Severe Asthma

Severe Asthma

Robert S. Hutcheson, Jr., M.D. Lectureship Severe Asthma Venkat K Kollipara, M.D Pulmonary and Critical care Physician 4/22/2021 • No conflict of interest Objectives Clinical scenario of asthma presentation Asthma phenotypes, endotypes and biomarkers Changes in new GINA guidelines 2019 and EPR-3 2020 update Management for severe asthma Case • Beth is a 25-yo-old schoolteacher with history of asthma, allergic rhinitis presented with chief complaint of worsening shortness of breath and cough. • She was diagnosed with asthma a kid and has been using inhalers since then. • She recently needed to use her albuterol about 3 x wk and is waking up nightly for cough. • She also states that she notes that at times she gets winded when climbing up the stairs to her classroom. Case • Currently she is taking Symbicort 160/4.5 bid, Singulair, OTC Allegra and Albuterol prn • Further pertinent history: o She had allergy shots while living in NC as a teenager for about 4-5 years, which she states did help o Lives in a house with mainly wood floors/linoleum. Central air and central heat. She has one indoor cat for the past 6 years. No other pets Exam • BP 125/77, Pulse 89, Temp 98.8 °F, Resp 15, BMI 31.2 kg/m2, SpO2 98% • ENT: no nasal polyps • Chest: clear to auscultation. No wheezes and no crackles • ACT 19, NIOX 45 What questions do you ask her next? Assess inhaler technique Types of inhaler devices • Metered dose inhalers, MDIs • Dry powder inhalers • Soft mist inhalers • Nebulizers • Spacers Mitigation Strategies • Allergen mitigation interventions are recommended only in individuals with asthma who are both exposed to and either sensitized to or develop symptoms on exposure to specific allergens • Multicomponent Allergen Mitigation Strategies • Dust mite–impermeable pillow and mattress covers • HEPA vacuums, carpet removal • Mold mitigation • Integrated pest management (rodents and/or cockroaches)- block infestation (eg, filling holes in walls, reducing standing water) and abatement (eg, traps, fumigation) Asthma • Asthma is a chronic inflammatory disorder of the airways characterized by bronchial hyperresponsiveness and variable airflow limitation • Affects > 300 million people worldwide • Majority of patients with asthma can achieve disease control with standard controller therapy • Approximately 5-10% have severe asthma that remains inadequately controlled despite adherence to standard treatment with a high-dose ICS plus LABA/LAMA Prevalence and burden of asthma The direct costs of uncontrolled asthma in adolescents and adults in the United States over the next 20 years is likely to be a staggering $1.5 trillion National Center for Environmental Health, CDC, 2017 Contributing Factors to Asthma Genetic Factors Environmental Factors Triggers Viral infections Exposure to allergens Occupational exposure Tobacco smoke Aspirin Indoor and outdoor pollutants Factors Influencing the Development of Atopy and Allergic Inflammation Mediated by Th2 Cells A.B. Kay, M.D, N Engl J Med 2001; 344:30-37 Asthma characteristics • Variable and recurrent symptoms • Reversible Airflow obstruction • Bronchial hyperresponsiveness • Airway inflammation Case cont.. Next clinic visit, patient stated she is using inhalers as prescribed and demonstrated good technique Still complaining of shortness of breath and episodic wheezing What further workup do you need? Terminology • Phenotype: The observable characteristics of a disease, such as morphology, development, biochemical or physiological properties, or behaviors. • Examples: allergic asthma, aspirin-exacerbated respiratory disease, severe eosinophilic asthma • Endotype: A subtype of disease, defined functionally and pathologically by a distinct molecular mechanism or by distinct treatment responses (Anderson, Lancet 2008) • Examples: emphysema due to alpha1-antitrypsin deficiency • Biomarker: A defined characteristic measured as an indicator of normal biologic processes, pathogenic processes or response to an intervention • Potential examples: FeNO, blood eosinophils – but these may not meet quality criteria for biomarkers Anderson, Lancet 2008; Reddel, ERJ Open Res 2019 © Global Initiative for Asthma, www.ginasthma.org Asthma endotypes • Heterogeneous disease with multiple phenotypes that are caused by a variety of pathophysiologic mechanisms, or endotypes • There are two specific endotypes, • Type 2 (T2) high • T2 low • These endotypes are defined based on their level of expression of cytokines such as IL-4, IL-5, and IL-13 that may be secreted by the classic T-helper cell type 2 (Th2)-type cells, such as the CD4 lymphocytes, or nonclassic immune cells, such as the innate lymphoid cells–type 2 (ILC-2) Mary Clare McGregor et al, Am J Respir Crit Care Med, Feb 15, 2019 Major biomarkers in Asthma • Blood