1. COPD
Siby joseph

2. Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not fully reversible.
Otherwise known as chronic obstructive airway disease(COAD) or chronic obstructive lung disease.
The most common conditions comprising COPD are chronic bronchitis and emphysema.

3. Chronic bronchitis is associated with chronic or recurrent excess mucus secretion into the bronchial tree with cough that occurs on most days for
at least 3 months of the year for at least 2 consecutive years when other causes of cough have been excluded.
Emphysema is defined as abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of
their walls, but without obvious fibrosis.

4. ETIOLOGY
Tobacco smoking is the most important risk factor
Other noxious contributory particles are -exposure to chemical fumes , dust and gases .
The age when cigarette smoking started, total pack years of smoking & current status of smoking---predict COPD mortality
Total pack year = (number of cigarettes per day / 20) X number of years of smoking
Additional risk factor-natural ageing process of lungs
Genetic factor-alpha-1 antitrypsin deficiency

5. RISK FACTORS 1. Environmental tobacco smoke 1. Genetic predisposition
EXPOSURES
Environmental tobacco smoke
2. Occupational dust and chemicals
3. Air pollution
HOST FACTORS
1. Genetic predisposition
Airway hyperresponsiveness
Impaired lung growth

6. Pathophysiology
Inhalation of noxious particles and gases stimulates the activation of neutrophils, macrophages, and CD8+ lymphocytes, which release a variety of chemical mediators, including tumor necrosis factor-α, interleukin-8,and leukotriene B4.
These inflammatory cells and mediators lead to widespread destructive changes in the airways, pulmonary vasculature, and lung parenchyma.

7. Increased oxidants generated by cigarette smoke react with and damage various proteins and lipids, leading to cell and tissue damage.
Oxidants also promote inflammation directly and exacerbate the protease-antiprotease imbalance by inhibiting antiprotease activity.
The protective antiprotease α1-antitrypsin (AAT) inhibits several protease enzymes, including neutrophil elastase.
In the presence of unopposed AAT activity, elastase attacks elastin, which is a major component of alveolar
walls.

8. A hereditary deficiency of AAT results in an increased risk for premature development of emphysema. In the inherited disease, there is an absolute deficiency of AAT.
In emphysema resulting from cigarette smoking,
the imbalance is associated with increased protease activity or reduced activity of antiproteases.
oxidative stress reduces antiprotease activity.
An inflammatory exudates is often present in the airways that leads to an increased number and size of goblet cells and mucus glands.

9. Parenchymal changes affect the gas-exchanging units of the lungs (alveoli and pulmonary capillaries).
Smoking-related disease most commonly results in centrilobular emphysema that primarily affects respiratory bronchioles.
Panlobular emphysema is seen in AAT deficiency and extends to the alveolar ducts and sacs.

10. Vascular changes include thickening of pulmonary vessels that may lead to endothelial dysfunction of the pulmonary arteries.
Later, structural changes increase pulmonary pressures, especially during exercise. In severe COPD, secondary pulmonary hypertension leads to right-sided heart failure (cor pulmonale).

11. Noxious particles and gases
Lung inflamation
Antioxidants
Antiproteinases
Oxidative stress
Proteinases
Repair mechanism
COPD pathology

12. CLINICAL PRESENTATATION
chronic cough and sputum production; then dyspnoea
When airflow limitation becomes severe, patients may have cyanosis of mucosal membranes, development of a “barrel chest”due to hyperinflation of the lungs, an increased resting respiratory rate,shallow breathing, pursing of the lips during expiration.
chest tightness, increased need for bronchodilators, malaise, fatigue, and decreased exercise tolerance

13. DIAGNOSIS Pulmonary function test
Assessment of airflow limitation through spirometry is the standard for diagnosing and monitoring COPD.
The forced expiratory volume after 1 second (FEV1) is generally reduced except in very mild disease.
The forced vital capacity (FVC) may also be decreased.
The hallmark of COPD is a reduced FEV1:FVC ratio to less than 70%.
A postbronchodilator FEV1 that is less than 80% of predicted confirms the presence of airflow limitation
that is not fully reversible.

14. An improvement in FEV1 of less than 12% after inhalation of a rapid acting bronchodilator is considered to be evidence of irreversible airflow obstruction.
A low peak expiratory flow is consistent with COPD but not used as a diagnostic tool.

15. Severity Classification for Chronic Obstructive Pulmonary Disease
Severity Stage
Classification
Predicted FEV1
At risk
≥80% 1
Mild 2
Moderate
≥50% and <80% 3
Severe
≥30% and <50% 4
Very Severe
<30% (or <50% with chronic respiratory failure or right sided heart failure)

16. ARTERIAL BLOOD GASES
Significant changes in arterial blood gases are not usually present until the FEV1 is less than 1 L.
Patients with severe COPD can have a low arterial oxygen tension (PaO2 45 to 60 mm Hg) and an elevated arterial carbon dioxide tension (PaCO2 50 to 60 mm Hg).
Hypoxemia results from hypoventilation (V) of lung tissue relative to perfusion (Q) of the area.
The low V:Q ratio progresses over several years, resulting in a consistent decline in the PaO2.

