COPD/Asthma/ILD (8/27-9/4)

Question 1

What part of the airway is the most susceptible to significant airflow obstruction?

Answer 1

Bronchioles - not supported by cartilage - lack submucosal glands - contain circumferential smooth muscles

Question 2

What type of lung defect is COPD?

Answer 2

obstructive (air intake is limited)

Question 3

What two diseases fall under COPD?

Answer 3

chronic bronchitis emphysema

Question 4

What is the main symptoms of COPD?

Answer 4

dyspnea

Question 5

Bronchitis has what type of lung defect?

Answer 5

obstructive (air intake is limited)

Question 6

What is the pathogenesis of/causes bronchitis?

Answer 6

1) hypertrophy of the mucus-secreting glands in the bronchi leads to:
a) hypersecretion -> mucus plugging
b) thickening of the bronchial wall

2) (recurrent) infections due to altered epithelium, cilia, and mucus production (inadequate clearance) -> inflammation/formation of lymphoid follicles
3) intermittent bronchospasms of smooth muscle surrounding airways

all impedes air flow

Question 7

What are pathological findings of bronchitis? (4)

Answer 7

1) inflammatory cells (macrophage, neutrophils) and lymphoid follicles
2) thickening of bronchiole wall due to hypertrophy of mucus glands (reid index >50%)
3) luminal mucus plugging

Question 8

How is chronic bronchitis diagnosed?

Answer 8

productive cough >3 months for 2 consecutive years

Question 9

What are some general characteristics of emphysema in terms of: type of defect? histological finding? elastic recoil? compliance? fibrosis?

Answer 9

• obstructive lung defect
• permanent enlargement of airspaces distal to the terminal bronchioles + destruction of alveolar walls/decrease in airway tethering
• loss of elastic recoil
• increased compliance
• NO FIBROSIS

Question 10

What are the 2 main patterns of emphysema? Where are they located? What are they caused by?

Answer 10

1) centriacinar - focal destruction of respiratory bronchioles due to cigarette smoking 2) panacinar - destruction of alveoli distal to the terminal bronchioles due to A1AT deficiency

Question 11

What is the role of A1AT? How does it protect against smoke?

Answer 11

Alpha-1-antitrypsin - blocks elastase Smoke recruits inflammatory cells, which increase elastase production to destroy lung parenchyma, thus reducing elastic recoil

Question 12

How does smoking cause emphysema?

Answer 12

Smoke does 2 things: 1) it recruits inflammatory cells, which increase elastase production to destroy lung parenchyma, thus reducing elastic recoil. 2) it inactivates A1AT, which causes results in increased elastase activity, thus resulting in an increased lung parenchyma destruction and ultimately reduction of elastic recoil.

Question 13

What type of lung defect is asthma?

Answer 13

obstructive defect (air can’t get in)

Question 14

What is asthma?

Answer 14

hyper-responsiveness of the tracheobronchial tree to stimuli, which leads to repeated episodes of reversible bronchoconstriction

Question 15

What are the two main types of Asthma?

Answer 15

EXtrinsic

• allergic/Type I hypersensitivity
• atopy/genetic predisposition to producing IgE to allergens
• may be due to increased Th2 production, which secrete IL’s to stimulate B cells to produce IgE and activate eosinophils to produce major basic protein.

INtrinsic
- non-allergic - non-hereditary

Question 16

Which T cell is a key player in the extrinsic pathway of asthma?

Answer 16

Th2 - secrete IL’s to stimulate B cells to produce IgE, which stimulates mast cells - activate eosinophils to produce major basic protein both result in damage to the epithelium and airway constriction

Question 17

What are the pathological findings of asthma? 93)

Answer 17

1) thick mucus plugs
2) thickened epithelial basement membranes
3) eosinophils
4) inflammation
5) edema
6) hypertrophied smooth muscle + submucosal gland proliferation

Question 18

What is bronchiectasis?

Answer 18

permanent airway DILATION due to the sequelae of continued airway damage (repeat infections, aspirations of drugs and chemicals, obstruction)

Question 19

What is the pathology of bronchiectasis?

