Airway & Lung Diseases

Question 1

Asthma stats

Answer 1

affects ~10% population (39.5 million ppl)

• higher in blacks
• higher in females
• higher in children

Question 2

Pathophysiology of Asthma

Answer 2

-chronic inflammatory disease involving episodes of REVERSIBLE airway obstruction (reversibility distinguishes asthma from COPD)

Question 3

Asthma characterized by:

Answer 3

A) Chronically inflamed airways

B) Airway Hyperreactivity

C) Airway Smooth Muscle Hypertrophy

D) IgE-Mediated Immune Response

Question 4

A) Chronically Inflamed Airways

Answer 4

• epithelial damage
• mucosal edema
• inflammatory cell infiltration (eosnophils, lymphocytes, neutrophils)
• mediator release

Question 5

Mediator Release

Answer 5

• PGs : bronchoconstriction
• Leukotrienes C4/D4 : bronchoconstriction, airway hyperreactivity
• Platelet Activating Factor: airway hyperreactivity
• Histamine: no role
• Adenosine: bronchoconstriction, mast cell activation -Cytokines: IL5-eosinophil recruitment, IL4-IgE production
• Tryptase: airway inflammation (PAR2: protease activated receptors)

Question 6

What evidence could you provide that argues against histamine or PGs being important mediators of asthma?

Answer 6

Antihistamine and COX-inhibitors do not help in asthma!

Question 7

B) Airway Hyperreactivity

Answer 7

-increased responsiveness to a variety of stimuli (bronchoconstrictors, irritants, exercise)

Question 8

C) Airway smooth muscle hypertrophy

Answer 8

-increase bronchial reactivity

Question 9

D) IgE mediated immune response

Answer 9

• mast cells have an important role in asthma
• continual exposure to antigen
  
  • inflamed airways
  • increased airway reactivity

Question 10

Hygiene hypothesis

Answer 10

in early life, decreased exposure to infections + increased antibiotic use + decreased exposure to noxious pulmonary stimuli causes a change in immune system development

• decreased Th1 response (infection fighting)
• increased Th2 response (allergic diseases, asthma)

Question 11

Bronchoconstriction precipitated by variety of stimuli:

Answer 11

A) Environmental (house dust mite, animal dander, tobacco smoke, air pollutants, ozone)

B) Occupational (grain dust, red cedar)

C) Drugs (propanolol, aspirin)

D) Exercise

Reducing exposure–>less asthmatic episodes

Question 12

Asthmatic episodes divided into:

Answer 12

A) Early response

B) Late Response

Question 13

Early Response

Answer 13

bronchoconstriction occurring immediately after exposure

Question 14

Late Response

Answer 14

bronchoconstriction occurring hours after exposure

• hyperreactivity lasts for several weeks
• may relate to release of mediators from infiltrating inflammatory cells and the time it takes for them to infiltrate

Question 15

Asthmatic episodes exacerbated by:

Answer 15

• viral respiratory infection
• rhinitis
• sinusitis
• cigarette smoke
• pollution
• gastroesophageal reflux

Question 16

Clinical features of Asthma

Answer 16

• wheezing, chest tightness
• non-productive cough
• episodic airflow obstruction
• increased airway reactivity to non-specific stimuli

Question 17

Episodic airflow obstruction

Answer 17

A) During remission: PFTs may be normal

B) During partial remission: no clinical signs, but may see decreased pulmonary function from peak flow meter (bronchoconstriction without knowing it, flow meter can detect the bronchoconstriction without them knowing it is present)

Question 18

Diagnosis

Answer 18

PFTs (pulmonary function test):

• decreased expiratory flow rate, FEV-1, FVC
• increased residual volume, FRV
• decreased ability to exhale, causes increased residual volume

Question 19

Diagnosis

Answer 19

2) Bronchial provocation tests:
- airway hyperreactivity correlates with severity of asthma
- PFTs performed before and after admin. of incrementally-increased conc. of bronchoconstrictor aerosol (e.g. methacholine)
- the more hyperreactive your airways are, the more likely you are to have bronchoconstriction

Question 20

COPD epidemiology

Answer 20

-affects ~6% of population of industrialized countries -15 million people in USA diagnosed in 2011

Question 21

COPD prevalence

Answer 21

• whites,black>hispanic
• women>men
• older>younger
• Smoker>non-Smoker, and former smoker>non-smoker
• less education>more education

–unemployed>employed

Question 22

COPD stats

Answer 22

-3rd leading cause of death in US -2nd leading cause of disability -# of death declining, but declining more in men than in women -$43 billion cost of COPD–> significant impact on healthcare

Question 23

COPD Pathophys.

