1. COPD Dr. Tanvir us Salam, FCCP Associate Professor of Medicine
Post Graduate Medical Institute/LGH Lahore

2. Chronic Obstructive Pulmonary Diseases
Asthma
Chronic Bronchitis
Emphysema
Bronchiectasis
Cystic fibrosis

3. Definition Asthma Atopy Airway Hyperresponsiveness
Chronic inflammatory disorder of the airways
Airway obstruction
Recurrent and reversible
Atopy
Production of abnormal amounts of IgE antibodies in response to contact with aeroallergens
Airway Hyperresponsiveness
This is an abnormality of the airways that allows them to narrow too easily and too much

4. COPD
Chronic Bronchitis is defined by the presence of a productive cough for more than three months' duration in two successive years
Emphysema is a pathological definition, with enlargement of air spaces and destruction of lung parenchyma, loss of lung elasticity distal to terminal airways

5. Asthma Chronic inflammatory disease of airway
Most common chronic disease of childhood
5-10% of population are affected
More common in developed countries
2:1 male/female ratio in childhood
Is asthma increasing?
Causing restricted activity and hospitalization
Death rate on the rise

6. COPD 14 million people in the united states have COPD
14 percent of white male smokers, as compared with approximately 3 percent of white male nonsmokers
COPD is now the sixth leading cause of death and it is the only common cause of death that is increasing in incidence
The world health organization predicts that by 2020 COPD will rise from its current ranking as the 12th most prevalent disease worldwide to the 5th and from the 6th most common cause of death to the 3rd

7. Relationship of Wheeze, Asthma, AHR
Atopy
Current
asthma
wheeze
AHR

8. RV-Induced Airway Inflammation
Hyperresponsiveness
Plasma
leakage
Mucus
hypersecretion
Inflammatory
cell recruitment
and activation
Neural activation
Virus-infected
epithelium
The mechanism of RV-induced airway inflammation is thought to depend on viral replication within respiratory epithelial cells. This viral replication triggers intracellular signaling pathways that lead to increased secretion of multiple cytokines (tumor necrosis factor-alpha, granulocyte colony-stimulating factor, and interferon-gamma [IFN-]), and chemokines (interleukin-8 [IL-8] and RANTES), and also to increased expression of adhesion molecules.1
These chemokines and cytokines are increased in airway secretions during viral infections. Their actions are thought to involve recruitment and activation of the inflammatory cells (neutrophils, eosinophils, and activated T cells) that have been linked to asthma exacerbations.1 Neutrophils are the main cells found in nasal and lower airway secretions during acute viral infections,1 and increases in blood and nasal neutrophils correlate with cold and asthma symptom scores and cold-induced changes in airway hyperresponsiveness.2
1. Gern JE, Busse WW. The role of viral infections in the natural history of asthma. J Allergy Clin Immunol. 2000;106:
2. Grünberg K, Timmers MC, Smits HH, et al. Effect of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin-8 in nasal lavage in asthmatic subjects in vivo. Clin Exp Allergy. 1997;27:36-45.

9. Types Persistent asthma Obstructed asthma Episodic asthma
Asthma in remission
Potential asthma
Trivial wheeze
Extrinsic/Atopic asthma
Occupational asthma
Intrinsic asthma

10. Risk Factors Inducers Allergens House dust mites
Respiratory infections
Passive smoking
Genetics
Trigger
Allergens
Exercise
Infections
Air pollution
Weather
Smells and irritants
Emotional factors
Food

11. Causes of Asthma Exacerbations
The fact that asthma is a chronic inflammatory disease of the airways with recurrent exacerbations has implications for prevention and treatment. Asthma symptoms may vary according to patient age, contributing mechanisms, and response to medications. Identifying the pattern of exacerbations is important for developing appropriate therapeutic strategies.1
VRIs are recognized as a major cause of wheezing in all age groups and as a major cause of exacerbations in those with established asthma.1 Evidence has shown VRIs to be the cause of asthma exacerbations in approximately 80% of children2 and in 60% to 80% of adults.3 RVs were the predominant virus detected in these studies.
Furthermore, Corne and associates4 found that although people with asthma are not at greater risk for RV infection than healthy persons, they do suffer more frequent lower respiratory infections (LRIs) and have more severe and longer-lasting lower respiratory tract symptoms.
1. Lemanske RF Jr, Busse WW. Asthma. JAMA. 1997;278:
2. Johnston SL, Pattemore PK, Sanderson G, et al. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ. 1995;310:
3. Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbations of asthma in adults. BMJ. 1993;307:
4. Corne JM, Marshall C, Smith S, et al. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet ;359:

