1. Pathophysiology of asthma and chronic obstructive pulmonary disease
M. Tatár

3. OBSTRUCTIVE LUNG DISEASES
localized: laryngeal constriction, tracheal and bronchial carcinoma, foreign bodies
generalized: asthma, COPD, bronchiectasis, cystic fibrosis
OBSTRUCTIVE VENTILATORY DISORDER - spirometry
Airflow limitation

5. End of quiet expiration
- 0.5
- 2.5
0.5
Inspiration

6. Inspiration
- 2.5
+ 2.0
Forced
expiration
0.5
- 2.0
- 1.5
- 1.0
- 0.5

7. Forced expiration
+ 2.0
0.5
+ 2.5
+ 2.0
+ 1.5
+ 1.0
EPP

8. Bronchial asthma

9. ASTHMA - definition
Heterogeneous, multifactorial disease with variable and mostly
reversible respiratory pathway obstruction based on a chronic
bronchial inflammatory reaction.
Symptoms (wheezing, cough particularly at night and early morning, dyspnoea – chest tightness or shortness of breath)
are variable and correlated with expiratory flow limitation.
Bronchial hyperresponsiveness is often present

10. Volume
Normal subject
Asthmatic (after bronchodilator)
Asthmatic (before bronchodilator)
FEV1
Time (seconds)

11. Classification A. Allergic asthma atopy, genetic predisposition
 IgE, mast cells and eosinophils response to allergens
A. Nonallergic asthma
no environmental causes can be identified
negative skin test to common airborn allergens
rather negative family history
C. Occupational asthma
sensibilisation of airways to inhalant chemicals

12. Development of asthma Risk factors Predisposing - atopy, gender
Causal - allergens, aspirin, chemicals
Contributing - respiratory infections, diet,
air pollution, smoking
Factors that exacerbate asthma - triggers
allergens, respiratory infections, exercise, emotions

13. Triggers – mechanisms of action
Respiratory infections
epithelial damage
airway inflammation
Exercise
hyperventilation (reflex airflow limitation)
- cooling of mucosa
- osmolarity changes of fluid lining epithelium
Emotions (laughing, crying, anger, fear)
hyperventilation
hypocapnia (bronchioloconstriction)

14. Key factor - airway inflammation Mechanisms - direct and indirect
Bronchial hyperresponsiveness
Instability of the airways = exaggerated bronchoconstrictor response to a wide variety of stimuli
Key factor - airway inflammation
Mechanisms - direct and indirect

15. Airway hyperresponsiveness
Direct antagonists
(methacholine)
Nerve
Airway with
limited airflow
SO2, bradykinin
Mediators
Indirect agonists
(exercise, hypotonic or
hypertonic aerosols
Mast cell

16. antihyperreactive factors prohyperreactive factors
2-adrenergic
-adrenergic
VIP/PHM
cholinergic
anticholinergic
SP/NK
neutral peptidases
free radicals
antioxidants
peptidases (Neu)
corticoids

17. Pathological changes in airways
normal
asthma
epithelium
basement membrane
smooth muscle
mucus plug
mucus glands

18. Mechanisms of asthma 1. Airway inflammation
- recruitments of inflammatory cells from circulation
- endothelial adhesion molecules
- activation of T lymphocytes (Th2 clone)
-  production of IgE, leukotriens, prostanoids
- cytokines (CD4+ Th subtype)
- mast cells, eosinophils

19. Neural control of airways - neurogenic inflammation
Antigen etc.
Macrophage
Mast cell
T-lymphocyte
Neutrophil
Eosinophil
Mucus plug
Epithelial shedding
Vasodilation
Subepithelial fibrosis
Sensory nerve
Plasma leak
Efferent nerve
Oedema
Airway constriction and smooth muscle hypertrophy/hyperplasia

20. Mechanisms of expiratory flow limitation
1. Acute bronchoconstriction
2. Swelling of the airway wall
- vasodilation
- infiltration (Eo, Neu)
3. Chronic mucus plug formation
4. Airway wall remodeling

21. Bronchoconstriction  airflow resistance
muscle constriction 35 %
Normal
R = 1
R = 10
muscle constriction 35 %
Asthma
R = 2
R = 40

22. (for development of asthma)
Risk factors
(for development of asthma)
INFLAMMATION
Airway
hyperresponsiveness
Airflow limitation
Risk factors
(for exacerbations)
Symptoms

25. Chronic obstructive pulmonary disease (COPD)

26. Definition
Disease characterized by persistent airflow limitation that is
usually progressive and associated with an enhanced chronic
inflammatory response in the airways and the lung to inhaled
noxious particles or gases.
Chronic expiratory flow limitation
-  maximum expiratory flows
- slow forced emptying of the lungs
Combination of two pathological processes
- airways damage
- emphysema

27. COPD Chronic bronchitis Emphysema defined in clinical terms
chronic cough with sputum production
- (3 months a year,
2 successive years)
- excluded cardiac or
other pulmonary causes
Emphysema
defined anatomically
permanent, destructive enlagrement of airspaces distal to the terminal bronchioles without obvious fibrosis

28. Chronic airflow limitation - mechanisms
Chronic inflammation causes:
- structural changes and narrowing of the small airways (obstructive bronchiolitis)
- destruction of the lung parenchyma leads to the loss of alveolar attachments to the small airways and decreasing lung elastic recoil
- these changes diminish the ability of the airways to remain open during expiration

31. 1 - antitrypsin deficiency Heavily polluted environments
Risk factors
Cigarette smoking
1 - antitrypsin deficiency
Solid fuel used for indoor heating or cooking without adequate ventilation
Heavily polluted environments

32. Never smoked Smoked regularly Stopped at age 45 yrs Disability
100
Never smoked 75
Smoked regularly
FEV1 %
Stopped at
age 45 yrs 50
Disability 25
Stopped at
age 65 yrs
Death 25 75 50
Age yrs

33. Cellular and biochemical mechanisms
Inflammation: alveolar macrophages, CD8+ T lymphocytes,
neutrophils
 production of elastase, cathepsine G, collagenase
 oxidative stress in smokers and in COPD patients
Neutrophil and macrophage enzymes and oxidants
destroy components of extracellular matrix (collagen, elastin, fibronectine, proteoglycans)
Loss of cellular components of lung parenchyma:
- elastase can induce apoptosis
- cells exposed to oxidants may undergo necrosis

34. Imbalance
proteases
antiproteases system
oxidants
antioxidants
Destruction of lung
parenchyma
Small airways
disorder

39. Pathology of peripheral airways
mucus plugging
goblet cell hyper/metaplasia
fibrosis
smooth muscle hypertrophy

40. Maximal expiratory efforts
Peak exp. flow 12
Maximal
expiratory efforts 6
V´ ( l.s-1 )
- 6 25 50 75
100
VC ( % exhaled)

41. COPD phenotypes symptoms obstruction severity risk of exacerbations
occurrence of comorbidities

42. Frequent comorbidities
Loss of weight Dysfunction of skeletal muscles Osteoporosis Progression of aterosclerosis and coronary artery disease

43. Systemic inflammation

44. Local and systemic inflammation