Clara cell protein as a biomarker for ozone-induced lung injury in humans

Abstract

Exposure to ozone (O 3 ) 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 O 3 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 O 3 and filtered air for 2 h. Blood samples were drawn and lung function assessed at 2 h preexposure, immediately before and immediately after exposure as well as 2 and 4 h postexposure.O 3 increased CC16 serum concentrations at 2 h (12.0¡4.5 versus 8.4¡3.1 mg?L -1 ) and 4 h postexposure (11.7¡5.0 versus 7.9¡2.6 mg?L -1 ) compared with air concentrations. Archived samples from O 3 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 mg?L -1 ) with concentrations returning to baseline by 18 h (7.7¡2.9 versus 6.6¡1.7 mg?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. Eur Respir J 2003; 22: 883-888.

Exposure to diesel exhaust nanoparticles does not induce blood hypercoagulability in an at‐risk population

“…The present findings do not support the hypothesis of diesel exhaust nanoparticle-induced systemic effects in a susceptible group of individuals with COPD. Neither was, in contrast to studies after ozone exposure [7], any sign of DE-induced injury on the lung epithelium present, as CC16 plasma levels remained unchanged. It cannot be excluded that this study has certain limitations.…”

Diagnostic and prognostic values of Club cell protein 16 (CC16) in critical care patients with acute respiratory distress syndrome

“…Considering the large blood‐tissue exchange surface area of lung tissues, serum CC16 is almost solely derived from the respiratory tract and is, therefore, considered lung‐specific. Increased circulating CC16 levels have been observed in patients with pulmonary injuries caused by inhaled ozone, chlorine, and LPS 7, 8, 9. It has been suggested as a disease marker for pulmonary sarcoidosis, chronic obstructive pulmonary disease, and severe chest trauma 10, 11, 12.…”

Clara Cell Protein (CC16), a Marker of Lung Epithelial Injury, Is Decreased in Plasma and Pulmonary Edema Fluid From Patients With Acute Lung Injury

“…10 Furthermore, CC16 appears to be activated by tissue transglutaminases including activated Factor XIII, 11 and inhibits thrombin-stimulated platelet aggregation, 12 suggesting a possible role in modulating the dysregulated coagulation characteristic of ALI/ARDS. 13 CC16 has been investigated as a potential biomarker of lung epithelial injury in numerous disease states including idiopathic pulmonary fibrosis, 14 sarcoidosis, 14 -17 COPD, 14,15 asthma, 14,18 -21 occupational or environmental lung injury, [22][23][24][25] bronchiolitis obliterans, 26,27 chronic tobacco use, 15,28 and ALI/ARDS. 29 -33 Several studies have examined whether CC16 levels in BAL fluid or plasma can discriminate patients with ALI/ARDS from those at-risk for ALI/ARDS or healthy control subjects, 29 -32 but results to date have been contradictory.…”