DPLD, Resp Physiology, Transplant Flashcards
CHEST Videos, SEEK questions
Respiratory pressure associated with
(a) Inspiratory pressure associated with hypercapnia
(b) Weak cough/difficulty clearing secretions
(a) Max inspiratory pressure under (1/3) predicted normal associated with hypercapnia
(b) Weak cough expected with max expiratory pressure under 60
Most sensitive lung volume for obesity
ERV = expiratory reserve volume (amount you can exhale more after tidal volume exhalation)
Which lung volume decreases with age?
(a) Why does TLC remain the same?
(b) FEV1 reduction
Lung volumes with age- vital capacity reduces (inspiratory reserve volume + tidal volume + expiratory reserve volume) but residual volume increases
(a) TLC RTS because even though VC reduces, RV increases
(b) FEV1 reduces by 30 ml per year after age 30
What correlates with good DLCO maneuver?
(a) Inspired volume
(b) Duration of breath hold
Good DLCO maneuver
(a) Inspired volume at least 90% of vital capacity (TV + ERV + IRV)
(b) At least 10 second breath hold
Which drugs to hold before methacholine challenge?
Hold LAMA for at least a week
What is considered a positive methacholine challenge?
20% reduction in FEV1 from escalating doses of methacholine (up to 400 ug)
Who to consider for hypoxia altitude simulation testing?
PO2 lower at higher altitude- consider testing in pts with SpO2 under 92% correlating to PaO2 under 70
Minimal clinical importance difference for 6MWT
30m = minimal important difference for 6MWT
Which system is the limiting step for exercise in most healthy ppl?
Cardiovascular system (HR and stroke volume)
Not limited by vital capacity, in fact should have respiratory reserve (normal flow-volume loop, not at max MV) and normal gas exchange (no desat)
Desat of more than 5% from baseline is abnormal
What is the clinical diagnosis that fits the lung injury pattern of
(a) UIP
(b) DAD
Histologic pattern of
(a) UIP
If has a cause: CTD, asbestos, chronic HP, genetic disorders (ex: Hermansky-Pudlak syndrome)
If idiopathic = IPF
(b) Diffuse alveolar damage is the histologic finding of ARDS
If has a cause: infection, drugs, radiation
If doesn’t have a cause = AIP (acute interstitial PNA)
BAL findings characteristic of
(a) NSIP
(b) OP
(c) PLCH
BAL cells
Normal: 85% macrophages, 10-15% lymphocytes (slow immune cells, adaptive immune response), under 3% neutrophils (acute inflammation, innate immune response), under 1% eos
(a) NSIP = nonspecific interstitial PNA
over 20% lymphocytes, ‘BAL lymphocytosis’
(b) OP = mixed but high lymphocytes (20-40%) and neutrophils 10%, can have eos 5%
(c) PLCH pathognomonic- positive CD1a stain
Describe radiographic features of typical UIP
Radiographic features of UIP
-subpleural and basilar predominance
-reticular changes, bronchiectasis
-basilar honeycombing
-absence of other findings like ground glass or nodules (more c/w NSIP)
Describe histologic features of UIP
Histologic features that makes UIP
-fibroblast foci
-heterogeneity: normal lung next to fibrotic (homogenous more NSIP)- ‘patchy’ involvement
-basilar and peripheral predominant (as correlated on imaging)
-architectural distortion, honeycombing
-no features suggesting alternate diagnosis (granulomas)
NSIP
(a) Radiographic findings
(b) BAL findings
(c) Prognosis compared to IPF
NSIP
(a) Radiographically- ground glass, absence of honeycombing, possibly subpleural sparing
(b) BAL lymphocytosis (over 20%, when under 10% is nromal)
(c) Better prognosis than IPF in general, more likely to respond to steroids
How we subtype NSIP
NSIP now subtyped as
-cellular
-fibrotic
Normal BAL cell pattern
Normal BAL cell pattern
85% macrophages
10-15% lymphocytes (slower immune response, adaptive immune response)
Under 3% neutrophils (fast immune response, innate immune response)
Under 1% eos
Expect lymphocytic or neutrophilic BAL cell pattern in:
(a) IPF
(b) sarcoidosis
(c) NSIP
(d) ARDS
BAL cell pattern
(a) IPF- neutrophilic
(b) Sarcoidosis- lymphocytic (then CD4/8 elevated)
(c) NSIP- lymphocytosis (over 20%, normal under 10%)
(d) ARDS- neutrophilic (more acute inflammatory cells)
Differentiate histology of IPF from NSIP
Histologically
IPF- fibroblast foci, temporal heterogeneity (normal lung dispersed with fibrosis). subpleural/basilar predominance
NSIP- homogeneous, can have more cellular (inflammatory, lymphocytic) or fibrotic subtype
Expect lymphocytic or neutrophilic BAL cell pattern in:
(a) OP
(b) Fibrotic HP
(c) Infection
BAL pattern
(a) Organizing PNA- lymphocytic (slower inflammatory cells, adaptive immune response)
(b) Fibrotic HP- lymphocytic
(c) Infection: neutrophils (acute inflammatory cells, innate immune response)
Definition of IPF acute exacerbation
(a) Tx
Worsening symptoms/hypoxia with worsening infiltrates for up to 1 month without another cause (really exclude cardiac-induced pulmonary edema)
(a) No tx just supporitve
-anti-fibrotics to try to reduce incidence
Proven role of antifibrotics
Antifibrotics- both nintedanib and pirfenidone most strongly shown to reduce decline in lung function (specifically FVC)
-probably reduces exacerbations
Mechanism of nintedanib vs. pirfenidone
Nintedanib- TKI- blocks receptors of tyrosine kinases used in fibroblastic growth
Pirfenidone- anti-TGFbeta
Side effect profile nintedanib vs. pirfenidone
(a) Labs to monitor
Nintedanib- diarrhea
Pirfenidone- rash, nausea
(a) For both- baseline LFTs and LFTs q1-3 months
Hereditary syndrome with subtypes causing IPF with albinism and bleeding
Hermansky-Pudlak syndrome = autosomal recessive defect in lysosomes (intracellular protein trafficking)
Albinism (hair, skin)
Increased bleeding risk
Progressive pulmonary fibrosis, typically IPF pattern, in certain subtypes
Aside from antifibrotics- other helpful mgmt tips in IPF patients
IPF management
-consider transplant
-GERD management: very high overlap even if asymptomatic
Differentiate OP and COP
Organizing pneumonia- histologic pattern (granulation tissue plugs, patchy) can be seen in multiple clinical entities: CTD, vasculitis, infection
If idiopathic OP pattern = COP clinically
Histology buzzwords
(a) fibroblastic foci
(b) granulation tissue plugs
(c) hyaline membranes
(d) pigmented macrophages
(e) congo red stain
(a) Fibroblastic foci = UIP
(b) granulation tissue plugs = organizing pneumonia
(c) hyaline membranes = DAD
(d) pigmented (smoker’s macrophages) in RB-ILD and DIP
(e) Congo red stain = amyloid deposits
Most common cause of histologic pattern of DAD
(a) When is it called AIP
Histologic pattern of DAD (hyaline membranes, granulation, fibroproliferative) correlates with the clinical syndrome ARDS, most common overall due to infection, next from drugs
(a) If idiopathic then = AIP (acute interstitial pneumonitis)
What is LIP?
