RPA Respiratory Flashcards
age onset of Aspirin-Exacerbated Respiratory Disease
adult acquired condition onset in 30s
clinical features of Aspirin-Exacerbated Respiratory Disease
symptoms after aspirin 30-90 min
mucosal swelling of sinuses and nasal membranes, formation of polyps and asthma
triggered by alcohol
upper and lower airway symptoms, hayfever symptoms
What has a high specificity in Aspirin-Exacerbated Respiratory Disease
normal sinus CT is a good rule out test
surgery and nasal polyps in Aspirin-Exacerbated Respiratory Disease
nasal polyps will recur
treatment for Aspirin-Exacerbated Respiratory Disease
ICS, leukotriene antagonists (monteleukasts), nasal steroids, antihistamines
definitive: desensitisation to aspirin then long term aspirin after debulking surgery
diagnositic test of Aspirin-Exacerbated Respiratory Disease
aspirin challenge test
who does the fleischner guidelines not apply to
under 35, known cancer, immunosuppressed
what kind of nodules should be monitored for a longer time as per Fleischner Guidelines
ground glass nodules:
adenocarcinoma in situ, slower growing
recommended for 5 years of monitoring (instead of the normal 2 years)
risk factors for pulmonary nodules
- older age
- smoking history 30 years and cessation within 15 years
- larger nodle
- spiculated
- upper lobe location
classification of interstitial lung disease (7)
- idiopathic interstitial pneumonias
- Iatrogenic drug induced (bleomycin most severe; radiotherapy - gives a non anatomical straight line)
- Occpational/environmental
- Silicosis - jack hammers, stone masons, kitchen bench tops
- Hypersensitivity pneumonitis
- Granulomatous disease
- Collagen-vascular (scleroderma, lupus, sjgoren’s)
- Inherited (alpha-1-AT)
- Unique entities
3 lung manifestations of alpha-1- AT deficiency
emphysema
interstitial lung disease
bronchiectasis
What ILDs are associated with smoking?
Respiratory bronchiolitis-interstitial lung disease
desquamative interstitia pneumonia
what major idiopathic interstitial pneumonais are steroid insensitive
interstitial pulmonary fibrosis
onset of breathlessness of interstitial pulmonary fibrosis
months
what sign will all patients with symptomatic interstitial lung disease have
fine inspiratory crepitations
which condition relies on the distance for 6MWT vs hypoxia on 6MWT
PulHTN for distance for 6MWT, hypoxia for 6MWT
what is the first test to change in LFT in interstitial lung disease
DLCO (function of alveolar membrane)
What kind of films are required for HRCT for ILD
inspiratory/expiratory; prone/supine (differentiate between normal atelectasis changes due to gravity vs early IPF)
basal/lower lobe predominance in CXR ILD condition
interstitial pulmonary fibrosis
terminoogy w fibrosis vs ground glass
ground glass is no architectural distortion
fibrosis/honey has architectural distortion
key radiological featuers of IPD
lower lobe predominant
disease of architectural distortion
often prone film
predominantly subpleural
minimal ground glass
temporal heterogenity (pathognomonic) - on 1 scan, there is different ages of fibrotic disease; does not need biopsy
Diagnosis
Sjogren’s
cysts and ground glass (Lymphoid interstitial pneumonia)
pulmonary lymphomas
why have inspiratory and expiratory CTs
the black bits (with more air) should get smaller during expiration.
If the black bits get bigger, that’s gas trapping.
