Symposium : Issues in difficult asthma management Difficult asthma : Assessment and management , Part 1

A minority of asthma patients have disease that proves difficult to control with usual medications and experience ongoing symptoms, poor quality of life, and limitations in activity and/or frequent asthma exacerbations. This group of patients accounts for much of the expense associated with asthma care and is the focus of national and international collaborative study groups. Distinguishing between “difficultto-manage asthma” and truly “therapy-resistant asthma” is helpful and promotes a systematic consideration of contributory factors. Critical evaluation of factors contributing to difficult-to-manage asthma including adverse environment, comorbidities, nonadherence, and incorrect diagnosis is recommended in a systematic fashion in Part 1 of this contribution. (Allergy Asthma Proc 33:305–312, 2012; doi: 10.2500/aap.2012.33.3583) I recent years, as modern asthma therapies have made good asthma control achievable in a majority of patients, difficult or refractory asthma has become the focus of intense interest from the perspectives of basic science, translational research, and clinical care. The following questions have come to the forefront: What is different about asthma in some patients such that it does not respond satisfactorily to conventional therapy with bronchodilators, inhaled corticosteroids, and leukotrienes modifiers; and how can we as asthma specialists best manage these patients? In Part 1 of this review, we will discuss the scope of the problem, reference ongoing efforts nationally and internationally to study this subpopulation of asthmatic patients in a systematic way, and consider various working definitions of “difficult asthma.” We will focus on the assessment of difficult asthma, emphasizing the distinction between “difficult-to-manage” asthma and asthma that is truly therapy resistant. We will offer our recommendations for a systematic evaluation of the patient with difficult-to-control asthma and explore potential explanations for the failure of current treatments to provide adequate control in all patients. In Part 2 we will consider treatment options for difficult asthma. We will focus on therapies approved by the Food and Drug Administration, including lipoxygenase inhibition with zileuton, anti-IgE monoclonal antibody therapy (omalizumab), and bronchial thermoplasty. We will briefly consider other therapeutic options not approved by the Food and Drug Administration for use in asthma, including ultrahigh-dose inhaled corticosteroids, longacting anticholinergic bronchodilators, macrolide antibiotics, and vitamin D, along with other more toxic and experimental interventions, such as methotrexate, tumor necrosis factor inhibition, and cyclosporine. Our discussion of the management of difficult asthma will conclude with consideration of specific asthma subtypes, each with potentially distinct therapeutic approaches. The prevalence of difficult asthma is uncertain. Estimates have put the number at 5–10% of patients with asthma. Telephone surveys of randomly selected American households found the prevalence of active asthma (defined by the presence of asthmatic symptoms within the past year and report of a doctor’s diagnosis of asthma) to be 10% among the general population. Among this denominator of patients with asthma, those who reported symptoms consistent with severe asthma (as defined by the criteria of Expert Reports of the National Asthma Education and Prevention Program) constituted 18%. Because these telephone surveys were unable to collect information about lung function, it is likely that the true prevalence of severe asthma was underestimated. Asthma severity reflects an intrinsic property of the disease process such that low-to-medium doses of inhaled corticosteroids, combined with long-acting bronchodilators and/or leukotriene modifying drugs, are inadequate to achieve control. However, many patients with severe asthma find their disease well controlled on high-dose inhaled steroids together with a second or third controller agent. These patients require intenFrom the Partners Asthma Center and the Allergy and Clinical Immunology Division at Massachusetts General Hospital and the Pulmonary and Critical Care Division at Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Presented at the Eastern Allergy Conference, Palm Beach, Florida, June 4, 2011 The authors have no conflicts of interest to declare pertaining to this article Address correspondence and reprint requests to Aidan A. Long, M.D., COX Room 201, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114 E-mail address: [email protected]: Copyright © 2012, OceanSide Publications, Inc., U.S.A. Allergy and Asthma Proceedings 305 DO N OT C OP Y