1
Q
Approach to asthma management for 6-11 year olds, as per GINA guideline?
A
Step 1: SABA prn is generally what we do, but for GINA, they make an off label recommendation of SABA-ICS prn. (In general, GINA’s emphasis on no SABA only treatment is a much stronger recommendation for adults/adolescents; they don’t make as strong of a statement for this age group)
Step 2: this is the step where you start daily therapy with daily low dose ICS
Step 3: GINA gives the option of low ICS-LABA or medium dose ICS
Step 4: medium dose ICS/LABA
2
Q
Approach to asthma management for 6-11 years olds, as per CTS guidelines?
A
Step 1: SABA prn
Step 2: low dose ICS
Step 3: medium dose ICS
Step 4: medium ICS with LABA or LTRA (so at this step, CTS gives an option. GINA seems to be more pro LABA)
3
Q
What are the differences between GINA and CTS for managing asthma in 6-11 years of age?
A
- Step 1 is mostly similar, though GINA technically mentioned ICS prn with SABA
- Step 2: GINA gives an option of adding LABA versus medium dose ICS, but CTS does not
- Step 3: CTS gives option of either adding LABA or LTRA to medium dose ICS
4
Q
Medium dosing for various ICS in 6-11 years and >12 years of age?
A
For 6-11 years, in general 201-400 is medium dose for qvar, flovent, alvesco, except for budesonide (which is twice as potent) so 401-800 is medium dose.
For >12 years, it’s the same dosing range for budesonide and ciclesonide, except for qvar and flovent, which have a dosing range of 251-500.
For mometasone, they only give a dosing range for >=12 years, which is similar to budeonisde. So 401-800 is medium dose
5
Q
What are the common colors of inhalers?
A
Qvar: brown
Flovent: orange
Alvesco: red
6
Q
What are side effects of ICS?
A
- Local: thrush, dysphonia
- Adrenal insufficiency: hypoglycemia, altered mental status, fatigue, weakness, anorexia, Cushingoid features, growth failure, or weight loss. (There have been cases of pediatric death related to adrenal crisis from flovent, ? stopping flovent)
- Height: Height: decreased growth velocity in prepubertal children in first 1-2 years of treatment, but this is not progressive or cumulative. Final result of 0.7% decrease in adult height
More relevant for adults:
- Cataract - uptodate says that adults taking regular ICS should be monitored with regular eye exams
- accelerated decline in bone mineral density
7
Q
When should patients with asthma be tested for adrenal insufficiency?
A
- Symptoms of adrenal insufficiency like fatigue, poor growth, weakness, anorexia, altered mental status, cushingoid, growth failure
- High dose ICS, especially with low BMI, for >=3 months
8
Q
When should you screen an asthma patients for adrenal insufficiency in the absence of them having any symptoms?
A
- exceeding threshold ICS dose for >= 3 months
- ICS of any dose in combination with CYP3A4 inhibitor (eg. HIV drugs, anti fungal agents, some antidepressants) for >3 months
Threshold doses corresponds to the upper limit of medium dose range for everything except, flovent:
- Flovent >=400 mcg for 4-11 years, but >=500 mcg for 12 years and up
9
Q
How do you screen for adrenal insufficiency?
A
- AM cortisol
- Patients needs to stop glucocorticoid for 24 hours prior to test
- testing should be repeated every 3 months for patients at threshold dose of ICS
10
Q
Describe technique for using MDI
A
- Shake cannister x 5 seconds
- Attach cannister to spacer
- Patient exhales normally to FRC
- Place mouthpiece in mouth and close lips
- Begin slow inspiration and complete inhalation over several seconds (4-5 seconds)
- Activate cannister
- Hold breath x 10 seconds
- Wait 30-60 seconds in between doses to repeat steps above (pitfall: should NOT be dispensing several doses at once)
- (Need to make sure that there are doses left)
- Infant: 5-10 tidal breaths per puffer dose
11
Q
How would you escalate acute asthma therapy beyond back to back ventolin and atrovent?
A
Steroids- either oral (eg. Dexamethasone) or IV (methylpred 1-2 mg/kg to maximum of 125 mg) - both are equivalent. (key reason for IV steroids would be inability to tolerate oral therapy, can give IV steroids every 24 hours)
- MgSO4
- Continuous ventolin (0.15 mg/kg/hour to max of 15 mg)
- Subcutaneous/IM epinephrine (0.01 mg/kg to max of 0.3 mL)
- IV ventolin
- ipratroprium 500 mcg every 4-6 hours (in Kendig’s, not in CPS statement)
Less typical:
- Heliox
- Theophylline
12
Q
Complications of MgSO4?
A
- hypotension
- Headache
- Weakness (think hypotonia). Adverse effects on neuromuscular function can happen in patients with neuromuscular disease
- Hypermagnesemia –patient with renal disease are at higher risk for this and hypermagenesemia can cause cardiac arrhythmia, respiratory failure to due to severe muscle weakness, sudden cardiopulmonary arrest
- Bradycardia
4 x H’s = hypotension, headache, hypotonia, hypermagnesemia
13
Q
Complications of IV ventolin?
A
- Tachycardia
- Arrhythmia
- Myocardial injury
- (The use of IV ventolin is considered a non-standard therapy)
- Hypokalemia
14
Q
What are the complications of intubation for asthmatic?
A
- hypotension
- hypoxemia
- challenges related to ventilation, such as dynamic hyperinflation
- laryngoscopy can precipitate bronchospasm
15
Q
Ventilator strategy for an asthmatic?
A
Goals:
- minimize hyperinflation and barotrauma (overall, you are mimizing the amount of pressure and volume that you are shoving in the lung)
- permissive hypercapea
- Slow ventilator rate so more time in exhalation–>you basically want the lower respiratory rate
- I:E ratio of 1:3 or more (since airflow obstruction is worse on exhalation)
- Low tidal volume since there is already hyperinflation (about 4-6 mL/kg)
- Low PEEP (PEEP should be lower than auto-PEEP)
Other:
- plateau pressure <30 (this is just the same idea as minimizing tidal volume)
Additional info from Kendig:
* At risk for hypotension with intubation since auto-PEEP decreases systemic venous return:
* Adequate hydration before intubation * avoid excessive positive pressure ventilation immediately after * Permissive hypercapnea-->you don't need to normalize ventilation * The goals: treat hypoxemia, relieve work of breathing (muscle fatigue) * Principles of ventilation: * Volume ventilation--lowest volume and flow to minimize peak pressure and volume damage * Maximize expiratory time * Respiratory rate should be low (Eg. 8-10 breaths/min) * Low tidal volume (eg. 6-8 mL/kg) * prolonged expiratory time * Can tolerate a pH as low as 7.2 * Continue all regular medications, including bronchodilator. MDI can be given through the endotracheal tube
16
Q
Reason for hypoxemia in asthma?
A
V/Q mismatch causes intra-pulmonary shunt (atelectasis) and dead space (due to airway over distension)
17
Q
What is the key change in GINA 2019 guidelines?
A
Key change is in management of mild asthma, in particular for adolescent and adult age group. Mild asthma tends to managed in a symptom driven fashion, previously with SABA prn. But SABA prn has been associated with increased risk of exacerbations and death. So, GINA advises that for the mild group where treatment is symptom drive, it should be ICS/formoterol or SABA/ICS.
Key point: patient with mild asthma are still at risk for severe or fatal exacerbations so it makes to sense to have ICS on board. As well, it’s challenging to get patients with mild asthma (symptoms<2x per month) to take ICS regularly so then they are basically just on SABA only treatment
(This is directly in contrast with CTS 2012 which specifically said they favour in SABA prn instead of ICS/LABA prn in the mild asthma patients who are on no maintenance medication)
18
Q
After severe exacerbation leading to hospital admission, how soon should follow up be arranged?
