomisation (months) Symbicort Formoterol Budesonide Placebo p<0.001 Symbicort vs placebo and budesonide; p=0.002 Symbicort vs formoterol; p<0.001 formoterol vs placebo

44 Pre dose FEV1 in FSC, S, F and placebo Pre dose FEV1 in FSC, S, F and Placebo 1,352 patients screened in this study, 691 randomized Am J Respir Crit Care Med Vol 166. pp , 2002

45 Cumulative Risk of Acute Exacerbations Lancet 2003; 361:

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47 Effect of Medications in COPD Outcome Short-acting β agonists Ipratropium bromide Long-acting β agonists FEV1 Lung volume Dyspnoea HRQoL AE Exercise endurance Disease modifier by FEV1 Mortality Side-effec ts Yes A Yes B Yes A NA NA Yes B NA NA Some Yes A Yes B Yes A No B Yes B Yes B No NA Some Yes A Yes A Yes A Yes A Yes A Yes B No NA Minimal Tiotropium Yes A Yes A Yes A Yes A Yes A Yes B NA NA Minimal Inhaled corticosteroids Yes A NA Yes B Yes A Yes A NA No NA Some Theophylline Yes A Yes B Yes A Yes B NA Yes B NA NA Important ATS/ERS COPD Standard

48 Pulmonary Rehabilitation Reduce symptoms Improve quality of life Increase physical and emotional participation in everyday activities

49 Psychoscocial Consequence of COPD Lack of Fitness COPD Dyspnea Immobility Depression Social Isolation

50 Benefits of Pulmonary Rehabilitation Improves exercise capacity Reduces the perceived intensity of breathlessness Improve health related quality of life Reduce number and days of hospitalization Reduce anxiety and depression with COPD Upper extremity training improve arm function Improves survive Respiratory training is beneficial Psychococial intervention if helpful

51 Indication of Rehabilitation No definite describe of indication Beneficial from exercise in all stage Beneficial from inpatient, outpatient, and home setting Choosing patient Functional status Severity of dypsnea Motivation Smoking status

52 Pulmonary rehabilitation ERS ATS BTS Overview Indication Muscle weakness Utilisation, symptoms Function on optimal therapy Mod/sev disease Education Exercise training Lower extremity Upper extremity + Inspiratory muscle - - -

53 Components of Rehabilitation Exercise training Nutrition counseling education

54 Pulmonary rehabilitation ERS ATS BTS Overview Indication Muscle weakness Utilisation, symptoms Function on optimal therapy Mod/sev disease Education Exercise training Lower extremity Upper extremity + Inspiratory muscle - - -

55 Assessment of Exercise Tolerance Bicycle ergometry (treadmill exercise) Maximal oxygen consumption, heart rate and work performed 6 minutes walking (self placed, timed) Shuttle walking test

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57 Training Program (I) Frequency : daily to weekly Duration: 10 to 45 minutes/session Intensity : 50% peak oxygen consumption to maximum Length : 4 to 10 weeks Longer program result in larger effects

58 Training Program (II) Goals Predetermined target heart rate (difficult for COPD) Walk to a symptom-limited maximum, rest, continue to walk till 20 minutes Exercise their own (benefit?) Other strength training Upper extremity Inspiratory muscle

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62 Components of Rehabilitation Exercise training Nutrition counseling education

63 Pulmonary rehabilitation (cont d) ERS ATS BTS Breathing retraining + Psychosocial support Nutrition Home mechanical ventilation Elective? - Non-elective?? Follow-up + + Home care + +

64 Nutrition in COPD Nutritional status is an important determinant of symptoms, disability and prognosis in COPD 25% of patients with moderate to severe patients reduce their body mass index and fat free mass ( independent risk factor for mortality in COPD) Nutrition recommendation comes from expert opiion and some small randomized clinical trials

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67 Nutrition in COPD Identify the reasons for reduced calorie intake Poor dentition?, dyspnea while eating? Improved nutrition status can improve inspiratory muscle strength Cost effective? Best accompanied by exercise regimens

