PC1 - Asthma

FEV1

forced expiratory volume in 1 second

FVC

forced vital capacity - amount of gas that can be forcibly and rapidly exhaled after a full inspiration

"Emptying the tank"

Asthma

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

4 different types of asthma

• Allergic

• Aspirin-sensitive

• Neutrophilic

• Exercise-induced

T/F Asthma is one of the most common, chronic, noncommunicable diseases in the world.

True

What medications can trigger asthma

aspirin, NSAIDs, beta blockers

What viral respiratory infections can cause asthma and worsen it?

RSV, Influenza, COVID-19

Clinical presentation of asthma

Coughing, wheezing, chest tightness, shortness of breath

Asthma action plan personal best PEF (L/min)

Green: 80-100%

Yellow: 50-80%

Red: <50%

What plans are made for the asthma action plan?

• maintenance

• exercise

• exacerbation

• emergency

Risk factors for asthma exacerbation

Medications

• SABA overuse (≥3 x 200-dose canisters/year)

• inadequate ICS (not prescribed, poor adherence, wrong techn.)

Comorbidities

• obesity, chronic sinusitis, GERD, pregnancy

Exposures

• smoking, e-cig, vaping, air pollution

Setting

• Psychological/socioeconomic problems

PMH

• ≥ 1 severe exacerbation in past year

• intubation/intensive care for asthma treatment.

Lung f(x)

• Low FEV1, <60% predicted, high bronchodilator responsiveness

Spirometry

Pulmonary function test that measure lung volumes and airflow

Asthma or COPD diagnosis

• FEV1/Predicted FEV1 <70%

• Pre-bronchodilator FEV1/FVC <70%

Spirometry procedure

1. Pt seated upright and understands procedure

2. Explain importance of tight seal around mouthpiece

3. Instruct pt to take deep, full breath in.

4. Exhale forcefully and as quick as possible into spirometer

5. Repeat at least 3 times for reproducibility and accuracy

Asthma diagnosis reversibility

Post-bronchdilator FEV1 increases ≥12% and ≥200 mL OR

Post-bronchodilator PEF increases ≥20%

Most frequent finding in asthma physical exam?

Wheezing on auscultation

Bronchodilator reversibility test

1. Forcefully exhale (preFEV1/FVC)

2. Bronchodilator

3. Wait ~15 min

4. Forcefully exhale (postFEV1/FVC)

• compare pre and post

- reversible if FEV1 or FVC ≥12% and ≥200 mL

A 45-y.o patient presents with recurring cough and wheezing. His spirometry shows:

Pre-bronchodilator - FEV1=2.1 L; FVC = 3.5 L

Post-bronchodilator - FEV1 = 2.4 L; FVC = 3.9 L

Which of the following is most accurate related to his spirometry results?

A. Pre-bronchodilator FEV1/FVC = 0.6(60%); meets criteria for asthma reversibility

B. Pre-bronchodilator FEV1/FVC = 0.75 (75%); does not meet criteria for asthma reversibility

C. Post-bronchodilator FEV1/FVC = 0.67 (67%); meets criteria for asthma r

A. Pre-bronchodilator FEV1/FVC = 0.6(60%); meets criteria for asthma reversibility

Asthma guidelines

NAEPP (last updated 2020) - National Asthma Education and Prevention Program

Key concepts

• SMART

• Asthma severity classification

- intermittent, mild, moderate, severe

GINA

Global Initiative for Asthma (annually updated)

• prioritizes symptom presentation

Key concepts

• terminology - AIR, MART

• two treatment tracks

• SMART

• various relief inhalers

Treatment goals for asthma

1. Control short and long-term symptoms

2. Prevent exacerbation

3. Prevent airway damage

4. Prevent medication s/e

Bronchodilators

SABA

• Short-acting Beta-2 agonist

ICS

• inhaled corticosteroid

ICS + LABA

LAMA

Leukotriene Receptor antagonist

Montelukast

Zileuton

Antibiotics (asthma management)

Azithromycin

Biologics

Omalizumab

Mepolizumab

Reslizumab

Benralizumab

Dupilumab

Tezepelumab

Systemic corticosteroids

Prednisone

Prednisolone

Methylprednisolone

SABA

MOA - Relaxes bronchial smooth muscle (duration ~4-6h)

