Bronchial Asthma (BA) vs Chronic Obstructive Pulmonary Disease (COPD)

Dr Chua Keong Tiong Division of Respiratory Medicine Department of Medicine

Case 1
24, , feels SOB at night. She gets the symptoms half of the time. The other half of the time, she is very well without limitation to her exercise.
A. B.

C.
D.

Bronchial Asthma COPD Combination of A+B I dont know, thats why I am here

Case 2
60, , feels SOB on exertion. She gets the symptoms all the time. Her SOB is persistent and gradually worsened over a 2-year period. She is a chronic heavy smoker.
A. B.

C.
D.

Bronchial Asthma COPD Combination of A+B I dont know, thats why I am here

Case 3
50, , feels SOB at night. She gets the nocturnal symptoms half of the time. She also has reduced in effort tolerance in the past 2 years. She noticed there was a steady trend towards worsening. She is a chronic heavy smoker.
A. B.

C.
D.

Bronchial Asthma COPD Combination of A+B I dont know, thats why I am here

Case 4
50, , feels SOB on exertion. She has a history of poorly control asthma for 30 years. She usually gets her nocturnal symptoms, but over the past 2 years, she noticed that she was getting the similar symptoms during the daytime especially on exertion. The SOB was persistent and progressive, and it did not seem to respond to her bronchodilator. She is a life-long non smoker.
A. B. C. D.

Bronchial Asthma COPD Combination of A+B I dont know, thats why I am here

Overview

Bronchial Asthma

COPD

Definition Pathophysiology Pathogenesis Epidemiology Symptomology Physical Signs Investigations Treatment plan

Definition Pathophysiology Pathogenesis Epidemiology Symptomology Physical Signs Investigations Treamtent plan

Comparison of BA vs COPD

Bronchial Asthma
Chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment.

BA - Pathophysiology

Triggers Exercise Animals Pollen Aerosol chemicals Dust mites Respiratory tract infection Smoke Changes in temperature Drugs Strong emotional expression

BA - Pathophysiology
Cells in Asthma Mast cells Eosinophils Neutrophils T Cells Macrophage and Dendritic Cells Airway Smooth Muscle Cells Epithelial Cells and Goblet Cells

Mast Cells and Basophils

Expression of the high-affinity IgE receptor Activated by IgE-allergen complex Release

Histamine Tryptase Leukotrienes Prostaglandins Cytokines

Eosinophils
Actively recruited into the airway by chemokines upon allergen exposure Release

Granule proteins Leukotrienes Prostaglandins Cytokines

BA - Pathophysiology
Molecular Mediators Cytokines Chemokines IgE Leukotrienes Prostanoids Nitric Oxide Granule Proteins

Cytokines
Key mediators in the pathogenesis of the crhonic inflammation IL-5

Activates Eosinophils

Chemokines
Recruitment or chemotaxis of inflammatory cells Important for localisation of inflammatory cells into the airways

IgE
Triggering mast cells activation High level is present especially in allergic asthma

MODERN VIEW OF ASTHMA

Allergen
Macrophage/ Dendritic cell Th2 cell Neutrophil Eosinophil Epithelial shedding Nerve activation

Mast cell

Multiple Mediators (>100) Mucus plug

Subepithelial Plasma leak Oedema fibrosis Sensory nerve activation Cholinergic reflex Bronchoconstriction Hypertrophy/hyperplasia

Mucus Vasodilatation hypersecretion New vessels hyperplasia

BA - Epidemiology

Worldwide, 300 million people of all ages, and all ethnic backgrounds suffer from asthma. In SouthEast Asia, the number of persons with asthma is around 17.5 million. Higher in urban compared to rural population

Asthma Prevalance and Mortality

GINA 2007

BA - Symptomology
Shortness of breath Wheeze Chest tightness Cough Variable and precipitated by non-specific irritants Worsening at night Respond to Asthma treatment

Questions to Consider in the Diagnosis of BA

1. 2. 3. 4.

5.

6.

Has the patient had an attack or recurrent attacks of wheezing? Does the patient have a troublesome cough at night? Does the patient wheeze or cough after exercise? Does the patient experience wheezing, chest tightness, or cough after exposure to airborne allergens or pollutants? Do the patients colds go to the chest or take more than 10 days to clear up? Are symptoms improved by appropriate asthma treatment?

BA - Physical examination

Wheezing

Turbulent airflow through narrowed airways Usually expiratory Maybe absent in very mild or very severe disease

Signs of rhinitis, sinusitis and nasal polyps During acute exacerbation

Lung hyperinflation Use of accessory muscles of respiration Prolonged expiratory phase of breathing

BA - Investigations
Peak

Expiratory Flow Rate Spirometry

Bronchial Challenge Test Blood tests

ABG, systemic eosinophilia, serum IgE levels

Eosinophils counts Skin prick test, Patch test, IgE RAST tests

Sputum tests Allergy Tests Exhaled Nitric Oxide

Important Information in PEFR Chart

1.

