Introduction to classification and pathogenesis of major respiratory diseases

1. Hypoventilation Disorders
Obstructive
Hypoventilation
Central
and Sleep Related
Hypoventilation
Restrictive Hypoventilation

2. Hypoventilation Disorders
Obstructive
Lung
Diseases
Central and Sleep
Related
Hypoventilation
Restrictive
Lung
Diseases
Upper
Airway
Lower
Airway
Parenchymal Extra-
Parenchymal
Congenital Acquired

3. Inspiration Expiration
Upper
Airway
Lower
Airway
Differential
Effects of
Obstruction of
Upper and
Lower Airway
(Extra- versus
Intra-
Thoracic
Obstruction)

4. • Upper airway obstruction is usually more severe during inspiration.
Adventitious sound produced: Stridor.
• Lower airway obstruction is usually more severe during expiration.
Adventitious sound produced: Wheezes.
Wheezes Hyperinflation Atelectasis
Possible Consequences of Bronchial Obstruction

5. Tidal Volume
Vital
Capacity
End Normal Exp
End Normal Insp
End Maximal Insp
End Maximal Exp
Peak Flow Meter
To Measure
Peak Flow Rate
(PFR)

6. Tidal Volume X RR = Minute Ventilation (Minute Volume) (MV)
Forced Vital Capacity X RR = Maximum Breathing Capacity (MBC)
(FVC) (Maximum Voluntary Ventilation) (MVV)
….Multiplying by Respiratory Rate (RR):

7. (> 0.7)
(< 80%)
(< 80%) (< 80%)
FEV1
FVC
FEV1
FVC
Obstructive
(with Hyperinflation)
Restrictive
Two Main Patterns
of Hypoventilation Disorders

8. Obstructive Lung Diseases
Bronchial Asthma: a heterogeneous disease, usually characterized by
chronic airway inflammation. It is defined by the history of respiratory
symptoms such as wheezes, dyspnoea and cough that vary over time
together with variable expiratory airflow limitation (GINA 2015).
Chronic Bronchitis: chronic cough with expectoration for at least
6 months in a year or 3 months/Y for 2 successive years,
not due to lung disease.
Emphysema: persistent abnormal dilatation of the air spaces distal to
the terminal bronchioles (respiratory bronchioles, alveolar ducts,
alveoli), accompanied by destruction of the elastic tissues of the lungs.
Bronchiectasis: a chronic suppurative condition where the walls of the
bronchi are thickened from inflammation and infection.
Cystic Fibrosis: an inherited disease characterized by the build-up of
thick, sticky mucus that can damage many of the body's organs.
The thick mucus in the bronchial tree leads to variable degrees of
obstruction which become complicated by infection, lung damage and
ensuing respiratory failure.

9. Bronchial Asthma
Extrinsic
(Allergic)
Intrinsic
(Non-Allergic)
Atopic Non-Atopic Exercise Induced
Bronchoconstriction
(EIB)
Aspirin
Exacerbated
Respiratory
Disease
(AERD)
Some examples of etiologic types of BA

10. Type I (immediate – Anaphylactic) Hypersensitivity Reaction

11. Effector Cells and Biologic Mediators in Atopic Asthma
Mast Cells, Basophils
Eosinophils
• Preformed Mediators in Secretory Granules
• Histamine.
• Proteolytic enzymes.
• Membrane- Derived Lipid Mediators
• Prostaglandins.
• Cysteinyl Leukotrienes (CysLTs)
• Cytokines
• IL 3,4,5,6
• TNF α
• IFN γ
• GM-CSF.
• Cysteinyl Leukotrienes (CysLTs)
• Eosinophil cataionic protein
(ECP).

