Clara cell protein as a biomarker for ozone-induced lung injury in humans.
Exposure to ozone (O3) impairs lung function, induces airway inflammation and alters epithelial permeability. Whilst impaired lung function and neutrophilia have been observed at relatively low concentrations, altered lung epithelial permeability is only seen after high-dose challenges. The appearance of Clara cell protein (CC16) in serum has been proposed as a sensitive marker of lung epithelial injury. Here, the use of CC16 as an injury biomarker was evaluated under a controlled exposure to O3 and the relationship between this marker of lung injury and early lung function decrements was investigated. Subjects (n=22) were exposed on two separate occasions to 0.2 parts per million O3 and filtered air for 2 h. Blood samples were drawn and lung function assessed at 2 h pre-exposure, immediately before and immediately after exposure as well as 2 and 4 h postexposure. O3 increased CC16 serum concentrations at 2 h (12.0+/-4.5 versus 8.4+/-3.1 microg x L(-1)) and 4 h postexposure (11.7+/-5.0 versus 7.9+/-2.6 microg x L(-1)) compared with air concentrations. Archived samples from O3 studies utilising the same design indicated that this increase was sustained for up to 6 h postexposure (9.1+/-2.6 versus 7.1+/-1.7 microg x L(-1)) with concentrations returning to baseline by 18 h (7.7+/-2.9 versus 6.6+/-1.7 microg x L(-1)). In these studies, the increased plasma CC16 concentration was noted in the absence of increases in traditional markers of epithelial permeability. No association was observed between increased CC16 concentrations and lung function changes. To conclude, Clara cell protein represents a sensitive and noninvasive biomarker for ozone-induced lung epithelial damage that may have important uses in assessing the health effects of air pollutants in future epidemiological and field studies.
Blomberg
A
A
Dept of Respiratory Medicine and Allergy, University Hospital, Umeå University, Umeå, Sweden. anders.blomberg@lung.umu.se
Mudway
I
I
Svensson
M
M
Hagenbjörk-Gustafsson
A
A
Thomasson
L
L
Helleday
R
R
Dumont
X
X
Forsberg
B
B
Nordberg
G
G
Bernard
A
A
D000328:Adult; D015415:Biomarkers; D018592:Cross-Over Studies; D004780:Environment, Controlled; D005260:Female; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008171:Lung Diseases / Q000139:chemically induced / Q000276:immunology*; D008297:Male; D010083:Oxidants, Photochemical / Q000009:adverse effects*; D010126:Ozone / Q000009:adverse effects*; D011506:Proteins / Q000032:analysis / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology*; D016037:Single-Blind Method; D014598:Uteroglobin
D015415:Biomarkers; D010083:Oxidants, Photochemical; D011506:Proteins; C556389:SCGB1A1 protein, human; D010126:Ozone; D014598:Uteroglobin