Asthma

asthma

complex disorder which affects airways of the lung, characterized by variable and recurring respiratory symptoms, airflow obstruction, bronchial hyperresponsiveness, and underlying inflammation

true

T/F: The incidence of death related to asthma is higher in black and Puerto Rican patients than white patients.

1. Allergens: pollen, mold, dust, cockroaches

2. Viral respiratory infections: RSV, Influenza, COVID-19

3. Irritants: perfumes, gases, fumes, cold/hot air

4. Smoke: inhaled, secondhand, fireplaces

5. Exercise: long-term, strenuous

6. Medications: beta-blockers, NSAIDs

list some asthma triggers

beta-blockers and NSAIDs

list some medications that can trigger asthma

SABA overuse: ≥3 x200-dose canisters/year

Inadequate ICS: not prescribed, poor adherence, wrong technique

list some medications that can exacerbate asthma

obesity

chronic sinusitis

GERD

pregnancy

list some comorbidities that can exacerbate asthma

high blood eosinophiles

list the type 2 inflammatory marker that can exacerbate asthma.

intubation or intensive care for asthma treatment

≥ 1 severe exacerbation per year

list things in a patient's PMH that can exacerbate asthma

spirometry

a pulmonary function test that measures lung volumes and airflow.

- Forced Expiratory Volume in 1 second: FEV1

- Forced Vital Capacity: FVC

- "predicted": standard value based upon age, sex, and height

FEV1/Predicted FEV1 <70%

Pre-bronchodilator FEV1/FVC <70%

what is the FEV1 value that is used as diagnostic criteria for asthma and COPD?

wheezing on auscultation

what is the most frequent finding on a PE for asthma?

Post-bronchodilator ≥ 12% and ≥200 ml

OR

Post-bronchodilator PEF increases ≥20%

There is variable expiratory airflow for the diagnosis of asthma. One objective measure is the reversibility of expiratory airflow. What levels indicate asthma reversibility?

[(Post FEV1 - Pre FEV1) / Pre FEV1] x 100

* should be ≥ 12%

Post FEV1 - Pre FEV1 should be ≥ 200 ml

what is the formula to determine if airway obstruction is reversible?

SABA

**decreased effectiveness with beta-blockers (use cardioselective)

** AVOID SABA MONOTHERAPY

relaxes bronchial smooth muscle

- duration: 4-6 hours

- place in therapy: quick relief of symptoms and acute bronchospasm; pretreatment for exercise

- use lowest dose and frequency as needed

- avoid monotherapy

- increases risk of severe exacerbations (>3 inhalers/year) and asthma-related death (>12 inhalers/year)

1-2 puffs Q4-6 hours PRN

Dosing for Albuterol inhalers

- ProAir Digihaler

- ProAir Respiclick

- Proventil HFA

- Ventolin HFA

1 unit 3-4 times daily PRN

Dosing for Albuterol nebulizer

1-2 puffs Q4-6 hours PRN

Levalbuterol (Xopenex HFA) dosing

1 unit Q6-8 hours PRN

Levalbuterol nebulizer dosing

Tremor

Tachycardia

Tachyphylaxis

AEs of Albuterol and Levalbuterol (SABAs)

ICS

Suppress multiple inflammatory processes characteristic of asthma within airways; decreases airway responsiveness and symptoms and increases lung function

- place in therapy: ALWAYS included in asthma regimes

- available as monotherapy or combination

Oral candidiasis (counsel patients to rinse and spit)

Dysphonia (hoarse voice)

Inhaled AEs of ICS.

Osteoporosis

Cataracts, glaucoma

Systemic AEs associated with long-term, high dose ICS

ICS + SABA

ICS + Formoterol

ICS combos used as needed (reliever) for asthma

ICS + LABA

ICS + LABA + LAMA

ICS combos used as maintenance therapy for asthma

LABA

** decreased effectiveness when used with beta-blockers (use cardioselective)

Relaxes bronchial smooth muscle

- duration: 12-24 hours

- place in therapy: always in combination with an ICS

- BBW: risk of asthma-related deaths in monotherapy

- SEs: tachycardia, headache

LAMA

block acetylcholine bronchoconstrictor effect on airway smooth muscle

- place in therapy: Step 5 [severe] in combination with ICS-LABA

- modest improvement in lung function, but not asthma symptoms.