Answer 19

loss of cilia increased mucus destruction of alveolar wall due to inflammation w. or w.o microabscesses, squamous metaplasia, peribronchial fibrosis

Question 20

What inflammatory cells predominate in COPD lungs?

Answer 20

macrophages, CD8, and neutrophils, which promote inflammation that ultimately lead to small airway narrowing and alveolar destruction.

Question 21

What is the difference betwen reversible and irreversible airflow limitation in COPD lungs?

Answer 21

Reversible: airway inflammation + airway remodeling

Irreversible: parenchymal destruction, loss of elastic recoil

Question 22

What are 5 mechanisms of airflow obstruction?

Answer 22

1. mucus hypersecretion -> luminal obstruction
2. disruputed alveolar attachments -> easier for airway to collapse (ie emphysema)
3. mucosal inflammation/fibrosis -> thickened alveolar walls (ie bronchitis)
4. reduced elastic recoil -> reduced airflow (emphysema)
5. smooth muscle contraction -> narrowing of the airways (ie bronchitis)

Question 23

How are the symptoms of chronic bronchitis different than that of emphysema, even though they both fall under the umbrella term of COPD?

Answer 23

Chronic bronchitis:

1) productive cough
2) hypoxemia
3) pulmonary HTN

Emphysema

1) breathlessness
2) adequate oxygen saturation
3) cachexia (wasting disease - loss of weight, muscle atrophy, fatigue, weakness)

Question 24

What is the elastase hypothesis?

Answer 24

A1AT is a major inhibitor of serine proteases in the lungs, and it antagonizes the effects of the neutrophils in the lungs.

Deficiency is caused by a recessive mutation, where the liver (site of A1AT production) does not synthesize it or release it.

Thus, a smoker with A1AT deficiency is at high risk of developing COPD at an earlier age (30-50) compared to the usual onset (50-60)

Question 25

In what diseases would you see a decreased FEV1/FVC ratio? (3) What is the name of this type of defect?

Answer 25

COPD asthma Cystic fibrosis aka **_O**_BSTRUCTIVE DEFECT - can't get air _**O_**ut

Question 26

Predict and compare what you would see for emphysema vs chronic bronchitis in terms of: FRC RV FVC TLC DLCO FEV1/FVC ratio

Answer 26

Emphysema FRC - increase due to elastic recoil (less inward force, more outward force of the thorax) RV - increase due to air trapping/loss of elastic recoil FVC - decrease due to air trapping TLC - increase DLCO - decrease due to neutrophil-mediated alveolar destruction FEV1/FVC ratio - decrease, since it's an obstructive defect Chronic Bronchitis FRC - normal because only the conducting zones of the airway are altered RV - increase due to air trapping since patient is unable to exhale all of the air completely due to thickened walls and phlegm FVC - decrease or normal due to air trapping TLC - normal because elastic recoil is NOT affected DLCO - normal, since the respiratory zones (site of gas exchange) is not affected FEV1/FVC ratio - decrease, since it's an obstructive defect

Question 27

What are 3 types of bronchodilators? What is their mode of action?

Answer 27

1) b-agonists: albuterol, salmeterol, formoterol 2) anti-cholinergics: block muscarinic reeptors that release ACh (normally bronchoconstrictors): ipratropium and tiotropium 3) methylxanthines: phosphodiesterase inhibitor (increases cAMP bi**oavailability) - theophylline** **All serve to increase cAMP, which causes smooth muscle relaxation**

Question 28

Why are glucocorticosteroids used for treatments with COPD?

Answer 28

**anti-inflammatory** inhaled - for patients with COPD and FEV1 \<50% of predicted + frequent exacerbations oral - long-term treatment not recommended due to site effects

Question 29

What is the # 1 therapy for patients with COPD/emphysema?

Answer 29

STOP SMOKING. shiz.

Question 30

What are the 4 characteristic symptoms of asthma? What are some of the physical findings of asthma?