A
Within 2 days (eg. family doctor) and again 3-4 weeks
19
Q
What are the diagnostic criteria for asthma, as based on GINA? Based on CTS?
A
- Want to try and make a diagnosis BEFORE starting treatment. Once you start, there may be less variability in lung function.
- Combination of symptoms + objective testing
- Variable respiratory symptoms + variable expiratory airflow limitation/obstruction
- Key symptoms: cough, SOB, wheeze, tightness. These symptoms vary over time, within same day and with particular triggers
- Objective testing: expiratory airflow limitation + excessive variability in lung function:
- Airflow obstruction/limitation: when FEV1 is reduced, FEV1/FVC is also reduced. Normal ratio is children >0.9
- Variability in lung function:
- Positive BD reversibility/responsiveness (more likely if BD has been witheld): increase in FEV1 by >=12% and >=200 mL from baseline in adults, and just >=12% in children. (This definition is different than ATS definition, which says either increased in FEV1 or FVC by both >=200 mL and >=12%)
- Excessive variability in twice daily PEF >=13% for children, >10% for >=12 years
- Positive exercise challenge test
- Positive methacholine challenge, while acknowledging lower specifity
CTS is very similar to GINA. I actually like the layout of their tables better.
- Preferred: spirometry showing reversible airway obstruction either with bronchodilator or course of controller therapy so: decreased FEV1/FVC with BD reversibility–>increase in FEV1 by >=12% in children. For adults: >=12% and >=200 mL.
- Alternate: Peak expiratory flow variability after bronchodilator, with a course of controller therapy or diurnal variation. (They don’t provide the option of diurnal variation for 6-11 years). –>the threshold for definition of diurnal variation is all over the place: >8% based on twice daily readings, >20% based on multiple daily readings, >10-15% when using PEF to assess control
- Alternate: positive challenge test with methacholine or exercise.
Methacholine: PC20 <4 mg/mL
Exercise: >=10-15% decrease in FEV1 post exercise
20
Q
What is the role of FeNO in diagnosis of asthma?
A
- FeNO correlates with serum and sputum eosinophilia
- Associated with type 2 airway inflammation, but also: eczema, allergic rhinitis, eosinophilic bronchitis
- Not elevated in neutrophilic asthma
May predict ICS responsiveness, but there are no studies examining safety of with-holding ICS on basis of FeNO (GINA)
21
Q
How do you confirm a diagnosis of asthma in a patient already on ICS?
A
Few options in relation to symptoms and variable expiratory flow limitation:
- Option 1: ongoing symptoms + expiratory flow limitation –>confirm asthma, optimize treatment
- Option 2: ongoing symptoms but no expiratory flow limitation. Key question: is this asthma as main cause of symptoms or something else?
- If safe to do bronchial challenge (FEV1>70%)–>bronchial challenge
- If it’s not safe, then escalate asthma treatment and reassess symptoms
- Option 3: no symptoms and no expiratory flow limitation. key question: either asthma that is well controlled or not a diagnosis of asthma. Plan: wean ICS and repeat spirometry
Practically, I think the index of suspicion for a diagnosis of asthma, affects the willpower to proceed with trying to prove the diagnosis. It’s important to rule out alternate diagnoses and asssess for co-morbidities
(GINA, keeping in mind this is more of an adult based guideline)
22
Q
If you did want to prove a diagnosis of asthma in a patient referred to you on controller treatment who is asymptomatic with no evidence of variable airflow limitation, how would you wean controller?
A
- Decrease ICS dose by 25-50% or stop second controller treatment (eg. LABA, LTRA)
(GINA, more of an adult based guideline)
23
Q
How is asthma severity defined?
A
It’s defined based on the retrospective treatment to control symptoms
24
Q
What are the key things to assess when seeing a patient regarding their asthma management? (Things you would evaluate on a follow up visit)
A
4 things to assess for asthma patients at every visit:
- Control, as assessed retrospectively over the past 4 weeks
- Risk factors for adverse outcomes (persistent air flow limitation), exacerbation, side effects
- Treatment utilization: adherence, technique, action plan
- Co-morbidities
(It’s important to separately assess control and risk factors for adverse outcomes. Although control is intuitively linked to exacerbations, they are not perfectly correlated and there are independent risk factors for exacerbations. Hence, even individuals with mild asthma can have severe exacerbations and death)
25
After the diagnosis of asthma, how often should spirometry be repeated?
- 3-6 months after diagnosis and then periodically therefter
26
What are the asthma control criteria as per GINA?
These criteria are actually more strict than CTS
- Retrospective assessment over the last 4 weeks
- Daytime symptoms > 2 days per week (3 days or greater)
- Any night time symptoms
- Reliever use >2 times per week (not including pre-exercise)
- any activity limitation due to asthma (this a a very important question b/c for any respiratory disease, the patient can limit symptoms by limiting physical activity
- Based on the above, patients can be classified as well controlled, partly controlled or not controlled
27
What are the risk factors for an exacerbation, as per GINA? (Of note, these risk factors should be assessed at diagnosis and periodically, especially for patients who are having exacerbations)
- Poor asthma control
- Low lung function (FEV1<60%)
- High BD reversibility
- >= 1 severe exacerbation in the last 12 months (as per CTS, severe exacerbation is where oral steroids are needed)
- Ever being intubated or in ICU for asthma
- high blood eosinophils
- elevated FeNO
- comorbiities: GERD, food allergy, pregnancy
28
Risk factors for developing persistent airflow limitation?
- Preterm birth
- Low birth weight
- Tobacco exposure
- Lack of treatment with ICS
- Low initial FEV1
29
Risk factors for asthma medication side effects?
- Frequent oral steroids
- High dose ICS, especially if with CYP450 inhibitor
- Local side effects for high dose ICS or poor inhaler technique
30
How is diurnal variation in PEF calculated?
* Diurnal PEF measurements:
* PEF is done twice daily x 2 weeks
* (Day’s highest - day’s lowest)/(mean of day’s highest and lowest)x100 —>average with other values over 1-2 weeks
31
After confirming a diagnosis of asthma, is it necessary to with-hold controller medication?
No, you care more about where their lung function is at on treatment. If they still have BD reversibility while on treatment, then you know that they are high risk for an exacerbation. Likely uncontrolled and either non-adherent or need an escalation in treatment.
32
How does FEV1 change in response to asthma therapy?
- Improves in first 2 months, then plateaus
33
What is the role of PEF in long term monitoring of asthma?
- PEF can be used for long-term monitoring or short-term monitoring.
- Short term:
- identify occupational or domestic triggers
- monitor recovery post exacerbation or after a change in treatment
- if excessive symptoms and you want objective evidence
Long-term monitoring:
ONLY for severe asthma and individuals with poor perception of symptoms
- Earlier perception of exacerbations in patients with poor perception or sudden severe exacerbation
34
How is asthma severity defined?
- Severity is defined based on treatment required to control symptoms, after spending several months figuring out the ideal treatment regimen. (Key point: we can't make this determination when seeing a patient for the first time. It depends on where they stabilize out to)
- Mild asthma: step 1 (symptom driven therapy with ICS-formoterol) or step 2 (same as step 1 or daily low dose ICS)
- Moderate asthma: needing LABA
- Severe: high dose ICS-LABA and above so step 5
35
What is the relationship between asthma control and risk of exacerbation?
There is not a 1:1 relationship between symptom control and risk of exacerbation.
There is more a relationship for mild asthma, but for severe asthma it's not uncommon to have a patient with mild symptoms, who is an exacerbator.
36
What is the role of sputum eosinophils in asthma management?
