COPD UPDATE 2012 ıdr Shitrit David ıhead of the Pulmonary Department ımeir Medical Center
Definition of COPD COPD is a preventable and treatable disease with some significant extra pulmonary effects that may contribute to the severity in individual patients. Healthy Alveolus The airflow limitation is usually progressive associated with an abnormal inflammatory response of the lung to noxious particles or gases. COPD
Of the six leading causes of death in the United States, only COPD has been increasing steadily since 1970. Source: Jemal A. et al. JAMA 2005 2
COPD Mortality by Gender, U.S., 1980-2000 70 Number Deaths x 1000 60 50 40 30 20 10 0 1980 1985 1990 1995 2000 Men Women
COPD Mortality Worldwide Ischaemic heart dis Cerebrovascular dis Lower resp infection Diarrhoeal disease Perinatal disorders COPD Tuberculosis Measles Road Traffic Accidents Lung Cancer 6th 1990 2020 3rd Stomach Cancer HIV Suicide Source: Murray & Lopez. Lancet 1997
Diagnosis of COPD SYMPTOMS cough sputum shortness of breath EXPOSURE TO RISK FACTORS tobacco occupation indoor/outdoor pollution è SPIROMETRY
Classification of COPD Severity by Spirometry (2008) Stage I: Mild FEV 1 /FVC < 0.70 FEV 1 > 80% predicted Stage II: Moderate FEV 1 /FVC < 0.70 50% < FEV 1 < 80% predicted Stage III: Severe FEV 1 /FVC < 0.70 30% < FEV 1 < 50% predicted Stage IV: Very Severe FEV 1 /FVC < 0.70 FEV 1 < 30% predicted or FEV 1 < 50% predicted plus chronic respiratory failure 6
ıbode Index FEV1 6MWD MMRC Dyspnea scale BMI Celli BR, NEJM 2004
Symptom variability in patients with severe COPD: a pan-european cross-sectional study ı
Symptom variability in patients with severe COPD: a pan-european cross-sectional ıstudy
Obstructive Pattern
GOALS of COPD MANAGEMENT Relieve symptoms Prevent disease progression Improve exercise tolerance Improve health status Prevent and treat complications Prevent and treat exacerbations Reduce mortality 01
Therapy at Each Stage of COPD I: Mild II: Moderate III: Severe IV: Very Severe FEV 1 /FVC < 70% FEV 1 /FVC < 70% FEV 1 /FVC < 70% 50% < FEV 1 < 80% predicted ı ı FEV 1 /FVC < 70% 30% < FEV 1 < 50% predicted ı FEV 1 < 30% predicted or FEV 1 < 50% predicted plus chronic respiratory failure FEV 1 > 80% predicted Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed) Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations Add long term oxygen if chronic respiratory failure. Consider surgical treatments
Early Therapy Improves Outcomes of Exacerbations of Chronic Obstructive Pulmonary Disease Wilkinson et al. AJRCCM 2004 Effect of early treatment on recovery of exacerbation symptoms
Severe acute exacerbations and mortality in patients with COPD Soler-Cataluña et al. THORAX 2005 Kaplan-Meier survival curves by severity of exacerbations in patients with COPD: (1) no acute exacerbations of COPD (2) patients with acute exacerbations of COPD requiring emergency service visits without admission (3) patients with acute exacerbations of COPD requiring one hospital admission; (4) patients with readmissions
COPD EXACERBATIONS An event in the natural course of the disease characterized by a change in the patient s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.
COPD EXACERBATIONS- Precipitating factors Infections (respiratory and nonrespiratory) Exposure to respiratory irritants and air pollution Co-morbid diseases (CHF, PE, IHD, Pneumothorax)
Severe acute exacerbations and mortality in patients with COPD Soler-Cataluña et al. THORAX 2005 ı Kaplan-Meier survival curves by frequency of exacerbations in patients with COPD: group A, patients with no acute exacerbations of COPD group B, patients with 1 2 acute exacerbations of COPD requiring hospital management group C, patients with 3 acute exacerbations of COPD
COPD EXACERBATIONS-Management Inhaled BD Treatment Systemic steroids (PO vs IV) Usually 2 weeks course Oxygen supply- at the lowest level needed Antibiotics No extensive evaluation for the cause of the exacerbation if it responds to initial treatment.
