Lecture 22-28 Asthma

Question 1

Asthma Epidemiology

Answer 1

chronic condition, school aged children have it, 40% more prevalent in First Nations, Inuit, and Metis

Consequences: loss of productivity, disruption to the family, health care utilization, psychological impact, activity limitation

Question 2

Asthma Pathophysiology

Answer 2

grumpy or sensitive, triggers, hard to breathe

airway disorder characterized by: airway hyperresponsiveness, paroxysmal or persistent sx, variable airflow limitation, chronic airway inflammation

patterns: many unique phenotypes

allergen or stimuli trigger hypersensitivity rxn: inflammatory cell infiltration ⇒ T-cell and IL, mast cell degranulation, mucous hypersecretion ⇒ high goblet cell activity, smooth muscle contraction, vasodilation and local edema

contributions to airflow obstruction and epithelial damage

chronic inflammation can lead to basement membrane thickening, fibrosis, smooth muscle hypertrophy

Consequences: loss of reversibility on lung tests, reduced response to short acting bronchodilators

Question 3

Diagnosis of Asthma

Answer 3

misdiagnosis is high (30%), lung function tests needed, TEST before TREATING

Clinical History: coughing, wheezing, chest tightness, SOB

Spirometry: Children (> 6) - FEV1/FVC < lower limit of normal (< 0.8-0.9) and increase in FEV1 after a bronchodilator or after a course of controller therapy of > 12%

Adults - FEV1/FVC < LLN (< 0.75 - 0.8) and increase in FEV1 after a bronchodilator or after a course of controller therapy of > 12% and a minimum of > 200 mL

Question 4

Clinical Notes as a Pharmacist for Testing for Asthma

Answer 4

short acting bronchodilators hold for at least 6-8 hours prior to testing

long acting bronchodilators hold for 12-24 hours prior to testing

notation should be made on the test results regarding the last dose of any long or short acting bronchodilator

beta blockers will blunt the effect of the beta agonists

Question 5

Peak Expiratory Flow Meter

Answer 5

this is the measurement of the maximum exhaled flow rate, monitoring of lung fxn, available as mechanical and digital

Question 6

Possible Triggers to Asthma

Answer 6

cold air, food, molds, pollution, pollen, pets, infections, dust mite, smoking, exercise, medicines, stress

Question 7

Risk Factors for Asthma

Answer 7

allergies, atopic dermatitis, family hx of this or atopy - allergic rhinitis, this and atopic dermatitis

Question 8

Screening Tools and Assessment of Asthma Questions

Answer 8

in past 4 weeks has pt had: daytime asthma sx more than 2xweek?

any night waking due to asthma?

reliever for sx more than 2xweek? any activity limitation due to asthma?

Question 9

Risk Factors for Exacerbation of Asthma

Answer 9

high SABA use > 3 x 200 dose canisters/year, increased mortality if > 1 canister/month, inadequate ICS, obesity, chronic rhinosinusitis, GERD, confirmed food allergy, pregnancy, smoking, e-cigarettes, allergen exposure, air pollution, psychological or socioeconomic concerns, low FEV1, high bronchodilator responsiveness, high blood eosinophils, elevated FeNO in adults with allergic asthma taking ICS, intubated, admitted to ICU for asthma, > 1 severe exacerbation in last 12 months

Question 10

Non-Pharmacological Management of Asthma

Answer 10

pt education ⇒ avoiding triggers, goals of therapy, proper medication use (improper technique in up to 80% of pt)

assessing control: sx, PEF,, smoking cessation

vaccinations: influenza, pneumococcal, COVID

physical activity

weight management

control comorbid conditions (rhinosinusitis, GERD)

Question 11

Inhaled Devices for Asthma

Answer 11

Metered Dose Inhalers (MDI) - often with holding chamber (Aerochamber)

Dry Powder Inhalers (DPI) - dose drawn out by pt breath

Soft Mist Inhaler (SMI) - slow mist release for drug delivery

Nebulizers - delivers mist for delivery, uncommon in adults

Question 12

S/LABA

Answer 12

short/long acting beta agonist

Question 13

S/LAMA

Answer 13

short/long acting muscarinic antagonists

Question 14

Inhaled Corticosteroids for Asthma (Drugs, Effect, AE)

