RC Respirology Flashcards
What is an abnormal pulsus paradoxus?
> /10 mmHg change of systolic BP between inspiration and expiration
DDX for abnormal pulsus
Tamponade
Asthma exacerbation
COPD exacerbation
Constrictive pericarditis
PE
Morbid obesity
Effects of hyperoxia on respiratory system
Hypercapnia, CO2 retention
Direct O2 toxicity from ROS - interstitial and alveolar edema due to leaky capillary endothelium, hyperoxic bronchitis
Absorption atelectasis
Instability of units with low V/Q ratios causing shunt
Retinopathy of prematurity (not respiratory)
Benefits of HFNC in patients with respiratory failure
Heated and humidified - reduces WOB, allows secretion clearance
Provides PEEP - decreases WOB, prevents atelectasis
Provides PEEP - prevents atelectrauma
High flows - washours out upper airway dead space, reliable FiO2 delivery due to minimal entrainment, decreases upper airway resistance
Who should have extubation to HFNC
Extubation of surgical patients
Extubation of non surgical patients at low/mod risk of extubation failure
Sources of physiological shunt
Bronchial arteries emptying into pulmonary veins
Thebesian veins emptying into left ventricle
Functional shunt: V/Q <1
Limitations/assumptions of the shunt equation
CcO2 = CAO2 = perfect diffusion between alveoli and capillaries
We assume PcO2 = PAO2 (from alveolar gas equation)
We assume that SaO2 = 1
Assumes all gas exchange occurs with ideal V/Q matching.
Differences between central and mixed venous gas
ScvO2 = central line, normal is 65-70% (>80% (high PaO2 or left to right shunt) vs <65% (impaired tissue oxygenation))
SvO2 = pulmonary artery, normal is 60-65%
basically ScvO2 should have higher O2 because it doesn’t get the low O2 blood from the IVC
DDX for high O2 Extraction Ratio
Sepsis, fever
Shock
Seizures
Hyperthyroidism
Hypoxemia
Anemia
DDX for low O2 Extraction Ratio
Hypothyroidism
Hypothermia
Sedation
Mitochondrial dysfunction in sepsis
Cyanide toxicity
Hyperbaric oxygen
Hyperoxia
Polycythemia
Impact of Positive Pressure Ventilation on the heart
Decreased preload to RV and LV
Increased afterload to RV, decreased afterload to LV
Overall, decreased SV and CO, decreased cardiac work
Impact of Positive Pressure Ventilation on dead space
Increased zone 1 respiration with high V/Q areas
Increases both alveolar and anatomic dead spaces
Lung volume is raised resulting in radial traciton on the airways increasing volume of anatomic dead space
Raised airway pressures divert blood flow away from ventialated regions causing high v/q ratio or even unperfused areas
Most common in uppermost regions of the lung.
Capillaries pressures fall below airway pressure and they collapse
Different Ventilator modes and settings
Assisted= mandatory patient triggered
Controlled= mandatory Time/volume triggered
Supported= spontaneous (patient triggered) flow terminated
PCV- you set inspiratory pressure. Volume will vary
VCV - you set TV peak flor and flow pattern. Pressure will vary
PSV - (Spontaneous Pressure Support Ventilation) al breaths supported (whatever TV the patient generates)
ASV - set EPAP, PS mirrors ventilation (higher at low flow periods)
SIMV (synchronized Intermittent Mandatory Ventilation- set RR with either Volume or PRessure target), patient can do what they want in between the set breaths
APRV - airway pressure release ventilation - Bilevel ventilation where you set PEEP and plateau. rescue therapy for ARDS, helps with recruitment to help with oxygenation, spontaneous breathing (increased WOB), risk of volutrauma, risk of DH
What are PIP, Pplat, driving pressures, delta P, airway resistance
PIP: (peak inspiratory Pressure) P to overcome resistance (airways, ETT) and lung elastic properties, target <35
Pplat: P to distend alveoli, reflects compliance, target <30 cmH2O
Driving pressure: Pplat - PEEP
Delta P: PIP-Pplat, reflects resistance: both elevated within 5 means reduced lung compliance or chestwall/diaphragm/pleural. Only Elevated PIP means increased airway resistance
Airway resistance: PIP-Pplat/Flow
Types of Respiratory Maneuvers on the ventilator
Inspiratory hold → Pplat
Expiratory hold → intrinsic PEEP
Only in volume control
DDx of reduced peak inspiratory pressure
Air leak
Hyperventilation
What do changes to the volume pressure curve represent on a ventilator?
Slope = static compliance
Width = dynamic compliance and airway resistance
Bird beaking = over distension = turn TV down
What are Static and dynamic compliance on a ventilator?
Static: chest wall and lung tissue compliance
Dynamic: chest wall, lung tissue compliance and airway resistance
what is the DDX for sudden increase in mechanical ventilation in critically ill patients
Increased dead space - collapsed lung, mucous plug, mainstem intubation/dislodged
Increased demand - sepsis, fever
Pain, anxiety
Decreased compliance
Benefits of PEEP
Improve oxygenation -improve atelectasis/VQ, moves peripheral edema into interstitium
Lessens required FIO2 and O2 toxicity
Improves lung compliance - think of equation Compliance = delta V/Delta P
Prevent atelectrauma
Decrease WOB
Decrease LV work/afterload
Mechanisms of hypotension with PEEP
Reduced preload to RV and LV
Increased RV afterload, RV failure
Reduced LV compliance
Consequences of autoPEEP
Barotrauma
Dynamic hyperinflation
Decreased lung compliance
Decreased tidal volumes and minute ventilation
Increased WOB
Cardiac - decreased preload, decreased CO, increased PVR
Neuro - increased ICP due to reduced central venous return
DDX of increased autoPEEP
Increased airway resistance e.g. bronchospasm, kinked tube, clogged tube
Increased tidal volume
Increased respiratory rate
Increased I:E time or ratio
Decreased expiratory time
Increased inspiratory time
Decreased inspiratory flow rate
Treatment of autoPEEP
Treat bronchospasm or reason for resistance
Decrease respiratory rate
Decrease tidal volume
Decrease I:E ratio
Increase expiratory time
Increase inspiratory flow rate
Increase or add PEEP **
Permissive hypercapnia ** (reduce demand)
Sedation and paralysis if dyssynchronous, treat anxiety/pain ** (reduce demand)
Relative Contraindications to PEEP
High ICP
Hypotensive
RV failure
Right to left shunt
Barotrauma
Bronchopleural fistula
Causes for difference between PaCO2 and PETCO2
PETCO usually lower
Due to anatomical dead space
Causes of increased PETCO2
ROSC (increase by 10-20)
Effective CPR
Hyperthyroidism
Hyperthermia
Fever, sepsis
Hypoventilation
Bronchial intubation
Causes of decreased PETCO2
Hypotension, shock
Cardiac arrest
Hypothyroidism
Hypothermia
Hyperventilation
Apnea
Extubation, sudden kink
Ventilatory parameters for obstructive lung disease
Mode:volume (but no data > pressure)
FiO2: SpO2 88-92
PEEP: minimal, 5
RR: 10-12%
Vt: <8 mL/kg PBW
I:E target: 1:5
Permissive hypercapnia (pH >7.2, pCO2 <90)
Ventilatory parameters for ARDS
Mode: volume
FiO2: 88-95%
PEEP: Modest
RR: 25-35
Vt: 4-6 mL/kg/PBW
I:E target: 1:2
Permissive hypercapnia (pH >7.2)
Pplat </30 (mortality benefit)
Driving pressure </15 (mortality benefit)
Physiological benefits of permissive hypercapnia
Reduced autoPEEP
Reduce barotrauma
Decrease WOB
Rationale for permissive hypercapnia in ventilation
Obstruction - prevent autoPEEP
Restriction - low tidal volumes
Possible complications of permissive hypercapnia
Increased ICP
Decrease seizure threshold
Arrhythmias, irritable myocardium
Increased PVR 2/2 acidosis
Decreased placental flow
In addition to ventilator settings, what else do you have to take into consider in Mechanical Ventilation asthma?
Not opioids for sedation 2/2 histamine
Large ETT to reduce resistance
Consider inhaled isoflurane
Consider heliox
Consider Hodder’s maneuver
Consider ECMO
Characteristics of Heliox
Low density
Density is important in turbulent flow (large airways)
Viscosity is important in laminar flow (smaller airways)
Importance of the Winters Equation
Tells you what CO2 should be if appropriately compensated
Use this to determine goal Ve
Berlin’s criteria for ARDS - NOTE NEW CRITERIA!
Within 7 days of a known insult or worsening symptoms
Non cardiogenic pulmonary edema, not due to intravasc volume overload
Bilateral pulmonary opacities not explained by nodules, atelectasis, effusion, etc. (CXR OR CT, or lung ultrasound by trained professional) Seen in 2 quadrants (bilat or unilat)
Severity grading on PEEP 5
PaO2/FiO2<300
SpO2/FiO2 <315
Causes of ARDS
Inhalation exposures
Aspiration
Fresh water, salt water aspiration, drowning
Fat embolism
Reperfusion injury
Infections, pneumonia, sepsis
Pancreatitis
Transfusion reaction
Pathology of ARDS
- Early exudative: 1 week, high permeability pulmonary edema, proteinaceous fluid fills alveoli, hyaline membrane formation, pathology shows DAD
- Fibroproliferative: 2 weeks, interstitial inflammation, disordered healing, fibrosis
- Fibrotic: fibrosis, obliteration of normal lung architecture
Image findings of ARDS
Dependent opacities, consolidation
Bilateral, symmetrical
Ways to improve oxygenation in ARDS
Increase PEEP, mortality benefit in mod-severe
Prone positioning, 12hrs/day, PF <150 mortality benefit (It should be administered within 48 hours, evaluated daily and stopped within 48 hrs if possible)
Euvolemia
Steroids in some
Neuromuscular blockade
Inhaled NO
ECMO
Physiological benefits of prone positioning in ARDS
Improve V/Q matching
Improve secretion mobilization + drainage
Decrease compressive effects of heart
Indications for ECMO
PaCO2 >60 for >6 hours
PF <80 for >6 hours
PF <50 for >3 hours
Mechanically ventilated <7 days, BMI <40, age 18-65
Contraindications to ECMO
Disseminated malignancy
Known severe brain injury
Severe chronic organ dysfunction
Severe pulmonary hypertension
Complications of Positive Pressure Ventilation
Hypotension
Barotrauma
VALI
VAP
Airway complications e.g. stenosis, tracheobronchomalacia, fistula formation
Critical illness polyneuropathy, myopathy
Risk factors for barotrauma
High Pplat*
High PIP*
High PEEP*
Low compliance* e.g. ILD, COPD, overload
Maneuvers to reduce risk of barotrauma
Reduce RR
Reduce Vt
Increase expiratory time
Permissive hypercapnia
Increase sedation
Reduce PEEP
Benefits of tracheostomy
Reduced sedation
Phonation
Better secretion management, better mouth care
Allows mobility
Prevents laryngeal injury
Can leave ICU
Acute complications of tracheostomy
Bleeding
Surgical site infection
Dislodgement
Tube is kinged or clogged
Laryngeal nerve damage
Pneumothorax
Chronic complications of tracheostomy
Dislodgement
Trach blockage
Tracheal stenosis
Tracheobronchomalacia
Tracheoesophageal fistula
Tracheoarterial fistula
What is VALI?
Due to volutrauma
Alveolar overdistension
Presents with edema, hemorrhage, loss of compliance
Indicators of readiness to wean
Underlying resp condition resolved or improving/on active treatment
GCS >8
PaO2 >60 on FiO2 requirements <40% on PEEP <8
PF ratio >150
PaCO2 normal
Adequate cough
Not requiring frequent suctioning e.g. <q2 hours
Hemodynamically stable - minimal or improved pressor requirements
Abnormal RSBI (Rapid Shallow Breathing Index)
RR/TV >105
Predictive of failed extubation
Predictors of successful weaning during SBT
RR/VT = RSBI <105
Maintaining adequate ventilation
Maintaining adequate oxygenation
No signs of severe fatigue
Definition of extubation failure
Reintubation within hours-days
Risk factors for extubation failure
Age >65
Underlying cardiorespiratory disease
RSBI >105
Abundant endotracheal secretions
Weak or absent cough
Positive fluid balance in last 24 hours
Respiratory failure was for cardiac origin, PNA, neurological condition
Factors that may limit weaning
Reduced drive from over sedation or neurological problem
Underlying disease not yet resolved
Respiratory muscle weakness, deconditioning
Development of atelectasis, mucous plugging - poor/weak cough
VAP/VALI development
Oversedation
Under Sedation - anxiety, pain
Neuropathy or myopathy from prolonged intubation
Malnutrition - respiratory muscle weakness
Overnutrition - increased CO2 production
Cardiomyopathy, cardiac ischemia
Anemia
Clinical signs of failure during SBT
Anxiety, agitation, diaphoresis
Hypertension or hypotension - not between 90-180
Tachycardia - HR >140, arrhythmia
Tachypnea - RR >35 x 5 mins
Increased work of breathing - accessory muscle use, thoracoabdominal paradox
Fall in O2 (<90%), increase in CO2 - hypoxemia and hypercapnia
Stridor
What causes Right shift in the hb-dissociation curve
Increased CO2 (Bohr effect)
Increased H
Increased temperature
Increased 2,3 DPG
What causes Left shift in the hb- dissociation curve
Decreased CO2 (Bohr effect)
Decreased H
Decreased temperature
Decreased 2,3 DPG
Increased CO
Determinant of PaO2
PAO2 - POI2, PaCO2
Architecture of the lungs
Major determinants of SaO2
PaO2
Temperature
H
CO2
2,3 DPG
DDX for saturation gap
Carboxyhemoglobinemia
Methemoglobinemia
Sulfhemoglobinemia
DDX for lower SpO2 for given PaO2
Nail polish
Pigments, methylene blue
Poor circulation - Raynaud’s, peripheral vascular disease, shock
Hemoglobinemia - e.g. methemoglobinemia, sulfhemoglobinemia, thalassemia, sickle cell anemia, spherocytes etc
Motion or artifact
Technical factors
Clinical manifestations of CO poisoning
Headaches, decreased LOC, personality changes, headaches, seizures
Arrhythmias, cardiac ischemia
Cherry red skin and lips
Treatment options for CO poisoning
Supplemental oxygen
Hyperbaric oxygen
Eucapnic hyperventilation
Indications for hyperbaric oxygen in CO poisoning
Severe end organ sx e.g. MI
CO-Hb >/25%
CO-Hb >/15% if pregnant
Severe metabolic acidosis pH <7.1
Blood gas findings in CO poisoning
PaO2 normal
SpO2 normal
SaO2 decreased
CaO2 decreased
CvO2 decreased
Blood gas findings in cyanide poisoning
PaO2 normal
SpO2 normal
SaO2 decreased (I think Normal)
CaO2 normal
CvO2 increased
Treatment for cyanide poisoning
Supplemental oxygen
Hydroxocobalamin
Nitrites
Avoid dialysis
Safe amount of lidocaine to prevent toxicity
5 mg/kg without epi
7 mg/kg with epi
Treatment of lidocaine toxicity
BZD
Lipid emulsion
At what pressure is O2 delivered at in hyperbaric O2?
2.5-3 atm
Contraindications to HyperBaric Oxygen Therapy
Pneumothorax untreated - absolute
Obstructive lung disease - relative
Blebs or bullous disease - relative
Indications for HyperBaric Oxygen Therapy
CO poisoning
Venous or arterial air embolism
Decompression sickness
Medications that can cause methemoglobinemia
Lidocaine, benzocaine
Methylene blue
Metoclopramide
Dapsone
Nitrates
Primaquine
Indications for methylene blue for methemoglobinemia
Levels >30%
Very symptomatic
Indications for intubation in someone with thermal/fire airway injury
Neck, facial burns
Laryngeal injury - Stridor
Tracheobronchial injury - cough, wheezing, melanoptysis
Paryncheal injury
Systemic toxicity e.g. CO poisoning etc
Broad categories for International Classification of Sleep Disorders
Insomnia
Sleep disordered breathing - OSA, CSA, OHS, Nocturnal Desaturation
Hypersomnolence
Parasomnias
Sleep related movement disorders
Circadian rhythm sleep wake disorders
Other
Definition of compliance with Sleep Therapy
4 hrs per night
At least 70% of nights in last month
As per CMA guide, which patients with OSA should not be driving?
Moderate-severe OSA, not compliant
Compliant but involved in MVC where they were at fault - x 1 month until compliance reassessed
Drivers admit to experiencing excessive sleepiness during major wake periods or while driving
As per the Ontario MTO, who should not be driving?
AHI >/30 in treated or untreated
As per CMA guide, which patients with narcolepsy should not be driving?
Uncontrolled cataplexy (on or off treatment) in the past 12 months
Uncontrolled daytime sleep attacks or sleep paralysis in the past 12 months
Generally no long distance commercial driving
For a commercial driver with OSA, what conditions need to be met for them to drive?
AHI <20
On effective treatment
Does not experience excess sleepiness during major wake periods
Which drivers do we screen for OSA?
Everyone should be screened with questionnaires, BMI and studies as needed
Recertified annually
When can commercial drivers be recertified?
PAP - one week, good compliance, good AHI, no sleepiness
Oropharyngeal surgery or trach - one month, good AHI, no sleepiness
Bariatric surgery - six months, good AHI, no sleepiness
Distribution of sleep
N1 - 5%
N2 - 50%
N3 - 20%
REM - 25%
Sleep spindle
Usually in N2
Fast burst 0.5-2s of 12-15 Hz activity
K complex
Usually in N2
Go up first, then down
How much theta waves do you require in N1/N2 sleep?
At least 50% of the epoch
How much delta do you need in N3 sleep?
At least 20% of the time
Other names for N3 sleep
Slow wave sleep
Deep sleep
Features of REM sleep
Low amplitude, mixed frequency
REM atonia → low chin EMG
Rapid eye movements
May see sawtooth waves
How do sleep disorders change during REM sleep
OSA worsens, CSA improves (reduced chemosensitivity so won’t be as sensitive to changes in Co2
Hypovent and hypoxemia in NMD or chest wall disorders (bc loss of accessory muscles during atonia) **
What does a short REM latency suggest? What are the causes of REM rebound?
- Narcolepsy
- REM Rebound
2a. Depression
2b. Medication withdrawal e.g. SSRIs, BZD, alcohol
2c. REM sleep deprivation
2d. Patients undergoing CPAP titration
Causes of REM suppression
SSRIs
Monoamine oxidase inhibitors
Sedative hypnotic drugs, barbiturates
Antiepileptics
Alcohol
Medications stimulate breathing vs suppress breathing
Stimulate: theophylline, acetazolamide, progesterone, thyroid hormone
Inhibit: BZD, barbiturates, gabapentinoids, alcohol
Effect of aging on sleep
Decrease in N3
Increase in N1 and N2
No change in REM
Increased WASO - wake after sleep onset
More arousal
Lower sleep efficiency
Body’s clock shifts earlier
Physiological changes during sleep
Decreased BP, HR, CO (increase in phasic REM)
Decreased RR, VT, VE; RR generally increase in REM
PaCO2 increase 3-5 mmHg
PaO2 decrease 5-8 mmHg; SpO2 decrease 1-2%
Increased upper airway resistance
Minimum requirements for an adequate sleep study
At least 2 hours of sleep
Other normal values (not required): 80% efficiency, <30 mins sleep onset, <90 mins REM onset
Components of a PSG
EEG
EOG
EMG
ECG
Airflow (2)
Respiratory efforts (2)
SpO2
CO2 measurement
Ways to measure airflow
Oronasal thermistor - apnea
Nasal pressure transducer - hypopnea, RERA
Ways to measure respiratory effort measured
RIP belt (respiratory inductance plethysmography)
Esophageal pressure monitoring
Diaphragmatic EMG
When should patients with sleep apnea be followed up on?
Within 4 weeks if high risk
Within 6 months for all others
Who is a level II-IV sleep study appropriate for? What are Contraindications?
Moderate-high pretest probability
Do not suspect other sleep disorders
Do not have other comorbid diseases
Not a titration study
Criteria for moderate-high pretest probability of OSA
Excessive Daytime Sleepiness on most days with 2 of the following:
Snoring
Witnessed apneic episodes
Witnessed choking during sleep
Witnessed gasping during sleep
Diagnosed HTN
Criteria for comorbid/complicated disease (sleep disordered breathing)
Cardiorespiratory disease
History of stroke
Respiratory muscle weakness, NMD
Suspicion for hypoventilation
Levels of Home Sleep Apnea Testing
II: Full PSG but done at home
III: airflow, effort, ECG, pulse oximetry
IV: pulse oximetry
Requirements that need to be met to be able to do split night study
Moderate-severe OSA based on at least 2 hours of recordings
3 hours available for titration
Definition of apnea vs hypopnea
Apnea: decrease in flow >/90% from baseline x >/10 seconds
Hypopnea: decrease in flow >/30% from baseline x >/10 seconds and accompanied by desaturation of SaO2 by 3% or arousal
Definition of obstructive vs central HYPOPNEAs
Obstructive: snoring, thoracoabdominal paradox, increased insp flattening of nasal pressure compared to baseline
Central: None of the above
Definition of mixed apneas
Starts out as central, then obstructive
Definition of a RERA
Increase in resp effort or flattening of nasal pressure waveform
Event causes arousal or desaturation without meeting appropriate criteria x 10 s
Definition of hypoventilation on a PSG
Increase in PaCO2 >55 mmHg x 10 mins
Increase in PaCO2 by >/10 mmHg to a value above 50 mmHg x 10 mins
AHI vs RDI
AHI = Apnea + hypopnea/total sleep time
RDI = Apnea + hypopnea + RERA/total sleep time
DDX for EDS
Insufficient sleep
Sleep disordered breathing - OSA, CSA, hypoventilation, etc.
Central Sleep disorders-Narcolepsy, Kleine-Levin syndrome, Idiopathic hypersomnelence.
Circardian rhythm sleep disorders
Sleep related movement disorders
Parasomnias- RBD, sleep walking, sleep terrors, confusional arousals.
Neurologic disorders - Parkinson’s, dementia, stroke, MS
Medical: -Hypothyroidism , Adrenal insufficiency , Anemia, iron deficiency , CKD, renal failure, hepatic encephalopathy
Depression, other psychiatric conditions
Medications, substances
What medical conditions should make you think about screening for OSA?
OHS
Difficult to control HTN
Recurrent atrial fibrillation post cardioversion or ablation
Pulmonary Hypertension
Neurological control of upper airway muscles
Cranial nerves 5,7,9,10,11,12
Risk Factors for OSA
Smoking
Elevated BMI
Family history
Increased age
Male, post menopausal
Increased mallampati score
Tonsil or adenoid hypertrophy
Increased neck circumference
Retrognathia
Micrognathia
Macroglossia
Nasal abnormalities
Low lying palate
Hypothyroidism
Acromegaly
Neuropathy or myopathy
Mechanism of hypoxemia in OSA
Underlying lung disease
Baseline supine SaO2
Low FRC (e.g. obesity)
Duration of apneic/hypopneic episodes
Frequency of apneic /hypopneic episodes
Respiratory efforts in between apneic/hypopneic episodes
Possible complications of OSA
Hypertension
Coronary artery disease
Arrhythmias
Stroke
Heart failure
PH if concomitant OHS
Diabetes
Erectile dysfunction
Depression
Cognitive deficits
MVCs
Screening questionnaires for OSA
Berlin questionnaire
STOP-Bang questionnaire (high sensitive, poor specificity)
Diagnostic criteria for OSA
Symptoms/complications + AHI >/5
AHI >/15
Severity of OSA
Mild: >/5 - 14.9
Moderate: 15 - 29.9
Severe: >/30
Positional sleep apnea definition
Supine AHI is at least double non supine AHI
Indications for PAP treatment in OSA
Moderate to severe OSA/ AHI >/15
Mild but symptoms (e.g. EDS), reduced QOL, or hypertension
Critical occupation
Starting pressure and max pressure for PAP
Start at 4 cm H2O
Switch to BPAP 15 cm H2O
Absolute max 20 cm H2O
Min and max pressures for BPAP
Min difference of 4 cm H2O
Max difference of 10 cm H20
Min pressure 4 cm H2O, Max pressure of 30 cm H2O
How to progress titrating to next pressure during titration study
> /2 apneic events
/3 hypopneic events
/5 RERAs
/3 mins snoring
Any of this within a 5 min period
Want >/ 30 mins without breathing event
Criteria for optimal titration achieved
- Optimal: RDI <5 for at least 15 mins, supine sleep observed, REM sleep not interrupted by spontaneous arousals, O2 sat >90%
- Good: RDI </10 or by 50% of baseline RDI if baseline <15, supine sleep observed, REM sleep not interrupted by spontaneous arousals O2 sat >90%
- Adequate: RDI not </10 but reduced by 75% from baseline or one in which above met but supine REM did not occur at selected pressure, O2 sat >90%
- Unaccepted: None of the above are met
Causes of persistent sleepiness in OSA despite treatment
Non adherence/compliance
Additional medical condition
Additional sleep disorder
Treatment emergent central sleep apnea
Inadequate pressures/not fully controlled
Sleep deprivation/insufficient sleep
Once the other causes are ruled out, how can you treat patients with OSA who still have EDS?
Modafinil
Solriamfetol
Indications for modafinil in OSA
Ongoing EDS despite appropriate treatment
Concomitant narcolepsy
Concomitant circadian rhythm disorder
Certain occupations - shift workers (Temporary)
Methods to increase adherence to PAP therapy
Education
Humidity
Nasal mask vs. full face mask
Treatment of nasal congestion
Polypectomy
Oral appliance
APAP
Benefits of treatment (PAP, OA, MMA)
Improved AHI (all stages)
Improved symptoms: Definitely moderate-severe, unclear mild
Decreased BP: moderate-severe
PAP also improves responsiveness of Afib to tx, ?improve outcome after stroke
Contraindications to APAP
Chronic lung disease e.g. COPD
Previous UPPP (Uvulopalatopharyngoplasty)
Heart failure
Central sleep apnea
OHS/hypoventilation syndrome
Medications causing hypoventilation e.g. chronic opioid use
Neuromuscular disease, chest wall disorder
Treatments for OSA other than PAP
Positional therapy
Oral appliances
Surgery
Hypoglossal nerve stimulation
Weight loss
Indications for oral appliance
Primary snoring disorder without OSA
OSA but intolerant of or unwilling to try PAP (vs. no treatment)
To reduce PAP pressures
Not responsive to CPAP
Complications associated with OA
Dental malocclusion
TMJ pain
Gum pain
Drooling or dry mouth
Surgical options in OSA
UPPP (Uvulopalatopharyngoplasty)
Mandibular advancement
Tonsillectomy, adenoidectomy
Tracheostomy
Reasons to consider tracheostomy for sleep disordered breathing
Intolerant of PAP/high pressures
Cannot achieve control with other treatment
Other abnormalities prevent adequate mask fitting
Other reasons for tracheostomy e.g. craniofacial weakness
Patient preference
Main things you should assess on overnight oximetry
Mean nocturnal saturation (92)
Nadir SpO2
Time spent </88% (5 mins)
% of study spent <90% (20%)
Cutoffs for the Oxygen Desaturation Index
<10 = unlikely moderade-severe OSA
10-30 = possible moderate-severe OSA
>30= highly suggestive of moderate-severe OSA
but technically <5 is normal and >10 is abnormal
What are the abnormal hypoxemia times on an overnight oximetry
Spo2 <88% for >5min
Spo2 <90% for >10% of sleep time.
What is considered an oxygen desaturation for an ODI?
