This document provides an overview of COPD and emphysema pathogenesis. It discusses: 1. The case of a 55-year-old male smoker presenting with dyspnea and a history of 20 pack-years of smoking. 2. The pathogenesis of emphysema, which involves chronic smoke exposure leading to lung inflammation and damage, structural cell death, and ineffective repair of lung tissue. 3. Definitions and classifications of COPD, emphysema, and chronic bronchitis from leading health organizations.

1. Pratap Sagar Tiwari, MD,
Internal Medicine, NMC
COPD -PART 1

2. CASE SCENARIO
• 55 years old male ,a chronic smoker with
history of 20 pack years presented with
complaints of dyspnea.
• Note: 20 cig/day /year = 1 pack year
• Copd is unlikely when it is < 10 pack/year.

3. STEP 1
• Lungs had Chronic exposure to cigarette smoke 
recruitment of inflammatory cells within the terminal
airspaces of the lungs.

4. STEP 2
• These inflammatory cells release elastolytic
proteinases that damage the extracellular matrix of the
lung.
Proteinases: examples are neutrophil elastase,
Cathepsins etc
Note: Cathepsins inhibitor: odanocatib
neutrophil elastase inhibitor: sivelastat

5. STEP 3 & 4
• Loss of matrix cell attachment plus Oxidant stress
leads to Structural cell death.
• Ineffective repair of elastin and other extracellular
matrix component
Airspace enlargement

6. PATHOGENESIS OF EMPHYSEMA
1. Chronic exposure to cigarette smoke may lead to
recruitment of inflammatory cells within the terminal
airspaces of the lungs.
2. These inflammatory cells release elastolytic proteinases
that damage the extracellular matrix of the lung.
3. Structural cell death result from oxidant stress and loss of
matrix cell attachment.
4. Ineffective repair of elastin and other extracellular matrix
component result in airspace enlargement.

8. EMPHYSEMA
• Emphysema affects the structures distal to the terminal
bronchiole, consisting of the respiratory bronchiole, alveolar ducts, alveolar
sacs, and alveoli, known collectively as the acinus.
• These structures in combination with their associated capillaries and
interstitium form the lung parenchyma.
• The part of the acinus that is affected by permanent dilation or destruction
determines the subtype of emphysema.
1. Proximal acinar (centrilobular) emphysema
2. Panacinar emphysema refers to enlargement or destruction of all
parts of the acinus.
3. In distal acinar (paraseptal) emphysema

9. • Smoking results in tracheo-bronchial mucous gland
enlargement and goblet cell hyperplasia leading to cough
and mucous production that defines chronic bronchitis.
• Although not as prominent as in asthma, patient may have
smooth muscle hypertrophy and bronchial hyperreactivity
leading to airflow limitation.
(Note: Goblet cells are glandular simple columnar epithelial cells
whose function is to secrete gel forming mucins, which are the
major component of mucus.)

10. COPD
• The Global Initiative for Chronic Obstructive Lung Disease (GOLD) – a project initiated by the National
Heart, Lung, and Blood Institute (NHLBI) and the World Health Organization (WHO) defines COPD as
follows [1]:
• COPD is chronic obstructive disease of airways
that is characterized by airflow limitation that is
usually progressive and not fully reversible. It
associated with an enhanced chronic
inflammatory response in the airways and the lung
to noxious particles or gases.
Reference:
1. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: Revised 2011. Global
Initiative for Chronic Obstructive Lung Disease (GOLD). www.goldcopd.org

11. SUBTYPES OF COPD
• Emphysema, chronic bronchitis, and
chronic obstructive asthma.
• Note: Extrapulmonary manifestations include
impaired nutrition, weight loss and skeletal
muscle dysfunction.

12. COPD :SUBTYPES
• Emphysema is an anatomical condition characterized by
abnormal and permanent enlargement of the airspaces distal to
the terminal bronchioles that is accompanied by destruction of
the airspace walls, without obvious fibrosis.1
• Chronic bronchitis is a clinically defined condition that is
characterized as a chronic productive cough for three months in
each of two successive years in a patient in whom other causes
of chronic cough (eg, bronchiectasis) have been excluded .2
References:
1. Rennard SI. COPD: overview of definitions, epidemiology, and factors influencing its development. Chest 1998; 113:235S.
2. Celli BR, MacNee W, ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the
ATS/ERS position paper. Eur Respir J 2004; 23:932.

