Infection, COPD, Asthma Flashcards
Differentiate acute bronchitis and bronchiolitis
Bronchitis = inflammation of larger and midsize airways, typically viral, normal CXR self-limited x3 weeks
Bronchiolitis- inflammation of bronchioles (smaller airways) again mostly viral (RSV)
Main use/indication for flucytosine
Replication inhibitor, use as adjunct for candida and cryptococcus
Differentiate mechanism of antifungals
(a) amphotericin B
(b) azole
(c) echinocandins
Antifungal mechanism
(a) Amphotericin = disturbs cell membrane by binding to ergosterol (main sterol in fungal membrane)
(b) Azoles- inhibits ergosterol synthesis => cell membrane dysfunction
(c) Echinocandins (micafungin, caspofungin)- 1,3-beta D glucan synthetase in cell wall
Main indications for echinocandins (caspo/mica)
Echinocandins- only IV
Indications: empiric tx of neutropenic fever, candidemia, invasive aspergillus
First line treatment for mucormycosis
Invasive mucor tx: surgical debridement for source control with amphotericin B
Step-down once responding to posaconazole or isavuconazole
-posaconazole second line/salvageif ampho not tolerated
What can cause a false positive galactamannan
Antibiotics, mainly zosyn and augmentin
Describe spectrum of disease caused by aspergillus and risk factors
Depends on degree of immunosuppression, worsening immune status
(Least immunosupp)
Allergic: ABPA
Chronic/cavitary: aspergilloma, chronic cavitary aspergillosis
Semi-invasive: chronic necrotizing aspergillosis
Invasive: invasive pulmonary aspergillosis, tracheobronchial aspergillosis
(Worsening immune status)
Which antifungals have activity against aspergillus?
Active against aspergillus: voriconazole, itraconazole, amphotericin B
NOT fluc!
Limitation of micafungin for candidemia
Echinocandins lack good eye penetration => if candida endopthalmitis seen on dilated retinal exam need to add fluconazole or amphotericin B
Antifungals to avoid in pregnancy
First line- amphotericin, echinocandins, azoles except vori are category C
Contraindicated: flucytosine and voriconazole given fetal abnormalities in animal studies
Some clinical differentiating factors from pulmonary mucormycosis and invasive pulmonary aspergillus
Clinically both can have diffuse pulmonary nodules in immunocompromised patient
-more nodules (over 10) or presence of pleural effusions favor mucor (pleural effusions uncommon in invasive pulmonary aspergillosis)
-sinopulmonary or angioinvasive involvement favor mucor
Mucormycosis
(a) Particular risk factor
(b) Typical extrapulmonary manifestations
Mucor
(a) Immunocompromised, poorly-controlled diabetics
(b) Sinupulmonary (ENT), angioinvasive (vessels)
Cryptococcus neoformans
(a) Particular risk factor
(b) Utility of serum cyptococcus antigen in pulmonary disease
Cryptococcus neoformans
(a) HIV, post-transplant
(b) Serum crypto not very sensitive for limited pulmonary disease, very sensitive in disseminated disease
Tx of cryptococcus neoformans
(a) Mild pulmonary disease
(b) Severe pulmonary disease or CNS Involvement
Cryptococcus neoformans treatment
(a) Mild pulmonary disease alone (w/o CNS involvement) = fluconazole 6-12 months
(b) Severe pulmonary disease or CNS involvement = induction with amphotericin and flucytosine
then consolidation and maintenance with fluconazole (higher dose x8 weeks then lower dose for at least a year)
Which endemic mycosis most clearly mimics sarcoidosis (and must be ruled out prior to starting immunosuppression)
(a) How to rule out
Histoplasmosis (Mid W and S central US, Ohio and Mississippi River Valley)- calcifications, granulomas, extensive nodularities, and mediastinal lymphadenopathy (mimics sarcoid closely)
(a) Serum and urine histo Ag together have over 90% sensitivity
(b) If very concerned can do histology: caseating granulomas and narrow-based budding yeast
Cryptococcus vs. coccidio
(a) Risk factor
(b) Most common manifestation
(a) Cypto- more immunocompromised, HIV
Most common disseminate into CNS, also with limited pulmonary and disseminated pulmonary disease
(b) Coccidio- more endemic to SW (Arizona)
local, diffuse, and fibrocavitary PNA
What extrathoracic findings suggest histoplasmosis as the cause of a patient’s fibrosing mediastinitis?
Fibrosing mediastinitis (PH risk factor) look for splenic and liver calcifications to suggest histo
Fungal infection with classic presentation of rose gardener injuring finger with a thorn
(a) Tx
Sporothrix schenckii- fungus typically cutaneously inoculated
-typically causes lymphocutaneous features, can cause chronic cavitary fibronodular disease
(a) Itraconazole
General tx differentators for endemic mycoses
Histo, coccidio, blasto, and paracoccidio all treated similarly
If mild disease/only pulmonary- itraconazole
If severe disease (hypoxia, diffuse imaging findings, extrapulmonary manifestations)- amphotericin then itraconazole
Noninvasive testing for endemic mycoses
(a) Histo
(b) Coccidio
Noninvasive testing for endemic mycoses
(a) Histo- urine and serum histo Ag, when together are 90% sensitive for disease
(b) Coccidio- Cocci IgG and IgM antibodies for screening,
Which endemic mycosis is associated with PH specifically due to fibrosing mediastinitis?
Histoplasmosis (Ohio/Mississippi river valley) can cause fibrosing mediastinitis, risk factor for PH
How to differentiate sarcoidosis and histoplasmosis on histology
Both sarcoid and histo can look very similar on imaging: diffuse nodules, mediastinal lymphadenopathy, calcifications
Histology- both granulomas
Sarcoid- noncaseating granulomas diffuse
Histo- caseating granulomas with fungal elements (narrow based budding yeasts)
Indications for steroids in PJP treatment
Steroids indicated for:
-PaO2 under 70mmHg, SpO2 under 92% on room air (aka any hypoxia)
-Aa gradient over 35
Name the most common of the following diseases associated with HIV
(a) Malignancy
(b) Interstitial pneumonitis
(c) Vascular complication
HIV-associated
(a) Malignancies- Kaposis sarcoma (most common), then non-Hodgkin’s lymphoma
(b) Lymphoid interstitial pneumonitis (LIP)- cystic lung 54321disease
(c) Vascular complication- group I PAH
CD4 cutoffs for infectious prophylaxis in AIDS patients
CD4 under 200: PJP ppx with bactrim (typically 1 DS TIW)
CD4 under 100: already on bactrim, but also now covering for toxo ppx
CD4 under 50: consider azithro for MAC ppx but not always necessary if starting ART (data for azithro ppx is pre-ART)
Which HIV patients get screened with quantiferon?