12. Pathological Features
Macroscopic features
Over inflated lungs
Wide spread plugging of the airways with thick secretions
Normal lung parenchyma

13. Pathologic Features Microscopic features
Infiltration of epithelium with inflammatory cells
Shedding of the epithelium
Thickened basement membrane
Increased cells in lamina propria
Smooth muscle and mucous glands are hypertrophied

14. Cellular Mechanisms Involved in Airway Inflammation
ANTIGEN
IgE
Mast cell
B cell
Macrophage
Bronchospasm
T cell
Eosinophil
Neutrophils
Macrophage
INFLAMATION

15. Pathophysiology Reduction in airway diameter
Contraction of smooth muscles
Vascular congestion and edema of bronchial walls
Tenacious secretions
Increased airway resistance
Decreased forced expiratory volumes
Hyperinflation
Mismatched V/P

16. Molecular Genetics in COPD
In patients with (alpha)1-antitrypsin deficiency
Early emphysema develops that is exacerbated by smoking, indicating a clear genetic predisposition to COPD
However, less than 1 percent of patients with COPD have (alpha)1-antitrypsin deficiency

17. Molecular Genetics in COPD
A polymorphic variant of microsomal epoxide hydrolase, an enzyme involved in the metabolism of epoxides that may be generated in tobacco smoke, has been associated with a quintupling of the risk of COPD.

18. Risk Factors
In industrialized countries, cigarette smoking accounts for most cases of COPD
In developing countries other environmental pollutants, such as particulates associated with cooking in confined spaces, are important causes
Air pollution (particularly with sulfur dioxide and particulates), exposure to certain occupational chemicals (such as cadmium), and passive smoking may all be risk factors

19. Inflammation
Now apparent that there is a chronic inflammatory process in COPD
But it differs markedly from that seen in asthma, with different inflammatory cells, mediators, inflammatory effects, and responses to treatment
In contrast to the situation with asthma, eosinophils are not prominent except during exacerbations or in patients with concomitant asthma

20. Most inflammation in COPD occurs in the peripheral airways (bronchioles) and lung parenchyma.
The bronchioles are obstructed by fibrosis and infiltration with macrophages and T lymphocytes.
Destruction of lung parenchyma and an increased number of macrophages and T lymphocytes, which are predominantly CD8+ (cytotoxic) T cells.

21. Acute Exacerbations
It is now evident that many exacerbations in COPD, as in asthma, are due to upper respiratory tract viral infections (such as rhinovirus infection) and to environmental factors, such as air pollution and temperature.
There is an increase in neutrophils and in the concentrations of interleukin-6 and interleukin-8 in sputum during an exacerbation, and patients who have frequent exacerbations have higher levels of interleukin-6, even when COPD is stable.

22. Acute Exacerbations
Bronchial biopsies show no increase in sputum eosinophils during exacerbations in patients with severe COPD.
An increase in markers of oxidative stress and exhaled nitric oxide, presumably reflecting increased airway inflammation, is observed during exacerbations.

23. Medical History in Asthma
Development of disease
Age of onset and diagnosis
History of early life injury
Progress of disease
Present management
Co-morbid condition
Family history
History of asthma, allergy, sinusitis, rhinitis, or nasal polyps in close relatives
Social history
Characteristics of home
Smoking
School characteristics
Work place
Level of education

24. Medical History in COPD
Aggravating factors
All smokers!
Viral respiratory infection
Environmental allergens, indoor and out door
Exercise
Occupational chemicals
Irritants
Aggravating factors
Emotional expressions
Drugs
Food, food additives and preservatives
Change in weather, exposure to cold air
Endocrine factors