(a) Common secondary causes
(b) Treatment
LIP = lymphocytic interstitial PNA- type of interstitial PNA with lymphocytic infiltrate
(a) HIV, Sjogrens most common, CVID or hypogammaglobulinemia
(b) ART (if HIV), steroids, immunosuppression
If histologic diagnosis of LIP made on lung biopsy- what lab tests to check?
LIP on surgical biopsy, should trigger checking
-HIV status (secondary LIP)
-Anti-Ro/La (SSA/SSB)- Sjogrens can cause secondary LIP
-RF and ANA (other CTDs)
HRCT findings of LIP
HRCT findings of lymphocytic interstitial pneumonia (can be idiopathic or due to HIV, Sjogrens):
-ground glass can be similar to NSIP
-thin-walled cysts (differs from NSIP)
-septal thickening
Key to differentiate LIP from pulmonary lymphoma
Key in LIP (lymphocytic interstitial PNA) is that the lymphocytes are polyclonal/benign
Clinical significance of CD4/8 ratio
-reduced ratio (under 1) correlates with organizing PNA
-higher, specifically over 4 rather specific for sarcoidosis
Interstitial pneumonia associated with immunodeficiencies (CVID, hypogammaglobulinemia)
LIP (lymphocytic interstitial PNA)- patchy GGOs, nodules and cysts on imaging, lymphoid infiltrates on histology
Differentiate AFOP from DAD histologically
AFOP- another rare idiopathic pneumonia (like LIP and PPFE)
Fibrinous balls associated with organizing PNA (OP with granulation tissue plugs) but no hyaline membranes (charateristic of DAD).
Also AFOP more distal- terminal bronchioles and alveoli while DAD involves all aspects of parenchyma)
What is pleuroparenchymal pulmonary fibrosis?
PPFE and LIP- two rare forms of idiopathic interstitial pneumonias
PPFE- fibrosis of upper-lobe pleura and subpleural parenchyma
pleural thickening
upper lobe volume loss
very prone to PTX
Organizing pneumonia
(a) Typical HRCT findings
(b) Treatment
OP
(a) patchy, fleeting ground glass or consolidative infiltrates
(b) Long-term steroids (6-12 months) with risk of recurrence if taper too quickly
Hamman-Rich syndrome
(a) Clinically
(b) What differentiates from ARDS
(c) Biopsy findings
Hamman-Rich syndrome = acute interstitial pneumonia (AIP)
(a) Clinically- acute hypoxic RF, rapid progression to respiratory failure (less than 7 days)
(b) Idiopathic, if isn’t idiopathic can call it ARDS
(c) Diffuse alveolar pattern on histo (same as ARDS)- diffuse hyaline membranes and alveolar architectural distortion
Histologic defining feature of respiratory bronchiolitis
(a) When becomes RB-ILD
Respiratory bronchiolitis = tan-pigmented (‘smokers’) macrophages in respiratory bronchioles (smallest airways partially surrounded by alveoli, differentiated from alveolar ducts which are fully surrounded by alveoli)
(a) Becomes RB-ILD when there’s clinical evidence of ILD in a smoker with no other pathologic finding
Differentiate RB-ILD from
(a) PLCH
(b) NSIP
(c) IPF
(d) DIP
(e) HP
RB-ILD
(a) PLCH- both associated w/ cigarette smoking with nodules but PLCH has upper lung zone cysts with honeycomb changes. Key is CD1a+ Langerhand cells in BAL for PLCH
(b) NSIP- basilar reticular and ground glass changes (vs. upper centrilobular changes of RB-ILD)
(c) IPF- honeycombing, no honeycombing in RB-ILD
(d) DIP- spectrum of same process but DIP more diffuse (vs. centrilobular in RB-ILD) with lower lobe predilection (vs. upper lobe for RB-ILD). Path is the differentiator
(e) HP- poorly formed noncaseating granulomas or mononuclear infiltrates
RB-ILD
(a) Typical imaging findings
(b) Typical PFT findings
RB-ILD
(a) Imaging- vague nodules, patchy GGOs due to smokers macrophages in and around respiratory bronchioles
(b) Mixed restrictive and obstructive
How to differentiate LIP from follicular bronchiolitis
Hard b/c both are on the spectrum of lymphoproliferative pulmonary diseases, associated with Sjogrens and immunodeficiences (CVID, HIV) but do have different path and imaging
LIP = Lymphoid interstitial PNA- cysts on imaging
LIP path- mix of cells (lymphocytes, plasma cells, histiocytes
FB- hyperplastic lymphoid follicles with germinal centers (but no plasma cells)
CTD-related ILDS
(a) Most common pattern overall
(b) Most common pattern in RA
CTD-related ILDs
(a) Overall most common: NSIP
(b) In RA specifically UIP is most common
Antibody in the following associated with higher risk of ILD
(a) Anti-synthetase syndrome
(b) Systemic sclerosis
(a) Anti-JO = anti-tRNA synthetase
Anti-synthetase = subset of polymyositis/dermatomyositis spectrum
(b) Anti-SCl70 (topoisomerase-1 Ab) associated with higher risk of ILD
CTD related to increase risk of primary pulmonary lymphoma
Sjogrens- think of association with lymphocytic spectrum of diseases (follicular bronchiolitis, lymphoid interstitial PNA) and primary pulmonary lymphoma = MALToma
For which CTD-ILD would steroids not be first line treatment?
(a) And what is first line treatment
Systemic sclerosis specifically MMF (mycophenolate mofetil = cellcept) has good data
Then if fibrosis persists after MMF initiation can consider adding nintedanib
BAL findings consistent with sarcoidosis
Sarcoidosis BAL: lymphocytic (over 15%)
CD4/CD8 high, specifically over 4 (vs. low c/w organizing PNA and HP)
Stages of sarcoidosis based on chest imaging
(a) Why stage like this?
Stages of sarcoidosis
0- no lung involvement (8% at time of diagnosis)
I- bilateral hilar adenopathy withOUT parenchymal involvement (40%)
II- bilateral hilar LN with parenchymal involvement (35%)
III- parenchymal involvement w/o hilar lymphadenopathy (10%)
IV- progressive fibrosis with/without cavitation (5%)
(a) Radiographic stage correlates with rate of spontaneous remission
Which drug is typically first-line steroid sparing agent for sarcoidosis?
Methotrexate
Clinical features of Lofgren’s syndrome
Lofgren’s syndrome = triad of arthritis (most commonly bilateral ankes), erythema nodosum, and bilateral hilar lymphadenopathy
-Diagnostic for sarcoid with high rate of spontaneous remission (so doesn’t require treatment)
vs. Loffler’s syndrome = transient pulmonary eosinophilia from parasitic infection
What is lupus pernio?
Lupus pernio- hyperpigmentation on central face, typically on nose, characteristic of sarcoidosis
Describe probable UIP pattern on HRCT
Probable UIP = peripheral and basilar predominant fibrosis but no honeycombing
-sometimes seen as early UIP (so honeycombing just not there yet)
What is Loffler syndrome?