eosinophils • Sputum eosinophils • FeNO • Periotin • Serum IgE Eosinophil as an Inflammatory Biomarker • Variable numbers of blood and airway eosinophils are present in patients with type 2 cytokine profiles • Likely relates to level of type 2 activation • Eosinophils in blood and airway are correlated with: • Frequency of asthma exacerbations • Degree of airflow limitation • Presence and severity of chronic rhinosinusitis/nasal polyposis Sputum Eosinophil Count • Sputum is induced with hypertonic saline (subject inhales aerosol of hypertonic saline for 15-minute periods and then is encouraged to cough up a sample of sputum) • Normal sputum eosinophils is 3% in adults Sputum Eosinophils • Sputum eosinophils appear to correlate well with disease severity, lung function, and BHR • Asthmatics treated with ICS show a decrease in sputum eosinophils NITRIC OXIDE • In asthma, there is some evidence that this enzyme is up-regulated, and elevated levels of NO have been detected in the exhaled air of asthmatic subjects • Potent vasodilator and bronchodilator • Utility of exhaled NO may be in monitoring asthma control, guiding therapy and providing an indication of corticosteroid sensitivity Source of exhaled nitric oxide • Current thinking is that exhaled NO is derived from the upper and lower respiratory tract (airway & alveolar) and diffuses by gaseous diffusion down a concentration gradient, thus conditioning exhaled air • Exhaled NO is produced by NO synthase in respiratory epithelium under direct control of IL-13 and possibly other factors • often, but no always correlated with sputum/blood eosinophil numbers • is a moderately reproducible marker of Th2 phenotype Periostin • Up-regulated by type 2 cytokines IL-4 and IL-13 • Serum periostin can predict the efficacy of anti-IL 13 antibodies (lebrikizumab) and anti-IgE antibodies (omalizumab) • Periostin-high asthma patients have several unique characteristics, including eosinophilia, high fraction of nitric oxide, aspirin intolerance, nasal disorders, and late onset Asthma Control Test (ACT) Case cont.. Component Value o Alternaria Alternata <0.10 kU/L o Cat Dander (E1) IgE 31.00 kU/L o Cladosporium Herbarum IGE <0.10 kU/L • Right now, using ICS/LABA and o American Cockroach (I206) IGE <0.10 kU/L PRN SABA o Common Ragweed IGE 1.04 kU/L • ACT 18, NIOX 45 o Dust Mite(D.Farinae) (D2) IGE <0.10 kU/L o Dust Mite(D.Pterno.) (D1) IGE <0.10 kU/L o Dog Dander (E5) 1.26 kU/L o Elm (T8) IGE 0.44 kU/L • What is your next step? o IgE 164 kU/L WBC 11,300, 3.6% eosinophils = 396 eosinophils Goals of asthma treatment • Few asthma symptoms • No sleep disturbance Symptom control • No exercise limitation • Maintain normal lung function • Prevent flare-ups (exacerbations) • Prevent asthma deaths Risk reduction • Avoid medication side-effects • The patient’s goals may be different from these • Symptoms and risk may be discordant – need to assess both The best predictor of future exacerbations was a history of previous exacerbation © Global Initiative for Asthma, www.ginasthma.org ATS/ERS Task Force Recommendations to diagnose Severe asthma • Consider and treat comorbidities • Exclude other diagnosis • Poor asthma control due to inadequate understanding of disease management by the patients must be excluded International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. European Respiratory Journal . 2014 43: 343-373. © 2019 Global Initiative for Asthma SMART (Single Maintenance And Reliever Therapy) • SMART is recommended in adolescents (aged 12-17 years) and adults (aged 18 years or older) with moderate persistent asthma as the preferred therapy for steps 3 and 4 (strong recommendation, high certainty of evidence). • SMART has been reported only with formoterol as the LABA, which is why the recommendation is specific to formoterol therapy. • Regular daily use in SMART is defined as 1 to 2 puffs once to twice daily. • As-needed use in SMART is defined as 1 to 2 puffs (4.5 μg of formoterol per puff) every 4 hours as needed for asthma symptoms, up to a maximum of 12 total puffs per day for individuals aged 12 years or older. 2020 Asthma Guideline Update From the National Asthma Education and Prevention Program 2020 Asthma Guideline Update From the National Asthma Education and Prevention Program Case cont.. • You get all the labs results (+RAST, IgE- 164, blood eosinophils 396, FeNO 54, ACT 17) • Follow up clinic visit, patient is compliant with her inhalers, good tech, no triggers, well controlled allergies • Patient still symptomatic and recently admitted to hospital for asthma exacerbation • What treatment options do you have to better control her asthma? How to investigate uncontrolled asthma © 2019 Global Initiative for Asthma N Engl J Med 2012; 367:1198-1207

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