AE-COPD: Etiology 25% viruses 26% bacteria 27% combination of the two 22% other causes
COPD EXACERBATIONS-Management Inhaled BD Treatment Systemic steroids (PO vs IV) Usually 2 weeks course Oxygen supply- at the lowest level needed Antibiotics No extensive evaluation for the cause of the exacerbation if it responds to initial treatment.
Treatment failure of AE-COPD Change antibiotics with good coverage against P. aureginosa. Exclude Cor Pulmonale or CHF by Echo. Exclude PE and Pneumothorax Add aminophylline Exclude GERD
Pneumothorax in COPD Patients COPD is the most common cause for secondary spontaneous pneumothorax ı Due to rupture bleb hyperinflation mechanical ventilation Always in the DD of COPD Exacerbation CT scan should be perform in difficult cases. Definite treatment: VATS -pleurodesis
Core Pulmonale in COPD Causes Chronic alveolar hypoxemia Lung hyperinflation Increase blood viscosity Physical findings are late signs Peripheral edema is poorly correlated with RHF Echo measures of PAP are often inaccurate and may over diagnose pulmonary hypertension. No evidence to Anticoagulation Very important prognostic factor with 2 years survival less than 50% if PAP >45mmHg.
Co-morbidity in COPD l Cardiovascular morbidity. l Muscle wasting. l Osteoporosis. l Metabolic syndrome.
CVD and COPD Univariate Multivariate adjusted for age, sex, race, smoking status, pack-years, diabetes mellitus, BMI, education level, hypertension, HDL-C, LDL- C, fibrinogen Johnston et al, Thorax 2008
Prevalence of CVD in COPD Odds ratio 8 7 6 5 4 3 2 1 0 Arrhythmia Angina Acute Myocardial Infarction Congestive Heart Failure Stroke Pulmonary Embolism Other Cardiovascular Disease Curkendall et al, AEP 2006
Cachexia in COPD CHRONIC ILLNESS e.g. Chronic heart failure, Chronic obstructive pulmonary disease, Chronic kidney disease, Chronic infection & Sepsis, Cancer Anorexia Inflammation Insulin resistance Hypogonadism FAT LOSS MUSCLE WASTING Evans et al, Clin Nutr 2008
Body composition in COPD Percentage Source: Eclipse study
Clinical consequences of osteoporosis Acute and chronic pain Kyphosis Loss of height Loss of mobility Bulging abdomen, reflux and other GI symptoms Breathing difficulties Depression Loss of independence REDUCED QUALITY OF LIFE
Prevalence of osteoporosis in COPD 35 30 Osteoporosis: Tscores 2.5 25 20 15 male female 10 5 0 no mild moderate severe Sin et al, Am J Med 2003
Co-morbidity and prognosis Time to first hospitalisation within 5 years Predict time to first hospitalisation within 5 yrs by modified GOLD category and the presence of no ( ), one ( ), two ( ) or three ( ) comorbid diseases (diabetes, hypertension or cardiovascular disease). Mannino et al, ERJ 2008
Co-morbidity and prognosis Death within 5 years Predict death within 5 yrs by modified GOLD category and the presence of no ( ), one ( ), two ( ) or three ( ) comorbid diseases (diabetes, hypertension or cardiovascular disease). Mannino et al, ERJ 2008
Disease network of COPD CV Muscle wasting
COPD management moving from reductionism to an integrated approach to define, identify, and treat the multiple organ involvement of this complex syndrome.
Treatment of stable COPD Smoking cessation. Drug medications. Vaccinations. Oxygen therapy. Rehabilitation. Nutrition. Surgery.
