Biological markers of intermediate outcomes in studies of indoor air and other complex mixtures.

Abstract

Biological markers of intermediate health outcomes sometimes provide a superior alternative to traditional measures of pollutant-related disease. Some opportunities and methodologic issues associated with using markers are discussed in the context of exposures to four complex mixtures: environmental tobacco smoke and nitrogen dioxide, acid aerosols and oxidant outdoor pollution, environmental tobacco smoke and radon, and volatile organic compounds. For markers of intermediate health outcomes, the most important property is the positive predictive value for clinical outcomes of interest. Unless the marker has a known relationship with disease, a marker response conveys no information about disease risk. Most markers are nonspecific in that various exposures cause the same marker response. Although nonspecificity can be an asset in studies of complex mixtures, it leads to problems with confounding and dilution of exposure-response associations in the presence of other exposures. The timing of a marker's measurement in relation to the occurrence of exposure influences the ability to detect a response; measurements made too early or too late may underestimate the response's magnitude. Noninvasive markers, such as those measured in urine, blood, or nasal lavage fluid, are generally more useful for field studies than are invasive markers. However, invasive markers, such as those measured in bronchoalveolar lavage fluid or lung specimens from autopsies, provide the most direct evidence of pulmonary damage from exposure to air pollutants. Unfortunately, the lack of basic information about marker properties (e.g., sensitivity, variability, statistical link with disease) currently precludes the effective use of most markers in studies of complex mixtures.

The Effect of Air Humidification on Symptoms and Nasal Patency, Tear Film Stability, and Biomarkers in Nasal Lavage: A 6 Weeks' Longitudinal Study

“…Measurement of tear film breakup time have been applied in studies in offices [14,15] and hospitals [7,16] and acoustic rhinometry has been used in studies on school personnel [17,18]. Nasal lavage (NAL) is a well-documented technique to study inflammatory effects in the nasal mucosa related to inhalatory exposure [15][16][17][18][19][20]. There are many possible biomarkers in NAL, including tryptase, albumin, lysozyme, eosinophilic cationic protein (ECP) emitted from the granula of activated eosinophil granulocytes, and myeloperoxidase (MPO) from activated neutrophil granulocytes [21,22].…”

IMMUNE BIOMARKERS IN RELATION TO EXPOSURE TO PARTICULATE MATTER: A Cross-Sectional Survey in 17 Cities of Central Europe

“…It has been suggested that the function of the immune system may be in uenced by air pollutants (American Thoracic Society, 1996;WHO, 1996;Wilkosky, 1993). Chemical and biological air pollutants may affect the immune system locally, in the lung, or systemically, through antigen-dependent and antigen-independent activation pathways of the immune response.…”

Introduction

“…In "Indoor Air and Other Complex Mixtures," Mauderly addresses the respective roles of toxicologic and epidemiologic research (16), Wilcosky examines the use of laboratory-derived markers of early disease (17), and McDonnell examines the incorporation of controlled human exposure studies into epidemiologic research protocols (18). The theme of integration of knowledge from experimental biology and epidemiology appears again in "Electric and Magnetic Fields," in which Stevens (19) proposes biologically based epidemiologic research on the carcinogenicity of electric and magnetic fields and in "Tropospheric Ozone," in which Devlin (20) discusses possible approaches to the development of biologic markers of exposure to ozone and early effects of this exposure.…”