- SEs: dry mouth, urinary retention

2 puffs daily

Spiriva Respimat (Tiotropium) dosing

1 puff daily

Trelegy Ellipta (Fluticasone furoate, vilanterol, umeclidinium) dosing

Leukotriene Receptor Antagonist

- Montelukast (Singulair)

- Zileuton (Zyflo) [technically not an LRA; is a 5-lipoxygenase inhibitor that prevents the formation of leukotrienes]

Block effects of leukotrienes (inflammatory cascade factor)

- place in therapy: add-on alternative in maintenance therapy; useful in allergic rhinitis

- steroid sparing (can reduce the need for steroids)

10 mg PO once every evening

dosing and administration for Montelukast (Singulair)

600 mg CR PO BID within 1 hour of meals

dosing and administration of Zileuton (Zyflo)

elevated LFTs

Zileuton (Zyflo) can cause elevated ______

serious neuropsychiatric events: suicidal thoughts or actions have been reported

BBW of Montelukast (Singulair)

Azithromycin (Zithromax)

antibacterial, antiviral, and anti-inflammatory effects, limiting mucus airway secretions

- place in therapy: severe asthma only after specialist referral in persistent symptoms despite therapy with ICS-LABA

- AEs: n/v/d, abdominal pain, elevated LFTs, tinnitus (long-term use)

- concern for increased antibiotic resistance

- PRIOR to therapy, screen: baseline hearing, QTc prolongation, major drug-drug interactions

500 mg PO TIW ≥ 6 months

dosing for Azithromycin (Zithromax)

Benralizumab (Fasenra)

binds IL-5 and depletes eosinophils

- indication: severe eosinophilic asthma

- dose: 30 mg SQ monthly

- AEs: injection site reactions

Reslizumab (Cinqair)

binds IL-5 and depletes eosinophils

- indication: severe eosinophilic asthma

- dose: 3 mg/kg IV monthly

- BBW for anaphylaxis

Mepolizumab (Nucala)

binds IL-5 and depletes eosinophils

- indication: severe eosinophilic asthma

- dose: 100 mg SQ monthly

- AEs: injection site reactions

Dupilumab (Dupixent)

inhibits IL-4, 13 signaling in B, CD4, and T cells in smooth muscle

- indication: severe eosinophilic asthma and OC-dependent asthma

- dosing: 300 mg SQ every 2 weeks

- AE: injection site reaction

Omalizumab (Xolair)

binds IgE, inhibiting mast cell and basophil binding

- indication: severe allergic asthma

- dose: 75-375 mg SQ every 2-4 weeks

- BBW for anaphylaxis

Tezepelumab (Tezspire)

blocks thymic stromal lymphopoietin, reducing inflammatory cytokiines

- indication: severe asthma

- dosing: 210 mg SQ monthly

- AE: injection site reaction

Prednisone (Prelone)

Prednisolone (Omnipred, Orapred)

suppress multiple inflammatory genes within airways to reduce inflammation; systemic

- place in therapy: mild-moderate exacerbation (outpatient)

- short-term AEs: insomnia, hyperglycemia, mood changes

- long-term AEs: cataracts, glaucoma, HTN, T2DM, adrenal suppression, osteoporosis

Methylprednisolone sodium succinate (Solumedrol)

suppress multiple inflammatory genes within airways to reduce inflammation; systemic

- place in therapy: severe exacerbation in hospital setting

- short-term AEs: insomnia, hyperglycemia, mood changes

- long-term AEs: cataracts, glaucoma, HTN, T2DM, adrenal suppression, osteoporosis

40-50 mg PO x 5-7 days

dosing for Prednisone (Prelone) or Prednisolone (Omnipred, Orapred) for a mild-moderate asthma exacerbation in the outpatient setting

1-2 mg/kg IV daily or in 2 divided doses

dosing for Methylprednisolone sodium succinate (Solumedrol) for a severe asthma exacerbation in a hospital setting

2 weeks

systemic steroid taper is indicated when steroids are used ≥____ weeks

Ritonavir

Ketoconazole

Itraconazole

**all are CYP3A4 inhibitors

list the major drug-drug interactions with Prednisone (Prelone), Prednisolone (Omnipred, Orapred), and Methylprednisolone sodium succinate (Solumedrol)

false; dose is not high enough to treat exacerabtion

T/F: Medrol DosePak can be used to treat an asthma exacerbation.

Aminophylline and Theophylline

previously recommended oral bronchodilators that have life-threatening side effects at high doses and have a lack of efficacy in treating asthma

SMART (Single Maintenance And Relief Therapy)

- Symbicort (Budeosonide/formoterol 160/4.5 mcg)

- Breyna (Symbicort generic)

**Dulera has been utilized in the USA as SMART alternative to Symbicort; however, it has not been studied or approved by NAEPP or GINA

one inhaler for relief and maintenance in asthma

- simpler administration technique

- more effective compared to traditional therapy in reducing exacerbations

- do NOT exceed 12 doses within 24 hours

low dose ICS-formoterol (Symbicort or Breyna)

what is the recommended reliver in GINA Track 1?

