Respiratory and Sleep Medicine Flashcards
1
Q
Other than sleepiness, how can children with sleep disorders present?
A
Anxiety, irritability, impulsive, inattentive or have poor concentration
2
Q
DIMS (Sleep)
A
Disorders of initiation and maintenance of sleep
3
Q
DOES (sleep)
A
Disorders of excess sleepiness
4
Q
What is a parasomnia?
A
f
5
Q
Screening tool for sleep
BEARS
A
B - Bedtime problems E - Excessive daytime sleepiness A - Awake at night R - Regularity and duration of sleep S - Snoring and Apnoea
6
Q
How common are sleep problems in well children?
A
10-30% of children
7
Q
What are the normal physiological changes that occur in sleep?
A
Changes in blood pressure and body temperature
Decreased tone - leads to upper airwat resustence (x 2 in REM) + reduction in tidal volume.
- Any impairment of ventilation when awake will be worse in sleep
8
Q
What is the function of sleep?
A
Unclear - beneficial in learning, consolidation, restoration
9
Q
Effects of sleep depreivation
A
Tremor, reflex changes
Blunted hormone secretion (GH, prolactin)
Elevated pro-inflammatory cytokines
Impaired psychomotor performance
Behavioural changes (pre-frontal cortex + executive function
Associated with obesity
10
Q
How does sleep deprivation lead to obesity?
A
Add picture of sleep + obesity (males)
11
Q
What are the elements of Polysomnography?
A
EEG EMG Airflow to detect apnoea Effort (obstructive / central) Oxygen saturations, CO2, heart rate
12
Q
What are the stages of Sleep?
A
N1 - transition to light sleep, easily roused
N2 - light sleep (K complexes + spindles)
N3 - Deep sleep “slow wave sleep”, still, very hard to rouse, regular breathing - big triangluar waves
“ if in a dingy on the ocean , you would be sea sick”
REM - “dream sleep” , decreased tone, partial paralysis, vivid dreams, irregular breathing, increased upper airway resistance
13
Q
Stages of sleep in newborns + cycle length
A
Active sleep = N1,2 and REM
Quiet sleep = N3
= 40 minute cycle
14
Q
How long is the adult sleep cycle?
A
90 minutes
15
Q
Which part of the night is REM sleep more prevalent?
A
2nd half of the night
16
Q
Which part of the night is DEEP sleep more prevalent?
A
1st half of the night
17
Q
Example of sleep spindle + K-complex
A
Image
18
Q
What percentage of children stop daytime sleep by 5?
A
95%
19
Q
Behavioural insomnia (3 types)
A
Type 1 - Sleep association type (poor sleep hygiene)
- not innate to know how to fall asleep
Type 2 - Limit setting disorder type (if parents have issues setting limits during the day, the night is even worse
Type 3 - Mixed
20
Q
Management of behavioural insomina
A
Manage as if mixed
- exclude physiological causes (restless legs, OSA< reflux, eczema
- Day time behaviour / limit problems?
- Sleep hygiene and new sleep associations
Evidence Based Techniques:
1) Sudden / graduation extinction (controlled crying)
2) Fading with positive bedtime routines (20 mins quiet play / reading) - routine + regularity!
21
Q
ADHD and sleep
A
Also hyperactive in sleep
Easily wake, move more
daytime sleepiness
? due to OSA ? due to stimulants ? not enough stimulants
- consider atomoxetine, clonidine or melatonin + behavioural therapy
22
Q
Autism and sleep
A
up to 80% have issues with sleep
Difficulty settling
Waling between 1-5am + wake entire house
- Early morning waking
Behavioural therapy - look at perpetuating factors
Melatonin - short half life (may need long acting) - have issues swallowing tablets
23
Q
What is delayed sleep phase?