Minimal role for children
- in adults, use of sputum eosinophils has been shown to decrease exacerbations, though similar to control with traditional management
- On a population scale, sputum eosinophils is NOT recommended (GINA)
- CTS: recommend considering use of sputum eosinophils in adults with moderate to severe asthma who are being followed in a specialized centre
37
What is the role of FeNO in asthma management?
- Using FeNO is better than traditional management in terms of exacerbations, but similar for daily asthma control
- Complementary
- Withdrawing treatment on the basis of low FeNO is NOT recommended (though it may make sense to not escalate treatment in patients with low FeNO)
- On a population scale, FeNO is not recommended (GINA)
- CTS: insufficient evidence to use FeNO in any way (either as adjunctive or on it's own)
- GINA emphasizes how guideline based recommendations are made on a population scale
38
What threshold level of FeNO level in children is associated with eosinophilic inflammation and ICS responsiveness?
FeNO > 35
39
What is the big change in the GINA 2019 guideline?
- The big change is in the management of mild asthma, which is typically through symptom drive driven and historically with SABA prn.
- For adults and adolescents, they do not recommend SABA alone prn therapy.
- As needed low-dose ICS formoterol compared to SABA prn reduces risk of exacerbations by 2/3.
- Although this is also part of the diagram in approach to children, the strength of this recommendation is much more so for >12 years of age. (we actually don't see as many patients on just symptom drive therapy)
40
For adult/adolescent who has poor control on low dose ICS, what is the next step as per GINA? (step 3 options?)
- the preferred step 3 is low dose-ICS/LABA with SABA prn
- But for frequent exacerbators, it's better to do ICS/LABA as maintenance and reliever since there will be fewer exacerbations.
41
For child 6-11 years who has poor control on low dose ICS, what is the next step as per GINA? (step 3 options?)
- Medium dose ICS or low dose ICS/LABA with SABA prn
| - Either of these options is preferable
42
When should step down of asthma therapy be considered?
when patients have been stable for 3 months
- step down the dose to find the lowest dose, which would effectively manage symptoms. (At this point, patients could be classified based on severity)
43
Dry cough differential diagnosis? (think about this differential in patients presenting for asthma evaluation, but with only cough as the symptoms.
- GERD
- Rhinitis
- Cough variant asthma (main symptom of asthma is just cough)
- ACE inhibitor
44
What are the options for initiating asthma treatment for adult/adolescent with symptoms <2x per month?
- ICS/formoterol as needed (preferred) or ICS/SABA prn
(with very infrequent symptoms, we are taking a symptom drive approach)
- there are not very many patients we see who would fall into this category
45
What are the options for initiating asthma treatment for adult/adolescent with symptoms >=2x per month?
Either low dose ICS with SABA prn or ICS/formoterol prn
- Preferred option is low dose ICS daily since there is better symptom control and improved FEV1, but if patient won't take treatment consistently, then it's better to use ICS/formoterol prn and at least have some ICS on board
Second line: LTRA-->not first line since not as effective in terms of exacerbations, but consider for patients with allergic rhinitis or who don't want take ICS
46
How would you initiate asthma treatment on adult/adolescent with troublesome asthma symptoms most days or waking due to asthma?
Start with ICS/LABA either with SABA prn or as maintenance and reliever therapy
- If frequent exacerbations, then maintenance and reliever therapy is better as there will be fewer exacerbations
47
How would initiate asthma treatment on adult/adolescent who presents with severe uncontrolled asthma or with acute exacerbation?
Oral steroids + controller with high dose ICS or medium dose ICS/LABA
(Practically, keep this in mind for hospital consults. I've seen patients started on this more intense treatment and then seen in followup to wean therapy) .
GINA mentions using this increased controller dose for 2-4 weeks
48
When should allergen immunotherapy be considered in children with asthma?
- Allergic rhinitis, especially if ongoing symptoms in spite of environmental control/drug treatment or if they can't tolerate drug treatment
- At step 2 (daily low dose ICS) or above, with allergic rhinitis and FEV1>70% and sensitization (such as house dust mite (GINA)
- Consider it in patients with new onset allergic rhinitis and asthma because the immunotherapy can be disease modifying for asthma (studies have shown that immunotherapy for allergic rhinitis has decreased development of asthma)
- Recall that there are certain burdens of therapy - subcutaneous versus oral, duration of therapy: 3 years (Kendigs)
49
What dose of ICS do most patients need to be on for response?
- Low dose
| - Some patients will need medium dose, but the majority respond to low dose
50
Is ICS-formoterol on a purely prn basis for mild asthma recommended for children <12 years of age?
No
51
Is formoterol as effective as SABA for acute symptom relief? What about exercise symptoms?
Yes to both!
52
For what age groups is symbicort approved?
- approved by health canada for ages 12 and older
| - approve by FDA for >= 6 years of age
53
When should ICS-formoterol maintenance and reliever therapy be considered?
GINA:
>= 12 years (though I have seen it used off label)
- >=1 exacerbation in the last year
- Exacerbator
CTS:
- exacerbation prone individual 12 years of age and older who is having poor control on fixed-dose ICS/LABA. Reliever dose at same maintenance ICS dose
- on ICS/LABA fixed dose, but poor control/persistent symptoms. Can switch to formoterol maintenance and reliever therapy as an alternative to increasing ICS dose.
- so i would practically think about this at step 3/4 if poor symptom control. makes sense to try this before tiotropium or biologic
54
For what ages is spiriva approved?
6 years and older
55
Before labelling someone as having severe asthma, what do you need to consider? (Basically want to differentiate between uncontrolled asthma due to severe asthma versus uncontrolled asthma due to suboptimal management)
- Consider alternate diagnosis. It can be hard to prove the diagnosis of asthma in severe asthma since patients might not safely be able to withold medications for methacholine or exercise challenge or with longstanding disease in adults, they may have fixed obstruction. Try and look for old PFTs.
- Medication adherence and technique--look for old pharmacy records. Review technique
- Co-morbidities: rhinitis, GERD, obesity, OSA, psychiatric
- Persistent environmental exposure or allergen. (Don't forget to ask kids about smoking, vaping, NSAID use)
56
Predominant cell type in children with severe asthma?
- Eosinophil
| in contrast to neutrophils being predominant in adult severe asthma
57
What are the broad phenotypes of preschool and childhood asthma?
- Preschool asthma: episodic viral wheeze (neurophilic) versus multitrigger wheeze (eosinophilic)
- Childhood asthma: atopic (eosinophil) versus non-atopic (neutrophil)
58
Dose of prednisone for asthma exacerbation? When does the dose need to be tapered?
CTS: 1 mg/kg/day x at least 3 days (maximum dose of 40 mg)
| Dose does not need to be tapered if used for <2 weeks
59
Can a LTRA be used as monotherapy for asthma?
Yes, it can be used in children >=6 years of age, but it would be second line. ICS is first line. In general, LTRA will be less effective in terms of symptoms of preventing exacerbations.
(may consider LTRA by itself if there is steroid phobia or allergic rhinits. But with new black box recommendation, parents may be less keen on this option)
60
As per CTS, if there is poor asthma control on low dose ICS, what is the next step?
12 years and older: low dose ICS-LABA
6-11 years: medium dose ICS
61
Child who is 6-11 years with inadequate control on medium dose ICS?
CTS presents addition of LABA or LTRA as equivalent options.
62
Describe the findings of the sygma studies?
- Patients >=12 years of age
- Randomized, double blind trial
- Assigned either to terbutline prn, budesonide-formoterol prn or bid low dose budesonide + SABA prn
- Findings:
- Exacerbations:
- More exacerbations and worse symptom control with SABA prn alone compared to budesonide-formoterol prn
- Symbicort prn compared to regular low dose budesonide: non-inferior with respect to exacerbations
- Regular low dose budesonide was better than symbicort prn in terms of symptom control
Symptom control: low dose daily budesonide > symbicort prn > SABA prn
Exacerbations: low daily budesonide = symbicort prn > SABA prn
63
What is a severe asthma exacerbation?
