MOC-CME ReviewNew and emerging therapies for asthma
Introduction
A 34-year-old woman with severe persistent asthma, atopic dermatitis, and allergic rhinitis presents for evaluation of asthma refractory to conventional therapy. The patient has a history of asthma commencing in early childhood, with progression to uncontrolled disease in the past 2 years. Allergen skin prick testing in childhood showed positive reactions to dust mites, cat and dog dander, and multiple pollens. Her principal triggers are inhaled allergens, especially animal dander, and irritants including tobacco smoke. Despite compliance with maximal dose inhaled corticosteroid and long-acting β-agonist, leukotriene receptor antagonist, nasal corticosteroid, and avoidance measures, she continues to experience nightly wheezing and chest tightness that requires daily β-agonist inhalations. Furthermore, in the past year she has been hospitalized twice for asthma exacerbations after viral infections and has received 5 courses of oral corticosteroids. Her Asthma Control Test score at initial consultation is 7.
Physical examination is notable for bilateral expiratory wheezes in the lower lung fields. Total IgE level is 650 IU/mL and previous allergen sensitivities are confirmed. Lung function testing shows a baseline forced expiratory volume in 1 second (FEV1) of 50% of predicted by age, improving to 66% after bronchodilator administration (460-mL increase). Fraction of exhaled nitric oxide (FeNO) levels are 125 and her peripheral eosinophils are elevated at 1,350 cells/μL. In addition, the patient's inhaler technique is assessed and she demonstrates excellent technique with the controller and rescue devices.
Further questioning addresses any gaps in her asthma management. The patient has excellent medication compliance corroborated by her significant other, has installed dust mite covers, and denies first- or secondhand smoking or furry animal ownership or exposure. A recently performed pregnancy test showed negative results, and she denies a history of chronic sinus disease, including nasal polyposis, aspirin or nonsteroidal anti-inflammatory drug sensitivity, occupational exposures, or gastroesophageal reflux disease. There are no socioeconomic or psychological stressors identified as possible contributors to her uncontrolled asthma and no clinical evidence to support paradoxical vocal fold motion. Evaluations for eosinophilic granulomatosis with polyangiitis and allergic bronchopulmonary aspergillosis are negative. What therapeutic strategies (present and future) can be used to optimize her severe uncontrolled asthma?
Section snippets
Background
Asthma afflicts more than 330 million people and aside from the significant morbidity for patients across many demographics, the financial burden of asthma is enormous. In the United States, asthma care was estimated to cost $56 billion in 2007 and severe asthma has been associated with increased health care expenditures and usage.1 An estimated 12% of patients with asthma in the Severe Asthma Research Program required intensive care unit management.2 Despite implementation of the National
Targeting IL-4 and IL-13
Interleukin-4 and IL-13 have distinct and overlapping roles in asthma pathophysiology. Both cytokines signal through the type 2 IL-4 receptor (IL-4Rα and IL-13Rα1 heterodimer) and are regulated by the master TH2 transcription factor GATA3. IL-4 induces IgE class switching of B cells and is critical for TH2 cell differentiation, whereas IL-13 promotes cellular influx, airway hyperresponsiveness, and remodeling features.[3], [5], [6]
Given the myriad of roles of IL-4 in TH2-mediated asthma,
Conclusion
In the patient presented, medication adherence and correct device technique were confirmed and allergen avoidance strategies were implemented. Moreover, comorbidities were ruled out that are known to negatively affect asthma. Available add-on therapeutic options were discussed, and while waiting for omalizumab approval, a trial with inhaled tiotropium was started. Depending on the patient's response, bronchial thermoplasty could be pursued in the future. For similar patients, several biologics
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Harmonized outcome measures for use in asthma patient registries and clinical practice
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