68 Inspiratory Muscle Training in COPD Improve in inspiratory muscle strength

69 Inspiratory Muscle Training in COPD Improve in functional exercise capacity

70 Maintenance of Rehabilitation Am J Respir Crit Care Med Vol 167. pp , 2003

71 Manage Stable COPD --- Pulmonary Rehabilitation All COPD-patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A).

72 Summary of PR guidelines Frequency: 2-5 sessions per week for OPD min per session Duration: 6-8 weeks, 12 weeks Intensity: 60-80% maximal VO2 or 60-90% pred maximal HR High intensity(60-80%) with greater magnitude of effect Specificity: Endurance training ( ET) or Strength training (ST) Peripheral m training: Lower extremities (LE) and Upper extremities (UE) Inspiratory m training (IMT) and Breathing technique

73 Outcome ( summary by BTS, 2001) 1.Functional exercise capacity (Ia) 2.Health status (Ia) 3.Dyspnea (Ia) 4.Economic advantage (Ib)

74 Surgical Treatment Bullectomy Lung volume reduction surgery (LVRS) Lung transplantation

75 Bullectomy in COPD Indication Alleviate local symptoms Hemoptysis, chest pain, infection Reducing dyspnea? Patients choice Bullus occupy more than 50%,displacement signs, reduction in perfusion Normal DLCO, less hypoxemia Pulmonary hypertension, hypercapnia and sever emphysema are not absolute contraindication

76 Factors of Outcome in Bullectomy Parameter Favourable Unfavourable Clinical Rapid progressive dyspnoea despite maximal medical therapy Ex-smoker Physiological Normal FVC or slightly reduced FEV1 >40% pred Little reversibility High trapped lung volume Normal or near normal DL, CO Normal PaO 2 and Pa, CO 2 Older age Co-morbid illness Cardiac disease Pulmonary hypertension >10% weight loss Frequent respiratory infections Chronic bronchitis FEV1 <35% pred Low trapped gas volume decreased DL, CO Imaging CXR Bulla > 1/3 hemithorax Vanishing lung syndrome Poorly defined bullae CT Large and localised bulla with vascular crowding and normal pulmonary parenchyma around bulla Multiple ill-defined bullae in underlying lung Angiography Isotope scan Vascular crowding with preserved distal vascular branching Well-localised matching defect with normal uptake and washout for underlying lung Vague bullae; disrupted vasculature elsewhere Absence of target zones, poor washout in remaining lung ATS/ERS COPD Standards

77 Lung Volume Reduction Surgery Resects parts of lung to reduce hyperinflation Respiratory muscle more effective pressure generation Increase elastic recoil pressure of lung (improve flow rate)

78 Lung Volume Reduction in COPD National Emphysema Treatment Trial (NETT)

79 Lung Volume Reduction in COPD National Emphysema Treatment Trial (NETT)

80 Group B: lower mortality, better exercise capacity and health status Groups C and D: did not benefit from improved survival but had signifi cant improvements in exercise capacity and health status Group A and E had higher mortality and would, therefore, not be candidates for LVRS

81 Lung Volume Reduction Surgery Patients selection FEV1< 35%, PaO2< 45 mmhg at rest Predominant upper lobe emphysema on CT Residual volume > 200% predicted Procedure Bilateral upper part resection Median sternotomy or VATS Perioperative mortality less than 5% Outcome Increase FEV1 from 32-93%, decrease TLC 15-20% Effect lasting more than one year

82 LVR Cost Effectiveness All patients except those who were at high risk for death from LVR the cost-effectiveness ratio for surgery as compared with medical therapy was $190,000 per qualityadjusted life-year gained. One quarter of patients identified by the NETT investigators as the ones most likely to benefit, the costeffectiveness ratio at three years was lower but still high, at $98,000 per quality-adjusted life-year gained. Other medical procedures, such as dialysis or coronaryartery bypass grafting, carry lifetime cost effectiveness ratios of approximately $60,000 per quality-adjusted lifeyear gained or less.

83 Lung Transplantation Patients selection FEV1 < 35% predicted, PaO2 < mmhg, PaCO2> 50mmHg and pulmonary HT Improve in quality of life and functional capacity in selected patients Not confer survive benefit two years later (network for Organ Sharing, 1998) Limitation Donor High cost ( 110,000 to 200,000) and annul cost

84 Management of COPD In selecting a treatment plan, the benefits and risks to the individual, and the direct and indirect costs to the individual, his or her family and the community must be considered.