Asthma is a multifactorial disease with a major inflammatory component and numerous clinical triggers. New technologic modalities such as bronchoprovocation and bronchoalveolar lavage and the novel use of older techniques such as spirometry to identify late-phase responses and bronchial hyperirritability have confirmed the inflammatory nature of asthma and provide techniques that offer new opportunities to evaluate therapy. Previous animal models have not been predictive of therapies useful in humans. Newer animal models with sustained obstruction and inflammatory components will be useful in this regard. It has become clear that placebo-controlled, double-blind studies and comparisons with standard effective therapy are necessary before final decisions about the place of a new agent in the therapeutic armamentarium can be made. Previous studies have demonstrated the need to consider carryover and placebo effects, environmental influences on the disease process, and requirements for longer studies to complement those of short duration. Long-term studies are also required to uncover unsuspected modes of action, drug interactions, or toxicities. Critical features of administration, such as dose, frequency, technique of aerosol inhalation, and patient compliance, all need to be addressed. Concentration on single-drug therapy, as with theophylline, isoproterenol, or atropine, has often not been practical for long-term management of asthma. Therefore, regimens that combine drugs from different pharmacologic categories need to be considered in the evaluation of NBAAD. The traditional criteria for the determination of clinical efficacy, such as normalization of the abnormal physiology of asthma, improvement in the quality of life, and decreased use of other medications, continue to be fully pertinent to the evaluation of new NBAAD. However, these criteria are insufficient to define the mechanism of action of various new modalities that will be useful for the treatment of asthma. Additional criteria appropriate for specific agents have included changes in bronchial response to allergen or exercise. Long-term changes in airway reactivity to histamine or methacholine have correlated well with efficacy, as illustrated by the experience with cromolyn sodium. It has also proved very useful to evaluate the effect of a drug on the late phase of the allergic reaction. Often the efficacy of new agents has not been studied sufficiently in children to allow labeling of the drug for use in pediatric patients. Clinical trials of NBAAD should therefore be initiated in children at an earlier stage of drug development. Many studies have not benefited from the participation of a statistician in the early stages of study design, and therefore these studies have had inadequate power or have involved inappropriate methods of data analysis.
ASJC Scopus subject areas
- Immunology and Allergy