If the black bits get smaller, the grey bits are abnormal
ground glass definition
alveolitis
opposite of fibrosis
acute inflammatory change
who needs a biopsy in ILD
if clinical picture does not match radiological picture
first line treatment for sarcoidosis
prednisolone
treatment of IPF
- Antifibrotic drugs - slows the rate of decline; MDT required for diagnosis; works better earlier in disease progression
- Nintedanib
- Tyrosine kinase inhibition
- PIrfenidone
- Inhibition of TGF-beta production and downstream signaling, collagen synthesis, fibroblast proliferation
- Nintedanib
- lung transplant
Treatment of comorbidities: reflux; pulm HTN
Treatment criteria PBS:
- FVC >50%
- PEV1/FVC >0.5
- DLCO >30%
which IPF drug causes hypersensitivity rashes
Pirfenidone
Which IPF drug causes diarrhoea
Nintedanib
definition of bronchiectasis
radiological definition
small airway that is bigger than the vessel that it runs with
classification of bronchiectasis
focal and diffuse
causes of focal bronchiectasis
- Luminal blockage: foreign body, slow growing cancer
- Extrinsic narrowing due to enlarged lymph node (middle lobe syndrome)
- Twisting or displacement of airway after a lobar resection
Presents with recurrent persistent lobar pneumonia
Next step is bronchoscopy
Patient presents with recurrent lobar pneumonia in the same area and CT shows bronchiectasis. WHat is the next step
bronchoscopy
Causes of diffuse bronchiectasis
- Infections (need pneumonitis from the disease that go on to develop bronchiectasis)
- TB most common cause worldwide
- Post-viral
- Severe bacterial infection
- Congenital conditions
- Immunodeficiency conditions
- Rheumatological conditions
- Toxins or drug exposure
Bronchiectasis in upper lobes cause
Cystic fibrosis (and Allergic bronchopulmonary aspergillosis)
Upper airway disease out of proportion to bronchiectasis
Primary ciliary dyskinesias
Primary ciliary dyskinesias genetics
autosomal recessive with variable penetrance
diagnosis of Primary ciliary dyskinesias
nasal swab biopsy w cilia studies
“ciliary studies”
Primary ciliary dyskinesias clinical symptoms
Bronchiectasis
CHornic sinusitis
agenesis of frontal sinuses
recurrent otitis media
some will have Kartagener’s syndrome (embrological consequence of severe back to ciliary things
proportion of RA w bronchietasis
30%
Management of bronchiectasis
- Sputum clearance
- Treat acute exacerbation (14 days)
- Prophylactic antibiotics (pseudomonas, who has >2 infections in a 12 mon period, who do not have non tuberculous mycobacterium)
- Macrolides; nebulised aminoglycosides
- Treatment of underlying conditions (e.g. IVIG for IgG def)
- Reduction of excessive inflammatory response (e.g. inhaled steroids)
- Contral of bronchial haemorrhage
- Surgical removal of segments/lobes
definition of difficult to treat asthma
symptoms despite high dose steroids
Common reasons for poor control
Puffer technique
Smoking
Upper respiratory tract infecitons
Medications (BB - note eye drops, NSAIDs, dustmites, molds)
Storms
Reflux
Upper airway disease
APBA
Churg Strauss (eosinophilic granulomatosis with polyangiitis)
definition of severe asthma
see slides
Which plant triggers thunderstorm asthma
Ryegrass
Other optiosn to add to high dose ICS/LABAB
tiopropium (only lama) - shown to increase lung funciton and time to first exacerbation
Macrolide
Leukotriene modifier
THeophylline (not commonly used and not on guidelines)
Oral steroids (not on guidelines)
then biologics
biologics for asthma
- omalizumab - subcutaneous injection into patients with moderate allergic asthma who have a raised IgE concentration and are already taking steroids
- forms complexes with free IgE to prevent it binding to mast cells
- mepolizumab
- Anti IL-5
- benzalizumab
- Anti IL-5
Types of asbestos related lung disease
pleural plaques
which type of asbestos is worst for mesotheliuoma
blue (crocidolite)
latency period of asbestos
30-40 years
which asbestos related lung disease is related to the highest amount of asbestos exposure
asbestosis
which asbestos related lung disease can occur from minimal (once-only) exposure
mesothelioma
pleural plaques CXR findings
benign
calcified
discrete plaques in the pleural
classically seen on diaghragm or cardiac line
number of plaques correlates to the exposure
monitor for 3 years
asbestos related pleural disease CT findings
benign, not pre-malignant
requires second most exposure after asbestosis
can present with pleural thickening or pleural exposure
diagnosis on CT - >25% of circumference of pleural disease OR rounded atelectasis - pleural is thickening and encroaches on normal lung; it is directly contiguous with the pleural; also has crow’s feet) also need other areas of asbestos related disease
asbestosis CT features
UIP pattern
nornally also need plaques
someone who has worked for decades
no treatment except for oxygen
mesothelioma clinical presentation
pleural effusion, with chest wall pain (dull ache keeps them awake at night) due to neural invasion
can be in peritoneum
diagnosis of mesothelioma
pleural biopsy (not just pleural fluid) - but be careful that mesol can seed the tract of the biopsy
CT has mediastinal reflection (unlike parapneumonic effusion)