12. 1122
33
PathogenesisPathogenesis
of BAof BA
1)1) Lumen:Lumen: Mucus plugsMucus plugs
2)2) Mucosa:Mucosa: SwellingSwelling
3)3) Smooth Muscles:Smooth Muscles: SpasmSpasm

13. – AtopyAtopy, the genetic predisposition for the development of an, the genetic predisposition for the development of an
immunoglobulin E (IgE)-mediated response to commonimmunoglobulin E (IgE)-mediated response to common
aeroallergens, is the strongest identifiable predisposingaeroallergens, is the strongest identifiable predisposing
factor for developing asthma.factor for developing asthma.
– However, not all people with allergies have asthma, and notHowever, not all people with allergies have asthma, and not
all cases of asthma can be explained by allergic response.all cases of asthma can be explained by allergic response.
– Viral respiratory infectionsViral respiratory infections are one of the most importantare one of the most important
causes of asthma exacerbation.causes of asthma exacerbation.
– In some patients, persistent changes in airway structure
occur, including sub-basement fibrosis, mucus
hypersecretion, injury to epithelial cells, smooth muscle
hypertrophy, and angiogenesis (remodeling)

14. Exercise Induced Bronchoconstriction (EIB)
Etiology
Osmotic Theory (most likely)
Hyperventilation during exercise → Water of airway surface liquid (ASL) is
evaporated faster than it is returned by condensation or from submucosa
→ ↑ osmotic pressure of ASL. Mast cells and basophils release mediators in
response to changes in osmolarity. Exercise itself is not needed to cause
bronchoconstriction, but just the creation of a hyperosmolar environment.
Moreover, dehydration of ASL ↓ its volume → ↓ mucocilliary clearance.
Thermal Theory (inadequate)
Exposure of airways to cool air → vasoconstriction of bronchial vasculature.
After cessation of exercise, ventilation ↓ and airways rewarm
→ reactive hyperaemia and oedema of airways.
Other Factors
• Poor air quality can be associated with a high prevalence of EIB in athletes.
• In swimmers, chloramines above the water can trigger EIB.

15. Occurrence
• EIB is reported frequently in asthmatics, but can also occur in
absence of chronic asthma.
• In asthmatics, the presence of EIB is a marker of poor control and
suggests the need to step up therapy.
• Commoner in athletes than in the general population.
Diagnosis
Self- reported symptoms are not reliable for diagnosis.
Formal diagnosis requires spirometry and
a bronchoprovocation challenge:
• Exercise: should be ramped up rapidly so that target heart rate is
achieved within 2 – 3 minutes and maintained for 6 minutes.
• Inhalation of dry mannitol powder.

16. Aspirin Exacerbated Respiratory Disease (AERD)
Hypersensitivity Reactions to Aspirin
• Type (A): Respiratory (15%): rhinosinusitis, BA.
• Type (B): Dermatologic (75%): Urticaria, angio-oedema.
• Type (C): Other Presentation (10%): erythema multiforme,
Stevens Johnson syndrome.
Epidemiology
AERD afflicts about 0.5% of the population.
Prevalence ↑ to 10 – 20% among asthmatics
And to 30 – 40% among asthmatics with nasal polyps.
Age at onset 40 – 60 y.
Females are affected twice as common as males.
Symptom onset in females is earlier and significantly more severe.
This may be explained by differences in sex hormones.

17. Pathogenesis
This is an extra- immunologic (pseudo- allergic) reaction which affects
both upper and lower airways.
Aspirin (and some other NSAIDs to variable extent) block
cyclooxygenase 1 (COX1) in mast cells, basophils and eosinophils →
dysregulation of arachidnonic acid (AA) metabolism with diversion
from COX1 to LOX5 (lipooxygenase 5) pathway →
↓ production of PGE1, ↑ production of CysLTs (LT C4, D4, E4).
CysLTs are highly effective proinflammatory mediators →
• Mucus hypersecretion.
• ↑ Vascular permeability.
• Bronchoconstriction.
• Eosinophilic infiltration.

18. COX Inhibitors
(Aspirin, NSAIDs)
_

19. Clinical Picture: Aspirin Triad: Samter`s Triad
Features may be seasonal or perennial.
Features may be triggered by stimuli other than aspirin.
Avoidance of aspirin and other NSAIDs does NOT lead to resolution of
BA or rhinosinusitis.
1) Aspirin Intolerance This is the main dysfunction:
Acute upper and lower respiratory tract reactions to aspirin ingestion
occurring 20 mins to 3 hours after its intake:
• Nasal congestion, oedema, eosinophilic infiltration
→ rhinorrhoea, anosmia, nasal obstruction.
• Post- nasal drip → dry irritant cough.
• Halitosis.
• Conjunctivitis → red eye, lacrymation.
• Laryngeal spasm.