Transient, self-limiting pulmonary eosinophilia with fleeting/migratory infiltrates and peripheral eosinophilia
Acute onset cough, dyspnea, wheeze, occasionally fever
Mechanism thought to be an allergic response to helminth (ascaris, strongy, and hookworms)
Typical antibody panel for drug-induced lupus
Positive ANA
Anti-histone Ab
(anti-dsDNA more in idiopathic SLE)
Drugs most likely to cause drug-induced lupus
Hydralazine, procainamide, INH
How long after getting drug is immune-checkpoint inhibitor induced pneumonitis most likely?
1-3 months, median 3 months
(basically not right after infusion)
Hepatopulmonary syndrome
(a) Aa gradient cutoff
(b) Describe the two mechanisms of anatomic shunt
(c) When supplemental O2 works less
HPS
(a) Aa gradient over 15
(b) Dilated capillary beds (so not all blood gets oxygenated) and new capillaries that bypass alveoli completely
(c) As the shunt fraction worsens, supplemental O2 correcs less
What group of PH does portopulmonary HTN fall into?
Group I
Which cirrhotic would you transplant- portopulmonary hypertension or hepatopulmonary syndrome?
HPS is an indication for transplant- PaO2 under 60 counts as a MELD exception
While portopulmonary HTN Is a contraindication to transplant, and may not improve with transplant
Name autoantibodies expected in each CTDs
(a) MCTD
(b) Sjogrens
(c) SLE
(d) RA
(e) Systemic sclerosis
(f) Anti-synthetase syndrome
CTD autoantibodies
(a) MCTD: anti-RNP
(b) Sjogrens: anti-SSA/SSB (Ro/La)
(c) SLE: anti-dsDNA
(d) RA: Anti-CCP and RF
(e) Systemic sclerosis/scleroderma: anti-SCl-70 (DNA topoisomerase)
(f) Anti-Jo1
For which CTD is annual PH screening recommended?
Annual screening with TTE for systemic sclerosis/scleroderma (anti-SCl-70 at highest risk) patients
PAH develops in over 15% of SS patients due to elevated endothin-1 => vasconstriction, vascular endothelial cell proliferation, smooth muscle hypertrophy
LAM
(a) Brief pathophysiology
(b) Immunohistochemical stain
(c) Imaging findings
(d) Effusions
LAM
(a) proliferation of muscles in bronchovascular bundle forming thin-walled homogenous cysts
(b) HMB-45 (muscle marker)
(c) Imaging: homogeneous thin-walled cysts
(d) Recurrent chylous effusions (from lymph accumulation)
LAM treatment
LAM treatment
-avoid estrogen containing compounds
-sirolimus = mTOR inhibitor to reduce smooth muscle proliferation
-pleurodesis given high risk (50-80%) of recurrent PTX
How can a male have LAM?
Tuberous sclerosis related, secondary LAM
Otherwise primary is all pre-menopausal F thought to be estrogen mediated
Name 4 ILDs most commonly associated with smoking
- RB-ILD
- DIP
- PLCH
- Acute eosinophilic PNA
Which cells/stains are pathognomonic for
(a) PLCH on BAL?
(b) LAM
(c) Amyloidosis
(a) Langerhan cells that stain +CD1a and S-100
(b) Muscle markers (actin, desmin); HMB-45
(c) Apple-green birefrigence with congo red staining on polarized microscopy
Found in acute or chronic eosinophilic PNA
(a) Pleural effusions
(b) Elevated serum IgE and eos
(c) Radiographic negative of pulmonary edema
(d) Interstitial fibrosis on TBBx
Eosinophilic PNA
(a) effusions in acute, not chronic
(b) Elevated serum IgE and peripheral eosinophilia more common in chronic
(c) Chronic- peripheral predominance = negative of pulmonary edema
(d) Fibrotic changes = chronic
What exposure to screen for that can identically mimic sarcoidosis
Berylliosis- from aerospace exposure, circuit boards/electronics, cuaseing cell mediated immune response in the lungs causing noncaseating granulomas
Lofgrens syndrome triad
Lofgrens- clinical triad of sarcoidosis with high rate of remission
-erythema nodosum
-bilateral hilar lymphadenopathy
-arthralgia (most commonly bilateral large joints like ankles)
BAL findings consistent with sarcoidosis
Sarcoidosis
-lymphocytic predominant BAL (over 20%)
-CD4/CD8 elevated (normal 1.5-2.0, sarcoid over 3.5)
Classic sarcoidosis imaging findings
Nodules along bronchovascular bundle/peri-bronchovascular (and fissure)
Typical first line treatment algorithm for sarcoidosis
Sarcoidosis treatment- start with steroids
Typically high-dose steroids 4-6 week burst followed by 6 month maintenance
Start MTX as steroid-sparing agent
Differentiate congenital and acquired pulmonary alveolar proteinosis
PAP
Congenital- due to congenital mutation in surfactant or GM-CSF receptor
Acquired (more common) due to autoantibody against GM-CSF
PAP
(a) Serum lab tests
(b) Expected PFT findings
(c) 2 classic chest imaging findings
PAP
(a) Elevated serum LDH and surfactant (not necessary but supportive)
(b) As with any alveolar filling process expect restriction and reduced diffusion
(c) Imaging findings
-bat wing appearance on CXR b/c of perihilar predominance of consolidations
-crazy paving due to alveolar filling and septal thickening with preserved architecture
PAP pathology
(a) BAL appearance
(b) Electron microscopy
(c) Stain
PAP pathology
(a) BAL- milky effluent, proteinaceous, acellular
(b) Electron microscopy with diagnostic lamellar bodies = laminated phospholipid structure
(c) PAS stain +
Treatment for PAP
PAP treatment
First line- whole lung lavage, typically require mor ethan one, average duration of repsonse about 15 months
Then inhaled or subQ GM-CSF proven to improve lung function in acquired PAP
Key opportunistic infections seen in PAP
PAP- increased risk for opportunistic infection, mnemonic ‘MAN’
Non-tuberculosis mycobacteria
Aspergillus
Nocardia
Pulmonary amyloidosis
(a) Mechanism of injury
(b) Possible supporting serum lab test
Pulmonary amyloid
(a) Deposition of insoluble proteins (beta-pleated sheet formation) in airways and parenchyma
(b) SPEP or UPEP with monclonal spike consistent with gammaopathy
Pulmonary amyloidosis
(a) Most characteristic imaging findings
(b) Role of laser therapy
Pulmonary amyloidosis
(a) Can be very variable but most classic are diffuse nodules that can cavitate and calcify
(b) Laser therapy for airway involvement (ex: tracheobronchial stenosis)
Birt-Hogg-Dube
(a) Mechanism/gene
(b) Clinical triad
Birt-Hogg-Dube
(a) Autosomal dominant mutation in folliculin gene
(b) Clinically:
-lung disease: cysts and high rate PTX
-fibrofolliculomas = dome shaped papules on face, upper extremities, trunk
-malignant renal tumors = renal cell carcinoma, clear cell, high lifetime risk so screening recommended
Mgmt of Birt-Hogg-Dube
-usual care for PTX
-routine screening for renal malignancy given high lifetime risk
Give ddx for noninfectious cystic lung disease
Birt-Hogg-Dube
LAM
PLCH (langerhan cell histiocytosis)
LIP (lymphocytic interstitial PNA)
Amyloidosis
Lipoid PNA
(a) How to differentiate from infectious PNA on imaging
(b) Typical pathology finding
Lipoid PNA- random from lipoid material filling alveoli, can be from laxatives containing mineral oil
(a) Lipoid PNA has characteristic low, or even negative, Hounsfield units
(b) Lipoid vacuoles, lipid-laiden macropahges in the alveolar space
Name key drugs associated with these drug-induced lung injuries
(a) Cough
(b) Bronchospasm
(c) Noncardiogenic pulmonary edema
(d) VTE
Drug-induced lung injury
(a) Cough- ACEi
(b) Bronchospasm- Beta-agonists
(c) Noncardiogenic pulmonary edema- tocolytics (terbutaline)
(d) VTE- estrogen containing compounds (OCPs)
Name key drugs associated with these drug-induced lung injuries
(a) Hypersensitivity pneumonitis
(b) Sarcoidosis mimic
(a) Drug-induced HP- MTX, sulfa drugs (nitrofurantoin), bleomycin
(b) Sarcoidosis mimic (drug-induced sarcoid-like reaction/granuloma-formation): MTX, infliximab, immune checkpoint inhibitors, IFNs
Name key drugs associated with these drug-induced lung injuries
(a) Drug-induced lupus (name 4 drugs)