All of them! All HIV patients should be screened for LTBI with quant
At what CD4 count do you expect the following
(a) PJP
(b) CMV
(c) Kaposi sarcoma
(d) Toxo
(a) PJP at CD under 200
(b) CMV under 50
(c) Kaposis under 100
(d) Toxo under 100
Name two filamentous bacteria that cause pulmonary cavitation
Typical filamentous bacteria causing pulmonary cavitation = actinomyces and nocardia
Actinomyces vs. nocardia
(a) Imaging features
(b) Treatment
(a) Imaging:
Consider both for nonresolving PNA, especially if cavitary
if involves pleura or chest wall think actino
(b) Tx:
Actino- PCN
Nocardia- TMP-SMX
Actinomyces vs. nocardiac
(a) Which expected in immunocompetent patient
(b) Which sulfur granules
(c) Which weakly AFB positive
(d) Which associated with cervicofacial abnormalities
(a) Immunocomptent- expect actino
(b) Sulfur granules = grouped actino filaments
(c) Weakly AFB positive gram positive aerobe = nocardia
vs. not AFB positive gram positive anerobe = actino
(d) Actino associated with cervicofacial abnormalities
Candidemia treatment
(a) Preferred initial agent
Duration of tx
(b) With endopthalmitis
(c) W/o endopthalmitis
Candidemia
(a) Start with echinocandin (micafungin) at least until know sensitivities
Duration of tx:
(b) With endopthalmitis: 4-6 weeks
(c) Without: 2 weeks from negative cultures
Regular surgical facemask vs. N95
(a) VZV PNA
(b) Influenza
(a) VZV extremely infectious- wear N95
(b) Influenza- large droplets, regular surgical facemask adequate
Differentiate yeast and mold
(a) Explain how a fungi can be dimorphic
Fungi can exist in two forms: unicellular yeast or multicellular mold (multicellular hyphae)
(a) Dimorphic fungi [ex: endemic mycoses] are yeast at cold temp, mold at hot/body temp
-fungi can be different forms depending on temperature, pH, cysteine levels
Differentiate which patient/risk factors get
(a) ABPA
(b) Aspergilloma
(c) Chronic necrotizing aspergillosis
(d) Invasive pulmonary aspergillosis
Ubiquitous exposure to aspergillus, then underlying immune status dictates what disease pt develops
(a) Overactive, atopic immune system- think ABPA
(b) Pre-existing cavity- aspergilloma (won’t just form a fungal ball on its own)
(c) Mild immunosuppression with potentially COPD- chronic necrotizing aspergillosis
(d) Neutropenic => IPA
Classic imaging feature of aspergilloma ‘fungal ball’
Moves within the cavity in supine vs. upright films
Differentiate clinical manifestations of chronic necrotizing aspergillus from invasive pulmonary aspergillosis
Clinical presentation
-chronic necrotizing aspergillus in mildly immunosuppressed pt: insidious onset, think of in PNA that just won’t go away
vs.
-IPA: nodules, cavitary lesions, acute systemic infectious signs
ABPA diagnostic criteria
(a) Predisposing conditions
(b) Mandatory major
(c) 2 of 3 minor ABPA
Diagnostic criteria for ABPA:
(a) Have to either be asthmatic or CF pt
(b) With elevated IgE (typically over 1000) and positive aspergillus skin test or elevated anti-A fumigatus IgE
(c) 2 of 3 minor criteria
-A fumigatus IgG
-radiogrpahic pulmonary opacities (mucus plugging)
-total eos over 500
Typical management of ABPA
Steroids +/- itraconazole
Middle-aged M returns from hunting trip in Arkansas with respiratory illness and infiltrates not responsive to abx. Dog also acutely ill
Arizona- just W of Mississippi, N of Texas, right in that Mississippi River Valley which puts at risk for both histo and blast
-dogs also get infected with blasto
Blasto! broad-based budding yeasts with bubba (bubba the dog)
Tx of blastomycosis in pregnancy
Need to avoid azoles in pregnancy so for all endemic fungi (histo, coccidio, blasto, paracoccidio) use amphotericin
What fungi does beta-D glucan NOT detect
Beta-D glucan good for invasive aspergillus, invasive candidiasis, and other invasive mycoses EXCEPT does NOT detect mucor and crypto
Endemic mycoses classic for
(a) Skin involvement
(b) Valley fever
(c) Bird/bat droppings
(d) Spelunking, chicken coops
Endemic mycoses
(a) Skin involvement- violaceous ulcerating lesions in blastomycosis
(b) Valley fever = coccidiodomycosis, SW US
(c) Bird/bat droppings as reservoir for histo
(d) Spelunking and chicken coops as place of transmission for histo
Describe these unique manifestations of histoplasmosis
(a) Bronchiolithiasis
(b) Fibrosing mediastinitis
Histplasmosis- calcifying, necrotizing granulomas
(a) Bronchiolithiasis- calcified eroding nodes
(b) Fibrosing mediastinitis- mediastinum hardens like cement, can cause mass effect on vessels (PH) and airways
Describe link between defuroxime and certain fungal infection
(a) Which infection
(b) Mechanism
Defuroxime (iron chelators) put pts at increased risk for
(a) Mucormycosis
(b) Something to do with iron overload, possible that patients in DKA have more iron available which is a substrate for mucor growth
Standard duration of bactrim for PJP treatment
PJP: bactrim x21 days
Antimicrobial regimen options for PJP treatment in pts with sulfa allergy
If can use TMP-SMX
Mild disease
-TMP (trimethoprim) and dapsone
-atovaquone
Severe disease
-clindamycin and primaquine
-IV pentamidine
Differentiate galactomannan and beta-D glucan
Both serum assays developed to detect invasive aspergillosis, beta-D glucan more sensitive but less specific
-galactomannan more specific for asperillus
-beta-D glucan also for invasive candidiasis and other invasive mycoses EXCEPT for mucor and crypto
Compare % risk of Tb reactivation in general population vs. HIV pt
General population: 5-10% lifetime reactivation risk, 50% of which is within the first 1-2 years after exposure
While HIV patients have about 5% risk of conversion annually
Define MDR TB
MDR Tb = resistant to both INH and rifampin
-considered a precursor to XDR-Tb
Define XDR-TB
XDR-Tb = MDR Tb (resistant to INH and rifampin) AND fluoroquinolone (moxi or levaquin) AND to one of the second line IV agents (amikacin, kanamcin, capreomycin)
Sensitivity of
(a) AFB smear in cases of active Tb
(b) Gene Xpert in smear positive Tb
(c) Gene Xpert in smear negative Tb
Sensitivity of test
(a) AFB smear in active Tb about 70% (so about 30% of active Tb cases will be smear negative, hence why culture is gold standard)
(b) Gene XPert (PCR) about 99-100% sensitive in smear positive Tb
(c) Gene Xpert about 85% sensitive in smear negative
How does gene Xpert detect rifampin resistance?