mesothelioma treatment
limited options
pleuropneumectomy (12% 5 year survival)
1st line pemetrexed+platinum based; 2nd line - gemcitabine
pain relief (neuropathic agents)
early pleuradiesis (usually at the same time as the VATs pleural biopsy)
what other lung cancer is related to asbestos (not mesothelioma)
NSCLC
acute exacerbation of IPF definition
ground glass
acutely hypoxia
exclude infection
mortality +++ (close to 100%); tx: corticosteroids but no evidence of mortality benefit
diagnosis of restless legs syndromes
clinical diagnosis
diagnostic criteria: URGE
- urge to move limb
- rest (worse during rest)
- Getting up and moving or walking improves
- evening worsens or precipitates symptoms
non essential:
- family history
- response to dopaminergic therapy
- sleep disturbance
- PLMS (periodic leg movements 80%) or PLMW
secondary causes of restless legs
iron def most common
ESRF, pregnancy, meds (antidepressants, antihistamines, lithium, D2receptor blockers) are other causes
pathophysiology of restless legs
theories:
- central dopamine dysfunction
- reduced CNS iron stores
- endogenous opiate system dysfunction (opioids and exercise improves RLS)
treatment for restless legs
- Non-pharmacological
- replace iron aim ferritin >50
- abstinence from caffeine, nicotine and alcohol
- Pharmacological
- First line
- Dopaminergic agonists - pramipexol, sifero, ropinirole
- SE: impulsive behaviours, augmentation (paradoxical worsening of RLS)
- Alpha25delta ligands
- Pregabalin
- SE: suicide ideation and sleepiness
- Dopaminergic agonists - pramipexol, sifero, ropinirole
- Second line
- Opioids
- First line
periodic limb movements in sleep definition
it’s a finding in a sleep study, not a disorder by itself
PSG findings:
- 0.5-10 seconds
- Amplitude > 8 uV above baseline
- At least 4
There is a period limb movement disorder which is a rare condition - diagnosis of exclusion,
parasomnia - when do they occur
sleep-wake transition disorders
or occasionally during slow wave sleep
REM sleep parasominias might be remembered
NREM parasomnias pathogenesis
partial arousals from slow wave sleep
instability of sleep state
e.g. sleep walking, confusional arousals, sleep terrors
REM sleep behavioural disorder diagnosis
usually requires sleep study for diagnosis
characterised loss of muscle atonia during REM
EMG during the normal sleep study during REM should be a flat line (aside from eye movements)
REM sleep behavioural disorder clinical features
violent dreams
the next day there is a recollection of the dreams (differentiating feature with NREM sleep disorders)
pathophysiology - alpha-synucleinopathies (Parkinson’s LBD MSA)
50% of patients don’t have an underlying alpha-synucleopathy (but within 15 years 80% of these patients will develop clinical alpha-synucleonopathy
Management of REM sleep disorders
Safe home environment
Clonazepam
Melatonin (controversial)
Avoid changes in sleep routine
Avoid antidepressants
Neurology
definition of narcolepsy
sleep state dissociation - poor quality and fragmented sleep
demonstrated on sleep study
NT type 1
- with cataplexy
- low CSF hypocretin
NT type 2
- without cataplexy
symptoms and features of narcolepsy
irresistable urge to fall asleep
cataplexy (emotion driven loss of muscle tone) as a manifestation of REM sleep manifestation
links with other parasomnias
metabolic syndrome
type 1 narcolepsy genetic and phenotypes
HLA-DQB1*06:02 (sensitive but not specific)
LP shows low or no hypocretin
No hypocretin in hypothalamus
Chronic
Type 2 narcolepsy phenotype
some may improve without treatment
No or atypical cataplexy
diagnosed by multiple sleep latency test (mean sleep latency <8min and Sleep Onset REM periods - going into REM in the first 15 min)
Narcolepsy treatment
Non-pharmacological (schedule naps, work/school/driving)
Pharmacological
- nodafinil, amphetamine
Cataplexy
- antidepressant, sodium oxybate
Treatment of insomnia
CBT is the mainstay
pharmacology: benzo, zolpidem
Health conditions associated with OSA
AF highest OR (4.0)
CPAP evidence in OSA
SAVE study NEJM 2017
secondary prevention study
mod to severe OSA, CPAP use 3.3hr
No difference in mortality or other primary endpoints
but results may be confounded by CPAP duration use
Obesity hypoventilation syndrome definition
high CO2
obesity BMI >30
Hypoventilation during wakefulness
obesity hypoventilation syndrome pathophysiology
OSA is major phenotype
apnoeas is prolonged and they don’t resaturate (which happens in normal OSA); hence chemoreceptors reset to cause resting hypercapniea
10% of OHS do not have OSA - they have a more pure hypoventilation phenotype
These patients need BIPAP
Obesity hypoventilation treatment
OSA phenotype - CPAP
Hypoventilation phenotype - BIPAP
first branching of the bronchial tree that has gas exchanging capabilities
respiratory bronchioles
dynamic collapse
during forced expiration
there is increased pleural pressure onto the alveolar and respiratory tract. As you move proximally, there is decreased pressure in the respiratory tract, which creates an equal pressure point” where the pleural pressure equals the airway pressure. The airway proximal to that has “dynamic collapse”.
