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Asthma Phenotypes PowerPoint Presentation

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Description : This medical presentation titled ""Asthma Phenotypes"" evaluates the concept that asthma is not a single disease, identifies asthma phenotypes, and talks about a treatment approach based on the different phenotypes of asthma.

Tags : Allergy, Asthma, Phenotypes, treatment, Tightening, Airways, Airway Remodeling, Thick Mucous Production, Acute, Chronic Phases, Wheezing, Coughing, Shortness of Breath, syndrome, Eosinophils, Radioallergosorbant IgE, RAST, allergy testing, Occupational, Asthma-Exacerbated, Severe, refractory

Published on : Apr 24, 2021 | Views : 2405 | Downloads : 23

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Slide 1-

Asthma Phenotypes Neeta Thakur MD, MPH and George Su MD Zuckerberg San Francisco General University of California, San Francisco
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Disclosures Spouse employee of Roche/Genentech
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Learning Objectives Evaluate the concept that asthma is not a single disease Identify asthma phenotypes Develop a treatment approach based on the different phenotypes of asthma
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Living with asthma https://lindseykonkel.files.wordpress.com/2012/10/the-racial-discrimination-embedded-in-modern-medicine.pdf Photo Credit: Sam Oh
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What is asthma? Tightening of Airways Airway Remodeling Thick Mucous Production Acute and Chronic Phases Wheezing Coughing Shortness of Breath What causes asthma?
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Lötvall JACI 2011
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Asthma Phenotypes Fahy Nat Rev Immunol 2015 ALLERGIC Non-ALLERGIC
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curr opin allergy clin immunol. 2012 apr;12(2):193-201. doi: 10.1097/aci.0b013e32835090ac. severe asthma in childhood: recent advances in phenotyping and pathogenesis.
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Non-eosinophilic Childhood Adult Eosinophilic Asthma Phenotypes
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Dust mites Pollens Eosinophils Elevated in bronchial bx, induced sputum or peripheral blood Corticosteroid naïve ≥2.7% (blood) I: concordance between symptoms and airway eos “Childhood-onset” and allergy to airborne allergens II: discordance, fewer symptoms “Late-onset” non-atopic disease Persistence on high-dose ICS or PO steroids associated with symptomatic and exacerbation-prone disease
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Non-eosinophilic Childhood Adult Eosinophilic Asthma Phenotypes Allergic Intrinsic
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Dust mites Pollens How do you identify this group? Total IgE Sum of total IgE Sometimes reported as %total IgG (0.05% normal) 60% of allergic asthma (includes HMW OA) Poor PPV and NPV compared to allergen-specific IgE
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Dust mites Pollens How do you identify this group? Radioallergosorbant IgE (RAST) Allergen-specific IgE More expensive than skin-prick Less sensitive and specific Rational starting point: Specific HMW candidate antigen(s) (some LMW antigens) Determine positive aeroallergen Grasses, weeds, dust mites, molds Low predictive value for food allergies
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Dust mites Pollens How do you identify this group? Skin prick allergy testing More sensitive and specific than RAST False negatives: OTC antihistamines (48 hours) Allegra, Clarinex, Zyrtec and Astelin (Azelastin) nasal spray (5 days) PO steroids (25 mg prednisone) (3 weeks) High dose topical steroids (3 weeks)
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What’s the Asthma Phenotype? Occupational Asthma Beckett W., et al., NEJM 2000
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Occupational Asthma “Work-sensitized” (high MW >5000 daltons) IgE-mediated “asthma with latency” “Irritant-induced” (low MW <5000 daltons) Non IgE-mediated “asthma without latency” Irritant asthma Reactive airways dysfunction syndrome (RADS) “Low-dose RADS” “Work-exacerbated” (aggravated) > 250 workplace culprit substances Estimated 16% of all adult onset asthma Toren and Blanc 2009
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What do these have in common?
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When to do obstruction testing for Occupational Asthma? Preferably performed toward the end of a typical work week and within 24 hr of the occurrence of symptoms