13. • The National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3 gives the following definition of asthma.
• Asthma is a chronic inflammatory disorder of the airways
characterized by airflow limitation/obstruction that varies
markedly , both spontaneously and with treatment.
• There is a hyperresponsiveness to a wide range of
triggers leading to excessive narrowing with consequent
decrease in airflow and symptomatic wheezing and
dyspnea.
Reference:
• GINA report, global strategy for asthma management and prevention 2006. Global Initiative for Asthma (GINA) file://www.ginasthma.org (Accessed on may
13, 2014).

14. EXTRA NOTES:
• Patients with asthma whose airflow obstruction is completely
reversible are not considered to have COPD.
• Persons with chronic bronchitis, emphysema, or both are not
considered to have COPD unless they have airflow obstruction.
• Patients with airflow obstruction due to diseases that have a
known etiology or a specific pathology (eg, cystic
fibrosis, bronchiectasis, obliterative bronchiolitis) are not
considered to have COPD .

15. CLINICAL FEATURES
• COPD should be suspected in any patient over the age of 40
years who presents with symptoms of chronic bronchitis and/or
breathlessness.
• Cough and associated sputum production are usually the first
symptoms, often referred to as a 'smoker's cough'.
• Breathlessness usually brings about the first presentation to
medical attention.
• In advanced disease, enquiry should be made as to the
presence of oedema (which may be seen for the first time during
an exacerbation) and morning headaches, which may suggest
hypercapnia.

16. MMRC

17. • In COPD there is air trapping (increased residual volume) AND hyperinflation
(increased total lung capacity) late in the disease. Despite compensating for
airway obstruction, hyperinflation can push the diaphragm into a flat position
with a number of adverse effects.
1. Firstly, by decreasing the zone of apposition between the diaphragm and
abdominal wall, positive abdominal pressure during inspiration is not applied
as effectively to the chest wall, hindering ribcage movement and impairing
inspiration.
2. Second, because the muscle of flat diaphragm are shorter than the normal
curved diaphragm, they are less capable of generating Inspiratory pressure
than normal.
3. Third, the flattened diaphragm (with increased radius if curvature, ) must
generate greater tension to develop the pressure required to produce tidal
breathing.

18. RISK FACTORS
• Family history
• Smoking history
• Age at initiation
• Average amount smoked per day since initiation
• Environmental history

19. SYMPTOMS
Dyspnea
• Ask about the amount of effort required to induce uncomfortable breathing. Many
individuals will deny symptoms of dyspnea, but will have reduced their activity levels
substantially.
Cough
• Cough with or without sputum production.
• The presence of chronic cough and sputum has been used to define chronic
bronchitis.
Wheezing
• Wheezing occurring during breathing indicate the presence of airflow obstruction
Acute chest illnesses
• Inquire about occurrence and frequency of episodes of increased cough and sputum
with wheezing, dyspnea, or fever.

20. BEDSIDE EXAMINATION IN EMPHYSEMA
Inspection
• Purse lip respiration
• Barrel shape chest
Palpation
• Non localisation of apex beat
• Diminished chest expansion
• Diminished vocal fremitus
Barrel shape chest
Circular
Horizontal ribs
Wide subcostal angle
Slight kyphosis
Prominent sternal angle

21. BEDSIDE EXAMINATION IN EMPHYSEMA
Percussion
• Hyperresonant
• Loss of liver and cardiac dullness
Auscultation
• Diminished breath sound
• Wheeze and ronchi may be present
• Force expiratory time prolonged

22. MUSCLES OF RESPIRATION
Normal Respiration
• Inspiration: Diaphragm, External Intercostal Muscles
• Expiration: elastic recoil of the lungs
Forceful Respiration
• Inspiration: scalene muscles - Elevate the first two
ribs, sternomastoids - Raise the sternum, alae nasi -
Flare the nostrils, Pectoralis major and minor
• Expiration: intercostal muscles and abdominal muscles

23. PURSE LIP BREATHING
• Improves ventilation
• Releases trapped air in the lungs
• Keeps the airways open longer and decreases
the work of breathing
• Prolongs exhalation to slow the breathing rate
• Relieves shortness of breath
• Causes general relaxation

24. PHYSICAL EXAMINATION
Other
• Unusual positions to relieve dyspnea at rest
• Digital clubbing suggests the possibility of lung
cancer or bronchiectasis.
• Mild dependent edema may be seen in the
absence of right heart failure

27. END OF PART 1