PCR for rpoB gene which accounts for over 90% of rifampin resistance
Can smear negative still transmit Tb?
Yes- smear negative can still be contagious
If bronching a patient to r/o Tb what else is a good idea?
Do post-bronch AFB culture! high yield and sometimes the only thing that is positive
After what duration of tx can active Tb pt be considered noninfectious?
After 2 weeks of treatment can be considered noninfectious
Differentiate radiographic findings of Tb reactivation from primary disease
Classic radiogrpahic findings of
(a) Tb reactivation: upper and posterior lobe predominant cavitation
(b) Primary disease- necrotic/calcified lymphadenopathy, pleural effusion, miliary disease
4 instances where Tb treatment requires extension from 6 to 9 months
-CNS tb
-severe cavitary disease
-if PZA cannot (or is not) used for the first two months
-if sputum does not convert by 2 months (obv also check sensis then too)
IRPE alteration typically required to treat HIV pts with Tb
Rifampin typically interferes with ART => use rifabutin for fewer drug drug interactions
How to change LTBI tx for HIV patients
RIfabutin often used in place of rifampin due to drug drug interactions with ART
Drugs to consider in treatment of MDR-Tb
US: first line for MDR-Tb 18 months of bedaqueline, linezolid, floroquinolone, clofazimine
or BPaL = bedaqueline, pretomanid, lienzolid
When to start ART in relation to IRPE for Tb treatment HIV patients
If CD4 count under 50 improves mortality to start ART within 2 weeks of Tb treatment
-otherwise not huge rush but start within 1-2 months
Which environmental exposure is specifically correlated to higher risk of Tb reactivation
Silicosis- thought to be mediated by detrimental effect of silica on alveolar macrophages
exposure- mining, sandblasting, construction
Benefit of BCG vaccine
Has been shown to prevent meningeal (CNS) and miliary Tb in children
Differentiate classic imaging findings of primary Tb vs. reactivation
Imaging findings
Primary Tb: middle and lower lobe predominance with ipsilateral hilar lymphadenopathy
Reactivation: upper lobe predominance with cavitation
CSF studies characteristic of Tb meningitis
Tb meningitis
-elevated white count (100-500) with lymphocytic predominance
-elevated opening pressure
-elevated CSF protein (100-500, normal under 40)
-low CSF glucose (under 10)
2 ways in which CNS involvement of Tb alters treatment
CNS Tb
-extends treatment from 6 to 9 months
-add steroids
Which bacterial cause of CAP associated with
(a) Most common etiology of post-influenza PNA
(b) Severe necrotizing disease
(c) Gram negative in those w/ underlying lung disease (COPD, CF), hint not pseudomonas
(d) Severe infection in asplenic pts
Bacterial CAP
(a) Post-influenza PNA: strep pneumo (also most common overall)
(b) Necrotizing/cavitary or empyema raises suspicion for staph aureus
(c) H. influenza
(d) Strep pneumo (encapsulated)
Which bacterial cause of CAP associated with
(a) Hemolytic anemia
(b) Exposure to contaminated water
CAP causes
(a) Hemolytic anemia associated with mycoplasma- cold agglutinin due to IgM autoantibodies
(b) Legionella- contaminated water, cruise ships
Causative organism for PNA associated with exposure to
(a) Wild rodents
(b) Bat droppings
(c) Birds
(d) Rabbits
(e) Farm animals
Exposures causing PNA
(a) Wild rodents, especially in SW US = hantavirus
(b) Bat droppings = histoplasmosis
(c) Birds = chlamydia psittaci (psittacosis)
(d) Rabbits = francisella tularensis
(e) Farm animals = coxiella burnetti (Q-fever)
Current PNA vaccine guidelines
(a) What vaccine
(b) For what groups
PNA vaccine
(b)-all pts over 65 OR
under 65 with another comorbidity: COPD, CHF, DM, DM, EtOH, asplenic
(a) Either PCV-20 alone or
PCV-15 then one year later PPSV-23
What does ceftaroline cover?
Covers MRSA
does NOT cover pseudomonas
Allergy to what cephalosporin makes you cautious before using aztreonam
Aztreonam can be used safely in those w/ cephalosporin allergy except prior serious reaction to ceftazidime given similar side chain => higher risk of cross reaction
(sidebar ceftazidime = 3rd gen cephalosporin like ceftriaxone and cefpo)
MAC ppx in HIV patients
(a) When indicated
(b) What med
MAC ppx in HIV pts with CD4 under 50 with azithro (or clarithro)
Differentiate treatment for M. kansasii and M. abscessus
Slow-growing NTM = MAC and M. Kansasii- both same tx of azithro, rifampin, ethambutol
Rapid-growing M. abscessus- much more complicated tx based off sensitivities: clofazimine, amikacin, cefoxitin, imipenem, linezolid
80F with productive cough x4 years and RML bronchiectasis, two recent sputum samples one with MAC one with M. kansassi
Next step
Stupid trick question-
Either get another sputum or undergo bronch for additional cultures b/c one sputum culture doesn’t prove disease
Once have two + imaging features + clinical features can treat: for both slow-growing NTMs (MAC and M. kansassi) tx is the same with azithro, rifampin, ethambutol x12 months from sputum conversion
Risk of reactivation of LTBI for pt on TNFalpha blockers compared to not
Pts on anti-TNF have 12x increased risk of LTBI activation
Differentiate activity of the following in asthma
(a) IL-4
(b) IL-5
(c) IL-13
Role of the following cytokines, all released by Th2 cells
(a) IL-4: secreted by basophils to stimulate B-cells to make IgE
(b) IL-5 regulates eosinophil production and maturation
(c) IL-13 secreted by basophils and Th2 cells
-stimulates B-cells to make IgE (like IL-4)
-stimulates degranulation of mast cells to release proinflammatory mediators
Pathophysiology of changes in asthma by layers of the bronchial epithelium
(a) Goblet cells
(b) Basement membrane
(c) Subepithelium
(d) Smooth muscle
Epithelium
(a) Goblet cell hyperplasia => more mucus to plug airways
(b) Basement membrane thickening
(c) Subepithelial fibrosis
(d) Smooth muscle hyperplasia => worsening bronchospasm
Differentiate role of Th1 and Th2 in asthma
Th1 to recruit neutrophils
Th2 to stimulate IgE synthesis, stimulate mast cell production and degranulation, stimulate eosinophil production and migration
Which PFT loops expected in larygneal dysfunction?