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Active panel patients with DM Non-eosinophilic Occupational (non-sensitized) Asthma Phenotypes Childhood Allergic Intrinsic Adult Eosinophilic Occupational (sensitized)
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What’s the Asthma Phenotype? 34 year old man Persistent rhinitis at age 30, watery rhinorrhea Cough, wheeze Sudden acute event requiring ED visit No previous history of asthma
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B. Ghorayeb, MD
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Case: Diagnosis Exacerbation after ingestion of aspirin or other non-NSAIDs Starts with intractable nasal congestion and watery rhinorrhea Refractory to pharmacologic Treatment Progressive, may become associated with anosmia Specific IgE tests negative Nasal polyposis Total or near-total opacification of the sinus cavities (on CT) An individual with rapid onset of a severe attack with no previous insult who necessitates acute emergency care, intensive care unit admission, or endotracheal intubation
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Asthma-Exacerbated Asthma
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Aspirin-Exacerbated Asthma: diagnosis Sample oral challenge protocol Starting dose of 40.5 mg Doses given at 3 hour intervals, up to a maximum dose of 325 mg Time interval between doses can be shortened to 90 minutes unless the patient specifically reports that symptoms began within 90 minutes Protocols are carried out over one to two consecutive days Observation and spirometry
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Active panel patients with DM Non-eosinophilic Childhood Adult Eosinophilic Aspirin Cough variant Air pollution Asthma Phenotypes Allergic Intrinsic Occupational (sensitized) Occupational (non-sensitized) EIA Cigarette
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Leiria, 2014 Obese Asthma Phenotype
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Active panel patients with DM Non-eosinophilic Childhood Adult Eosinophilic Aspirin Cough variant Air pollution Asthma Phenotypes Allergic Intrinsic Occupational (sensitized) Occupational (non-sensitized) EIA Cigarette Obesity
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Active panel patients with DM Non-eosinophilic Childhood Adult Eosinophilic Aspirin Cough variant Air pollution Asthma Phenotypes Allergic Intrinsic Occupational (sensitized) Occupational (non-sensitized) EIA Cigarette Obesity Infection-related
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Severe/refractory asthma (ATS workshop) Continuous or near-continuous oral steroids High-dose ICS Additional daily controller Use of SABA on a near-daily basis Persistent airway obstruction FEV1 < 80% Diurnal variation in PF ≥ 25% ≥ 1 urgent care visit per year ≥3 or more steroid bursts per year Prompt deterioration with 25% reduction in steroid dose Episode of near-fatal asthma Minor (2) Major (≥1)
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Active panel patients with DM Non-eosinophilic Childhood Adult Eosinophilic Aspirin Cough variant Air pollution Asthma Phenotypes Allergic Intrinsic Occupational (sensitized) Occupational (non-sensitized) EIA Cigarette Obesity Infection-related Exacerbation-prone
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Emerging Treatment Options Based on Phenotypes TARGETED AT Th2 (ALLERGIC) ASTHMA
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Treatments based on Phenotypes - Omalizumab Best Candidates: High IgE Known Allergen BMI
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Hanania Ann Intern Med 2011, Busse NEJM 2011 Treatments based on Phenotypes - Omalizumab Asthma Exacerbations
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IL-5: Key cytokine in eosinophil Differentiation Recruitment Activation Survival Best Candidates: - High Eosinophils - 2 or greater exacerbations/yr - On high dose ICS Fulkerson Nature Review Drug Discovery 2013 Treatments based on Phenotypes - Mepolizumab
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MENSA trial (RCT), selected for high eosinophils, mod-high dose ICS Treatments based on Phenotypes - Mepolizumab Asthma Exacerbations and FEV1 at 32 Weeks. Ortega NEJM 2014 (Sponsored by Glaxo-Smith Kline)
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Side Effects and Adverse Reactions Omalizumab Anaphylaxis (must have epi-pen) 0.1-0.2% Can occur as late as 1 year ? Malignancy (0.5 vs. 0.2% in RCT) Longer observation trials underway Pain and arthralgia Injection site bruising/pain Mepolizumab No observed risk of anaphylaxis Muscle pain Fatigue Injection site bruising/pain
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In Summary ASTHMA IS COMPLEX!!! Look at multiple data points, including Age Patient specific data: BMI, occupation Triggers Disease course Biomarkers