(b) PAH
Drug-induced lung injury
(a) Drug induced lupus (+anti-histone Ab): biggest offenders = hydralazing and procainamide
(b) PAH- methamphetamine, fenfen, dasatinib
Occupational lung disease that histologically mimics
(a) secondary PAP
(b) sarcoidosis
(a) Secondary PAP- alveolar filling with proteinaceous material that stains PAS+, same thing found in acute silicosis (sandblasting, tunneling, mining, masonry)
(b) Berylliosis with non-necrotizing granulomas and nodules on CT
Buzzwords for what occupational/environmental lung disease
(a) sandblasting, tunneling
(b) shipbuilders
(c) aerospace, aircraft
(d) moldly hay
(e) electricians
(a) Sandblasting, tunneling- think silica quartz = silicosis
(b) Shipbuilders = asbestosis
(c) Aerospace, aircraft = berylliosis
(d) Moldy hay = farmer’s lung- HP
(e) Electricians- asbestosis b/c asbestos is a good insulator
What is Caplan syndrome?
Caplan syndrome- when patients with rheumatoid arthritis get exposed to coal dust and have a pulmonary nodular reaction
-specific type of coal worker’s pneumoconiosis
Which environmental/occupational exposure is associated with
(a) Melanoptysis
(b) Long and short fibered crystals on electron microscopy
(c) Cavitation and calcification on imaging
(a) Melanoptysis- coughing up black stuff seen in coal miners pneumoconiosis
(b) Long and short fibered crystals- asbestos exposure
(c) Cavitation and calcification on imaging = asbestos
How to differentiate chronic asbestosis from IPF
Both chronic asbestosis and IPF- septal fibrosis and honeycombing
Chronic asbestos- pleural involvement with calcification and possible cavitation, while IPF wont typically have pleural involvement
Bird fancier lung
(a) Causes which type of ILD
(b) Path findings
Bird fancier lung
(a) Hypersensitivity pneumonitis
(b) Poorly organized non-necrotizing granulomas
Differentiate imaging findings of acute vs. chronic hypersensitivity pneumonitis
Acute HP- tons of (diffuse) ground glass
Chronic HP- ground glass with reticular micronodules, honeycombing, and fibrosis
BAL findings of HP
BAL in hypersensitivity pneumonitis
-lymphocytosis (over 50%)
-elevated CD8 so ratio of CD4/CD8 inverts (reduced)
What type of work-related asthma is baker’s lung?
Occupational asthma (de novo): Immunologic, work-caused asthma not work-exacerbated
-sensitizer-induced, latency period, immunologic phenomenon
Effect of Hb dissociation curve in response to high altitude
Altitude => respiratory alkalsosis (due to hyperventilatory drive), alkalosis shifts dissociation curve to the left
-increased affinity of Hb for O2 => Hb picks up more O2 at alveolar-capillary membrane
Describe body’s acclimation to high altitude
(a) ventilatory response
(b) bicarbonate handling by kidney
(c) Hb dissociation curve shift
High altitude
(a) hyperventilate => respiratory alkalosis
(b) kidneys get rid of more bicarb to neutralize pH
(c) Hb dissociation curve shifts to the left due to alkalosis- increased affinity of Hb for O2 so Hb will pickup more O2 at alveolar-capillary membrane
High altitude pulmonary edema
(a) Mechanism
(b) Management
High altitude pulmonary edema
(a) Mechanism- hypoxic vasoconstriction causing capillary leak
(b) Oxygen (can consider hyperbaric), descent, CCB or PDE5 inhibitor
High altitude cerebral edema
(a) Mechanism
(b) Management
High altitude cerebral edema
(a) hypoxia-induced cerebral edema (more severe than acute mountain sickness)
(b) To reduce symptoms- descend as quickly as possible (not gradually), dexamethasone, hyperbaric
-ppx with acetazolamide
Differentiate pulmonary cyst vs. cavity
Cyst- thin (<2mm) wall, typically filled with air
Cavity- typically within a consolidation, thicker walled
Cystic lung disease associated with
(a) Elevated VEGF-D
(b) BRAF mutation
(c) folliculin gene
(d) tuberous sclerosis
Cystic lung disease
(a) Elevated VEGF-D = LAM
(b) BRAF mutation in PLCH
(c) follicular gene auto dominant = birt-hog-dube
(d) tuberous sclerosis = LAM
Cystic lung disease associated with
(a) chylothorax
(b) Skin lesions
(c) Renal tumors
Cystic lung disease
(a) Chylothorax = LAM
-think smooth muscle proliferation in interstitium prevents adequate lymphatic drainage
(b) Skin lesions = folliculomas seen in Birt-Hogg-Dube (aut dom mutation in folliculin gene)
(c) Renal tumors seen in
-LAM = angiomyolipomas
-Birt-Hogg-Dube = renal cell and clear cell, high lifetime risk of renal malignancy so screening recommended
Differentiate risk factors between cystic lung diseases
(a) PLCH
(b) LIP (lymphoid interstitial pneumonia)
Cystic lung diseases
(a) PLCH associated with smokers
(b) LIP associated with immunocompromised (CVID, HIV) and CTDs (Sjogrens)
Cavitary lung disease associated with
(a) Severe PH out of proportion to lung disease
(b) Regular diffuse cysts (vs. irregular/cavitating)
Cavitary lung disease
(a) Severe PH (classically group V- multifactorial and poorly understood) = PLCH
(b) Regular diffuse cysts = LAM, vs irregular and cavitating seen in PLCH and amyloid
Most common pathognesis of pulmonary alveolar proteinosis
PAP- 90% are acquired/autoimmune due to Anti-GM-CSF antibody which interferes with macrophage metabolism of surfactant
Autoimmune (acquired) PAP
(a) Classic lab test
(b) PFT finding
(c) 2 characteristic chest imaging findings
Autoimmune PAP
(a) Anti-GM-CSF Ab in serum or BAL
(b) PFTs- same as any alveolar filling process = restricted with reduced DLCO
(c) Chest imaging
-bat wing appearance given perihilar predominance
-crazy paving: ground glass of alveolar filing with thickened interlobular septa but maintained pulmonary architecture
Cystic vs. noncystic rare lung diseases associated with BRAF mutation
Cystic lung disease associated with BRAF mutation = PLCH (irregular cysts in young smokers)
Cd1a positive langerhan-cells
Non-cystic typically pleural features of abnormal histiocyte deposition from BRAF mutation = Erdheimer-Chester disease
Non-langerhan cell histiocytic disorder (so CD1a negative)
Differentiate radiation-induced pulmonary fibrosis from radiation-induced organizing PNA
Radiation-induced pulmonary fibrosis typically in field of radiation, see classic port lines
While radiation-induced OP is a response typically found outside of radiation field
Name some primary bronchiolar disorders (vs. ILD or large airway diseases that have some bronchiolitis)
Bronchiolitis (inflammation of bronchioles) can be due to ILDs or large airway disorders, or primary
Some primary:
-follicular bronchiolitis due to lymphocytic proflieration
-constrictive (aka obliterative) bronchiolitis seen post-lung transplant or from neuroendocrine tumorlets (DIPNECH)
-Respiratory bronchiolitis from smoking
Classic clinical presentation of DIPNECH
Middle-aged F, nonsmokers with years of cough, breathlessness, and wheezing found to have tumorlets (little groups of overproliferated neuroendocrine cells) on imaging
Constrictive bronchiolitis
(a) Etiologies
(b) Characteristic PFT findings
(c) CT findings
(d) Response to steroids
Constrictive bronchiolitis- primary disorder of small airways
(a) If after transplant = BOS (bronchiolitis obliterans syndrome)
CTD-related
Post-infectious
DIPNECH
Inhaled toxins/drugs
(b) Obstruction without bronchodilator response
(c) CT- mosaic with air trapping due to obstruction, small airway thickening
(d) Response to steroids typically poor
Differentiate DIPNECH syndrome from asymptomatic patients with well-differentiate NETs
Well-differentiated neuroendocrine tumors- can be asymptomatic
if symptomatic- aka showing clinical disease (chronic cough, wheezing, dypsnea) = DIPNECH syndrome
What is bronchopulmonary sequestration?