Flattening during inspiratory loop (C) consistent with extrathoracic obstruction
Describe the PC20 used during methacholine bronchoprovocation test
PC20 = concentration of drug (typically methacholine) that causes a 20% drop in FEV1, this is when the provocation test is stopped
PC20 at or under 8 has good negative predictive value for asthma
Differentiate occupational asthma and reactive airway dysfunction syndrome
(a) Which will be reproducible by inhalation challenge
(b) Duration of symptoms
Occupational asthma- immunologic phenomenon (sensitization to allergen, IgE involved) only have symptoms at work
(a) Reproduced by inhalation challenge of small amounts of allergen b/c immunologic pathway
(b) Symptoms improve after work or during holidays/weekends
vs.
RADS- abrupt onset of symptoms following exposure
(a) Not reproduced by inhalation challenge b/c not immunologic, due to intensity and duration of exposure
(b) Symptoms can persist after exposure
Triad of aspirin sensitivity and asthma
(a) Presumed mechanism- IgE?
(b) Tx
Samter’s triad = asthma, chronic rhinosinusitis w/ nasal polyps, ASA (COX-1 including ASA and NSAID) sensitivity
(a) Not IgE! thought to be a ‘pseudoallergy’ of an abnormal response to NSAID exposure due to inability to breakdown byproduct
(b) Tx- typical asthma tx, intranasal glucocorticoids, leukotriene inhibitor ** (montelukast)
When to consider ASA desensitization in pt with aspirin-exacerbated respiratory disease
-refractory nasal polyposis (to intranasal steroids and even surgery)
-strong indication for ASA (ex: PCI)
-strong indication for NSAID (ex: inflammatory condition)
What symptoms trigger change in treatment from PRN ICS-formoterol to maintenance?
PRN to maintenance when symptoms go from intermittent (less than 2x/week, no nightnighttime awakenings, no limitation w/ normal activity) to mild persistent (symptoms or SABA use more than 2x per week, 3-4 per month nighttime awakening, minor interference with normal activity)
Differentiate intermittent and persistent asthma
(a) Tx
Intermittent asthma- symptoms or SABA use less than 2x week, less than 2x/month nighttime awakenings, no limitation of normal activity
(a) Tx- PRN low-dose ICS-formoterol, can consider standing low-dose ICS
Persistent- mild when symptoms more than 2 days a week but not daily (moderate)
Nighttime awakening 3-4 times a month but not yet weekly (moderate)
Mild interference w/ normal activity
(a) Tx- standing low-dose ICS, LABA
Differentiate mild, moderate, severe persistent asthma
(a) Inhaled treatment stepup
Persistent once symptoms more than 2x/week, nighttime awakenings more than 2x/month
Mild: symptoms (or SABA use) more than 2x a week, nighttime awakenings 4 or more per month (but not weekly), mild interference with normal activity
(a) Maintenance low dose ICS-LABA
Moderate: symptoms (or SABA use) daily, nighttime awakenings at least once a week (but not nightly), moderate interference w/ normal activity
(b) Maintenance medium/high dose ICS-LABA
Severe: symptoms (or SABA use) throughout the day, nighttime awakenings almostly nighly
(b) Maintenance high dose ICS-LABA, add LAMA, adjunctive tx (Mabs, bronchial thermoplasty) etc
50M s/p renal transplant on MMF, tacro, pred p/w cough, fever, draining skin lesions
CXR attached, gram stain attached
(a) most likely dx
(b) next mgmt step
PNA in immunocompromised, gram stain with gram positive (purple) branching/filamentous bacteria = nocardia
(a) Nocardia
(b) CNS imaging given propensity of nocardia to have extrapulmonary symptoms (skin and CNS)
Differentiate appearance of gram positive vs. gram negative on gram stain
Gram stain: purple stain that then the thick cells walls of gram positive organisms keep it purple
Thin cell walls of gram negative => don’t hold on to purple so are pink
Bioterrorism agents:
francisella tularensis vs. yersinia pestis
(a) Vector
(b) Tx
Francisella tularensis
(a) Rabbits
(b) Aminoglycosides (gentamycin, streptomycin)
Yersinia pestis = plague!
(a) Rodents
(b) Gentamycin
Differentiate gram-negative rods by lactose vs. non-lactose fermenters
Gram negative rods
Non-lactose fermenters: pseudomonas, proteus
Lactose-fermenting: serratia, E. coli, klebsiella, enterobacter
Pertussis
(a) Typical clinical presentation
(b) Tx
(a) Prodromal phase which fever, rhinorrhea, sore throat (mimics viral URI) then persistent whopping cough w/ possible spasms, possibly associated with emesis
Typically self resolves
(b) Azithro for ppl with suspected (or proven) pertusis with symptoms for 4 weeks or less
-after 4 weeks azithro not shown to do anything
36M s/p renal transplant p/w SOB, fever, night sweats after failing levaquin.
