CHRONIC OBSTRUCTIVE PULMONARY DISEASE

RESPIRTORY DEPARTMENT RENJI HOSPITAL

DEFINITION OF COPD
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease state characterized by air flow limitation that is not fully reversible. Air flow limitation is usually progressive and is associated with an abnormal inflammatory response of lungs to noxious particles or gases,primarily caused by cigarette smoking.

Component of COPD
The definition Include chronic bronchitis ,emphysema with airflow limitation. The definition exclude other causes of chronic airflow obstruction such as Pulmonary cystic fibrosis , diffuse panbronchiolitis and bronchiectasis etc.

COPD
Component part :

Process of copd
Chronic Bronchitis Obstructive emphysema COPD airflow limitation Pulmonary artery hypertension Col pulmonal heart disease

Chronic Bronchitis

Chronic Bronchitis
Chronic bronchitis is defined clinically as the presence of a cough productive of sputum not attributable to other causes on most days for at least 3 months over 2 consecutive years. Clinical and epidemiological term

Chronic Bronchitis
Chronic nonspecific inflammation Symptoms of cough and sputum production with or without gasping Recurrent attacks Chronic proceeding

Classification of Chronic Bronchitis

Simple type of Chronic Bronchitis (without gasping) Chronic Bronchitis with gasping Cough Sputum expectoration

Cough Sputum expectoration Gasping

Stages of Chronic Bronchitis

Stages
Exacerbation Chronic lag phase stable

Time Courses
In a week One month or longer Lasts for two months

Diagnosis of chronic bronchitis

Cough & Sputum expectoration & Gasping Three months /per year or longer Continuously longer than two years Exclude other lung and heart disease
If shorter than three months /per year then definite objective evidences are demanded (such as X-Ray and lung function et al.)to diagnose.

Obstructive Emphysema

Definition of Emphysema
Pulmonary emphysema (a pathological term) is characterized by abnormal,permanent enlargement of air spaces distal to the terminal bronchioles ,accompanied by destruction of their walls and hyperdistension leading to reduction in lung elastics recoil and airway obstruction.

Classification of Emphysema
Obstructive Emphysema senile Emphysema emphysema(Physiological) without Interstitial Emphysema Obstruction Compensating Emphysema Scarred Emphysema

Risk factor for COPD

Genes Exposure to particles Tobacco smoke
Occupational dusts, organic and inorganic Indoor air pollution from heating and cooking with biomass in poorly vented dwellings Outdoor air pollution

Lung Growth and Development Oxidative stress Gender/ Age/ Respiratory infections /Socioeconomic status Nutrition Comorbidities

Pathogenesis of COPD

Pathogenesis
The inflammation in the respiratory tract of COPD patients appears to be an amplification of the normal inflammatory response of the respiratory tract to chronic irritants such as cigarette smoke.
Inflammatory Cells Involve neutrophils, macrophages, and lymphocytes. These cells release inflammatory mediators and interact with structural cells in the airways and lung parenchyma. Inflammatory Mediators The inflammatory mediators attract inflammatory cells from the circulation (chemotactic factors), amplify the inflammatory process (proinflammatory cytokines), and induce structural changes (growth factors).

Oxidative Stress

Oxidative stress may be an important amplifying mechanism in COPD. Oxidants are generated by cigarette smoke and other inhaled particulates, and released from activated inflammatory cells such as macrophages and neutrophils.

Protease-Antiprotease Imbalance Protease-mediated destruction of elastin, a major connective tissue component in lung parenchyma, is an important feature of emphysema and is likely to be irreversible.

Difference in inflammation between COPD and asthma

Although both COPD and asthma are associated with chronic inflammation of the respiratory tract, there are marked differences in the inflammatory cells and mediators involved in the two diseases, which in turn account for differences in physiological effects, symptoms, and response to therapy .