Answer 14

Drugs: fluticasone (propionate, Flovent MDI), ciclesonide (Alvesco MDI) (prodrug, inert until activated by esterases in lung), mometasone, budesonide, beclomethasone, etc

Effect: direct local anti-inflammatory effect

AE: fungal infections of throat or mouth - rinse mouth after use, spacers decrease risk, voice changes or hoarseness, sore throat/mouth, adrenal crisis (rare), growth reduction in children by 1-2.5 cm (fluticasone furoate, beclomethasone, triamcinolone), high systemic doses: osteoporosis, cataracts, skin thinning

Question 15

Short/Long Acting Beta Agonists for Asthma (S/LABA) (Drugs, Effect, AE)

Answer 15

Drugs ⇒ Short: salbutamol (Ventolin MDI), terbutaline (rarely used)

Long: salmeterol, indacaterol, vilanterol, formoterol

Effect: activates beta2 airway receptors that result in bronchodilation by relaxation of airway SMCs

AE: tremors or shakiness, nervousness, tachycardia/palpitations, insomnia (long acting)

long acting cannot be used as monotherapy as can increase risk of asthma-related death

Question 16

Short/Long Muscarinic Antagonists for Asthma (S/LAMA) (Drugs, Effect, AE)

Answer 16

Drugs ⇒ Short: ipratropium (not used as prn as often as SABA preferred)

Long: tiotropium, glycopyrronium, aclidinium, umeclidinium

Effect: competitively and reversibly inhibits action of ACh at M3 receptors in bronchial SMC causing bronchodilation

AE: dry mouth, metallic taste, mydriasis and glaucoma if release into eye

Question 17

Systemic Steroids for Asthma (Drugs, Dose, MOA, AE)

Answer 17

x of acute exacerbations

Prednisone dose adults: 40-50 mg/day usually for 5-7 days, Pediatrics: 1-2 mg/kg/day to a max of 40 mg/day usually for 3-5 days

MOA: systemic anti-inflammatory effect

AE: short term - fluid retention, glucose intolerance, increase BP, increase appetite, mood alterations, weight gain, leukocytosis

long term - adrenal axis suppression, avascular necrosis of hip, cataracts, dermal thinning, diabetes, glaucoma, HTN, myopathy, osteoporosis

short term use (14 days) doesn’t require a taper

Question 18

Omalizumab for Asthma (MOA)

Answer 18

aka Xolair

biologic therapy for asthma, IgE neutralizing antibody

moderate to severe persistent asthma + positive skin test or in vitro reactivity to a perennial aeroallergen + inadequately controlled

MOA: inhibits IgE binding to mast cells and basophils receptors = decreases degranulation and mediator response, binds to both serum free IgE levels and high affinity IgE receptors

Question 19

Mepolizumab, Benralizumab, Reslizumab for Asthma (MOA)

Answer 19

biologic therapy, IL-5 inhibitors

IV dosage

all have eosinophil criteria

MOA: inhibit IL-5 signaling = decrease in eosinophils and/or basophils

Question 20

Tezepelumab for Asthma (MOA)

Answer 20

biologic therapy,, anti-thymic stromal lymphopoietin

add on for severe asthma

MOA: binds to human thymic stromal lymphopoietin (TSLP) = reduces inflammatory signal and response

Question 21

Dupilumab for Asthma (MOA)

Answer 21

biologic therapy,, anti IL-4 and 13

adjunctive tx of moderate to severe eosinophilic asthma

MOA: blocking IL-4Ralpha = inhibits IL-4 and 13 cytokine induced inflammatory responses

Question 22

Steps for Tx of Asthma (order)

Answer 22

First line therapies: 1. Start on an ICS (second line LTRA) then depending on age ⇒ 2. add LABA (older than 12) or increase ICS (1-11) ⇒ 3. add LTRA (over 12)/add LAMA (over 12) or LABA (6-11) or LTRA (6-11) ⇒ 4. severe asthma and refer pt

Question 23

bud/form

Answer 23

budesonide-formoterol in a single inhaler

Question 24

Why should we shift away from using a SABA alone?