Reduction in SpO2 >/4% for >/10 seconds
Components of insomnia
Difficulty sleeping or maintaining sleep
Adequate opportunities for sleep
Affect functioning
PSG findings of insomnia
Increased WASO
Increased sleep latency >/30 minutes
Reduced sleep efficiency
Reduced sleep time <6-6.5 hours
Medical causes of insomnia
Medications e.g. stimulants, coffee
Psychiatric e.g. depression, anxiety
Neurologic e.g. parkinsons, dementia
Chronic pain, diabetes, HTN, cancer
Classification of central sleep apnea
- Primary central sleep apnea
- Primary central sleep apnea of infancy or prematurity
- CSA with Cheyne stokes
- CSA due to medical disorder without Cheyne Stokes
- 4a. Central insult e.g. tumour, stroke, encephalitis, polio
- 4b. Respiratory muscle weakness e.g. NMD, chest wall disease
- 4c. Renal failure
- 4d. Atrial fibrillation - High altitude periodic breathing
- Treatment emergent central sleep apnea
- Medication or substance related
Medications that can cause CSA
Opioids
Benzodiazepines
Gabapentinoids
Antidepressants
PSG findings in general CSA
Cessation or reduction in ventilatory effort x >/10 seconds
Most common in N1/N2
No effort via RIP belt or diaphragmatic EMG
>/5 central events per hour and >50% of total events
Snoring and desats are less prominent than OSA
PSG definition of Cheyne Stokes Respiration
- > /3 consecutive central apnea/hypopneas with crescendo and decrescendo changes in breathing amplitude with a cycle length of at least 40 seconds (typically 45 to 90)
- > /5 central apneas/hypopneas per hour associated with crescendo,decrescendo breathing in between recorded over min 2 hours
Diagnostic criteria of Cheyne Stokes Respiration (CSR)
Symptoms/predisposing condition (HF, neurologic dz, AF)
PSG criteria
Not better explained by other disorder
Cheyne Stokes Respiration vs. Central Sleep Apnea
Cycle length longer >40 seconds
Period of hyperpnea is longer
O2 saturation nadir is more delayed (prolonged circulation time)
Arousals during hyperpnea whereas at end of apnea with CSA
Causes of Cheyne Stokes Respiration
Heart failure
Renal failure
Central disease e.g. stroke, tumors
Medications e.g. sedatives
Pathophysiology of Cheyne Stokes Respiration
- Apnea
- Increased circulatory time
- Increased chemoreceptor responsiveness to CO2
- Increased loop gain - increase in response size
- Apnea
Pathophysiology of other CSAs
TECSA: obstruction relieved, CO2 falls, apnea, high loop gain (treatment emergent central sleep apnea)
Altitude: increased vent due to O2, CO2 falls, apnea, high loop gain
Opioids: hypoventilation
Impact of CSR on HF
Increased mortality
Occurs in 30% of patients with HF
Treatment options for CSR
GDMT of HF, transplantation
Nocturnal oxygen
CPAP therapy - (not the other OSA tx) - BPAP used with caution bc can have same effect as ASV, so avoid
Phrenic nerve stimulation
?Acetazolamide, theophylline [limited evidence]
Benefits of CPAP in CSR
Improve AHI
Improve arrhythmias
May improve LV function
SERVE-HF trial
adaptive servoventilation (ASV) increased all cause mortality in HFrEF <45%
Contraindicated
Management of general CSA
Idiopathic → BPAP-ST, ASV, CPAP
CSA 2/2 hypoventilation → BPAP-ST, ASV > CPAP
Altitude → descend, oxygen, acetazolamide
Treatment emergent → expectant, ASV > BPAP-ST, oxygen, acetazolamide
Biot’s breathing
Hyperpnea mix with apnea
Associated with meningitis
Changes that occur to the sleep architecture with altitude
Increased WASO (Wakefullness after sleep onset)
Increased N1, N2
Decreased N3
Kind of like aging
Mechanism of action of acetazolamide
Carbonic anhydrase inhibitor
Leads to increased bicarbonate excretion
Causes metabolic acidosis, stimulates breathing
Classification criteria for sleep related hypoventilation (types of hypoventilation)
Idiopathic central alveolar hypoventilation syndrome
Congenital central alveolar hypoventilation syndrome
Obesity hypoventilation syndrome
Sleep related hypoventilation due to disorder, medication, substance
Cause of congenital central hypoventilation syndrome
Autosomal dominant
PHOX2B gene mutation → loss of RTN
Also known as Ondines Curse
Role of obesity in OHS
Fat produces more CO2
Leptin suppresses respiratory drive
Altered respiratory mechanics(TLC N/reduced at BMI>40, FRC reduced, RV normal/increased, RV/TLC normal/increased, ERV low, ).
Indications for screening for OHS
BMI >30 with OSA (known or suspected)
BMI >30 with:
- Unexplained dyspnea
- Unexplained awake hypoxemia
- Pulmonary hypertension, signs of it
- Polycythemia, sx of it (e.g. facial plethoraX)
- Elevated bicarbonate
How do you screen for OHS?
Bicarbonate >27
Straight to PaCO2 if high pretest probability
Diagnostic criteria for OHS
BMI >30
Awake PaCO2 >45
Hypoventilation not explained by another disorder e.g. lung disease
(PSG is required to assess for OSA, not absolutely needed for diagnosis but almost always done)
Treatment of OHS
AHI >30 → CPAP first
AHI <30 → BIPAP-ST
No OSA → BiPAP-ST
Weight loss (25-50%), not sole treatment
If admitted with resp failure → BIPAP-ST> APAP until sleep study
Treatments that are associated with HARM in the management of OHS
Oxygen
Respiratory stimulants
Classification criteria for hypersomnolence
Primary
- Idiopathic hypersomnia
- Kleine Levin syndrome
- Narcolepsy
Secondary
- Genetic disorder
- CNS disorder e.g. stroke
- Parkinsons
- Post traumatic
- Metabolic encephalopathy
DDX of Sleep Onset REM Periods
Narcolepsy
Idiopathic hypersomnolence
Due to PD, post traumatic, genetics, central tumour, metabolic
REM rebound:
- Depression
- Medication withdrawal e.g. SSRIs, BZD, alcohol
- REM sleep deprivation
- Patients undergoing CPAP titration
Requirement prior to MSLT
PSG the night before (NOT split night)
>/ 6 hours of sleep on PSG
Withhold REM suppressing medications x 2 weeks
Causes of narcolepsy
Idiopathic
Autoimmune, post infectious
Neurosarcoid
CNS - strokes, tumors
Features of narcolepsy
Sleep attacks during the day and EDS
Hypognogic
Sleep paralysis
+/- cataplexy
PSG/MSLT features of narcolepsy
Mean sleep onset latency </8 minutes
>/2 SOREMPs </15 mins
Loss of REM atonia
Increased N1 sleep
Reduced sleep efficiency, spontaneous awakenings
Drug categories used in treatment of narcolepsy
Selective DA reuptake inhibitor
- Modafinil
Selective NE and DA reuptake inhibitor
- Methylphenidate
- Solriamfetol
DA reuptake inhibitor
- dextroamphetamine
H3 blocker
- pitolisant
Other
- Sodium oxybate: GHB
- Venlafaxine for cataplexy
Conditions that are associated with REM sleep behavior disorder
Parkinsons
MSA, other forms of dementia
Stroke, tumour
Narcolepsy
SSRIs
Treatment for REM sleep behavior disorder
Changes to make sleeping area safe
Melatonin
Clonazepam
Sleep disorders can occur secondary to Parkinsons Disease
Insomnia
Hypersomnolence
REM sleep behavior disorder
Restless leg syndrome
Excessive daytime sleepiness
Examples of opioid related disorders
Central sleep apnea
Hypoventilation
Obstructive sleep apnea
Insomnia
Causes of RLS
Iron deficiency
Pregnancy
Uremia
Parkinson disease, spinal cord disease, prolonged immobility
SSRIs + other meds
Family history
Thyroid dysfunction
Scoring a PLM (periodic leg movement)
4 consecutive flexion movements, 5-90 s apart is a series (counts as 1).
The movement is 0.5-10 s, 8mV in amplitude above resting EMG
Can’t be during a resp event.
Diagnosis of PLMD (periodic leg movement disorder)
Periodic leg movement index (PLMI) >/15 per hour
Not explained by another cause e.g. other sleep disorder
Diagnostic criteria for RLS
Urge to move limbs
Rest worsens symptoms
Getting up/moving relieves
Evenings/Night are worse
Dysfunction (causes concern)
(URGE-D)
Treatment of RLS
Iron replacement
-if serum ferritin <75ng/mL or TSAT <20%
IV or oral iron supplementation
-If serum ferritin 75-100 then only IV iron
-If ESRD then use IV iron Sucrose when ferritin <200 and TSAT <200
-IV ferric carboxymaltose (strong recommendation)
can use IV LMW iron dextran, IV ferumoxytol, ferrous sulfate, but conditional recommendations
Alpha-2-delta calcium channel ligands (Strong recommendation)
-gabapentin
-gabapentin encarbil (long acting gabapentin)
- pregabalin
Opioids
Peroneal nerves stimulation
Dipyridamole
Vitamin C if ESRD
DO NOT USE:
Gabapentinoid - pregabalin, gabapentin
DA agonist - pramipexole, ropinirole
DA analogue - carbidopa-levodopa
Examples of circadian rhythm disorders
Advanced sleep- wake phase Disorder (light therapy)
Delayed sleep phase wake phase Disorder (melatonin)
Irregular sleep-wake rhythm disorder (light therapy and no sleep aids for elderly. For younger patients=melatonin)
Non 24H Sleep wake rhythm disorder (Strategic melatonin in blind patients)
Caused by inbalance between process C and S
Criteria for sleep related hypoxemia
SpO2 </88% x 5 mins
No hypoventilation
What innervates the respiratory muscles?
Diaphragm - C3/4/5
Intercostals - thoracic nerves
Abdominal - lumbar nerves
Upper airways - cranial nerves
Levels of neuromuscular disease
Cerebral cortex - stroke, cancer
Brain stem/basal ganglia - stroke, cancer
Spinal cord - trauma, MS
Anterior horn cell - polio, post polio, ALS
Motor nerves - ALS
NMJ - MG, LEMs
Muscles - muscular dystrophy (duchenne and becker)
DDX for elevated Residual Volume
ALS
Mid-low c-spine injury
airways disease
DDX for low ERV
Obesity
T spine injury
pregnancy
Measures of respiratory muscle strength
Sitting and supine VC
MIP, MEP
SNP
Sniff esophageal pressure
Phrenic nerve EMG
Sniff transdiaphragmatic pressure
Clinical manifestations of ALS
Bulbar symptoms
UMN symptoms: spasticity, hyperreflexia, extensor plantar
LMN: atrophy, fasciculations
Causes of nocturnal hypoxemia in ALS
Concomitant OSA (?CSA, mixed>OSA)
Concomitant hypoventilation - resp muscle weakness
Central hypoventilation (loss of cortical drive to breath)
Underlying lung (e.g. VQ mismatch due to microatelectasis), heart, PVD disease
Upward shift in ventilatory setpoint for PaCO2 by 2-3 mmHg
In hypoventilation due to muscle weakness, what is the progression of symptoms?
REM → NREM → daytime
Loss of accessory muscles in REM
What Monitoring every 2-6 months in ALS
Clinical symptoms
FVC sitting
Supine FVC, MIPS, MEPS, SNPs
Cough hx, PCF
Arterial blood gas/TcCO2 if hypercapnia suspected, or bulbar sx preclude PFT
Nocturnal oximetry/PSG if SDB suspected
Indications to start NIV in ALS
Orthopnea
FVC <50% predicted (Upright reliable<65% Canadian Best Practice 2020)
Sitting or supine FVC <80% predicted with sx and other indicator of resp muscle weakness
MIPS or SNPS <-40 cm
Daytime PaCO2 >45 mmHg
Abnormal nocturnal oximetry or symptomatic Sleep disordered breathing:
- Sleep disordered breathing as defined by oxygen saturation < 90% for > 5% of the night or < 88% for 5 consecutive minutes or a 10 mmHg increase in TcCO2 during sleep AND any of the following symptoms: dyspnea, morning headache, daytime sleepiness, or non-refreshing sleep.(CTS 2019)
*Start with S/T mode over S mode (CTS 2019)
Best predictors of death at 6 months in ALS
FVC <50% predicted
SNP <-40
MIP <-40
Benefits of NIV in ALS
HrQOL
Some physiological parameters e.g. slowing VC decline, daytime PaCO2
Mortality
What does not yet have a clear goal in ALS treatment?
Respiratory muscle training
Diaphragmatic pacing
Benefits of tracheostomy in ALS
HrQOL
Mortality
Medications should be avoided in myasthenia
Fluoroquinolones
Aminoglycosides
Macrolides
Beta blockers
Procainamide
Checkpoint inhibitors
Iodinated contrast
Treatment of MG
Maintenance - pyridostigmine
Flare - steroids, PLEX, IVIG
Lambert Eaton Syndrome vs. MG?
More proximal muscle weakness
More ANS abnormalities
Less bulbar muscle involvement
Respiratory risks/manifestations associated with GBS
Weak cough
Bulbar dysfunction - Aspiration pneumonitis, aspiration pneumonia
Respiratory muscle weakness - hypoventilation, atelectasis
Sleep disordered breathing
Dysautonomia and bronchospasm
Predictors of respiratory failure in GBS requiring mechanical ventilation
FVC <60% predicted
Onset to admission <7 days
Inability to stand, life arms up, life head off pillow
Presence of facial weakness
Inability to cough
Indications for intubation in GBS
20-30-40 rule (each as separate point) :
VC<20
MIP < -30
MEP < 40
Severe bulbar weakness, cannot protect airway
Respiratory rate sustained >30
Hypoxemia/SpO2 <92%
Hypercarbia >50mmHg
Hemodynamic instability
Treatment of GBS
IVIG, PLEX
What are the types of muscular dystrophy?
BMD (Becker)
DMD (Duchenne)- worse
Predictors of nocturnal hypoventilation in muscular dystrophy?
VC <40% in DMD
VC <60% in other muscular dystrophies
Therefore, screening PaCO2 in those with VC <40%
What are causes of unilateral vs bilateral diaphragmatic paralysis?
Most common cause of unilateral hemidiaphragm
Trauma
Idiopathic
Clinical manifestations of diaphragmatic paralysis
Exertional dyspnea
Orthopnea
Bendopnea
Sleep disordered breathing symptoms
Physical examination findings in diaphragmatic paralysis
Paradoxical motion in unilateral
Paradoxical abdominal wall retraction
Diagnostic tests to assess for paralysis
Imaging
Sniff test - ultrasound, fluoroscopy
Sitting and supine test
MIP, SNP
EMG of diaphragm, transdiaphragmatic pressure
Values of MEP/MIP that are concerning for diaphragmatic paralysis
MEP/MIP >1.5 for unilateral
MEP/MIP >3 for bilateral
Complications of diaphragmatic paralysis
Unilateral: occasional hypoventilation, atelectasis
Bilateral frequent hyperventilation, atelectasis, PNA, resp failure
Treatment of diaphragmatic weakness
Unilateral: plication
Bilateral: NIV, pacing
Indications for NIV for NMD in general
- FVC < 80% associated with symptoms such as tachypnea and use of accessory muscles, tachypnea, excessive fatigue, excessive daytime sleepiness
- SNIP < 40 mmHg
- MIP < 60 mmHg (?<40 ALS)
- Daytime hypercapnia PCO2 > 45 mmHg
- Nocturnal saturation < 88% for 5 consecutive minutes
Causes of kyphoscoliosis
Idiopathic
Congenital - spinal/vertebral malformations at birth
Cartilage disorders - Marfan syndrome, EHD
Bony disorders - e.g. osteopenia, osteoporosis
Neuromuscular disorders - e.g. muscular dystrophy, cerebral palsy, Charcot Marie Tooth
Post thoracoplasty
Risk factors for respiratory failure in kyphoscoliosis
Cobb’s angle >110 degrees
VC <45 degrees in surgically untreated (we start monitoring at VC <50%)
Concomitant NMD
Concomitant lung disease
Screening for NIV needs in patients with kyphoscoliosis
Once FVC <50%, we look for hypercapnic resp failure
Treatment of respiratory failure in kyphoscoliosis
Nocturnal NIV +/- O2
Nocturnal O2 if just hypoxemia
Benefits of airway clearance
Secretion clearance
Reduce airway resistance
Improve respiratory system compliance
Prevent atelectasis
Prevent pneumonia
Prevent respiratory failure, prevent need for trach or intubation
Decrease work of breathing
Markers of a weak cough
PCF <270 L/minute
MEP <60 cm H2O
Bulbar dysfunction
Expiratory cough flow tracing - absence of transient increase in expiratory flow (cough spikes)
Secretion management strategies in DMD
Atropine
Scopolamine
Botox injection into salivary glands (submandibular and parotid)
Salivary gland RT
Indications to start a cough support device in NMD
PCF <270 L/minute
Methods to enhance cough in NMD
Lung volume recruitment - glossopharyngeal breathing, bag valve mask
Manually assisted cough
Mechanical insufflation and exsufflation device
Contraindications to lung recruitment in NMD
Unconscious or unable to communicate
Increased ICP, severe TBI
SIgnificant hypotension
Pneumothorax, risk for barotrauma e.g. bullous disease
Hemoptysis
?Cannot protect their airway e.g. severe bulbar weakness
Contraindications to NIV
Loss of consciousness, unable to protect airway
Requiring intubation
Hemodynamic instability
Facial trauma or deformity
Hemoptysis
Upper GI bleeding, perforation or recent surgery
Causes of hypercapnia in patient with NMD on BPAP?
Non compliance or low duration
Pressures are not optimal
Disease progression
Underlying lung disease
Compensation for metabolic alkalosis
Other than BiPAP, other ways to optimize respiratory status in NMD
Cough assist
Secretion mobilization and volume
Daytime mouthpiece ventilation
Smoking cessation
Vaccination
DDX for a lymphocyte predominant BAL pattern
Lymphoproliferative disorders
Connective tissue diseases
Cryptogenic organizing pneumonia
Radiation pneumonitis
Sarcoidosis
Hypersensitivity pneumonitis
NSIP
Drug induced pneumonitis
DDX for an eosinophilic predominant BAL pattern
Infections - fungal, PJP, helminthic
ABPA
Hodgkin’s lymphoma
Eosinophilic pneumonia
Asthma, bronchitis
EGPA
Drug induced pneumonitis
Bone marrow transplant
DDX for a neutrophil predominant BAL pattern
Infection
Bronchitis
Aspiration pneumonia
UIP/IPF
Asbestosis
ARDS, DAD
Connective tissue diseases
What BAL value of lymphocytes is suggestive of granulomatous inflammation?
> 25%
50% is especially suggestive of HP or cellular NSIP
Pulmonary manifestations of drug induced disease
Eosinophilic pneumonia
Hypersensitivity pneumonitis
Organizing pneumonia
Occupational asthma
Diffuse alveolar hemorrhage
ARDS
Drug induced sarcoid reaction, vasculitis and lupus
Bronchiolitis - obliterative bronchiolitis
Fibrosing mediastinitis
Pleural effusions
Pulmonary hypertension
Alveolar hypoventilation
RFs for development of amiodarone induced lung toxicity
Older age
>/2 months of therapy
>/400 mg oral daily
Total cumulative dose
High FiO2 administration
Underlying lung disease
RFs for development of bleomycin induced lung toxicity
Older age
Cigarette smoking
Higher doses (>400 units)
Concomitant radiation
Concurrent cisplatin or cyclophosphamide
High FiO2 administration
Underlying lung disease
RFs for development of nitrofurantoin lung toxicity
Older age
Female
Renal impairment
Medications that cause mediastinal lymphadenopathy
Phenytoin
Methotrexate
Benefits of O2 therapy in ILD
Resting hypoxemia: dyspnea, QOL, ?PH
Ambulatory hypoxemia: Exercise tolerance
DDx for ILD with preserved lung volume
CPFE*
Chronic sarcoidosis*
Chronic HP*
RB-ILD*
LAM
PLCH
Lymphangitic carcinomatosis
Heart failure
General Approach to DDx of radiographic patterns in ILD
Definition of honeycombing
Clustered cystic airspaces, 3-10 mm in diameter with walls 1-3mm thick usually subpleural
Reticular Pattern Definition
Small linear opacities with intra and interlobular thickening
Ground Glass Definition
Hazy increased lung opacity with preservation of bronchial and vascular markings
Consolidation Definition
Increased attenuation that obscures the margins of vessels and airways
Cyst Definition
Well defined focal lucency with variable wall thickness bust usually thin (less than 2mm)
Micronodule Definition
small round focal opacity <3mm in size
Mosaic Attenuation Definition
Patchwork of regions of differing attenuation
Outline the components of a secondary pulmonary lobule.
Important studies in the treatment of ILD
INPULSIS 1 and 2: nintedanib in ILD (Primary outcome: annual change in FVC
* INPULSIS-1: 125.3 ml/year
* INPULSIS-2: 93.7 ml/year
Myocardial infarcts:
* higher incidence in Nintedanib group 1.5% vs 0.5%
* MACE 0.6% nintedanib vs 1.8% placebo
Kolb et al. Thorax 2017 (nintedanib)
* IPF and preserved lung volume FVC >90%
Same rate of lung function decline
Same benefit
Start early!
Less risk of exacerbations
ASCEND: Pirfenidone in ILD Primary outcome:
* >/= 10% decline in FVC or all cause mortality
* 16.5% vs 31.8% (RRR 47.9%; P<0.001; NNT 7) (Mortality benenifit not proven but subsequent metanalysis do support that there is a mortality benefit)
SENSIS: Nintedanib in SSc-ILD
INBUILD: Non IPF fibrosing ILD
PANTHER: Steroids had increased mortality in IPF
Numerical cutoffs for surgical lung biopsy
FVC <55%
DLCO <35%
Possible adverse events post surgical lung biopsy
Prolonged air leak
Pneumothorax, hemothorax, pleural effusion
Infection
Delayed wound healing
ILD exacerbation
Requirement for intubation
Benefits of PR in ILD
Improved dyspnea
Improved QOL
Management of refractory dyspnea in ILD
Breathing retraining
Relaxation techniques
Fans
Body positioning
Low dose opioids
RFs for IPF
Genetics - TERC/TERT/MUC5B
Smoking
Environmental pollution
?Microaspiration
Definitions of familial pulmonary fibrosis
Fibrotic ILD in at least 2 related family members
Conditions are associated with UIP pattern
IPF
Familial IPF
CTD-ILD (SARD- ILD)
Drugs
Asbestosis
Chronic hypersensitivity pneumonitis
Radiographic pattern of UIP + associated level of confidence
Confident - 90%
Probable - 70 to 90
Indeterminate - 50 to 70
Alternative - <50%
Mediastinal findings that would suggest an alternative diagnosis to UIP
Esophageal dilatation
Pleural plaques
Type of biopsy is recommended for IPF
Surgical lung biopsy
Cryobiopsy
Histopathological findings in IPF
Subpleural and/or paraseptal predominance
Patchy involvement
Dense fibrosis with architectural distortion +/- honeycombing
Fibroblastic foci
Absence of features suggesting alternative diagnosis e.g. granulomas
Poor IPF prognostic factors on initial diagnosis
Older age
Male
FVC <50%
DLCO <35%
Greater extent of fibrosis on CT
Hypoxemia at rest or with exertion
Low 6MWT, especially <250 meters
Lower BMI
Certain comorbidities e.g. PH
Poor IPF prognostic factors on follow up
Absolute reduction in FVC by 10%
Absolute reduction in DLCO by 15%
Worsening fibrosis on HRCT
Worsening level of dyspnea
Poor UIP prognostic factors
IPF as opposed to secondary dx
Male
Older age
Heavy smoking
Poor baseline FVC
Poor baseline DLCO
Decline in FVC by 10%, DLCO by 15% over 6 months
CPFE
PH
“Appropriate clinical setting” for IPF?
Male
Smoker
>60 years old
Comorbidities that need to be managed in IPF
GERD
Pulmonary hypertension
Obstructive sleep apnea
Lung cancer
Therapies that improve survival in IPF
Antifibrotics: nintedanib and pirfenidone
Lung transplantation
Benefits of antifibrotics
Improve QOL
Reduce the decline of FVC
Reduce rate of exacerbation and hospitalization
Reduce the mortality
Requirements for antifibrotic initiation/who would benefit
Age >40
FVC >/50
DLCO >/30
Overall prognosis for IPF
Death within 4-5 years of diagnosis
Possible triggers for an IPF flare
Bad disease at baseline - low FVC, DLCO, 6MWD
Infection
Pulmonary embolism
Aspiration
Lung biopsy, bronchoscopy, other procedures
Immunosuppressive therapy
Prognosis of an IPF flare
50-90% in hospital mortality
Median survival 3-4 months
Diagnostic criteria for IPF flare
Acute respiratory deterioration
<1 month in duration
Bilateral GGO with or without consolidation on background of fibrosis
Not explained fully by another cause e.g. volume overload
Criteria for progressive pulmonary fibrosis
Need two of the three criteria
Need them to be occurring in the past year
1. Progression of symptoms
2. Decline in PFTs
- FVC >5% within one year
- DLCO >10% within one year
3. Worsening radiographic progression
DDX of PPFE (pleuroparynchymal fibroelastosis)
Idiopathic
CTD e.g. scleroderma
Chronic HP
Occupational exposures
Chemotherapy
Post HSCT, bone marrow, lung
Imaging findings in PPFE
Pleural thickening
Associated subpleural fibrosis
Concentrated in the upper lobes
Histopathological findings in PPFE
Upper zone pleural fibrosis
Subjacent intra alveolar fibrosis and alveolar fibroelastosis
Radiographic findings of CPFE
Emphysema in upper lobes
Fibrosis (usually UIP pattern) in lower lobes
Notable complications of CPFE
Lung cancer
Pulmonary hypertension
Diagnostic criteria for IPAF
Presence of interstitial pneumonia (imaging or pathology)
Does not meet CTD criteria
Exclusion of other etiologies
At least 2 of: clinical criteria, serological criteria, morphological criteria
Secondary causes of NSIP
Idiopathic
Connective tissue diseases
Drugs/medications
Exposures - hypersensitivity pneumonitis
Infections, including HIV
Radiographic features of NSIP
Basilar, peripheral OR diffuse
Cellular is GGO dominant
Fibrotic is reticulation, traction, bronchovascular bundle thickening +/- honeycombs
Subpleural sparing
General Pathology findings for UIP, NSIP, OP, fHP, and PPFE
UIP→ fibroblastic foci, honeycombing
NSIP→ homogenous fibrosis, no Honey Combing, few fibroblastic foci
OP→ MASSON bodies (buds of intraalveolar granulation tissue)
Fibrosing HP→ poorly formed granulomas, peribronchiolar, SHAUMANN bodies
PPFE→ fibroelastosis, spindle cells.
Causes of drug induced sarcoidosis
TNF alpha inhibitors
Immune checkpoint inhibitors
HAART
Interferons
Pulmonary manifestations of sarcoidosis
Interstitial lung disease
Progressive massive fibrosis
Alveolar sarcoid
Tracheal stenosis, subglottic stenosis
Lower airway obstruction
Lymphadenopathy
Pulmonary hypertension
Mechanisms of PH in sarcoidosis
Interstitial lung disease
Cardiac disease e.g. cardiomyopathy
PVOD like lesions
Granulomatous inflammation and involvement of vessels → intrinsic sarcoid vasculopathy
Fibrosing mediastinitis
External compression of PA by lymphadenopathy
Portal hypertension
Non pulmonary manifestations of sarcoidosis
Neuro - hydrocephalus, aseptic meningitis, facial nerve palsy, small fiber neuropathy, optic neuritis, encephalopathy, psychosis
Ocular sarcoidosis - anterior uveitis
Cardiac sarcoid - cardiomyopathy, heart block, arrhythmias
Renal sarcoid - nephrolithiasis
Hepatic sarcoid - transaminitis, cholestasis
Hypercalcemia, hypercalciuria
Rashes
Other: spleen, bone marrow
Clinical features that make diagnosis of sarcoidosis highly probable
Uveitis
Optic neuritis
Lofgren’s syndrome
Lupus pernio
Erythema nodosum
Hypercalcemia or hypercalciuria
Bilateral hilar adenopathy
Perilymphatic nodules
Gadolinium enhancement
Parotid uptake
Osteolysis, cysts/punched out lesion
DDX for erythema nodosum
Medications e.g. OPC, TNF alpha inhibitors
Infections e.g. hepatitis B, streptococcus, fungal
Inflammatory e.g. sarcoidosis, IBD
Malignancy
Pregnancy
How does small fiber neuropathy present?
Paresthesias
Numbness
Pain
Autonomic dysfunction - palpitations, orthostasis, sexual dysfunction
How is Erdheim Chester syndrome differentiated from sarcoidosis?
BRAF V600 somatic mutation
CD68 marker on biopsy
Also is from proliferation of foamy histiocytes rather than granulomas
Pulmonary manifestations of IgG4 disease
Lymphadenopathy
Nodules or masses
Interstitial lung disease
Fibrosing mediastinitis
Subglottic stenosis, tracheal stenosis
Pleural thickening
Pleural effusions
Diagnosis of IgG4 disease
Serum and BAL IgG4 can be suggestive
Biopsy definitive
Manifestations of cardiac sarcoidosis
Conduction e.g. AV block, BBB, tachyarrythmias, sudden death
Cardiomyopathy
Coronary artery disease from vasculitis
How do you investigate cardiac sarcoidosis?
