Treatment with omalizumab, the monoclonal humanized anti-IgE antibody, and with any of the monoclonal anti-IL-5 antibodies is reserved for patients with chronic severe asthma inadequately controlled by ICS/LABA treatment. Omalizumab reduces lymphocytic, eosinophilic bronchial inflammation, oral and inhaled corticosteroid dose requirements, and the frequency and severity of exacerbations. It is reserved for patients with demonstrated IgEmediated sensitivity (by positive skin test or radioallergosorbent test [RAST] to common allergens) and an IgE level within a range that can be reduced sufficiently by twice-weekly subcutaneous injection. Other options for treatment of severe asthma uncontrolled by ICS/ LABA therapy, especially if associated with peripheral eosinophilia, are the monoclonal antibodies reviewed earlier—mepolizumab, reslizumab, and benralizumab.
In addition to their high cost, several factors have limited the use of targeted therapies. First, they must be given parenterally at 2to 4-week intervals. Second, some can cause anaphylactic reactions or other hypersensitivity reactions, albeit in a small percentage (<0.5%) of patients, so they cannot be self-administered but must be monitored for a period of time after the injection in a setting equipped to manage anaphylaxis. In addition, a small number of patients receiving mepolizumab developed herpes zoster infection, and administration of the varicella-zoster vaccine to adults age 50 or older 4 weeks prior to initiation with mepolizumab is recommended.
For the 5–10% of the asthmatic population with severe asthma inadequately controlled by standard therapies, the development of an alternative treatment is an important unmet medical need. This is particularly important for patients with “T2-low” asthma, who are less likely to respond to corticosteroids and for whom targeted therapies against IgE or IL-5 are unlikely to be of benefit. The initial promise of oral methotrexate or gold salt injections has not been fulfilled. While the benefit from treatment with cyclosporine seems real, this drug’s toxicity makes this finding only a source of hope that other immunomodulatory therapies will ultimately emerge. Advances in understanding the immunopathogenesis of asthma may permit the identification of specific phenotypes of asthma and identification of biomarkers of their importance in particular patients. In this respect, asthma may benefit from the rapid advances in treatments developed for other chronic inflammatory conditions such as rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel disease.
The treatment of acute attacks of asthma in patients reporting to the hospital requires close, continuous clinical assessment and repeated objective measurement of lung function. For patients with mild attacks, inhalation of a β-receptor agonist is as effective as subcutaneous injection of epinephrine. Severe attacks require treatment with oxygen, frequent or continuous administration of aerosolized albuterol, and systemic treatment with prednisone or methylprednisolone (0.5 mg/kg every 6–12 hours). Even this aggressive treatment is not invariably effective, and patients must be watched closely for signs of deterioration. General anesthesia, intubation, and mechanical ventilation of asthmatic patients cannot be undertaken lightly but may be lifesaving if respiratory failure supervenes.