ASTHMA

COPD

CD4+ T-

COPD CD8+ T-

Pathology
Pathological changes characteristic of COPD are found in the proximal airways, peripheral airways, lung parenchyma, and pulmonary vasculature. These changes include chronic inflammation, and structural changes .

Proximal airways (trachea, bronchi > 2 mm internal diameter) Goblet cells, enlarged submucosal glands (both leading to mucus hypersecretion), squamous metaplasia of epithelium Peripheral airways (bronchioles < 2mm i.d.) Airway wall thickening, peribronchial fibrosis, luminal inflammatory exudate, airway narrowing (obstructive bronchiolitis) Increased inflammatory response and exudate correlated with disease severity.

Lung parenchyma (respiratory bronchioles and alveoli) Alveolar wall destruction, apoptosis of epithelial and endothelial cells. Centrilobular emphysema: dilatation and destruction of respiratory bronchioles; most commonly seen in smokers Panacinar emphysema: destruction of alveolar sacs as well as respiratory bronchioles; most commonly seen in alpha-1 antitrypsin deficiency

Normal distal lung acinus

Centriacinar(centrilobular) emphysema

Panacinar emphysema

Pulmonary vasculature Thickening of intima, endothelial cell dysfunction, smooth muscle

pulmonary hypertension.

PATHOPHYSIOLOGY
Airflow Limitation and Air Trapping The inflammation, fibrosis, and luminal exudates in small airways is correlated with the reduction in FEV1and FEV1/FVC ratio. The peripheral airway obstruction traps air during expiration,resulting in hyperinflation. Emphysema is more associated with gas exchange abnormalities than with reduced FEV1.

Gas Exchange Abnormalities VA/Q imbalance Reduced pulmonary vascular bed Mucus Hypersecretion Pulmonary Hypertension
Hypoxic vasoconstriction of small pulmonary arteries eventually result in structural changes that include intimal hyperplasia and later smooth muscle hypertrophy/hyperplasia. The loss of the pulmonary capillary bed in emphysema may also contribute to increased pressure in the pulmonary circulation. Progressive pulmonary hypertension may lead to right ventricular hypertrophy and eventually to right-side cardiac failure (cor pulmonale).

Systemic features
They have a major impact on survival and comorbid diseases. Cachexia a loss of skeletal muscle mass and weakness increased likeliness of having osteoporosis, depression and chronic anemia. Increased concentrations of inflammatory mediators, including TNF-, IL-6, and oxygen-derived free radicals, There is an increase in the risk of cardiovascular diseases.

Clinical Manifestation
History :
History of exposure to risk factors,
Tobacco smoke. Occupational dusts and chemicals Smoke from home cooking and heating fuels.

Age of onset :After middle age Season:winter

Clinical Manifestation
Symptoms:

Gradually progressive dyspnea is the most common presenting character.

Dyspnea that is: Progressive (worsens over time) Usually worse with exercise Persistent (present every day) Described by the patient as an increased effort to breathe,heaviness, air hunger, or gasping.

Chronic Cough May be intermittent and may be unproductive. Chronic sputum production:

Recurrent respiratory infection Recurrent attacks leading to cor pulmonal heart disease Unexpected weigh loss Decreased food appetite

Physical Signs:

Earlier period:Minimal/Nonspecific signs Advanced Stage:

*Inspection: Barrel-shaped chest , accessory respiratory muscle participate , prolonged expiration during quiet breathing. *Palpation: Weakened fremitus vocalis

Clinical Manifestation
*Percussion : Hyperresonant depressed diaphragm, dimination of the area of absolute cardiac dullness. *Auscultation: Prolonged expiration reduced breath sounds; The presence of wheezing during quiet breathing Crackle can be heard if infection exist. The heart sounds are best heard over the xiphoid area.

Auxillary Examination
Chronic bronchitis

Chest Radiograph(X-Ray) Non apparent abnormality Or thickened and increased of the lung markings are noted.

