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Eosinophilic Asthma: Medications & ManagementApril 29,2021
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OUR SPEAKER
Disclosures: NONE
Disclaimer: Focus on FDA-approved treatments for Eosinophilic Asthma
Dr. Marissa Shams
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NHLBI. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. No. 08-4051. 2007.
Inflammation
Airway hyper-responsiveness
Reversible airway obstruction
Clinical symptoms(cough, wheezing, dyspnea)
Environmental and genetic factors
Asthma is a syndromerather than a single disease!
Understanding Asthma
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What is Asthma?
Chronic obstructive inflammatory lung “syndrome”
Recurrent episodes of wheeze, cough, shortness of breath and chest tightness
Symptoms vary over time and in intensity
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What is Asthma?
Confirmed airflow obstruction:
•Spirometry with positive response to bronchodilator “reversibility”•Positive bronchial challenge test (Methacholine or Exercise test)
Inflammatory cells infiltrate airways: edema, thickened mucus, bronchospasm
Heterogeneous mix of subtypes “phenotypes”
•Allergic Asthma•Aspirin Exacerbated Respiratory Disease•Eosinophilic Asthma•TH2-Low Asthma
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Asthma Phenotypes & Assessment
Phenotype: unique pathophysiology that drive symptoms, mucosal inflammation and airway smooth muscle contraction
Phenotype assessment:
• Co-Morbidity• Induced sputum analysis• Bronchoscopy• Complete blood cell count (AEC) • Serum IgE• Environmental allergy assessment (spt, sIgE)• FeNO (fractional exhaled Nitric Oxide)
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What is Eosinophilic Asthma?
§ Develops in adulthood§ Severe & persistent form of asthma§ Frequent exacerbations§ Refractory symptoms despite steroids § Fixed airway obstruction§ Eosinophil inflammation within the
airwaysü Lung tissue or sputum (Bronchoscopy)ü Peripheral blood is a surrogate marker
§ Co-Morbidities: ü Chronic Sinusitis & Nasal Polyposis ü Aspirin / NSAID Hypersensitivity
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Asthma Management: Assessing Control
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Asthma Management: Treatment
Goal of Treatment: Reduce symptoms and flares, Improve quality of life, Maintain control• Short Acting-Bronchodilator:
• As needed for symptoms• Inhaled Steroids (+/- Long Acting-Bronchodilator):
• Oral thrush, dysphonia• Oral Corticosteroids:
• Greater bioavailability of medication• Increased risk of side effect with higher doses and longer duration of use• Easy bruising, osteoporosis, cataracts, glaucoma, adrenal suppression, diabetes, hypertension
• Biologic Therapies:• Precision therapies that target the specific source of inflammation • Reduction in exacerbations & symptoms, Improvement in quality of life• Taper / Discontinue use of oral glucocorticoids• Indication: severe asthma, adherent to high-dose inhaled steroids, frequent flares
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© Global Initiative for Asthma, www.ginasthma.orgGINA 2020, Box 3-4A
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Biologic Therapies for Eosinophilic Asthma
Route Frequency Target Biomarker Side effects Other indications
Mepolizumab(Nucala)
SC q4weeks Binds IL-5; reduction in eosinophil production and survival
EAC Herpes ZosterAnaphylaxis / Hypersensitivity Parasite infection
EGPAHES
Reslizumab(Cinquair)
IV q4weeks (weight based dosing)
Binds IL-5; reduction in eosinophil production and survival
EAC Anaphylaxis / HypersensitivityParasite infection
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Benralizumab(Fasenra)
SC q4weeks x 3; q8 weeks
Binds IL-5 receptor, reduction in eosinophil production and survival, activates NK to induce apoptosis of eosinophils & basophils
EAC Anaphylaxis / HypersensitivityParasite infection
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Dupilumab(Dupixient)
SC q2 weeks Binds IL-4 receptor a subunit, inhibit IL-4 & IL-13 cytokines
EAC,FeNO,Oral steroid dependence
Anaphylaxis / HypersensitivityKeratitis
Atopic Dermatitis, Chronic Sinusitis w/ Nasal Polyposis
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Mechanism of Biologic Therapies
WAO Journal 2018
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Questions posed by Biologic Therapies
• Which is the most effective? ?• Best biomarkers to predict effective response??• Therapeutic non-responders: when to switch / stop
medications? ?• Combination of biologic agents or combination of
targets??• Length of treatment? ?• New agents in development?