Cardiac MRI (ATS suggests this first line)
Cardiac PET
Transthoracic echocardiogram
Lab findings in sarcoidosis
Anemia, thrombocytopenia, leukopenia
Hypergammaglobulinemia
Hypercalcemia, hypercalciuria
Elevated rheumatoid factor
DDX for elevated serum ACE
Sarcoidosis
Hypersensitivity pneumonitis
Silicosis
Berylliosis
Asbestosis
Tuberculosis
Coccidioidomycosis
Hodkin’s lymphoma
Gaucher’s disease (lysosomal storage disorder caused bya deficiency in the enzyme glucocerebrosidase leading to the accumulation of glucocerebroside in tissues)
Hyperthyroidism
PBC
Imaging findings in sarcoidosis
Perilymphatic distribution of nodules
Miliary nodularity
Lymph node enlargement, can have eggshell calcification
Galaxy sign (small nodules surrounding larger conglomerate masses)
Garland sign (bilateral hilar lymphadenopathy and right paratreacheal lymphadenopathy)
Progressive massive fibrosis
Signs of fibrosis - reticulation, traction, volume loss
Alveolar sarcoidosis
Lambda sign (bilateral hilar lymphadenopathy and right paratreacheal lymphadenopathy but lights up on a gallium 67 scan)
Panda sign (parotid uptake)
Patterns of calcification often seen in sarcoidosis LN
Eggshell
Icing sugar
Cutoffs for CD4-CD8 count for sarcoid
<1 → highly unlikely
>4 → highly likely
Staging criteria for sarcoidosis ( and spontaneous remission %)
I: LN → 90%
II: LN and parenchymal changes → 70%
III: parenchymal changes →20%
IV: fibrosis → 0%
Diagnosis of sarcoidosis
If lofgrens or heerfordt no biopsy.
If asymptomatic but radiographic findings can do EITHER biopsy OR close follow up.
If not confirmed then biopsy (EBUS recommended)
Screen with CBC,Cr, ALP (not ALT), Ca, (if Vit D needed do 25 adn 1-25), ECG (not holter or TTE), eye exam
Pathological finding in sarcoidosis
Non caseating granuloma
Discrete, well organized granulomas composed of giant cells, histiocytes and surrounded by lymphoblasts
Granulomas distributed along lymphatics and bronchovascular bundles
Sparse surrounding lymphocytic infiltrate
Difference between HP and sarcoidosis pathology
Non caseating granulomas in both
Poorly formed, small, loosely arranged in HP
Distribution around bronchioles in HP vs. perilymphatic in Sarcoid
Inflammatory infiltrates found at interstitial sites distant from granuloma.
Marked lymphocytosis on BAL in HP and >4CD4/CD8 ratio in sarcoid
Who can forgo lymph node sampling in suspecteted sarcoid?
Heerfordt’s syndrome
Lofgren’s syndrome
Lupus pernio (blue red to violet smooth shiny nodules and plaques on the head and neck, predominantly on the nose, ears, lips, and cheeks)
DDX for non caseating granulomas
Sarcoidosis
Sarcoid like reactions to malignancies
Lymphoma
Hypersensitivity pneumonitis
Berylliosis
IgG4 disease
PLCH
Erdheim Chester disease
GI diseases e.g. PBC, IBD
DDX for usually necrotizing granuloma
Tuberculosis, fungal infections, syphilis
Vasculitis
Rheumatoid nodules
GLILD
Bronchocentric granulomatosis
Sensitivity and specificity of biopsies in sarcoidosis
Endobronchial - 70% sensitive
EBUS - 80% sensitive; highest yield
Transbronchial- 30-50%
RFs for difficult to treat sarcoidosis
African american
Age >40
Progressive pulmonary involvement
Neuro, cardiac, eye involvement
Good prognostic indicators of sarcoid
Erythema nodosum
Lofgren’s syndrome
Stage I disease
Spontaneous improvement or resolution
Benefits of treatment in sarcoid
Improve sx/accelerate remission
Improve imaging
Increases risk of recurrence
Things need to be screened at baseline in sarcoid
CBC
Crea
ALP
Calcium
ECG
Eye examination
Things need to be followed up on in sarcoid BW
CBC
Crea
ALP
Calcium
Indications for treatment of pulmonary sarcoidosis
Reduced FVC, reduced DLCO
Moderate to severe pulmonary fibrosis
Precapillary pulmonary hypertension
Deterioration in symptoms, lung function or imaging on follow up - as per BTS, DLCO <65% or drop by >/15%, FVC >70%, or drop by >/10%
Indications for treatment of extra pulmonary sarcoidosis
Ocular
Neuro
Renal
Hypercalcemia
Cardiac
Treatment options for sarcoidosis
Glucocorticoids
Methotrexate
TNF-alpha inhibitors
Other: MMF, AZA, lef, JAK inhibitor, rituximab
Immune Suppressive Therapies that have RCT level of evidence in sarcoidosis
Steroids
MTX
Infliximab
to improve/preserve FVC and QoL
How much steroids do you give them in Sarcoid treatment?
Steroid 20-40 x 4-6 weeks (0.25-0.5mg/kg) evidence 20 as good as 40.
Taper 6-18 months
Indications to add on second Immune Suppressive Therapy in sarcoid treatment
Progression of disease despite steroids
Steroid intolerant
Unable to tolerate steroids below 10-15 mg oral daily
Strong patient aversion to steroids
Presence of major comorbidities made worse by steroids e.g. DM, osteoporosis
Agents treat hypercalcemia in sarcoidosis
Steroids
Ketoconazole
Possibly TNF alpha inhibitors
Management of fatigue in sarcoidosis
Exercise training
Inspiratory muscle training
Methylphenidate, modafinil
Treatment of the skin manifestations of sarcoidosis
Topical steroids
Oral steroids, MTX (ok evidence)
Infliximab* best evidence
Treatment of Small Fiber Neuropathy in sarcoid
Symptomatic - gabapentin
TNF alpha or IVIG
Treatment of neurosarcoidosis
Steroids
MTX
Infliximab
Treatment of cardiac sarcoidosis
Steroids
Other IST, but not RCT
Poor prognostic variables in cardiac sarcoidosis that would help management decisions
Age >50
Ventricular tachycardia
NYHA III-IV
LVEF <40%
Echo evidence of abnormal global longitudinal strain
Interventricular septal thinning
Elevated BNP or trop
Cardiac inflammation by PET
Late gadolinium enhancement by MRI
Symptoms that would trigger cardiac work up in Sarcoid
Palpitations
Chest pain
Syncope, near syncope
Tachycardia, bradycardia
New ECG findings
Vision changes that would trigger a vision work up in Sarcoid
Floaters
Blurry vision
Visual field loss
Who would be “suspected” to have PH in Sarcoid?
Fibrotic lung disease
Exertional chest pain
Syncope
Prominent P2, S4
Reduced 6MWD
Desaturation with exercise
Increased PA diameter on CT
Elevated BNP
DDX of dyspnea disproportionate to lung function impairment
Cardiac sarcoidosis
Pulmonary hypertension
Benefits of steroids in pulmonary sarcoidosis
Improve symptoms (accelerate remission but increase risk of recurrence)
Improve or preserve QOL
Improve or preserve FVC
Improve radiographic disease burden
Clinical features are highly suggestive of HP
Female, non smoker
Relevant exposure history
Hx getting worse with exposure (4-8 hrs), better away.
Squawks on examination
Poor prognostic markers/increased mortality in HP
Older age
Male
Smoker
Unidentified exposure
Ongoing exposure
Low FVC, low DLCO
Evidence of fibrosis, extent of fibrosis
UIP pattern on imaging, histology
Fibrotic NSIP pattern
Lower BAL lymphocytosis (<20%)
Difference of HP from silo filler’s disease and organic dust toxic syndrome
HP is granulomatous disease
ODTS and Silo Filler’s disease cause obliterative bronchiolitis
Inorganic causes of HP
Isocyanates - spray paints, polyurethane foam, insulation
HFA-134a - coolants
Drug induced - MTX, bleo, nitro
Organic causes of HP
Infectious - Mycobacterium avium, thermophilic actinomyces, aspergillus, bacillus subtilis
Animal proteins - bird serum proteins, droppings, feathers
Plants - wood dust, flour dust, seaweed
Usual lab findings in HP
Lymphocytosis (in BAL)
Neutrophilia, lymphopenia
Usually no eosinophilia
Usual radiographic findings in non fibrotic HP
parynchemal infiltration (GGOs, mosaic attenuation)
small airway disease (ill defined centrilobular nodules, air trapping)
Distribution (diffuse with possible basal sparing)
What are the usual radiographic findings in fibrotic HP
- irregular linear opacities/coarse reticulations with lung distortion (may have some mild traction bronchiectasis and honeycombing)
- distribution (random or mid lung zone predominante with sparing in the lower lobes)
- ill definied centrilobular nodules/GGOs
- 3 density pattern often in lobular distribution
Features of pathology for non-fibrotic
Features of pathology for fibrotic HP
Preferred mode of biopsy in HP
Transbronchial in HP
Cryobiopsy in fibrotic HP
Surgical in both when the others fail
When is BAL for assessment of lymphocytosis recommended in HP
Recommended in non fibrotic HP
Suggested in non fibrotic HP
Depends on ATS vs. Chest
Treatment of HP
Observation- Antigen removal
Prednisone 0.5 - 1 mg/kg/day x 4-6 weeks then taper over 3 months
Steroid sparing agent
Antifibrotics
Steroid sparing agents that are used in HP
MMF
Azathioprine
Antifibrotics
Normal composition of pleural fluid
75% macrophages
23% lymphocytes
1% mesothelial cells
Rare PMNs and eosinophils
pH usually 7.6
Pressure of the pleura at FRC and at TLC
-5 cm and -30 cm
Causes of transudative and exudative effusions
What are the 2 and 3 test rules for pleural fluid
Pleural LDH >0.45 ULN
Pleural Cholesterol >45
+/- Pleural protein >29
Note light’s (LDH>0.6 ULN, PleurProtein>0.5 SerumProtein, PleurLDH>0.6 SerumLDH)
Ddx for eosinophilic pleural effusion.
Blood or air in the pleural space
Medications
Fungal infections, parasitic infections e.g. paragonimiasis
ABPA
Malignancies
EGPA
BAPE
PE
Ddx for lymphocytic pleural effusion.
Post CABG, PCIS
Pseudochylothorax, chylothorax
Malignancy (including mesothelioma), lymphoma
Tuberculosis
Rheumatoid arthritis
Sarcoidosis
Uremic pleuritis
Cardiac failure
What is the difference between lymphocytic and very lymphocytic?
> 50% vs >80%
Especially TB, lymphoma, RA
Ddx for neutrophilic pleural effusion
Empyema
Esophageal rupture
Acute or chronic pancreatitis
Pulmonary embolism
SLE can start out neutrophilic
TB can start out neutrophilic
Causes of low pH/glucose in pleural fluid
Empyema
Paragonimiasis
RA/SLE effusion
Malignancy related effusion
Esophageal rupture
Hemothorax
Causes of elevated pleural protein
Tuberculosis
MM, WM
How can you tell apart an exudative from pseudoexudative?
P:S albumin <0.6
S-P albumin >12 g/L
S-P protein >31 g/L
Medication causes of pleural effusion
Methotrexate
Nitrofurantoin
Amiodarone
Phenytoin
Ergot alkaloids e.g. bromocriptine
Dasatinib
Beta blockers
DDX for pleural thickening
Benign and malignant masses
Pleural infections
CTD causes
Pleural plaques
Post hemothorax
Post pleurodesis
DDX for pleural calcification
Pleural plaques, previous asbestos exposure
Mesothelioma (~20%)
Malignancy e.g. extraskeletal osteosarcoma of the pleura
Previous radiation
Previous infection e.g. TB, empyema
Previous pleurodesis
Previous hemothorax
DDX for positive pleural PET?
Malignancy
Infection
Autoimmune
Previous talc pleurodesis
Etiology of fibrothorax
Previous infection, empyema
CTD - e.g. RA or SLE related effusion
BAPE
Previous hemothorax
Previous pleurodesis
Drug reactions
Features of trapped lung
Transudate or borderline exudate fluid
Drainage results in pneumothorax ex vacuo
Initial (-) intrapleural pressure
Pressure falls rapidly bc extremely high elastance
No improvement in dyspnea with drainage
Management of Hepatic Hydrothorax
Salt and fluid restricted diet
Diuresis e.g. furosemide, spironolactone
TIPS
Transplantation
?Thoracentesis
Causes of pleural effusions post CABG
Early post CABG effusion
Late post CABG effusion
Post cardiac injury syndrome
Hemothorax
Chylothorax
Pneumothorax/hydropneumothorax
Parapneumonic effusion
Infectious mediastinitis
HF related effusion
How do you differentiate between early and late nonspecific pleural effusions?
Both are usually left sided
Both exudative
Early usually bloody, eosinophilic (or neuts)
Late usually lymphocytic
pH and glucose normal
How does PCIS present? (Post Cardiac Injury Syndrome)
Fever, pleuritis, pleural effusion
Exudative, lymphocyte predominance
Anti myocardial antibodies
pH and glucose normal
Pleural fluid characteristics of RA
Exudative
Glucose <1.6
Pleural to serum glucose <0.5
pH <7.3
LDH >700
Protein >30
Lymphocyte predominant
Cholesterol >5.18 mmol/L
RF elevated >1:320
C3/C4 reduced
Cytology shows multinucleated giant cells (tadpole sign)
How is SLE related fluid different from RA related fluid?
More symptomatic - almost always has pleuritis
Association with lupus flare
More likely to be bilateral
Requires tx with NSAIDs or prednisone
Causes of chylothorax
Idiopathic
Trauma
Surgery, especially esophageal
Lymphoma, metastatic adenocarcinoma
Tuberculosis
LAM
Yellow nail syndrome
Chylous ascites
Lymphatic malformations
Pleural fluid features of chylothorax
Milky white
Exudative
Lymphocyte predominant
TG >1.24 mmol/L or evidence of chylomicrons (lipoprotein electrophoresis)
pH, glucose, LDH normal
Pleural fluid features of pseudochylothorax
Milky white
Exudative
Lymphocyte predominant
Cholesterol >5.18 mmol/L or presence of cholesterol crystals
Causes of pseudochylothorax
Tuberculosis
Helminth infection e.g. paragonimiasis
Rheumatoid arthritis
Hemothorax
Treatment of chylothorax
Dietary changes (low fat, high protein)
Fat soluble vitamins
Chest tube (unless v small and asx)
May need somatostatin/octreotide
Sirolimus in LAM
Intervention/surgical
Triad in yellow nail syndrome
Yellow nails
Lymphedema
Pulmonary symptoms - sinusitis, bronchiectasis, recurrent PNA, effusions
Microbiology of pleural effusions
Staph aureus
Strep pneumo
GNB (pseudomonas, acinetobacter, klebsiella, enterobacteria)
Anaerobic bacteria (baceroides, fusobacterium, etc.)
Signs of pleural infection on CT scan
Lentiform shape
Split pleura sign (most reliable to differentiate from abscess)
Does compress surrounding lung
Obtuse angle with the pleura
Contrast enhancement
Hypertrophy of extrapleural fat
If you do not have pleural pH available, what else can you use as guide?
Pleural glucose <3.3
Things that affect the clinical outcome (need for sx, mortality) in pleural infections
RAPID score components
CT/US septations
Pleural contrast enhancement
Size >400 cc
Pleural fluid microbubbles
Increased attenuation f extrapleural fat
Things do not affect clinical outcomes in pleural infections
Size of tube
Causative organism
Components of the RAPID score for pleural fluid evaluation
Renal function (BUN)
Age (50-70 or >70)
Purulent - yes or no (point if not purulent)
Infection source CAP/HAP
Diet - Serum albumin
What does the RAPID score correspond with?
Mortality at 3 and 12 months
Indications for chest tube insertion
Empyema - pus, positive gram stain, positive culture
Very loculated
Very septated
Massive effusion (>50% of hemithorax)
pH <7.2
Intermediate pH but LDH >900
Complications of pleural infections
Bronchopleural fistula
Pleural calcifications
Pleural thickening
Empyema necessitans (pus extending into the chest wall, common with TB)
Fibrothorax
Antibiotic for treatment of parapneumonic effusion
Beta lactam + beta lactamase inhibitor
Ceftriaxone/FQ + metronidazole
Carbapenems
Clindamycin
Carbapenem + vanco if HAP
Duration 2-6 weeks
If needed, when is surgery ideally performed RE: pleural effusion?
Within day 3
Should not be favored over chest tube initially
VATS is preferred over medical pleuroscopy and thoracotomy
Surgical options
Drainage
Debridement (removal of lose debris/dead tissue)
Decortication (peel of a thick fibrous layer of pleura)
Benefits of intrapleural enzyme therapy
Reduces volume on imaging
Reduces LOS
Reduces requirement for thoracic surgery
Indications for giving a reduced dose of intrapleural lytics
Very hemorrhagic fluid at baseline
Disease with hemorrhage risk e.g. RCC with lung mets
Anticoagulation that cannot be stopped
Note: Anticoagulation increases risk to 10% (overall risk 4%) but half dose did not change risk
RFs for enzyme related bleeding
Concurrent administration of anticoagulation
Elevated RAPID score
Plt count <100,000
Sites of pneumomediastinum
Alveolar sacs (most common)
Tracheobronchial tree
Esophageal
Bowel rupture
Physical examination findings of pneumomediastinum
Hamman’s crunch (crunching with each heart beat or mediastinal crunch)
Subcutaneous emphysema
High pitched voice
Image findings of esophageal rupture
Pneumomediastinum - air around the mediastinum
Widened pneumomediastinum
Pneumothorax
Pleural effusion
Subcutaneous emphysema
Air under the diaphragm
What are the causes of spontaneous pneumothorax (categories)
Catamenial
Primary
Secondary
Causes of primary pneumothorax
Asthenic body habitus
Subpleural blebs
Smoking - cigarettes, marijuana, snorting cocaine
Diving
Causes of secondary pneumothorax
Bullous lung disease
LAM
PLCH
COPD
Asthma
Bronchiectasis
Thoracic endometriosis
Ehler Danlos, Marfans
RF for tension pneumothorax development
Traumatic pneumothorax
Post CPR pneumothorax
On NIV or mechanical ventilation
Blocked or kinked chest tube
Hyperbaric oxygen treatment
Underlying lung disease
Mechanisms of hypotension in tension pneumothorax
IVC compression → reduced RV preload
RV compression → reduced LV preload
Increased LV afterload
Increased RV afterload
Imaging findings in a tension pneumothorax
Visible lung edge
Shifting of mediastinum, deviated trachea
Splaying of the ribs
Adequate size for intervention for a pneumothorax
> /2 cm laterally or apically on CXR
If using CT, any size that can safely be accessed with imaging support
Note PSP can often monitor regardless of size
Borders of the triangle of safety
Lateral edge of pectoralis muscle
Lateral edge of latissimus dorsi
Fifth intercostal space/nipple line/breast line (base of breast tissue)
Base of axilla
High risk features in the treatment algorithm of pneumothorax
Underlying lung disease aka Secondary pneumothorax
Age >/50, smoking history
Bilateral pneumothorax
Hemopneumothorax
Tension pneumothorax/hemodynamic compromise
Significant hypoxemia
Indications of applying suction for a pneumothorax
The pneumothorax increases in size despite chest tube insertion
Fails to improve after 24-48 hours
There is persistent air leak
Percentage of pneumothorax that resolves per day
1.25 - 2.2% per day
Increased by 4-6X via oxygen
Indications for a surgical consultation in pneumothorax
Recurrent pneumothorax, ipsilateral or contralateral
First pneumo BUT:
- SSP and significant physiological compromise
- Tension pneumothorax/hemodynamic compromise
- Spontaneous hemothorax
- Bilateral pneumothorax
- Persistent air leak 5-7 days, or lung fails to re expand
- Pregnant
- High risk occupation
What surgical technique is preferred for pneumothorax
VATS > thoracotomy
Can do any: bullectomy, pleurectomy, mechanical pleurodesis, chemical pleurodesis
When would you consider non surgical but definitive management, e.g. talc slurry?
Unwilling to do surgery
Unable to do surgery
This is because surgical options more effective
Recurrence rate for pneumothorax
PSP → 33%
SPS → 13-39%
After first recurrence → 60%, after second recurrence → 80%
Causes of persistent air leak
Conditions: Pneumothorax, Barotrauma, Infections, Malignancies
Procedures: wedge biopsies, lobectomy, LVRS, trauma
Treatment options for persistent air leak
Treat underlying infection
Add suction
Second chest tube or bigger chest tube
Blood patch
Chemical pleurodesis
Surgical options
Recommendations re: activities post pneumothorax
No PFTs x 2-4 weeks
No flying until resolved at least x 1 week, but can be longer especially if underlying lung disease (Canadian Association of Thoracic Surgeons recommend 1-3 weeks)
No diving ever
Management of bronchopleural fistula volume of leak in a vented patient
Reduce Pplat
Reduce autoPEEP → increase expiratory time, reduce Vt, permissive hypercapnia
Causes of malignant pleural masses
Mesothelioma
Metastases
Lymphoma
Malignant fibrous tumour
Askin tumour (same as ewing sarcoma, chest wall tumour and is malignant)
Sarcoma
Extraskeletal osteosarcoma
What type of malignancy is primary effusion lymphoma?
Usually diffuse large b cell lymphoma
Usually no associated lymphadenopathy
DDX for malignant effusions in patients with HIV
Lymphoma
Primary effusion lymphoma
Kaposi sarcoma
Other cancers
Most common causes of pleural metastases
Lung (adeno)
Breast
Lymphoma
GI/GU
Where in the pleural do malignancies usually start?
Mets - visceral pleura
Meso - parietal pleura
Non malignant causes of pleural masses
Solitary fibrous tumour of the pleura
Lipoma
Mesothelial cyst
Pleural endometriosis
Pleural plaques, thickening (not really masses)
What are the associated paraneoplastic syndromes with solitary tumour of the pleura?
Hypoglycemia, Doege-Potter syndrome (elevated IGF)
Hypertrophic pulmonary osteoarthropathy
Concerning features of pleural malignancy on imaging
Thickness > 1 cm
Circumferential thickening
Involvement of the mediastinal pleura
Diaphragmatic thickening > 7
Nodular thickening
Sensitivity of pleural fluid for malignancy
Overall, 60%, increase by 15% with the second tap (MAM paper says 20%)
Adenocarcinoma 80%
Breast 70%
Small 50%
Mesothelioma 30%
Squamous cell 20%
Definition of non expandable lung in MPE
> /25% of the lung is not opposed to the chest wall
Is based on CXR
Treatment for MPE
Aspiration has shorter LOS but more need for intervention
IPC vs chest tube with talc slurry or poudrage
Management of MPE in mesothelioma
Talc poudrage preferred
Other options IPC, slurry, PP
Benefit of MPE management
Improved dyspnea
Improved QOL
Agents for pleurodesis
Talc
Doxycycline
Bleomycin
Rate of spontaneous pleurodesis once an IPC is inserted
25%
Clinical factors suggest will gain improvement with IPC
Improvement after therapeutic thoracentesis
Rapid reaccumulation
Prognosis is >1 month
Supports to have home care
Possible side effects from pleurodesis
Chest pain
Fever
ARDS
Treatment of infected/loculated MPE with IPC inserted
Abx
Intrapleural enzymes
Intrapleural normal saline
Extra chest tube
Surgical - VATS, decortication
How long after asbestos exposure does mesothelioma occur?
~40 years after exposure
3 main subtypes of mesothelioma
Epithelioid
Biphasic
Sarcomatoid (worst prognosis)
Causes of mesothelioma
Asbestos (?dose response)
Erionite fibers
Thoracic radiation
SV40 infection, other viral infections
Chronic pleural disease
Imaging features are concerning for mesothelioma
Pleural thickening with concerning features (see previous)
Presence of asbestos exposure
Local invasion - chest wall, mediastinum, diaphragm, ribs
Usually unilateral changes, usually right side predominance
Spreads along pleura and fissures
Starts at parietal pleura
Diagnosis of mesothelioma
Image guided biopsy
Medical pleuroscopy
Surgical pleuroscopy/VATS
Management of mesothelioma
Double immunotherapy - ipilimumab + nivolumab (previously was chemo, but studies show immunotherapy better)
Debulking surgery if candidate (epithelioid and ECOG 0-1)
Both improve survival
SMART TRIAL NEGATIVE (For radiating ports after BUT trend to significance so maybe underpowered)
remuniration and palliative care
Poor prognostic markers in mesothelioma
Histology (Sarcomatoid worst)
Stage
Age
Poor performance status
Malignant causes of lymphangitic carcinomatosis
Cervical
Colon
Stomach
Breast
Prostate, pancreas
Thyroid
Lung
Mneumonic: certain cancers spread by plugin the lymphatics
Diagnosis of lymphangitic carcinomatosis
Biopsy - TBBx or surgical
Histological findings of lymphangitic carcinomatosis
Obstruction and distension of lymphatics by tumour cells
Treatment of lymphangitic carcinomatosis
Treat underlying cancer
Steroids, but no clear data
Opioids for symptom control
How many segments are there in each lobe of the lung?
RUL: 3
RML: 2
RLL: 5
LUL: 5
LLL: 5 or 4
Equations for PPO lobectomy and pneumonectomy
Lobectomy PPO FEV1 = FEV1 x [1 - (resected segments/19)]
Pneumonectomy = PPO FEV1 = FEV1 x [1 - fraction of perfusion to resected lung]
Using absolute value
Both greater than 60→ Low risk
30-60% stair climb or shuttle walk
Any < 30% then CPET
Examples of important post operative complication predictors
VO2 max
FEV1
DLCO
In place of CPET can use stair climb or shuttle walk.
In post operative planning, what are the cutoffs for SWT and stair climbing? Low technology exercise test.
SWT <400 m
Stair climb <22m
In post operative planning, what are the cutoffs for VO2 max?
<10 mL/kg/minute (<35%)→ high
10-20 → moderate (35-75%)
>20 (>75% predicted) → low
Patient factors that increase post op complications from non-pulmonary surgery
Age
Smoking
ASA class
OSA
COPD (especially if FEV1 <60%)
Pulmonary hypertension
Low albumin
Obesity is not a risk factor
Surgical factors that increase post op complications from non-pulmonary surgery
Aortic > intrathoracic > upper abdominal > abdominal
Duration of surgery
Emergency surgery
General anesthesia (epidural better)
Paralytics
How can post operative complications be prevented?
Optimize underlying lung disease prior to surgery
Smoking cessation (>8 weeks previous surgery)
Avoid GA if possible; regional blocks if possible
Avoid long acting neuromuscular blockade
Shorter surgery (<3 hours)
Laparoscopic
CPAP if OSA
Lung expansion techniques
Pain control
Physiological changes that occur after a pneumonectomy
FEV1, FVC, lung volumes, DLCO decrease
Decrease compliance
Increased resistance
Dead space can increase or decrease
RV EF reduces, LV function does not change
No change in blood gasses
What normally happens to the post pneumonectomy space?
Fills with air, then with fluid
Complete opacification takes 4 months
Post pneumonectomy complications
Post pneumonectomy syndrome
Post pneumonectomy empyema
Bronchopleural fistula
Esophagopleural fistula
Pulmonary embolism
Pneumothorax
Hemorrhage
Arrhythmias, MI
When does post pneumonectomy syndrome occur and what is it?
After 6 months following surgery
Almost exclusively after right sided pneumonectomy
(it is excessive mediastinal shift/rotation resulting in compression and stretching of the tracheobronchial tree and the esophagus)
When does post pneumonectomy pulmonary edema occur?
Within 72 hours
Non cardiogenic edema/ARDS
More common during right vs left
RFs for post pneumonectomy pulmonary edema
Right sided resection
Large perioperative fluid load
Single lung ventilation
High inspired O2 concentrations
Inclusion criteria for NSLT?
Age 55-74
Current smoker or quit within the last 15 years
Has at least 30 pack year smoking history
Experienced centers
Exclusion criteria for NSLT?
Lung cancer
Hemoptysis
Lost >/15 lb in the last 1 year
Chest CT in the prior 18 months
Key differences between the NLST and NELSON trials
Different proportion of males/females
Inclusion criteria
Nodule management protocol - diameter vs volume
Control comparison - CXR vs nothing
Follow up - different # and intervals
What are the IHC stains for the different cancers?