Auxiliary Examination
Chest X-Ray --emphysema
Chest findings are also varible. Marked over inflation is noted with flattend and low diaphragm Intercostal space becomes widen A horizontal pattern of ribs A long thin heart shadow Decreased markings of lung peripheral vessels

Chest X-Ray

Auxiliary Examination
Pulmonary function Test
Determination of a forced vital capacity and FEV1is necessary for the diagnosis and assessment of the severity of the disease and helpful in following its progress.

FEV1 /FVC is the best index of airflow obstruction

Auxiliary Examination
Pulmonary function Test diagnostic criteria
A post-bronchodilator (FEV1)/forced vital capacity(FVC) 70% confirm the presence of airflow limitation that is not fully reversible. FEV1 %pred is used for evaluation of the severity of pulmonary function status. The FEV1 and the FEV1/FVC ratio fall progressively as the severity of COPD increases.

Pulmonary function Test

Elevations of total lung capacity (TLC) Functional reserve capacity(FRC) Residual volume(RV) RV/TLC>40% for emphysema Vital capacity (VC) Peak expiratory flow(PEF)

spirometric classification of COPD FEV1/FVC mild <70% moderate <70% severe disease <70% Very severe < 70% FEV1%pred
80% 50~80% 30~50%

30%or<50% 30%or<50% following with respiratory failure & right heart failure

Auxiliary Examination
CT(Computed tomography) :
greater sensitivity and specificity for emphysema than CXR , especially for the diagnosis of bronchiectasis and evaluation of bullous disease

Computed Tomography

Labortory Examination
Blood examination In excerbation or acute infection in airway, leucocytosis may be detected. Sputum examination streptococcus pneumonia Haemophilus influenzae Moraxella catarrhalis klebsiella pneumonia

Auxiliary Examination
Blood gas analysis:
Arterial blood gas analysis may reveal hypoxemia,particularly advanced disease. In patients with severe hypoxemia ,CO2 retention,it shows low arterial PO2 and high arterial PCO2.

Diagnosis of COPD
Clinical manifestation Auxiliary examinations Significant importance of Pulmonary function test

Spirometry should be obtained in all patients with :

Exposure to cigarettes ; Environmental or occupational pollutants; presence of cough ,sputum production or dyspnea

Stage
Exacerbation: Gradually progressive Cough and sputum & Dyspnea and gasping Increased purulence sputum followed by recurrent respiratory infection. Stable : Stable systoms of Cough and sputum ,gasping and dyspnea are alleviated.

Differential Diagnosis of COPD

Diagnosis 1. Mid-life onset COPD 2. Slowly progressing symptoms
3. Long history of smoking 4.Dyspnea during exercise 5.largely irreversible airflow limitation

Suggestive features

Asthma 1.Early onset 2. Symptoms vary from day to day --3. Symptoms at the night/early morning 4. A family history 5. Airflow limitation that is largely reversible 6.largely reversible airflow limitation 7.Allergy,rhinitis,eczema

Differential Diagnosis of COPD

Suggestive features Diagnosis Pulmonary carcinoma  Commonly occurs in patients

- --

over 40 years old  with cigarette smoking.  Obvious radiological abnormality

Onset at all ages Tuberculosis toxic syndrome Lung infiltrate on chest radiography Microbiological confirmation Sputum examination of positive TB bacterium can confirms the diagnosis

Tuberculosis ---

Differential Diagnosis of COPD

Diagnosis Suggestive features Bronchiect 1. Large volume of purulent sputum asis 2. Commonly associated with bacterial
infection 3. Coarse crack/clubbing on auscultation 4. Bronchial dilation and bronchial wall thickening on X-ray /CT Nonobstructivee mphysema

pulmonary function tests

Complication
chronic respiratory failure Pneumothorax Chronic pulmonary heart disease

TREATMENT
Aim
Based on the principles of prevention of further progress of disease preservation and enhancement of pulmonary functional capacity avoidance of exacerbations in order to improve the quality of life.