25. Medical History both Symptoms Cough Wheezing Shortness of breath
Chest tightness
Fever
Sputum production

26. Physical Examination Tachypnoea Tachycardia Pulsus Paradoxus Cyanosis
Accessory muscle use
Prolonged expiration
Wheeze
Anxious look
Position and diaphoresis

30. Investigations Chest x-ray Sinuses x-ray ECG DLC (eosinophilia)
Sputum examination
Pulmonary function test
Spirometry
ABG
Pulse oximetery

37. Classification of Asthma Severity

38. Treatment of Asthma Beta2-agonist Anticholinergics Methylxanthines
Inhaled
Short acting
Long acting
Oral
Anticholinergics
Methylxanthines
Mast cell stabilizer
Cromlyn sodium
Nedocromil
Corticosteroids
Inhaled
Systemic
Leukotrine modifiers

39. Therapeutic Measures in COPD
Antismoking Measures
Bronchodilators
Antibiotics
Oxygen
Corticosteroids
Noninvasive Ventilation
Pulmonary Rehabilitation
Lung-Volume-Reduction Surgery

40. Short Acting Inhaled Β2 Agonist
Indications
Relief of acute symptoms
Preventive prior to exercise
Mechanism
Smooth muscle relaxation
Adverse effects
Tachycardia, Skeletal muscle tremor, Hypokalemia, headache, increased lactic acid
Therapeutic issues
Drug of choice for acute spasm
Mild intermittent asthma

41. Long Acting Β2 Agonist Indications Mechanisms Adverse effects
Long term prevention of symptoms, nocturnal
Not to be used to treat acute attack
Mechanisms
Smooth muscle relaxation
Inhibit mast cell mediator release
Onset ( min.), Duration (>12 hours)
Adverse effects
QT prolongation
Other same as short acting
Therapeutic issues
Added to standard treatment with inhaled Corticosteroids

42. Systemic Β2 Agonist
Inhaled beta agonist are preferred because they have fewer side effect

43. Anticholinergics Indication Relief of acute symptoms Mechanisms
Competitive inhibition of muscarinic cholinergic receptors
Reduces intrinsic vagal tone to the airways
Decrease mucus gland secretions
Adverse effects
Dry mouth and respiratory secretions
Therapeutic issues
Reverses only cholinergically mediated bronchospasm
Additive effect to β agonist
Treatment of choice for spasm induced by beta-blocker

44. Methylxanthines Indications Mechanisms Adverse effects
Long tern control and prevention of symptoms, especially nocturnal symptoms
Mechanisms
Smooth muscle relaxation from phosphodiestrase inhibition
Increase diaphragm contractility and mucocilliary clearance
Adverse effects
Dose related toxiicities include tachycardia, nausea, vomiting SVT, headache, seizures
Usual doses include insomnia, gastric upset, increase in hyperactivity in children, difficulty in urination in elderly

45. Therapeutic Measures in COPD
Antismoking Measures
Bronchodilators
Antibiotics
Oxygen
Corticosteroids
Noninvasive Ventilation
Pulmonary Rehabilitation
Lung-Volume-Reduction Surgery

46. Antismoking Measures
Smoking cessation is the only measure that will slow the progression of COPD
Nicotine-replacement therapy (by gum, transdermal patch, or inhaler) provides help to patients in quitting smoking
The use of the recently introduced drug bupropion, a noradrenergic antidepressant, has proved to be the most effective strategy to date
A recent controlled trial showed that after a 9-week course of bupropion, abstinence rates were 30 percent at 12 months, as compared with only 15 percent with placebo
The abstinence rate was slightly improved with the addition of a nicotine patch.

47. Bronchodilators are the mainstay of current drug therapy for COPD.

48. Bronchodilators
Bronchodilators cause only a small (<10 percent) increase in FEV1 in patients with COPD
These drugs may improve symptoms by reducing hyperinflation and thus dyspnea
They may improve exercise tolerance, despite the fact that there is little improvement in spirometric measurements

49. Bronchodilators
Several studies have demonstrated the usefulness of the long-acting inhaled (beta)2-agonists salmeterol and formoterol in COPD.
An additional benefit of long-acting (beta)2-agonists in COPD may be a reduction in infective exacerbations, since these drugs reduce the adhesion of bacteria such as Haemophilus influenzae to airway epithelial cells.