Answer 30

**Clinical symptoms:** 1. dyspnea 2. cough 3. wheeze 4. chest tightness symptoms are worse at night. **Physical findings:** 1. expiratory wheezes 2. hyperresponsance 3. diminshed breath sounds 4. use of accessory muscles to breath 5. CXR: hyperinflation of the lungs NOTE: physical exam may be normal if the patient isn't undergoing an attack

Question 31

What is the most important risk factor for asthma?

Answer 31

atopy - a genetic predisposition to forming IgE and Th2 phenotypes

Question 32

What are the 4 clinical manifestations of asthma?

Answer 32

1. airway inflammation (narrow, reddened, edematous) 2. enhanced bronchial responsiveness -\> bronchoconstriction 3. reversible airway obstruction 4. excess mucus secretion 5.

Question 33

What is the gross pathological features of asthma? microscopic features?

Answer 33

**Gross**: 1. narrowed, reddened, and edematous airways **Microscopic**: 1. inflammation - eosinophils, Th2, mast cells 2. thickened basement membrane due to collagen deposition 3. decreased attachment to airway walls 4. increased epithelial cells (hyperplasia) lining the lumen 5. hypertrophied smooth muscle 6. mucus plugging 7. airway edema (exudative) 8. vascular congestion

Question 34

T/F Asthma pathology is observed throughout lung parenchyma

Answer 34

False. It is only observed in the conducting airways and does NOT extend into the lung parenchyma

Question 35

Asthma is characterized by acute inflammation, chronic inflammation, and remodeling. What is the difference between these three stages?

Answer 35

**Acute**: altered airway pathophysiology - hyperresponsiveness, mucus production, and bronchoconstriction (all leads to airflow obstruction **Chronic**: increased airway dsfunction due to epithelial cell damage **Remodeling**: permanently injured/altered lung function due to hyperplasia

Question 36

Would you expect to find exudate or transudate in asthmatic lungs?

Answer 36

Exudate - extravascular fluid with high protein content due to vessel obstruction during inflammation

Question 37

What is the expected spirometry results of a patient with Asthma?

Answer 37

decreased FEV1 (due to obstructive airflow limitation) decreased FEV1/FVC ratio

Question 38

What is the pathogenesis of asthma?

Answer 38

allergens that trigger acute or chronic responses: acute: mast cell and IgE mediated bronchoconstriction chronic: eosinophil-mediated inflammation

Question 39

What are some viral causes of asthma?

Answer 39

RSV - triggers a Th2 response; infections early in life have been linked to asthma development Rhinovirus \*\* most common cause of acute episodes of wheezing

Question 40

How does exercise trigger asthmatic attacks?

Answer 40

hyperventilation increases osmolality of fluid in the airway, which leads to mast cell degranulation

Question 41

What are the 3 diagnostic tools used to diagnose asthma?

Answer 41

1. spirometry 2. methacholine test - delivers various concentrations to induce bronchoconstriction and measures FEV1 3. exhaled NO test Note that CXR is not a useful diagnostic tool for asthma

Question 42

What is the difference between rescue therapy and controller therapy for asthma treatment? What are some examples of each?

Answer 42

* *rescue**: quick relief fo bronchoconstriction and associated symptoms - **b2 agonist** (albuterol) - **antichoinergics** (ipratropium) - **corticosteroids** * *controller therapy**: long-term management/antiinflammatory medication - **cortiosteroids - b-agonists - anti-leukotrienes - immunomodulators - allergen immunotherapy - mast-cell stabilizers - theophylline**

Question 43

What is ILD?

Answer 43

interstitial lung disease - diffuse parenchymal lung disease that is affected by interstitial inflammation and/or fibrosis

Question 44

ILD is broken down into 3 major branches: 1. Granulomatous 2. Non-granulomatous (idiopathic) 3. Known cause What are some examples of each?

Answer 44

* *Granulomatous** - Sarcoidosis - hypersensitivity pneumonitis * *Non-granulomatous (idiopathic)** - Usual interstitial pneumonitis, UIP (Idiotpathic pulmonary fibrosis) - Non-UIP * *Known cause** - ARDs - Pneumoconiosis (coal miners, silicosis, asbestosis) - Collagen dz - SLE/RA - Drugs

Question 45

What is the biological processes that lead to iLD? What is the INITIAL step of ILD? What is the END-STAGE step of ILD?