(a) Most common location
Congenital abnormality of lower respiratory tract- nonfunctioning mass of lung tissue w/o communication to tracheobronchial tree
-separate blood supply typically off aorta (from systemic circulation)
(a) LLL
Pulmonary disorder characterized by abnormal phosphorus metabolism by type II pneumocytes
(a) Tx
Pulmonary alveolar microlithiasis- phosphorus precipitates with Ca forming CaPO4 crystals = microliths
(a) Lung transplant
Cytokine most specific for eosinophils
IL-5
Hence mepolizumab (anti-IL5 for EGPA and severe eosinophilia asthma)
Typical presentation of pulmonary strongyloides
Pulmonary strogngyloides- think immunocompromised host with acute onset hypoxic resp failure, progresses rapidly to ARDS (bilateral diffuse infiltrates) with peripheral eosinophilia
-ARDS in immunocompromised pt with peripheral eosinophilia
Most common causes of drug-induced acute eosinophilic PNA
Drug-induced AEP
-antibiotics (most typically daptomycin, nitrofurantoin)
-NSAIDs
Illness script for ABPA
(a) Clinical features
(b) Imaging
ABPA- asthmatic or CF pt with unrelenting symptoms, mucoid impaction, chronic productive cough
(a) asthma
(b) transient opacities due to mucus plugs, ‘finger in glove’
central/proximal bronchiectasis
Tx for ABPA
ABPA treatment
-steroids b/c it’s a hypersensitivity to inhaled mycosis/fungi
-in severe can consider azole
ABPA
(a) Most common comorbidities
(b) Lab values
ABPA
(a) asthma and CF
(b) Elevated IgE (over 1000), serum precipitins to aspergillus, anti-A fumigatus IgE and IgG
-notably not galactomannan
What is Loffler syndrome?
Loffler syndrome = syndrome of transient pulmonary radiographic opacities and peripheral eosinophilia, likely due to transpulmonary passage of helminth larvae
- transient, self-limiting, benign pulmonary eosinophilia lasting less than one month
-pulmonary infiltrates on imaging, elevated serum eos, acute symptoms (cough, dyspnea, wheeze)
-thought to be an allergic response to transpulmonary migration of helminth larvae
Tx for Loffler syndrome
Loffler syndrome = simple pulmonary eosinophilia- transient pulmonary eosinophilia due to allergic reaction to transpulmonary migration of helminth larvae
generally doesn’t require treatment but can consider antihelminth tx if other symptoms
Illness script for acute eosinophilic PNA
Acute onset febrile illness either idiopathic or with trigger (daptomycin, NSAIDs, smoking) with rapid progression to ARDS with bilateral infiltrates on CXR
Histopath findings of acute eosinophilic PNA
Eos everywhere (intra-alveolar, interstitium)! then also DAD (diffuse alveolar damage) = histopath finding for ARDS
Eos + DAD
More common in acute vs. chronic eosinophilic PNA
(a) Pre-existing asthma
(b) Relapse with steroid taper
(c) Peripheral eosinophilia
(d) BAL eosinophilia
(e) Elevated IgE
(f) Weight loss
AEP vs. CEP
(a) Pre-existing asthma in 50% of pts who develop CEP
(b) CEP has high rate of recurrence while AEP doesn’t
(c) Peripheral eosinophilia uncommon in AEP, common in CEP
(d) Both with elevated BAL eos over 25%
(e) Elevated serum IgE more common in CEP
(f) Subacute weight loss, cough, wheezing etc in CEP (AEP 5-7 days too fast for weight loss)
Characteristic imaging findings of acute eosinophilic PNA
AEP- diffuse ground glass b/c eos infiltrate alveolar space and interstitium
Bilateral small pleural effusions in 2/3
Buzzword: photographic negative of pulmonary edema
Photographic negative of pulmonary edema- peripheral dense consolidations, classic of chronic eosinophilic PNA
Illness script for chronic eosinophilic PNA
(a) Age, comorbidities
(b) Clinical feature
Middle aged F with history of asthma with nonresolving pneumonia, maybe wheeze dyspnea and some weight loss over months
Idiopathic hypereosinophilic syndrome
(a) Difference from chronic eosinophilic PNA
(b) Treatment
Idiopathic hypereosinophilic syndrome- systemic hypereosinophilia
(a) Systemic manifestations, only 50% have pulmonary findings, typically more chronic course in IHS (years) vs. months in CEP
(b) Tx for both is steroids
EGPA vs ABPA
(a) Diagnostic similarities
(b) Diagnostic differentiators
Same
-peripheral and BAL eosinophilia, peripheral elevated IgE
-tx of steroids
Different
-EGPA: vasculitis, multisystem effects mainly asthma, peripheral nervous system (mononeuritis multiplex), sinus disease, skin involvement, lung involvement 50%
-ABPA: allergic response to mycosis (typically aspergillus), mucus impaction with bronchiectasis
Mepolizumab
(a) Mechanism
(b) Indications (name at least 3)
Mepolizumab
(a) Anti-ILD5 (main cytokine specific for eosinophilic signaling)
(b) Indications: need for strong anti-eos
-idiopathic hypereosinophilia syndrome
-EGPA (elevated eos vasculitis with asthma, sinusitis, mononeuritis multiplex)
-refractory chronic eosinophilic PNA
-severe eosinophilic asthma (peripheral eos at least 150)
-rhinosinusitis with nasal polyps
What toxicity to treat with
(a) Fomepizole
(b) Flumazenil
(c) Methylene blue
(d) Hydroxycobalamin
(e) Sodium thiosulfate
Toxicities
(a) Fomepizole for ethylene glycol toxicity (antifreeze) or methanol
(b) Flumazenil for benzo toxicity
(c) Methylene blue for methemoglobinemia (from drugs typically)
(d, e) Hydroxycobalamin (cyanokit) and sodium thiosulfate in combo for cyanide toxicity
Which way does carbon monoxide poisoning shift the Hb-dissociation curve?