Quick relief of symptoms and acute bronchospasms + pre-treatment for exercise

Albuterol

Levalbuterol

Proair Digihaler, Proair Respiclick, Proventil HFA, Ventolin HFA

Albuterol

SABA

MDI, DPI - 90, 117, 120 mcg

1-2 puffs q4-6h PRN

A/e: tremor, tachycardia (tachyphylaxis), increased airway responsiveness, decreased effectiveness with beta blockers

Xopenex HFA (MDI)

Levalbuterol

SABA

- MDI - 45 mcg; 1-2 puffs q4-6h PRN

- Nebulizer - 0.63 mg/3mL (0.021%) 1 unit q6-8h PRN

- 1.25 mg/3mL (0.042%)

A/e: tremor, tachycardia (tachyphylaxis), increased airway responsiveness, decreased effectiveness with beta blockers

ICS

• MOA - suppresses multiple inflammatory processes characteristic of asthma w/i airways

• Place in therapy - ALWAYS included in asthma regimens

- decreases airway responsiveness and symptoms

- increases lung function

• inhaled a/e - oral candidiasis - thrush; dysphonia (hoarse voice)

• systemic a/e - osteoporosis (chronic use), cataracts, glaucoma

LABA

• MOA - relaxes bronchial smooth muscle (duration: ~12-24 hours)

• place in therapy: Combined w/ ICS -> ICS+LABA

• NEVER use LABA w/o ICS

BBW: increased risk of asthma-related deaths in LABA monotherapy.

Advair Diskus, Wixela Inhub (generic)

ICS + LABA

Fluticasone Propionate + Salmeterol (DPI)

A/e = tachycardia, h/a, decreased effectiveness w/ B-blockers

Airduo respiclick

ICS + LABA

Fluticasone propionate + Salmeterol (MDI)

A/e = tachycardia, h/a, decreased effectiveness w/ B-blockers

Advair HFA

ICS + LABA

Fluticasone Propionate + Salmeterol xinfoate (MDI)

A/e = tachycardia, h/a, decreased effectiveness w/ B-blockers

Breo Ellipta

ICS + LABA

Fluticasone Furoate + Vilanterol (SMI)

A/e = tachycardia, h/a, decreased effectiveness w/ B-blockers

Symbicort, Breyna

ICS + LABA

Budesonide + Formoterol Fumarate (MDI)

A/e = tachycardia, h/a, decreased effectiveness w/ B-blockers

Dulera

ICS + LABA

Mometasone Furoate + Formoterol Fumarate (MDI)

A/e = tachycardia, h/a, decreased effectiveness w/ B-blockers

Qvar Redihaler

ICS

Beclomethasone dipropionate - MDI

Low dose 100-200

Medium dose >200-400

High dose >400

Pulmicort Flexhaler (DPI)

Pulmicort Respules (Neb)

ICS

Budesonide

LD: 200-400

MD: >400-800

HD: >800

Alvesco HFA (MDI)

ICS

Ciclesonide

LD: 80-160

MD: >160-320

HD: >320

Arnuity Ellipta (SMI)

ICS

Fluticasone Furoate

LD + MD: 100

HD: 200

ArmonAir Respiclick

fluticasone propionate (ICS)

LD: 100-250

MD: >250-500

HD: >500

Asmanex HFA (MDI)

Asmanex Twisthaler (DPI)

Mometasone Furoate (ICS)

HFA

• LD-MD: 200-400

• HD: 400

Twisthaler

• LD: 110-220

• MD: >220-440

• HD: >440

Atrovent HFA

Ipatropium - SAMA

AirSupra

Albuterol and budesonide (SABA/ICS)

Combivent Respimat

albuterol/ipratropium bromide (SABA+SAMA)

DuoNeb

albuterol sulfate/ipratropium bromide (SABA+SAMA)

Wixela Inhub

Fluticasone propionate/Salmeterol xinfoate (ICS/LABA)

Triple Therapy

ICS - LABA - LAMA

Trelegy Ellipta (Fluticasone, vilanterol, umeclidinium)

Breztri Aerosphere (budesonide, glycopyrrolate, formoterol fumarate)