Exacerbation requiring oral steroids
64
What does CTS recommend regarding intermittent ICS?
- Intermittent ICS (just initiated at the start of an exacerbation) is not recommended
- For individuals with mild asthma who are not therapy at baseline, you could consider committing them to regular ICS
65
What does CTS recommend regarding escalating ICS dose during exacerbation?
- 6-11 years: they do NOT recommend increasing ICS dose
- Adults who have had an exacerbation requiring oral steroids in the last year: ICS dose can be increased 4-5 times x 7-14 days. (this recommendation is a bit confusing throughout the statement. in some places, age cut off seems like 12 years or 16 years of truly adult; i will just remember that this more of an adult recommendation)
- doubling of dose is not recommended for any age category
66
What are the components of symbicort?
Symbicort 100 or 200
100: 100 mcg/puff budesonide and 6 mcg of formoterol
200: 200 mcg of budesonide and 6 mcg formoterol
67
What are 3 different ways that symbicort can be used?
- purely PRN (CTS2012 does not acknowledge this option)
- Daily maintenance therapy with SABA prn
- Maintenance and reliever therapy
68
Why is LABA monotherapy not recommended?
Increased risk of asthma related death
| Ongoing research if concurrent use of ICS decreases this risk - as per CTS 2012
69
Is doubling the ICS dose at start of an asthma exacerbation recommended?
No
(there are subgroups of adults of age in whom a 4 or 5x increase in dose is recommended)
(CTS)
70
In children <12 years with asthma, when should you consider oral steroids as part of management in the yellow zone?
Yellow zone is the zone where you are considering controller step up therapy
- Only consider having oral steroids for yellow zone if: recent severe exacerbation (=need for oral steroids) and suboptimal response to SABA.
(They don't define what a recent severe exacerbation is)
(CTS)
71
In a child >12 years with asthma on symbicort (either as maintenance with prn SABA or as maintenance and reliever therapy), how can dose be changed in the yellow zone? (CTS)
Symbicort 4 puffs bid x 7-14 days or SMART (max 8 inahalations/day)
- They present either of these as options for patients on some form of regular symbicort
72
Asthma control criteria as per CTS?
- Severe asthma statement has the most comprehensive control criteria:
- Poor control as per CTS criteria or standardized questionnaire, such as ACQ
CTS control criteria:
History:
Daytime symptoms <4 days per week (daytime symptoms >3 days per week)
No night time symptoms
SABA doses <4 doses per week (>3 doses per week)
No physical activity limitation
Not missing any work or school
Mild, infrequent exacerbations
Objective testing:
FEV1>=90% of personal best
Diurnal variation of PEF <10-15% (recall that diurnal variation is not recommended for diagnosis of asthma in children, but maybe it's ok for control follow up?)
Sputum eosinophils <2-3%
Also:
- Frequent severe exacerbations: 2 or more times of needing systemic steroids in the last year
- Severe exacerbations, requiring hospitalization, ICU or mechanical ventilation
- Airflow limitation - FEV1<80% of personal best after bronchodilator withold (this is more strict than above)
73
State the dosing ranges for ICS
Look at CTS guideline
74
ICS/LABA on a prn basis whether purely prn or in maintenance/reliever approach, what is the age cut off?
12 years
75
Approach to asthma management in ages 12 years and up, as per CTS?
- Low dose ICS
- Low dose ICS-LABA
- Low dose ICS-LABA + LTRA
- Severe asthma management
76
Why is SABA only use not recommended for individuals 12 years and older?
Similar to LABA monotherapy, SABA monotherapy is associated with increased risk of exacerbation and death in individuals with mild asthma (I'm not sure about death part. I'm pretty sure since there is a reference to increased morbidity and mortality with SABA only. The part about exacerbations is supported by the Sygma studies)
77
For a patient on a non-formoterol ICS such as advair, what does GINA advise for using for prn?
- They would advise use of SABA (as per traditional management)
- (It's not ok to combine ICS/formoterol with another LABA produce mainly due to concerns about using 2 different LABAs)
78
Is symbicort approved as a reliever in Canada?
Yes, so there shouldn't be any challenges following the GINA recommendation
79
Mild versus severe asthma exacerbation?
| How many severe asthma exacerbations per year to be considered poorly controlled?
Mild: no need for oral steroids
Severe: need oral steroids
Allowed 1 severe exacerbation per year
80
Definition of severe asthma?
Key points:
- retrospective assessment
- based on therapy required
- high dose ICS + second controller (they don't specify what this is) over the last 1 year OR
- oral steroids for 50% of the previous year
- it makes sense that you want to truly make sure a patient has severe asthma before applying this label, it could take a long time to work through co-morbidities. I don't think you have to wait a year before formally applying the diagnosis.
81
What are the most common reasons for poorly controlled asthma?
Adherence and technique
82
In a patient with severe asthma, what alternate diagnoses should be considered and corresponding investigations?
- CF -->sweat chloride
- Non-CF bronchiectasis -->CT chest
- aspiration -->VFSS
- Vasculitis -->vasculitis screen (ANCA, CRP)
- ABPA -->IgE, IgE aspergillus
- immunoglobulins, CBC
- CT sinus (ANCA and CT sinus is related to EGPA on differential)
- BNP, echocardiogram
- Tracheobronchomalacia
- Atypical mycobacterial infection (sputum sample)
83
Is the eosinophil count reliable in a patient on chronic oral corticosteroids?
No. So when phenotyping a patient with severe asthma on oral steroids, you need to repeat the eosinophil count when off steroids
84
Biomarkers of Th1 and Th2 inflammatory pathways in asthma?
Th2:
- blood and sputum eosinophils
- FeNO
- total IgE
- blood periostin (but not readily available assay, less helpful in children where periostin is elevated due to normal growth)
Th1:
- sputum neutrophils
(The cut off values for biomarkers in relation to various asthma drug initiation is related to studies that look at which subgroups of patients will benefit)
85
Which biomarkers should be completed when phenotyping a patient with severe asthma?
- IgE
- blood eosinohpils
- if possible: sputum eosinophils and FeNO
86
What is the role of FeNO in predicting response to omalizumab and anti-IL5?
- Inconclusive
87
What is the role of blood eosinophils in predicting response to anti IL5 therapy and omalizumab?
- Blood eosinophil count if above a certain threshold predicts fewer exacerbations for anti-IL5 and omalizumab
- Blood eosinophils above 260 cells/microL predicts response to omalizumab
88
Within the approved range, does a higher IgE level correlate with better response to omalizumab?
No, it doesn't predict higher magnitude of benefit
89
When should use of tiotropium bromide be considered in patients who are symptomatic despite combination ICS/LABA?
CTS Severe asthma guideline:
- Age 12 years and up, with severe asthma and uncontrolled symptoms despite being on ICS and second controller
- In 12 years and up, it's been shown to improve lung function and decrease exacerbation frequency
- At time of guideline, it was not Health canada approve for children of any age
- It is FDA approved for age 6 and up
- In children 6-11 years, it improved lung function, but didn't reduce exacerbations
- Safe, minimal adverse events
(GINA includes tiotropium as part of algorithm for 6-11 years)
- Dosing: 2 inhalation of 2.5 mcg taken once daily (since it lasts 24 hours)
90
What are side effects of marcolide use?