-CO shifts Hb dissociation curve left and down
CO binds to Hb with 200x affinity, reducing total oxygen-carrying capacity (so shift curve downward)
CO binding also increases Hb affinity for O2 so increased O2 binding and less offloading into tissues = left-ward shift
Compare exposures for the following toxicities/poisonings
(a) Carbon monoxide
(b) Cyanide
Exposures
(a) CO- tasteless, odorless gas typically from car fumes, house fires, wood-burning stoves, ovens (any organic burning of oxygen)
(b) Cyanide- ‘bitter-almond’ taste from building fires and drugs (nitroprusside)
Mechanism of carbon monoxide poisoning
(a) Diagnostic lab test
CO poisoning- reduces oxygen carrying capacity of Hb and reduces O2 offloading into tissues => tissue hypoxia
(a) CO-Hb over 15%
-over 25% consider hyperbaric
Treatment for CO poisoning
(a) When to use hyperbaric
CO poisoning- want to give highest oxygen possible to outcompete CO for Hb binding sites
= 100% nonrebreather
(a) Consider hyperbaric for any AMS/unconsciousness or when CO-Hb exceeds 25% (abnormal over 15%)
Mechanism of methemoglobinemia
(a) Etiologies
Methemoglobinemia = oxidize iron group in heme reducing the transport of oxygen
(a) Drugs
-dapsone, nitrates, benzocaine (ex: topical lidocaine)
-reglan
Clinical/lab data to support
(a) methemoglobinemia
(b) cyanide poisoning
Clinical features/lab data
(a) Methemoglobinemia- cyanosis, can’t see it on VBG, see saturation gap (classically between finger sat vs. blood gas b/c finger sat can’t differentiate)
(b) Cyanide poisoning- lactic acidosis, venous hyperoxia (bright red venous blood)
Mechanism of cyanide toxicity
(a) Most common etiologies
Cyanide toxicity- CN binds to cytochrome and inhibits oxidative phosphorylation
-so not that the tissues don’t get oxygen (methemoglobinemia, CO poisoning) but they can’t use it
(a) Etiologies
-fires
-drugs: nitroprusside
Treatment for
(a) Methemoglobinemia
(b) cyanide poisoning
Tx/mgmt
(a) Methemoglobinemia- methylene blue (de-methylate heme in hemoglobin so it can carry oxygen again)
(b) Cyanide poisoning- cyanokit (hydroxycobalamin) and sodium thiosulfate
3 infections consider relative contraindications to lung transplant
- M. abscessus- very hard to eradicate, high recurrence in transplanted lung
- B. cepacia
- Resistant pseudomonas
2 diseases where double really preferred to single lung transplant and why
-cystic fibrosis or bronchiectasis given high risk of infection recurrence post-transplant if leave an infected lung in
-PH b/c high PVR in old lung stays and pt much more vulnerable to any injury/insult to new lung
ex: gets single lung, gets PNA in single lung, not using any of native lung => womp womp
Typical backbone of starting maintenance immunosuppression post-lung transplant
Typical maintenance
-calcineurin inhibitor: tacrolimus, cyclosporine
-antimetabolites (DNA synthesis inhibitor): azathioprine, mycophenolate mofetil (cellcept)
-prednisone
Name two of each
(a) calcineurin inhibitors
(b) antimetabolites
(c) mTOR inhibitors
Immunosuppression post-transplant
(a) Calcineurin inhibitors- tacrolimus, cyclosporine
(b) Antimetabolites (DNA synthesis inhibitors)- MMF (cellcept), azathioprine
(c) mTOR inhibitors- sirolimus, everolimus
Possible clinical features of post-transplant wound dehiscence
Diagnose on bronchoscopy- but may have persistent PTX or mediastinal air on imaging
Why wait until ~3 months to start sirolimus post lung transplant?
Because sirolimus significantly impairs wound healing, higher risk of wound dehiscence
Primary graft dysfunction
(a) Clinical presentation
(b) Expected timeline
(c) Proposed mechanism
PGD
(a,b) ARDS within first 72 hrs of transplant
bilateral hazy opacities, profound hypoxia
(c) Ischemic-reperfusion injury
Primary graft dysfunction
(a) Histology
(b) How to grade severity
(c) Mgmt
PGD
(a) ARDS = DAD (diffuse alveolar damage)
(b) Severity graded like ARDS, by P:F ratio
(c) Mgmt- supportive- iNO, ECMO
Name the most common of the following types of infection post-transplant
(a) Fungal
(b) Bacterial
(c) Viral
Post transplant
(a) Fungal- most common aspergillus (acute angle branching hyphae) and candida
(b) Bacterial- staph and pseudomonas
(c) Viral- CMV
How is most acute rejection detected?
Acute rejection typically detected on surveillance bronchoscopy
-some can be symptomatic, or sometimes see as decline on PFTS (should peak and plateau around month 3)
Acute rejection
(a) Timeline post-transplant
(b) How graded on pathology
Acute rejection
(a) Typically first 3-12 months
(b) Pathology graded by severity
A- around vessels 0-4
B- around bronchioles 0-2
BX if airways not sampled
Treatment for acute rejection
Tx for acute rejection = pulse-dose steroids!