TREATMENT
Stop smoking Avoid environment pollution Antibiotic therapy Bronchodilators Glucocorticoids Expectorant Respiratory stimulant Oxygen therapy Rehabilitation care Lung volume reduction surgery

stable COPD(I) avoid risk factors Education and smoking cessation

Smoking cessation has the greatest capacity to influence the natural history of COPD.

Control the occupational and environmental pollution

stable COPD(II) Drug therapy:

Prevent and control symptoms , increase exercise capacity, reduce the frequency and severity of exacerbations , improve health status.

Drug Therapy
1.Bronchodilators
Bronchodilators are central to the symptomatic management of COPD. improve emptying of the lungs,reduce dynamic hyperinflation and improve exercise performance .

Drug Therapy
Bronchodilators
Three major classes of bronchodilators:

2 - agonists: Short acting: salbutamol & terbutaline Long acting :Salmeterol & formoterol Anticholinergic agents: Ipratropium,tiotropium Theophylline (a weak bronchodilator, which may have some anti-inflammatory properties)

Drug Therapy
2.Glucocorticoids Regular treatment with inhaled glucocorticoids is appropriate for symptomatic patients with anFEV1<50%pred and repeated exacerbations. Chronic treatment with systemic glucocorticoids should be avoided because of an unfavorable benefit-torisk ratio.

3. COMBINATION THERAPY Combination therapy of long acting 22-agonists and inhaled corticosteroids show a significant additional effect on pulmonary function and a reduction in symptoms.
Mainly in patients with an FEV1<50%pred

Drug Therapy
4.Others: Antioxidant agents--Immunoregulators--Vaccine--Traditional Chinese medicine--Alpha-1 antitrypsin augmentation Mucolytic(mucokinetic,mucoregulator) agents Antitussives

Oxygen Therapy
Oxygen ->15 h /d

Long-term oxygen therapy (LTOT) improves survival,exercise,sleep and cognitive performance in patients with respiratory failure. The therapeutic goal is to maintain SaO2 90% and PaO2 60mmHg at sea level and rest .

Long-term Oxygen therapy LTOT

Indication:
For patients with a PaO2 55 mmHg or SaO288% , with or without hypercapnia For patients with a PaO2 of 55~70 60 mmHg or SaO289% as well as pulmonary hypertension / heart failure / polycythemia (hematocrit >55%)

Pulmonary rehabilitation Nutrition Surgery:

Bullectomy Lung volume reduction surgery( Lung transplantation

Manage exacerbation
Identify the cause of exacerbation:
Virus or Bacteria or Other uncertain reasons

Assessment of severity:
The proceeding history and disease must be considered and comparison is very important.

Oxygen therapy
Controlled oxygen therapy. Supplemental oxygen should be titrated to improve the patients hypoxemia. Adequate levels of oxygenation (PaO2 > 8.0 kPa, 60 mm Hg, or SaO2 > 90%) are easy to achieve in uncomplicated exacerbations, but CO2 retention can occur insidiously with little change in symptoms. Once oxygen is started, arterial rrr blood gases should be checked 30-60 minutes later to ensure satisfactory oxygenation without CO2 retention or acidosis.

Bronchodilators : Increase dose and times properly Atomization and inhalation Glucocorticoids: Oral or intravenous glucocorticosteroids are recommended. Thirty to 40 mg of oral prednisolone daily for 7-10 days is effective and safe.

Antibiotics Respiratory infection is the usual predisposing factor. It is advocated to select antibiotics according to culture of sputum and drugsensitivity test. Mechanical Ventilation Noninvasive mechanical ventilation Invasive mechanical ventilation Others:

Chronic Pulmonary Heart Disease

Respiratory Department Renji Hospital

DEFINITIONS
Enlargement of the right ventricle (RV)

due to pulmonary artery hypertension

which arises from structural or functional abnormalities of the lungs, chest wall ,vascular.

RV FAILURE

Cor pulmonale may be acute or chronic.

