Mediator Assays and Modulation of Inflammation in Asthma: Introduction

The vital role of inflammation in the induction and perpetuation of asthmatic responses is now a widely accepted concept. Effective management of asthma requires modulation of asthmatic inflammatory responses. Eosinophils play a critical role in producing inflammation within the asthmatic lungs. Serologic assessment of the level of eosinophilic cationic protein (ECP) may be useful in assessing the degree of activation of eosinophils in asthma and the effect of pharmacotherapy on activated eosinophils. Several clinical trials have noted that ECP levels fluctuate in direct relationship to the amount of ongoing bronchospasm and asthmatic inflammation. Modulation of inflammation in asthma can occur through pharmacologic means. Nedocromil sodium has been demonstrated to significantly affect both early-phase and late-phase inflammatory events including effects on mast cell activation and effects on eosinophil function. Nedocromil sodium has also been noted to affect production and activity of cytokines that are vital to the perpetuation of the asthmatic late-phase response. Unlike cromolyn sodium, nedocromil sodium inhibits late-phase inflammation even when administered after the early phase of the allergic response and has also been demonstrated to be a steroid-sparing agent in mild-to-moderate asthmatics who require inhaled beclomethasone. Modulation of the metabolism of arachidonic acid, thereby affecting levels of prostaglandins and leukotrienes, may be extremely useful in selective asthmatic patients. Those patients having aspirin sensitivity and chronic rhinitis associated with asthma seem to be particularly responsive to arachidonic acid metabolites. In such patients, use of aspirin desensitization may be considered. Newer anti-inflammatory agents being investigated as treatments for asthma include methotrexate, hydroxychloroquin, auronifin, and sulfonylureas, among others. Most of these agents have been employed in the treatment of other inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, spondyloarthropathies, and dermatitis herpetiformis. Methotrexate has been demonstrated to be a steroid-sparing agent in rheumatoid arthritis and psoriatic arthritis. Trials with methotrexate, including double-blind placebo-controlled investigations, have generally demonstrated it to be a steroid-sparing agent in asthma, although not all patients respond to methotrexate, and those who do respond often have some residual corticosteroid requirement. New agents investigated as therapies for inflammation in asthma clearly must undergo double-blind placebo-controlled trials because open trials often fail to consider the significance of placebo effects that can occur in patients subject to intense clinical scrutiny.