A
“permanent jet lag”
Common in adolescent due to decreased and delayed melatonin peak
- promoted by late homework, TV, texting, internet
- TAKE AWAY DEVICE
Exam Q - actigraphy - delayed sleep phase
24
Q
Treatment of delayed sleep phase
A
Sleep hygiene - dim light before bed, no computer / TV in room No steroe, texting Bright light when should be awake Advance bedtime by 15 mins each 3 mights Melatonin as adjuvant
25
Disorders of sleep with movements
Sleep stage specific
| Non-sleep stage specific
26
Parasomnias
= Confusional arousals, night-terrors and seep walking
- - partial awakening from N3 (SWS) - usually 60-90 minutes into sleep, 1-2 x per night
- - strong family history
- - Thinks of causes of abnormal arounsal (OSA)
27
Night terror
N3
Child is unable to be comforted, goes straight back to sleep, cannot recall event, usually in deep sleep (60-90 mins from sleep onset)
39% of children occasionally
3% persistent
Clonazepam if extreme
28
Night mare
Able to be comforted, recall event in the morning, waking from REM sleep
29
Frontal lobe seizures
Stereotypical features of pointing and pelvic thrusting, more likely to stand, sudden onset, ALWAYS THE SAME MOVEMENTS
- Post-ictal state can look like parasomina / night terror
30
Sleep walking
N3
Occasional 15%, frequent 3%
Primary + preschool age
- primary concern is safety (lock doors) - direct to bed
Dont try to wake them up
Clonazepam if extreme - especially if anticipatory awakening
31
Rhythmic movement disorder
| = head dropping / head banging
Normal variant
Just before sleep onset / stage 1
increased in autism and developmental delay
may result in injury
32
Periodic limb movements of sleep
Part of spectrum of Restless leg syndrome
- increased frequency of leg movements in sleep
Partial iron deficiency in CNS - aim ferritin > 50 (PO or IV)
33
Definition of Restless legs syndrome
AKA - Willis-Ekbom Dx
- Common, treatable neurological disorder impacting sleep, often co-existing with ADHD, mood and anxiety disorders
Diagnostic Criteria
--> Urge to move the leg, usually accompanied by uncomforatble sensation in the legs
- Symptoms worsen / begin with inactivity and relieved by movement
-- Occur exclusively / predominatly at night / evening
-- can not be attributed to by another medical or behavioural condtion
34
Hypersomnias = excess sleepiness
Fall asleep at inappropriate circumstances
Process S - sleep homeostasis
Process C - circadian alerting (work together)
= constantly fighting sleep or falling asleep in inappropriate situations
* most common cause is lack of sleep *
Duration, routine, regularity
35
Orexin - hypocretin 1 - involved in .....
| + treatment
Narcolepsy
high levels of orexin
Treatment - scheduled naps (30 mins), regular sleep routine, methylphenidate / dexamphetamine or modafinil (best)
Catoplexy - extreme emotions (sadness, laughing)
Tx - sodium Oxybate (GHB), SSRI's, TCA, Venlafaxine
36
Primary hypersomnia
| - constant vs periodic
```
Constant = narcolepsy (+/- cataplexy); primary idiopathic hypersomnia
Periodic = Klein Levin Sx, (obese, 5-7 days of increased sleepiness and sexual behaviours); menstrual-related hypersomnia
```
37
What is a multiple sleep latency test
Measure time to go to sleep in a dark room
- normal = 1-2 , no rem, > 8 minutes
