Host defenses against respiratory tract infection: implications for anti-inflammatory drug development and treatment.

The human respiratory tract is exposed to a constantly changing environment which may bring it into contact with a variety of pathogenic organisms. A range of innate and acquired defence mechanisms have evolved to counter these threats. Several new classes of therapeutic agent which may interfere with these defence mechanisms have recently been marketed or are under clinical development; this paper reviews some key examples, with the potential implications for disease management.

Summary of recommendations for the design of clinical trials and the registration of drugs used in the treatment of asthma.

With new drugs being introduced to treat asthma it is timely to review criteria that can be used to assess efficacy in clinical trials. Anti-asthma drugs are classified into symptoms-modifying, symptom preventers and disease modifying agents. Attention is drawn to the types of experimental evidence required in preclinical studies to support further clinical development of a new therapy. Clinical trials demand careful selection of patients to maximise the strength of the efficacy signal according to the type of trial being designed. While provocation tests are useful in suggesting efficacy, negative tests do not necessarily indicate lack of anti-asthma activity. Therapeutic trial designs need to take account of duration of treatment, dose-response relationships and confirmatory trials. Outcome measures include symptoms, lung function, reduction in concomitant medication, exacerbations, quality of life and measures of inflammation. Interpretation of results need to include the clinical relevance of any changes as well as statistical significance. Special consideration needs to be given to the evaluation of drugs for acute severe asthma, asthma in children and older people, co-morbidity such as rhinitis, and inhaler devices. As with all drugs introduced into practice, careful attention needs to be paid to both short- and long-term safety.