BAL AFB, gram stain, CXR below
(a) Dx
(b) Tx and duration
AFB+, positive gram stain with purple = gram positive organism
Gram positive organism causing pulmonary consolidation in immunocompromised = nocardia (a)
(b) Bactrim + amikacin, keep amikacin until sensitivities known
Duration: 6-12 months, if continued immunosuppression use lifelong secondary prophylaxis
New HIV+ (CD4 30) Tb diagnosis
Treatment
IRPE
-ART within 2 weeks (better outcomes for CD4 under 50 if started within 2 weeks, otherwise can wait for up to 12 weeks)
PLUS steroids (prednisone) within 4 weeks given 50% change of Tb-IRIS for HIV pts with CD4 under 100
Which carbapenem does NOT cover pseudomonas?
Ertapenem- nice b/c daily administration but does not cover pseudomonas
While meropenem and imipenem covers pseud
Pseudomonas resistant to cefepime, mero, avycaz
Next-line agent?
Cefiderocol = siderophore cephalosporin (inhibits bacterial cell wall synthesis)
-good for extremely resistant gram negatives such as pseudomonas, acinetobacter, E. coli, klebs, and serratia
Colistin next in line but choose cefiderocol first b/c colistin has high toxicity/side effect profile
23F no PMH works in pet store: grooms exotic birds, cleans bird cages p/w days of fevers, headaches, cough. Mild splenomegaly and patchy basilar predominant infiltrates w/o lymphadenopathy
(a) Most likely dx
(b) Tx
(a) Psittacosis (parrot disease, parrot fever) from chlamydophila psittaci
(b) Tx- doxy
Bird droppings trigger thoughts of histo but endemic, not likely in immunocompetent, and would expect lymphadenopathy
LTBI tx in HIV negative patient on OCPs
Have to avoid rifamycin agents b/c of interaction with OCPs => INH x6 months
Top 3 immunosuppressing conditions that are associated with cryptococcus
- HIV
- Iatrogenic immunosuppression
- Cirrhosis
Differentiate fungi based on the following histology
(a) PJP- round, oval, helmet shaped yeasts
(b) Thick-walled spherules = coccidio
(d) Narrow-based budding yeast in clusters inside macrophages = histo
Two most common extrapulmonary sites of blasto
(1) Lungs
(2) Skin- verrucous lesion w/ irregular borders, can ulcerate and form microabscesses
(3) Bone and joint, osteomyelitis
32F at 30 weeks gestation has influenza- mgmt?
Oseltamivir
-both oseltamavir and zanamivir are safe and effective in pregnancy, oseltamivir has better data in pregnancy so preferred
33F with hacking cough x4 weeks after flu-like illness 6 weeks ago
-forceful coughs during expiration, sometimes w/ vomiting
-had all childhood vaccinations
-normal CXR
(a) Dx
(b) Mgmt
(a) Long pertussis, past the initial catarrhal phase (viral-like of rhinorrhea, malaise). then paroxysmal coughing phase which can persist 3-6 months
(b) After 4 weeks abx not recommended (before 4 weeks- use azithro) b/c it’s the toxins, not the bacteria itself that cause the cough => antibiotics do not offer clinical benefit in the paroxysmal phase
Describe brief pathophysiology of abnormal balance of proteins in emphysema that causes destruction
Emphysema- inflammatory cells (neutrophils, macrophages) release tons of MMP (matrix metalloproteinases), proteases, and elastases causing destruction of elastin
Presumed mechanism of cough in chronic bronchitis
Goblet cell hyperplasia => mucus impaction causing airway narrowing
Epithelial thickening and smooth muscle hypertrophy => airflow obstruction
Annual expected drop in FEV1 after age 30 in
(a) Smokers
(b) Nonsmokers
(a) 60 ml annually
(b) Nonsmokers- 30ml annually
Mechanism of emphysema in alpha-1 anti trypsin
Lack of alpha-1 anti trypsin protein which is the main anti-elastase enzyme to protect lung from elastin degradation
High vs. low risk genotypes in alpha-1 anti trypsin deficiency
Low risk genotypes = MM, SS
High risk genotypes = ZZ, null
Ratio of inspiratory capacity to what is an independent mortality predictor in COPD?
Inspiratory capacity to TLC (total lung capacity) under 25% is an independent predictor of mortality in COPD
Differentiate GOLD A, B, C, D
GOLD 2x2
Y-axis:
FEV1: above or below 50%
Exacerbation history: high if one requiring hospitalization or 2 total in past 2 months
(go with the higher one)
X-axis = symptoms
Low: CAT under 10, mMRC 0-1
High: CAT above 10, mMRC 2 or above
(go with higher one)
Utility of BODE index?
(a) Components
BODE index = 10 point scale to predict 4-year mortality in COPD. out-performs any single parameter
(a) BODE
B- BMI, lower BMI portends worse prognosis
O- obstruction based on %predicted FEV1
D- dyspnea based on mMRC
E- exercise based on 6MWT
Asthma vs. COPD
(a) Type of lymphocytes implicated
(b) Cytokines mainly involved
Asthma
(a) Th2 (type 2 helper T cells), CD4+
Lymphocytes and eosinophils
(b) IL4, IL-5, IL-13
COPD
(a) Th1 (type 1 helper T cells), CD8+
Lymphocytes and neutrophils
(b) TGFbeta and TNFalpha, CXC (CXC chemokine), IL-8
56F with COPD- dyspnea when hurrying on level ground. Post-BD FEV1 45% with no history of exacerbations
What GOLD combined assessment?
C
First column for symptoms (mMRC 1), higher column for FEV1 cutoff (under 50%)
????
One way to differentiate COPD and asthma on spirometry
Asthma- technically reversible airway obstruction so expect ratio to improve (be above .7) post-bronchodilator
Of course can have more permanent airway remodeling with long-standing disease but generally COPD ratio stays under .7 while asthma improves w/ BD
Compare smoking cessation aids: bupropion vs. varenicline
(a) Benefit
(b) Contraindications
Buproprion (wellbutrin) (a) doubles likelihood of quitting and improves abstinence at 1 year
(b) seizure d/o b/c lowers seizure threshold
Varenicline/chantix
(a) triples quit rate, increases abstinence at 6 and 12 weeks
(b) SI
(c) Head to head RCT varenicline (chantix) superior to buproprion
Mechanism of roflimulast
(a) Indication
Roflumilast- PDE4 inhibitor
(a) Reduces exacerbation in chronic bronchitis phenotype (chronic cough) with FEV1 under 50% and history of exacerbations (2 or more in the yera)
What non-pharmacologic intervention for COPD improves survival?