Short latency + REM = narcolepsy
Short latency + no rem = hypersomnia
* Don't forget hypothalamic tumour *
38
Melatonin effect on gonads
* In Rats * testicular cancer, brings estrous forward, can delay puberty
- lowers seizure threshold
- being tired also reduces seizure threshold + stimulated immune system (contraindicated post transplant)
39
Cystic Fibrosis
- Incidence (Australia)
- Inheritance pattern
Autosomal recessive
1:2500 (Australia)
Asia 1:300,000
Carrier 1:25
40
Cystic Fibrosis
| - Gene and protein involved
CFTR - Cystic Fibrosis Transmembrane conductance Regulator
= CFTR Gene (Chr 7), 27 exons (large)
- Encodes chloride channel in apical membrane of exocrine epithelial cells, when faulty, have abnormal secretions
>2000 mutations, most common F508del G542X
41
Cystic Fibrosis
| - Pathophysiology
Excessive sodium into the cell, drys out ciliary layer causing thick sticky mucous
* Insert picture of channels *
42
CFTR malfunctioning classes (6 types and genetic mutations)
*Insert picture of malfunctioning proteins *
Type 1 - NO PROTEIN - G542X
Type 2 - defective endoplasmic reticulum processing F508D
Type 3 - protein at cell surface but non functioning G551D
Type 4/5/6 - Increasing levels of protein but may be less stable * milder mutations *
43
c.1521_1253delCTT mutation
F508delta
44
Newborn screening for CF
```
4-6 weeks average age of diagnosis
Tests IRT (Immune reactive trypsin) -
+ 4 genes (F508del, G551D, G542X, R117H)
Picks up 95% of cases
Can pick up carriers
Leads to early diagnosis and ? better outcomes (no evidence)
```
45
Diagnosis of classical CF
2 Genetic mutations
Positive sweat test
Pancreatic elastase (low)
46
CFSPID
Cystic Fibrosis Screen Positive Inconclusive Diagnosis
- either mild or no disease
- close follow up
47
Sweat Test
Chloride measurement
>60 = Cystic Fibrosis
40-60 - borderline
Need to be >2kg and after 2 months of age
Need Sweat weight >75mg (trad) or >15microL macroduct
48
Causes of False positive and false negative sweat tests
* Insert table *
49
Flow chart of pathophysiology of CFTR dysfunction
* Insert picture *
50
Clinical manifestations of CF (Lung and ENT)
Lung
- Increased thick, sticky mucous
- Chronic, productive cough
- Chronic Bronchitis (bacterial / fungal)
- Obstructive airways on lung function
- Bronchiectasis
ENT
- Nasal Polyps
- Sinusitis
51
Common Pathogens in CF
Most common = Staph Aureus (60-80%)
Pseudomonas (20% under 2, 50% by 18)
* Insert graph *
52
CF Treatment approach
Treat infection (antibiotics)
Keep inflammation under control (azithomycin)
Increase airway clearance (physio, hypertonic saline, pulmozyme nebs )
53
CF Treatment - Staph Aureus
Some centres use prophylaxis until age 2
Exacerbation - Fluclox 2-4 weeks
Staph Eradication - IVABS - usually 2 x anti-staph agents for one month
54
CF Treatment - Pseudomonas
First Isolation - eradication trial (IV Tobramycin + Ceftazidime 2 weeks, or oral cipro 3 weeks + Tobra nebs 2 months)
- Chronic infection - suppress it
- -> lung function declines
Oral - Ciprofloxacin
Neb - Tobramicin,
IV - Tobramycin, ceftazidime, meropenem
55
CF Treatment - Burkholderia capacia complex
First isolation - IV eradication (meropenem, temocillin, bactrim
Chronic - Nebulised tobra, oral doxy