Adenocarcinoma: TTF1 (if negative but adeno much worse prognosis)
Squamous cell: CK5/6. P63
Small cell: TTF1 but also neuroendocrine markers (chromogranin, CD56, synaptophysin)
General features of different lung cancers
Small cell - usually central, small primary, usually arises in airways, early mets
Squamous cell - usually central, bulky lesion, may cavitate
Adenocarcinoma - usually peripheral
RFs for lung cancer
Smoking
Exposures - nickel, radon, asbestos, silica, beryllium, pollution
Underlying conditions - IPF, scleroderma-ILD, COPD, HIV
Radiation exposure
Health Canada recommendations in regards to radon
If >200, have to hire professional
If 200-600, have 2 years to fix
If >600, have to fix within 1 year
Clinical manifestations of superior sulcus tumour
SVC syndrome (more common if R)
Horner’s syndrome (T1)
Brachial plexus injury (C8, T1, T2)
Recurrent laryngeal nerve involvement (more common if L)
Also called a pancoast tumour
Neurological findings in superior sulcus tumour
Miosis, ptosis, anhidrosis
Laryngeal nerve dysfunction
Ulnar nerve distribution abnormalities/brachial plexus involvement
Cerebral edema
Also called a pancoast tumour
Physical exam findings in SVC syndrome
Confusion 2/2 cerebral edema
Facial plethora, Proptosis
Facial and neck edema
Elevated JVP
Collateralization of superficial vessels
Cyanosis, hypoxemia
Causes of SVC syndrome
Malignancy - lung ca, lymphoma
Thrombosis
Indwelling intravascular device
Post radiation fibrosis
Fibrosing mediastinitis
External compression from sarcoidosis, thyroid goiter
Management of SVC syndrome
Emergency → stent; radiation if not surgical candidate
Steroids if already have answer, steroid responsive
Anticoagulation if thrombosis
Chemotherapy if applicable
Paraneoplastic syndromes are associated with lung cancer
Encephalitis
LEMS
Cushing’s syndrome
Hyponatremia
Hypercalcemia
Hypertrophic pulmonary osteoarthropathy (Triad: digital clubbing, periostitis (new bone growth on the bones), and arthropathy)
Rashes - dermatomyositis, acanthosis nigricans, erythema multiforme, pruritus, urticaria
Imaging and clinical findings of hypertrophic pulmonary osteoarthropathy
Bone scan - Symmetrical, increased linear uptake along diaphyseal and metaphyseal surfaces of long bones
XR - smooth periosteal reaction
Triad: digital clubbing, periostitis (new bone growth on the bones), and arthropathy
Paraneoplastic syndromes are associated with thymoma
Myasthenia gravis
Red cell aplasia
Cushing’s syndrome
Addison’s disease
Mechanisms of hypercalcemia in malignancy
Bone metastases
PTHrP
Granulomas increasing 1,25 vitamin D
Ectopic production of PTH e.g. parathyroid carcinoma
Where can lung cancer metastasize to?
Brain
Pleura
Adrenals
Liver
Bone
Bone marrow
Lung cancers that usually cause hemoptysis
Squamous cell carcinoma
Carcinoid tumour
Kaposi sarcoma
Lymph node stations and their borders
Superior mediastinal nodes
1: Highest mediastinal
2R inferior border innominate/brachiocephalic vein). 2L Inferior border aorta on left
3: prevascular adn retrotracheal
4R Upper Border innominate/brachiocephalic. Inferior azygos vein. 4L upper border Aortic arch and inferior Pulmonary artery
Aortic nodes
5: subaortic
6 para aortic
Inferior mediastinal nodes
7 subcarinal
8 paraesophageal nodes
9 pulmonary ligament nodes
Hilar nodes, lobar and subsegmental nodes
10 hilar nodes : 10R azygus 10L Pulmonary Artery
11 Interlobular: 11s between upper lobe bronchus and bronchus intermedius. 11i between the middle and lower lobe bronchi
12 lobar: adjacent to lobar bornchi
13 segmental nodes: adjacent to segmental bronchi
14 sub segmental: adjacent to subsegmental bronchi.
Suspicious features of lymph nodes?
Canada Lymph node score:
Clear margins
Loss of central hilar structure
Central necrosis
Short axis diameter >/1 cm
Also known as Canada Lymph Node Score
What stations can be accessed by different methods
Molecular markers for adenocarcinoma
EGFR (15% of canadians with adeno)
ALK
ROS1
PDL-1
BRAF
Molecular markers for squamous
PDL-1
Who requires brain imaging?(In Lung Ca)
Clinical signs or symptoms concerning for brain metastases
Clinical stage II, III or IV non small cell lung cancer
Maybe IB but definitely not IA
When would you consider staging the mediastinum
- Discrete mediastinal node enlargement, no distant mets
- Node SUV >/2.5
- Peripheral tumour BUT:I nner ⅔ of lung (more central); >/3 cm = greater than T1; Associated with enlarged mediastinal LN >1 cm
- Central tumour: Radiographically enlarged or PET avid nodes
When would you NOT need to do mediastinal staging?
Peripheral T1N0 disease not meeting criteria above
Bulky tumour invading mediastinal structure - need tissue, but does not need to be from nodes
Metastatic disease - biopsy whatever gives you highest stage
Sensitivity and specificity of CT, PET, EBUS, mediastinoscopy for mets
CT: sp 80/sn 55
PET: sp 85/sn 80
EBUS: sp 100/sn 90 (ONLY 55% for LYMPHOMA but sp 100%)
Mediastinoscopy: sp/100/sn 80
Treatment for SCLC
Limited
- Chemo + radiation followed by adjuvant immunotherapy
- If good response and normal brain MRI can do prophylactic cranial radiation
- If VERY Limited consider surgery
Extensive
- Chemo + immunotherapy
- Immunotherapy adds 2-3 months of survival
- Cranial Radiation
Indications for cranial radiation in SCLC
- Prophylaxis
- Limited stage, good response to chemo
- Extensive stage - Evidence of brain mets
Benefits of prophylactic cranial rad in SCLC
Limited disease: decrease brain mets, improve survival
Extensive disease: decrease brain mets, no change in survival ? (Lancet review 2024 says PCI is associated with survival benefit but when factor in MRI to exclude brain mets then this benefit disappeared suggesting more therapeutic benefit rather than prophylactic)
Indications for cranial radiation in NSCLC
Brain mets with no targeted mutations
Otherwise, we use targeted therapy and if symptomatic/risk herniation, surgical
Treatment for NSCLC
Possible side effects of immunotherapy
Cutaneous/rash
Uveitis
*Pneumonitis
Hypothyroidism, hyperthyroidism
*Hepatotoxicity
*Colitis, diarrhea
Pancreatitis
*all
EGFR -Rash/acne
ALK -Cardiac (Bradycardia, HTN)
When does checkpoint inhibitor toxicity usually occur?
Median 3 months, can be up to 19 months
When should you discontinue checkpoint inhibitor permanently after pneumonitis?
G3 or higher
Checkpoint inhibitor lung related toxicity
Immune related pneumonitis
Radiation recall pneumonitis
Grading of Immune therapy toxicity and treatment.
Grade 1: Asymptomatic with radiographic changes
Grade 1: Continue therapy with close observation, escalate to treatment for symptoms or radiographic worsening
Grade 2: Symptomatic but no limitation of usual activity
Grade 2: Hold therapy, consider bronchoscopy, institute oral prednisone 1 mg/kg/day if no improvement
Grade 3: Symptomatic, with oxygen requirement or limitation of activity
Grade 3-4: Discontinue therapy, bronchoscopy, institute oral prednisone 1-2 mg/kg/day or IV corticosteroids at equivalent dose
Grade 4: Severe or life-threatening
Side effects of tyrosine kinase inhibitors (ex. dasatinib)
Cutaneous, rash
Ocular toxicity
Pulmonary - pneumonitis
Colitis, diarrhea
Hepatic toxicity
Side effects that should lead to permanent discontinuation of tyrosine kinase inhibitors
Confirmed ILD as a result
Ulcerative keratitis
GI perforation
SJS, severe skin disease
Treatments for bony met pain
Opioids, NSAIDs
Bisphosphonates, denosumab - osteoclast inhibitors
Radiation
Steroids
Regional anesthesia
Pathological types of adenocarcinoma spectrum of disease
- Atypical adenomatous hyperplasia
- Adenocarcinoma in situ (<3cm and formerly BAC)
- Minimally invasive adenocarcinoma (<3cm lepidic predominant with <5mm invasion)
- Invasive adenocarcinoma (>5mm)
- Lepidic
- Acinar
- Micropapillary
- Papillary
- Solid predominant - Variants of invasive
- Invasive mucinous
- Colloid
- Fetal
Radiographic abnormalities for adenocarcinoma spectrum
Solid nodule
GGO nodule, subsolid nodule
Mass
Multiple pulmonary nodules
Patchy consolidation, lobar consolidation
Crazy paving
Differences between typical and atypical NETS
DIPNECH = preinvasive - <5 mm
Typical = > 5 mm, <2 mitoses/10 HPF, no necrosis
Atypical: 2-10 mitosis or necrosis
SCLC: >11/10 mitoses HPF
Clinical manifestations of carcinoid tumors
Dyspnea, wheeze
Hemoptysis
Carcinoid syndrome - flushing ,telangiectasias, diarrhea
Cushing syndrome
Acromegaly syndrome
Investigation options in carcinoid tumors
Serum chromogranin A
5-HIAA
Somatostatin receptor based imaging e.g. OctreoScan, Gallium
PET - low grade/typical only weakly positive
Bronchoscopy features of carcinoid tumour
Mainly proximal airways
Well vascularized
RFs for malignant nodules
Number - increased 1-4, decreases >/5
Size
Doubling time 20-400 days
Enhancement
Appearance - subsolid, spiculated, lobular, Carona Radiata (LR 14)
Calcification pattern
Location - upper lobe
Evidence of emphysema
Smoking history
Usually benign patterns of calcification
Diffuse
Central
Lamellar
Popcorn
Causes of a negative PET scan
Less metabolically active tumors
Solid component <8 mm
Uncontrolled hyperglycemia
Who do the Fleischner Society Guidelines apply to?
> /35 years old
Not immunocompromised
No history of cancer
Not for cancer diagnosis (applies to incidentally found nodules)
No symptoms attributable to lesion
Low vs high risk by the Fleischner Guidelines
Low: minimal or absent smoking hx or other RF
High: hx of smoking or other known RF (e.g. fhx first degree, asbestos/radon/uranium exposure)
How long do pulmonary nodules need to be followed?
Solid nodules - 2 years
Subsolid nodules >/5 years
DDX for benign pulmonary nodules
Infectious nodules
Inflammatory, vasculitic
Vascular (AVM)
Hamartoma
Hemangioma
Fibroma
Lipoma
Leiomyoma
Amyloidoma
Radiographic features of a hamartoma
Popcorn calcification
Heterogeneous attenuation
Rounded or lobular borders
Difference between teratoma and hamartoma
Teratoma occur in anterior mediastinum
Teratoma also include teeth and bone
Teratomas may become malignant
Draw out the TNM 8th edition and 9th edition.
Draw out the Fleishner Society Nodule Chart.
Sources of asbestos exposure
Pipefitter
Plumbers
Motor vehicle mechanic
Construction worker
Shipyard worker
Different types of asbestos fibers
Serpentine (long) and amphibole (short) are the two general types
1. Serpentine
* Chrysotile (most common)
2. Amphibole
* Actinolite
* Anthophylllite
* Amosite
* Tremolite
* Crocidolite (Most dangerous/highest risk of mesothelioma)
RFs for developing asbestosis
Exposure at a young age
Duration and extent of exposure
Amphibole > chrysotile
Concomitant smoking
Pulmonary manifestations of asbestos
Rounded atelectasis
Asbestosis
Pleural plaques
Pleural thickening
Benign asbestos related pleural effusion
Mesothelioma
Imaging findings of asbestosis
Lower lobe distribution
Reticular changes
Rounded atelectasis
Pleural plaques
Honeycombing and interlobular septal thickening
Lower lobe distribution
Reticular changes
Pathological findings of asbestosis - How is it different from UIP?
2 or more asbestos bodies per square centimeter of a 5-mu thick lung section in combination with interstitial fibrosis are indicative of asbestosis
Asbestos has presence of asbestos bodies
Has mild fibrosis of the visceral pleura
Fibroblastic foci are infrequent
How do you diagnose asbestosis?
ATS 2004 need 3/3
2. 1. Evidence of structural change as demonstrated by one or more
* Imaging
* Histology
1. Evidence of exposure/cause
* occupational/environmental history with latency
* Markers of exposure (pleural plaques)
* Asbestos bodies
1. Exclusion of other diagnosis
What is the treatment of asbestosis?
Supportive care:
* Steroids pred 0.5-1mg/kg for 1-3 months then taper for 1-3 months and steroid sparing agents can be used but unclear benefit.
* Smoking cessation and co-existing airways disease treatment
* Immunizations
* Oxygen
* decortication
* Lung transplant
Where do pleural plaques usually occur?
Bases (posterolateral) and mediastinal pleura
Can also involve the diaphragm
Spares apices and costophrenic angles
May be calcified but most are not
What is the CT definition of pleural thickening?
In general >3 mm thick
Fluid features of BAPE
Exudative
Eosinophilic usually
Can be bloody
Usually spontaneously resolves, can recur
Occupations with beryllium exposure
Electronics
Nuclear industry, nuclear weapons
Aerospace industry
Fluorescent light bulbs
Beryllium mining
Ceramics
Routes of sensitization for beryllium
Inhalation
Skin
Pulmonary manifestations of berylliosis
Acute pneumonitis
Chronic beryllium disease
Non pulmonary manifestations of berylliosis
Conjunctivitis (no uveitis, or retinal involvement unlike sarcoid)
Periorbital edema
Nasopharyngitis
Tracheobronchitis
Imaging findings of berylliosis
Acute pneumonitis: ARDS, non-cardiogenic pulm edema
Chronic beryllium disease: sarcoid but LN less likely
Biopsy findings of CBD (chronic berylliosis disease)
Typically on TBBx
Granulomas
Distribution paraseptal, interlobular septa, peribronchovascular
Diagnostic criteria of CBD (chronic berylliosis disease)
Positive BeLPT (blood or BAL) (Beryllium lymphocyte proliferation test)
Non caseating granuloma and/or mononuclear cells on biopsy
Clinical dx if no bx: BAL lymphocytosis or imaging
Definition of positive BeLT (Beryllium lymphocyte proliferation test)
1 BAL BeLPT
2 blood BeLPT
Positive skin patch sensitization test (DON’T do because can lead to sensitization in beryllium naive individuals)
+2 Simulation Indices =abnormal BeLPT , + 1 Simulation Indices =borderline
Difference between beryllium sensitization and Chronic Berylliosis disease)
Sensitization: sensitization, no sx, normal biopsy
Subclinical: sensitization, + biopsy, no sx/rads
CBD: sensitization, + biopsy, +sx/rads
Treatment of CBD
Observe
Steroids if symptoms or PFT change with consideration for steroid sparing agents if not tolerated
Pulmonary manifestations of silicosis
Acute silicoproteinosis
Accelerated proteinosis
Chronic, simple silicosis
Complicated silicosis, progressive massive fibrosis
Complications of silicosis
Tuberculosis, NTM
Lung cancer
CTD/Erasmus syndrome (Systemic Sclerosis)
PAP
Fibrosing mediastinitis
Radiographic manifestations of silicosis
Crazy paving
Perilymphatic nodules and upper lobe
Mediastinal and hilar LN, eggshell calcification
Progressive massive fibrosis
Hyperinflation, COPD
Cavitary lung disease
Ground glass nodules/opacities
Diagnosis of silicosis
Exposure history
Imaging findings
BAL if silicoproteinosis
Biopsy avoided due to PNTX risk
Treatment of silicosis
Acute → steroids
Chronic → supportive
Pulmonary manifestations of CWP
Simple chronic CWP
Complicated CWP, progressive massive fibrosis
Caplan syndrome (rheumatoid pneumoconiosis)
Not associated with lung cancer unlike others
Imaging findings of CWP
Crazy paving
Perilymphatic nodules
Mediastinal and hilar LN, eggshell calcification
Progressive massive fibrosis
Hyperinflation, COPD
Cavitary lung disease
(eggshell less common )
Similar as above, but eggshell less common
Typically diffuse perilymphatic small nodules
30% have hilar/mediastinal lymph node enlargement but calcification less likely
Examples of hard metal lung disease
Cobalt related lung disease
Siderosis (iron dust)
Metal fume fever (zinc fumes)
Lung diseases that are associated with cobalt exposure
Occupational asthma
Interstitial lung disease - giant cell interstitial pneumonia
Obliterative bronchiolitis
Inorganic and organic inhalational causes of pneumoconiosis
Inorganic: coal, silica, beryllium, asbestos
Organic: cotton, tobacco, sugarcane, basically anything can cause HP
Pulmonary manifestations of byssinosis
Airway obstruction
Uniquely worse on the first day of work and then improves
Typically with raw cotton exposure
Causative agent of Silo Filler’s disease
Silo gas = combination of nitrogen dioxide and carbon dioxide
Nitrogen dioxide + water in lungs → nitric acid
Pulmonary manifestations of silo filler’s disease
ARDS
Obliterative bronchiolitis
Exposures associated with lung cancer development.
Uranium mining
Beryllium
Asbestos
Silica
Causes of PMF?
Sarcoidosis
Berylliosis
Silicosis
CWP
Talcosis
CTD causes of UIP
RA
SSc
SLE
DM/PM
Extraparenchymal findings on CT that suggest CTD-ILD
Esophageal dilatation
Pleural or pericardial effusion
Lymphadenopathy
C1-2 subluxation
RFs for development of RA-ILD
Male
Older
Smoking
RF positive
Anti-CCP positive
Disease activity
MUC5B
RFs for RA pulmonary nodules
Subcutaneous nodules
Longstanding RA
RFs for RA pleural effusion
Male
Older age
Rheumatoid nodules
Pulmonary manifestations of RA
RA-ILD - UIP, NSIP, LIP, OA, CPFE
Diffuse alveolar hemorrhage
RA pulmonary nodules
Caplan syndrome
Pulmonary hypertension
Pleural effusion
Pneumothorax
Follicular or obliterative bronchiolitis
Bronchiectasis
Cricoarytenoid arthritis
Vasculitis of vocal cords
RA nodules on vocal cords
Imaging features of RA related lung disease
Nodules
Cavities
Pleural effusions
Pneumothorax
Bronchiectasis
UIP pattern or others
Findings of PH e.g. edema, enlarged heart, etc.
BAL cell count and differential in RA-ILD
Lymphocytic in NSIP
Neutrophilic in UIP
Treatment of RA related lung disease
RA-ILD: steroids, MMF, cyclophosphamide, antifibrotics
Bronchiectasis: same as others
Bronchiolitis: treat RA, consider azithromycin
What are pulmonary manifestations of scleroderma?
ILD - NSIP, UIP, OP, PPFE
Pulmonary hypertension, PVOD
Airway disease - follicular/obliterative bronchiolitis, bronchiectasis
Aspiration pneumonitis or pneumonia
Lung cancer
Chest wall restriction
Features associated with early development of SSc-ILD
African american
Extensive disease
Scl-70 positive
CK elevated
Cardiac involvement
Hypothyroidism
eatures associated with SSc-ILD progression
Extent - >20% of lung involved
FVC <70% predicted
Within 4 years of diagnosis
Anti scl-70
Diffuse cutaneous disease
Treatment of SSc-ILD
Mycophenolate
Cyclophosphamide
Tocilizumab
Rituximab
Nintedanib
Nintedanib + mycophenolate
Benefits and evidence of SSc-ILD management options
Improve FVC, DLCO → Mycophenolate and cyclo
Reduce decline in FVC → ritux, toci, nintedanib
Nothing has mortality benefit
How often should patients with SSc-ILd be followed?
6 months x 5 years
Annually after 5 years (if they were stable
Pulmonary manifestations of myositis
ILD - NSIP, UIP, OP, DAD
Respiratory muscle weakness
Aspiration pneumonia
Pneumothorax
Pulmonary hypertension
Antisynthetase syndrome
- 2 of:
- Fever
- Raynaud
- Mechanics hands/hiker’s feet
- Polymyositis
- Non-erosive arthritis
- ILD - Positive autoantibody (Anti-Jo-1)
Treatment options for myositis-ILD
Cyclo if very sick
MMF, azathioprine
Pulmonary manifestations of lupus
Interstitial lung disease - NSIP, UIP, LIP
Acute pneumonitis (similar to AIP)
Organizing pneumonia
DAH
Pleural effusion * most common
Shrinking lung syndrome
VTE
Pulmonary hypertension - PVOD, PAH, Group 2,3,4
Subglottic stenosis, tracheal stenosis
Bronchiolitis obliterans
Opportunistic infections
Skin manifestations of lupus
Acute cutaneous lupus erythema
Panniculitis
Discoid lesion
Childpain lupus erythematosus (pernio)
Pulmonary manifestations of Sjogren’s syndrome
Interstitial lung disease - e.g. NSIP, LIP, UIP
Organizing pneumonia
Bronchiolitis - follicular, obliterative
Bronchiectasis
Xerotrachea
Aspiration pneumonitis and pneumonia
Pulmonary hypertension
Nodular hyperplasia
Pulmonary nodular amyloidosis
Pulmonary lymphoma (transformation)
Pulmonary manifestations of amyloidosis
Nodular pulmonary amyloidosis
Diffuse amyloidosis
Tracheobronchial amyloidosis
Amyloidosis of the pleura
Clinical Features of patients with CTD-ILD (SARD-ILD)
ACR 2023 Screening guidelines for SARD-ILD
How to screen people with SARD of interest?
What are the first line therapies by disease type according to ACR 2023?
Management of Rapidly progressive ILD.
Skin manifestations that may be seen in vasculitis
Palpable purpura
Leukocytoclastic vasculitis
Lacrimal gland inflammation
Skin ulcerations
?saddle nose deformity
?stawberry gums (gingivitis)
Differential diagnosis for ANCA elevation
Vasculitis
CTD
Malignancies
Infections - hepatitis B/C/HIV
Drug induced (PTU, methimazole, hydralazine, allopurinol)
IBD
% of ANCA elevation in different conditions
GPA - 90% c anca/ PR3
MPA - 70% p anca/mpo
EGPA - 50% p anca/mpo
Anti-GBM - 10%
Classic triad of DAH
Hemoptysis
Anemia
Alveolar opacities
DDX of DAH
1.Vasculitis
- GPA
- EGPA
- MPA
- Drug induced vasculitis
2. Connective tissue diseases
- SLE
- Anti-GBM
- Rheumatoid arthritis
- Scleroderma
- Others
3. Drugs
- TNF-alpha inhibitors
- Hydralazine
- Anticoagulation
- GPIIb/IIIa platelet inhibitors
- Amiodarone
- Crack cocaine
4. Others
- IPH Idiopathic pulmonary hemosiderosis
- Left sided pressure increase e.g. mitral stenosis
- HHT hereditary hemorrhagic telangiectasias
BAL findings of DAH
Hemosiderin laden macrophages >/20%
Progressively bloody sequential lavage
ANCA + vasculitis that cause DAH
GPA
MPA
EGPA (very rarely)
Drug induced ANCA vasculitis
Isolated pulmonary capillaritis
Anti-GBM/ANCA positive vasculitis
DDX for pulmonary renal disease
Anti-GBM
GPA, MPA, EGPA
ANCA negative vasculitis e.g. cryo, IgA disease
SLE
RFs for GBM development
Smoking
Cocaine use
Hydrocarbon fume exposure
Hair dye exposure
Metallic dust
Genetics
Sensitivity and specificity of anti-GBM
Sensitivity 95-100%
Specificity 90-100%
Causes of false positive anti-GBM
Hepatitis C
HIV
Poor prognostic factors in anti-GBM
Advanced age
Anti-GBM titre
Renal function - crea & need for dialysis at presentation, oligoanuric, % crescents (only pathological parameter)
Treatment of anti-GBM
Steroids, cyclophosphamide
PLEX
No maintenance
Abx if pulmonary involvement
Role of anti-GBM in disease monitoring
Monitor regularly (Weekly for 6 weeks and should be undetectable x2 occasions then q2weekly x2, then monthly x 6 months
Should disappear with treatment
May signal recurrence (re-treat)
Pulmonary manifestations of GPA
Wedge shaped opacities due to infarction
Nodules
Cavities
Interstitial lung disease - NSIP, UIP
Diffuse alveolar hemorrhage
Subglottic or tracheal stenosis
Tracheobronchomalacia
Extrapulmonary manifestations of GPA
Cutaneous - palpable purpura, leukocytoclastic vasculitis
ENT - hearing loss, sinusitis, nasal septal perforation, saddle nose, nasal ulcers
Renal - GN, renal failure
Systemic symptoms
Diagnostic criteria of GPA
What is the treatment for GPA?
What is considered a severe vs non severe GPA?
Severe = organ threatening disease
E.g. RPGN, DAH, mononeuritis multiplex, optic neuritis
What are indications to use cyclophosphamide over rituximab in induction treatment?
RPGN with crea >354
if not available
What are indications in which PLEX Is needed in GPA/MPA?
RPGN crea >500, need for dialysis (KDIGO)
DAH salvage therapy
Double positive (with Anti-GBM)
Indications in which PLEX is indicated for DAH
Anti-GBM disease
Anti-GBM/ANCA double positivity
DAH salvage therapy, critically unwell
TTP related DAH
Catastrophic APLS DAH
PEXIVAS trial re: PLEX in ANCA vasculitis
No mortality benefit
No impact on ESRD (trend towards improving ESRD progression in high risk patients)
Increased risk of infection
General differences between MPA and GPA
p-ANCA (in MPA)
Mainly renal, less ENT, less pulmonary (in MPA)
Absence of granuloma formation (In MPA)
What is the diagnostic criteria for MPA
What vasculitis is associated with PA aneurysms?
Behcet’s disease (vasculitis with mouth ulcers, swollen joints and eye inflammation)
Hugh Stovin syndrome (large vessel similar to Behcet’s) M 20-40 with dvt and bronchial aneurysms.