- Breztri not indicated for asthma

Incruse Ellipta

Umeclidinium (LAMA)

Lonhala Magnair

Glycopyrrolate (LAMA)

Spiriva handihaler

tiotropium (LAMA)

SMI

1.25 mcg; 2 puffs daily

A/e: dry mouth, urinary retention

Tudorza Pressair

Aclidinium bromide (LAMA)

Yupelri Neb

Revefenacin (LAMA)

Brovana Neb

Arformoterol (LABA)

Perforomist Neb

Formoterol fumarate dihydrate (LABA)

Serevent diskus

Salmeterol xinafoate(LABA)

Striverdi respimat

Olodaterol HCl(LABA)

Cinqair

Reslizumab

Dupixent

Dupilumab

Fasenra

Benralizumab

Nucala

Mepolizumab

Tezspire

Tezepelumab-ekko

Xolair

Omalizumab

Singulair

Montelukast sodium (Leukotriene inhibitor)

Asthma

10 mg PO once every evening

FDA warning - serious neuropsychiatric events such as suicidal thoughts or action have been reported.

Zyflo

Zileuton (Leukotriene Inhibitor)

600 mg CR PO BID w/i 1 hour of meals

Elevated LFTs

LAMA

MOA: Blocks acetylcholine bronchoconstrictor effect on airway smooth muscle.

Place in therapy: Step 5 (severe) or triple combination inhaler

Comments: Modest improvement in lung function, but not asthma symptoms.

Zithromax

Azithromycin

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

Dosing: 500 mg PO TIW ≥ 6 months

Place in therapy: Severe asthma only after specialist referral in persistent symptoms

A/e: elevated LFTS, tinnitus (long-term use), abdominal pain

Concern for increased Ab resistance.

Prior to therapy with Zithromax, screen for:

Baseline hearing

QTc prolongation

Major drug-drug interaction

Fasenra

Benralizumab

IL-5 antagonist for asthma w/ eosinophilia

30 mg Subcutaneous monthly

A/e Injection site reaction

Cinqair

Reslizumab

Anti-IL-5; depletes eosinophils

3 mg/kg IV monthly

Indicated for severe eosinophilic asthma

BBW for anaphylaxis

Nucala

Mepolizumab

Binds IL-5 and depletes eosinophils

100 mg subcutaneous monthly

Indicated for severe eosinophilic asthma

Injection site reaction

Dupixent

Dupilumab

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

300 mg subcutaneous every 2 weeks

Indicated for severe eosinophilic asthma, OC-dependent asthma.

Injection site reaction

Xolair

Omalizumab

Binds IgE, inhibiting mast cell, basophil binding

75-375 mg subcutaneous every 2-4 weeks

Indicated for severe allergic asthma

BBW for anaphylaxis

Tezspire

Tezepelumab-ekko

Blocks thymic stromal lymphopoietin-reducing inflammatory cytokines

210 mg subcut monthly

Indicated for severe asthma

Injection site reactions

Prelone

Prednisone (systemic corticosteroid)

Omnipred, Orapred

Prednisolone (systemic corticosteroid)

A/e of systemic corticosteroid

Short term: insomnia, hyperglycemia, mood changes

Maintenance: cataracts, glaucoma, HTN, T2DM, adrenal suppression, osteoporosis.

Major drug-drug interaction w/ Systemic corticosteroids

Ritonavir - metabolism boosting agent

Ketoconazole

Itraconazole

T/F: Aminophylline and theophylline are recommended in asthma

False

- previously recommended oral bronchodilator

- life-threatening s/e at high doses.

- lack of efficacy

General principles of treating asthma

• Avoid SABA and LABA monotherapy

• always include ICS

• relief inhaler options

Why is SABA and LABA monotherapy avoided in treating asthma?

- exacerbation

- asthma related death

- reduced bronchodilator response

- allergic response

Relief inhaler options in treating asthma

• SMART rescue inhaler

- ICS - formoterol

• combination rescue inhaler

- ICS - SABA

• maintenance inhaler + rescue inhaler

- ICS + SABA

____ is utilized as a SMART alternative in the USA but it has not been studied or approved by NAEPP or GINA

Dulera