Mild Sx - Bactrim
56
CF Treatment - Non TB mycobacteria
```
MAC (Mycobacetium avium)
M Abscessus
Consider in non-improving cases
Need smear / bronchoalveolar lavage
Treatment - 12-15 months from first negative culture - need 2-3 anti TB drugs (lots of side effects )
```
57
CF Treatment - Viral infections
Treat more aggressively, admit for RSV bronch
Ensure flu vaccine
Give Tamiflu if Flu +
58
CF Fungal infections
Aspergillus fumigatus 40-60% - no invasive disease, IgE mediated disease
- hypersensitivity disease, avoid high damp areas (building sites, hay, compost)
- - tick sputum with brown/black bronchial cast, increased wheeze, high serum IgE, eosinophillia, pulmonary infiltrates, positive asperigillus IgG and IgE
- Treat with steroids (oral, pulse melthyl pred), Itraconazole
- Invasive disease - IV caspofungin
Candida Albicans 75-90% - usually from mouth
59
GIT manifestations of CF (x 6)
Meconiium ileus (20%), DIOS (Distal intestinal obstruction syndrome
GORD
Pancreatic insufficiency (90%) - creon
Pancreatitis (in pancreatic sufficient patients )
Malabsorption - often bacterial overgrowth, poor intake of creon
CF liver disease (cirrhosis with portal hypertension)
60
Endo manifestations of CF (x 4)
CF related diabetes (50% by age of 30) 0 usually pancreatic insufficient
Poor growth, delayed puberty and low bone mineral density
Fertility - 95% male infertility- congenital bilateral absence of Vas deference; 20% female infertility - normal tract
61
Rheumatoid manifestations of CF ( x 2)
CF related arthropathy (10%)
- Episodic arthritis with pain and swelling of large joints, occasionally low grade fever and rash
- treat with NSAIDS
Hypertrophic pulmonary osteoarthropathy (HPOA) - arthritis, joint effusion, tenderness and pain over long bones - treat with anti-inflammatory
NOTE - Ciprofloxacin can cause arthropathy
62
Pseudo-Bartter's syndrome
Metabolic alkalosis with ow K, Cl Na
| - in hot weather with inadequate salt and fluid replacement, may be preceeded by gastro, not clinically dehydration
63
Mechanism of action
| - Ivacaftor / Lumacaftor / Elexacaftor
Ivacaftor
- Type 3 mutations, partially correct channel defect allowing chloride transport (potentiator)
- $250K/yr, 10 % improvement in lung function
Lumacaftor/Tezacaftor
- Improved protein folding and increased trafficking to cell surface
Elexacaftor
- Improves trafficking to cell surface
ORKAMBI - Lumacaftor and ivacaftor
64
Trikafta mechanism of action
| - % improvement in lung function
TRIKAFTA - elexacafrot, tezacaftor, ivacaftor
* Insert image *
reduced exacerbations, improved BMI, reduced sweat chloride, reduced symptom scores (14.3% improvement maintained)
65
CF related diabetes
- when it presents
- how to diagnose
Presents in second decade of life
Does not usually present with DKA
Diagnosed by fasting glucose and HbA1C
Girls > Boys
66
When to go to lung transplant for CF
```
FEV1 less than 30% Pred Lung function
Poor exercise tolerance / nutritional status
Rapid decline in lung function
Major life threatening complications
Quality of Life complications
```
67
Child presents with large volume greazy stools, 3 months of weakness, poor coordination, mild ataxia, decreased vibratory sense, bilateral hyporeflexia
--> Which vitamin is deficient?