- Nausea, vomiting, diarrhea - common
- hepatotoxicity
- QT prolongation so be careful with their use in patients bradycardia, hypokalemia, hypomagenesemia, other QT prolonging drugs
- Hearing loss is possible, though less common, could be reversible or irreversible
- marcolide resistance in patients with non-tuberculous mycobacterium (most common: Mycobacterium avium complex intracellulare). so before starting long-term treatment, send sputum samples for mycobacterial smear and culture
91
Are chronic marcolides indicated in children with severe asthma (high dose ICS and second controller)?
- No
- In adults, there is limited evidence that chronic macrolide use may decrease frequency of exacerbation and this was independent of phenotype
(I've only seen it used in one adolescent pediatric patient who still had significant symptoms and exacerbations despite chronic steroids and omalizumab)
92
What is omalizumab?
recombinant humanized monoclonal antibody to IgE
93
How often is omalizumab given?
Every 2-4 weeks, depending on IgE level and weight of patient
94
What is the evidence for efficacy of omalizumab?
Difference in benefits seen for children and adults:
Adults:
- reduction in exacerbations, including severe exacerbations leading to hospitalization
- improvement in symptoms and quality of life
- reduction in use of SABA
- reduction in mean ICS dose
- more individuals able to stop ICS use completely
Children:
- decreased exacerbation rate by 50%
- decreased hospitalizations
- decreased seasonal exacerbations in the fall
- LESS consistent effect in terms of symptom control, quality of life, ability to decrease ICS dose.
- NO studies showed improvement in lung function or quality of life.
(The fact that there's limitations to what omalizumab can realistically achieve means that we should really try and exhaust other options before getting to this one biologic approved for kids in Canada)
95
What is the efficacy of omalizumab in individuals with IgE above the dosing range?
- No RCTs have been conducted outside the dosing range, but there seems to be similar benefit
96
What are the adverse effects of omalizumab?
- Minor injection site reactoin
- Anaphylaxis: risk is 0.09% and majority (80%) of these reactions happen in first 2 hours and within the first 3 doses
- Patients need to receive the dose in a clinical setting, observed for 2 hours after first 3 doses and for 30 minutes after subsequent doses
- concerns about malignancy, but a long term cohort did not find a difference between omalizumab and standard asthma therapy. (of note, the study referred to in the guideline followed patients >=12 years for a duration of 5 years)
- So it's very time intensive for a patient to be on this treatment-->injection every 2-4 weeks, injection can't be given at home
97
Indications for initiating omalizumab?
- Approved for ages 6 and up
- Patients who meet definition of severe asthma (high dose ICS + second controller)
- Sensitized to at least one perenniel allergen (either by skin test or in vitro reactivity)
- IgE within appropriate dosing range: 30-1300 (6-11 years), 30-700 (>=12 years)
98
What predicts responsiveness to omalizumab?
- recurrent exacerbations
| - blood eosinophil count >=260-300
99
What are examples of anti-IL5 biologics?
- Mepolizumab (nucala) - subcutaneous
- Resolizumab - IV
- Benralizumab - investigational, not approved for use in Canada
100
which biologics are approved for use of children in Canada?
- omalizumab
| - mepolizumab (anti-IL5)
101
Indications for starting mepolizumab (Nucala)
- 6 years of age or over
- meet the definition of severe sthma
- have to meet target eosinophil level since IL5 stimulates eosinophil activity
- mepolizumab: eosinophils >=150 cells/microL at initiation of >=300 cells/microL in the last year
- monthly subcutaneous injection
(Also approved for EGPA in children)
102
What is the evidence like for use of anti-IL5 in children?
- children 12-17 years old were included on the initial RCT trials of mepo, but CTS severe asthma guideline felt that there weren't enough adolescents to really assess efficacy and safety
- Although mepo has the Health Canada approval, there's very few children who have been included in research studies. (I would feel more comfortable starting with Xolair if the patient meets criteria)
- Individuals with more exacerbations, adult onset asthma and nasal polyposis are more likely to respond.
103
What are the benefits of anti-IL5 therapy, at least based on the primarily adult data?
- reduces asthma exacerbations
- Mepo has been shown to have steroid sparing properties (in terms of reducing oral corticosteroid dose), improve quality of life, improve FEV1
104
Side effects of mepolizumab?
- Rhinosinusitis
- Headache
- injection site reaction
- Anaphylaxis - observation post injection for ?1 hour (though CTS didn't seem very sure)
- back pain
- studies with children: pharyngitis, abdominal pain, eczema
Prior to starting treatment:
- treat helminthic infections (since eosinophils are part of this response)
- Varicella immunization
105
What sort of general counsellng should all asthma patients receive?
- Self management education
- Action plan
- Environmental control
106
When a biologic is initiated, how long should it be tried for?
try for at least 4 months
If good response, then try and wean other medications patient is, starting with oral steroids. Generally, don't wean inhaled steroids below medium dose (not sure if there is a time point at which this would change)
107
Definition of preschool asthma, as per CTS guideline?
For the question about 5 operationalized diagnostic criteria:
- Documentation of airflow obstruction: ideally documented by healthcare provider, recurrent episodes >=2
- Parental report of wheezing or other symptoms of airflow obstruction
- Documentation of reversibility of airflow obstruction:
- Ideal: documented by healthcare provider with SABA +/- oral steroids
- Convincing parental report of symptomatic response to 3 month medium dose ICS trial
- Convincing parental report of symptomatic reponse to SABA
- No clinical features suggestive of alternate diagnosis
3 things:
- Airflow obstruction and reversibility and no alternate diagnosis. This includes symptoms that may happen only in context of viral illness.
- symptoms of airflow obstruction by: wheeze, cough, dyspnea. (The most objective sign of airflow obstruction is wheeze). Extent of symptoms: >=8 days per month or recurrent exacerbations (2 or more)
- Reversibility:
- Physician observed reversal of wheeze and other obstruction symptoms by SABA +/- corticosteroid
- Parental history of improvement in symptoms 3 month medium dose ICS trial or improvement with SABA pen
- See table 1 in CPS statement for further details
How do you operationalize this definition in practice?
- Seeing preschooler on ward or follow post ED: clarify if wheeze and physician documented response to SABA. If hard to sort this out, then give parent clear instructions to monitor response to SABA and ICS
- seeing a sick preschooler: listen pre and post ventolin to see if it helps
108
What proportion of preschool wheezers will have resolution of their wheeze by 6 years of age?
about 60%
Way to remember: 1/3 will have persistent wheezing, 2/3 will "outgrow" wheezing
(from CPS preschool asthma statement)
109
What is the best way to demonstrate reversible airflow obstruction in a preschooler (CPS)?
healthcare provider documented improvement in symptoms post SABA in context of an acute exacerbation
110
At what age does preschool asthma start?
1-3 years of age.
It is possible for symptoms to start in the first year of life, though bronchiolitis is more common in the first year of life.
(I think asthma is defined as recurrent episodes of wheezing b/c first episode of wheeze in a child <12 months is usually bronchiolitis)
111
Preschooler with first episode of asthma like exacerbation. Signs of airflow obstruction and reversibility with bronchodilator. No features concerning for alternate diagnosis. Is this enough to diagnose asthma?
No, they have to recurrent exacerbations (>=2). The diagnosis of asthma is suspected, but not proven. (It's as if patients have a free first pass)
112
At how many minutes after administration do you expect a response to SABA? Oral steroids?
20 minutes for SABA peak response, though guideline advises a time to reassessment of 30 minutes
4 hours is when oral steroid starts work (as per preschool statement)
113
In a preschool child, is parental report of response to SABA reliable?
No (preschool statement)
114
What is the onset of action for ICS?
1-4 weeks (preschool statement)
| - To do: look this up in Kendig's
115
If a preschooler is initiated on a 3 month trial of medium dose ICS, when should they be seen in follow up?
