Airways disorders
Asthma biologics: which patients?
Biologic therapies targeting specific inflammatory pathways promise “precision” medicine for severe asthma. Because these therapies are expensive and have different mechanisms of action, appropriate patient selection is crucial. To date, the biologics have been primarily used in severe asthma.
Severe asthma has been defined as “asthma which remains uncontrolled on high-dose inhaled corticosteroids plus a second controller for the previous year or systemic corticosteroids (for 50% or more of the previous year) to prevent it from becoming uncontrolled, or which remains uncontrolled despite this therapy” (Chung, et al. Eur Respir J. 2014;43:343).
Severe asthma is an infrequent to rare occurrence. Only 5% to 10 % of patients have severe asthma (Varsano, et al. Respir Med. 2017;123:131). Indeed, one study suggests that only 3.6% of patients meet criteria for it (Hekking, et al. J Allergy Clin Immunol. 2015;135[4]:896).
Dr. Megan Conroy
Not all difficult to control asthma is severe. With aggressive management of comorbidities and appropriate assessment of medication adherence/inhaler technique, up to 50% of uncontrolled asthmatics can reach therapeutic goals with traditional stepwise inhaler-based therapies (Tay, et al. J Allergy Clin Immunol Pract. 2017;5[4]:956; Hekking, et al. J Allergy Clin Immunol. 2015;135[4]:896). Yet, incorrect inhaler technique (MDI and DPI) is unacceptably frequent and has not improved over the past 40 years (Sanchis, et al. Chest. 2016;150[2]:394). Furthermore, correct inhaler technique was found in only 15.5% of health-care providers and has worsened in recent years (Plaza, et al. J Allergy Clin Immunol Pract. 2018;6[3]:987).
Dr. Stuart M. Garay
After establishing appropriate diagnosis, control of comorbidities, proper inhaler technique, and medication adherence, evaluation of a severe asthmatic’s inflammatory phenotype is necessary. Several phenotypes have emerged, including the severe allergic asthma phenotype and the severe eosinophilic asthma phenotype. Molecular phenotyping allows stratification into type–2–high vs type–2-low patients, which helps guide selection of the appropriate biologic. Options include: (1) anti-IgE (omalizumab); (2) anti-interleukin–5 (mepolizumab and reslizumab); (3) anti-interleukin-5 receptor alpha (benralizumab); and (4) anti-interleukin-4 receptor alpha and interleukin-13 (dupilumab).
Targeted biologics for specific severe asthma phenotypes may be cost effective long-term. However, long-term side effects need to be assessed and pharmaco-economic studies need to be performed.
Megan Conroy, MD
Steering Committee Fellow-in-Training
Stuart M. Garay, MD, FCCP
Steering Committee Chair
Clinical research and quality improvement
Anew, redefined, and enriched
CHEST Physician readers may not know that Clinical Research recently changed its name to include quality improvement (QI). Its new mission is “to provide a forum for clinical research, QI, research ethics, and regulatory aspects, as topics of multidisciplinary discussion and collaboration.” Medical education has become a natural addition to our NetWork’s scope, as this field of scholarly activity has emerged and grown tremendously in the past decade. Interestingly, the number of session submissions to CHEST 2019 increased by a whopping 32% vs 2018, while our NetWork saw an even more impressive increase of 42% in submissions deemed Clinical, Education Research, or QI.
The initial concept of a CHEST Clinical Research NetWork was narrower, aiming to fill gaps between our members’ interests and activities with those of pharmaceutical industry partners and equipment and device manufacturers. Its scope evolved, and our NetWork became the home of all clinical research endeavors not pinned to a specific condition, disease class, or membership category.
QI emerged in other industries long ago, using scientific methods and known to be foundational for any organization’s capacity to survive in competitive environments, become more efficient, satisfy customers, improve outcomes, and develop better work flows and conditions for employees and business partners.
If the QI world strives to achieve certainty with confidence levels less than 0.0001, it is interesting that in our scientific quest we settle for P less than .05. Self-indulgence? Simplistically speaking, are we tolerating “defect rates” of 5%, while others aim for 6 sigma thresholds? These are a few thoughts on how health care can learn from other industries and apply more stringent standards for scholarly activities in clinical research, education, and QI.
Dr. Octavian C. Ioachimescu
In conclusion, while it continues to strive to build the infrastructure of future CHEST clinical research nodes for randomized or observational multicentric studies, Clinical Research and QI NetWork enthusiastically embraces the fields of medical education and QI into its enriched activity scope and scale.
Octavian C. Ioachimescu, MD, PhD, FCCP
Steering Committee Member