Vitamin E
| - weakness, hypotonia ? cerebellar component
68
Definition of Asthma
Variable, chronic airway inflammation, periods of exacerbation and remission
- Reversible airway obstruction
- Increased mucous production (mucous plugging)
- Bronchospasm
- - Thickened and inflammed bronchial walls
- -> Hyperinflation
10% prevalence in Aus/NZ
69
Contribution to development of asthma
```
Family History (only 4% explained)
Tobacco Smoke
Air Pollution
Mould / Damp
Animals (reduces prevalence)
Antibiotics ? Paracetamol
Diet/obesity
Breast feeding
```
70
Naive T-Cells --> Atopic response pathway (3 x interleukins)
Th2 cells
- produce IL 4, 5, 13 --> B-Cell production --> Atopy (IgE dominance and eosinophillic inflammation
Th2 suppressed by interferon gamma
Only explains 50% of children
71
Naive T-Cells --> NON-atopic response pathway (2 cytokines)
Th1 cells
| --> Produce IL-2 and interferon Gamma --> IgG dominant and cell mediated immune response
72
Natural history of asthma
Even children who lose overt symptoms of asthma have persistent airway obstruction
- airway inflammation may persist in the absence if symptoms
- Frequently reoccurs
73
How to diagnose asthma
Recurrent / persistent wheeze / nocturnal cough / chest tightness
Triggers - exercise, cold air, allergen, viral infections, stress, aspirin, recurrent / seasonal
Family Hx asthma / atopy
Absence of physical findings suggesting alternative diagnosis
Tests that support diagnosis (spirometry in children)
Response to bronchodilators / preventers
74
Preschool Wheeze
Preschool asthma - multitrigger wheeze - usually respond to ICS
Infrequent
Frequent
75
* Insert image*
Normal lung function
76
* Insert image *
Obstructed intrapulmonary airways
- concave shape to exhalation
- Reduction in FEV1 and FEV1/ FVC ratio
77
* Insert image*
Restrictive lung disease
| - Normal shape but squashed
78
* Insert image *
Fixed central or upper airways obstruction
| - Flattend loops
79
Insert image
Variable upper airway obstruction
80
Insert image
Inadequate effort
| - common - not really a curve at all
81
Insert image
Incomplete exhalation
82
Asthma spirometry
```
Concave pattern
FEV1 reduced
FEV1/FVC reduced
Bronchodilator responsive - FEV1 increase of at least 12% from baseline
Normal does not exclude asthma
```
83
Direct challenge test
Inhalation of increasing concentrations of histamine or methacholine - falling FEV1 of >20%
84
Indirect challenge test
- Exercise - negative response to an exercise challenge test is helpful excluding asthma in children with exercise related breathlessness
- Inhaled mannitol
85
Peak expiratory flow monitoring
Variability of up to 20% in children
| - not good diagnostically but a trend can show worsening disease activity (still not well correlated)
86
Fractional exhaled nitric oxide (FeNO)
Positive - suggests eosinophillic inflammation and provides supportive but not conclusive evidence of asthma (> 35PPB, some use 25)
--> not for diagnosis
FeNO higher in :
- Asthma, atopic children, eosinophillic bronchiitis
FeNO lower in:
- smokers, early phase allergic response, neutrophilic asthma
Difficult to do in under 8-9 year olds
87
Long acting beta agonists
Formeterol / salmeterol
Always use with ICS
Not for use under age 4
Should not be initiated when clinically unstable
Cause reduction of b-receptors
88
SMART / AIR therapy
Use the same puffer for preventer and reliever
- Low dose budesonide / formeterol (symbicort)
- 1 puff BD (maintenance), up to 1 puff QUD for reliever
- use salbutamol as needed
- not used in young children
S/E: Fine tremor, palpitations, arrhythmia, tachycardia, paradoxical bronchospasm
89
Gina report - 2019
Adolescents
Recommend no longer just use ventolin alone to manage acute symptoms
increased risk of severe exacerbations by 2/3 if you do not also use steroid
Increases allergic response
B-receptor down-regulation, decreased broncho-protection, rebound hyperresponsiveness, reduced response
90
MoA - Omalizumab
Binds to IgE - stops IgE binding to receptors and reduction in allergic response, reduced high-affinity receptors
S/C injection 4 weekly
When treatment stopped, asthma often never as bad
Need to be on maximum asthma treatment
91
MoA - Mepolizumab, ( Resilizumab, Benralizumab)
Anti - IL-5
Inhibits proliferation of eosinophils
Need high eosinophils and over age 12
Need to be on maximum asthma treatment
92
When do you use nasal nitric oxide test?
Primary ciliary dyskinesia (PSD)
Use from age 5
nNO - sensitivity 97.5% Specificity 96.4%
- false positive in acute viral infection / sinusitis
- Need to repeat on two seperate occasions
93
How to diagnose ciliary dyskinesia
```
nasal Nitric Oxide (1st) - functional
Electron Microscopy (invasive) - structural
Gene testing - 30 genes (panel - 93.9% sensitive)
```