6 weeks and 3 months
| Follow up 6 weeks since there is likely to be poor adherence and poor recall
116
What would be considered an adequate response to therapy for preschooler on 3 month trial of ICS?
- 50% decrease in number of exacerbations requiring oral steroids
- shorter duration and severity of exacerbations
- fewer symptoms in between exacerbations
117
How long should a preschool child on asthma therapy be stable for before trying to step down medication?
3 months
(practically, I think we wait a longer time frame before step down and we generally don't try to step down in winter unless they are doing really well)
*there is a high rate of symptom resolution in this age group
My thoughts: if patient is stable, it makes sense to try them on a lower dose or off. Only need 3 months of stability. I don't think the phenotype would dictate will power to try off since the phenotype can change at this age. That being said, if the child was admitted or in ICU, I think most people would continue ICS for at least 6 months to 1 year post.
118
How is symptom control defined in preschoolers?
```
Poor control if symptoms are:
>= 8 days per month
>= 8 times SABA use per month
Any night time symptoms
Any exercise limitation
Absence from usual activities
Moderate or severe exacerbation (oral steroids or hospital admission)
```
119
Definition of medium dose and low dose ICS in preschoolers?
Qvar: low is 100 mcg/day, medium is 200 mcg/day
Alvesco: low is 100 mcg/day, medium is 200 mcg/day
Flovent: low is 100-125 mcg/day, medium is 200-250 mcg/day
120
Definition of ABPA in a patient with asthma? How do you differentiate ABPA from asthma with fungal sensitization?
ABPA general definition (slightly different from CF guideline definition):
- Predisposing condition: asthma or CF
- Worsening lung function not attributable to another etiology
- obligatory for both of the following:
- Elevated IgE (>1000 for asthma, >500 to meet minimal criteria for CF)
- Elevated IgE to aspergillus or immediate cutaneous hypersensitivity to aspergillus
- Supportive criteria: 2 or more of:
- Eosinophilia >500 cell/microL
- Imaging findings
- Additional antibody: serum precipitating or IgG antibody to aspergillus
Severe asthma with fungal sensitization:
- severe asthma
- positive skin test or IgE to >=1 filamentous fungi
- exclusion of ABPA
121
CF patient suspected to have ABPA, but IgE is only 200-500. What's the next step?
- Make sure that IgE wasn't done while they were on steroids
| - Repeat IgE in 1-3 months
122
Treatment of ABPA?
- Prednisone 0.5-2 mg/kg/day x 1-2 weeks, then wean the dose to 0.5 mg/kg/day every other day, want to completely wean by 2-3 months
- Would make sense to check IgE before weaning the dose. IgE decreases by 25% after 1 month of treatment, 60% after 2 months-->I imagine that before the first wean, there may not be a huge change in IgE.
(CF guideline doesn't give specific recommendations for how often to check IgE after weaning steroid or stopping steroid at end of treatment)
- Second line: itraconazole 5 mg/kg/day x 3-6 months. Need to do therpeutic drug monitoring and watch liver enzymes
123
Equivalent dose of symbicort to advair?
- Budsonide to flovent 2:1
- Formeterol to salmeterol 1:4
Symbicort:
(steroid/LABA)
- 100/6 or 200/6 or 400/12 (symbicort forte, I haven't seen this preparation)
Advair:
- MDI: 12525/ or 250/25
- Diskus: 100/50 or 250/50 or 500/50
- Advair 125/25 = symbicort 200/6
124
Effect of hyperinflation on airway resistance and compliance?
- Hyperinflation-->decreased compliance, but increased airway caliber
- with asthma exacerbation, the biggest issue is decreased airway compliance-->WOB
- hyperinflation-->increased VQ mismatch-->decreased oxygenation
(to review in physiology: elastic and resistance work of breathing)
125
What are the side effects of singulair? What is the FDA black box warning?
- Headache
- Abdominal pain
- Sleep disturbance, nightmare
- Neuropsychiatric--aggression, depression, suicidal ideation-->incidence is 12%
- FDA warning says that there are limited data about neuropsychiatric side effects, but that "suicide completion" has been reported as a side effect. They say that for some studies, the side effects resolve with cessation of therapy and other studies say that side effects don't resolve with cessation of therapy. They acknowledge the poor quality data, but they have decided to have a black box recommendation. Key point: NEED to ask about neuropsychiatric conditions before prescribing singulair and warn families of this side effect. (It seems like there is almost a legal obligation with this black box warning, this is probably why all the staff are quite particular). FDA warning says that singulair should not be the first choice for mild allergic rhinitis.
126
Is there such thing as a hypoallergenic pet?
- No
- Allergens are found not only in fur, but also on in saliva, dander, perianal glands
- So even if an animal does not have fur, there are still other allergens
- Hypoallergenic animals can have higher allergen levels or lower allergen levels
- Even within a species, there can be variable allergen levels
127
Respiratory side effects of second hand smoke?
- Increased frequency of LRTIs in infants
- Increased frequency of otitis media
- Increased prevalence of asthma (second smoke increases risk of developing asthma)
- Increased severity of asthma -->this is why we strongly encourage families to stop smoking
- increased risk of SIDS
128
What is Harrison's sulcus and 2 causes of this?
- Indentation of lower margin of thorax by pull of the diaphragm attachment on lower ribs (basically pull of diaphragm on an infant's soft chest wall)
- Causes:
- chronic respiratory disease like SEVERE Asthma
- Ricket's
129
How do you manage asthma in a patient with long QT syndrome?
- Long QT syndrome: risk of torsades de pointes-->sudden cardiac death
- Treatment of long QT is with beta blocker
- Typical asthma treatment with beta agonist-->increased risk of cardiac events, but NO fatal cardiac events
- Use of ICS with beta agonist further increased risk of cardiac event (unclear why ICS has this effect since systemic steroids don't have the same effect)
- Use of beta blocker decreases the risk of cardiac event, seeming to outweigh the negative effect of beta agonist
- Approach to management in patient with long QT:
- can they be treated with beta blocker for long QT?
- short acting: prefer atrovent, which has slower onset (20-30 minutes) than ventolin
- no problem with oral or IV steroids
- LTRA is preferred over ICS since ICS is associated with cardiac events (I'm not sure if this would practically affect management)
- MgSO4 is great since it's a bronchodilator and the treatment for torsades de pointes
- Avoid IV theophylline (aminophylline) since it increases heart rate
- Would be important to develop a personalized action plan for these patients
130
Asthma management in patients with long QT syndrome?
- Risk for cardiac events with B agonist like ventolin
- surprisingly ICS is also associated with increased risk of cardiac event (oral or IV steroids doesn't seem to be associated with increased risk of cardiac event)
- practically:
- atrovent for rescue
- LTRA would be preferred for daily management
- there is a lower risk for cardiac events for patients on B blocker, so ideal for long QT syndrome to be treated
- acute management: atrovent, may need to use ventolin but monitor K+ and for arrhythmia, MgSO4 since it's bronchodilator and would deal with arrhythmia
131
What is the advantage of symbicort maintenance and reliever therapy compared to ICS/LABA with SABA prn?
- compass and cosmos study showed similar daily symptoms control, but fewer exacerbations and lower overall steroid dose
132
Which ICS are pro-drugs?
- Qvar and ciclesonide, but ciclesonide is more of a pro-drug (The activated drug is 100x more potent then the parent compound. With qvar, the activated drug is 25x more potent than the parent compound)
133
Advantages of ciclesonide?
- Smaller particle size-->less oral deposition and more pulmonary deposition
- Less local oral side effects like thrush
- Less growth suppression, compared to flovent
- Once daily dosing
- Less adrenal suppression
134
What is the mechanism of xolair?