Treatment of stable COPD Smoking cessation. Drug medications. Vaccinations. Oxygen therapy. Rehabilitation. Nutrition. Surgery.
Long-acting anticholinergics Tiotropium bromide Duration of action of more than 24 hours Regular use improves lung function 1,2, symptoms and health status, 1,2 reduces exacerbations, 3,4 and improves the effectiveness of a pulmonary rehabilitation programe 5 A long-term study is currently evaluating the effect on tiotropium bromide in the rate of decline in lung function 6 Side-effects Urinary retention, dry mouth, constipation 1. Casaburi R. Eur Respir J 2002; 2. Vincken W et al. Eur Respir J 2002; 3. Niewoehner DE et al. Ann Intern Med 2005; 4. Dusser D. Eur Respir J 2006; 5. Casaburi R et al. Chest 2005; 6. Decramer M. COPD 2004
GOLD steps of management I Mild II Moderate III Severe IV Very severe FEV 1 /FVC <0.70 FEV 1 80% predicted FEV 1 /FVC <0.70 50% FEV 1 <80% predicted Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed) FEV 1 /FVC <0.70 30% FEV 1 <50% predicted FEV 1 /FVC <0.70 FEV 1 <30% predicted or FEV 1 <50% predicted plus chronic respiratory failure Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations GOLD guidelines. www.goldcopd.com Add long-term oxygen if chronic respiratory failure Consider surgical treatments
Combination ICS/bronchodilator therapy - Triple therapy ıbackground An inhaled glucocorticosteroid combined with a long-acting β 2-agonist is more effective than the individual components in reducing exacerbations and improving lung function and health status ı(evidence A).
Formulations and typical doses of COPD medications Updated GOLD 2010 Drug Inhaler Oral Duration of Action (Hours) ıindacaterol Long Acting ıroflumilast ı150-300(dpi) ı24 ı500 mcg (Pill) ı24 PDE4 Inh.
ıpreventive treatment in COPD LABA LAMA ICS
Management of Stable COPD Non-Pharmacologic Treatments Rehabilitation: All COPD patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A). Oxygen Therapy: The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival (Evidence A). 32
Pulmonary Rehabilitation Improve the dyspnea, exercise ability, health status. Minimal effects on PFTs. Multidiscipilinary program. Should be considered for patients with symptomatic COPD. For patients with moderate to severe COPD (FEV1<80%)
Maximal Exercise Capacity Walking distance - Endurance capacity Relief of symptoms ( dyspnea and fatigue) Quality of life Utilization of health care resources Mortality?
COPD Indications for Hospitalization ATS/ ERS Guidelines Sudden onset of new or severe symptoms Severe or very severe underlying COPD Onset of new physical findings (edema, change in mental status) Failure to respond to initial medical treatment Associated comorbidities Diagnostic uncertainty (pneumonia? PE?) Older age Inadequate home or social support History of poor adherence with treatment
ADULT LUNG TRANSPLANTATION( Alpha-1 COPD CF IPF PPH Re-Tx Other* 13% 6% 2% 17% 29% 9% 24% ISHLT 2008
ADULT LUNG TRANSPLANTATION 100 HALF-LIFE 18-34: 5.2 Years; 35-49: 5.6 Years; 50-59: 4.7 Years; 60-64: 3.9 Years; 65+: 3.4 Years Survival (%). 75 50 25 0 ISHLT 18-34 (N= 3,718) 35-49 (N= 5,687) 50-59 (N= 7,402) 60-64 (N= 2,764) 65+ (N= 710) 0 1 2 3 4 5 6 7 8 9 10 Years Survival comparisons 18-34 vs. 50-59: p <0.0001 18-34 vs. 60-64 and vs. 65+ : p < 0.0001 35-49 vs. 50-59, 60-64 and 65+: p < 0.0001 50-59 vs. 60-64 and vs. 65+: p < 0.0001 60-64 vs. 65+: p =.0548