Answer 23

-COPD is a common preventable and treatable disease characterized by persistent airflow limitation that is USUALLY PROGRESSIVE and assoc. w/ enhanced chronic inflammatory response in airways and the lung to noxious particles or gases

=syndrome of progressive, NON-REVERSIBLE airflow limitation caused by chronic inflammation of the small airways and alveoli

Question 24

COPD pathophys. con’t

Answer 24

• umbrella term that encompasses chronic bronchitis, emphysema, and small airway diseases (asthma affects central airways more)
• Primary cause is the EXPOSURE TO PARTICLES, e.g. TOBACCO SMOKE

Question 25

COPD features

Answer 25

A) Chronically inflamed Airways B) Imbalance between Protease and Anti-Protease Activity C) Airway Remodeling D) Pulmonary Vascular Changes

Question 26

A) Chronically Inflamed Airways

Answer 26

* inflammatory cell infiltration of the (small) airways and alveoli (macrophages, lymphocytes, neutrophils) * mucus hypersecretion * decreaed ciliary motility * mediator release

Question 27

B) Imbalance Between Protease and Anti-Protease Activity

Answer 27

* Imbalance in favor of proteolysis --\> remodeling --\> emphysema * Proteolytic activity correlates with disease severity

Question 28

C) Airway Remodeling

Answer 28

* bronchiolar scar tissue development * airway narrowing/fixed airway obstruction * airflow limitation NOT FULLY REVERSIBLE (vs. asthma) * emphysema * centrilobular (respiratory bronchiole destrcution) * panlobular (respiratory bronchioles and alveolar ducts/sacs destruction) * decreased tethering of airways * decreased gas exchange

Question 29

D) Pulmonary Vascular Changes

Answer 29

- endothelial cell dysfunction (changes gas exchange) - inflammatory cell infiltration of vessel wall (changes gas exchange) - smooth muscle hypertrophy (changes flow)

Question 30

Pathophysiological Consequences

Answer 30

* mucus hypersecretion + ciliary dysfunction --\> increased cough & sputum * airway narrowing + peripheral airway destruction--\> expiratory flow limitation (irreversible) * inflammatory cell infiltration + mucus hypersecretion--\> expiratory flow limitation (reversible) * peripheral airway remodeling --\> impaired elastic recoil --\> increased lung volume (gas gets trapped in lungs) * airway obstruction + pulmonary vascular changes --\> hypoxia/hypercapnia

Question 31

Based on pathophys. consequences, what would happen to FEV-1 and residual volume in a patient with moderate COPD?

Answer 31

\* Residual volume increases \* FEV decreases

Question 32

Risk Factors

Answer 32

A) Noxious Particles/gases \* tobacco smoke \* environmental particulates \* occupational dusts & chemicals B) Genetic \* AAT-deficiency (genetically predisposed to emphysema) (important inhibitor of neutrophil elastase and serine proteases) C) Older age \>40yrs D) Poor socioeconomic status E) Lower Respiratory Tract infections F) Low Birth weight \* poor nutrition of fetus, small lungs, start life w/ reduced lung function

Question 33

Pathogenesis

Answer 33

1) Inhaled Noxious stimulus \* epithelial cell damage \* alveolar macrophage activation cytokine release fibroblast activation (--\>fibrosis) \* mac, neutrophil recruitment

Question 34

Pathogenesis

Answer 34

2) Macrophage & Neutrophil Activation \* ROS/Protease release \* CD8- cell recruitment \* Tissue damage/remodeling--\>emphysema \* goblet cell hyperplasia--\> mucus

Question 35

Macrophages and neutrophils in COPD pts (i) have reduced capacity to phagocytize bacteria and (ii) are less responsive to the effects of corticosteroids.

Answer 35

Bacteria in the airways are trapped in the mucus, have a lot of mucus and have less ability to clear the mucus, the inflammatory cells have less capacity to phagocytize bacteria, and steroids have less capacity in their anti-inflammatory effects in patients with COPD as opposed to asthma patients

Question 36

Co-morbities

Answer 36

\* lung cancer \* cardiovascular disease \* depression \* skeletal muscle wasting \* osteoporosis

Question 37

Clinical features

Answer 37

\* Persistent Dyspnea \* Chronic Cough \* Sputum Production \* Wheezing/Chest Tightness

Question 38

Diagnosis

Answer 38

Suspect COPD in a pt \> 40 if: \* persistent or progessive dyspnea (difficult gas exchange) \* chronic cough \* chronic sputum production \* history of exposure to risk factors (smoking) \* family history of COPD

Question 39

Diagnosis

Answer 39

spirometry (PFT) required to validate clinical diagnosis of COPD

Question 40

Spirometry diagnosis

Answer 40

\* decreased expiratory flow rate, FEV-1, FVC, FEV-1/FVC \* increased residual volume, FRC

Question 41

What are the differences in the causes of decreased FEV-1 in COPD vs asthma? (hint think about causes of flow limitation)

Answer 41

- Drop in FEV-1 in asthma is due to bronchoconstriction - Drop in FEV-1 in COPD is due to REMODELING plus bronchoconstriction (COPD pt's FEV will not look like a normal pt's FEV b/c there is remodeling and thus not fully reversible, over time, the non-bronchodilator sensitive component will get worse and FEV will decrease more over time)