Pulmonary hypertension
Congenital heart disease
Syphilis
Tuberculosis
Behcet’s disease
Hugh Stovin syndrome
Congenital heart disease
Syphilis
Tuberculosis
DDX of pulmonary angiitis and granulomatosis
Bronchocentric granulomatosis
Lymphomatoid granulomatosis
Necrotizing sarcoid granulomatosis
GPA, EGPA
Non-pulmonary clinical manifestations of EGPA
Asthma /obstructive airways disease
Peripheral nerve (mononeuritis multiplex)
Skin disease (purpura, sub cutaneous nodules, urticaria, leukocytoclastic vasculitis)
ENT (Nasal polyps), cardiac: effusions, dilated CM, GI, renal
What is the diagnostic criteria for EGPA
What is the management of EGPA
Five factor score
Age >65
Cardiac insufficiency
Renal insufficiency
GI involvement
Absence of ENT symptoms
For prognosis and higher score associated with higher mortality
Monitoring in management of EGPA and GPA
EGPA - ESR and eos count TTE (Don’t stop leukotriene receptor antagonists)
GPA - not ANCA
What is the KDIGO 2024 treatment algorithm for Anca Associated Vasculitis
Non-infectious complications of illicit drug use
Eosinophilic pneumonia
Hypersensitivity pneumonitis
Organizing pneumonitis
Obliterative bronchiolitis
Pneumothorax
Pneumomediastinum
Drug induced ANCA vasculitis, DAH
Pulmonary hypertension
Alveolar hypoventilation
Aspiration
Foreign body granulomatosis
Non cardiogenic pulmonary edema
E-VALI
Complications associated with vaping
Lipoid pneumonia*
Eosinophilic pneumonia
Organizing pneumonia
Hypersensitivity pneumonitis
AIP, ARDS
VALI
Causative agent of vaping induced injury
Vitamin E acetate in e-liquids
Diagnostic criteria for EVALI
E cigarette use in 90 days before symptoms
Pulmonary infiltrates
Negative viral panel, negative cultures, negative other workup
IST that are not teratogenic
Azathioprine (purine synthesis inhibitor)
Hydroxychloroquine (antimalarial)
Cyclosporine, tacrolimus (Calcineurin inhibitors)
Patterns of drug induced lung disease
- Most common:
Pulmonary edema (usually w/o effusion)
Pulmonary hemorrhage
DAD
OP, NSIP, UIP
EoPNA - Less common:
HP
Sarcoid like rxn
LIP, DIP
Constrictive bronchiolitis -predominantly penicillamine
PHTN, vasculitis
Risk factors for MTX induced lung toxicity
Age >60
Underlying pleuroparenchymal lung disease
Low albumin
Reduced kidney function
Third spacing e.g. pleural effusion
Higher weekly doses
Previous use of DMARDS
Diabetes
Pulmonary manifestations of MTX toxicity
Hypersensitivity pneumonitis*
NSIP
AIP with non cardiogenic edema*
Eosinophilic pneumonia
Organizing pneumonia*
Diffuse alveolar damage
Pleural effusion*
Lymphadenopathy
Infections e.g. PJP
Extrapulmonary manifestations of MTX toxicity
Transaminitis
Stomatitis, nausea/vomiting
Mouth sores
Macrocytosis, myelosuppression (Increased risk of lymphoproliferative disorders)
nephrotoxicity
Diagnostic criteria for MTX toxicity
1.Major criteria
HP by histopathology without evidence of infection
Imaging findings (diffuse pulmonary ground glass or consolidative opacities)
Negative blood culture and sputum culture
2. Minor criteria
Dyspnea <8 weeks
Non productive cough
SpO2 </90% on RA
WBC </15,000
DLCO </70
3. Define = Major criteria 3+ ½ AND ⅗ minor
4. Probable = Major 2 and 3 AND minor ⅖
Differentiate between RA-ILD and MTX toxicity
Clinical presentation - toxicity more subacute/acute
Blood work - Eos in toxicity
Imaging - NSIP/HP in toxicity, UIP in RA-ILD
BAL - both can have lymphocytes
Biopsy - NSIP/HP/others in toxicity, UIP in RA-ILD
Causes of drug induced lupus
Procainamide
Isoniazid
TNF-alpha inhibitors
Hydralazine
Normal pulmonary pressures
sPAP: 15-30
dPAP: 4-12
mPAP: 8-20
Hemodynamic diagnosis for pre capillary PH
mPAP > 20
PVR > 2
PCWP </15
Indications to screen for pulmonary hypertension
Scleroderma - annual with DLCO and TTE (ERS DETECT algorithm, CTS position statement on PH)
Portal hypertension, prior to transplantation
Causes of Group 1 PH
Causes of group 2 PH
Causes of Group 3 PH
Mechanisms of PH in COPD
Causes of Group 4 PH
What are hereditary causes of PH
BMPR2 (Most Common)
EIF2AK4
ALK-1
SMAD9
Infectious causes of pulmonary hypertension
Schistosomiasis
HIV
Hepatitis B/C → cirrhosis
Drugs are associated with the development of PH
Toxic rapeseed oil
Amphetamines
Dasatinib
Fenfluramine
St John’s Wort
Cocaine
Cyclophosphamide (alkylating agents)
Features make PH-LHD likely
Age >70
Atrial fibrillation
Diabetes, DLP, HTN, Obesity (>2 factors)
LBBB or LVH on ECG
LA dilation, LVH, or grade >2 mitral flow on echo
Valvular diseases are most implicated in PH
Mitral stenosis**
Aortic stenosis*
Mitral regurgitation
Causes of PA obstruction
CTEPH
Foreign body emboli
Schistosomiasis/parasitic infection
Vasculitis
PA sarcoma, uterine sarcoma, germ cell tumors, RCC
Congenital stenosis, other causes of stenosis
Obstruction by lymph nodes
Causes of group 5 PHTN
Polycythemia vera
Essential thrombocytosis
Paroxysmal nocturnal hemoglobinuria
CML
Sickle cell anemia
Thalassemia
Hereditary spherocytosis
Fibrosing mediastinitis
Sarcoidosis
PLCH
Neurofibromatosis
Gaucher’s disease
CKD with or without dialysis
Pulmonary tumour thrombotic microangiopathy
Pathogenesis of PAH
Altered tone → vasoconstriction
Smooth muscle medial hypertrophy
Neointimal formation/hyperplasia and fibrosis
Microthrombi/n situ thrombosis causing plexiform lesions
Mechanisms for sarcoidosis related PH
Interstitial lung disease
Cardiomyopathy
Granulomatous inflammation and involvement of vessels → intrinsic sarcoid vasculopathy
PVOD lesions
Lymph node compression of PA
CTEPH
Portal hypotension
Fibrosing mediastinitis
Mediators of portopulmonary hypertension
Estrogen
Endothelin 1
Deficiency of prostacyclin
Physical examination findings of PH
Loud P2
RV heave
Tricuspid or pulmonary regurgitation murmurs
Elevated JVP, peripheral edema, ascites
Features associated with poor prognosis in PAH
NYHA IV **
Syncope
Rapid symptom progression
pro-BNP >1100 ng/L or BNP > 800 ng/L **
6MWD <165 m **
RA size >26 cm^2
Pericardial effusion
VO2 max <11 mL/kg/minute
VE/VCO2 >45
CI <2, SvO2 <60%
Poor RHC prognostic factors
CI <2
RAP >14
SvO2 <60%
Vasoreactivity
Echocardiographic features of PH
TRV >2.8 m/s
RVSP 35 - 40 mmHg
RV hypertrophy, RV and RA dilation
Flattening of the interventricular septum (can also get bowing)
Pericardial effusion
Tricuspid regurgitation
TAPSE <18 mm
IVC >21 mm, <50% collapse with sniff testing
Additional echo signs as per the ERS guidelines
Ventricle: RV/LV basal diameter >1, flattening of septum
PA: RV outflow doppler acceleration time <105 ms, PA diameter >/25 mm
IVC and RA: diameter >21 mm with <50% collapse with deep inspiration, RA >18 cm^2
ECG findings of PH
RV strain pattern - most sensitive
Right axis deviation
RBBB
RV hypertrophy - R/S >1 in V1
RA enlargement - P pulmonale, P wave >0.25 mV in lead II
CXR findings in PH
Vascular pruning
Enlarged pulmonary arteries
Enlarged heart - enlarged RV and RA
CT findings in PH
Mosaic attenuation
Enlarged PA >3 cm
PA: aorta ratio > 1
RV increased thickness, interventricular septum changes
Ways of measuring CO in PH
Direct Fick method
Indirect Fick method
Thermodilution method
Indications for iron replacement in PH therapy
Ferritin <100
Ferritin 100-299 but tSAT <20%
Indications for prophylactic anticoagulation in PH
Idiopathic
Hereditary
Drug and toxin induced (related to anorexigens)
It is “suggested” and warfarin is the agent
NOTE: This is 2015 recommendation. 2022 says not generally recommended but consider individually
Agents used in vasodilator testing
Inhaled nitric oxide
IV epoprostenol
IV adenosine
Positive vasodilator response in PH
> 10 mmHg reduction to </40 mmHg with increased or unchanged CO
MOA of PH medications
Prostacyclin → activates cAMP → inhibits platelet activation, promotes vasodilation
Selexipag is prostacyclin receptor agonist
Nitric oxide: PDE5i reduce breakdown of cGMP, riociguat stimulates guanylate cyclase which increases production of cGMP. cGMP
Endothelin receptor antagonist → inhibition → vasodilation
Side effects associated with PH medications
Prostacyclin - hypotension, flushing, headaches, jaw pain, rebound PH
PDEf5 - headaches, flushing, volume overload, priapism
Riociguat - headaches, headache, GERD
ERA - fluid retention, hepatotoxicity, anemia
Contraindications to PH therapies
Teratogenic: ERAs, riociguat
Heart failure: prostacyclins
Combination of which drugs have RCT level of evidence in PH
Tadalafil + ambrisentan
AMBITION trial
Treatment of PH, what are considered cardiopulmonary comorbidities?
Conditions associated with left ventricular diastolic dysfunction.
1. Cardiac
Obesity
Hypertension
Diabetes
CAD
2. Pulmonary
Parenchymal disease (DLCO usually <45%)
Treatment of refractory PH
Treatment of refractory PH
Transplantation
Right to left shunt creation
Tests for PH need to be done at EVERY follow up
WHO FC
6MWD
BNP
ECG
ABG or pulse oximetry
Clinical classification of PAH associated with CHD and their treatment
Small/coincidental defects (<1 c, VSD, <2 cm ASD) → defect closure is C/I
Prevalent systemic to pulmonary shunt → may be correctable or non correctable
Eisenmenger Syndrome → defect closure is C/I
PAH persisting post defect correction
In lung disease, what factors actually favor group 1?
Moderate to severe PH rather than mild-moderate
FEV1 >60% in COPD
FVC >70% in IPF
Low diffusion capacity out of keeping
CT abnormalities only modest
What differentiates non severe from severe group 3 PH?
PVR >5
This is also prognostic indicator
Percentage of patients with acute PE develop CTEPH
3%
Risk factors for CTEPH
Large burden of disease
Recurrent PEs
Insufficiency anticoagulation
Hypercoagulable states e.g. splenectomy, antiphospholipid syndrome, ET/PCV, malignancy
Sensitivity and specificity of imaging in CTEPH
VQ scan >97% sensitive, 90% specific
CT PA 99% specific, 51% sensitive
CT findings in CTEPH
Webs and Slits
Ring like stenosis
Total occlusions
Conditions that mimic CTEPH on Imaging
Pulmonary artery sarcoma
Fibrosing mediastinitis
Sarcoidosis
Large vessel vasculitis including takayasu
Peripheral pulmonary artery stenosis
Congenital pulmonary artery abnormalities
In situ pulmonary artery thrombosis
Pulmonary Veno Oclusive Disease
Moyamoya disease
Treatment options for CTEPH
Blood thinners for all (lifelong)
Pulmonary artery endarterectomy
Balloon pulmonary angioplasty
Riociguat
Possible post endarterectomy complications
Reperfusion injury
Possible post Balloon Pump Angioplasty complications
Dissection
Perforation
Over dilation
Imaging findings in PVOD
Smooth interlobular septal thickening
Centrilobular nodules
Mediastinal lymphadenopathy
Etiologies that have been associated with PVOD
Hereditary - BMPR2, EIF2AK4
Medications e.g. cyclophosphamide, bleomycin
CTD e.g. scleroderma, SLE, sjogren’s, etc.
Infections e.g. influenza, HIV, EBV, CMV
HSCT
Clinical features that differentiate PCH from PVOD
Hemoptysis
Hemorrhagic pleural effusions
Histological features of PVOD
Obliteration/extensive and diffuse occlusions of pulmonary veins
Colander like lesions (recanalized thrombus)
No plexiform lesions
Reasons for immediate refferal to PH Centre
- Warning signs :
* 1. rapid progression of symptoms
* 1. severely reduced exercise capacity
* 1. pre-syncope or syncope on mild exertion
* 1. signs of right heart failure. - PAH suspected
- CTEPH suspected
Diagnostic Algorithm for PH
Components of the 3 strata model
Components of the 4 strata Model
Treatment algorithm for PAH
Definition of platypnea and orthodeoxia
Platypnea = dyspnea in upright position that improves when supine
Orthodeoxia = SaO2 drops by >/5% and PaO2 drop by 4 mmHgwhen rising from supine to upright
Causes of orthodeoxia
Hepatopulmonary syndrome
PAVMs
Intracardiac shunts e.g. PFO
Pulmonary parenchymal disorders
Other causes of VQ mismatch
Mechanisms of hypoxemia in HPS
V/Q mismatch - Intrapulmonary vascular dilatations
Shunt - Pulmonary arteriovenous malformations
Diffusion limitation - due to increased diameter from dilatation
Triad of HPS/What is the diagnostic criteria?
Liver disease
Intrapulmonary vascular dilatation
Abnormal oxygenation (abnormal A-a gradient or PaO2)
Treatment options for HPS
Supplemental oxygen
Liver transplantation
Causes of PAVMs
Idiopathic
HHT (>80% of AVM’s are from this)
Hepatopulmonary syndrome
Trauma, prior cardiac surgery
Malignant e.g. metastatic thyroid
Infections e.g. TB, schistosomiasis
CTD e.g. behcet’s, GPA, takayasu
Manifestations of PAVMs
Brain abscess
Embolic stroke
Platypnea, orthodeoxia
Hemoptysis, hemothorax
Dyspnea (orthodeoxia), Hypoxemia, cyanosis
Pulmonary hypertension
Additional manifestations of Hereditary Hemorrhagic Telangiectasia (HHT)
PAVM 30%
Epistaxis - 90%
Telangiectasias - 80%
Cerebral AVMs - 10%
Hepatic AVMs → high output heart failure
GI bleeding, iron deficiency
Manifestations of a liver AVM
Portal hypertension
Encephalopathy and other signs of liver dysfunction
High output heart failure
Physical examination findings in HHT
Mucosal and skin telangiectasias
Pulsatile liver
Murmurs and bruits
Platypnea and orthodeoxia
Cyanosis and clubbing
Signs of heart failure e.g. peripheral edema
Investigations to diagnose shunt or PAVMs
O2 saturation on room air
Contrast echo/bubble echo
100% oxygen
Radiolabeled perfusion scan
Investigations to assess the PAVM
CT PA
Pulmonary angiography
Treatment options for PAVMs
Observation, repeat CT q3-5 years
Embolization/embolotherapy
Surgical resection
Laser ablation
Indications for PAVM treatment
Symptomatic, complications, regardless of size
Feeding vessel > 3 mm
Progressive enlargement
Genetics of HHT
Autosomal dominant
ACVRL1, ENG, SMAD4
Diagnostic criteria for HHT
Curacao Criteria
- Mutation OR (3 for definite, 2 for suspected)
- First degree relative with HHT
- Multiple mucocutaneous telangiectasias
- Visceral involvement of telangiectasias or AVMs
- History of recurrent and spontaneous epistaxis
Screening for in patients with HHT
Iron deficiency anemia*
Pulmonary AVMs*
Cerebral AVMs*
GI AVMs
Hepatic AVMs
Diagnostic criteria for amniotic fluid embolism
During labor/delivery or within 30 mins of placenta delivery
[Cardiopulmonary collapse or sBP <90] AND resp compromise (hypoxemia, dyspnea, cyanosis)
DIC
Absence of fever
Diagnostic criteria for fat embolism
Petechiae
Neurological symptoms e.g. coma, seizure
Hypoxemia
Causes of fat embolism
Fractures, orthopedic surgeries
Liposuction, lipoinjection
Panniculitis
Burns
Pancreatitis
Fatty liver disease
Sickle cell disease
Osteonecrosis
Treatment of amniotic fluid embolism, fat embolism, Venous air or arterial air embolism
Amniotic fluid - supportive
Fat embolism - supportive, ?steroids controversial
Venous air embolism - left lateral decubitus (durant Mavouver), hyperbaric O2
Arterial air embolism - hyperbaric O2
Indications for bilateral lung transplantation
CF/bronchiectasis/suppurative lung disease
Pulmonary hypertension
Contraindications to single lung transplant in IPF
Colonization with resistant organisms, bronchiectasis
Pulmonary hypertension
Overall survival post lung transplant
Overall mean 6.5 years
Double lung transplant mean 8 years
Single lung transplant mean 5 years
Associated side effects with CNIs
Neuro - tremors, headaches, visual abnormalities, seizures
Cardiovascular - hypertension
Renal - AKI, hyperkalemia, hyperuricemia, gout
MSK - osteoporosis
Endo - hirsutism, hyperglycemia
Drug drug interactions
1. 1. CYP3A4 enzyme inhibitors
* 1. increases calcineurin inhibitor levels
* 1. Macrolides (except azithromycin), Azoles, Calcium channel blockers, Grapefruit juice
1. CYP3A4 enzyme inducers
* 1. Decreases calcineurin inhibitor levels
* 1. Rifampin, Carbamazepine, pheobarbital, pheytoin
* 1. St. John’s wort
Classes of Immunosuppresion in transplant
General SE for Lung Transplant immunosuppressive medications
Required prophylaxis post lung transplant
PjP prophylaxis for all
CMV prophylaxis for those at risk
HSV for all
EBV for those at risk
Aspergillus for those at risk
General Lung Transplant Criteria
Chronic end stage lung disease who meet both criteria
* >50% risk of death from lung disease within 2 years if lung transplant not performed
* >80% likelihood of 5-year post transplant survival froma general medical perspective
Absolute Contraindications to Transplant
When to refer a COPD patient for lung transplant?
When to refer for ILD Lung transplant?
When to refer CF to Lung Transplant?
When to refer PAH for transplant?
Complications post auto-BMT?
EARLY:
Infections
Diffuse alveolar hemorrhage
Post engraftment respiratory distress syndrome
Radiation pneumonitis
Pulmonary edema
Aspiration pneumonitis or pneumonia
LATE:
Infections
Organizing pneumonia
Obliterative bronchiolitis
PPFE and other ILDs
PVOD lesions
Malignancy (recurrence or secondary)
Complications post allo-BMT?
EARLY:
Infections
Diffuse alveolar hemorrhage
Hyperacute and acute GVHD
Pulmonary edema
Aspiration pneumonitis or pneumonia
LATE:
Infections
Organizing pneumonia
Obliterative bronchiolitis
PVOD lesions
Malignancy (recurrence or secondary)
Risk factors for PGD (primary graft dysfunction)
Age >20 <45 donor
African American donor
Female donor
Donor smoking history
Trauma to donor
Blood products
ECMO used as bridge
Recipient diagnosis of IPF, PAH
Presentation of PGD (primary graft dysfunction)
Usually within 72 hours
Reperfusion injury (the mechanism)
Bilateral patchy opacities, ARDS like
DAD on pathology
How is PGD graded (ISHLT)?
Only GRade 3 has been shown to be associated with poor outcomes
Airway Complications of Transplant
- Early (<8 weeks) : infection and dehiscence
- Late (>8 weeks): stenosis and bronchomalacia
- Need bronchoscopy to diagnose.
Difference between Acute Rejection types
- Acute cellular rejection: T cell mediated highly associated with CLAD and decreased immunosuppression
- Acute Antibody Mediated Rejection: B cell binding. DSA and AMR associated with CLAD
Diagnosis of acute rejection
Cellular: TBBx (Perivascular monoculear infiltrates)
Antibody mediated: DSA, TBBx, CD4 staining
Histological findings in acute rejection
Perivascular and interstitial mononuclear infiltrates → A score
Lymphocytic bronchiolitis → mononuclear cell infiltrates in submucosa of bronchioles → B score
Treatment of PGD vs acute rejection
PGD: Supportive, ARDS ventilation
Acute:
* steroids for all, switching maintenence therapy, anti thymocyte (ATG), Basiliximab
* ab mediated no standard of care but PLEX/IVIG often tried with anti thymocyte (ATG)
Definition of CLAD
FEV1 decline by >/20% from baseline that lasts for at least 3 months (For definite), and change is not explained by something else (e.g. infection)
BOS: FEV1/FVC <0.7
RAS: TLC<90% baseline (or FVC <80% baseline), persistent fibrotic opacities
Risk factors for CLAD
Previous PGD or acute reflection
Infection, especially CMV, colonization with PsA or aspergillus
GERD
Aspiration
Medication/IST non compliance or underdosed
Increased donor age
Male to female donor
Imaging findings in BOS vs RAS (restrictive allograft)
BOS: mosaic attenuation, centrilobular nodules, gas trapping/hyperinflation, bronchiectasis with time, usually not significant opacities
RAS: Pleuroparenchymal fibroelastosis, NSIP
Histological findings in BOS vs. RAS(restrictive allograft)
BO: Lymphocytic inflammation of submucosa, intraluminal lesion formation, obliteration of airway
RAS: PPFE
Treatment for BOS vs. RAS
Address risk factors e.g. GERD
Optimize immunosuppression (MMF > Aza, Acro > cyclo)
Consider azithromycin (those with neutrophilic BAL especially responsive)
Complications post lung transplant
Early:
Acute or hyperacute rejection
Infectious complications e.g. bacterial, viral, fungal, empyema, surgical site, line infections
Bleeding e.g. hemoptysis, hemothorax
Dehiscence
Anastomotic leak, prolonged air leak
Phrenic nerve injury causing diaphragmatic dysfunction
Pulmonary embolism, DVT
Cardiac arrhythmias
Late:
Chronic rejection
Infectious complications e.g. viral, fungal, bacterial
Tracheal stenosis
Tracheobronchomalacia
Tracheoesophageal and tracheoarterialfistulization
Dehiscence
PTLD, non melanomatous skin cancer, other malignancies
Disease recurrence
Timeline for infectious complications
First month: MRSA, VRE, pseudomonas, candida, HSV
Month 1-6: PJP, aspergillus, nocardia, CMV, EBV, endemic fungi, TB, NTM
>6 months: Community organisms
Examples of post transplant malignancies
PTLD, lymphoma (B cell predominant)
Non melanomatous skin cancer
Primary lung cancer
Breast cancer
Causes of PTLD (post transplant lymphoproliferative Disease)
EBV virus, serostatus (highest in R-/D+)
Degree of immunosuppression (T cell immunosuppression)
Treatment of PTLD
Decrease immunosuppression
Rituximab
Chemotherapy (CHOP)
Surgery/Rads PRN
Diseases with recurrence post transplantation
Bronchogenic carcinoma
Idiopathic pulmonary hemosiderosis
Giant cell interstitial pneumonitis
A1AT deficiency (if smoking)
PVOD
PAP (hereditary cases)
LAM
PLCH
Sarcoidosis → most common
DIP
Diffuse panbronchiolitis
Difference between CMV infection and CMV disease
CMV infection: evidence of active replication and shedding (e.g. antigenemia, PCR, culture) without attributable signs or symptoms
- CMV isolation in the blood by viral isolation, rapid culture, antigenemia, QNAT
CMV disease: infection with attribute signs or symptoms; can be viral syndrome or tissue invasive disease
- CMV isolation in the lung tissue by viral isolation, rapid culture, histopathology, immunohistochemistry
- Also CMV PCR in the blood needed
Risk factors for CMV post lung transplant
D+/R- (highest risk)
D+/R+
D-/R+
Risk factors for CMV post allogeneic BMT
R+/-D-
Degree of immunosuppression, use of high dose steroids
GVHD
Prior CMV viremia
Treatment of CMV disease
Oral valganciclovir
IV ganciclovir
Foscarnet is second line treatment
Reduction in IST should be considered
Congenital causes of non CF bronchiectasis
- Cystic fibrosis
- Primary ciliary dyskinesia
- Young syndrome ( Men with sinusitis, infertility due to vas deferens obstruction and bronchiectasis)
- Williams- Campbell (bronchomalacia with decreases/absent cartilage around subsegmental bronchi. You get cystic bronchiectasis)
- Alpha 1 antitrypsin
- Yellow nail syndrome
- Mouniere Kuhn syndrome (tracheobronchomegaly and lung sequestration
- Kartaaganer syndrome ( situs inversus, chronic sinusitis, and bronchiectasis)
Cause of PCD
Autosomal recessive
Loss of or dysfunctional cilia
Clinical manifestations of primary ciliary dyskinesia
Chronic sinopulmonary infection
Bronchiectasis
Male infertility
Situs inversus
Kartaganer syndrome
Bronchiectasis
Chronic rhinosinusitis
Situs inversus
Diagnosis of PCD
Low or absent nasal nitric oxide
Genetic testing for confirmation
Can do sinus biopsy but can be falsely negative
Cause of Young syndrome
- Abnormally viscous mucous
- Triad of bronchiectasis, chronic rhinosinusitis and infertility due to vas deferens obstruction
- Can appear to be similar to CF and primary ciliary dyskinesia (PCD) patients, but they have had normal sweat chloride tests and normal cilia
Clinical manifestations of young syndrome
Chronic sinopulmonary infections
Bronchiectasis
Male infertility
Triad for yellow nail syndrome
Yellow nails
Respiratory symptoms
Lymphedema
Most common causes of bronchiectasis
Post infectious
Idiopathic
Immunodeficiency
Connective tissue disorders
2 most common causes of non CF bronchiectasis exacerbations
PsA
H. influenzae (SA in CF instead)
Blood work would you send for everyone with bronchiectasis
CBC
IgE, Asp IgG, workup ABPA
IGAMs
Sputum cultures
Imaging findings of bronchiectasis
Signet ring sign/broncho arterial ratio >1
Tram tracking, non tapering peripheral airways
Mucous plugging
Bronchial wall thickening
Gas trapping
Airway clearance techniques
- Active cycle of breathing technique
- Autogenic drainage
- Gravity positioning
- OPEP
- Nebulized saline
- Remember NMD:
Lung volume recruitment (LVR) (aka “breath stacking”)
Glossopharyngeal breathing
Manual resuscitator
Mechanical inspiration
Mechanical cough assistance
Manually assisted cough (MAC)
Mechanical insufflator-exsufflator (MIE)
Airway clearance techniques that are not recommended
Inhaled mannitol
Inhaled NAC
Inhaled dornase alpha
Carbocysteine
Treatments in non-CF bronchiectasis to reduce exacerbations
Airway clearance
Pulmonary rehabilitation
Mucoactive therapy
Chronic abx - azithro for non PsA, inhaled for PsA
Abx choices for prophylaxis in those who have recurrent exacerbations
Azithro if non PSA
Inhaled anti pseudomonas if PSA - tobra, collistin, gentamicin (or azithro if none of these are tolerateD)
When should you offer long term antibiotics to patients with non cf bronchiectasis (how many exacerbations)?
ERS 2017 says >3 per year should be offered chronic Abx.
Inhaled for those with PSA+/- macrolide
Definition of bronchiectasis exacerbation
Worsening symptoms
Over last 48 hours
Role of bronchodilators in management of bronchiectasis
LABA in those with significant breathlessness
Indications for resection in bronchiectasis
Localized disease not controlled with medical treatment
Post obstructive bronchiectasis due to tumors
Massive hemoptysis
Recurrent exacerbations
Overwhelming sputum production
Outline possible treatment alogorithm for newly discovered PSA on a sputum in NON-CF bronchiectasis
Median age of survival in CF
68 years after Trikafta (2022)
Pathogenesis of CF
CFTR transmembrane protein mutation
Chromosome 7 gene (long arm)
Transepithelial chloride channel
Abnormally thick mucus, difficulty clearing, infections and colonization
Classes of mutations in CF
- Class 1 – absent or defective protein synthesis
- Class 2 – abnormal processing or transport of the protein to the cell membrane
- Class 3 – abnormal regulation of CFTR function, inhibiting chloride channel activation
- Class 4 – normal amount of CFTR but reduced function (defective conduction)
- Class 5 – reduced synthesis of fully active CFTR
- Class 6 – decreased stability of fully processed and functional CFTR
Bacteria that classically cause colonization in CF
Staphylococcus aureus **
Pseudomonas **
H. Influenza **
Burkholderia cepacia
Aspergillus fumigatus
NTM
Stenotrophomonas
Pulmonary manifestations of cystic fibrosis
Bronchiectasis
Bacterial colonization
Recurrent pulmonary infection
Mucous plugging and collapse
Pneumothorax
Hemothorax
Gas trapping and obstruction
Extrapulmonary manifestations of cystic fibrosis
Sinus - sinusitis, nasal polyps
Intestinal - Meconium ileus, DIOS, SIBO, chronic constipation
Pancreas - pancreatic insufficiency with steatorrhea and vitamin ADEK deficiency, chronic pancreatitis, diabetes
Liver - transaminitis, biliary cirrhosis, fatty liver disease, cirrhosis
Reproductive - male/female infertility; absence of vas differences, thickening of cervical mucus
MSK - osteopenia or osteoporosis
Depression
Causes of abdominal pain in CF
Chronic constipation
DIOS (distal intesinal obstruciton syndrome)
SIBO (small intestine bacterial overgrowth)
Pancreatitis
Appendicitis
Intussusception
Colon cancer
Colon cancer screening in CF
Age 40 and q5 years or as dictated by polyp
Age 30 if previous transplant
Diagnostic criteria for cystic fibrosis → See figure. Tests that can be used to diagnose CF
Clinical: NBS, family history, sx
Sweat chloride test
Genetic testing
Extended CFTR analysis
Functional assays
Newborn CF screens
- Serum immunoreactive trypsinogen assay (elevated is positive)
- DNA assay
DDx of positive sweat chloride test
Malnutrition
Anorexia, bulimia
Pancreatitis
Untreated adrenal insufficiency
Untreated hypothyroidism
Hypophysitis
Technical/test factors
DDX of negative sweat chloride test
Dehydration
Physiologic low sweat rate
Hypoproteinemic states
Drugs e.g. mineralocorticoids
On CFTR modulators (e.g. baby of mother on CFTR modulator during pregnancy)
Technical/test factors
Malnutrition
How to interpret a sweat chloride test in CF
What is the difference between CFTR-related disorder and CFTR-Related Metabolic Syndrome.