- Binds to free IgE and prevents it from binding to mast cells and basophils
- It binds to IgE at the same part where IgE would bind to these other cells
- Recall that the binding of IgE will cause release of histamine and leukotriene
- It is NOT able to bind to IgE that is already bound to mast cells or basophils
135
What are the benefit of xolair as based upon RCT?
Key point: decrease exacerbation rate by 50%, but less of a benefit in terms of asthma control
- There were 3 RCTs involving children with moderate to severe asthma. Findings for omalizumab:
- decreased exacerbation rates by 50% (RR0.5)
- Decreased percentage of individuals with at least 1 exacerbation
- Decreased hospitalizations
- But:
- Less consistent effect on asthma control
- Less consistent effect on ability to decrease ICS dose
- NO study showed improvement in lung function or quality of life
- So seems like omalizumab for children is good from a safety perspective, but less so from a control perspective
- In contrast, adult studies show:
- Reduction in asthma exacerbations
- Reduction in asthma exacerbations leading to hospitalization
- Significant improvement in asthma symptoms scores
- Significant improvement in quality of life
- Variable findings for improvement in lung function. At best, some studies have shown small improvements in FEV1
- Reduced SABA use, reduction in ICS dose, reduction in oral corticosteroid bursts
136
Monitoring of IgE during xolair treatment?
- IgE criteria for xolair as based on RCTS: 30-1300 (6-11 years), 30-700 (12 years and above); that's not to say that patients beyond these dosing ranges won't have response
- • Serum IgE levels increases because the test measures IgE/xolair complexes. This elevation can persistent for up to 1 year following discontinuation. (Omalizumab document)
137
How do you dose xolair?
- Dosing depends on pretreatment IgE and body weight
Maximum dose for a single injection site is 150 mg
Dosed every 2-4 weeks
Standard dosing tables, which is found on the packet insert of xolair
138
Side effects of xolair?
- Usually well tolerated
- Most common side effect is a minor injection site reaction
- Risk of anaphylaxis: 0.09% (post marketing surveillance) to 0.2% (product monograph). 78% of reactions are within 2 hours post injection and within the first 3 doses. So individuals should be observed for 2 hours after the first 3 doses and 30 minutes after subsequent doses.
- There have been concerns raised regarding malignancy, but a long term cohort of children>12 years showed no increased risk of malignancy between omalizumab versus placebo
139
Treatment for non-allergic rhinitis?
- intranasal saline irrigation
- intranasal glucocorticoid, antihistamine
- intranasal atrovent
- decongestant, but use with caution
140
What is the chemical pathway that glucocorticoids act in asthma?
They act on the IL5 pathway
141
Which cytokines are most important for eosinophil activity?
- IL5
-GMCSF
others: IL4, IL13
"Eosinophils require various growth factors, GM-CSF and IL-5 appear to be the most important, without these they undergo apoptosis"
142
Why do we not want to intubate asthmatics?
- Dynamic hyperinflation-->auto PEEP
- heterogeneous airway narrowing with different time constants
- some areas that are atelectatic (shunting) and some areas that are hyperinflated (risk of barotrauma)
High risk for morbidity and death
In 1/4 of cases: pneumothorax, decreased venous return because of increased intrathoracic pressure, cardiovascular collapse
143
Side effects of salbutamol?
- tachycardia
- hypokalemia
- hyperglycemia
144
Acute management of an asthmatic?
- Salbutamol: 5 or 10 puffs, depending on if above or below 20 kg
- Atrovent (20 mcg/puff): 3 or 6 puffs, depending on weight above or below 20 kg x3 doses
- Oral steroid: 1-2 mg/kg of prednisone or 0.15-0.3 mg/kg of dexamethasone
- IV MgSO4 40 mg/kg IV
```
If failure to respond:
- IV salbutamol
- IV aminophylline
- Heliox
- Endotracheal intubation
(They surprisingly don't mention biPAP)
```
- Consider subcutaneous epinephrine for possible anaphylaxis
- Maintain saturations >=94%
- Continuous cardiorespiratory monitoring
- NPO
- IV access
- Gas, electrolytes
- call ICU physician
145
Instructions for discharge of a patient from hospital who had asthma exacerbation?
- Ventolin 200 mcg/dose every 4 hours (basically 2 puffs every 4 hours)
- 3-5 day course of oral steroids
- written action plan
- demonstrate technique, how to maintain/clean aerochamber
- follow up with PCP within 2-4 weeks post discharge
146
Intubation medications and considerations for the asthmatic?
- Need an experienced intensivist
- Appropriation hydration
- Sedation: ketamine 2 mg/kg is followed by an infusion of 20 to 60 micrograms/kg/min
- largest endotracheal tube possible and cuff inflated (to accomodate the high intrathoracic pressure, I don't fully understand this)
- Avoid extensive bagging after intubation (to avoid risks of hypotension in context of autoPEEP and decreased venous return)
147
For MDI:
- what are the constituents in the cannister?
- why is it important to shake?
- why is it critical to use aerochamber
- Cannister: the majority if propellant. There is also surfactant and drug
- Surfactant will decrease airway surface tension and increase the bioavailability of the drug
- Shaking is criticial since it will re-suspend the drug in the propellant
- Aerochamber is very important. The propellant creates a high velocity plume and particle size is big at 20 micrometers. The aerochamber provides time for the propellant to evaporate so that particles can become smaller in size
148
Dry powder inhaler: what is the contained in each dose? Pros and cons?
- 2 types of DPI: turbohaler and diskus
- Diskus dose contains drug + carrier/exipient (which is usually lactulose). (Beware of the lactulose for patients with associated allergy)
- Turbohaler is just the drug, no exipient
- With the forceful inhalation, the drug is de-aggregated from the carrier. Carrier is left in the oropharynx and drug is deposited in lungs
- For the turbohaler, the spheronized particles are broken into microparticles during the forced inspiration as the drug moves through the mechanics of he drive
- Advantage: portable
- Disadvantage: need to generate a high peak inspiratory flow rate
- Generating a mid to high peak inspiratory flow is important so that the drug can either be de-aggregated or broken into smaller particles
149
Propellant for DPI?
HFA, as opposed to CFC
150
What are the factors that determine aerosol deposition?
- Drug specific factors:
- particle size, velocity, visocsity, hydroscopic properties, suspension versus solution
- Patient related factors: age, inspiratory flow rate, breathing pattern, nasal versus mouth breathing, adherence
151
1 advantage and 1 disadvantage for MDI, DPI versus nebulization?
MDI:
- Advantage: portable, can be used in a patient with trach/intubated, non-breath activated
- Disadvantage: requires patient coordination (though can still be done in infants), can get high pharyngeal deposition, hard to deliver high dose
DPI:
- advantage: portable, breath activated (this could be a disadvantage since requires coorindation), doesn't require propellant
- disadvantage: oropharyngeal deposition, hard to deliver high dose, can't give to intubated patient
Nebulizer:
- advantage: no patient coordination required, can give a high dose
- disadvantage: contamination, device preparation is required
152
Salbutamol versus salmeterol versus formoterol?
- Formoterol: onset at 3 minutes, peak effect 15 minutes, duration: 12 hours
- salmeterol: onset 30-48 minutes, peak effect 3 hours, duration: 12 hours
- salbutamol: onset 5-8 minutes, peak 25 minutes (time to peak serum level), duration 4-6 hours
- Formoterol is slightly more rapid than salbutamol, but quite similar in terms of fast acting properties
- Salmeterol is a partial B2 agonist, whereas formoterol and salbutamol are full B2 agonists
153
Why is EIB called EIB as opposed to exercise induced asthma?
