Resp Flashcards
Regarding classic anatomical location of embryological respiratory abnormalities:
Pulmonary Sequestration?
Congenital lobar over-inflation
Sequestration - Left lower lobe, posterior aspect, obtaining blood supply from aorta - either intra or extra lobar (with its own pleura)
Over inflation - Left upper lobe, ball valve effect from compressed airway or cause unknown
What are the respiratory considerations regarding scoliosis and its surgical management?
Scoliosis results in a restrictive pattern of lung disease due to relatively rigid thoracic cage
Hence FVC is the most critical measurement
Earlier onset correlates with more severe respiratory disease
Conservative/Bracing may be appropriate, or a more intensive surgical management including implants that may be adjusted with growth
Multidisciplinary preoperative assessment of sleep and respiratory function identifies individuals who should be established on respiratory support e.g. BiPap prior to post-operative respiratory failure
Cystic Fibrosis
Principles of Screening in Victoria?
1:2500 - Vic 50,000 births so 20/annum
NST - Day 3 Heelprick
IRT - Immunoreactive Trypsin
Top 1% get screened for 12 common genotypes (Vic)
2x mutations is CF
1x mutation requires sweat test 60mmol/l Chloride
Nil common mutation is discharged and if affected will present with pancreatic insufficency/fat malabsorption
// Early identification Early treatment to reduce pseudomonas exposure
CFTR Class 1?
CHROMOSOME 7
G542X
6 Subclasses of protein abnormalities
Class 1: Premature termination of mRNA (Stop codon) - INCOMPLETE PROTEIN
“Ataluren” can overide premature stop codon - generate Ataluren facilitated functioning protein - Used in duchennes muscular dystrophy but not CF
“Safety mechanism” - extended lifespan, concern is premature cancer
CFTR Class 2
6 Subclasses of protein abnormalities
Class 2:
Delta 508 - Processing defect, trapped in ER, doesn’t reach apical membrane
LUMICAFTOR - Transport along with IVACAFTOR (Potentiator) - Orcambi - 3-4% FEV, no quality of life, no nutrition, 34% exacerbatoins
Approved age >12yo in Aus (as of 2018)
Failure of secretion of chloride
Subsequent increased sodium and water into cell, dehydration of airway surface liquid, thick tenacious movement/airway clearance
Modification of pH of ASL impairs antimicrobial clearance
CFTR Class 3
6 Subclasses of protein abnormalities
Class 3:
Regulatory failure, reaches membrane but doesn’t respond
- CHANNEL GATING (Closed all the time)
G551 D (Celtic) IVACAFTOR - 10% improvement in FEV, PERSISTENT EFFECT POTENTIATOR Sweat chloride from ~100mmol to ~ 50mmol Weight gain 2.7kg!
Approved from 2yo (2018)
CTFR Class IV
6 Subclasses of protein abnormalities Class 4 Defective channel properties Works at low percentage function R117H
(Channel CONDUCTANCE low)
CFTR
Class 5
Class 6
BOTH RARE
Class 5
Reduced RNA
Class 6
Accelerated turnover
Chronic diarrhoea with rectal prolapse?
Missed cystic fibrosis diagnosis
Pattens of stool Ix
Fat crystal - malabsorption (mucosal defects)
Fat globule - maldigestion, insufficiency fecal elastase (>200ug/g is consistent with sufficiency) (Pancreatic insufficiency)
Which microbes in Cystic Fibrosis cause problems and when?
Age <3 (AND THROUGHOUT) - Staph Aureus and non-typeable Haemophillus influenzae
Anti staph agents for first 2 years
Burkholida Cepacia - More international problem
Genomovars 1-9 to explain varied presentations
Non-3 are mild disease
3 is Cenocepacia Haemorhagic Pneumonia - never at RCH
Rx with oral bactrim, nebulised colistin/minocycline, clearable
Aspergillus - Fungus (May cause ABPA, infection, colonisation)
BROWN SPUTUM, LOCALISED CXR finding
Psuedomonas -
Eradication is difficult - intensive 2/12 including 2/52 IV ABx (Aminogylcoside and other), if unsuccesful then cycling
Tobramycin (Nebulised b.d.) or TIPS Tobramycin inhalation powder
Ciproxin- resistance rapidly, achilles tendonitis, sun sensitivity
(Colistin)
Cayston - TDS works, BD doesn’t work
If colonised then 6-8/12 later PsA produce alginate in response to H2O2 that improves biofilm
Azithromycin as an anti-inflammatory (15 ring macrolide) causes improved FVC/FEV1 in chronic PsA pts, three times/weekly
Non Tuberculous Mycobacterium (NTM)
Increasing incidence
Invasive therapy (4-8/52 dual IV) - Tigicycline, cefoxitin, + Azithromycin
Bone marrow suppression
Nausea
Then 6/12 consolidation phase - oral and inhaled antibiotics
NOTE:
Can’t identify without collection, get at least 4 samples yearly to identify pathogens
Dx ABPA?
