The following information about steroid resistant asthma was originally developed for a healthcare professional audience and was published in Allergy, Rheumatology, Immunology and Asthma (ARIA), a journal produced by National Jewish Health and The Children's Hospital of Denver.

Management of Steroid Resistant Asthma: Nine Steps to Success

By Donald Y.M. Leung, MD, PhD

The management of patients suspected of having steroid resistant asthma requires a systematic, stepwise approach.

Step 1 is to obtain a thorough history, physical examination and appropriate laboratory tests to confirm the diagnosis of asthma.

Concomitant medical disorders which can complicate themanagement of patients with chronic asthma should be ruled out. In our experience, the diagnosis of vocal cord dysfunction, which involves abnormal vocal cord closure during inspiration, is often missed. This diagnosis can only be made by direct laryngoscopy when the patient is symptomatic and should be suspected in any adolescent or adult with recent onset of steroid-dependent or steroid resistant asthma. Gastroesophageal reflux and/or aspiration, sinusitis, allergic bronchopulmonary aspergillosis, anatomical abnormalities and immunodeficiencies are some of the concomitant factors that must also be ruled out.

Step 2 is to rule out psychosocial factors affecting the asthma.

A large proportion of patients with apparent steroid resistant asthma has an inadequate response to therapy simply due to non-compliance with recommended therapy. The basis for noncompliance is complex and can range from simple forgetfulness to the inability to pay for the medications or severe psychologic problems such as depression which impair the patient's ability to function and adhere to a suggested medical regimen. In addition, it is important to keep the medication regimen as simple as possible, prioritize recommendations, educate the patient regarding their asthma management and tailor the dosing to the patient's schedule.

Step 3 is to review the patient's technique of medication administration.

This should be incorporated as a routine part of the follow-up as patients often forget proper inhaler technique. Spacerdevices should be used to optimize medication delivery and reduceadverse effects of medications.

Step 4 is to assure appropriate environmental control for asthma at home, in school and at work.

The focus should be on areas where the patient spends the greatest time, for example, the bedroom, or areas of high indoor allergen exposure. A number of studies have demonstrated that atopic patients who live with animals at home require higher doses of steroids to maintain control of their asthma. Several studies have also implicated schools as a major source of animal dander exposure.

Step 5 is to modify inhaled glucocorticoid therapy in an effort to reduce requirements for systemic GC therapy as patients with acquired steroid resistant asthma frequently develop steroid side effects.

One approach is to increase the dose and frequency of inhaled GCs. This is based on the assumption that higher doses would be more effective and also that adverse effects would be less than those commonly associated with high dose systemic GC therapy. The majority of patients with steroid resistant asthma have the acquired form, which is associated with reduced GCR binding affinity. Studies of their T cells indicate a shift to the right in their dose response to steroids rather than an absolute resistance. Thus, higher doses of corticosteroid or a change to a corticosteroid with a higher binding affinity is a reasonable initial approach to gain control of their asthma.

Step 6 is to maximize anti-inflammatory and bronchodilator therapy for control of nocturnal asthma exacerbations.

Inhaled salmeterol administered at bedtime can be very useful in controlling nocturnal asthma. A once daily sustained-release preparation of theophylline can also be effective in the treatment of nocturnal asthma.

Step 7 is to develop a written action plan for acute asthma exacerbations.

Emphasis should be placed on appropriate use of rescue medications such as bronchodilators and when to notify the physician. A written care plan should also be used to summarize routine prophylactic medications including recommendations for pre-treatment programs for exercise and anticipated exposure to irritants or allergens.

Step 8 is to evaluate systemic corticosteroid pharmacokinetics and receptors to maximize pulmonary function with oral corticosteroids, and assess the basis of corticosteroid insensitivity in patients with poorly controlled asthma.

The purpose of these studies is to determine whether there is incomplete corticosteroid absorption, failure to convert to an active form, rapid elimination, reduced GCR number or binding affinity, or a combination of abnormalities. This evaluation is particularly important in a patient who fails to demonstrate the anticipated adverse effects of longterm, high-dose corticosteroid therapy. Patients with poor absorption of prednisone, frequently respond well to oral liquid corticosteroid preparations.In patients with rapid corticosteroid elimination, a split dosing regimen, with the second dose of the day administered in the afternoon, should be considered. In such patients, the morning dose should be titrated, then the afternoon dose converted to a morning dose, then a reduction to alternate day therapy attempted.

Step 9 the final step, is to consider alternative anti-inflammatory and immunomodulator approaches.

This is of particular importance in patients with the Type II or primary form of SR asthma who have a generalized primary resistance to steroid therapy. Unfortunately, there have been no wellcontrolled studies of alternative therapies in SR asthma. Treatment with methotrexate, gold, cyclosporine, and intravenous immunoglobulin, have been reported to have steroid sparing effects, and may be potentially useful in patients who fail steroid therapy. Recent studies suggest that T cells from steroid resistant asthma will respond to the anti-inflammatory actions of intravenous immunoglobulin and enhance their GCR binding affinity thus providing a rationale for use of this agent in the management of these patients.

This information has been approved by Donald Leung, MD, PhD (April 2006) Original Publication August 2000; updated August 2003.