Lecture 17-18: Interstitial Lung Disease and Pathology

Question 1

PFT shows what in interstitial lung disease

Answer 1

Restrictive physiology and impaired gas exchange

Question 2

ILD: acute or chronic?

Answer 2

Chronic typically

Question 3

ILD: symptoms

Answer 3

Nonspecific: dyspnea, dry cough

Question 4

ILD: FVC & TLC, DLCO, A-a gradient

Answer 4

Decreased FVC and TLC with PRESERVED FEV1 / FVC ratio, decreased DLCO, increased A-a gradient

Question 5

ILD: hypoxemia?

Answer 5

Yes

Question 6

ILD: imaging dx

Answer 6

High resolution CT scan to visualize fibrosis

Question 7

Signs of fibrosis from early –> late

Answer 7

Increased reticular densities, traction bronchiectasis, honeycomb changes, cysts

Question 8

What does reticular densities look like? Early or late?

Answer 8

Increased “lines” (thickened interalveolar septum); early fibrosis

Question 9

What is traction bronchiectasis?

Answer 9

Dilated airways pulled apart (traction) by fibrosis

Question 10

Honeycomb and cysts are evidence of what stage of firbrosis

Answer 10

Advanced

Question 11

What is the histological pattern identified for idiopathic pulmonary fibrosis? Can this be associated with other disease?

Answer 11

Usual interstitial pneumonia (UIP); yes, known causes of pulmonary fibrosis can look like this

Question 12

Is idiopathic pulmonary fibrosis deadly? Survival length?

Answer 12

YES: most deadly, median survival is 2.8 years

Question 13

IPF: clinical features

Answer 13

Subacute, insidious dyspnea, cough, rales, CLUBBING, PFT’s restrictive, impaired gas exchange (DLCO, A-a gradient)

Question 14

IPF: diagnostic blood test?

Answer 14

Nope

Question 15

IPF: dx (2 findings from two different modalities)

Answer 15

CT scan: interstitial lung disease and biopsy: fibrotic changes –> fibroblast foci

Question 16

IPF: gross

Answer 16

Dense, collagenous, dilated airways with large ares of scarring

Question 17

IPF: pathogenesis

Answer 17

Alveolar epithelial cells injured (unidentified) with PERMANENT cell death and ABNORMAL cell growth = myofibroblast –> collagen and vascular remodeling

Question 18

What is a myofibroblast

Answer 18

Both a SM cell (contractile properties) and a fibroblast cell that produces collagen

Question 19

IPF: genetics (AD or AR?)

Answer 19

25% of IPF patients have a family member with interstitial lung disease; AD

Question 20

If someone has family members with IPF and they get IPF, what is their course like?

Answer 20

More aggressive and occurs at a younger age

Question 21

IPF: medical tx (2) and surgical tx

Answer 21

Pirfenidone (blocks pro-fibrotic cytokines) and nintedanib (trile tyorsine kinase inhibitor); lung transplant

Question 22

Pirfenidone blocks what two factors?

Answer 22

TGF-beta and PDGF (platelet derived GF)

Question 23

Nintedanib inhibits what three factors?

Answer 23

VEGF (vascular endothelial GF), FGF (fibroblast GF), PDGF

Question 24

Lung transplant survival

Answer 24

5 year = 50%

Question 25

Pulmonary manifestations of CT disease: systems that can be affected (5)

Answer 25

Parenchyma, airway, vasculature, serosal membranes (including effusion) and MSK

Question 26

What is a drug-induced cause of interstitial lung disease?

Answer 26

Nitrofuranton (used to treat UTIs)

Question 27

Describe sarcoidosis: main finding and organ systems

Answer 27

Noncaseating granulomas: delayed hypersensitivity reaction with unknown cause; multi-systemic disease (lungs in 80% of cases)

Question 28

Sarcoidosis is a diagnosis of...

Answer 28

Exclusion (must rule out TB, fungal infections)

Question 29

Sarcoidosis: radiological and histological finding

Answer 29

X-ray: enlarged lymph nodes in hilar areas; biopsy = large granulomas with multinucleated giant cells and NO NECROSIS

Question 30

What is a typical outcome of ILD?

