1. Book review: Harrison Ch.254 COPD

2. Chronic obstructive pulmonary disease (COPD)
Global Initiative for Chronic Obstructive Lung Disease (GOLD)
airflow limitation that is not fully reversible
Emphysema: anatomical destruction and enlargement of the lung alveoli
chronic bronchitis: clinically defined condition with chronic cough and phlegm
Small airways disease: condition in which small bronchioles are narrowed

3. Risk factors Cigarette smoking Major risk factor Decline FEV1
dose-response relationship to the intensity of cigarette smoking
pack-years of cigarette smoking is the most highly significant predictor of FEV1
Cigar, pipe smoking (?)

5. Airway Responsiveness and COPD
COPD also share this feature of airway hyperresponsiveness
increased airway responsiveness is clearly a significant predictor of subsequent decline in pulmonary function

6. Respiratory Infections
important causes of exacerbations of COPD
development and progression of COPD: unproven
Occupational Exposures
Ambient Air Pollution
Passive, or Second-Hand, Smoking Exposure
Exposure of children to maternal smoking:reduced lung growth
In utero tobacco smoke exposure :reductions in postnatal pulmonary function
passive smoke exposure
reduction pulmonary function
Development COPD(?)
alpha-1 antitrypsin deficiency

7. Natural history Pulmonary function
Steady increasing pulmonary function with growth during childhood and adolescence
Gradual decline with againg
Effect of cigarette smoking
Intensity , timing, baseline lung function

9. Pathophysiology
COPD
Persistent reduction in forced expiratory flow rates: most typical finding
Increased RV
RV/TLC ratio
Nonuniform distribution of ventilation
Ventilation-perfusion mismatching

10. Airflow obstruction
Chronically reduced FEV1, FEV1/FVC
FEV1 responsiveness to inhaled bronchodilator
Common improvement up to 15%

11. Gas exchange
FEV1~50% : PaO2 nearly normal
FEV1<25%: elevation of PaCO2
FEV1<25% with chronic hypoxemia: Pulmonary HTN ( cor pulmonale and RHF)
Nonuniform ventilation, VQ mismatching
Heterogenous disease nature
Hypoxemia major cause
Effectiveness of elevation inspiratory O2
Incorrected hypoxemia to O2 therapy?

12. Pathology Cigarette smoke Large airways : cough,sputum
small airways, alveolar space: physiologic alteration

13. Large airways
Mucous gland enlargement, Goblet cell hyperplasia
Cough, mucus production chronic bronchitis
Not relation to airway limitation
Bronchial squamous metaplasia
Carcinogenesis, disruption of mucociliary clearance
Smoothmuscle hypertrophy, bronchial hyperreactivity
Neutrophil influx

14. Small airways
Major site of increased resistance
<2mm diameter
Goblet cell metaplasia
Replacement of surfactant-secreting Clara cells with mucus secreting and mononuclear inflammatory cells
Reduction surfactant

15. Clinical presentation
History
Gradual process
Symptoms (C/S, DOE) for months or years
Physical findings
In early stage: normal
More severe disease: prolonged expiratory phase, expiratory wheezing, hyperinfilation
Advanced disease: systemic wasting—poor prognostic factor

16. Lab findings
Pulmonary function
Exercise performance, dyspnea, body mass index: better predictor of motality than PF alone
ABGA: pH ventilator failure
CT: emphysema
Serum D1 AT level

17. Treatment Stable phase Influence the natural history of COPD
Only 3 intervention
Smoking cessation
Oxygen therapy in chronically hypoxic Pt
Lung volume reduction therapy in selected patients with emphysema
Current suggestion: inhaled corticosteroids may alter mortality (not lung fuction)

18. Pharmachotherapy
Bronchodilator: symptomatic Pt, inhaled route
Anticholinergic agents
Ipratropium bromide
Tiotropium : improved symptoms and reduce exacerbations
Beta agonist
Addition to inhaled anticholinergic

19. Inhaled glucocorticoids
Regular inhaled CS
fail to effect to decline of lung fuction, FEV1
oropharyngeal candidiasis, osteoporosis
Reduce exacerbation frequency by ~25% (?)
Reduce motality by ~25% (?)
Trial of ICS in Pt with frequent exacerbation ( 2 or 3/year)

20. Oral glucocorticoids
Chronic use of oral CS : Not recommendation
Theophylline
modest improvement in expiratory flow rates and vital capacity, improvement PaO2, PaCO2
Oxygen
only pharmachologic Tx to decrease mortality in COPD resting hypoxemia with cor pulmonale
N-acetyl cystein
mucolytic and antioxidant properties
IV d1AT augmentation therapy

21. Nonpharmachological therapys
General medical care
influenza vaccine annually, polyvalent pneumocaccal vaccine
Lung volume reduction surgery
mortality benefit and symptomatic benefit in certain patiens with emphysema
Lung transplantation
COPD is the single leading indicaton for lung transplantation

22. Flow diagram for the management of stable COPD

23. Treatment Exacerbation of COPD
Increased dyspnea and cough
Change in amount and character of sputum
May or may not other signs
Frequency of exacerbations increases as airflow obstruction increases
GOLD III, IV: 1-3 episodes per year

24. Streptococcus pneumonia, Haemophilus influenza, Moraxella catarrhalis
Bronchodilator
Antibiotics
Streptococcus pneumonia, Haemophilus influenza, Moraxella catarrhalis
Mycoplasma pneumonia, Chlamydia pneumonia
“rotating” antibiotics: not beneficial in COPD VS bronchiectasis
Low risk
amoxicillin and trimethoprim-sulfamethoxazole
10 days
High risk
newer macrolides (azithromycin, 500 mg on day 1, 250 mg on days 2 to 5) fluoroquinolones (levofloxacin, 500 mg/day)
7 to 10 days

25. Glucocorticoids
Inpateints, CS
Reduce the length of stay
Hasten recovery
Reduce the chance of subsequent exacerbation or relapse for a period of up to 6 months
GOLD : 30-40mg of oral prednisolone or its equivalent for days

26. Oxygen
Mechanical ventilatory support
NIPPV with repiratory failure
Reduction in motality, need for intubation, complications of therapy, hospital length of stay
Contraindication
Cardiovascular instability, impaired mental status, inability to cooperate, copius secretions, inability to clear secretins..

27. Invasive mechanical ventilation
Life-threatening hypoxemia, severe hypercapnea, acidosis, impaired mental status, repiratory arrest, hemodynamic instabillity
Sufficient expiratory time : severe obstruction or auto-PEEP