Elsevier

Clinics in Chest Medicine

Volume 33, Issue 3, September 2012, Pages 571-583
Clinics in Chest Medicine

Severe Asthma in Adults: An Orphan Disease?

https://doi.org/10.1016/j.ccm.2012.06.008Get rights and content

Introduction

Although asthma is a prevalent chronic disease, severe asthma that is refractory to treatment is rare. Epidemiologic data on severe asthma prevalence are missing, but severe asthma probably affects approximately 10% of patients with asthma, whereas severe treatment-resistant/refractory asthma probably affects 1% to 2%.1, 2 Moreover, severe asthma is an extremely heterogeneous disease in terms of clinical presentation and pathophysiologic mechanisms. Studies of severe asthma cohorts, such as the European Network for Understanding Mechanisms of Severe Asthma (ENFUMOSA), Severe Asthma Research Program (SARP), the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study (TENOR), and single-center cohorts (Table 1),3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 provide important information on severe asthma and introduce the concept of specific phenotypes in terms of clinical, physiologic, pathophysiologic, and treatment response characteristics. Moreover, some patients exhibit concordant disease, such as severe symptoms, inflammation, and impairment, whereas others show discordant disease, with very poor correlation between symptoms, inflammation, bronchial tissue damage, and functional impairment.22 Although important new information has been gained from these recent severe asthma studies, many questions remain unanswered and the issue of treatment is still unresolved.

Management of severe asthma follows the general principles of overall asthma management, and inhaled steroids and long-acting β-agonists remain the cornerstone of treatment. However, severe asthma requires more classes of medication, including oral steroids and omalizumab, and some newer compounds are currently being tested. Nevertheless, a substantial number of patients have severe asthma that remains uncontrolled. Given the poor response to treatment and the side effects associated with medications for severe asthma, such as oral steroids, new pharmaceutical compounds must be developed and their effects examined. However, patients with severe asthma are few, and pathophysiologic mechanisms and responses to treatment must be examined in each phenotypic group within this small population. Therefore, this severe spectrum of the disease likely fits the definition of a rare or orphan disease.

This article briefly describes severe asthma and its definition, risk factors, phenotypes, and treatment options, and provides a definition of orphan disease. Severe asthma remains a challenge to treat, greatly affects the lives of patients, and represents a huge cost to patients and society. New treatment options are needed and their effectiveness should be examined in long-term studies and meticulously characterized cohorts.

Section snippets

Definition of severe asthma

The concept of asthma severity has evolved substantially over the years. In the early Global Initiative for Asthma (GINA) and National Asthma Education and Prevention Program (NAEPP) guidelines, overall asthma severity was assessed primarily based on the patient's clinical characteristics before treatment initiation.23, 24 According to the 2009 World Health Organization Consultation,25 severe asthma comprises three groups: untreated, difficult-to-treat, and treatment-resistant severe.

Untreated

Evaluation and monitoring

In evaluating the patient, the diagnosis of severe asthma must be confirmed and other diseases excluded, such as vocal cord dysfunction, Churg-Strauss syndrome, panbronchiolitis, chronic obstructive pulmonary disease (COPD), and many others that may be associated with asthma.28 Once the diagnosis is confirmed, the physician should assess frequency/severity of symptoms and exacerbations. Validated measures to examine symptom severity, such as dyspnea scales, are valuable indicators of a

Severe asthma phenotypes: a cluster of rare diseases?

Until a few years ago, severe asthma was usually classified in terms such as severe occupational, aspirin-induced, premenstrual, intrinsic, and brittle. These classifications still stand; however, it is more important to classify asthma in terms of clinical presentation, pathophysiologic characteristics, and response to treatment (Box 1). These features include frequency and severity of exacerbations, age of onset, lung function status, risk factors, and comorbidities, and also the extent,

Rare diseases and orphan drugs

No single, satisfactory, worldwide-accepted definition for rare or orphan diseases exists. The United States and Europe have a different set of rules and definitions regarding orphan diseases, whereas country-specific regulations also exist. Most definitions for orphan diseases usually involve the number of people affected by the disease and other factors, such as the lack of available treatments or the severity of the disease.

In the United States, orphan diseases are defined by the Rare

Summary

Is severe asthma, then, an orphan disease? Should severe asthma be disassociated from asthma that responds to treatment? Is it a different disease? And should resources be allocated into research for severe asthma drugs under the orphan drug act? Clearly, a group of patients with severe asthma fits this orphan disease description. They are few, experience symptoms and debilitating restrictions to their daily activities, often experience life-threatening attacks, have asthma that does not

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    Financial disclosures and/or conflicts of interest: The authors have nothing to disclose.

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