Answer 45

inhaled substance/immune host response causes INTERSTITIAL DAMAGE, which activates type II neumocytes, causes alveolar capillaries and epithelial cells, and macrophages. * Type II pneumocytes become reactive and stick out from the interstitium * Alveolar capillaries become leaky, which allows fibroblasts + fibrin + inflammatory cells to enter the interstitum and organize granulation tissue * fibroblasts organizes fibrin into granulation tissue AND produce collagen, which ultimately leads to fibrosis * macrophages recruits inflammatory cells and engulfs debris. all of these ultimately leads to honeycomb lungs, which is the end-stage fibrosis **Initial: alveolitis** **End stage: honeycomb lungs**

Question 46

What is granulation tissue?

Answer 46

healing/reparative tissue response

Question 47

What is ARDs? What causes ARDs? What cell types are affected in ARDs? (this will also help you answer the next question) What is the pathophysiology of ARDs? What is the histolocal appearance of ARDs? How does it resolve?

Answer 47

Acute respiratory distress caused by acute lung injury due to: 1) trauma 2) sepsis 3) infections 4) gastric aspiration cells affected: 1) alveolar capillary/endothelial cells → **edematous fluid** + inflammatory cells in interstitum NOTE: edematous fluid mixes with cellular debris to form a **hyaline membrane** 2) type I pneumocytes get damaged and die → altered surfactant production 3) type II is also damaged, but the remaining cells try to repopulate the damaged alveoli. * *Pathophysiology**: formation of the hyaline membrane results in a thickened diffusion barrier, which does two things: 1) lack of oxygen diffusion → hypoxemia and cyanosis 2) makes the surface more "sticky", which increases the surface tension and consequently increases the Histological appearance: 1) **edema in interstitial space** 2) **hyaline membrane** (when edematous fluid mixes with cellular debris in the alveolar septum) * *early: typical diffuse alveolar damage (DAD) late: organization into fibrous tissue OR complete resolution**

Question 48

What is pneumoconiosis? What are examples of pneumoconiosis?

Answer 48

Pneumoconiosis - ILD caused by inhalation of dust, characterized by inflammation, coughing, and fibrosis; many are related to occupational exposures Examples: coal minors lungs silicosis asbestosis

Question 49

What is coal minors pneumoconiosis? What are the 2 phases of the disease?

Answer 49

ILD that results in progressive fibrosis due to coal dust +/- silica inhalation **Early phase**: presence of * anthracosis - carbon-laden macrophage * macules - aggregates of carbon-laden macrophages * nodules - macules + fibrosis **Complex phase**: coalescence of nodules, leads to progressive massive fibrossi (mostly silica-induced)

Question 50

What is silicosis pneumoconiosis? There are two types of silica (crystalline/quartz and amorphous silica), which one is more dangerous? What are the 2 phases of the disease?

Answer 50

ILD due to silica inhalation Crystalline/quartz is most fibrogenic and is harder to get rid of; impairs macrophage form **Early**: fibrotic nodules with collagen core (usually in upper lobe) **Complex**: coalescence into hard scars, esp. in the lungs + lymph nodes

Question 51

What is asbestosis pneumoconiosis? There are two types of abestos (serpentine and amphibole), which one is more dangerous? What is the histological features of asbestosis pneumoconiosis?

Answer 51

ILD due to inhalation of crystalline-hydrated silica (asbestos), causes diffuse interstitial fibrosis amphibole is the more pathogenic form histological feature: long asbestos fibers present as iron coated bodies within macrophages.

Question 52

What is hypersensitivity Pneumonitis? What type of hypersensitivity dominates the early stages? later stages? What type of lung pathology would you expect to see?

Answer 52

**ILD - granulomatous type** it is an ** immune response** to inhaled **organic** dust, mold, occupational antigens. early stages: **Type III** - immune complex later stages: **Type IV** - delayed hypersensitivity Pathology: **granulomatous inflammation**, thickened interstitium, late stage **fibrosis** + **honeycomb lungs**

Question 53

What is sarcoidosis? What type of lung pathology would you expect to see?

