Human interindividual variability in susceptibility to airborne particles.

Area of Science:

• Environmental Health
• Toxicology
• Pulmonary Medicine

Background:

• Epidemiological studies show links between air particle exposure and mortality/morbidity.
• Individual susceptibility to particle effects is a proposed explanation for these findings.

Purpose of the Study:

• To quantify interindividual variability in pharmacokinetic and pharmacodynamic responses to inhaled agents.
• To assess the potential impact of this variability on health outcomes from airborne particle exposure.

Main Methods:

• Assembled a database of quantitative observations on human variability.
• Analyzed pharmacokinetic parameters (breathing rate, deposition, clearance).
• Examined pharmacodynamic responses (lung function changes) to methacholine, flour dust, ozone, and metabisulfite.

Main Results:

• Pharmacodynamic variability was generally greater than pharmacokinetic variability.
• Interindividual variability in breathing rate, deposition, and clearance showed geometric standard deviations (GSDs) of 1.26-1.58.
• Deep lung deposition variability had a GSD of approximately 2.
• Responses to methacholine and particulate allergens showed the highest variability (GSD > 1.0).
• Highly susceptible individuals may respond to doses 150-450 times lower than median individuals.

Conclusions:

• Significant interindividual variability exists in human responses to inhaled agents.
• This variability, particularly in pharmacodynamic responses, may explain enhanced mortality/morbidity in sensitive populations exposed to air pollution.
• Lognormal distribution of responses suggests a mechanistic basis for observed epidemiological associations.