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Risk Factors for Exacerbations
Poor asthma control
Lack of medication adherence
Incorrect inhaler technique
Smoking
Exposure to triggers
Uncontrolled co-morbid disease
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Inhaler technique is crucial
Metered Dose Inhalers
Dry Powder Inhalers
Breath-actuated devices
Respimat devices
VHC / Spacers
Nebulizer
Allergy & Asthma Network is a national nonprofit organization dedicated to ending needless death
and suffering due to asthma, allergies and related conditions through outreach, education, advocacy
and research.
Short-acting Long-acting
Short-acting Long-acting
relax tight muscles in airways and offer quick relief of symptoms such as coughing, wheezing and shortness of breath for 3-6 hours muscles in airways and offer lasting relief of symptoms such as coughing, wheezing and shortness of breath for at least 12 hours
SHORT-ACTING BETA2-AGONIST BRONCHODILATORS LONG-ACTING BETA2-AGONIST BRONCHODILATORS relax tight
INHALED CORTICOSTEROIDS reduce and prevent swelling of airway tissue; they do not relieve sudden symptoms of coughing, wheezing or shortness of breath
contains inhaled corticosteroid, COMBINATION MEDICATIONS contain both long-acting beta2-agonist (LABA) long-acting beta2-agonist (LABA) and
MUSCARINIC ANTAGONIST (ANTICHOLINERGIC) COMBINATION MEDICATIONS
relieve cough, sputum production, wheeze and chest tightness associated with chronic lung diseases contains muscarinic antagonist and beta2-agonist
contain both inhaled corticosteroid and long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) long-acting muscarinic antagonist (LAMA)
BIOLOGICS target cells and pathways that cause airway inflammation; delivered by injection or IV BRONCHIAL THERMOPLASTY PDE4 INHIBITORS
ease lung inflammation and reduce exacerbations
Respiratory Treatments2021
©2021 Allergy & Asthma Network Reviewed by Dennis Williams, PharmD
ProAir® Digihaler™
117 mcgalbuterol sulfate
ProAir® HFA100 mcgalbuterol sulfate
ProAir RespiClick® 117 mcgalbuterol sulfate inhalation powder
Ventolin® HFA 90 mcgalbuterol sulfate
Serevent® Diskus® 50 mcgsalmeterol xinafoate inhalation powder
Xopenex HFA® 59 mcglevalbuterol tartrate
Striverdi®
Respimat®
2.5 mcgolodaterol hydrochloride
ArmonAir® RespiClick® 55, 113, 232 mcgfluticasone propionate inhalation powder
ArmonAir® Digihaler™ 55, 113, 232 mcgfluticasone propionate inhalation powder
Asmanex® Twisthaler® 110, 220 mcgmometasone furoate inhalation powder
Asmanex® HFA 100, 200 mcgmometasone furoate
Flovent® Diskus® 50, 100, 250 mcg fluticasone propionate inhalation powder
Flovent® HFA 44, 110, 220 mcgfluticasone propionate
Pulmicort Flexhaler® 90, 180 mcgbudesonide inhalation powder
QVAR® Redihaler™ 40, 80 mcg beclomethasone dipropionate
Arnuity® Ellipta®
50, 100, 200 mcgfluticasone furoate inhalation powderAlvesco®
HFA 80, 160 mcgciclesonide
Advair Diskus® 100/50, 250/50, 500/50 mcgfluticasone propionate and salmeterol inhalation powder
Advair® HFA45/21, 115/21, 230/21 mcgfluticasone propionate and salmeterol xinafoate
AirDuo® RespiClick®
55/14, 113/14, 232/14 mcgfluticasone propionate and salmeterol inhalation powder
AirDuo® Digihaler™
55/14, 113/14, 232/14 mcgfluticasone propionate and salmeterol inhalation powder
Anoro® Ellipta®
62.5/25 mcgumeclidinium and vilanterol inhalation powder
Bevespi Aerosphere® 9/4.8 mcgglycopyrrolate and formoterol fumarate
Breo® Ellipta®
100/25, 200/25 mcgfluticasone furoate and vilanterol inhalation powder
Dulera® 100/5, 200/5 mcgmometasone furoate and formoterol fumarate dihydrate
Symbicort® 80/4.5, 160/4.5 mcg budesonide and formoterol fumarate dihydrate
Wixela™ Inhub™ 100/50, 250/50, 500/50 mcg fluticasone propionate and salmeterol xinafoate (approved generic of Advair Diskus)
Stiolto™ Respimat®
2.5/2.5 mcgtiotropium bromide and olodaterol
Trelegy® Ellipta®
200/62.5/25 mcg, 100/62.5/25 mcgfluticasone furoate, umeclidinium and vilanterol inhalation powder
Breztri Aerosphere™
160/9/4.8 mcgbudesonide, glycopyrrolate and formoterol fumarate
= DOSE INDICATOR = GENERIC AVAILABLE DISEASE STATES: = ASTHMA = COPD