Supplemental O2 for those who meet criteria at rest (PaO2 under 55)
Differentiate mechanism of ipratropium and tiotropium
Both muscaranic antagonists
(a) Ipratropium- SAMA, blocks M3 and M4 receptors
(b) Tiotropium- LABA, blocks M3
Inhaled COPD med(s) that improve survival
None! All are to improve symptoms, reduce exacerbations and hospitalizations
None with proven survival benefit aside from LTOT (long term oxygen therapy)
TORCH trial main takeaway for salmeterol/fluticasone (NEJM 2007)
TORCH trial- combo salmeterol/fluticasone (ICS/LABA) reduced exacerbations and hospitalizations vs. either alone
-no difference in mortality
UPLIFT trial main takeaway for tiotropium (NEJM 2008)
UPLIFT- tiotropium (LAMA) reduced COPD exacerbations
-didn’t reduce rate of FEV1 decline or improve mortality
Differentiate GOLD B and C
Numbers based on FEV1 cutoffs, letters based on symptoms and risk of exacerbation
B- high symptoms (mMRC 2 or above, CAT over 10) but low exacerbations (less than one in the past 12 mo, no hospitalizations)
C- low symptoms (mMRC 0-1 and CAT under 10), higher exac (2 or more in past 12 months or one hospitalization
TORCH trial- adverse effect of ICS/LABA
Anything with ICS involved has increased risk of PNA
TORCH showing ICS/LABA reduced exacerbations/hospitalizations vs. either alone
MCID for CAT score
2 points = minimal clinically important difference
CD4/CD8 T-cells in
(a) Asthma
(b) COPD
(a) Most of asthma very active Th2 (CD4) cells, ‘type 2’ asthma
(b) While COPD more involved shift towards CD8 (Th1) cytotoxic T-cells
Differentiate mMRC grade 1 and 2
0- breathless only with strenuous exercise
1- SOB when hurrying on level or walking up slight hill
2- walk slower than ppl of same age b/c of dyspnea, or have to stop when walking at own pace on level ground
3- stop for breath every 100m on level surface
Tiotropium alone vs. salmterol alone to reduce COPD exacerbatons
COPD mMRC dyspnea grade >2 symptoms, compare indacaterol/glycopyrronium vs. salmeterol/fluticaseone
LABA/LAMA reduced rates of annual COPD exacerbations vs. LABA/ICS
FLAME trial, NEJM 2016
ETHOS trial for COPD, NEJM 2020
(a) Adverse effect of ICS
ETHOS trial, NEJM 2020- triple therapy (ICS/LAMA/LABA) improves lung function, symptoms, and exacerbations more than either ICS/LABA or LABA/LAMA
(a) Any arm with ICS (both ICS/LABA and triple therapy) had increased risk of PNA
Benefit of roflumilast in COPD chronic bronchitis w/ exacerbations
Reduced exacerbations, modest improvement in lung function
Not improved mortality
REACT trial, Lancet 2015
Describe GOLD group C COPD
(a) First line treatment
GOLD C
(a) LAMA or LAMA/LABA combo
Describe GOLD group A
(a) First line treatment
GOLD group A: low symptoms and low exacerbation risk
(a) SABA PRN
Describe GOLD group B
(a) First line treatment
GOLD B- bottom R of 2x2
High symptoms but low exacerabtions (under two in the past year and no hospitalization)
(a) Tx- LAMA (spiriva) or combo LABA/LAMA
Things that reduce mortality in COPD
-smoking cessation
-long term oxygen therapy for PaO2 under 55 or SpO2 under 88 at rest
-noninvasive ventilation for GOLD class IV and pCO2 over 45, pH over 7.35 (so chronically compensated)
Things that don’t: all the inhaled and oral meds, pulmonary rehab
Treatment for alpha-1 antitrypsin
(a) Inhalers?
(b) Indications for replacement
Alpha-1 Antitrypsin
-autosomal dom
-ZZ, null
(a) Same inhalers based on obstruction level in COPD, use to control symptoms
(b) Exogeneous alpha-1 protein by pooled human given weekly for:
-AAT levels below critical threshold of 11 umol/L
Most common cause of viral exacerbation of COPD
Rhinovirus
Influenza in ICU, but not overall
Subgroup with most definitive mortality reduction with lung volume reduction surgery
Upper lobe heterogeneous emphysema with low baseline exercise capacity
Describe the tram-track sig of bronchiectasis
(a) In cross section is what sign?