2.
3.

Diurnal Variability Reversibility Current PEFR / Personal Best PEFR

Lung Function Test

Important Information in Spirometry

1.

FEV1/FVC

Indicating airflow obstruction

Indicating the severity of airflow obstruction FEV1% > 12% FEV1 > 200ml

2.

FEV1%

3.

Reversibility of airflow obstruction

BA - Management

Education

Improve patient understanding of BA Encourage adherence to treatment Engage patient in self-management practice Action plan during Asthma exacerbation
Avoidance of aeroallergens, viral respiratory pathogens, air pollution and certain drugs

Environmental Control

Vaccination

Influenza vaccine Pneumococcal vaccine

BA Management

CONTROL

Overview

Bronchial Asthma

COPD

Definition Pathophysiology Pathogenesis Epidemiology Symptomology Physical Signs Investigations Treatment plan

Definition Pathophysiology Pathogenesis Epidemiology Symptomology Physical Signs Investigations Treamtent plan

Comparison of BA vs COPD

What is COPD?

Pulmonary Component

Airflow limitation which is not fully reversible Mixture of airway disease and parenchymal destruction Progressive Abnormal inflammatory response
Co-morbidities associated with smoking and aging ?Systemic inflammatory disorder

Extra-pulmonary Component

Preventable and Treatable

Clinical Disorders associated with COPD

Emphysema

Airspace enlargment due to disappearance of alveolar septae, leading to loss of elastic recoil, airflow obstruction, hyperinflation and air-trapping
Daily chronic cough and sputum production for 3 months, two years in a row

Chronic Bronchitis

COPD - Risk factors

Fletcher Curve

COPD - Risk Factors

Tobacco Smoke

incl. cigarettes, cigars

Occupational Dust and Chemicals Indoor and Outdoor Air Pollution

?Haze Female is more susceptible

Gender

Infection
Childhood respiratory infection

Socioeconomic Status -1 anti-trypsin deficiency

COPD - Pathogenesis
Inflammation Proteinase-Antiproteinase Imbalance Oxidant-Antioxidant Imbalance Apoptosis Mucus Hypersecretion

Inflammation

Recruitment of inflammatory cells caused by smoking and other irritants The inflammation may persist long after smoking cessation Macrophage

Releases proteinase Produces chemotactic factors Produces matrix metalloproteinases

CD4+, CD8+ and B cells form bronchusassociated lymphoid tissue (BALT) Upregulation of IL-8, MIP 1-, MCP-1 and etc

Proteinase-Antiproteinase Imbalance
Neutrophil elastase Matrix metalloproteinases Effect of proteinase

Degrading matrix protein Releasing cell-bound and matrix-bound chemokines Activating growth factors Inducing expression of mucin genes

Antiproteinases : 1-antitrypsin

Oxidant-Antioxidant Imbalance

Reactive oxygen species

Hydrogen peroxide Hydroxyl radicals Superoxide radicals

Neutrophil myeloperoxidase Effects of Oxidant

Inhibit anti-proteinases Affect lipid and DNA Induce apoptosis Facilitate proteinase-mediated extracellular matrix degradation Participate in nonenzymatic degradation

Antioxidant : Nuclear factor E2-related factor, glutathione peroxidase

Apoptosis
Lost of alveolar tissue Alveolar vascular destruction Cigarettes smoking induces apoptosis

Mucus Hypersecretion
Hyperplasia of goblet cells Hypertrophy of glands ratio of glandular mucus cells to serous cells acidity mucin glycosylation antimicrobial peptides

Epidemiology of COPD
6th leading cause of Death worldwide in 1990 ? 3rd leading cause by 2020 In Malaysia

4.7% of population age >30 years old

COPD - Symptomology

Dyspnoea Effort Tolerance Chronic Cough Wheezing Chest Tightness

Weight loss Anorexia Depression / Anxiety

) ) Severe COPD )

History tends to be progressive with intermittent exacerbation

COPD Physical Signs

Physical Examination

Important but rarely diagnostic

Cyanosis Tracheal Tug Barrel Chested Intercostal recession Prolonged Expiratory Phase with Rhonchi Loss of Cardiac and Liver Dullness Signs of Cor Pulmonale

COPD - Investigation

Spirometry

FVC FEV1
FEV1/FVC

Total Lung Volume Residual Volume DLCO FEF 25%-75%

COPD - Investigation

Spirometry
FVC FEV1

FEV1/FVC

< 70%

Total Lung Volume Residual Volume DLCO FEF 25%-75%

COPD - Other Investigation

CXR ABG Alpha-1 Anti-trypsin Level

COPD - CXR

COPD - CT

COPD - Management

Overview

Bronchial Asthma

COPD

Definition Pathophysiology Pathogenesis Epidemiology Symptomology Physical Signs Investigations Treatment plan