Answer 30

Honeycomb lung

Question 31

Basics of ILD (4)

Answer 31

Decreased compliance, lung volumes, impaired diffusion/gas-exchange, development of pulmonary hypertension

Question 32

One theory of ILD points to _________ as a possible cause

Answer 32

Abnormal wound healing

Question 33

What components make up the interstitium

Answer 33

BM, fibroblasts, collagen fibers, elastic tissue

Question 34

Describe UIP

Answer 34

Age: 50+; insidious onset; can be idiopathic, due to drug rxn, or collagen vascular/autoimmune disease

Question 35

UIP pattern on histology plus idiopathic disease clinically =

Answer 35

IPF

Question 36

UIP: pathoglogy (2 prime findings)

Answer 36

PATCHY fibrosis pronounced beneath pleura/interlobular septa; fibrosis exhibits TEMPORAL HETEROGENEITY (not all the same age)

Question 37

What do we call the new region of temporal heterogeneity found on UIP?

Answer 37

Fibroblast focus (next to an area of dense, old fibrosis)

Question 38

Two subtypes of non-specific interstitial pneumonia (NSIP). Worse/better than UIP?

Answer 38

Cellular and fibrosing; better (affects younger patients)

Question 39

Cellular NSIP

Answer 39

Diffuse chronic inflammatory cell infiltrates without significant alveolar expansion; better prognosis than fibrosing

Question 40

Fibrosing NSIP

Answer 40

Diffuse interstitial fibrosis with uniform appearance (temporally uniform), preserved lung architecture and chronic inflammation

Question 41

How can we distinguish fibrosing NSIP from UIP

Answer 41

NSIP is not patchy and is all the same age

Question 42

Describe lymphocytic interstitial pneumonia (LIP): who gets it, presentation, radiological finding

Answer 42

Rare: seen primarily in patient's with Sjogren's syndrome and HIV; presents as cough/dyspnea; radiology shows diffuse ground glass changes with cysts

Question 43

LIP: histological finding

Answer 43

Small mature lymphocytes with variable numbers of plasma cells EXPANDING the alveolar septa

Question 44

Interstitial lung diseases with graulomas: two

Answer 44

Sarcoidosis, hypersensitivity pneumonitis

Question 45

Classic sarcoidosis findings (2)

Answer 45

Bilateraly hilar adenopathy and NON-NECROTIZING epithelioid granulomas

Question 46

Who gets sarcoidosis?

Answer 46

20-40 years of age, F > M, black, rare in Asia

Question 47

% sarcoidosis recovery, % with permanent pulmonary loss, rare outcome?

Answer 47

65%; 20%; small percentage progress to diffuse interstitial fibrosis

Question 48

Describe sarcoid granulomas

Answer 48

Non-necrotizing epithelioid granulomas with tightly packed epithelioid cells, giant cells, lymphocytes; generally adjacent to bronchioles/vessels, etc

Question 49

Dx of sarcoidosis requires...

Answer 49

Biopsy

Question 50

Describe hypersensitivity pneumonitis

Answer 50

Lung disease due to an organic antigen, can be acute (within hours of exposure) or chronic (extended exposure, maybe with progressive fibrosis)

Question 51

Hypersensitivity pneumonitis: classic triad

Answer 51

Chronic bronchiolotis, poorly-formed granulomas, organizing pneumonia

Question 52

Hypersensitivity pneumonitis: long-standing disease may evolve into...

Answer 52

Diffuse fibrosis mimicking UIP or NSIP

Question 53

Smoking-related interstitial lung disease (3)

Answer 53

Respiratory bronchiolitis associated interstitial lung diseae (RB-ILD), desquamative interstitial pneumonia (DIP), Langerhans cell histiocytosis

Question 54

Describe RB-ILD

Answer 54

Clinical symptoms of an interstitial lung disease and only finding on biopsy is RB (the accumulation of macrophages with finely granular brown pigment ONLY around airways)

Question 55

Describe Desquamative Interstitial Pneumonia (DIP)

Answer 55

Similar to RB-ILD but more diffuse and severe with insidious onset of SOB

Question 56

DIP: histological findings

Answer 56

DIFFUSE collections of intraalveolar macrophages (as opposed to only around airways)

Question 57

What is ABSENT in DIP

Answer 57

Minimal changes in alveolar septa and absent significant fibrosis

Question 58

Describe Langerhans cell histiocytosis (on EM?)

Answer 58

Bronchiolocentric fibrosis with "stellate" scar formation and variable numbers of Langerhans cells (EM = Birbeck granule)

Question 59

What does a Langerhans cell look like?

Answer 59

Polygonal with irregular nuclei with grooves

Question 60

What do we call a macrophage filled with brown smoke material?

Answer 60

Smokers' macrophages