1. COPD In the name of GOD Dr. Hassan Ghobadi
Assistant Professor of Internal Medicine
Ardabil University of Medical Sciences

2. COPD
COPD is present only if chronic airflow obstruction occurs.
Emphysema ,
An anatomically defined condition characterized by destruction and enlargement of the lung alveoli.
Chronic bronchitis,
A clinically defined condition with chronic cough and phlegm.
Small airways disease, a condition in which small bronchioles are narrowed.

3. COPD COPD is the fourth leading cause of death
COPD will rise from the fourth to the third most common cause of death worldwide by 2020.
COPD is characterized by airflow limitation that is not fully reversible.
The airflow limitation is usually progressive and associated with an abnormal inflammatory response.

4. Risk Factors Cigarette Smoking (90%)
Second-Hand, Smoking Exposure ( SHS )
Airway Hyper Responsiveness (AHR)
Respiratory Infections
Occupational Exposures
Air Pollution
Genetic Considerations
Alpha 1 Antitrypsin Deficiency (1–2%)

5. Natural History
The effects of cigarette smoking on pulmonary function appear to depend on the intensity of smoking exposure.
The timing of smoking exposure.
The risk of mortality from COPD is closely associated with reduced levels of FEV1.
Smoking cessation at an earlier age providing a more beneficial effect.
Genetic factors

6. Pathophysiology Persistent reduction in forced expiratory flow rates.
Increases in the residual volume and the residual volume/total lung capacity ratio.
Nonuniform distribution of ventilation, and ventilation-perfusion mismatching.

7. Pathophysiology Airflow Obstruction Hyperinflation (air trapping )
Gas Exchange
The PaO2 usually remains near normal until the FEV1 is decreased to ~50% of predicted,
An elevation of PaCO2 is not expected until the FEV1 is <25% of predicted.

8. Pathology
Cigarette smoke exposure may affect the large airways, small airways ( 2 mm diameter), and alveolar space.
Changes in large airways cause cough and sputum, while changes in small airways and alveoli are responsible for physiologic alterations.

9. Pathology

10. Pathology (Large Airway)
Mucous gland enlargement and goblet cell hyperplasia (not related to airflow limitation ).
Bronchi also undergo squamous metaplasia, which not only predisposes to carcinogenesis but also disrupts mucociliary clearance.
smooth-muscle hypertrophy and bronchial hyperreactivity.

11. Pathology (Small Airway)
The major site of increased resistance is in airways less than 2 mm diameter.
Infiltrating mononuclear inflammatory cells.
Smooth-muscle hypertrophy may also be present.
loss of elastic recoil and increased resistance to airflow in small airways.

12. Pathology (Parenchyma)
Emphysema is characterized by destruction of gas-exchanging airspaces.
Bronchoalveolar lavage fluid contains roughly five times as many macrophages as lavage from nonsmokers.
In smokers' lavage fluid, macrophages comprise >95% of the total cell count.
T lymphocytes, particularly CD8+ cells, are also increased in the alveolar space of smokers.

13. Pathology (Parenchyma)
Emphysema is classified into distinct pathologic types: Centriacinar, and Panacinar.
1- Centriacinar emphysema, the type most frequently associated with cigarette smoking, is characterized by enlarged airspaces found (initially) in association with respiratory bronchioles.
Centriacinar emphysema is most prominent in the upper lobes and superior segments of lower lobes and is often quite focal.
2- Panacinar emphysema refers to abnormally large airspaces evenly distributed within and across acinar units.
Panacinar emphysema is usually observed in patients with 1AT deficiency, which has a predilection for the lower lobes.

14. Pathogenesis
(1) Chronic exposure to cigarette smoke may lead to inflammatory cell recruitment within the terminal airspaces of the lung.
(2) These inflammatory cells release elastolytic proteinases which damage the extracellular matrix of the lung.
(3) Loss of matrix-cell attachment leads to apoptosis of structural cells of the lung.
(4) Ineffective repair of elastin and perhaps other extracellular matrix components result in airspace enlargement that defines pulmonary emphysema.

