Difficult asthma: assessment and management, Part 2.

Patients with severe asthma have considerable morbidity related to their asthma and are at risk for serious, life-threatening exacerbations. Their management requires an intensive and comprehensive approach, including attention to reducing exposure to environmental inciters of airway inflammation and triggers of symptoms, patient education (including an asthma action plan), and opportunity for close patient-provider communication. Approved medical options include the lipoxygenase inhibitor, zileuton; the anti-immunoglobulin E monoclonal antibody, omalizumab; and bronchial thermoplasty. Nonapproved interventions of potential benefit are ultrahigh-dose inhaled corticosteroids, anticholinergic bronchodilators (tiotropium), macrolide antibiotics, and vitamin D supplementation for the vitamin D-deficient patient. Potentially toxic, "steroid-sparing" therapies such as methotrexate, cyclosporine, and etanercept are best reserved for patients participating in clinical trials. Recognition of specific subtypes of patients with therapy-resistant asthma permits more targeted treatment approaches, such as for aspirin-sensitive asthma, persistent eosinophilic asthma, asthma complicated by allergic bronchopulmonary aspergillosis, asthma with persistent airflow obstruction, and asthma with life-threatening (near fatal) asthmatic attacks. Novel therapies based on an improved understanding of the pathobiology of therapy-resistant asthma are greatly needed.