ABPA (Allergic Bronchopulmonary aspergillosis) Exaggerated TH2 CD4+ immue response -
Classic is all 5 x features
Minimum is 4 of
Acute or subacute deterioration not attributable to another aetiology (Brown discoloured sputum)
IgE > 500 IU/mL
Immediate cutaneous reactive
Precipiated antibodies OR CXR Changes
CENTRAL Bronchiectasis
Rx Prolonged high dose steroids
Mucolytic therapies available in CF?
None are disease modifying
Pulmozyme
DNase mid 1990s Mean FEV 5-7.5%, reduced exacerbations
Hypertonic Saline 3-6%
Irritative
Premedication with ventolin to prevent bronchospasm
Mannitol
Dry powder, 10x capsule b.d.
Osmotic agent, 3 micromol
CF Related Diabetes?
Impaired glucose tolerance
20% by age 20 (end of childhood)
Progressive - 50% by mid 30yo
Correlates with fall in BMI, FEV1, FVC prior to a
Associated with increased mortality and long term microvascular changes
Diagnosis - 2hr glucose >11.1 or fasting plasma >7 mmol
Miscellaneous bowel/bone diseases of cystic fibrosis?
Less common x10 Coeliac disease in CF
C. Difficile due to high use antibiotics
Inflammatory bowel disease 7-17x more common
Osteoperosis in CF
Multifactorial
In protracted bacterial bronchitis a particular antibiotic is chosen - why?
Augmentin
Predominate organism is Haemophillus influenza which is commonly resistant to amoxil but sensitive to augmentin
Treat for 2-4/52
Regarding cough that isn’t asthma - any distinguishing features?
Post infectious cough - dry cough, usual cough triggers (dry/night)
Protracted bronchitis - moist cough, responsive to short course antibiotics before recurrence on stopping
What age is respiratory function test reliable?
From age 7
Any benefit between different inhaled corticosteroids?
Most equivalent
Once daily dosing with ciclesonide is appealing
Different delivery systems (pMDI)
Dry powder - turbuhaler is good and appealing to teenagers to avoid MDI with spacer
Brio - Potent steroid +++, limited role
Singulair - limited role, balance steroid vs. behavioural side effects, good at preventing exercise induced symptoms, intermittent used with viral associated, use at onset of cold can modify episode in some children, can be trialled and will prevent steroid use in that situation
What are the multi-system implications of cystic fibrosis?
Respiratory - exacerbations
Bronchiectasis/bronchitis/pnemonia/atelectasis/hemopthyis/pneumothorax/reactive airway disesase/cor pulmonale/ resp failure, ABPA
Pancreatic insufficiency - Growth failure (Can PRESENT) Fat soluble vitamin def Insulin deficiency Diabetes Pancreatitis
Hypersplenism
Nasal polyps
Sinusitis
Liver diesease - hepatitc steatosis and portal hypertension
GB = billary cirrhosis, neonatal obstructive jaundice, cholelithiasse
Bone
Osteoperosis
Arthritis
Hypertrophic osteoarthropathy
Intenstinal GERD Meconium illues (Can PRESENT) DIOS Rectal prolapse (Can PRESENT)
Reproductive
Congenital absence of vas defernse CAVD (Can PRESENT in adults with otherwise mild)
Infertility
Dehydration with hyponatremia (Can PRESENT) Sever anaemia (Can PRESENT)
Regarding cystic fibrosis - what value of chloride on sweat test?
> 60 mmol/L diagnostic
30-60 - uncertain
<30 unlikely to have CF
Can also use as biomarker in response to therapeutics
What sort of defect does IVACAFTOR fix?
CFTR Class III
Ivacaftor is a potentiator and fixes the gating defect in CFTR Class III such as G551
What sort of defect does LUMACAFTOR fix?
Lumacaftor is a corrector or transporter from ER to cell membrane
Useful with Class II mutations
Note the common Class II mutation Del508 also needs a potentiator because it also confers a Class III gating defect once it reaches the cell membrane
What sort of protein is CFTR?
A Protein Kinase A- activated ATP gated anion channel (For Chloride and bicarbonate)