50. Bronchodilators
COPD appears to be more effectively treated by anticholinergic drugs than by (beta)2-agonists, in sharp contrast to asthma, for which (beta)2-agonists are more effective.
A new anticholinergic drug, tiotropium bromide, which is not yet available for prescription, has a prolonged duration of action and is suitable for once-daily inhalation in COPD.

51. Antibiotics
Acute exacerbations of COPD are commonly assumed to be due to bacterial infection, since they may be associated with increased volume and purulence of the sputum.
Exacerbations may be due to viral infections of the upper respiratory tract or may be noninfective, so that antibiotic treatment is not always warranted.

52. Antibiotics
A meta-analysis of controlled trials of antibiotics in COPD showed a statistically significant but small benefit of antibiotics in terms of clinical outcome and lung function.
There is no evidence that prophylactic antibiotics prevent acute exacerbations

53. Oxygen Long-term oxygen therapy: reduced mortality
improvement in quality of life in patients with severe COPD and chronic hypoxemia (partial pressure of arterial oxygen, <55 mm Hg).
Oxygen does not increase survival in patients with less severe hypoxemia
The selection of patients is important in prescribing this expensive therapy.

54. In patients with COPD who have nocturnal hypoxemia, nocturnal treatment with oxygen does not appear to increase survival or delay the prescription of continuous oxygen therapy

55. Corticosteroids
Inhaled corticosteroids are now the mainstay of therapy for chronic asthma
However, the inflammation in COPD is not suppressed by inhaled or oral corticosteroids, even at high doses.
This lack of effect may be due to the fact that corticosteroids prolong the survival of neutrophils and do not suppress neutrophilic inflammation in COPD.

56. Approximately 10 percent of patients with stable COPD have some symptomatic and objective improvement with oral corticosteroids. It is likely that these patients have concomitant asthma, since both diseases are very common. Indeed, airway hyperresponsiveness, a characteristic of asthma, may predict an accelerated decline in FEV1 in patients with COPD.

57. long-term treatment with high doses of inhaled corticosteroids reduced the progression of COPD, even when treatment was started before the disease became symptomatic.
Inhaled corticosteroids may slightly reduce the severity of acute exacerbations, but it is unlikely that their use can be justified in view of the risk of systemic side effects in these susceptible patients and the expense of using high-dose inhaled corticosteroids for several years.

58. By contrast, two recent studies have demonstrated a beneficial effect of systemic corticosteroids in treating acute exacerbations of COPD, with improved clinical outcome and reduced length of hospitalization.
The reasons for this discrepancy between the responses to corticosteroids in acute and chronic COPD may be related to differences in the inflammatory response (such as increased numbers of eosinophils) or airway edema in exacerbations.

59. Noninvasive Ventilation

60. Noninvasive positive-pressure ventilation with a simple nasal mask
Which eliminates the necessity for endotracheal intubation,
Reduces the need for mechanical ventilation in acute exacerbations of COPD in the hospital,
used at home may improve oxygenation and reduce hospital admissions in patients with severe COPD and hypercapnia
The combination of noninvasive positive-pressure ventilation and long-term oxygen therapy may be more effective,

61. Pulmonary Rehabilitation
Pulmonary rehabilitation consisting of a structured program of education, exercise, and physiotherapy has been shown in controlled trials to improve exercise capacity and quality of life among patients with severe COPD and to reduce the amount of health care needed

62. Lung-Volume-Reduction Surgery
The reduction in hyperinflation improves the mechanical efficiency of the inspiratory muscles
Careful selection of patients after a period of pulmonary rehabilitation is essential.
Patients with localized upper-lobe emphysema appear to do best; relatively low lung resistance during inspiration appears to be a good predictor of improved FEV1 after surgery.

63. Functional improvements
increased FEV1,
reduced total lung capacity and functional residual capacity,
improved function of respiratory muscles,
improved exercise capacity, and
improved quality of life.

64. Thankyou