Lack of tapering as airway extends distally
(a) Signet ring sign
Kartagener’s syndrome in primary ciliary dyskinesia
Kartagener’s syndrome triad:
rhinosinusitis
bronchiectasis
situs inversus (heart on R, liver on L)
Differentiate class mutation of F508D and G551D for CF mutations
F508D- class II mutation, abnormal transport to cell membrane
G551D- class III mutation, abnormal regulation of function so inhibited chloride channel activation (but channel gets to cell membrane ok)
Explain direct consequence on electrolyte imbalance due to defective CFTR in respiratory epithelium
Defective CFTR (either doesn’t get to cell membrane, abnormal regulation etc)- Cl cant get out of cell, too much Na (and therefore water) gets into cell
Na/water into cell => decreased viscosity of mucus layer
How to confirm CF diagnosis if positive IRT (immunoreactive trypsinogen) screening in newborn
Positive screening test, have to check sweat chloride test
Definitive diagnosis if sweat chloride over 60 mmol/L on two tests
Unlikely test if sweat chloride under 29 mmol/L
30-59: test for CFTR mutation allele, c/w diagnosis of 2 mutations. If 0 or 1 mutation- repeat sweat chloride or send expanded DNA analysis
Differentiate effect of exocrine vs. endocrine pancreatic insufficiency in CF
Pancreatic insufficiency
endocrine => diabetes
exocrine => ingestion specifically of fat due to lack of pancreatic enzymes => replace with ADEK (fat soluble) vitamins
Put in order inhaled therapies for CF patients over the age of 6 years old
- Inhaled bronchodilator
- Hypertonic saline (3 or 7%)
- Dornase alpha (inhaled DNase)
- Airway clearance (chest vest, aerobika)
- Inhaled antibiotics if colonized with pseudomonas
Mechanism of dornase alpha
(a) Indication for CF pts
Dornase alpha = inhaled DNase, breaks down extracellular denatured DNA released by degenerating neutrophils
(a) All CF patients over 6 yers of age to thin mucus
Indication for aerosolized antibiotics in CF patients
Inhaled aztreonam or tobramycin in CF pts over 6 y/o colonized with pseudomonas (see on surveillance cultures every 3 months)
How to diagnosed primary ciliary dyskinesia
Nasal biopsy with electron microscopic examination of cilia
Mechanism of ivacaftor
(a) For which mutation
Ivacaftor = potentiates activity once on cell membrane
-doesn’t help much for F508D b/c class II mutation with difficulty getting to cell membrane
-does help with class III where abnormal regulation/activity on cell surface
(a) G551 mutaion
Asthma Pathophys
(a) What secretes IgE
(b) Function of IgE
(c) Cytokine specific for eosinophils
(a) B cells release IgE
-B cells stimualted by IL4/IL-13 released from Th2 cells
(c) IgE then activates mast cells and basophils => degranulation
(c) IL-5 specific for eosinophil maturation and survival
Differentiate functions of IL-4 and IL-13
Both IL-4 and IL-13 work on class switching to promote B-cells to release IgE
Then IL-13 also works on airway smooth muscle to mediate hyperresopnsiveness and mucus hypersecretion
Cytokine that mediates class switching of B-cells to release IgE
Both IL-4 and IL-13 mediate class switching
Type 2 vs. non-T2 asthma
(a) Main cytokines involved
(b) Main cells involved
T2 asthma
(a) IL-4, IL-5, IL-13
(b) Eosinophils, Th2
Non-type2 asthma
(a) IL-8, TNF, IFN
(b) Neutrophils
Cutoffs for type-2 biomarkers in asthma
Low, medium, high of
(a) Total IgE
(b) Blood eosinophils
(c) FeNO
Type 2 asthma biomarkers
(a) Total IgE: low under 30, moderate 31-149, high over 150
(b) Blood Eos: low under 150, medium 150-99, high over 400
(c) FeNO: low under 25 ppm, medium 26-49, high over 50
What is the sputum eos cutoff consider significant for T2 asthma?
Sputum eos 3 or above % considered high
FeNO
(a) Exhaled levels higher or lower in asthmatics?
(b) Changes to steroids?
(c) Cofounders
FeNO
(a) Higher levels in asthmatics, thought that eosinophilic inflammation triggers NO release => noninvasive marker of airway inflammation
(b) FeNO typically normalizes with steroid tx
(c) Age, smoking status, medications, steroid use (duh)
FeNO
(a) Exhaled levels higher or lower in asthmatics?
(b) Changes to steroids?
(c) Cofounders
FeNO
(a) Higher levels in asthmatics, thought that eosinophilic inflammation triggers NO release => noninvasive marker of airway inflammation
(b) FeNO typically normalizes with steroid tx
(c) Age, smoking status, medications, steroid use (duh)
Differentiate direct vs. indirect bronchoprovocation testing
(a) Methacholine is which one?
(b) Which has better sensitivity vs. specificity?
(c) FEV1 cutoff as positive
Direct- substance that directly causes bronchoconstriction
(a) Methacholine = direct
(b) Good sensitivity, negative methacholine challenge in a symptomatic pt rules out asthma
(c) Greater than 20% drop in 20% is positive
vs.
Indirect- typically dries out mucosal surface to cause bronchoreactivity
ex: exercise induced, hypertonic saline, mannitol, allergens
(b) Indirect- more specific, less sensitive
(c) Testing continues until 15% drop in FEV1 from baseline (lower cutoff than direct b/c of mechanism) ex: mannitol used in SEEK question
Describe steps of methacholine challenge and the PD20
Give escalating doses of nebulized methacholine with spirometry after each dose, stop the test when FEV1 drops to 20% of baseline
-dose of methacholine required to cause 20% drop in FEV1 = PD20, correlates with degree of airway hyperreactivity
Cutoff PD20 for a positive methacholine test
PD20 under 100 considered positive, under 25 is moderate
100-400 = borderline
25-100 = mild
Lower dose of methacholine required to drop FEV1 by 20% correlates with more severe airway hyperresponsiveness
Differentiate asthma severity and control
Severity marked by degree of medications required to achieve good control
vs.
Control- controlled, poorly controlled, uncontrolled- degree to which current treatment controls symptoms and reduces impairment/risk
Comparing step-up treatment for asthma vs. COPD
(a) ICS use
(b) LAMA monotherapy
Asthma vs. COPD
(a) ICS earlier in asthma- included PRN in step 2 and ICS-LABA standing in step 3
(b) LAMA monotherapy not recommended in asthma, but used for GOLD B or C in COPD
Mechanism of montelukast
(a) Benefit vs. placebo
(b) Benefit vs. ICS
(c) 2 cases when specifically to consider early in treatment
Montelukast = leukotrene receptor blocker
(a) Reduces exacerbations, improves symptoms
(b) Modest benefit, less than ICS
(c) Consider earlier in aspirin-exacerbated respiratory disease and exercise-induced bronchoconstriction
Name the asthma biologic with the following mechanism:
(a) Anti-IgE
(b) Anti-IL-5
(c) Anti-IL4Ra
(d) Anti-IL5R
Asthma biologic
(a) Anti-IgE = omalizumab (xolair)
(b) Anti-IL-5 = mepolizumab (nucala)
(c) Anti-IL4Ra = dupilumab (duplixent)
(c) Anti-IL-5R = benralizumab (fosenra)
Indications for omalizumab
Moderate-severe allergic asthma
-IgE level 30-700 AND allergen-sepcific IgE to perennial (year-long, not seasonal) allergen
Differentiate indications for mepolizumab and benralizumab
Mepolizumab (anti-IL5) and benralizumab (anti-IL5R) both for severe eosinophilic asthma (serum eos over 150)
-mepolizumab also FDA approved for EGPA
Which asthma biologic is first line for the following comorbidities?