In obstructive lung disease,the equal pressure point moves peripherally
FEF 25-75 reduction
early obstructive disease
FEF 25-75 is not dependent on effort
Respiratory physiology changes with age
More compliance but less elasticity
change in elastic properties:
- decrease in elastic fibres increaase in type 3 collage, changes in cross-linking and fibre orientation
Change in surface properties
- Decrease in number of alveoli
- Increase int he size of alveolar ducts
- Decrease in surface to volume ratio
effect of
1) venous congestion on lung compliance
2) emphysema on lung compliance
heart failure/venous congestion - decreased lung compliance
emphysema more compiant
gas trapping effects on spirometry
decreaed FVC
decreased FEV1
features of fixed airway obstruction on flow volume diagream
where the insoiratory and expiratory are both effected
e.g. subglottic stenosis
largyneal malacia vs tracheomalacia on flow volume loop
laryngeal malacia is reducd expiratory
tracheomalacia is deduced inspiration
how much does functional residual capacity take up
30%
layers for gas exchange in lungs
what causes reduced DLCO
- decrased membrane for gas transfer
- dodgy alveolar membranes
- decreased chest expansion
- lobectomy, pneumonectomy
- pulmonary fibrosis
- emphysema
- decreased blood in pulmonary capillaries
- volulme of capillary Hb (eg decreased cardiac output)
- less capillaries (emphysema, pulmonary fib)
- less blood (heart failure, pulmonary HTN)
how is DLCO measured
helium is used as it is not difused
the delium is diluted by the air in the lungs
that allows for the calculation of the alveolar volume (based on the assumption for homogenous gas mixing which is not true in obstruction or increased resistence in airways). ALveolar volume is compared with TLC (should be within 10%). If there is poor gas mixing, the TLCO will be underestimated.
The rate of diffusion is KCO (rate of carbon monoxide uptake)
DLCO = KCO x VA
what is assos w an increase in KCO
- when there is less lung, there is increased blood to lung ratio and the sink for carbon monoxide uptake is greater
- RBC in the airways (outside of capillaries) will also take up carbon monoxide. Of note, DLCO can be used to detect pulmonary haemorrhage withouth haemoptysis
- Obesity - cardiac output is increased in obesity
- Asthma - very large swings in intrathoracic pressure, there is more blood in the pulmonary circulation
essentially more blood in lungs will increase KCO
A-a gradient calculation
PAO2 = FiO2 x [Patm - PH20]-(PaCO2 / R)
= 150 - PaCO2/0.8
hypoventilation in hypoxaemia
PaCO2 >45 mmHg
Causes of elevated A-a gradient
R-> L shunt - cardiac, pulmonary
VQ mismatch - Most common cause of hypoxia in disease states
Diffusion limitation (rare)
most common cause of hypoxaemia in ILD
still VQ mismatch although diffusion limitation plays a small role
predominant physiological echanism for a normal A-a gradient (of 15 mmHg)
VQ inequality
bronchial provocation challenge
direct challenge
- histamine and metachonline
- sensitive but not specific
- >20% drop in FEV1
Indirect challenge - detect the presence of inflammatory cells in the airways and are more indication of current asthma
- Hypertonic saline, exercis and manitol
- Positive when >15% reduction FEV1 to stimulus
- More false negatives (specific)
what happens to VO2Max and heart rate with fitness
the curve does not shift but athletic peopleare able to reacher higher VO2Max
However, the heart rate relationship shifts as people can achieve higher VO2s with lower heart rates
Upper lobe fibrosis Ddx
see slides
pulmonary disease distribution associated with:
RA
mixed connective tissue
diffuse systemic sclerosis
Ankylosing spond
RA - can have either a UIP (slightly more common 8) or NSIP pattern
mixed connective tissue - an interstitial pneumonitis: 20-65%; pulmonary fibrosis: 20-65%
diffuse systemic sclerosis -
Ankylosing spond - unilateral/bilateral cystic changes with upper lobe distribution
criteria for reversibility in LFT
12% and 200mL improvement post bronchodilator
aspirin overdose
resp alkalosis
+/- raised anion gap
ABG in PEs
high variability
can even have normal A-a gradient
distribution of adenocarcinonas and pathological features
peripheral and spiculated - distinguises primary lung cancer with metastases
metastases early
squamous cell carcinoma location and pathology features
central
thick walled with large air fluid levels
“march” from parachyma to node to mets
assoc hypercalcaemia
relationship of vascular resistance and lung volume
at low volumes - atelectasis and distortion of vessels
at high volumes, the vessels are stretched - becomes longer but radius decreases
vascular resistance lowest at FRC
V:Q in different parts of the lungs
low V:Q ratio in bottom
high V:Q in top of the lungs
by which method does CPAP work in cardiogenic pulmonary pedema
CPAP restores FRC by alveolar recruitment, reducing right to left intrapulmonary shunt and improving oxygenation and lung mechanics
what cells are important in sarcoid
T-cells
pathogenesis: some antigen binds to a toll-like receptor, triggering a cascade of events leading to granulomas. T cells drive the disease to recruit macrophages and form granulomas (non-caseating)
Allergic bronchopulmonary aspergillosis clinical features
predisposing conditions: hypersensitivity to aspergillosis, total IgE levels (>1000), condidtent pulmonary opacities - fleeting pulmonary infiltrates relating to mucoid impact. They could simulate hilar lymphadenopathy.
