Asthma pharmacology: industrial/clinical interface.

Area of Science:

• Pharmacology
• Respiratory Medicine
• Drug Discovery

Background:

• Asthma pathogenesis is not fully understood, necessitating novel drug development.
• Current drug discovery approaches include targeting known bronchodilator, prophylactic, and anti-inflammatory actions.
• Alternative strategies involve inhibiting mediators like leukotrienes and cytokines or exploring novel pathways such as K+ channel activation.

Purpose of the Study:

• To evaluate the justification of current drug selection rationales for anti-asthma therapies.
• To highlight the critical need for clinical studies in asthma drug evaluation.
• To emphasize the limitations of using normal subjects for assessing asthma drug efficacy.

Main Methods:

• Comparison of physiological responses in asthma patients versus normal subjects.
• Assessment of drug action based on known mechanisms and emerging theories of asthma.
• Iterative testing of compounds in both preclinical animal models and clinical studies.

Main Results:

• Normal subjects do not exhibit asthma-like airway obstruction or hyperreactivity, limiting their utility in bronchodilator studies.
• Platelet-activating factor elicits different cellular responses in normal individuals (neutrophil-predominant) compared to atopic asthmatics (eosinophil-predominant).
• The rationale for drug selection requires validation through patient-specific studies.

Conclusions:

• Drug discovery and evaluation for asthma must be an iterative process integrating preclinical and clinical research.
• Clinical studies in asthma patients are essential to validate drug efficacy and safety.
• Preclinical findings must be supplemented by clinical data for successful anti-asthma drug development.