Answer 24

risk factor for severe exacerbations and asthma related death, more than two inhalers of SABA in a year, SABAs should only be used for sx relief, ICS-formoterol prn > SABA prn alone

ICS-formoterol > SABA reduced risk of exacerbations requiring OCS, ER visit or hospitalizations fewer AE

bud-form prn vs bud bid + SABA prn - no difference in exacerbations needed OCS, no difference in control, low steroid dose, no difference in AE

Question 25

Preferred Regimen GINA Guidelines Ages > 12 for Asthma Control

Answer 25

1. newly diagnosed with asthma start pt on Symbicort (ICS-formoterol) 200 mcg / 6 mcg 1 inhalation prn 2. Same as 1 3.schedule low dose Symbicort (ICS-formoterol) 200 mcg / 6 mcg 1 inhalation bid + prn 4.Symbicort 200 mcg / 6 mcg 2 inhalations bid + 1 inhalation prn,, max adult: 12 inhalations,, max children: 8 inhalations 5.add on a LAMA (ending in -ium) = pt now on triple therapy and refer

Question 26

Alternative Regimen GINA Guidelines Ages > 12 for Asthma Control

Answer 26

1.newly diagnosed with asthma start pt on ICS prn + SABA prn 2.be on a low dose ICS 3.upgrade to a medium-high dose ICS-LABA 4.make into triple therapy with LAMA and refer 5.other options - increase ICS, add LTRA, or HDM SLIT

Question 27

Pediatric Regimen GINA Guidelines Ages 6-11 for Asthma Control

Answer 27

1.low dose ICS taken whenever SABA taken, consider daily low dose ICS 2.daily low dose ICS, could also consider LTRA or same as step 1 3.low dose ICS-LABA, or medium dose ICS or very low dose ICS-formoterol maintenance and reliever (MART), could consider ICS+LTRA 4.medium dose ICS-LABA, or low dose ICS-formoterol maintenance and reliever therapy (MART), refer for expert advice, consider tiotropium or add LTRA 5.refer for phenotypic assessment + or - higher dose ICS-LABA or add-on therapy, ex. anti-IgE, anti-IL4Ralpha, anti-IL5, consider add-on low dose OCS but consider AE ⇒ just refer at this stage

Question 28

Symbicort 200 mcg/6 mcg Dosing

Answer 28

For 12 and Up: Step 1-2. one inhalation prn Step 3. low dose: one inhalation daily-bid + one inhalation prn Step 4-5. medium: two inhalation bid + one inhalation prn, high > 800 mcg/day 6-11 Dosing: Step 1-2. no evidence,, Step 3. very low dose: one inhalation daily + one inhalation prn Step 4. low dose: one inhalation bid + one inhalation prn Step 5. medium dose: two inhalations bid + one inhalation prn

Question 29

Tx for Pt with Infrequent Asthma Sx

Answer 29

meaning less than twice a month, no risk factors for exacerbations, no exacerbation in last 12 months 12 and Up: preferred is as needed low dose ICS-formoterol, alternative low dose ICS prn taken whenever SABA taken 6-11: low dose ICS whenever SABA taken

Question 30

Tx for Pt with Some Asthma Sx

Answer 30

meaning these more than twice a month or more, need for reliever more than twice a month 12 and Up: preferred as needed low dose ICS-formoterol, alternative low dose ICS scheduled taken whenever SABA taken 6-11: daily low dose ICS + SABA prn

Question 31

Tx for Pt with Troublesome Asthma Sx

Answer 31

meaning these on most days (4-5 days/week), waking up at night +/- risk factors 12 and Up: preferred low dose ICS-formoterol schedules + prn, alternative low dose ICS-LABA scheduled + SABA prn, medium dose ICS + SABA prn, reliever could also be ICS-SABA prn,, 6-11: low dose ICS-LABA or medium dose ICS or very low dose Symbicort maintenance and reliever