Methylpred 10-15 mg/kg/day x3 days then prednsione 0.5-1mg/kg/day tapered over months
Mechanism of chronic rejection of lung transplant
(a) Most important risk factor
(b) Typical clinical findings
Chronic rejection in lung transplant = BOS = bronchiolitis obliterans syndrome, type of constrictive bronchiolitis with progressive obliteration and fibrosis of terminal respiratory bronchioles
(a) Prior acute rejection
(b) Clinically- unexplained obstructive defect, progressive dyspnea on exertion
Chronic rejection = bronchiolitis obliterans syndrome
(a) Imaging findings
(b) How to stage severity
(c) Tx/mgmt
BOS
(a) Imaging- air trapping, thickened airways, hyperinflation
(b) Severity staged by change in FEV1 from baseline
(c) Typically not responsive to steroids like acute rejection, not much helps but can try to adjust (increase) immunosuppression
-Add chronic azithro
Differentiate how to diagnose acute vs. chronic rejection of lung transplant
Acute rejection diagnosed on TBBx
While chronic rejection more on clinical picture and PFTs, TBBx not helpful to diagnose BOS
Tx for invasive aspergillus
(a) What to be careful of when doing this in transplant patients
Invasive aspergillus treatment = voriconazole
(a) Vori significantly increases tacro levels => if starting vori need to drop tacro dose
Tx for fungal infections post-transplant
(a) Invasive aspergillus
(b) Candida
Tx
(a) Invasive aspergillus- voriconazole
(b) Candida- micafungin
azoles don’t do great in covering non-albicans candida species
Most common cause of post-transplant mortality depending on time frame
(a) Within first 30 days
(b) 30 days to one year
(c) After one year
Post-transplant mortality
(a) Primary graft dysfunction in first 30 days
(b) 1-12 months: infection
(c) After one year most common cause of death = BOS (chronic rejection)
Timeline post transplant- when to expect
(a) PGD
(b) Infection
(c) BOS
Timeline
(a) PGD typically within first 30 days, even more in first 72 hrs
(b) Infection first 1-12 months
(c) BOS- after 12 months
Most common side effects of immunosuppression drugs
(a) Sirolimus
(b) Tacrolimus
(c) MMF (cellcept)
Side effects
(a) Sirolimus- pancytopenia, wound dehiscence/poor healing
(b) Tacro- nephrotoxicity
(c) MMF- pancytopenia
Post-transplant immunosuppressants associated with pancytopenia
Sirolimus (mTOR inhibitor) and MMF (cellcept, antimetabolite, DNA synthesis inhibitor)
Post-transplant immunosuppressant associated with thrombotic microangiopathy
Calcineurin inhibitors (cyclosporine and tacrolimus) carry risk of drug-induced HUS
-nonimmune intravascular hemolysis producing schistocytes
-for calcineurin inhibitors thought to be dose-dependent, non-immune TMA (thrombotic microangiopathy) due to direct cellular damage
Post-transplant immunosuppressant associated with neurotoxicity
Neurotoxicty- calcineurin inhibitors (tacrolimus and cyclosporine)
Encephalopathy, PRES
What is PTLD?
(a) Why higher in lung transplant than other solid organs
PTLD = post-transplant lymphoproliferative disorder- mostly lymphoma
-over-immunosuppress that lymphocytes go cray
(a) B/c higher degree of immunosuppression in lung txp patients given lungs constantly exposed to outside triggers
Risk factor for PTLD
Biggest risk factor for PTLD = EBV status
-EBV R negative/ donor positive b/c recipient then has huge response to donor EBV
PTLD treatment
PTLD mgmt-
first line = reduce immunosuppression
-then can try rituxan, chemo
Cause of post-transplant progressive hypoxia that would be diagnosed on CT PE and is surgically reversible
Venous anastomosis stenosis- narrowing at anastamosis site of pulmonary vein
32F 4 months s/p DLT
immunosupp: tacro (prograf), cellcept, pred
ppx: valganciclovir, bactrim, posi d/ced 2 weeks ago
New DOE, 800cc drop in FEV1
(a) Most likely dx
(b) Best diagnostic step
4 months post-op, too early generally for CLAD/BOS, just in time for ACR (acute cellular rejection)
(a) Acute cellular rejection
-possibly due to stopping posiconazole which helps increase tacro levels => might have subtherapeutic tacro
(b) TBBx
Differentiate mechanism of acute cellular vs. antibody mediated rejection
Both forms of acute allograft rejection in lung transplant
-ACR = T-cell mediated, recipient T-cells recognizing foreign HLA
vs.
-AMR (‘humoral mediated’) = due to donor specific antibodies = Ab in recipient directly against donor => alloimmunity
Histologic finding of acute cellular rejection
Perivascular mononuclear infiltrate- meaning starts around vessels with tons of lymphocytes, then spreads out to parenchyma
A-grade on TBBx = finding around blood vessels
-increasing grade as more extensive perivascular involvement and as spreads to sub-endothelium
Differentiate CLAD and BOS in term of chronic rejection
CLAD = chronic lung allograft dysfunction = chronic rejection- main cause of mortality after first year, overarching term that has two phenotypes (BOS and RAS)
BOS (bronchiolitis obliterans syndrome) is the predominant form of CLAD, but RAS (restrictive allograft syndrome) also exists
BOS- obstructive (drop in FEV1 with reduced ratio)
RAS- restrictive PFTs (TLC decline from baseline of more than 10%)
CLAD risk factors
(a) Biggest overall
(b) Associated infection
(c) Non-infectious strong association
(d) Immunologic factor
CLAD, chronic rejection, risk factors
(a) Number and severity of acute rejections (both cellular or antibody mediated) is the biggest risk factor for CLAD
(b) CMV has strong association
(c) GERD
(d) DSA (donor specific antibody) panel is associated with CLAD independent of episodes of acute rejection
If starting rifampin 4 months post-transplant, what drug would likely need to be adjusted and by what dosing?
Rifampin = strong CYP3A4 inducer => will significant reduce the level of tacrolimus (to the point where sig increase risk of rejection)
=> would pre-emptively increase tacro dose if starting rifampin
Main drug-drug interactions with calcineurin inihibitors
Calcineurin inhibitors = tacro (prograf) and cyclosporin metabolized by CYP3A4 enzyme
CYP3A4 inhibitors => increase tacro levels: macrolides (azithro), azoles (posi), CCBs, grapefruit juice
vs.
CYP3A4 inducers => reduce tacro levels: rifampin, anti-siezures (carbamazepine, phenobarb, phenytoin)
Why use valgancyclovir ppx for 3-6 months post lung transplant
B/c CMV infection so highly associated with future risk of both acute and chronic rejection (CLAD) => valcyte as CMV prophylaxis
Which transplant drugs associated with
(a) Drug side effect of renal dysfunction
(b) Infection ppx associated with cytopenias
Transplant drugs
(a) Calcineurin inhibitors (tacro, cyclosporine) classic for renal dysfunction
(b) Valganciclovir (valcyte) => cytopenias
Drug interaction between posiconazole and tacrolimus
Posiconazole is a cyp3A4 inhibitor which tacro requires for metbalism => need to dose reduce tacro if adding posiconazole
(or likely increase dose of tacro if stopping posi)
Why might get bilateral PTXs after unilateral TBBx for surveillance of transplanted lung
‘Buffalo chest’ phenomenon of continuous hemithoraces due to disruption of mediastinum in clamshell incision (median sternotomy) => patency btwn hemithoraces
-named after unique buffalo anatomy
ex] R-sided TBBx causing pneumo causes bilateral PTX that then only need single chest tube to relieve air/pressure of both sides
Diagnostic BAL criteria for DAH
-serial alliquots of lavaged fluid increasingly bloody
-BAL cell dif with over 20% hemosiderin-laiden macrophages
First line treatment for BOS
BOS- chronic rejection, obstructive defect on PFTs over a year after transplant
Tx = azithro for immunomodultion
-eval for fundoplication (given association with GERD) if there is significant GERD
-alter immunosuppression: consider sirolimus, ATG (antithymocyte globulin)
Differentiate the two types of chronic rejection after lung transplant
more common = BOS- bronchiolitis obliterans syndrome, normal imaging (or bronchiectasis) typically with obstructive defect on PFTs
-hyperinflation on imaging
-bronchiolitis obliterans on path
-poor response to steroids
less common form of chronic rejection = restrictive allograft dysfunction = upper-lobe fibrotic changes with restrictive pulmonary function
Primary mechanism of hypoxia in hepatopulmonary syndrome
V/Q mismatch with a lesser contribution of shunt- more due to diffusion limitation
-vascular shunts mostly in the bases, true shunts => oxygen not responsive disease
-also dilated capillaries where diffusion cannot occur normally in the center = diffusion abnormality = part responsive to supplemental oxygen
Not only shunt, also big part diffusion limitation
Indication for liver transplant in hepatorenal syndrome
PaO2 under 50
Most common malignancy in recipients of solid organ transplants
1 and 2
- non-melanomtaous skin cancer
- PTLD
2019 guidelines by CF Foundation of when to refer for lung transplant
When FEV1 under 40% predicted with additional marker of shortened survival:
-6MWT under 400m
-hypoxia (at rest or exertion)
-hypercapnia
-PH
-BMI under 18
-2 or more exacerbations requiring abx or one requiring PPV in the past year
-massive hemoptysis requiring ICU or bronchial artery embolization
-PTX
Or by FEV1 alone if
-FEV under 50% pred and rapidly declining (20% or more decline within 12 months)
-FEV1 under 40% with marker of shortened survival
-FEV1 under 30%
When may hemoptysis be an indication for transplant in CF?