16. Amplifying mechanisms
Pathogenesis of COPD
Cigarette smoke
Biomass particles
Particulates
Host factors
Amplifying mechanisms
LUNG INFLAMMATION
Anti-oxidants
Anti-proteinases
Oxidative
stress
Proteinases
Repair
mechanisms
COPD PATHOLOGY 16

17. COPD ASTHMA Airflow Limitation Small airway narrowing
Alv macrophage
Ep cells
CD8+ cell
(Th1)
Neutrophil
Cigarette smoke
Small airway narrowing
Alveolar destruction
COPD
ASTHMA
Allergens Y
Ep cells
Mast cell
CD4+ cell
(Th2)
Eosinophil
Bronchoconstriction
AHR
Airflow Limitation
Reversible
Irreversible 17

18. Pathogenesis
The Elastase, Antielastase Hypothesis
This hypothesis was based on the clinical observation that patients with genetic deficiency in Alpha 1 AT .
Inflammation and Extra cellular Matrix Proteolysis
Exposure to oxidants from cigarette smoke.
Cell Death
Inflammatory cell proteinases degrade lung extracellular matrix , with subsequent loss of cell anchoring leading to apoptosis.
Ineffective Repair
Following injury, the ability of lung to repair damaged alveoli appears limited.

19. COPD (Clinical Presentation )
The three most common symptoms:
Cough, sputum production, and exertional dyspnea
Physical Findings
Nicotine staining of fingernails, prolonged expiratory phase, signs of hyperinflation, use of accessory muscles of respiration, tripod position, cyanosis, pink puffers, blue bloaters, weight loss, bitemporal wasting,
Hoover's sign (the result of alteration of the vector of diaphragmatic contraction on the rib cage as a result of chronic hyperinflation ).
Clubbing of the digits is not a sign of COPD

20. COPD (Laboratory Findings )
The hallmark of COPD is airflow obstruction reduction in FEV1 and FEV1/FVC .
With worsening disease severity, lung volumes may increase, resulting in an increase in total lung capacity, functional residual capacity, and residual volume.
In patients with emphysema, the diffusing capacity may be reduced, reflecting the parenchymal destruction characteristic of the disease.
The degree of airflow obstruction is an important prognostic factor in COPD and is the basis for the GOLD disease classification

21. COPD (PFT) Stage I: Mild FEV1/FVC < 0.70 FEV1 > 80% predicted
Stage II: Moderate FEV1/FVC < 0.70
50% < FEV1 < 80% predicted
Stage III: Severe FEV1/FVC < 0.70
30% < FEV1 < 50% predicted
Stage IV: Very Severe
FEV1/FVC < 0.70
FEV1 < 30% predicted or
FEV1 < 50% predicted plus
chronic respiratory failure

22. COPD (Imaging Findings )
Radiographic studies may assist in the classification of the type of COPD.
Obvious bullae, paucity of parenchymal markings, or hyperlucency suggest the presence of emphysema.
Increased lung volumes and flattening of the diaphragm suggest hyperinflation.
Computed tomography (CT) scan is the current definitive test for establishing the presence of emphysema.

23. Imaging Findings

24. indoor/outdoor pollution
Diagnosis of COPD
EXPOSURE TO RISK
FACTORS
SYMPTOMS
cough
tobacco
sputum
occupation
shortness of breath
indoor/outdoor pollution
A diagnosis of COPD should be considered in any patient who has cough, sputum production, or dyspnea and/or a history of exposure to risk factors. The diagnosis is confirmed by spirometry.
To help identify individuals earlier in the course of disease, spirometry should be performed for patients who have chronic cough and sputum production even if they do not have dyspnea.
Spirometry is the best way to diagnose COPD and to monitor its progression and health care workers to care for COPD patients should have assess to spirometry. è è è
SPIROMETRY 24