- CRMS: children with a positive newborn screen AND one of
** Sweat chloride <30 and 2 CFTR mutations of which 1 has unclear phenotypic consequences
** An intermediate sweat chlorid (30-59) and 1 or 0 CF causing mutations - Note: most will not devlop clinical CF and this has been combined with CF Screen positive Inconclusive Diagnosis (CFSPID)
- CFTR-Related Disorder: Do not meet diagnostic criteria for CF or CRMS but are affected by CF related Conditions.
CF management
Smoking cessation, vaccinations
Airway clearance, bronchodilators
Inhaled hypertonic saline
Inhaled DNAse
Chronic azithromycin
+/- modulator therapy
Airway clearance techniques for patients with CF
Active cycle of breathing
Autogenic drainage
Positional therapy
Oscillating PEP device - Aerobika, Acapella, flutter valve
Percussive vest
Risk factors for acquiring MRSA
Younger
F508 delta
Higher admissions
PsA co infection
Role of abx in CF
Eradication
Prevent exacerbations
Exacerbation
Indications for eradication abx therapy in CF
PsA
+/- MRSA
Abx that can be used to treat chronic PSA or PSA eradication
Aztreonam 500 mg oral MWF
Tobramycin 300 mg nebulized BID
Colistin 150 mg nebulized BID
Aztreonam 75 mg nebulized TD * weak evidence
28 days on and off
Indication for eradication abx and how to do it with PSA in CF.
Abx choices for CF exacerbation
MSSA: amoxi-clav, doxy, septra - cefazolin, nafcillin
MRSA: Septra, doxycycline - Vancomycin, linezolid
PsA: cipro - ceftaz, piptazo, mero, tobra, aztreonam
Steno: septra, doxy, levoflox - ceftaz, colistin
Duration of treatment for CF exacerbation
At least 2 weeks but often longer
Definition of massive hemoptysis in CF
Scant <5 cc
Mild to moderate 5-240 cc
Massive >240 cc
Management of hemoptysis in CF
Scant: +/- abx, continue everything
Mild/moderate: stop HS, no consensus DNAse, airway clearance; START abx
Massive: stop HS, airway clearance, no consensus DNAse; START abx
Stop BiPAP if on it (unless mild)
Add-on options for ongoing hemoptysis
Vitamin K, tranexamic acid
Bronchial artery embolization
Lung resection
Transplantation
Management of pneumothorax in CF
No consensus re antibiotics
Follow guidelines re: chest tube
Hold percussive therapies (including PEP devices)
Hold BPAP
Do not withhold mucous clearance and aerosols
Indications for pleurodesis
Not after first episode
After recurrence
Surgical pleurodesis is preferred
Recommendations post PNTX inCF
No travel x 2 weeks after resolution
No heavy lifting 5 lb x 2 weeks after resolution
No spirometry x 2 weeks after resolution
Different types of mutations in CF
Class I: Nonsense mutation, Decreased synthesis
Class II: processing mutation e.g. F508del
Class III: Gating mutation e.g. G55D,
Class IV: Conductance e.g. R117H
Class V: Decreased production
Class IV: Decreased stability
Who is eligible for CFTR modulator therapy?
F508 del
Gating mutation e.g. G551D
R117H
Benefits of CFTR modulator therapy
Improve symptoms
Improve quality of life
Improved lung function/FEV1 (10.4%)
Improved weight
Improve sweat chloride
Reduced exacerbation and admission
Improved mortality
What is the most common NTM in CF?
MAC complex
How often do you screen patients with CF for NTM?
Annually in spontaneously expectorating
Do not need to go hunting for sputum if not spontaneously expectorating and no sx
Do not use oropharyngeal swabs
Treatment of hemoptysis during bronchoscopy
Cold saline
Topical epinephrine 1:10,000
Bronchial blocker
Wedge with bronchoscopy
Lateral decubitus
Intubate
Benefits of BCG vaccine
Prevent CNS tuberculosis.
Prevents disseminated TB.
Protection is mainly during childhood (up to age 15)
Organisms are in the mycobacterium TB complex
Mycobacterium tuberculosis
Mycobacterium bovis
Mycobacterium carnetti
Mycobacterium africanum
Mycobacterium microti
Risk factors for developing primary infections? (18-24 months post is still considered primary disease)
Age <5
Immunocompromised e.g. HIV
Risk factors for CNS TB
Age <5
HIV
Risk factors for tuberculosis
Contacts e.g. household contacts
Birth in TB endemic area
Immunosuppression
Substance abuse
Socioeconomic status
Malnutrition
Certain systemic diseases e.g. COPD, DM, silicosis, renal disease, malignancy
How long after exposure does it take to develop positive TBST or IGRA?
3-8 weeks
Risk factors that increase the probability of TB transmission
Cavitary disease
Upper lung zone disease
Laryngeal disease
AFB smear positive disease
Level of exposure - proximity, time spent with them, environment
Coughing, sneezing
Modes of transmission of TB
Airborne
Droplet
Percutaneous
Ingestion
Isolation in TB
Smear negative → 2 weeks
Smear positive → 2 weeks if 3 consecutive smear negative AFB
Smear positive → 4 weeks if persistently positive sputums
For rifampin resistance, 4 weeks +/- 3 negative smears
Indications for hospitalization inTB
Complicated TB, comorbid conditions
Has acute complication of TB e.g. hemoptysis
Drug desensitization
Is non compliant with medication
Cannot isolate safety at home
What conditions must be met for someone isolating at home?
No shared ventilation with other units (non household members)
Everyone in household has already been exposed and if TBST negative, should accept risk of ongoing exposure
<5 or immunocompromised patients are already on treatment for latent or active TB
Differences in treating TB in HIV
Longer duration IF NOT ON ART
Rifampicin rather than rifampin
Consideration of timing of ART therapy +/- steroids
Imaging findings of primary TB
Lower lobe distribution
Parenchymal consolidation - Opacities, GGO, tree in bud nodules
May have cavities
Miliary TB
Hilar, mediastinal LN →RML collapse
More likely to have pleural effusion
Imaging findings of secondary TB
Upper lobe distribution (apical, posterior > sup segment > anterior)
Consolidation, tree in bud
Cavitation
5% have upper lobe fibrocalcific changes
Latent TB testing is not required in these situations
Low pretest probability
Diagnosis of active TB in those >12 years old
Trending response to treatment
Mass testing programs for e.g. immigrants (not including HCW/occupations)
Indications for latent TB testing?
CXR showing apical fibronodular changes typical of healed TB
Recent exposure to active TB
Certain occupations e.g. HCW, prisoner workers, shelter workers
HIV (any stage)
IVDU or use of illicit drugs
Post HSCT or organ transplant (and pre transplant workup)
On immunosuppressive therapies (includes chemo)
Lymphoma, leukemia, head and neck cancers
Chronic kidney disease requiring dialysis
Silicosis
What immune response does the TBST depend on?
Type IV delayed type hypersensitivity
TBST preferred over IGRA when:
Contact tracing
Serial testing HCP and others
Serial testing is required in TB when:
Contact investigation
Serial testing of HCW, other populations e.g. inmates, prison workers
IGRA is preferred when:
Unclear if patient will return
Children >10 received vaccine after age 1, unclear when, >/2 vaccines
Children >2 but <10 previously received vaccine
Adequate training, personnel, facility for TBST not available
TBST is contraindicated
Previous known NTM infection
Contraindications to TBST
Previous allergic reaction, blistering reaction
Causes of false positive TBST
Technical limitations
Prior vaccination
Sensitization to NTM (not an issue with IGRA)
Rupture of venule at time of injection
Causes of false negative TBST
Technical limitations
HIV
Active TB or fungal infection
Live virus vaccine in the last 4 weeks
Recent infection
Steroids >/15 mg x >2-4 weeks
Natural waning of immunity
Causes of false negative IGRA
Immunosuppression e.g. HIV, active TB
Technical variability
Sensitivity of TBST vs IGRA for latent TB
TBST: 77%
IGRA: 60-95%
Indications for both IGRA/TBST
Either can be done to increase sensitivity after negative test
IGRA can be done after positive TBST to increase specificity
Cutoffs for positive TBST - See table
<5
>/5
>/10
Available tests to assess for TB
AFB smear (Zeil Nielson, Auramine Rhodamine) - sensitivity 20-80%
PCR - sensitivity 70-95%
Culture
Histopathology
Diagnosis of active TB
Appropriate clinical and imaging findings
Positive TB culture, positive TB PCR +/- AFB
Samples that can be collected for diagnosis of TB
Sputum
Induced sputum
BAL
Tissue
Urine (guideline recommends against lipoarabinomannan but can still do culture)
Blood
Gastric aspirate
Stool
Pathological findings in tuberculosis
Caseating granulomatous inflammation
May see organisms, may stain positive for AFB
DDX for positive AFB stains
Tuberculosis
NTM, most likely MAC
Nocardia
Rhodococcus
Actinomyces
What percentage of patients with latent TB will develop active TB in their lifetime?
5-10%
50% of that risk is in the first 2 years
Canadian specific can use TSTin3D (McGill online calculator) to estimate the cumulative risk of disease for active TB
Drug regimens for the treatment of latent TB
3HP = isoniazid and rifapentine weekly x 3 months (First Line)
Rifampin daily x 4 months (First line)
Isoniazid daily x 9 months (Second Line)
Isoniazid daily x 6 months (Alternative)
Isoniazid and rifampin daily x 3 months (alternative)
Pretreatment testing before latent TB treatment
Assess for active TB - CXR → sputum AFB if CXR is abnormal
LFTs
Creatinine
CBC
HIV, hepatitis B, hepatitis C
Indications to treat pregnant patients with latent TB
Recent close contact with active TB
On immunosuppression
Has HIV
Treatment of pregnant patients with latent TB
Rifampin x 4 months
Treatment of non-resistant active TB - What are their benefits?
Isoniazid 5 mg/kg daily → prevent resistance - bactericidal
Rifampin 10 mg/kg daily → prevent resistance, relapse - bactericidal
Ethambutol 15 mg/kg daily → prevents resistance
Pyrizinamide 20 mg/kg daily - bactericidal
FQ (moxi/levo) when person has A/E requiring cessation of a first line drug
Preferred Treatment and alternatives treatments for active TB (TB disease)
- isoniazid, rifampin, pyrazinamide and ethambutol daily for the first 2 months followed by isoniazid and rifampin for 4 more months
- Suspected susceptibility:
** RIPE daily x 2 months then RIE daily for 4 months - Known susceptibilities:
** RIP daily x 2 months then RI daily x 4 months - Note: should add pyridoxine (Vit B6) 25-50mg/day for all those takine INH at risk for peripheral neuropathy
** people with diabetes, chronic kidney disease, human immunodeficiency virus (HIV) malnutrition, seizure disorder or a history of substance misuse, as well as pregnant or breastfeeding women
Alternative treatment regimens for active TB
R/I/E x 2 months then extend out to 7 months
Can also do the drugs in continuation phase (whether R/I or R/I/E 3 times per week)
Treatment with drug-susceptible pulmonary TB and what are the risk factors for relapse
extensive disease OR baseline cavitary disease on x-ray and smear or culture positive sputum at two months)
extension of the continuation phase to seven months for a total of nine months of TB drug therapy (poor evidence).
What do you do if a patient is missing tb treatment doses?
Potential side effects of TB treatment
Isoniazid - peripheral neuropathy, hepatic toxicity, drug induced SLE
Rifampin - drug-drug interaction, body fluid discolouration, hepatic toxicity, rash
Ethambutol - optic neuropathy, red-green color blindness
Pyrazinamide - hepatotoxicity
Examples of drug-drug interactions with rifampin
DOACs, warfarin
Oral contraceptives
Antifungals
Tacro, cyclo
Methadone
Phenytoin
When should you be concerned about liver toxicity with TB drugs?
Billi >3, serum, ALT > 3 ULN with sx, ALT >5 ULN with no sx
Can continue ethambutol; consider adding FQ
Discontinue, restart slowly with careful monitoring
Obviously assess for other causes of transaminitis
Indications to extend active TB treatment to 9 months
BASELINE Cavitary ON CXR + smear/culture positive at 2 months
Diabetes and cavitary disease
HIV not on ART therapy
Solid organ transplant recipients
On TNF alpha inhibitors
Did not use pyrazinamide in intensive phase
TB meningitis
TB bone disease if elevated inflammatory markers at end of 6 months
When do you start ART therapy in a patient with active TB and HIV?
TB meningitis or CD4>50- delay until after 2 weeks of starting TB therapy
**Out of concern for Immune REconstitution Inflammatory Syndrome (IRIS)
No TB meningitis and/or CD4 <50 - within 2 weeks of starting TB therapy
Pred 40 x 2 weeks if CD4 <100, unless active hepatitis B, kaposi, rifampin resistance
What is IRIS and how does it manifest?
Immune REconstitution Inflammatory Syndrome (IRIS)
Lymph node enlargement and pulmonary infiltrates.
Usually self limited but can warrant steroids.
Monitoring patients with active TB on treatment
CBC, crea, LFTs monthly
HIV, hepatitis B/C at start of treatment
CXR at baseline, then q2 months
Sputum smear, culture q2 weeks until smear negative; then 2 and 1 month before end
PFT within 6 months of finishing treatment
Recurrence vs relapse vs reinfection
Recurrence: can be due to either
Relapse: same strain
Reinfection: different strain
Risk factors for recurrence of TB
Cavitary disease, smear positive disease
Extensive or disseminated disease
Drug resistant disease
Immunosuppressed
Intermittent therapy (not daily), treatment interruptions
Was not adherent
Should monitor these patients for 12-24 months with sx/imaging/microbiological testing
Treatment of active TB in pregnancy
RIE (omit P) x 9 months
Indications to give pyrazinamide in pregnancy
Smear positive
Extensive disease
Disseminated
Intolerance to any first line drugs
Drugs that are contraindicated in pregnancy (TB)
+/-PZA
All injectables
Fluoroquinolones
Common locations for extrapulmonary tuberculosis
Pleural*
Abdominal*
Lymphadenopathy*
CNS - tuberculoma, CNS meningitis
Bone - vertebral disease, arthritis
Cutaneous
Genitourinary
Ocular
Definition and diagnosis of disseminated TB
Disease in >?2 non contiguous organs OR isolation in blood, bone marrow, or liver on bx
Milliary TB is subset of disseminated TB
Differential diagnosis for miliary pattern on CT
Disseminated tuberculosis
Other infections: histoplasmosis, mycoplasma, varicella
Sarcoidosis, pneumoconiosis, amyloidosis
Miliary metastases e.g. thyroid cancer, breast cancer, RCC, melanoma
Tests that can help assess for TB Pleuritis
Fluid analysis
Fluid adenosine deaminase
Fluid interferon gamma
Fluid AFB and culture
Histopathology
Fluid characteristics in TB pleuritis
Low - normal glucose
pH >7.3
LDH >500
Neutrophil predominant early on, the lymphocyte predominance
<5% mesothelial cells
Pseudochylothorax, chylothorax
Treatment of pleural TB
RIPE x 6 months
Chest tube if empyema, may need decortication
No steroids
No therapuetic thoracenteisis/chest tube for pleural TB associated effusions.
Extrapulmonary TB cases that require extended therapy
CNS x 9-12 months, requires higher doses of rifampin >15 mg/kg
Joint x 9-12 months if markers of severity at 6 months (CRP, ESR)
Imaging findings in CNS TB
Basal leptomeningeal enhancement
Hydrocephalus
Infarcts
Benefits of steroids in the treatment of TB meningitis
Mitigate increased ICP, reduce hydrocephalus and infarction, reduce short term mortality
Does not affect disabling neurological consequences or long term survival
Steroid regimen in the treatment of TB meningitis
120 mg x 1 week
90 mg x 1 week
60 mg x 1 week
30 mg x 1 week
15 mg x 1 wek
5 mg x 1 week
Treatment of TB pericarditis
RIPE x 6 months
Steroids in HIV negative
NOT HIV positive (ART or no ART)
Indications for steroids in the treatment of TB
Treating TB in HIV with CD4 <100 to prevent IRIS (Only if on HAART)
All patients with meningitis
HIV negative patients with pericarditis (No recommendation for or against if HIV+ on therapy with HAART and have TB pericarditis)
Definitions of TB resistance
Monoresistant: Resistant to any of the first line therapies.
Poly drug resistance: Resistant to 2 of the first line therapies (not rifampin)
MDR: Resistant to INH + Rifampin with/without resistant to other first line agents.
Pre-XDR: MDR TB with additional resistance to any FQ.
XDR: Pre-XDR + resistance to bedaquiline/linezolid
Treatment of MDR-TB
initial regimen should include levofloxacin or moxifloxacin AND bedaquiline AND linezolid AND clofazimine AND cycloserine.
5 to 7 months after culture conversion occurs, the total number of drugs in the regimen can be reduced to 4 for a total duration of 18-20 months.
Treatment of pre-XDR or XDR
Same as MDR. Ensure 5 drugs in the regimen initially. Cannot use resistant drugs.
In order of preference add on: ethambutol, pyrazinamide, delamanid, amikacin, imipenem-cilastatin or meropenem (plus clavulanic acid), ethionamide and p-aminosalicylic acid.
Is surgery indicated in MDR-TB
Partial lung resection in carefully selected patients can be used as an adjuvant.
Optimally after culture conversion is achieved.
Which Countries have the highest incidence of TB and MDR (According to WHO)
TB: Philippines, Pakistan, Somalia, India
MDR: Somalia, China
Most common NTM species to cause infection
MAC
M. Kansassi
M. abscessus
Modes of transmission for NTM
Soli aerosols(All but M. Kansasii)
Water aerosols
Soft tissue
Aspiration
Risk factors for development of NTM
Older age
Female
Lower BMI
Thoracic cage abnormalities, mitral valve prolapse
Immunocomp (e.g. HIV, IST, malignancy) but can happen in immunocompetent too
Underlying structural lung disease e.g. bronchiectasis, CF, ILD, COPD/asthma
Oral steroids >15 mg/day
Inhaled fluticasone >800 mcg/day
Anti TNF alpha
Risk factors for progression of NTM
Older age
Male
Lowe BMI
Immunosuppression - primary immunodeficiency, HIV infection, IST, anti TNF, steroids?
Labs: elevated ESR/CRP, hypoalbuminemia
Fibrocavitary disease
Extent of disease
Bacterial load and species and smear positivity
2 pulmonary phenotypes that are produced by NTM
Fibrocavitary
Nodular bronchiectatic
Other: HP, solitary pulmonary nodule, disseminated
Non pulmonary manifestations of NTM
Superficial lymphadenitis (especially cervical)
Skin and soft tissue infection
Disseminated disease
Radiographic findings of NTM
Fibrocavitary - thick walled cavities, upper lobe predominance
Nodules, tree in bud nodularity
Bronchiectasis
GGO, centrilobular nodules, gas trapping in HP
What other features are seen in Lady Windermere syndrome?
Scoliosis
Pectus excavatum
Mitral valve prolapse
Diagnostic criteria for NTM → See table.
Symptoms
Imaging consistent with pulmonary disease
Exclusion of other diagnoses
2 sputum or 1 BAL
If M. abscessus should be speciated ot the subspecies level and checked for macrolide resistance.
OR if disseminated x1 blood culture/culture from site of infection
What is special about the sputum cultures that are obtained in NTM diagnosis vs TB?
TB - 3 sputums, 1 hour apart is fine
NTM - 2 sputums, same species/subspecies should be isolated over interval of >/1 week
If monitoring patients, how and how frequently do you monitor them?
Sputum culture q2-3 months
Repeat imaging after 6 months
When do you treat NTM?
2020 guidelines say treat if diagnosed instead of watchful waiting. (condition and very low evidence)
Especially treat if:
Positive smear or cavitary disease
What is the treatment for NTM? other than Abscessus See table.
- Note rifampicin and rifampin are the same thing
- MAC should
** always have a azithromycin if susceptible and if cavitary/macrolide resistant/refractory should have amikacin or streptomycin addedd
**Treated 12 months post conversion - Kanasii
** Rifampin susceptible suggest Rifampin, Ethambutolo and either INH or azithro (daily is preferred in most cases)
** Rifampin resistant then add moxifloxacin
** Treated for at least 12 months (regardless of conversion) - Xenopi
** Moxi or Azithro with a total of minimum 3 drugs.
** If cavitary or adanced add amikacin
** Treat 12 months beyond conversion
How do we treat NTM Abscessus?
Abscessus
* There is an initial and continuation phase and you need to know if it is Mutational susceptible and inducible susceptible (14 days).
* Need 3 active drugs initially
* duration - “short vs. long”-Expert opinion
What is the definition of refractory disease in NTM?
Culture positive after 6 months
What makes treatment of abscessus unique?
Can have chromosomal mutations
Mutation and inducible resistance
Treatment categories for MAC
Fibronodular disease
Extensive disease/cavitary disease
Macrolide resistant disease
Refractory disease
Treatment categories for Kansasii treatment
Fibronodular disease
Extensive disease/cavitary disease
Rifampin resistance
Treatment categories for Xenopi treatment
Fibronodular
Extensive/cavitary disease
Indications for surgical management
Severe complication e.g. hemoptysis
Not responding to medical therapy, refractory disease
Duration of treatment for MAC, Kansasii and Xenopi
MAC x 12 months post first negative culture/culture conversion
Kansasii x 12 months fixed
Xenopi x 12 months post culture conversion
Abscessus - expert opinion
Which fungi require T cell mediated defense vs phagocytosis?
T cell mediated immune defense: PJP, endemic fungi, NTM/TB, crypto
Phagocytosis: candida, aspergillus, mucormycosis
Disease manifestations of aspergillus
ABPA
Aspergillus nodule
Aspergilloma - unusual to be caused by other fungus
Chronic cavitating pulmonary aspergillosis
Chronic fibrosing pulmonary aspergillosis
Semi invasive pulmonary aspergillosis
Invasive pulmonary aspergillosis
Tracheobronchitis
Available aspergillus microbiological testing
Aspergillus IgG - most sensitive IgE specific Aspergillus for ABPA)
Serum/BAL - PCR
Serum/BAL - galactomannan
Sputum/BAL/tissue/blood/other - culture
RFs for chronic cavitation aspergillosis
Pre-existing structural lung disease.
COPD
Tuberculosis
Cystic fibrosis
Others
Risk factors for invasive pulmonary aspergillosis
Prolonged neutropenia <500 for >10 days (biggest risk)
Transplantation - lung, HSCT
Hematological malignancy
Steroids >3 weeks
Chemotherapy
HIV/AIDs
Chronic granulomatous disease
How do you generally diagnose chronic pulmonary aspergillosis?
At least 3 months in duration
Consistent clinical and imaging features
Evidence of Asp IgG vs positive sputum/BAL/biopsy culture
Imaging findings for invasive aspergillosis
Nodules
Reverse halo sign (more common with OP and less commonly fungal but mucormycosis most common of the fungal)
Atoll sign (same as reverse halo sign)
Halo sign is most commonly associated with IPA
Air crescent sign (delayed finding)
Wedge shaped infarcts
Tree in bud opacities
Treatment for a pulmonary aspergilloma
Single - can observe or surgery/embolization if symptomatic
Multiple - antifungals (itraconazole)
Can give antifungals pre/post surgery if high risk spillage
Treatment of chronic cavitary pulmonary aspergillosis
Observe
Itraconazole, vori, posi x 6 months
Treatment for invasive pulmonary aspergillosis
Voriconazole x >/6 weeks
Imaging findings for ABPA
Finger in glove, mucous plugging
Mucous plugging can cause collapse
Bronchial wall thickening
Central bronchiectasis
Fleeting pulmonary alveolar opacities, usually upper lobes
Pulmonary fibrosis in chronic disease
diagnostic criteria for ABPA - new criteria
Treatment for ABPA
Prednisone 0.5mg/kg x 2-4 weeks then taper to complete over 4 months OR itraconazole for 4 months
Itraconazole x 16 weeks/voi/posi (old)
Do not use high dose ICS for treatment purposes
Do NOT recommend Anti-IL5 agent as first line (nt confirmed by RCT yet) Prednisone
Itraconazole x 16 weeks/voi/posi
Anti-IL5 agent (not confirmed by RCT yet)
Treatment of ABPA exacerbation
New treat same as Anewly diagnosed ABPA (pred or itraconazole) but no biologic
MIld → ICS (No)
More than mild → increase oral steroids
If refractory (>/=2 in last 2 years) can combine pred adn itraconazole)
Treatment response
Improvement in 8-12 weeks of:
* Chest radiograph
* IgE level (20% fall)
* Clinical symptoms.
NOTE: aspergillus IgE and IgG levels or eos may not fall so don’t recheck for response.
Risk factors for disseminated disease of endemic Fungi?
Medications e.g. TNF-alpha inhibitors, steroids, IST
HIV/AIDs
Immune disorders e.g. CVID
Hodgkin’s lymphoma
Extremes of age
Pulmonary manifestations of histoplasmosis
Acute localized pulmonary histoplasmosis
Diffuse pulmonary histoplasmosis
Chronic pulmonary histoplasmosis
Disseminated histoplasmosis
Radiographic manifestations of histoplasmosis
Acute localized pulmonary histoplasmosis
- Local infiltrates/pneumonitis (usually lower)
Diffuse pulmonary histoplasmosis
- Reticulonodular
- Miliary
Chronic pulmonary histoplasmosis
- Apical fibrocavitary
Disseminated histoplasmosis
- Miliary
Manifestations of chronic pulmonary histoplasmosis
Apical infiltrations, fibrosis
Cavitation
Fibrosing mediastinitis
Mediastinal granuloma
Can send secondary infection of cavitation
Broncholithiasis
Diagnosis of different manifestations of histoplasmosis
Use antigen (urine*, blood, BAL) + antibody for acute disease (local or diffuse) or disseminated disease
Use culture (BAL, TBBx) for chronic disease - sputum sensitivity is low
Mediastinal disease: ab usually positive; antigen -, culture
Histopathology of histoplasmosis
Small yeast with narrow based budding
Treatment of mediastinal manifestations of histoplasmosis
Broncholithiasis → observe, bronchoscopic preferred, surgical
Mediastinal granuloma → observe, surgical removal if needed
Fibrosing mediastinitis → stent if needed, no antifungals or steroids (unless sarcoid or vasculitis causing it, then can be trialed)
Manifestations of pulmonary coccidioidomycosis
Local primary
Diffuse pulmonary coccidioidomycosis
Chronic fibrocavitary disease
Disseminated
Diagnostic criteria for coccidioidomycosis
Combination of tests
Antigen (urine, serum, BAL)
Antibody (EIA preferred)
Direct visualization (sputum, BAL, bx material), path - can see spherules
Culture
Manifestations of pulmonary blastomycosis
Acute focal pulmonary blasto
Acute diffuse pulmonary blasto
Chronic pulmonary blasto
Disseminated
Extra pulmonary manifestations of blasto
Brain
Bone - OM
Cutaneous - crusting, verrucous lesion
GU tract
Diagnostic criteria for blasto
Combination of tests
Antigen
Antibody
Direct visualization, path
Culture - gold standard
Imaging findings of PJP
- Reticular changes, perihilar distribution (more often upper lobe)
- Crazy paving (also smooth septal thickening)
- Pneumatoceles
- Less commonly nodular pattern (granulomatous PJP)
- Often hypoxemia is out of proportion to degree of radiographic findings
General blood work to assess for PJP
LDH - sensitive
Beta D glucan - sensitive
Causes of positive beta d glucan
- Pseudomonas infection
- IVIG or olther blood products/albumin
- IHDialysis using cellulose membrane
- Presence of invasive fungal infection (candida, aspergillus,fusarium, histoplasmosis, PJP).
** Not mucormycosis.
When is beta d glucan usually negative?
Mucormycosis
Cryptococcus
Blastomycosis
False negative: Hyperpigmented serum (bilirubin or triglyceride elevation)
False negative: azitrhomycin or IV pentamidine
Diagnosis of PJP
Stained respiratory specimens - sputum, BAL - very sensitive in HIV (97% vs 50-60% HIV -)
PCR - blood, sputum, BAL - especially useful in HIV - (Sensitivity up to 100% but 20% of normal population colonized)
Beta D Glucan (serum) sensitive in HIV (BHIVA 2024)
Treatment of PJP
Septra x 21 days, 15-20 mg/kg IV of TMP component
Alternatives: IV pentamidine, primaquine + clinda, atovaquone, dapsone + septra
Plus steroids
Indications of treating with steroids
PaO2 <70 mmHg
A-a gradient >/35 mmHg
U2D: SpO2 <92%
Most effective within 72h of treatment initiation
Steroid Regimen (Classic)
Prednisone 40 mg BID days # 1-5.