Answer 53

**ILD - granulomatous type** it is a **T-CELL mediated immune response** to inhaled an unknown antigen. Pathology: * *- bilateral hilar lymphadenopathy** * *- granulomatous inflammation** that may ultimately fuse to form **non-nucleated giant cells** * *- fibrosis** Treatment: - asymptomatic patients: no treatment - severe symptoms: corticosteroids

Question 54

What are the two major symptoms of ILD? What is the underlying causes of these two major symptoms? What are the physical findings in a patient with ILD?

Answer 54

**dyspnea** 1. decreased lung compliance (stiffer) - lungs need to generate a greater inspiratory pressure to inflate the lungs 2. increased physiological dead-space - need to increase ventilation to maintain a nomral PCO2 **coughing** 1. stimulation of vagal afferent pathways + receptors in the airways **Physical findings:** 1. crackles (rales) 2. clubbing in distal phalynx

Question 55

What is idiopathic pulmonary fibrosis? What type of lung pathology would you expect to see? What is unique about IPF compared to all of the other ILD's?

Answer 55

IPF is an ILD of uknown etiology, but the pathology is the typical ILD pathology (**interstitial thickening + honeycomb lung).** note that IPF can occur **independently** of inflammation, ie there is excess pro-fibrotic growth factors and cytokines that promote fibrosis, rather than inflammation (as in the case with hypersensitivity pneumonitis)

Question 56

What is the expected PFT values for a patient with ILD? TLC FRC RV VC FEV1/FVC ratio flow rates

Answer 56

TLC, FRC, RV, and VC will decrease - there is LESS compliance in ILD lungs and therefore the inspiratory muscles can't overcome the elastic recoil of the lungs and can only inflate the lung to a lower volume FEV1/FVC ratio will INCREASE since this is a RESTRICTIVE disease Flow rate: decreased due to decreased TLC, but since the elastic recoil is increased (as a result of decreased compliance) the flow rate wil be higher at a given lung volume in an ILD patient compared to normal.

Question 57

Comment on the lung function of a patient with ILD in terms of: compliance diffusion VQ mismatch exercise

Answer 57

* **compliance** - decreased due to inflammation/collagen deposition * **diffusion** - decreased due to thickened alveolar-capillary interface/loss of surface area * **VQ mismatch** - increased due to less compliant areas that receive less ventilation + thickened septums increase equilibration time * **exercise** - induces O2 desaturation even with mdoest activities; mostly due to VQ mismatch

Question 58

What is the breathing pattern for a patient with ILD? Differentiate between when the person is asleep vs when they're awake.

Answer 58

Awake: patient has rapid shallow breathing to miminize discomfort associated with dyspnea. Asleep: no real difference in breathing pattern between normal and ILD patient since the patient is unaware of the dyspnea.

Question 59

What is the prognosis for a patient with ILD?

Answer 59

Shit hits the fan. It's bad. Mean survival time: 3years at the time of diagnosis.

Question 60

What are some of the diseases caused by inspired substances?

Answer 60

* *pneumoconiosis** - chronic inhalation of inorganic dust that leads to parenchymal inflammation and fibrosis * *asthma** - inhalation of inorganic dust exposure that causes acute symptoms * *hypersensitivity pneumonitis** - inhalation of organic particles (ie malt worker's lungs caused by Aspergillus fumigatus) * *occupational asthma** - inhalation of organic particles (ie grains)

Question 61

Smoking: what type of physiological responses does smoking cause?

Answer 61

Smoking contains nicotine, which binds to ACh receptors at autonomic ganglia, thereby * increase HR, BP, CO * increase catecholamine release + ACTH release from adrenal medulla * increase relaxation at the NMJ (due to persistant activation-inactivation of the NM receptors) * promotes mental stimulation, relaxtion, learning, memory, and attention * promotes thrombosis, platelet aggregation, and vasospasms

Question 62

What are 3 pharmacological agents used for smoking cessation?

Answer 62

Nicotine (patches) bupropion (Zyban) varenicline (chantix)