Question 32

Tx for Pt with Bad Initial Presentation of Asthma

Answer 32

meaning severely uncontrolled this, acute exacerbation, low lung fx 12 and Up: preferred medium dose ICS-formoterol scheduled + prn, alternative medium or high dose ICS-LABA scheduled + SABA prn, reliever could also be ICS + SABA prn, high dose ICS scheduled + SABA prn, short course of OCS may also be needed 6-11: medium dose ICS-LABA + SABA prn or low dose Symbicort maintenance and reliever, short course OCS may be needed

Question 33

Red Flags/Referral Reasons for Asthma

Answer 33

sx other than expected, suspected occupational this, persistent or severely uncontrolled, frequent exacerbations, risk factors for this related death, near fatal ICU admission, suspected or confirmed anaphylaxis, long term OCS use, two or more courses of OCS/yr, tx AEs, other phenotypes

Question 34

Mild Asthma

Answer 34

well controlled with low intensity tx, prn low dose ICS-formoterol, low dose ICS + prn SABA

Question 35

Moderate Asthma

Answer 35

well controlled with Step 3 of 4 of tx, low or medium dose ICS-LABA in either tx track

Question 36

Severe Asthma

Answer 36

uncontrolled despite tx with high dose ICS-LABA, high dose ICS-LABA to prevent it from becoming uncontrolled, ensure rule out inappropriate tx, pt inability to comply, tx of risk factors talking in words, RR > 30, accessory muscles used, pulse rate > 120, O2 saturation < 90%, PEF < 50%

Question 37

Asthma Flare/Exacerbations

Answer 37

progressive increase in SOB, cough, wheezing, chest tightness, progressive decrease in lung fx

Question 38

Risk of Asthma Related Death

Answer 38

intubation and mechanical ventilation, hospitalization or ER visit in last year, recent OCS or currently using, SABA overuse, poor adherence with ICS, lack of asthma action plan, psychosocial concerns, food allergy, several comorbidities

Question 39

Green Zone of Asthma

Answer 39

continue maintenance therapy, well controlled, no night time awakenings, sx no more than twice a week, reliever use no more than twice a week, no missed school or work due to this, can do activity and sports, PEF > 80% of personal best

Question 40

yellow Zone of Asthma

Answer 40

take caution, reliever therapy three or more times per week, daytime sx three or more times per week, physical activity limitations, night time awakenings, PEF 60-80% of personal best Action: increase controller/reliever, get help immediately if no improvement in 2-3 days could use OCS if fail to respond to increase maintenance, severe exacerbations, PEF or FEV1 follow up in 1-2 weeks

Question 41

Red Zone of Asthma

Answer 41

reliever therapy lasts 2-3 hours, continuous sx, continuous cough or wheeze, severe SOB, sudden severe attack, PEF less than 60% of personal best Action: need to see physician ASAP

Question 42

Hospital Management of Severe Asthma

Answer 42

oxygen therapy - maintain oxygen saturations of 93-95%, epinephrine for anaphylaxis, SABA and SAMA - improves PEF and FEV1, corticosteroids po = IV - 5-7 days in adults, 3-5 in children, 50 mg po daily in adults, 1-2 mg/kg in children up to 40 mg Mg IV - FEV1 < 25-30%, antibiotics only if bacterial infection

Question 43

Yellow Zone of Asthma Reliever Action

Answer 43

ICS-formoterol (Symbicort) prn, adults using 200/6 mcg, children 100/6 mcg ICS-SABA prn SABA prn - 2-4 inhalations every 20 min for 3 doses, good response ⇒ interval to every 3-4 hours prn incomplete response ⇒ interval to every 1-3 hours prn

Question 44

Yellow Zone of Asthma Maintenance Action

Answer 44

Symbicort MART ⇒ continue maintenance and increase prn maintenance ICS + SABA prn - 4 x ICS maintenance Symbicort + SABA prn - over 16 can have 4x Symbicort - 4 puffs bid for 7-14 days, use as both controller and prn ICS-LABA + prn SABA ⇒ increase ICS-LABA if able or add ICS along to 4x the dose LTRA - refer CTS - can add prednisone 30-50 mg po 5 days as second option if severe exacerbations, PEF or FEV1 < 60%