Prednisone 40 mg daily days #6-11.
Prednisone 20 mg daily days #12-21.
Hg
U2D: SpO2 <92%
Indications of PJP prophylaxis in HIV
CD4 <200 (continue until >200 for >3 months)
CD4 <14%
Options for PJP prophylaxis
Septra SS, DS
Pentamidine
Dapsone
Atovaquone
Risk factors for invasive candidal infection
Neutropenia
Immunosuppression
Broad spectrum abx use
Necrotizing pancreatitis
TPN
CVC
Intra abdominal surgical procedures
Risk factors for mucormycosis
Diabetes, especially DKA
Iron overload, deferoxamine tx
Hematological malignancies, HSCT, SOT
Glucocorticoid treatment
COVID-19 pneumonia
neutropenia
Imaging findings of mucormycosis
Like IPA
More pleural effusion
Diagnosis of mucormycosis
Culture (usually negative)
Histopathology*
Treatment of mucormycosis
Liposomal Amphotericin B
Surgical debridement
IV isavuconazole and IV/PO posaconazole also now recommended as an alternative first line.
Risk factors for the development of nocardia
HIV CD4<100
SOT, especially lung
- High steroids independent RF
- High CNI levels independent RF
- CMV in last 6 months independent RF
Long term steroids, other IST
Lymphoma
PAP
COPD, bronchiectasis
Extra pulmonary manifestations of nocardia
Brain - abscess, meningitis
Skin - abscess
Bone
Muscle
Imaging findings of nocardi
Nodule
LN rare
Teatment of nocardia
Septra
Imipenem
Cephalosporins 3rd generation
Amikacin
Treatment duration for nocardia
6-12 months normally
12 months at least if immunosuppressed
Compare and Contrast Nocardiosis and Actinomycosis
Treatment of Nocardiosis
- Mild or moderate pulmonary disease septra x 6-12 months
- Severe:
** Septra IV + amkacin 7.5mg/kg
** OR Imipenem + Amikacin - IV therapy if required is for at least 6 weeks then PO for 6-12 months
** Po options include Septra +/- either minocylcine or amox clav.
Treatment of Actinomycosis
- Mild-Moderate
** Oral pen V 2-4g divided into q6 dosing
** Alternative: amoxicillin or Amox clav. - Severe: IV peng G 10-20million units divided into q6h dosing
** CTX is alternative - Duration:
** mild -Moderate 2-6 months
** SeverE: 6-12 months
Causes of unilateral hyperlucent lung
Poland syndrome (a congenital unilateral absence of the pectoralis major and minor muscles and is a recognized cause of unilateral hyperlucent hemithorax)
Mastectomy
Pneumothorax
Pulmonary embolism - Westermark
Vascular pruning
Swyer james mcleod syndrome ( unilateral hemithorax lucency as a result of postinfectious obliterative bronchiolitis often adenovirus or mycoplasma pneumoniae)
Congenital lobar emphysema
CPAM
Giant bullous disease
Pneumatocele
Pneumonectomy
Imaging features of bronchial atresia
LUL predominantly
Mucous filled atretic bronchial stump
Hyperlucent lung due to hyperinflation of distal lung (Pores of Kohn)
Bronchial atresia is a developmental anomaly characterized by focal obliteration of the proximal segment of a bronchus associated with hyperinflation of the distal lung.
Imaging features of CLE (Congenital lobar Emphysema)
Unilateral hyperlucent lung
Larger affected lung
Decreased vascularity
Contralateral mediastinal shift
Complications of CLE( Congenital Lobar Emphysema)
Recurrent pneumonia
Cyanosis
Failure to thrive
Imaging features of CPAM(Congenital pulmonary airway malformation)
Type 1 (Most common 70% ) and 4 -1 or 2 large cysts - associated with malignancy
Type 2 - numerous cysts, appears bubbly (I found small mixed solid/cystic lesions with 90% associated to bronchial atresia)
Type 3 - large, solid homogeneous mass (numerous small cysts solid or mixed)
Technically there is a Type 0 but though are very rare and are lethal at birth
Indications for treatment of CPAM
Symptomatic
Asymptomatic but:
- >20% hemithorax
- Concern for malignancy
- Frequent complications
Difference between CPAM and Bronchopulmonary sequestration?
BPS has no connection to the tracheobornchial tree and receives its blood supply from systemic ciculation vs. CPAM gets its blood supply via pulmonary circulation
Imaging features of ILS (intralobar sequestration) and ELS (extralobar sequestration)
Predominantly LLL
Dense mass, sometimes with cystic areas
Feeding vessel
Differences between intralobar and extralobar sequestration
Epidemiology (ILS 1:1 ; ELS Male 3: 1)
Blood supply ( both from systemic circulation but ILS drains to pulmonary veins and ELS to systemic and is fed from smaller vessels)
Location (ILS 60% left base ELS 90% Left with most associated with posterioro congenital diaphramatic hernia)
Pleural supply
Connection with tracheobronchial tree (ILS has no connection directly but may have bronchopulmonary foregute malformation, ELS does not)
Clinical presentation (ILS most likely infections, ELS is asymptomatic through life)
Surgical indications for pulmonary sequestration
Symptomatic
Complications
>/20% of the hemithorax
Characteristics concerning for malignancy/pleuropulmonary blastoma
Imaging abnormalities in Scimitar syndrome
Anomalous pulmonary venous return - (tubular structure)*
Right lung hypoplasia*
Pulmonary artery hypoplasia*
Ipsilateral mediastinal shift
Dextroposition
Pulmonary sequestration
Causes of tracheobronchomalacia
Previous prolonged intubation
Previous tracheostomy
Previous surgery e.g. lung transplantation
Marfan’s syndrome, Ehlers danlos syndrome, scoliosis, pectus excavatum
Relapsing polychondritis, other autoimmune conditions
Chronic inflammation e.g. CF, bronchiectasis
Recurrent infections e.g. bronchitis
Multinodular goiter, malignant or benign lesions of neck and mediastinum
COPD, asthma, obesity
Diagnostic criteria for tracheobronchomalacia
Non contrast dynamic CT and bronchoscopy (gold)
<70% normal, 70-80 mild, 80-90 moderate, >90% severe
Treatment for tracheobronchomalacia
Treat underlying cause
PAP therapy
Airway clearance techniques
Stent trial → tracheobronchoplasty (really just focal and proximal tracheobronchial malacia)
Diagnostic criteria for tracheobronchomegaly
Trachea >3 cm
RMS > 2.4 cm
LMS >2.3 cm
Causes of tracheal and subglottic stenosis
Congenital and idiopathic
Previous intubation
Previous tracheostomy
Previous surgery e.g. lung transplantation
Inflammatory e.g. relapsing polychondritis, vasculitis, sarcoidosis, IgG4 disease, Ra, SLE, amyloidosis
Infectious e.g. tuberculosis, fungal, bacterial
Malignancy
Radiation
Management of tracheal stenosis
Treat underlying cause
Balloon dilatation
Laser cautery
Stenting
Surgical
Causes of tracheal thickening
- Post intubation, post trauma, post surgery
- Malignancy e.g. SCAMM ( da fuq? But squamous cell carcinoma is most common) - maybe they meant it as an acronym… )
- Squamous cell carcinoma
- Chondrosarcoma
- Carcinoid tumour
- Adenoid cystic carcinoma
- Mucoepidermoid carcinoma
- Metastatic disease
- Infectious - e.g. TB
- Inflammatory - e.g. RP, GPA, amyloidosis, sarcoidosis
- Other - e.g. TBM, TBP OCP
Causes of thickening spare the posterior membrane
TBM
TBPOCP (tracheobronchopathia osteochondroplastica - nodules of cartilage or bone in the submucosa along the tracheal rings)
Relapsing polychondritis (inflammation of cartilage in the body)
Benign causes of tracheal masses
Chondroma ( slow growing made of cartilage)
Leiomyoma (fibroid, smooth muscle tumor)
Lipoma
Amyloidoma
Squamous cell papilloma
Hamartoma
Hemangioma
Tracheobronchomalacia osteochondroplastica -Nodules of cartilage or bone in the submucosa along the tracheal rings)
Malignant causes of tracheal masses
Squamous cell carcinoma
Chondrosarcoma
Carcinoid tumour
Adenoid cystic carcinoma
Mucoepidermoid carcinoma
Metastatic disease
SCCAMM
Differential diagnosis for mediastinal masses
Anterior
- Teratoma
- Thymoma and other thymic tumors
- Thyroid - goiter, malignancy
- Terrible lymphoma
Middle - 3A’s
- Adenopathy - lymphoma, sarcoid, silicosis, castleman’s, meds, infxn
- Aneurysms - aortic aneurysm, fistulas
- Anomalies - bronchogenic cyst
- Other - lipomatosis, lymphangiomas, hernias
Posterior
- Neural tumors e.g. Schwannoma, neuroblastoma
- Esophageal process e.g. mass, diverticula
- Descending aortic aneurysm
- Extramedullary hematopoiesis
- Bochdalek hernia
Blood work in the assessment of teratoma
Beta HCG
AFP
LDH
Examples of thymic tumors
Thymoma
Thymic carcinoma
Thymic lymphoma
Thymic neuroendocrine (carcinoid tumour)
Thymolipoma
Differentiate a seminoma GCT vs nonseminoma GCT
Beta HCG is high, AFP normal in seminoma
Both high in non seminoma
Complications associated with fibrosing mediastinitis
Atelectasis & Recurrent infections, dyspnea, cough
SVC syndrome
Pulmonary hypertension
Dysphagia
Phrenic nerve paralysis
Causes of congenital hernias
Morgagni hernia (Anterior, asymptomatic)
Bochdalek hernia (More common, posterolateral, can cause newborn symptoms due to lung hypoplasia) - “Bochdalek is Back”
Pulmonary manifestations of relapsing polychondritis
Tracheobronchomalacia
Tracheal stenosis
Subglottic stenosis
Tracheal thickening
These can cause OSA, post obstructive PNA
Contraindications & complications for:
Thoracentesis
Chest tube insertion
Bronchoscopy
Transbronchial biopsies
Surgical lung biopsies
Management of anticoagulation
Warfarin x 5 days, INR <1.5
DOAC 24-48 hours
LMWH x 24 hours, 6 hours if DVTp
Plavix , prasugrel x 5-7? days
Ticagrelor x 7 days
Dipyridamol x 24 hours
Platelet count >50K
In what conditions is bridging required?
Complications of suction
Increased RPO
Increased pneumothorax
Increased hemothorax
Increased pain
Causes of hypoxemia post thoracentesis
RPO
Pneumothorax
Hemothorax
V/Q mismatch immediately post
Risk factors for RPO following thoracentesis
Age <40
Large volume removed >1.5L ( GRAVITAS study says no)
Pressure <-20 cm H2O
Duration of collapse >72 hours
Size of pneumothorax
Diabetes
Indications for large bore chest tube insertion
Pneumothorax not responding to chest tube
Pneumothorax on mechanical ventilation
Trauma patient
Hemothorax
Required for talc pleurodesis
Microorganisms may not be pathogenic on BAL
NTM
Aspergillus
Candida
Cryptococcus
CMV, HSV
Microorganisms are always pathogenic on BAL
Legionella
Endemic fungi
Tuberculosis
PJP
Influenza, RSV
Diagnoses can be made with TBBx
Sarcoidosis
Hypersensitivity pneumonitis
Pneumoconiosis
Lymphangitic carcinomatosis
Tuberculosis
CMV pneumonitis
Lung transplant rejection
Maximum dose of lidocaine that should be used during bronchoscopy
5 mL/kg without epinephrine
7 mg/kg with epinephrine
Respiratory changes that occur during pregnancy
No change: VC, RR, lung compliance, resistance
Increase: MV, tidal volume, VO2 max, PaO2
Decrease: TLC, FRC, ERV, RV, total respiratory compliance, PaCO2
What is the difference on PFTs between Pregnancy and Obesity?
In pregnancy RV will be decreased and will be increased/same in obesity
Cardiovascular changes that occur during pregnancy
SVR decreases, PVR decreases - BP decreases
SV increases, HR increases, CO increases
Increased blood volume
Acceptable upper limit in pregnancy for radiation
<50 milligrays or <50 mSv
<5 rad
DDX for dyspnea in pregnancy
Physiological dyspnea in pregnancy
Peripartum cardiomyopathy
Tocolytic pulmonary edema
Asthma
Pulmonary embolism
Amniotic fluid embolism
Venous air embolism
PAVM growth
Obstructive sleep apnea
PE/DVT treatment in pregnancy
LMWH
Warfarin and DOAC contraindicated
At least 3 months + 6 weeks postpartum
Antibiotics that are contraindicated in pregnancy
Fluoroquinolones
Aminoglycosides
Septra, sulfa drugs
Tetracyclines
Changes that occur at high altitude
Hyperventilation
Increased HR and CO
Hypoxic vasoconstriction
Renal compensation, bicarbonate secretion
Polycythemia
Muscle changes - increase vascularity, increase myoglobin concentration, decrease in muscle fiber size
2,3 DPG shifts the oxygen curve
RV hypertrophy
Blunted response to acute hypoxemia
Associated complications with high altitude
Acute mountain sickness
High altitude pulmonary edema
High altitude cerebral edema
Periodic breathing of altitude
Methods of assessing hypoxia at altitude
Normobaric hypoxic challenge
Hypobaric hypoxic challenge
Predictive equations
Walk test and SpO2
Hypoxic Challenge test
Indications for a HAST test (High altitude Simulation Test)Hypoxic challenge Test
The obstructive algorithm, if at risk for hypercapnia
The restrictive algorithm, if either PaO2 <70 OR TLC <50%
CF FEV1<50% predicted
Severe asthma
NMD or chest wall weakness FVC <1L
Baseline hypercapnia or risk of hypercapnia
Who does not require a HCT (Hypoxic challenge Test) BTS 2022
Stable disease previously underwent an HCT without exacerbation/change in treatment
COPD with baseline SpO2 >95% and EITHER
* MRC 1-2
* Desat to no less than 84% during 6MWT or SWT
Previous intolerance to air travel/have had an inflight emergency (should have 2L/min provided as long as no hypercapnia
Preterm infants as they should have 1-2 L prn
Indications for HCT (Hypoxic challenge Test) BTS 2022
COPD with resing SpO2 <95%, MRC score 3 or greater, or desat <84% on 6MWT or SWT and hypercapnia
Infants with neonatal resp problems
Severe asthma with persistent symptoms
ILD with SpO2 <95% on exercise or PaO2 <9.42kPa or whose TLCO is <50%.
Severe respiratory muscle weakness or chest wall deformity in whom FVC<1L
Hypercapnia and at risk of hypercapnia including on meds that are high risk
Anyone with type 2 resp failure on home O2.
Obstructive Lung Disease HCT Testing.
Restrictive lung disease HCT testing
Note kPa of 9.42 is ~ 70mmHg.
What is a hypoxic challenge test and possible outcomes?
Inspire 15% oxygen (estimate 8000 feet) for 20 min checking sats or ABG
ABG pO2 falls below 50 or O2sat <85%
When is flying not recommended based on the HAST test?
pH falls <7.35
pCO2 increases by 7.5from baseline (1kPa)
How soon after EBUS/Pneumothorax/PE should you fly?
If a procedure was done (EBUS, TBBx, etc)
* Always get opinion from interventionist.
* Wait 1 week post procedure or if pneumo 1 week post resolution on CT
* Note limited evidence but apparently trapped lungs are fine to travel with.
If PE/DVT
* Wait 2 weeks after diagnosis
Flying with PH
NYHA WHO class 3 or 4 should have O2 (2L/min if no hypercapnia)
If on O2 should double it for the flight if no hypercapnia.
Contraindication to flying?
Untreated pneumothorax or not out of time frame
Untreated respiratory failure
Active infection with risk to others w.g. COVID, TB
Bronchogenic cysts (Can cause cerebral air embolism after rupture)
Type 2 respiratory failure
Baseline O2 >4L (old, not really anymore?)
DDX of symptoms during descent
Barotrauma of descent
Nitrogen narcosis
Immersion pulmonary edema
DDX of symptoms during ascent
Barotrauma of ascent
Decompression sickness
Arterial air embolism
Mechanism of barotrauma on descent vs ascent
Descent - lung squeeze below RV, pulmonary edema and hemorrhage
Ascent - overinflation and possible rupture (have to exhale) → PNTX, pneumomediastinum, subcutaneous emphysema, air embolism
Complications of barotrauma
Non cardiogenic pulmonary edema
PNTX
Pneumomediastinum
Arterial gas embolism
Ear trauma
Sinus barotrauma
Dental barotrauma
Timeline of symptoms of decompression sickness
Upon surfacing
Can be delayed up to 24 hours
Risk factors for decompression sickness
Ascension to fast
Time of dive
Depth of dive (rare <10 m )
Air travel and altitude within 12 hours
Right to left shunt
DDx of complications while surfacing
Decompression sickness
Barotrauma of ascent - expanding pneumothorax or pneumomediastinum
Shallow water blackout(hyperventilation lowers Co2 prior to diving, during breath hold O2 drops, because Co2 is rising but starting at a lower point it never reaches a threshold to cause an inspiration and person loses consciousness seconcdary to hypoxemia, then person draws a breath breathing in water and drowning)
Diagnostic criteria of EIB
Reduction in FEV1 by >/10% within 30 minutes of exercise
Can use cycle ergometer or treadmill
Indications for EIB
Diagnosis of EIB
Assessment of management
Assessing fitness for scuba diving
Contraindications for EIB
FEV1 <75% predicted
Stroke or MI in the last 3 months
Uncontrolled hypertension
Aortic aneurysm
Recent eye surgery or ICP elevation risk
Procedure for EIB
2-4 mins ramp up → rapid needed, otherwise dampens response
4-6 mins at exercise target
60% MVV (preferred), 80-90% maximum HR
Causes of a false negative EIB
Exercise in last 4 hours
Took asthma medications
Took antihistamines in last 48 hours
Warm up too long, didn’t reach in 4 mins
Exercised for too long
Didn’t reach max exercise
Management of EIB
Treatment:SABA
Prevention: SABA before exercise, +/- mast cell stabilizing agent and SAMA
If using above daily or more: Controller therapy: 1) Daily ICS +/- 2) LABA, 3) LTRA
Samter’s triad
Chronic rhinosinusitis with nasal polyposis
Asthma
NSAID/ASA intolerance
Pathogenesis of AERD
NSAIDs that preferentially block COX-1 enzyme
Arachidonic acid metabolized through lipoxygenase pathway
Increased leukotrienes, cause bronchoconstriction
Management of AERD
Maintenance ICS
Add on LTRA
Nasal polyp surgery, intranasal steroids
ASA desensitization
Dupilumab
Indications for ASA desensitization in AERD
NSAID for another disease
Recurrent nasal polyps recurring after surgery
Risk factors for development of asthma
Personal history of atopy
Family history of asthma
Low birth weight, premature , IUGR
Maternal smoking
Pollution exposure - vehicle emissions, industrial waste
Allergen exposure - dust mites, mold, cockroaches, pet dander, mice
LTRIs
Roles of the different TH2 mediators
IL-5: maturation of eosinophils
IL-4: IgE production by cells
IL-13: mucous production, hyperresponsiveness, eos recruitment
IgE: mast cell degranulation
TSLP: downstream signaling
Symptoms that support a diagnosis of asthma
Variable symptoms and intensity
Worse at night, upon awakening or after viral infections
Often triggered by exercise, allergens, cold air or laughing
Severity of methacholine response
Contra-indications to methacholine challenge test?
Relative:
* Pregnancy and nursing mothers. No studies on association with fetal abnormalities/reproductive capacity and no known whether it is excreted in breast milk.
* Current use of cholinesterase inhibitor medication (for MG or PD)
Definition of Asthma severity CTS 2021.
Difference between difficult to treat asthma and Severe Asthma.
- Difficult to treat Asthma:
- Uncontrolled Symptoms and or exacerbations despite medium or high dose ICS/LABA or maintenance OCS. May still be issues with inhaler technique, poor adherence, smoking or comorbidities, or improper diagnosis
- Severe Asthma:
- Uncontrolled despite adherence with maximal optimized high dose ICS/LABA and all contributing factors or if high dose treatment is decreased.
When to hold medication prior to methacholine challenge.
Comorbidities that should be assessed for at every visit
Elevated BMI
OSA
GERD
Rhinosinusitis, post nasal drip
Anxiety, depression
Asthma control criteria CTS
Daytime symptoms </2/week
Night time symptoms <1 week and mild
Use of rescue SABA </2/week
Exacerbations are infrequent and mild
Physical activity level maintained/normal
No absences from work or school due to asthma
No missed work or hospitalizations
PEF and FEV1 >/90% personal best
PEF variability <10-15%
Sputum eosinophils <2-3%
Severity of asthma exacerbations
Mild: just change in bronchodilators
Severe: Systemic steroids, ED or hospitalization required
Near fatal: required ICU, mechanical ventilation, respiratory acidosis
Risk factors for severe asthma exacerbation
Current smoker (studies on tobacco, but others considered)
SABA use >2 canisters/year
Hx of severe exacerbation
Poorly controlled
FEV1 <70%
Older age
Female
Elevated BMi
Depression, anxiety
Others as per GINA: comorbidities (GERD, OSA etc), elevated blood eos
Risk factors for near fatal asthma exacerbation
History of near fatal asthma
History of severe asthma
Hx recurrent ED or hospitalizations in the last year
Non adherence
Missed appointments
Depression, anxiety
Substance use
Elevated BMI
Management options and their benefits in Asthma
Action plan - exacerbations
Inhaled steroids - symptoms/QOL, lung function, exacerbation, mortality
LABA - symptoms, lung function, exacerbation, need for reliever
LAMA - lung function, exacerbation (but increased if monotherapy)
LTRA - symptoms, lung function, exacerbation, need for reliever
Azithromycin - symptoms, exacerbations
Biologics
Bronchial thermoplasty - exacerbations (increased in first 3 months), not sx or fxn
Oral steroids
Dose and appropriate phenotype for azithromycin therapy in Asthma
500 mg oral 3/week
Inflammatory phenotype does not predict response
Indications/requirements for bronchial thermoplasty
Poor control despite max medical therapy
FEV1 > /60%
Non smoker >/1 year
No hx life threatening exacerbation
<3 hospitalization in last 12 months
Complications of bronchial thermoplasty
Increase exacerbation x 3 months
Atelectasis
Pneumonia
Benefits of aerochambers
Reduce oropharyngeal deposition and side effects
Improve pulmonary deposition and benefits
Make actuation coordination easier
Rating severity of asthma
Severe = high dose steroids + second controller OR oral steroids for >/50% of the year to keep asthma controlled or uncontrolled despite this
Definition of uncontrolled asthma - One of:
Poor control - control criteria, or ACQ >/1.5
Frequent exacerbations (>/2 per year) requiring OCS (>/3 days)
Serious exacerbations (>/1 per year) requiring hospitalizations, ICU, MV in the last year
Airflow limitation <80% personal best
Etiology of uncontrolled asthma
Non adherence
Inhalation technique
Exposures
Comorbidities e.g. GERD, OSA, PND, etc.
Alternative diagnosis
Severe asthma
Investigation of severe asthma
Rhinosinusitis - tx, CT sinus, ENT referral
GERD - 24 hour PH monitoring
OSA - PSG
Psychiatric - referral
EGPA - ANCA
ABPA - IgE, RAST, eos
VCD - ENT
Bronchiectasis - CT chest, CF testing, IGAM, sputum culture
Biomarkers in TH2 inflammation and their cut offs
FENO >/25 ppb
Sputum eosinophils >2%
Serum eosinophils >/150
Asthma allergen driven clinically
Role of FENO?
Etiology of respiratory symptoms -?inflammatory
Predict response to steroids or inhaled steroids
Monitor response
Guide management - step up, step down
Evaluate adherence
What is considered a significant increase or decrease in FENO?
Baseline over 50 ppb: >20% increase, >20% decrease
Baseline less than 50 ppb: >10 ppb increase, >10 ppb decrease
Causes of increased FENO
Atopic asthma
Atopy, allergic rhinitis, eczema
Eosinophilic bronchitis
COPD with mixed inflammatory phenotype
Viral infections
Acute/chronic rejection of lung including BO
Causes of decreased FENO
Smokers
LTRA
Rhinosinusitis
Non eosinophilic asthma
RADS
VCD
COPD
Bronchiectasis, CF
Benefits of biologic therapy in Asthma?
Improve symptoms
Improve FEV1
Reduce exacerbations
Reduce OCS - mainly mepo, benra, dupi; resi in post analysis, ?oma
Notable side effects of biologic therapy in Asthma?
Injection site pain and reaction, nasopharyngitis, headaches
Omalizumab - anaphylaxis
Dupilumab - hypereosinophilia (do not give if baseline >1.5)
Tezepelumab - anaphylaxis
Treatment options for NONtype 2 asthma
LAMA
Azithromycin
Anti-TSLP
Bronchial thermoplasty
(paucigranulocytic asthma)
When to hold medication prior to methacholine challenge.
Treatment of asthma exacerbation
All → SABA, steroids
Additional to consider:
SAMA
IV magnesium
High dose ICS
BPAP
HFNC if cannot tolerate BPAP
IV epinephrine - if anaphylaxis or angioedema component
Ketamine - acts as anxiolytic
Heliox if component of upper airway obstruction
Steroid equivalents in asthma CTS.
Diagnostic criteria for RADS(irritant induced asthma)
Consistent history (acute exposure preceding symptoms, no sx before)
Airflow obstruction on PFT, non specific bronchial hyperresponsiveness
Symptoms arise within 24 hours
Symptoms last at least 3 months
Exclusion of other causes
Causative agents for irritant induced asthma
Chlorine
Oxides of nitrogen
Acetic acid
Sulfur dioxide
Isocyanates
RFs for developing sensitizer induced OA
RFs for developing sensitizer induced OA
Atopy
Higher level of exposure
More frequent exposure
Cigarette smoking
Causes of sensitizer induced OA
LMW: isocyanates (polyurethane worker, insulation installer, spray painter), dyes and bleaches (hairdressers), wood dust (carpenter), metal salt (metal plating)
HMW: flour dust (baker), animal protein antigens e.g. murine urine (veterinarian, farmer) & shellfish (fish processing), natural rubber latex protein (HCW)
Extrapulmonary symptoms of sensitizer induced OA
Rhinitis
Urticaria, rash
Investigations to confirm the diagnosis of occupational asthma
PEF - best validated method - variability >/20%*
NSBHR - less sensitive and specific - > 3.2 fold* (NON-SPECIFIC BRONCHIAL HYPERRESPONSIVENESS)
Specific inhalation challenge test - FEV1 drop by >/15%*
Sputum eosinophils - increase by >1-2%
Spirometry - less sensitive and specific
Once occupational asthma is confirmed, how do we find out the causative agent?
IgE like RAST testing
Specific inhalation challenge test
Stages of change for smoking cessation
Pre contemplative
Contemplative
Preparation
Action
Maintenance
5A’s of smoking cessation
Assess
Advise
Ask
Assist
Arrange
Side effects of smoking cessation
Change in mood
Weight gain
Increased sputum production
Benefits of smoking cessation
Rate of FEV1 decline normalizes
Normal MI risk by 1 year
½ cancer risk by 10 years
½ risk of dying in next 15 years
Impact of smoking on fetus
IUGR
Premature birth
Low birth weight
SIDS
Bronchopulmonary dysplasia
Success rate of quitting with and without aid cessation
5% without
30% with
Side effects of cessation aids
NRT: Nausea, vomiting, diarrhea, insomnia, vivid dreams, local irritation, hypersensitivity
Varenicline: nausea, vomiting, diarrhea, bizarre dreams, sleep walking, insomnia
Bupropion: decreased seizure threshold, suicidal or homicidal ideation, psychosis, mania or hypomania
Contraindications of the cessation aids
NRT: recent ACS or stroke (<2 weeks), uncontrolled BP
Varenicline: kidney disease, hypersensitivity
Bupropion: <18 (suicidality), seizure disorder, AN/BN, on MAOI, on wellbutrin, hypersensitivity, discontinuation of BZD, alcohol (things that lower seizure threshold)
RF for COPD development
Men
Cigarette smoking (in utero, passive, active), cannabis, vaping
Air pollution, biomass fuel burning
Occupational exposures e.g. coal, pesticides
HIV, childhood infections
Genetics e.g SERPINA
Early life lung insults, low birth weight
Comorbidities that are associated with COPD
Lung cancer
Cardiovascular disease
Skeletal muscle dysfunction
Osteoporosis
Anxiety, depression
JAMA physical examination findings with the highest LRs for COPD
Wheezing
Barrel chest
Decreased cardiac dullness
Physiological causes of exercise limitation in COPD
Hypoxemia - V/Q mismatch
Hypercapnia - DH, reached MVV
Increased WOB - due to mechanics
Muscle deconditioning
Cardiac deconditioning, decreased preload for DH
Measures of exercise tolerance?