Symbicort or Breyna (Budesonide + Formoterol) 160/4.5 mcg: 1 puff PRN

- do not exceed 12 puffs within 24 hours

GINA Track 1 Step 1-2

Symbicort or Breyna (Budesonide + Formoterol) 160/4.5 mcg: 1 puff daily or BID (low dose) + 1 puff PRN (relief)

- do not exceed 12 puffs within 24 hours

GINA Track 1 Step 3

Symbicort or Breyna (Budesonide + Formoterol) 160/4.5 mcg: 2 puffs daily or BID (medium dose) + 1 puff PRN (relief)

- do not exceed 12 puffs within 24 hours

GINA Track 1 Step 4

Increase Symbicort or Breyna (Budesonide + Formoterol) 160/4.5 mcg to 2 puffs BID if not already AND add on LAMA (Spiriva Respimat) 2 puffs daily OR add on biologic therapy

OR

Switch to ICS-LABA-LAMA (Trelegy Ellipta) 1 puff daily

GINA Track 1 Step 5

GINA Track 1: Low dose ICS-formoterol PRN

Regarding initial therapy for newly diagnosed patients, what is the preferred therapy for a patient who presents with infrequent asthma symptoms (1-2 days/week or less)?

GINA Track 2: low-dose ICS taken whenever SABA is taken for asthma symptoms (combination or separate inhalers)

Regarding initial therapy for newly diagnosed patients, what is the an alternative therapy to GINA Track 1, ICS-formoterol for a patient who presents with infrequent asthma symptoms (1-2 days/week or less)?

GINA Track 1: medium-dose ICS-formoterol MART

Regarding initial therapy for newly diagnosed patients, what is the preferred therapy for a patient who presents with daily asthma symptoms, waking at night with asthma symptoms once or more a week, with low lung function, or current smokers?

GINA Track 2: regular daily medium or high dose ICS-LABA plus ICS-SABA PRN; regular daily high dose ICS plus SABA PRN

Regarding initial therapy for newly diagnosed patients, what is the alternative therapy to GINA Track 1, ICS-formoterol for a patient who presents with daily asthma symptoms, waking at night with asthma symptoms once or more a week, with low lung function, or current smokers?

In the past 4 weeks, has the patient had:

1. Daytime symptoms more than twice/week

2. Night waking due to asthma

3. SABA reliever needed more than twice/week (only for patients using SABA; do not include SABA taken before exercise)

4. Any activity limitation due to asthma

Well controlled: none of these

Partly controlled: 1-2 of these

Uncontrolled: 3-4 of these

How to assess symptom control in chronic therapy of asthma?

symptoms controlled + stable lung function ≥ 3 months

**reduce ICS potency, NEVER discontinue

when could you step down (reduce therapy) in asthma therapy?

- keep 2 inhalers: 1 inhaler at home and one with you at all times

- may space PRN doses minutes to hours apart

- do not exceed 12 puffs/24 hours

- rinse mouth after use

SMART patient counseling

1. ICS-SABA [Airsupra]

2. ICS + SABA (use separate inhalers) [Step 1]

3. SABA [Steps 2-5]

List the reliever options in GINA Track 2

Combination ICS-SBA: Airsupra (Albuterol + Budesonide) 90/80 mcg 2 puffs PRN

- max: 12 inhalations/24 hours

**may use Airsupra as reliever inhaler for track 2 steps 1-5

GINA Track 2 Step 1 Option 1

Separate ICS (low-dose) + SABA PRN

SABA: Albuterol 1 puff Q4-6 hours PRN

**separate reliever ONLY necessary for track 2 step 1!!

Low-dose ICS: (all 1 puff PRN)

- Arnuity Ellipta (Fluticasone furoate) 50 mcg [DPI]

- Flovent HFA (Fluticasone propionate) 44 mcg [MDI]

- Asmanex HFA (Mometasone) 50 mcg [MDI]; Asmanex Twisthaler 110 mcg [DPI]

- Pulmicort Flexhaler (Budesonide) 90 mcg [DPI]

- QVAR RediHaler (Beclomethasone) 40 mcg [MDI]

- Alvesco (Ciclesonide) 80 mcg [MDI]

GINA Track 2 Step 1 Option 2

Controller: Low-Dose ICS Maintenance DAILY

Reliever: ICS-SABA (Airsupra) OR SABA*

*may use Albuterol alone as a reliever inhaler for track 2 steps 2-5

GINA Track 2 Step 2

One puff daily:

- Arnuity Ellipta (Fluticasone furoate) 50 mcg [DPI]

- Flovent HFA (Fluticasone propionate) 44 mcg [MDI]

- Asmanex HFA (Mometasone) 50 mcg [MDI]; Asmanex Twisthaler 110 mcg [DPI]

One puff BID:

- Pulmicort Flexhaler (Budesonide) 90 mcg [DPI]

- QVAR RediHaler (Beclomethasone) 40 mcg [MDI]

- Alvesco (Ciclesonide) 80 mcg [MDI]

Low Dose ICS Maintenance inhalers for Track 2 Step 2

Controller: Low-dose maintenance ICS + LABA

Reliever: ICS-SABA (Airsupra) OR SABA

GINA Track 2 Step 3

- Symbicort or Breyna (Budesonide + Formoterol) 80/4.5 mcg [MDI]: 2 puffs BID

- Symbicort or Breyna (Budesonide + Formoterol) 160/4.5 mcg [MDI]: 1 puff BID

- Dulera (Mometasone + Formoterol) 100/5 mcg [MDI]: 1 puff BID

- Airduo Respiclick (Fluticasone + Salmeterol) 55/14 mcg [DPI]: 1 puff BID

- Advair Diskus (Fluticasone + Salmeterol) 100/50 mcg [DPI]: 1 puff BID

- Advair HFA (Fluticasone + Salmeterol) 45/21 mcg [MDI]: 2 puffs BID

- Breo (Fluticaone + Vilanterol) 100/25 mcg [DPI]: 1 puff daily

GINA Track 2 Step 3 Low-Dose ICS+LABA maintenance options

Controller: Med/High-dose maintenance ICS+LABA

Reliever: ICS-SABA (Airsupra) OR SABA

GINA Track 2 Step 4

- Symbicort or Breyna (Budesonide + Formoterol) 160/4.5 mcg [MDI]: 2 puffs BID (med)

- Dulera (Mometasone + Formoterol) 200/5 mcg [MDI]: 1 puff BID (med) or 2 puffs BID (high)

- Airduo Respiclick (Fluticasone + Salmeterol) 232/14 mcg [DPI]: 1 puff BID

- Advair Diskus (Fluticasone + Salmeterol) 250/50 mcg [DPI]: 1 puff BID (med) or Advair Diskus 500/50 mcg 1 puff BID (high)

- Advair HFA (Fluticasone + Salmeterol) 230/21 mcg [MDI]: 1 puff BID (med) or 2 puffs BID (high)

- Breo (Fluticaone + Vilanterol) 100/25 mcg or 200/25 mcg [DPI]: 1 puff daily

GINA Track 2 Step 4 Med/High-Dose ICS+LABA maintenance options

**Refer to specialist

Increase to High-Dose ICS-LABA if not already AND add on LAMA (Spiriva Respimat) OR add on biologic therapy

OR

Switch to ICS-LABA-LAMA (Trelegy Ellipta)

GINA Track 2 Step 5

Daily LTRA

third line controller option in track 1 or track 2

COVID-19

Pneumococcal

Influenza

RSV (Special populations)

routinely recommended immunizations in patients with asthma

rapid reversal of airflow limitation and if necessary, correction of hypercapnia/hypoxemia

goals of treatment for treatment of asthma exacerbations

mild-moderate

What is the severity of exacerbation below?

- Speech/alertness: talks in phrases, prefers sitting, not agitated

- PEF: >50% of best

- RR: > 20/min

- No use of intercostal muscles

- Pulse: 100-120 bpm

- O2 sat: 90-95%

severe

What is the severity of exacerbation below?

- Talks in words, hunches forward, agitated

- PEF: ≤50% of best

- RR: > 30/min

- Use of intercostal muscles

- Pulse: >120 bpm

- O2 sat: <90%

life-threatening

What is the severity of exacerbation below?

- Unable to speak, drowsy, confused

- RR: impending or actual respiratory arrest

- Use of intercostal muscles

- Pulse: >120 bpm

- O2 sat: <90%

SABA: Albuterol MDI with spacer 4-10 puffs Q20 mins for 1 hour

OCS: Prednisone 40-50 mg PO Daily x 5-7 days

Oxygen: titrate to 93/95%

treatment for mild-moderate asthma exacerbation

SABA: Albuterol 2.5-5 mg nebulizer Q20 minx 1 hour, then Q1-4 hours PRN OR Albuterol continuous nebulization

+/- SAMA: Ipratropium 500 mcg neb Q20 min x 3 doses, then hourly PRN up to 3 hours

**Ipratropium + Albuterol = Duoneb Nebulizer Solution

Methylprednisolone 1-2 mg/kg IV divided in 1-2 doses until PEF > 60-80% of personal best

Consider Magnesium sulfate 2 g IV over 20 minutes x 1 dose if inadequate response to above

Oxygen: titrate to 93-95%

treatment for severe asthma exacerbation

Smoking cessation

Physical activity

Investigate occupational asthma

Aspirin-exacerbated respiratory disease

non-pharmacological treatment for asthma