20. 2) Bronchial Asthma (Aspirin Sensitive Asthma)
(Aspirin Intolerant Asthma)
Asthma is severe and refractory to treatment.
3) Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
The presence of nasal polyps signifies higher chronic nasal inflammation
with eosinophilc activation.
Polyps tend to recur rapidly after polypectomy.
The usual sequence of appearance of the triad components is:
Chronic rhinitis then BA then nasal polyposis

21. Provocation Test (Aspirin Challenge)
This is the most defintive method for diagnosis:
Oral Challenge
FEV1 is assessed houly while the patient is given oral aspirin every
2 hours starting with 30 mg and gradually increased to a cumulative
dose of 1 gm.
Facilities for emergency resuscitation and treatment should be
available.
Bronchial or Nasal Challenge
These are less time consuming and less risky, but are probably less
sensitive.
They are better alternative in patients suspected to have high aspirin
sensitivity.

24. Destruction of Alveolar Walls and Reduction of Alveolar Membrane Surface Area
In Emphysema
Assumed Naked
Eye Appearance
Histopathology

25. Burden of COPD
 A leading cause of morbidity and mortality
worldwide.
 Burden expected to increase due to
continued exposure to risk factors and the
aging of the world’s population.
 associated with significant economic
burden.

26. +
-

27. Risk
FactorsHost factors Exposures
Genetic factors
Airway hyperreactivity
Smoking
Occupation
Environmental pollution
Recurrent bronchopulmonary infections

28. Airways Disease
• Luminal Plugs
• Mucosal Inflammation
• Muscle Spasm
• Bronchial wall fibrosis
(Remodelling)
Parenchymal
Destruction
• Loss of alveolar
attachments
• Decrease of elastic recoil
AIRFLOW LIMITATION

31. Asthma – COPD Overlap Syndrome (ACOS)
Chronic
Bronchitis
Emphysema
COPD
Bronchial
Asthma
COPD: a common preventable and treatable disease characterized by
persistent airflow limitation that is usually progressive and
associated with enhanced chronic inflammatory responses in the
airways and lungs to noxious particles or gases. Exacerbations and
comorbidities contribute to overall severity (GOLD 2015).
ACOS: includes heterogeneous conditions characterized by
persistent airflow limitation with combined features of asthma and
COPD.

32. Asthma COPD Overlap Syndrome (ACOS)Asthma COPD Overlap Syndrome (ACOS)
Distinguishing asthma from COPD can be problematic, particularly in
smokers and older adults.
The distinction is relevant for treatment and prognosis.
LABA monotherapy should be avoided in BA and ACOS.
ICS monotherapy should be avoided in COPD.
BA has better prognosis than COPD. ACOS has the worst prognosis
compared to either disease entity alone:
• More frequent exacerbations.
• Faster decline of lung functions.
• Worse quality of life.
• Higher mortality.

33. Asthma COPD
Onset
Main Initial
Symptoms
Diurnal Variation
Smoking
Triggering by
allergens, drugs
Past History
Family History
< 20 Y
Wheezes, dyspnoea
Worse by night and early
morning
---
Marked
Asthma
Asthma or other allergic
conditions
> 40 Y
Cough, expectoration
Not evident
+++
Minimal or absent
COPD
Smoking

34. Asthma COPD
Course Marked variation in
symptoms, signs, airflow
limitation, occurring either
spontaneously or with
treatment. During
remissions, the patient
returns at or near baseline,
ie, only no or little
obstruction
Although remissions and
exacerbations are common,,
some degree of fixed airflow
limitation on a background
of chronic complications
and comorbidities persist
and ensue a slowly
progressive course so that a
baseline of normal
spirometric parameters is
not achievable.
Spirometry after
Bronchodilator
X-Ray
FEV1/FVC > 0.7
↑FEV1 > 12% or > 200 mL
Normal
FEV1/FVC < 0.7
↑FEV1 < 12% or < 200 mL
Hyperinflation