cough, expectoration, wheezing, haemoptysis, fever, nasal symptoms
gold brown nasal plugs
diagnosis via
biggest cause of pulmonary hypertension
left heart disease (70%)
lung disease/hypoxia (15-20%)
pulmonary arterial hypertension (4%)
HOw to differential pre or post capillary causes for PH
If PCWP >15 it’s left heart disease or left vein aetiology
osteoarthritis pathogenesis
metalloproteinasa and TIMPs
catabolic cytokines - increased Il-1 in synovium and SF TNF in synovium
Anabolic cytokines - increased IGF-1 correlates with osteophyes
what type of OA is assoc w CV disease
knee>hand
symptomatic >asymptomatic
what is the most important modifiable risk factor for OA
knee injury
(but age carries the greatest risk overall)
what gender with XR change of OA are more likely to get pain
women
stratification of osteoarthritis
- knee only vs muti joint OA
- whether there are other comorbidities
Management of OA
which bisphosphonates are useful in OA
IV ones
what antidepressants are useful in OA
duloxetine
Intra-articular injections in OA
PRP has some improved funcitonal scores
genetics of RA
DR1, DR4 most important HLA that confers risk
PTPN22 (regulates activities for T and B cells) gain of function mutations
citrullination in RA
the conversion of the amino acid arginine in a protein into the amino acid citrulline
can be genetic and environment (e.g. smoking
what is the only biologic that is better than methotrexate as monotherapy
what biologic in combo with methotrexate is better than adalimumab and methotrexate?
tocilizumab (IL-6)
probably the go to drug in people who fail a TNF inhibitor
baricitinib in combo with methotrexate is better than ada and methotrexate. SE thrombosis
tofacitinib SE
elevated transaminitis
elevted creatinine
elevated lipids
neutropenia
increased risk of zoster
biologics and surgery
miss 1-2 cycles for surgery
can continue in minor surgery
biologics and pregnancy
TNF: remain on until falling pregnant then stop
certoluzimab is a very large molecule that probbaly does not cross the placementa
one of the big problems is that in the 3rd trimester, it will intefere with giving live vaccines to the baby
Class C: rituximab, abatacept, tociluzimab
solid malignancy <5 years and RA treatment
rituximab
>5 years any malignancy
where is urate reabsorbed
proximal tubule (URAT1 and OAT4)
what is the most important interleukin in gout
IL-1beta
that leads to the release of TNF, IL-6, neutrophil chemotactants
dosing of colchicine for acute gout
1mg stat, 500microg 1 hour later
Renal impairement
CrCl <80 mL/minute or hepatic impairment, do not use for acute attack if using colchicine for prophylaxis:
CrCl <30 mL/minute or severe hepatic impairment, dosage as above; do not repeat the course within 2 weeks.
Dialysis, oral 500 micrograms single dose, do not repeat within 2 weeks.
risk factoers for severe allopurinol hypersensitivity
renal impairement, increased age
thiazide use
initial high erdose
HLA-B*58:01 (test in Han Chinese; Thai; Korean)
what urate lowering therapy should not be used in cardiovascular disease
febuxostat
how is febuxostat metabolised
liver
where are uric acid crystals formed
in the urinary tract
(in tissue - monosodium urate monohydrate crystals)
what to do when there is ongoing frequent gout attacks despite being on urate acid lowering for 12 months and achieving satisfactory uric acid levels
add colchicine to control inflammation
