Obstructive Diseases, Bronchiectasis and Drug Injury

1
Obstructive Diseases, Bronchiectasis and Drug
Injury

• Rodney Schmidt MD, PhD
• HuBio 541

http//courses.washington.edu/hubio541/
2
Obstructive Lung Diseases
3
Obstructive Lung Diseases
4
(No Transcript)
5
(No Transcript)
6
Obliterative Bronchiolotis

• Idiopathic
• Concentric endo-luminal scarring of membranous
  bronchioles (lt 1 mm)
• Post-infectious injury suspected
• Middle-aged patients
• Female predilection
• Progressive
• Similar lesion seen in lung transplant recipients
  (chronic rejection)

7
(No Transcript)
8
Obstructive Lung Diseases
9
Obstructive Lung Diseases
10
Obstructive Lung Diseases
11
Bronchial asthma

• Disorder characterized by
• Increased irritability, causing
• Paroxysmal narrowing of bronchioles, resulting in
• Reversible obstruction
• Multiple variants with different triggers
• Unifying theme is abnormal airway sensitivity
  triggering stereotyped response

12
(No Transcript)
13
(No Transcript)
14
Chronic Bronchitis

• Functional disorder with anatomic correlates
• Persistent cough with sputum production for at
  least 3 months in two consecutive years
• Usually due to cigarette smoking but may be
  caused by dusty work environments (industrial
  bronchitis).

15
Morphologic Correlates

• Submucosal gland hypertrophy
• Goblet cell metaplasia
• Mucus plugging of bronchioles
• Inflammation of bronchioles

16
Submucosal glands
Normal
Chronic bronchitis
17
Chronic bronchitis
Normal
18
Obstructive Lung Diseases
19
Emphysema

• Defined anatomically
• Abnormal permanent enlargement of the airspaces
  distal to the terminal bronchiole, accompanied by
  destruction of their walls.
• i.e., loss of alveolar septa

20
Patterns of Emphysema
Normal
21
Patterns of Emphysema
Normal
Pan-lobular
22
(No Transcript)
23
Patterns of Emphysema
Normal
Centrilobular
24
(No Transcript)
25
Normal
Emphysema
26
(No Transcript)
27
Patterns of Emphysema
Normal
Centrilobular
Pan-lobular
Pan-acinar
Proximal acinar
28
Emphysema
29
Consequences

• Reduced gas exchange due to loss of alveolar
  septa
• Fewer capillaries
• Reduced surface area
• Airflow obstruction

30
Why Obstructive?

• Collapse due to loss of septa (Starling resistor)
• Loss of elastic recoil
• Elastin in septa
• Decreased surface tension
• Associated airway inflammation

Normal
Emphysema
31
(No Transcript)
32
(No Transcript)
33
Bronchiectasis

• Permanent abnormal dilatation of bronchi and
  bronchioles due to, or associated with, chronic
  necrotizing and scarring inflammation of the
  airways.

34
Bronchiectasis

• Localized post-obstructive
• Tumors
• Foreign bodies
• Diffuse airway clearance abnormalities
• Cystic fibrosis
• Ciliary dysmotility syndromes (e.g. Kartageners)
• Mucus impaction (asthma, chronic bronchitis)
• Immunodeficiency (IgA, certain IgG)
• Post-infectious childhood
• Measles, influenza, pertussis
• TB, Staph., mixed organisms

35
(No Transcript)
36
(No Transcript)
37
Drug-Induced Injury

• Drug reactions are relatively common
• Any pattern of lung injury is potentially due to
  a drug reaction
• Diagnosis of a drug reaction is usually clinical
  (NOT involving a biopsy)
• Most types of drug injury are reversible
• Prognosis varies with type of injury

38
Criteria for Drug Reaction

• Prior evidence that drug can be toxic
• Exposure to drug
• Sufficient dose
• Appropriate timing relative to exposure
• Improvement following drug withdrawal
• Re-emergence of symptoms during drug challenge
• Absence of confounding factors (e.g. infection)

39
Types of Drug Reactions

• Anaphylactic
• Bronchoconstriction
• Pleuritis and effusions
• Edema
• Acute/evolving injury (cytotoxic)
• Inflammatory
• Mononuclear/granulomatous
• Eosinophilic
• Vascular disease
• Airway Disease
• Fibrosis

40
Drug Reactions Clinical

• On-Set Drug Exposure
• Edema Insidious Current
• Acute/evolving Acute/subacute Delayed
• Mono.granulomatous Insidious Current
• Eosinophilic Insidious
  Current
• Vasculopathy Insidious
  Delayed
• BOOP Insidious Current
• OB Insidious Delayed

41
Drug Reactions - Prognosis

• Edema Reversible
• Acute/evolving Acute/often fatal
• Mono.granulomatous Reversible
• Eosinophilic Reversible
• Vasculopathy Fixed, may progress
• BOOP Largely reversible
• OB Fixed

42
Drug Reactions Therapy

• Edema Withdrawal
• Acute/evolving Steroids/withdrawal
• Mono.granulomatous Steroids/withdrawal
• Eosinophilic Steroids/withdrawal
• Vasculopathy None
• BOOP Steroids
• OB None