- trying to differentiate between how people can have EIB, but not have asthma
- i think if the symptoms are purely with exercise then we would say EIB; I wonder if this is similar to the idea with methacholine-->even for people without asthma, a high enough methacholine dose can trigger bronchoconstriction
154
Clinical presentation and pathogenesis of EIB?
- Pathogenesis: once a short period of eucapneic hyperpnea is stopped, there is bronchoconstriction + dessication of the airway
- Interestingly, EIB often happens after exercise stops. Initial period of bronchodilation with exercise. EIB can last from 30-90 minutes without treatment
- practically, asking patients about symptoms doesn't correlate with the objective findings
- technically, to say someone has EIB, there has to be objective testing
- specific environments (Eg. hockey rink, swimming pool) can trigger EIB
155
How is EIB defined?
- >=10% decrease in FEV1 within 30 minutes after cessation of exercise
- the use of a more strict criterion, like >15% for children
- Need to have 2 reproducible FEV1 maneuvers at 5, 10, 15, 30 minutes post exercise
156
what dose of flovent is associated with adrenal insufficiency?
>=500 mcg/day. in the adrenal insuffficiency, they mention that majority of cases of adrenal insufficiency related was from use of flovent >=500 mcg/day
157
Dosing categories for ICS for preschool?
Medium dose:
- flovent 200-250
- qvar (beclomethasone) 200
- ciclesonide (alvescro) 200
Low dose:
- flovent: 100-125
- qvar: 100
- alvesco: 100
158
For viral wheeze and atopic wheeze, what are the important cells and cytokines?
Viral wheeze: neutrophil, IL17
Atopic wheeze: eosinophil, IL5 (other cytokines: IL4, IL13)
159
reasons for intubation of asthmatic?
- silent chest
- cardiac arrest
- respiratory arrest
- progressive exhaustion
- silent chest
- severe hypoxemia with maximal oxygen delivery
160
What flow rate needs to be achieved on FeNO for it to be reliable?
50 mL/s expiratory flow
| ERS lecture
161
What is the definition of severe asthma?
Key point: Treatment needed: high dose ICS and second controller for previous year / oral steroids >50% last year -asthma either uncontrolled despite these or needing the above for prevention of loss of control
Supplemental points:
1) Asthma diagnosis confirmed by history and objective measures
2) Environmental factors, comorbidities, adherence and inhaler technique addressed before labelling as severe asthma
162
Asthma control criteria as per CTS?
```
History:
Daytime symptoms <4 days per week
No night time symptoms
SABA doses <4 doses per week
No physical activity limitation
Not missing any work or school
Mild, infrequent exacerbations
Objective testing:
FEV1>=90% of personal best
Diurnal variation of PEF <10-15%
Sputum eosinophils <2-3%
```
163
Definition of uncontrolled asthma, as per ATS?
- Not meeting control criteria, as based on CTS criteria or standardized questionnaires
- Frequent severe exacerbations: 2 or more exacerbations needing oral steroids for >=3 days
- After bronchodilator withold, FEV1<80% of personal best or
164
ABPA criteria for asthma?
- Based on ISHAM 2013:
- Total IgE>1000
- positive Aspergillus specific IgE or skin prick test
- 2 or 3 out of:
- Eosinophils > 500
- radiological features consistent with ABPA
- raised aspergillus IgG or precipitating antibody
165
Normal values for FeNO in child (<12 years) and adult
Child: 20-34
Adult: 25-50
166
What is considered significant difference in FeNO
For FeNO>50: 20% change is significant
| For FeNO<50: 10 point change is signifciant
167
What is the intepretation of an elevated FeNO?
- eosinophilic airway inflammation
- predsicts steroid responsiveness
- may suggest persistent allergen exposure
- can support the diagnosis of asthma, but there are also non-eoinophilic types of asthma
- can be used to monitor airway inflammation in asthma
168
Patient with asthma, ongoing symptoms, but low FeNO?
Unlikely eosinophilic airway inflammation or persistent allergen exposure, unlikely to benefit from increased ICS dose, look for other causes of symptoms
169
Asthma patient, no ongoing symptoms, low FeNO, manangement?
Consider weaning ICS and repeating FeNO in about 1 month
170
Asthma patient, ongoing symptoms, high FeNO?
- eosinophilic airway inflammation or persistent allergen exposure
- inadequate ICS--non-adherence, poor technique or need an increase in dose
- risk for exacerbation
171
Causes for low FeNO?
1) Adequately treated with steroids - no symptoms
2) Technical faults - constant expiratory flow is not maintained - will have symptoms
3) Smoking can cause lower FENO levels - can have symptoms
4) Non eosinophilic asthma(steroid resistant) - will have symptoms
172
Why shouldn’t you use PEF in children
- PEFR should NOT be used to diagnose asthma since it is very effort dependent and only reflects obstruction in large central airways
- Numbers can be artificially high with tongue thrusts or spitting. Or they may be artificially low due to not enough effort or poor technique
173
Onset of action for ipratropium and main side effect?
- Onset of action at 20 minutes, with peak at 60 minutes
| - S/E: dry mouth
174
Spiriva (tiotropium): drug category, receptor and duration of action?
- Anticholinergic
- Muscarinic receptor - M1, M2, M3 (it's a muscarinic receptor antagonist)
- Duration: 24 hours (this is why there is a long withhold time of up to 48 hours prior to bronchodilator testing)
- Peak onset of action: 1-3 hours
- Typical dose: 2 puff of 1.25 micrograms, given once daily
175
How is salmeterol different than formoterol?
- Salmeterol:
- slower onset of action (10-30 minutes) versus 5 minutes for formoterol
- shorter duration of action (9 hours) versus 12 hours - i double checked that it's actually 12 hours for both
- partial agonist of the B2 adrenergic receptor so flatter dose response curve and less bronchoprotection against methacholine (recall that bronchoprotection and bronchodilation are similar, but slightly different effects of LABA)
176
What is one respiratory condition that can get worse with bronchodilators?
Tracheomalacia
177
Dose of prednisone for asthma exacerbation?
1-2 mg/kg/day x 5 days
178
2 major phenotypes of preschool wheeze?
Viral episode wheeze (could also be called infection associated wheeze since wheezing happens with viral and bacterial infections): discrete episodes of wheezing with no symptoms in between. This is the subtype of preschool wheeze that is DIFFERENT than wheeze during school age
Multitrigger wheeze: symptoms during and in between episodes
179
Mechanism of action for ICS?
ICS: reduces cytokines involved with the whole Th2 pathway of inflammation: IL5, other cytokines
180
Limitations of asthma predictive scores, like API?
- Good for negative predictive value, but not for positive predictive value
181
When predicting progression from preschool wheeze to asthma:
- sensitization to multiple allergens at an early age (multiple early atopy)
- severe and frequent episodic wheeze (Even if viral) ?
- These groups both have a high chance of future asthma.
| - (Hard to predict progression for all other groups of patients)
182
Predominant inflammatory cell in patient with suppurative lung disease (CF, PCD, bronchiectasis
Neutrophil
183
Which chemokine attracts neutrophils?
IL1 (CXCL1), IL8 (CXCL8)
184
Which chemokine attracts eosinophils to airway?
CCCL5, IL5
185
What particles affect aerosol deposition?
```
Particle factors:
- Size
- Velocity
- Viscosity and surface
- Hygroscopic properties
Patient factors:
- age
- inspiratory flow rate (breathing pattern)
- nasal versus mouth breathing
- anatomy of upper and lower airway
- disease severity
- cognitive ability/physical ability
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186
Ideal particle size for deposition in lower airways?
1-7 micrometers is considered respirable range
>5 micrometers is likely to deposit in upper airway
<3 micrometers for lower airway deposition
Resp Exam
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