6MWT
ISWT, ESWT
CPET
Measures of health status
CRQ Chronic Respiratory Disease Questionnaire) Evaluated physical functional and emotional
CAT
SGRQ (St. George Respiratory Questionnaire)
CCQ (Clinical COPD Questionnaire)
Prognostic factors in COPD
BMI </21
Severity of obstruction/FEV1
Dyspnea level/mMRC
6MWD
Concomitant hypoxemia requiring O2
Concomitant hypercapnia requiring NIV
Concomitant pulmonary hypertension, CPFE
Male, older, smoker
What can the BODE score be used to?
Referral and listing for transplant
Predictor of mortality
Survival associated with BODE scores (4 year survival) and its components
BMI:
Obstruction (FEV1):
Dyspnea (mMRC)
Exertion Capacity (6MWT)
0-2: 80%
3-4: 70%
5-6: 60%
7-10: 20%
Recommended vaccinations for patients with COPD
Influenza annually
Pneumococcal
COVID-19 as per public health
Pertussis if have not had in adulthood
Shingles >/50
RSV (If >60 OR chronic lung/cardiac condition)
What do we use to determine treatment in COPD?per CTS VS. GOLD
mMRC <2
CAT <10
FEV1>/80% predicted
Risk of future exacerbations (CTS: High Risk of AECOPD” if ≥ 2 moderate AECOPD or ≥ 1 severe exacerbation in the last year (severe AECOPD is an event requiring hospitalization or ED visit))
How is the risk of AECOPD determined?
Low: </1 moderate exacerbation in the last year
High: >/2 moderate exacerbations in the last year, >/1 severe
What is moderate vs severe exacerbation in COPD?
Mild: only change in short acting bronchodilators
Moderate: required steroids or abx
Severe: required ED visit or hospitalization
Benefits of inhaler therapies
Improve dyspnea
Improve health status
Improve exercise tolerance
+/- Reduce risk of exacerbation
+/- improve mortality
When is stepping down COPD bronchodilators NOT appropriate?
Moderate-high symptom burden
High risk of exacerbation
Eos >300
Indications that strongly favour ICS (as per GOLD)
> /2 moderate exacerbations for AECOPD
ED visit or hospitalization for AECOPD
History of concomitant asthma
Blood eosinophils >/300
ICS not strongly favoured (as per GOLD)
Eosinophils <100
Recurrent pneumonias
Hx of NTM disease
Indications for oral therapies in COPD
Symptomatic, high risk AECOPD group
Exacerbate despite triple therapy
+ chronic bronchitis phenotype for 2 of them
Benefits of oral therapies in COPD
Decrease exacerbation
Treatments that improve exercise tolerance in COPD
Smoking cessation
Appropriate bronchodilators
Pulmonary rehabilitation
Supplemental O2 in those who qualify
LVRS in appropriate patients
Bullectomy in certain patients
Endoscopic procedures
Lung transplantation
Treatments that reduce the risk of exacerbation in COPD
Appropriate bronchodilators - dual and triple
Oral therapies as indicated
Case management AND education
Pulmonary rehabilitation within 4 weeks of AECOPD
Smoking cessation
Influenza vaccination
Treatments that reduce mortality in COPD
Smoking cessation
Triple therapy (SITT)
PR within 4 weeks of AECOPD
O2 in resting hypoxemia( PaO2 <55 or <60 with core pulmonale/evidence of elevated hgb)
NIV acutely, or chronic hypercapnia
LVRS in appropriate patients
?Transplant in some
Ways to manage dyspnea in COPD (CTS table)
Walking aids
Pursed lip breathing
Neuromuscular electrical muscle stimulation
Low dose opioids
Oxygen in resting hypoxemia
Possible intervention in the treatment of COPD
LVRS
Bullectomy
Endoscopic procedures
Lung transplant
Who would be eligible for LVRS?
Symptomatic from emphysema and not CB/asthma
Smoking cessation >4 months
Heterogeneous emphysema
Upper lobe predominant emphysema
TLC >/100%
RV >/150%
FEV </45%
6MWD >140 m
What are the contraindications to LVRS?
Comorbid disease with life expectancy <2 years
Severe CAD or other cardiac disorder
BMI >31
FEV1 </20% oro DLCO </20%
Homogeneous distribution of emphysema
Giant bullae >⅓ chest
Extensive pleural symphysis e.g. previous infection, pleurodesis
O2 >6L/min
PaCO2 >60 mmHg or PaO2 <45 on room air
PAP >/35 mmHg
Prednisone >20 mg oral daily
Benefits of LVRS
Dyspnea
HRQOL
Exercise tolerance
Lung function
Mortality in some → upper lobe emphysema, low baseline exercise tolerance
Indications for treatment of giant bullae
Symptomatic
Complications
>/30% of hemithorax
Risk factors for COPDE
Older age
Low FEV1 at baseline
Previous COPD exacerbations **
Eos >/300 **
Chronic mucous hypersecretion
Duration of COPD
Pulmonary HTN
GERD
Treatment of AECOPD
SABA, SAMA
Steroids 40 mg oral daily x 5 days - hasten recovery, reduce relapse, improve FEV1
Antibiotics if meet criteria - hasten recovery, reduce relapse
IV magnesium
Abx options for treatment AECOPD
Amoxi-clav
Fluoroquinolones
Macrolides
Tetracyclines e.g. doxycycline
Indications for NIV in AECOPD?
pH <7.35, PcO2 >/45
Worsening WOB
Persistent and refractory hypoxemia
Different allele variants in A1AT deficiency
Normal - M
Deficient - Z/S
Dysfunctional - F
Null
Genotypes that have the highest risk of A1AT (in order)
-/- (least common)
Z/Z
Z/S (if they smoke)
Z/M (if they smoke)
Indications to screen for A1AT
Age <65 OR
Pack year <20
Non pulmonary manifestations of A1AT
Transaminitis
Cirrhosis
HCC
Necrotizing panniculitis
GPA/ANCA vasculitis
Intracranial aneurysms
Fibromuscular dysplasia
Diagnosis of A1AT
Applicable genotype
A1AT level <11 mmol/L or 57 mg/dL (our units)
Indications for treatment of A1AT
AAT <11 umol/L or 57 mg/dL (our units)
FEV1 25-80%
On maximal pharmacological and non pharm therapy (including PR)
Have quit smoking - non-smokers or ex-smokers (nothing in guidelines, funding requires at least 6 months)
Benefits of augmentation therapy in A1AT
Improve lung density on CT
Improve FEV1
Improve mortality
Benefits of supplemental O2 therapy at rest in COPD
Mortality benefit in those that qualify
Improved dyspnea
Improved exercise tolerance
Improved physiological effect e.g. ?decreased PH
Benefits of supplemental therapy with ambulation in COPD
Improved HRQOL
Improved outdoor mobility
Not clear re: dyspnea, exercise capacity
3 types of patients with COPD that would benefit from O2
Resting hypoxemia
Resting hypoxemia and comorbidities listed
Patient planning for air travel if they meet criteria
?Ambulatory or exertional hypoxemia
Duration of PR programs
Minimum 8 weeks
Minimum 24 sessions, 16 should be supervised
Quality indicators of a PR program
Necessary HCP, and resources:
Cycle ergometer, treadmill, flat open space
Vital machines
Education material
Etc.
Baseline intake indicators:
Dyspnea
Health status
Exercise capacity
1 Repetition maximum
Aerobic exercise prescription
Strength training prescription
Exercise indicators
Monitoring indicators
Education and self management component
Post program
4 parameters that are needed for exercise prescription (aerobic)
Frequency - 3 sessions
Intensity - 60% VO2 max
Time - 20 mins each session
Type - aerobic - treadmill, free walking, stair climb, ergometer (NOT arm alone)
4 parameters that are needed for exercise prescription (strength)
Frequency - 2-3 times per week
Intensity - 60% of 1-RM
Time - 1-3 sets, 8-12 repetitions each
Type - weights, resistance bands
Minimum health outcomes that need to be measured before and after PR
Aerobic exercise endurance
Muscle function
Health status
Others case by case: psychological status, nutrition status, self efficacy, etc.
Indications for referral to PR
COPD - regardless of FEV1 or smoking status
ILD
PHTN
Proven benefits of PR
COPD - dyspnea, HRQOL, exercise capacity, social/physical fxn, reduce anxiety, depression, ??mortality
ILD - dyspnea, HRQOL, exercise capacity
PHTN - dyspnea, HRQOL, exercise capacity
Physiological benefits post PR for COPD
Improved VO2 max
Improved O2 pulse
Decrease in HR
Increased AT
Increased muscle mass
Decrease dynamic hyperinflation
Which post COVID patients are appropriate for PR referral?
New respiratory symptoms post COVID +
At least 1 of: new O2 requirements, persistent reticular/fibrotic changes on imaging, new and persistent restriction/obstruction/DLCO impairment on PFTs
Causes of eosinophilic lung diseases
Acute/chronic eosinophilic pneumonia
EGPA
HES
ABPA
Infections - parasites, fungal
Neoplastic - e.g. paraneoplastic
PLCH
Lung transplantation
Causes of AEP
Idiopathic
Smoking - new, increased uptake, different type
Inhalation drugs- cocaine, marijuana
Medications - daptomycin**, antidepressants
Occupational exposures
Infections - parasites, fungi
Imaging findings in eosinophilic pneumonia
Acute: diffuse, bilateral GGO, bronchovascular thickening, effusion, LN
Chronic: peripheral, bilateral GGO, upper lobe, migrating
Differences between AEP and CEP
Causes - allergic/atopic causes in chronic
Clinical manifestations - symptoms, timeline
Relapse - common chronic
Imaging
Peripheral eosinophils - seen in chronic
Both have elevated IgE
Both have BAL eos >25%
Both are treated with steroids
Diagnostic criteria for AEP
Acute onset, <30 days
Patchy infiltrates on CXR/CT
BAL eos >25%
Absence of other specific eosinophilic diseases
Diagnostic criteria for CEP is similar, except that timeline is 4-5 months and imaging is peripheral infiltrates
Diagnostic criteria of HES
HE + eosinophilic mediated damage + other causes excluded
HE: >1.5 on 2 occasions at least 1 month apart, and >20% (2024 says 10%) on BM, and extensive eos infiltration on pathology
How is surfactant produced?
Type II pneumocytes secrete surfactant
Surfactant is mix of proteins + lipids (mainly phosphatidylcholine)
Causes of PAP
Idiopathic
Primary:
Hereditary
Autoimmune
Secondary (HI/TII):
Infections e.g. nocardia, PJP, tuberculosis
Inhalation exposures e.g. silicosis, chlorine, bakery powder
Transplantation e.g. SOT, HSCT
Hematological malignancies e.g. MM, WM
Immunodeficiencies e.g. CVID
BAL findings in PAP
Cloudy
Foamy macrophages
Send for PAS stain on cytology → PAS+ macrophages on background of PAS material
Other investigations in PAP
Anti GM CSF antibodies
GM CSF serum levels
GM CSF receptor function
BAL
TBBx - not required for biopsy
Pathological findings of PAP
Normal alveolar structure
Lipo Proteinaceous material fills terminal bronchioles and alveoli
This material stains positive on PAS stain
If done, electron microscopy shows lamellar bodies
Treatment options for PAP
Anti GMCS replacement
Whole lung lavage
Treat secondary cause
Lung transplantation
Rituximab, PLEX - case reports
Indications for whole lung lavage
Definitive histological diagnosis +
PaO2 <65, or A-a >/40 or severe dyspnea/hypoxia at rest or exercise
Imaging findings and distribution of different cystic lung diseases
LAM = diffuse, random, small cysts
BHD = lentiform, paramediastinal, peripheral, subpleural
PLCH = bizarre shaped, upper lobe predominant, spare costophrenic angles, nodules/cavities
LIP = diffuse, random, GGO in between
Amyloid/LCDD = cysts varying sizes/shapes, nodules, cavitations, opacities lower lobes/subpleural
Special pathological tests for different cystic lung diseases
LAM = HMB-45 positive smooth muscle cells
PLCH = S100 and CD1 a positive langerhans cells, intracellular Birbeck granules
Amyloid = apple green birefringence by congo red stain
LCDD = kappa light chains lacking the above
Pulmonary manifestations of PLCH
Cystic lung disease
Group 5 HTN
Eosinophilic lung disease
Extrapulmonary manifestations of PLCH
Rash - brown papules
Lytic bone lesions
Central diabetes insipidus
Treatment of PLCH
Smoking cessation
Steroids in some
Chemotherapy in some
Transplantation
Extrapulmonary manifestations of BHD
Fibrofolliculomas
Skin tags
Renal tumors
Extraparenchymal manifestations of LAM
Angiofibromas
Leiomyoma
Angiomyolipoma
Lymphadenopathy
Pleural effusions
Meningiomas
Pathological features of LAM
Lung cysts
Smooth muscle-like cell (LAM cells) infiltration of parenchyma and lymphatics
Stain positive for HMB45, s.m. actin
Have ER/PR receptors
Express VEGFC/D
Diagnostic criteria for LAM → table
Differential diagnosis for cystic lung disease
Indications for treatment of LAM
FVC <70%
Case by case basis for those who:
Resting hypoxemia PaO2 <70
Exercise induced desaturation
RV >120%
DLCO <80%
Progression of disease (FVC loss >/90 cc per year
Heavy burden of cysts >30% of lungs
Chylous effusion
AML >4 cm
Benefits of mTOR inhibitor as per the MILES study in LAM(Sirolimus)
Improve symptoms
Improve QOL
Stabilize lung function
Reduce VEGFD
Management of complications of LAM
Pneumothorax:Pleurodesis after first episode, advised not to air travel x 1 month
Chylothorax: chest tubes, consider mTOR inhibitor
Angiomyolipoma: embolization, radiofrequency ablation, consider mTOR if >/4 cm
Screening investigations that are required in LAM
Abdominal CT for all
Brain MRI if symptoms, or increased risk (e.g progesterone)
Basically looking for evidence of TSC given that is more common
Secondary causes of LIP
Idiopathic
Connective tissue diseases
Immunodeficiency e.g. CVID
Infections e.g. HIV, tuberculosis
PAP
PFT findings in different bronchiolar disorders
Proliferative - restrictive
Obliterative - obstructive
Follicular - mixed, restrictive, obstructive
Diffuse panbronchiolitis - mixed, restrictive, obstructive
Imaging findings of different bronchiolar disorders
Proliferative: patchy airspace, migratory, reverse halo, with distribution subpleural/peripheral, peribronchovascular
Obliterative: mosaic attenuation, centrilobular nodules, gas trapping bronchial wall thickening, bronchiectasis
Follicular: centrilobular nodules, tree in bud
Diffuse panbronchiolitis: centrilobular nodules, tree in bud, bronchiectasis
3 features of COP on CT
Distribution peripheral, subpleural, migrating, peribronchovascular, bilat
GGO or consolidative alveolar opacities
Atoll sign (Reverse halo sign-more common with OP and less commonly fungal but mucormycosis most common of the fungal)
Diagnosis of bronchiolitis
Surgical lung bx
Post transplant BOS can be clinical
Pathological findings of bronchiolitis
Proliferative - intrabronchial polypoid protrusions (mason bodies)
Obliterative - Lymphocytic inflammation of submucosa, in growth of fibromyxoid granulation tissue into airway, obliteration of airway - extrinsic compression of bronchioles by fibroinflammatory process
Follicular: hyperplastic lymphoid tissue along bronchial walls that obliterate lumen
Diffuse panbronchiolitis: lymphoplasmacytic inflammation of bronchioles; infiltration with lipid laden foamy macrophages, lymphocytes, plasma cells
Causes of proliferative bronchiolitis/organizing pneumonia
Idiopathic
Immune deficiency
Inhalational injury
Infections e.g. COVID
Malignancy, chemotherapy, radiation
CTD
Medications
Aspiration
Post transplantation
Causes of obliterative bronchiolitis
Post allograft transplantation (HSCT, lung)
Inhalational injury e.g. silo, sulfur, silica, diacetyl
Infection
CTD, especially RA
Causes of follicular bronchiolitis
Idiopathic
CTD, especially Sjogren’s; RA, SLE
Infection e.g. TB, HIV
Immunodeficiency
Chronic inflammatory e.g. bronchiectasis, CF, asthma
Causes of diffuse panbronchiolitis
CTD e.g. RA
Ulcerative colitis
Lymphoma
Basically always nonsmokers in Japanese and Korean patients
Treatment of the bronchiolar disorders
Proliferative: steroids
Obliterative: depends on cause
Follicular: steroids
Diffuse panbronchiolitis: erythromycin, bronchodilators
Treatment of COP if not responding to steroids
Azathioprine
MMF
Obviously treat underlying cause
Pulmonary manifestations of immunodeficiency
GLILD
LIP
Follicular bronchiolitis
Bronchiectasis
Organizing pneumonia
PAP
Recurrent pneumonias
Non pulmonary manifestations of immunodeficiency
Granulomas in other organs
Non hodgkin’s lymphoma
Pernicious anemia
Thyroiditis
Imaging findings of GLILD
Hilar and mediastinal LN
Bronchiectasis
GG and solid nodular opacities
Malignancies at highest risk for Radiation Induced Lung Disease
Lung cancer
Mediastinal lymphoma
Breast cancer
RFs for development of radiation pneumonitis
Dose of radiation (usually >40, very rare <20)
Volume of lung irradiated (V20 >/30%)
Form of radiation e.g. SBRT lower risk
Fraction of radiation
Previous chemotherapy
Underlying lung disease e.g. ILD**, COPD
Concomitant chemotherapy
Female > male
Smoker
Older age
Phases of development of radiation pneumonitis
Initial = increased capillary permeability
Latent = increased goblet cells
Acute exudative = radiation pneumonitis = 1-3 months = epithelial cell sloughing, microvascular thrombosis, alveolar exudate and hyaline membranes
Intermediate = 3-6 months = resolution of hyaline membranes
Fibrosis = >6 months = fibrosis
Time line of radiation induced lung disease
Radiation pneumonitis - within 1-3 months
Radiation fibrosis - 6-12 months
Radiation recall pneumonitis - really anytime
* Pneumonitis in the same radiation field. Usually triggered by systemic treatment or infection.
Symptoms of radiation pneumonitis
Fever, malaise, weight loss
Dyspnea
Dry cough
Pleuritic chest pain
Imaging findings in radiation pneumonitis
GGO
Consolidation
Straight line pattern, radiation port edges
Small pleural effusion
Pathological findings of radiation pneumonitis
Epithelial and endothelial cell sloughing
Fibrin rich alveolar exudate
Hyaline membrane formation
Microvascular thrombosis
Lung diseases are associated with smoking
DIP
RB ILD
PLCH
Lung diseases that have smoking as a risk factor
IPAF
RA ILD
Lung diseases are actually less common in smokers
Sarcoidosis
HP
Other than smoking, causes of DIP
Idiopathic
Occupational exposures e.g. metal worker
Drug reactions
Autoimmune conditions
Imaging differences RB-ILD vs DIP
RB-ILD: centrilobular GGO nodules, upper lobe predominant, preserved lung volumes
DIP: GGO, +/- cysts, reticular opacities, lower lobe predominance
BAL findings RBILD vs DIP
RB-ILD: pigmented macrophages, unlikely to have other cells
DIP: pigmented macrophages, may have increased lymphs/eos/neuts
PFT RBILD vs DIP
RB-ILD: can be obstructive, restrictive or mixed
DIP: usually restrictive
Exogenous causes of lipoid pneumonia
E cigarettes
Mineral based laxatives
Petroleum jelly lubricants (used in tracheostomy care)
Nasal decongestants
Fire eaters
Endogenous causes of lipoid pneumonia
Bronchial obstruction
PAP
Lipid storage and metabolism disorders
Chronic inflammatory disorders e.g. CTD
Imaging findings of lipoid pneumonia
GGO or consolidation
Crazy paving pattern
BAL features of lipoid pneumonia
Lipid laden macrophages
Are detected by oil red O staining
Red flags for cough
Age - > 55 years old
Smoker, ex smoker
Hemoptysis
Dysphonia, dysphagia
Recurrent pneumonia
Prominent dyspnea
Systemic symptoms
Vomiting
How does albuterol cause lactic acidosis?
Type A lactic acidosis - hypoxic or hypoperfusion
Type B lactic acidosis - malignancies, drugs and inborn errors of metabolism
Albuterol, by creating hyperadrenergic state enhances glycogenolysis and gluconeogenesis, leading to more glucose, pyruvate production. Lipolysis and increased FFA inhibit pyruvate dehydrogenase enzyme, so it doesn’t enter krebs cycle and is reduced to lactate
Absolute and relative contraindications to cardiopulmonary exercise testing
How would you predict the maximal HR for a CPET according to ERS? (M and F)
Male MaxHR =207-0.78(Age)
Female Max Hr=209-0.86(Age)
Indications for cessation of exercise termination in a CPET (ATS)
What defines a maximal test according to ERS 2019
What defines an abnormal exercise response ERS 2019 on CPET.
What is the cause of limitation based on ERS 2019 on CPETs?
What is the cause of limitation based on ATS on CPETs?
What are the four phases of general CPET protocols based on ERS 2019.
Difference on CPET between cycling and Treadmill (ATS2001)
Difference between fibrosing mediastinitis and mediastinal granuloma?
What is the triad of hepatopulmonary syndrome
Liver disease
Intrapulmonary vasodilation
Gas exchange abnormalities
Define and write the equation for oxygen content (CaO2)
Oxygen content — The arterial oxygen content (CaO2) is the amount of oxygen bound to hemoglobin plus the amount of oxygen dissolved in arterial blood:
CaO2 (mL O2/dL) = (1.34 x hemoglobin concentration x SaO2) + (0.0031 x PaO2)
where SaO2 is the arterial oxyhemoglobin saturation and PaO2 is the arterial oxygen tension
Define and write the equation for oxygen delivery (DO2)
Oxygen delivery — Oxygen delivery (DO2) is the rate at which oxygen is transported from the lungs to the microcirculation:
DO2 (mL/min) = Q x CaO2
where Q is the cardiac output.
Define and write the equation for oxygen consumption(VO2)
Oxygen consumption — Oxygen consumption (VO2) is the rate at which oxygen is removed from the blood for use by the tissues. It can be measured directly or calculated. Both approaches assume that all unused oxygen passes from the arterial to the venous circulation.
VO2 (mL O2/min) = Q x (CaO2 - CvO2)
What are important bacteria for those with reduced cell counts?
<200: PJP, endemic fungi, aspergillus, candida
<100: Toxoplasmosis
<50: MAC, CMV
Causes of pulmonary disease in HIV?
ILD - OP, NSIP, LIP
PAP
Emphysema
Bronchiectasis
Bronchiolitis - obliterative, follicular
Pulmonary hypertension
HIV Cardiomyopathy causing pulmonary edema
Drug reaction to HAART or other medications
Various infections
Various malignancies
Manifestations of kaposi sarcoma
Skin disease
Parenchymal disease
Endobronchial disease
Mediastinal lymphadenopathy
Imaging findings in Kaposi Sarcoma
Flame shaped, ill defined opacities
Interlobular septal thickening
Lymphadenopathy
Publicly reported illnesses
Legionella
Invasive pneumococcal disease
Influenza
H. influenza
HIV
Tuberculosis
SARS
COVID
Legally, I have to share COVID-19 news
Most common bacterial causes of CAP
Strep
Staph
H influenza
Mycoplasma
Atypicals
Aerobic gram negative → klebsiella, e. Coli, enterobacter, pseudomonas, serratia, proteus, acintobacter
Anaerobes
Most common causes of VAP
Strep
Staph - MSSA and MRSA **
Pseudomonas **
Gram negative bacilli
Bacterial causes of cavitary pneumonia
Klebsiella
Staphylococcus
Anaerobes
Nocardia
Actinomyces
Rhodococcus
TB/NTM
Endemic fungi
Organisms that cause interstitial infiltrates
Legionella
Mycoplasma
Chlamydia
Viruses
Imaging features of viral pneumonia
Interstitial infiltrates - can be reticular, reticulonodular
Miliary pattern
Airspace opacities or consolidation
Peribronchial thickening
When is 5 days of antibiotic treatment OK vs. 10 days?
Afebrile x 48 hours AND
</1 sign of instability: HR >100, BP <90, RR>24, SpO2 <90%, normal mental status
Complications of MSSA pneumonia
Abscess
Cavitation
Pleural effusion
Bacteremia
Resistance to MRSA
Risk factors for VAP
Paralysis
Head injury or unconscious
Aspiration
Chronic lung disease
Nasogastric tubes
Condensate in ventilator tubing
Supine position
Diagnostic criteria for VAP
Occur >/48 hours of intubation
Not present before intubation/wasn’t the reason for intubation
New or progressive infiltrates on imaging
Clinical evidence of infection e.g. fever, purulent sputum, leukocytosis, hypoxemia
Positive pathogen required by some definitions
Methods to diagnose causative agent in VAP
Invasive (BAL, brush, biopsy) > non invasive (endotracheal aspirate)
Quantitative (colony forming units) > semi quantitative (1+/2+ growth rates)
Measures to reduce VAP
Head of bed elevated 30-45 degrees
Mouth hygiene (tooth brushing but no chlorhexidine)
Enteral over parenteral nutrition
Only clean tubing when there is visible soiling
Limit sedation
Subglottic drainage
Ventilator liberation where possible
Maintain physical functioning
Complications of strep pneumonia
Empyema
Meningitis
Endocarditis
Pericarditis
Septic arthritis
Invasive streptococcal disease - CSF, blood, pleural, pericardial, synovial
RFs for IPD
Age
Chronic heart disease
Chronic lung disease e.g. asthma requiring medical care in last year
Chronic liver disease
Chronic kidney disease
Diabetes
Malnutrition
Immunodeficiency
Splenectomy, functional asplenia from sickle cell
HIV infection
HSC transplant
SOT transplant
Leukemia and lymphoma
Immunosuppressive therapy
Risk factors for drug resistant strep pneumo
> 65 or <2
Daycare or institutional setting (exposure to child)
Beta lactam use within 3-6 months
Medical comorbidities
Immunocompromised
EtOH
Indications to test for legionella
Severe CAP
Not responding to beta lactam
Epidemiological factors e.g. outbreak
Diagnostic test for legionella
Urine legionella antigen
PCR
Culture
Treatment regimen for legionella
Azithromycin 500 or levofloxacin 750
Duration: 7 days (mild), 10 days (severe), 14 days (immunocompromised)
Viral causes of pneumonia
COVID-19
Influenza A and B
RSV
Parainfluenza
Rhinovirus
Adenovirus
RFs for a more severe response to influenza
> /65 years old
Pregnant
Postpartum up to 2 weeks
Long term care, nursing homes
Chronic medical condition - respiratory, renal, liver, etc.
Immunosuppression
The common superinfections post influenza
Staph aureus
Streptococcus
Diagnostic options for influenza and COVID
Rapid antigen test
RT-PCR
Cultures
Benefits of oseltamivir
Reduce duration of symptoms
Reduce risk of death in inpatients
Within 48 hours has best outcomes
COVID-19 imaging findings
GGO
Consolidation
Crazy paving
Bronchovascular thickening
Pleural effusion, LN
Current COVID-19 therapies
Mild: budesonide, remdesivir, Paxlovid, fluvoxamine
Moderate: dexamethasone, remdesivir, tocilizumab, baricitinib
Severe: dexamethasone, tocilizumab, baricitinib
COVID-19 vaccines available
MRNA - pericarditis, myocarditis, Bell’s palsy, anaphylaxis
Vector - VTE, GBS, anaphylaxis
Treatment of echinococcal cyst
Antiparasitic therapy e.g. albendazole
Consider surgical resection
Consider percutaneous aspiration