17. During COPD exacerbation respiratory distress occurs due to the sharp rise in PaCO2 resulting in an uncompensated respiratory acidosis.
The diagnosis of acute respiratory failure in COPD is made on the basis of an acute drop in PaO2 of 10 to 15 mm Hg or any acute increase in PaCO2 that decreases the serum pH to 7.3 or less.

18. Additional acute clinical manifestations include restlessness, confusion, tachycardia, diaphoresis, cyanosis, hypotension, irregular breathing, miosis, and unconsciousness.
The most common cause of acute respiratory failure in COPD is acute exacerbation of bronchitis with an increase in sputum volume and viscosity.
This serves to worsen obstruction and further impair alveolar ventilation, resulting in worsening hypoxemia and hypercapnia.

19. Goals of treatment To prevent disease progression,
To relieve symptoms,
To improve exercise tolerance,
To improve overall health status,
To prevent and treat exacerbations,
To prevent and treat complications
To reduce morbidity and mortality.

20. Treatment Non pharmacological
Smoking cessation is the most effective strategy to reduce the risk of developing COPD and the only intervention proven to affect the longterm decline in FEV1 and slow the progression of COPD.
Pulmonary rehabilitation programs include exercise training along with smoking cessation, optimal medical treatment, psychosocial support, and health education.
Annual vaccination with the inactivated intramuscular influenza vaccine is recommended.
One dose of the polyvalent pneumococcal vaccine is indicated for patients at any age with COPD.
Supplemental oxygen therapy increases survival in COPD patients with chronic hypoxemia.

21. Pharmacotherapy
Bronchodilators are used to control symptoms and inhaled therapy is generally preferred
Additional therapies should be added in a stepwise manner depending on response and disease severity.
Clinical benefits of bronchodilators include increased exercise capacity, decreased air trapping, and relief of symptoms such as dyspnea.
However, significant improvements in pulmonary function measurements such as FEV1 may not be observed

22. Sympathomimetics
Albuterol, levalbuterol, bitolterol, pirbuterol, and terbutaline are the preferred short-acting agents because they have greater β2 selectivity and longer durations of action than other short-acting agents (isoproterenol,metaproterenol, and isoetharine).
The use of oral and parenteral β2 agonist in COPD is discouraged because they are no more effective than MDI or DPI and the incidence of systemic adverse effects such as tachycardia and hand tremor is greater.

23. Formoterol and salmeterol are long-acting inhaled β2-agonists that are dosed every 12 hours on a scheduled basis and provide bronchodilation throughout the dosing interval.
They are not indicated for acute relief of symptoms.
It should be considered for frequent and persisitent symptoms.
LABAs are also used to reduce nocturnal symptoms.

24. Anticholinergics
When given by inhalation, anticholinergic agents such as Ipratropium or atropine produce bronchodilation by competitively inhibiting cholinergic receptors in bronchial smooth muscle.
Ipratropium bromide has a slower onset of action than short-acting β2-agonists but a longer duration of action.
Lack of systemic absorption of ipratropium diminishes anticholinergic side effects .
Tiotropium bromide is a long-acting agent that protects against cholinergic bronchoconstriction for more than 24 hours.

25. The combination of an inhaled anticholinergic and
β2-agonist is often used, especially as the disease progresses and symptoms worsen over time.
A combination product containing albuterol and ipratropium (Combivent) is available as an MDI for chronic maintenance therapy of COPD.

26. Methylxanthines
Chronic theophylline use in COPD has been shown to produce improvements in lung function, including vital capacity and FEV1.
Methylxanthines are no longer considered first-line therapy for COPD.
The role of theophylline in COPD is as a maintenance therapy in the non acutely ill patients .
Therapy can be initiated at a dose 200 mg twice daily and titrated upwards every 3-5 days to the target dose.
Inhaled bronchodilator therapy is preferred over theophylline for COPD.

27. Corticosteroids
The antiinflammatory mechanisms whereby corticosteroids exert their beneficial effect in COPD include
reduction in capillary permeability to decrease mucus, inhibition of release of proteolytic enzymes from leukocytes, and inhibition of prostaglandins.

28. Combination therapy
Bronchodilators and inhaled corticosteroids
An inhaled corticosteroid combined with a long acting beta agonist ( eg: salmeterol + fluticasone or formoterol + budesonoide ) is superior to the individual components in reducing exacerbations and improving lung function.
Combination inhaler makes administration of both ICs and long acting bronchodilators more convenient and decreases total number of inhalations needed daily.

