Editorial: The Role of Leukotriene Modifiers

Leukotrienes (LKs) are potent mediators that are released from various inflammatory cells, resulting in airway smooth muscle contraction, increased mucus production, and lead to the attraction and activation of other inflammatory cells within the airways of asthmatics.

Two LK modifiers, zafirlukast and zileuton (Accolate™ and Zyflow™) have recently been approved for oral administration. Both have been shown to improve lung function and decrease symptoms, and may be considered alternatives (according to the NHBLI guidelines) to low-dose inhaled steroid in patients with mild persistent asthma. As far as them having truly anti-inflammatory properties, the jury is still out.

Because of the safety and effectiveness of inhaled steroids, I believe the usefulness of these drugs is somewhat limited. This should be highlighted because of the recent, although very rare, association of a leukotriene modifier with Churg-Strauss Vasculitis. Less rarely, however, there have been associated liver enzyme abnormalities with one of these drugs.

Leukotriene modifiers, however, may be a great choice in the aspirin (ASA)-sensitive asthmatic, i.e., those with the triad of:

• usually moderate to severe asthma;
• exacerbation after ingestion of ASA;
• rhino-sinusitis and/or nasal polyps.

It is felt that LKs are particularly important mediators in this subset of asthmatic patients, so LK modifiers are theoretically very beneficial. In addition, one of the LK modifiers has been shown clinically to completely ablate the ASA response in these patients - providing a measure of protection against accidental ingestion.

They may also be a good choice for a patient with persistent asthma who is unwilling or unable to properly use inhaled steroids via an MDI device, and those who are afraid (unduly, I feel) of using any form of steroid.