Atrovent® HFA 17 mcgipratropium bromide
Combivent® Respimat® 20/100 mcgipratropium bromide and albuterol
Duaklir® Pressair® 400, 12 mcgaclidinium bromide and formoterol fumarate dihydrate
Incruse® Ellipta® 62.5 mcgumeclidinium inhalation powder
Spiriva® HandiHaler®
18 mcgtiotropium bromide inhalation powder
Spiriva® Respimat® 1.25, 2.5 mcgtiotropium bromide
Tudorza™ Pressair™ 400 mcgaclidinium bromide inhalation powder
AllergyAsthmaNetwork.org800.878.4403
Xolair®
omalizumabNucala®
mepolizumab Daliresp®
250, 500 mcg roflumilastCinqair®
reslizumab
Fasenra™
benralizumab Dupixent®
dupilumab
A minimally invasive procedure that uses mild heat to reduce airway smooth muscle, leading to fewer severe asthma flares, ER visits, and days lost from activities. www.btforasthma.com
Proventil® HFA120 mcgalbuterol sulfate
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Non-Pharmacologic Treatment: Avoidance of Asthma Triggers
§ Irritants: smoke, diesel exhaust§ Air pollution: Indoor & Outdoor§ Strong odors / fragrance § Respiratory infection:
ü Annual influenza vaccinationü Pneumococcal vaccination
§ Exercise§ Stress or strong emotions (laughing, crying)§ Sudden change in air temperature or humidity
(cold air)§ Hormonal changes
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Non-Pharmacologic Treatment : Assessment & Treatment of Co-Morbid Disease
§ Chronic Sinusitis with or without Nasal Polyposis
§ Aspirin / NSAID Hypersensitivity§ Obesity§ Tobacco abuse§ Obstructive Sleep Apnea§ GERD§ Depression & Anxiety§ Allergic conditions: Allergic Rhinitis,
Atopic Dermatitis, Food Allergy
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Asthma Management: Follow-Up
Follow-Up
Assess
Adjust
Review Response
Initial Visit§ Confirmation of diagnosis if necessary§ Symptom control § Modifiable risk factors & comorbidity§ Lung function § Inhaler technique and adherence§ Non-pharmacological strategy§ Patient (and parent) preferences and goals
§ Symptom control, Exacerbation frequency§ Medication side effect§ Lung function§ Asthma medications (adjust up or down)§ Patient satisfaction
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Monitoring SymptomsExpiratory Peak Flow Meter: device measuring peak expiratory flow rate
Frequency of symptoms: • Nocturnal awakenings• Activity limitation• Use of rescue inhaler
Symptom tracker app• AsthmaTracker• Asthma Storylines
Frequency of exacerbations:• Need for systemic steroids• ED / UC / Hospital visits• History of intubation need
Determination of asthma control and treatment decisions
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Management of Asthma Exacerbation
When to call your physician
§ Asthma symptoms are worsening§ Asthma symptoms are not responding to
asthma action plan
When to call 911
§ Unable to take a good deep breath § You can only talk in short phrases§ Persistent cough§ Feel too exhausted to breath§ Increased work to breathe§ Easier to breathe when sitting & leaning
forward§ Lips and/or fingernails bluish-gray§ Sweating even though skin feels cold and
clammy
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Preparation for Physician Visit
Seek care of allergist/immunologist or pulmonologist
Symptom logs (apps, journals, pfm values)
Health records:
• Prior hospitalization & ED records• Prior medications including use of oral steroids
Bring all medications to your visit
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Discussion points with physician
§ Confirmation of asthma diagnosis§ Phenotype assessment indicated§ Treatment plan
ü Types of medications & indicationsü Frequency and duration of medicationü Inhaler techniqueü Medication side effectsü Patient preference
§ Asthma action plan & emergency asthma management
§ Determination if treatment is effective§ Frequency of follow-up visits§ Assessment of comorbidity
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Resources for more information
§ Eos Asthma ToolKit§ Eosasthma.org
§ Asthma & Allergy Network§ Allergyasthmanetwork.org
§ American Partnership for Eosinophilic Disorders
§ https://apfed.org/
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