FEV1 under 40% with massive hemoptysis (over 240cc) requiring ICU admission or bronchial artery embolization
not a contraindication to transplant just the opposite
PGD associated more with BOS or ACR?
No proven asociation between PGD (primary graft dysfunction) and acute cellular rejection
-PGD is associated with increased risk of BOS-phenotype of CLAD
48M with chronic pulmonary infections and the following imaging- diagnosis?
Bronchiectasis, sintus inversus (heart on R, liver on L), chronic sinusitis = Kartageners syndrome of primary ciliary dyskinesia
What does DIPNECH stand for?
(a) Mechanism of constrictive bronchiolitis
DIPNECH = diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
(a) proliferation of neuroendocrine cells in bronchial walls = premalignant condition
36M with CF: mutations F508D and G54X should get which modulator med(s)?
Triple modulator therapy with elexacaftor/tezacaftor/ivacaftor for all patients with at least 1 F508D mutation (regardless of second allele)- about 85% of CF pts
Improves FEV1, reduces exacerbations, improved BMI, improves QOL
Which autoantibody in myositis-associated ILD is associated with good vs. poor outcome/prognosis?
Myositis-associated ILD
Anti-MDA5 associated with poor prognosis and poor response to immunosuppression
-Anti-MDA5- poorer prognosis, 50% 5-year survival vs. 97% with myositis-specific autoantibodies such as anti-Jo1/Ha
PANTHER-IPF trial (NEJM 2012) told us what about steroid use in IPF?
Trial stopped early given increased moratlity in IPF pts treated with combo of prednisone, azathioprine, and NAC
-shifted us away from prior mainstay of tx for IPF as immunosuppression
Pt with LAM- aside from cystic lung disease what else might expect on
(a) Chest imaging
(b) CT A/P
Multiple thin-walled cysts w/ normal surrounding parenchyma associated with
(a) High association with chylous effusions and PTX
(b) Renal angiolipomas
Pt with scleroderma has restrictive defect on PFTs-
What test could help differentiate chest wall restriction from systemic sclerosis from parenchymal issue (ILD)
Pressure volume cure or esophageal pressure- basically pressure volume curve will tell you about static compliance of the lung, which if normal would suggest restriction of chest wall from scleroderma as the issue instead of ILD
Autoantibody expected in
(a) GPA
(b) EGPA
(b) MPA
Autoimmune vasculitis
(a) GPA- most commonly c-ANCA (anti-PR3)
(b) EGPA- most commonly (50-80%) p-ANCA (anti-MPO)
(c) MPA- can be either c/p-ANCA or neither
What does a homogeneous/diffuse pattern of ANA positivity reflect?
(a) Associated w/ which autoimmune disease?
ANA pattern refers to distribution of autoantibody staining
Homogeneous = diffuse staining of the nucleus and chromosomes
(a) Associated with many, but buzzword for SLE (b/c anti-dsDNA) and mixed connective tissue disease (anti-RNP)
vs. speckled meaning tons of little dots (doesn’t help differentiate btwn autoimmune diseases)
Describe mechanism of TERT/TERC gene mutations associated with pulmonary fibrosis
TERT and TERC are telomerase genes, mutations associated with reduction in telomerase activity => reduction in telomere length
Name some other clinical features of syndromes with TERT and TERC gene mutations
TERT and TERC are telomerase genes, mutations associated with reduction in telomerase activity
Dyskeratosis congenita = skin hyperpigmentation, oral leukoplakia (white lesions in mouth w/ many causes), premature graying, nail dystrophy
asplastic anemia and marrow failure = most common cause of death
ex: 67F with abnormal CT chest, macrocytic anemia, premature graying, father and uncle died of ‘lung hardening’- test for TERT/TERC
Think about which occupational exposures with
(a) 15 years working as a drilling operator forging tunnels for a railroad
(b) Maintenance technician for boiler operations in US navy
(c) Large anhydrous ammonia leak from a fertilizer tank on a farm
(a) Drilling, sandblasting, quarrying rocks such as tunnels- think silicosis
(b) Boilers, break linings, shipping industry = asbestosis
(c) ammonia = large hydrophilic compound that will affect the moist upper airways (conjunctiva, nasal mucosa) => cough, eye tearing, dysphonia, upper airway irritation, and RADS
Differentiate classic imaging findings of silicosis vs. asbestosis
Silicosis (tunnel digging)- innumerable upper-lobe nodules in perilymphatic distribution, hilar/mediastinal lymphadenopathy, eggshell calcification of lymph nodes
vs.
Asbestosis- 20-30 yr latency period then subpleural calcified plaques and fibrotic changes, can progress to traction bronchiectasis/honeycombing features similar to UIP pattern fibrosis
Which lung volumes are reduced in pregnancy
All expiratory volumes are reduced in pregnancy due to enlarged uterus pushing up diaphragm => reduced ERV, RV, and FRC
How does minute ventilation increase in pregnancy
(a) Presumed hormone mechanism
Tidal volume increases by 30-50% to cause 20-50% increase in minute ventilation
(a) Thought to be due to progesterone-mediated increase in central respiratory drive
Differentiate Langerhan cell histiocytosis from Erdheim-Chester disease
Both malignancies of myeloid progenitor cells associated with BRAF mutation
PLCH- Langerhan cell histiocytes causing long bone and cystic lung disease
ECD- non-Langerhan cell histiocytosis causing long-bone (lower extremity) disease in 95%, ~50% have some pulmonary involvement (mediastinal infiltration, pleural thickening, ground glass- nonspecific)
Post-transplant immunosuppressants associated with pancytopenia
Sirolimus (mTOR inhibitor) and MMF (cellcept, antimetabolite, DNA synthesis inhibitor)
Post-transplant immunosuppressants associated with pancytopenia
Sirolimus (mTOR inhibitor) and MMF (cellcept, antimetabolite, DNA synthesis inhibitor)
pH and pCO2 expected in 3rd trimester of pregnancy
As of 12 weeks of gestation there is a 20-50% increase in tidal volume driven by progesterone, thought to be progesterone mediated increase in chemoreflex response to CO2
Expect chronic respiratory alkalosis
ex: pH 7/44, pCO2 32, PO2 100