(a) Atopic dermatitis
(b) EGPA
(c) Nasal polyposis
Biologic based on comorbidity
(a) Atopic dermatitis- dupilumab (anti-IL4Ra)
(b) EGPA- mepolizumab (anti-IL5)
(c) Nasal polyposis- dupilumab anti-IL4Ra)
Which asthma biologic to use for oral corticosteroid dependent asthma w/ normal eos level
3 separate biologics are approved for oral corticosteroid dependent asthma: mepolizuab (anti-IL5), benralizumab (anti-IL5R), and dupilumab (anti-IL4Ra) but only dupilumab independent of eos level
so steroid dependent w/o elevated eos (eos under 150)- use dupilumab (anti-IL4Ra)
Discuss flow/algorithm for choosing an asthma biologic in patients on oral prednisone
- Of course confirm diagnosis, inhaler technique, compliance etc and maximize inhaled medications
- Severe asthma with vs. without oral glucocorticoid use, both go split by eos count
-OCS needed: then split by eos count
–Eos not elevated in last 12 months = Anti-IL4Ra (dupilumab)
–Eos elevated in last 12 months- have a choice of anti-IL4Ra (dupilumab), anti-IL5 (mepolizumab, nucala), or anti-IL-5Ra (benralizumab, fosenra)
Then taper oral pred gradually and assess response
Discuss flow/algorithm for choosing an asthma biologic in patients not requiring oral prednisone
- Of course confirm diagnosis, inhaler technique, compliance etc and maximize inhaled medications
- Severe asthma with vs. without oral glucocorticoid use
Typical biomarker cutoff for the following asthma biologics
(a) Omalizumab
(b) Mepolizumab
(a) Omalizumab (Xolair) IgE 30-700
(and allergen-specific IgE to perennial allergen)
(b) Mepolizumab (nucala, anti IL-5) typically requires serum eos over 150 in the past 12 months
Bronchothermoplasty
(a) How it works
(b) Benefit
Bronchothermoplasty
(a) Reduce smooth muscle mass
(b) Reduces exacerbations, no mortality change (AIR2 trial)
2 indications for ASA desensitization in patients with aspirin-exacerbated respiratory disease
Desensitization to ASA if:
- severe, refractory nasal polyposis
- another strong indication requiring ASA therapy (ex: PCI)
-desensitize then have to continue daily ASA
Exercise-induced bronchoconstriction
(a) proposed mechanism
(b) gold standard for diagnostic testing
(c) tx
Exercise-induced asthma
(a) Large volume cold air triggering airway hyperreactivity
(b) Indirect bronchoprovocation test, exercise challenge test
-positive if 15% reduction in FEV1
(c) Start with pre-treatment of SABA, can add ICS/LABA if needed
Main clinical benefits of asthma biologics
Really the 50% reduction in exacerbations, then also reduction in oral corticosteroid use
-typically FEV1 improvements are present but don’t always meet MCID
Ideal COPD pt candidate for initiation of long-term nocturnal noninvasive?
Chronic, stable COPD 2-4 weeks following discharge (so not upon discharge from hospital) for acute exacerbation of COPD with compensated hypercapnia (pCO2 over 45, pH over 7.35) after which OSA is already ruled out
-so not patient in hospital pending discharge, pending PSG, or worsening symptoms
2 groups for which long-term O2 therapy improves survival
- Resting hypoxia: PaO2 under 55 or SpO2 under 88% at rest
- PaCO2 56-59 with e/o polycythemia or cor pulmonale
–not those w/ exercise desat (LOTT trial) showed no sig difference in death, first hospitalization, or exacerbations
52M with frequent COPD exacerbations, negative alpha-1 antitrypsin, FEV1 21%. No cough or sputum. On high-dose LAMA/LABA
Next best step: triple therapy or add azithro?
First upgrade to triple therapy, thennn add azithro
-don’t be confused by tons of exacerbations, maintenance macrolide added to triple therapy
Describe how brensocatib (oral inhibitor of dipeptidyl peptidase 1) may work to reduce exacerbations in non-CF bronchiectasis
Works to reduce neutrophil serine protein activity
-DPP1 activates neutrophil serine protease enzymes (ex: neutrophil elastase) that are elevated in non-CF bronchiectasis (typically high neutrophils => IL-8 overexpression)
69M with COPD- former 1/2 PPD smoker x30 years. Symptoms controlled on LAMA, FEV1 68%
Next best test for COPD mgmt?
Trick question (eye-roll): doesn’t meet criteria for lung CA screening b/c under 20 pack years (current criteria: 50-80 yoa with at least 20 pack year history quit within last 15 years
Next best step- bone densitometry given high risk of osteoporosis
Bronchial atresia
(a) Pathogenesis
(b) MC affected lobe
(c) MC typical presentation
(d) Imaging finding
Bronchial atresia
(a) Congenital anomaly where airway doesn’t form
(b) Most commonly apicoposterior segment of LUL
(c) Typically asymptomatic, but can present w/ infection and air trapping
(d) Mucoid impaction at atretic area and distal hyperinflation
34F with CF with chronic cough unchanged from baseline p/w stable FEV1, surveillance Cx grows pseudomonas- next step?
Inhaled tobramycin x28 days
-not IV abx given asymptomatic, can used inhaled to try to eradicate for initial pseudomonas infection
-definitely don’t ignore, treatment of early pseudomonas leads to more sustained eradication, less overall abx use (though no clear benefit in mortality, rate of lung fxn decline, or mortality
20M poorly controlled asthma despite adherence to triple therapy inhaler and montelukast. Normal eos, normal IgE, no atopy, on low dose oral steroids for 6 months with persistent daily use of albuterol
Which mab is indicated?
Dupilumab (anti-IL4R)- effective as add-on maintenance for oral corticosteroid-dependent asthma regardless of phenotype
-not omalizumab (anti-IgE) b/c IgE levels 30-700 required
-mepolizumab and reslizumab (anti-IL5s) approved for add-ons for oral steroid-requiring asthma ONLY if pt has elevated eos count (over 150 for mepolizumab, over 400 for reslizumab)
Exclusion criteria for bronchial thermoplasty study
(a) number of exacerbations
(b) FEV1
(c) Good response to prior bronchial thermoplasty
(d) Asthma control
Bronchial thermoplasty to reduce large/medium airway smooth muscle mass
(a) Excluded pts with more than 3 exacerbations in the past year
(b) Excluded for FEV1 under 60%
(c) Excluded if had prior bronchial thermoplasty (so evidence of prior partial response is irrelevant)
(d) Need poor asthma control (ora steroid use) but in a chronic state at time of procedure
Most common adverse effect of endobronchial valve insertion
Pneumothorax in 25% in the first month, highest risk in first 3 days