Question 45

Yellow Zone of Asthma Follow Up

Answer 45

see clinical in 1-2 weeks, if on OCS assessment before stopping, opp for education, refer if 2 or more exacerbation in year if return to baseline increase maintenance - assess in 3-4 weeks to go down

Question 46

Exercise Induced Bronchospasm (Diagnosis, Pharm, Non-Pharm)

Answer 46

exact mech unknown - osmolarity changes, hyperresponsiveness narrowing of airways, peak after exercise Diagnosis - cough, wheeze, chest pain or tightness, SOB, dyspnea, excessive mucus, feel out of shape, FEV1 on spirometry after exercise, PEF, positive exercise challenge test, positive bronchial challenge test, increase in lung fx after 4 weeks of tx Pharm - ICS scheduled + SABA prn, SABA prior to exercise, ICS-formoterol prn prior to exercise Non-Pharm - warm up, cool down, heat exchange mask, nutrition

Question 47

Work-Related/Occupational Asthma

Answer 47

triggered here by irritants or aeroallergens Sensitizer Induced - induced by sensitizer and process is immunological and IgE mediated Irritant-Induced - after single or many exposures, reactive airway dysfunction syndrome (RADS) due to toxic injury from exposure

Question 48

Perimenstrual Asthma

Answer 48

cyclical deterioration, incidence is between 20-40% MOA likely multifactorial - exaggerated inflammatory response to triggers coinciding with fluctuations in sex hormones, reduced serum progesterone levels diagnosis via self-reporting sx or through reduction in PEF Management: standard approach, may involve increasing anti-inflammatory therapy prior to menstruation

Question 49

AE of Poorly Controlled Asthma in Pregnancy

Answer 49

low birth weight of fetus, increased prematurity of fetus, increased perinatal mortality, maternal complications, HTN disorders including preeclampsia, hyperemesis gravidarum, hemorrhage, placenta previa

Question 50

Asthma in Pregnancy Management

Answer 50

maintain adequate O2 to fetus by preventing exacerbations ICS first line - budesonide preferred, fluticasone, triamcinolone, flunisolide, beclomethasone all safe continue to suggest reliever (SABA) prn and monitor for increased usage and loss of asthma control montelukast may be used safely LABAs have not shown AE

Question 51

Asthma in Breastfeeding Management

Answer 51

SABAs, I/OCS, LABAs, mACh antagonists are all safe montelukast is transferred into milk however it is indicated in pt with asthma as young as 6 months

Question 52

Aspirin Exacerbated Respiratory Disease (AERD)

Answer 52

1/5 sensitive, aka Samter's triad: asthma, sinus disease with recurrent nasal polyps, sensitivity to this and NSAIDs dose dependent cross reactivity with acetaminophen, selective COX2 inhibitor MOA: shunting of arachidonic acid metabolism away from the COX pathway toward the lipoxygenase (LO) pathway, increases leukotrienes resulting in bronchoconstriction and a decrease in PG synthesis, mech is not thought to involve immune system but involves inhibition of IC COX in respiratory cells Management: avoid NSAIDs and this, COX2 selective agents may be considered in some pt

Question 53

Diagnosis of Asthma in Preschoolers

Answer 53

can't physically perform spirometry requires: signs or sx of airflow obstruction, reversibility of obstruction, no clinical suspicion of alternative diagnosis - ex. rhinosinusitis, foreign-body inhalation, pneumonia, GERD, cystic fibrosis, swallowing problems

Question 54

Asthma Management in Preschoolers

Answer 54

Persistent Sx or Moderate-Severe Exacerbations: 1st line = ICS at lowest effective dose with SABA prn, daily LTRA should be 2nd line only ⇒ Step Up Therapy: increase ICS to double low dose, if pt trialed and controlled on double then dose decreased by 50% every 2-3 months until lowest effective dose achieved, if control not achieved refer