25. COPD ( Treatment ) Emphysema is incurable, but it can be treated
COPD is a preventable and treatable disease
Smoking cessation,
Oxygen therapy in hypoxemic patients,
Lung volume reduction surgery in selected patients with emphysema,
Pharmacotherapy,

26. Treatment (Pharmacotherapy)
Anticholinergic Agents
Does not appear to influence the rate of decline of lung function,
It improves symptoms and produces acute improvement in FEV1.
Beta Agonists
These provide symptomatic benefit. The main side effects are tremor and tachycardia.
The addition of a beta 2 agonist to inhaled anticholinergic therapy has been demonstrated to provide incremental benefit.
Using a long-acting beta 2 agonist without concomitant inhaled corticosteroids have an increased risk of deaths from respiratory causes.

27. Treatment (Pharmacotherapy)
Inhaled Glucocorticoids
Inhaled glucocorticoids reduce exacerbation frequency by ~25%.
A more recent meta-analysis suggests that they may also reduce mortality by ~25%.
A trial of inhaled glucocorticoids should be considered in patients with frequent exacerbations, defined as two or more per year, and in patients who demonstrate a significant amount of acute reversibility in response to inhaled bronchodilators.
Oral Glucocorticoids
The chronic use of oral glucocorticoids for treatment of COPD is not recommended .
The chronic use of oral glucocorticoids is associated with significant side effects.

28. Treatment (Pharmacotherapy)
Theophylline
1- Theophylline produces modest improvements in expiratory flow rates and vital capacity .
2- Theophylline improve arterial oxygen and carbon dioxide levels in patients with moderate to severe COPD.
3- Nausea is a common side effect; tachycardia and tremor have also been reported.
4- Theophylline has an anti inflammatory effects.

29. Treatment (Pharmacotherapy)
Oxygen
1- Oxygen therapy decrease mortality in patients with COPD.
2- Oxygen therapy have a significant impact on mortality.
3- For patients with resting hypoxemia resting O2 sat. <88%
4- For patients with resting hypoxemia resting O2 sat. <90%
with signs of pulmonary hypertension
Right heart failure
COPD with erythrocytosis.
5- Supplemental O2 is commonly prescribed for patients with exertional hypoxemia or nocturnal hypoxemia.

30. Non pharmacologic Therapies
COPD patients should receive the influenza vaccine annually.
Polyvalent pneumococcal vaccine is also recommended, although proof of efficacy in this patient population is not definitive.
In COPD, pulmonary rehabilitation has been demonstrated to improve health-related quality of life, dyspnea, and exercise capacity.
Lung Volume Reduction Surgery (LVRS)
Lung transplantation

31. Exacerbations of COPD
Bacterial infections play a role in many, but by no means all, episodes.
Viral respiratory infections are present in approximately one-third of COPD exacerbations.
In a significant minority of instances (20–35%), no specific precipitant can be identified.
chronic suppressive or "rotating" antibiotics are not beneficial in patients with COPD.

32. Exacerbations of COPD (2)
Chronic oral glucocorticoids are not recommended for this purpose.
Inhaled glucocorticoids did reduce the frequency of exacerbations by 25–30% .
The use of inhaled glucocorticoids should be considered in patients with frequent exacerbations .
In COPD exacerbation most frequent CXR findings being pneumonia and congestive heart failure.

33. Acute Exacerbations 1- Bronchodilators 2- Antibiotics
Inhaled beta 2 agonist, often with anticholinergic agent, methylxanthines.
2- Antibiotics
The choice of antibiotic should be based on local patterns of antibiotic susceptibility of the common pathogens as well as the patient's clinical condition.
3- Glucocorticoids
The use of glucocorticoids has been demonstrated to reduce the length of stay, hasten recovery, and reduce the chance of subsequent exacerbation or relapse for a period of up to 6 months.
The GOLD guidelines recommend 30–40 mg of oral prednisolone or its equivalent for a period of 10–14 days.

34. Acute Exacerbations
4- Oxygen
Supplemental O2 should be supplied to keep arterial saturations 90%.
5- Mechanical Ventilatory Support