The most common cause of acute cor pulmonale --- thromembolism The most common cause of chronic cor pulmonale ---copd

Bronchial pulmonary diseases:

The main diseases : chronic bronchitis, copd,(80%~90%) Others: asthma, bronchiectasis, pulmonary fibrosis,sarcoidosis

Severe thoracic deformity:

cause compression of the lung

Pulmonary vascular diseases:

primary pulmonary hypertention; pulmonary embolism

Neuromuscular disorder

PATHOLOGY
Primary lung :
Chronic bronchitis & pulmonary emphysema

Pulmonary vessel :
1. Stenosis of pulmonary artery & thicken of

the vessel wall 2. Loss and fracture of the alveolar capillary 3. Distortion of the pulmonary vascular bed

PATHOLOGY
Heart : Increase of the heart weight Thicken of the heart muscle The enlarged right ventricle

Cor pulmonale

PATHOPHYSIOLOGY Pulmonary arterial hypertension 1. Structural Smooth muscular thickening of the smaller arteries Anatomic reduction of the vascular bed Pulmonary vascular remodeling--

PATHOPHYSIOLOGY Pulmonary arterial hypertension 2. Functional Pulmonary vasoconstriction secondary to alveolar hypoxia, acidosis, and hypercapnia. 1.humoral factor 2.tissue factor--3.nerve factor---

PATHOPHYSIOLOGY Pulmonary arterial hypertension

3. The increase of pulmonary blood flow blood volume and blood viscosity caused by polycythemia secondary to hypoxia.

PATHOPHYSIOLOGY Failure of right ventricle: Pulmonary hypertension Myocardial anoxia Repeatedly pulmonary infection : effect of bacterial toxin to the heart Acid base disorder : arrhythmia

Clinical Manifestation
Historial information varies with the underlying etiology.
For COPD patient Productive cough and dyspnea, wheezing Breathlessness limits the patient's ability . Dyspnea and cardiopalmus after movement A history of emergency hospital admissions because of respiratory infection.

Dyspnea on exertion is the most common presenting manifestation of pulmonary hypertension.

Clinical Manifestation
Physical examination Compensation period : For copd
Pulmonary arterial hypertension signs (S3) and a systolic murmur of tricuspid regurgitant P2>A2

a right ventricular parasternale impulse

Clinical Manifestation
. Decompensation

period

Physical examination

Respiratory failure
Respiratory infection is the usual predisposing factor .
Clinical manifestation hypercapnia and hypoxia : Such as dyspnea,cyanosis,increase in heart rate,peripheral venous dilation. Sweaty and nero-psychiatric symptoms ( headaches, neroletharfy,exciation,delirium,tremor,tic,papilloedema,etc).

Clinical Manifestation
Physical examination

Right ventricular failure

Tachynea, elevated jugular venous pressure, right ventricular parasternum impulse hepatomegaly, peripheral edema positive hepatojugular reflux

total cardia failure with arrhythmia

X-Ray Diagnostic Criteria

(I) Distension of the low right pulmonary artery

trunk: Diameter transversa 15mm Or diameter transversa (right hyoppulmonary artery /trachea) 1 07 Or widen 2mm(compare to the primary right pulmonary artery trunk) (II) Midrange projecture of pulmonary artery trunk or the altitude 3mm

X-Ray Diagnostic Criteria

(III) Significant projecture of the conus portion 7mm (IV) Enlargement of the main pulmonary artery,rapid tapering of pulmonary arterial branches toward lung periphery
(V)

Right ventricle enlarged Various pulmonary parenchymal,pleural,and/or thoracic abnormalities dependent on underlying etiology of cor pulmonale. One item can be diagnosed.