29. α 1 antitrypsin replacement therapy
For patients with inherited AAT deficiency associated emphysema ,treatment focuses on reduction of risk factors such as smoking, symptomatic treatment with bronchodilators and augmentation therapy with replacement AAT.
Augmentation therapy consisit of weekly infusions of pooled human AAT to maintain AAT plasma levels over 10 micromolar.
Recommended dosing regimen for replacement AAT is 60mg/kg administered IV once a week at a rate of 0.08ml/kg/min.

30. Stage
1: Mild
2:Moderate
3:Severe
4:Very severe
Characteristics
FEV1 :FVC<70%
FEV1 ≥80%
With or without symptoms
50% >FEV1 <80%
30%>FEV1 <50%
FEV1 <30% or presence of chronic respiratory failure or right heart failure
Avoidance of risk factor(s);influenza vaccination pneumococcal vaccine
Add short-acting Bronchodilator when needed
Add regular treatment with one or more long-acting
bronchodilators
Add rehabilitation
Add inhaled glucocorticoids if
repeated exacerbations
Add long-term
oxygen if
chronic
respiratory
failure
Consider
surgical treatment

31. ACUTE EXACERBATION OF COPD
Staging
Mild (typeI )
One cardinal symptoms plus at least one of the following :URTI within 5 days ,fever with out other explanation ,increased wheezing , increased cough , increase in respiratory or heart rate >20%above base line
Moderate (type 2)
Two cardinal symptoms
Severe (type3)
Three cardinal symptoms
Cardinal symptoms include worsening of dyspnea ,increase in sputum volume and increase in sputum purulence

32. TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE EXACERBATION.
Oxygen therapy should be considered for any patient with hypoxemia during an exacerbation. Caution must be used because many COPD patients rely on mild hypoxemia to trigger their drive to breathe.
Overly aggressive oxygen administration to patients with chronic hypercapnia may result in respiratory depression and respiratory failure.
Oxygen therapy should be used to achieve a PaO2 of greater than 60 mm Hg or oxygen saturation of greater than 90%.
Arterial blood gases should be obtained after oxygen initiation to monitor carbon dioxide retention resulting from hypoventilation.

33. Bronchodilators
The dose and frequency of bronchodilators are increased during acute exacerbations to provide symptomatic relief.
Short-acting β2-agonists are preferred because of their rapid onset of action.
Anticholinergic agents may be added if symptoms persist despite increased doses of β2-agonists.
Nebulization may be considered for patients with severe dyspnea who are unable to hold their breath after actuation of an MDI
Clinical evidence supporting theophylline use during exacerbations is lacking.

34. Corticosteroids
Results from clinical trials suggest that patients with acute COPD exacerbations should receive a short course of IV or oral corticosteroids.
Although the optimal dose and duration of treatment are unknown, it appears that a regimen of prednisone 40 mg orally daily (or equivalent) for 10 to 14 days
can be effective for most patients.
If treatment is continued for longer than 2 weeks, a tapering oral schedule should be employed to avoid hypothalamic-pituitary-adrenal axis suppression.

35. Antimicrobial Therapy
Although most exacerbations of COPD are thought to be caused by viral or bacterial infections, as many as 30% of exacerbations are caused by unknown factors.
Antibiotics are of most benefit and should be initiated if at least two of the following three symptoms are present:
(1) increased dyspnoea;
(2) increased sputum volume;
(3) increased sputum purulence.

36. Selection of empiric antimicrobial therapy should be based on the most likely organisms. The most common organisms for acute exacerbation of
COPD are Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and H. parainfluenzae.
In uncomplicated exacerbations, recommended therapy includes a macrolide (azithromycin, clarithromycin), second- or third-generation cephalosporin, or doxycycline.

37. In complicated exacerbations where drug-resistant pneumococci, β-lactamase- producing H. influenzae and M. catarrhalis, and some enteric gram negative organisms may be present,
Recommended therapy includes amoxicillin/ clavulanate or a fluoroquinolone with enhanced pneumococcal
activity (levofloxacin, gemifloxacin, moxifloxacin).
In complicated exacerbations with risk of Pseudomonas aeruginosa, recommended therapy includes a fluoroquinolone with enhanced pneumococcal and P. aeruginosa activity (levofloxacin). If IV therapy is required, a β-lactamase resistant penicillin with antipseudomonal activity or a third- or fourth-generation
cephalosporin with antipseudomonal activity should be used.

38. COMPLICATIONS OF COPD Cor Pulmonale
Right sided heart failure secondary to pulmonary hypertension
Long term Oxygen therapy and diuretics are the main stay of therapy
Polycythemia
Polycythemia secondary to chronic hypoxemia in COPD patients can be improved by either oxygen therapy or periodic phlebotomy if oxygen therapy alon eis not sufficient
Acute phlebotomy is indicated if the haematocrit is above 55-60% .