Pathophysiology of COPD 건국대학교의학전문대학원

Transcription

1 Pathophysiology of COPD 건국대학교의학전문대학원 내과학교실 유광하

2 Rate per 100 0,000 population Heart disease Cancer Stroke Year of Death 75,000 population 50 Accidents Chronic Obstructive Pulmonary Disease Rate per Diabetes Melitus Year of Death JAMA 2005;294:1255 2

3 전체 (40 세이상 ) 남자여자 대상자수 정상 (0.9) 80.6 (1.5) 92.1 (1.0) GOLD (0.6) 8.0 (1.0) 2.9 (0.6) 94% GOLD (0.6) 10.1 (1.1) 4.8 (0.8) GOLD (02) (0.2) (04) (0.4) (01) (0.1) GOLD (0.1) 0.2 (0.1) 0.0 (-) Total 13.4 (0.9) 19.4 (1.5) 7.9 (1.0) Respirology 2011;16:659

4 Definition of COPD COPD is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually yprogressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases. GOLD 2008

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6 Smoking

7 Cigarette smoke Biomass particles Particulates Pathogenesis of COPD Host factors Amplifying mechanisms Anti-oxidants LUNG INFLAMMATION Anti-proteinases t i Oxidative stress Proteinases Repair mechanisms COPD PATHOLOGY GOLD 2008

8 Variation of Inflammatory cells and markers in the Variation of Inflammatory cells and markers in the bronchial submucosa

9 Proteases and Antiproteases involved in COPD

10 Oxidative Stress-Mediated Lung Injury in COPD Oxidative stress Epithelial permeability Lipid peroxidation Depletion of Antioxidant glutathione NK-KB activation and histone acetylation Transcription of Transcription of proinflammatory cytokine genes APOPTOSIS INJURY INFLAMMATION

11 만성기관지염 (Chronic Bronchitis) 특별한원인없이 1 년에기침을유발할정도의과도한객담이일년에 3개월이상최소한2년이상지속될때 : 임상적진단 Normal Chronic bronchitis

12 폐기종 (Emphysema) 종말기관지 (terminal bronchiole) 이하폐포중격 (alveolar septa) 의 파괴로인해 air space 가확장되는것 : 해부학적진단

13 Pathophysiology of COPD 1. Mucus hypersecretion & ciliary dysfunction 2. Airflow limitation it ti & hyperinflation - inflammation and narrowing of pph airways 3. Gas exchange abnormalities - parenchymal destruction of emphysema 4. Pulmonary hypertension & Cor pulmonale 5 5. Systemic effects GOLD. AJRCCM 2007;176:532

14 Glandular hypertrophy

15 Lung resection from 10 smoker with CB and chronic airflow limitation, 10 smoker with normal lung function, 9 non-smoker FEV 1 /F FVC (%) r = p = Goblet cells/mm 2 Am J Respir Crit Care Med 2000;161:1016

16 Mechanisms of airflow limitation Pel= Palv - Ppl V = Pel / R V = Pel / R Airway dysfunction V = Pel /R Loss of elastic recoil

17 Parenchymal tethering 정상 Normal COPD

18 Inspiration small airway Normal Air Trapping in COPD Mild/moderate COPD Severe COPD alveolar attachments loss of elasticity loss of alveolar attachments Expiration closure Health status Dyspnea yp Exercise capacity Air trapping Hyperinflation GOLD 2008

19 Natural History of COPD TLC=IC+FRC=VC (IC+ERV)+RV RV/TLC

20 Emphysema Normal lung Bullous emphysema

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22 Decrease in inspiratory capacity with exercise in COPD 2.5 atory cap pacity (L) Inspir Endurance exercise time (min)

23 Irreversible airflow limitation Reduced FEV 1 Decline of FEV 1 Air trapping, Hyperinflation Worsens breathlessness Deconditioning Inactivity, reduced d exercise capacity Reduce HRQL Increase mortality

24 Current treatment guidelines GOLD 2009

25 Diffusion Lung Capacity (DLco)

26 Gas Exchange The PaO2 usually remains near normal until the FEV1<50% of pred. The elevation of PaCO2CO is not expected until the FEV1<25% of pred. Nonuniform ventilation and V/Q mismatching. -Ppr airway obstruction NO washout is delayed due to regions that are poorly ventilated. Emphysema: normal to dec PaO2 Chronic bronchitis: dec PaO2

27 Pulmonary Hypertension in COPD

28 Pulmonary Hypertension in COPD Chronic hypoxia Pulmonary vasoconstriction Pulmonary hypertension Cor pulmonale Muscularization Intimal hyperplasia Fibrosis Obliteration Death Edema GOLD 2008

29 Common feature of PH in COPD Exact incidence or prevalence is unknown Generally mild PH & slow progression 62/175 (35%) mod to severe COPD (mean FEV 1 = 40.2%) mpap = 19.8 ± 7.6 mmhg (Weitzenblum et al. Thorax 1981) 109/120 (91%) in NETT (mean FEV 1 = 27%) for LVRS mpap = 26.3 ± 5.2 mmhg (Scharf et al. AJRCCM 2002) 108/215 (50%) severe COPD (mean FEV 1 =243%)for= 24.3%) LT or LVRS mpap = 26.9 ± 8.9 mmhg (Thabut et al. Chest 2005) average rate of increase in PAP is mmhg/yr Prognostic impact reduced d survival and increased exacerbation

30 PAP 18 mmhg PaCO 2 44 mmhg PAP > 18 mmhg PaCO 2 > 44 mmhg Adverse prognostic factor - mean PAP > 18 mmhg Independent -pco 2 > 44 mmhg predictors -po 2 65 mmhg - BMI 20 kg/m2-6-min-walk 367 m AJRCCM 1999;159:158

31 Distinctive features and worse prognosis of out-of-proportion pul HTN Distinctive features of 11 patients with mpap 40mmHg marked dyspnea (grade 4 or 5) profound hypoxemia (median: 46mmHg) hypocapnia (median: 32mmHg) moderate obstruction (median FEV 1 : 50% predicted) very low DLco significantly worse survival AJRCCM. 2005;172; 189

32 Working ggroup recommendation summary - Dx and assessment of PH in chronic lung dis - Majority of COPD-PH is mild to moderate Severe or out-of-proportion PH in COPD exhibit distinctive clinical i l pattern with reduced d survival The underlying lung disease should be optimally treated according to the respective guidelines, including the use of long-term oxygen therapy in patients with chronic hypoxemia (E/A) There is no sufficient evidence that the drugs currently used for PAH are safe and effective in patients t with PH associated with chronic lung disease (E/A) JACC 2009;54; S85

33 Systemic Feature of COPD Cachexia: loss of fat free mass Skeletal muscle wasting: apoptosis, disuse atrophy Osteoporosis Depression Normochromic normocytic anemia Increased risk of CV disease: associated with increased CRP

34 Pathophysiology of COPD 1. Mucus hypersecretion & ciliary dysfunction 2. Airflow limitation it ti & hyperinflation - inflammation and narrowing of pph airways 3. Gas exchange abnormalities - parenchymal destruction of emphysema 4. Pulmonary hypertension & Cor pulmonale 5 5. Systemic effects GOLD. AJRCCM 2007;176:532