Electrocardiogram Diagnostic Criteria

Main Conditions: Mean QRS axis 90 Vl R S1 Marked clockwise rotation of the electric axis(V5 R S 1 P-pulmonary pattern (an increase in P-wave amplitude ) RV1 SV5 1 05mV aVR R S or R Q1 (except for myocardial infarction) V1 3 :QS Qr qr pattern

Electrocardiogram Diagnostic Criteria

Secondary Conditions: Low-voltage ORS in Limb lead Right bundle-branch block (Incomplete or rarely complete) One item in main condition can be diagnosed; Two or more than two items in secondary condition is to suspect.

Echocardiogram Diagnostic Criteria

Main Conditons(I) Internal diameter of right ventricular outflow
tract 30mm Right ventricular internal dimension 20mm The thickeness of right ventricular anterior wall 5 0mm Left/right ventricular internal dimension 2

Echocardiogram Diagnostic Criteria

Main Conditons(II)
Internal dimension of right pulmonary artery 18mm or pulmonary artery trunk 20mm Right ventricular outflow tract/internal dimension of left atrium 1 4 Pulmonary artery hypertension signs(low awave 2mm) or midsystolic closure

Echocardiogram Diagnostic Criteria

Reference conditions:
Interventricular septal thickness 12mm Pulsation altitude 5mm or paradoxical motion Right atrium enlarged 25mm Curve DE EF of anterior tricuspid leaflet accelerate; E-peak sharp ;AC period prolong . Low curve amplitude of anterior leaflet of mitral valve ,CE 18mm;CD section slowly upgrade and prolong as horizontal position;EF rate of decay 90mm s

Echocardiogram Diagnostic Criteria

Notice: The diagnostic criteria is only fit for the Detection Position of praecordium Patient who has lung or chest disease,could be diagnosed if he or she has two items above (including one main condition at least)

Auxiliary Examination echocardiogram

Arterial blood gases Analysis of blood

Diagnosis
Chronic respiratory disease or thoracic cage disease: Pulmonary arterial hypertension Right ventricular hypertrophy or dilatation Right heart insufficienacy Other reason heart diseases must be ruled out

Differential Diagnosis
Coronary artery disease: --Angina cordis, Myocardial infarction history & Left ventricular hypertrophy (EKG) Rheumatic heart disease:--History & echocardiogram Myocardial disease: --Without chronic respiratory disease Echocardiogram The total heart enlarged

Complication:
Pulmonary encephalopathy Acid-base disorder and electrolyte disturbances Shock DIC Arrhythmia Gastrointestinal hemorrhage

Treatment
Acute exacerbation period Antibiotics Respiratory insufficiency therapy: * Airway Management
(Oxygen,Bronchidilator ,secretion clean)

*Respiratory stimulant *Mechanical ventilation Acid-base imbalance and electrolyte disturbance

Treatment(I)
Acute exacerbation period
Therapeutic principle of heart failure: *Antibiotics: most important *Oxygen : low concentration and careful administration are essential to avoid depressing respiratory drive and causing hypercapnea. * Bronchodilator: can reduce the effort of breathing and decrease dyspnea. beta-adrenergic stimulants, theophylline compounds

Treatment(II)
*Diuretic

agent: low dose ,short course *Cardiant: Low dose,fast effect, quick metabolism Hypoxemia,acidosis and catecholamine excess can increase the adverse effects of digitalis. indications: left heart failure; Infection has been controlled and diuretic agent has been used,heart failure still exist; Right heart failure without severe infection; Cardiac arrhythmia

Vasodilating agent: Control the arhythmia: Corticosteroids: The value is depend on the likely responsiveness of the underlying ventilatory functional abnormality. Others: prevent complication

Treatment(III)
Compensation:
Breath training Elevate the power of resistance: Chinese medicine and immunoenhancer Improve nutritional status Home oxygen therapy
Long term oxygen therapy is indicated for patients with persistent arterial hypoxemia at rest or after exercise (arterial oxygen tension consistently below 55mmHg while breathing room air.

Treatment
Preventive measure: Prevent respiratory infection Physical exercise Environmental health Stop smoking Lung function monitoring