Definition Pathophysiology Pathogenesis Epidemiology Symptomology Physical Signs Investigations Treamtent plan

Comparison of BA vs COPD

COPD Asthma

COPD is NOT Asthma

Different Causes
Different Inflammatory Cells Different Mediators

Different Inflammatory Consequences

Different sites

Different response to treatment

Different Causes
COPD Asthma Inhalational Exposures Sensitising Allergen Cigratte Smoke Domestic Mites Occupational Dust and Animal Fur Chemical Cockroach Allergen Environmental Tobacco Pollen Smoke Indoor and Outdoor Air Pollution

Different Causes
COPD Asthma Genetic Genetic 1-antitrypsin Heritable Deficiency Other Other Childhood Respiratory Childhood Infection Infection (Hygiene Theory)

Different Causes
COPD Other risk factors Male Gender Lower Socioeconomic Status Asthma Other risk factors Gender Breastfeeding Tobacco Smoke Obesity

Pathophysiology of COPD and Asthma

Noxious agent
CD8+ lymphocyte

COPD
Alveolar macrophage

Asthma
Mast cell

Sensitizing agent
CD4+ lymphocyte

Eosinophil Cytokines (IL-8) Mediators (LTB4) Neutrophil

Histamine Cytokines (IL-4, IL-5, IL-13) Mediators (LTD4)

Proteases
Alveolar wall destruction Mucus hypersecretion

Epithelial shedding

Inflammatory mediators

Airway thickening

Airway hyperreactivity Barnes PJ (1999; 2000)

COPD vs ASTHMA Clinical Differences Feature

Age of onset Smoking history Sputum production Disease Course Clinical symptoms Airway Reversibility

Asthma
Usually < 40 years Not causal Infrequent Stable (with exacerbations) Intermittent & variable Largely reversible Usually near-normal pulmonary function

COPD
Usually > 40 years Usually > 20 packs years Often (purulent) Progressive worsening (with exacerbations) Persistent & progressive Not fully reversible Only partially reversible with bronchodilator use Smoking cessation can slow lung function decline

Peter J Barnes, 1999 CTS Guidelines Committee Can Respir J 2003; 10 (Suppl A): 11A-33A CTS Guidelines Committee Can Respir J 2003; 10 (Suppl A): 11A-33A, p. 16A

COPD vs ASTHMA Clinical Difference Feature

Cough (most prominent) Eosinophil Neutrophil Elevated IgE Family History

Asthma
Early morning

COPD
Persistent ( post exercise)

Common Uncommon Common Usually

Uncommon Common Uncommon Uncommon (except 1- antitrypsin disease)

Allergies
Spirometry

Often
Often normalizes (Usually return to almost normal lung function)

Infrequent
Never normalizes (Never return to normal lung function)

Peter J Barnes, 1999 CTS Guidelines Committee Can Respir J 2003; 10 (Suppl A): 11A-33A CTS Guidelines Committee Can Respir J 2003; 10 (Suppl A): 11A-33A, p. 16A

Overview

Bronchial Asthma

COPD

Definition Pathophysiology Pathogenesis Epidemiology Symptomology Physical Signs Investigations Treatment plan

Definition Pathophysiology Pathogenesis Epidemiology Symptomology Physical Signs Investigations Treamtent plan

Comparison of BA vs COPD

Case 1
24, , feels SOB at night. She gets the symptoms half of the time. The other half of the time, she is very well without limitation to her exercise.
A. B.

C.
D.

Bronchial Asthma COPD Combination of A+B I dont know, thats why I am here

Case 2
60, , feels SOB on exertion. She gets the symptoms all the time. Her SOB is persistent and gradually worsened over a 2-year period. She is a chronic heavy smoker.
A. B.

C.
D.

Bronchial Asthma COPD Combination of A+B I dont know, thats why I am here

Case 3
50, , feels SOB at night. She gets the nocturnal symptoms half of the time. She also has reduced in effort tolerance in the past 2 years. She noticed there was a steady trend towards worsening. She is a chronic heavy smoker.
A. B.

C.
D.

Bronchial Asthma COPD Combination of A+B I dont know, thats why I am here

Case 4
50, , feels SOB on exertion. She has a history of poorly control asthma for 30 years. She usually gets her nocturnal symptoms, but over the past 2 years, she noticed that she is getting the similar symptoms during the daytime especially on exertion. The SOB is persistent and progressive, and it did not seem to respond to her bronchodilator. She is a life-long non smoker.
A. B. C. D.

Bronchial Asthma COPD Combination of A+B I dont know, thats why I am here

The End