Non-invasive biomarkers of pulmonary damage and inflammation: Application to children exposed to ozone and trichloramine Alfred Bernard T , Sylviane Carbonnelle, Marc Nickmilder, Claire de Burbure Unit of Toxicology, Catholic University of Louvain, 30.54 Clos Chapelle-aux-Champs 1200 Brussels, Belgium Received 17 March 2004; accepted 15 October 2004 Available online 24 March 2005 Abstract To date, airways injury or inflammation caused by air pollutants has been evaluated mainly by analysis of bronchoalveolar lavage, an invasive technique totally unsuitable to children. The assessment of respiratory risks in this particularly vulnerable population has thus for a long time relied on spirometric tests and self-reported symptoms which are relatively late and inaccurate indicators of lung damage. Research in the field of biomarkers is now opening new perspectives with the development of non-invasive tests allowing to monitor inflammation and damage in the deep lung. Blood tests measuring lung-specific proteins (pneumoproteins) such as Clara cell protein (CC16) and surfactant- associated proteins (A, B or D) are now available to evaluate the permeability and/or the cellular integrity of the pulmonary epithelium. The application of these tests to children has recently led to the discovery of a lung epithelium hyperpermeability caused by trichloramine (nitrogen trichloride), an irritant gas contaminating the air of indoor-chlorinated pools. Serum CC16 can also serve to detect increases of airway permeability during short-term exposures to ambient ozone. Indicators measurable in exhaled air such as nitric oxide (NO) appear more useful to detect airway inflammation. By applying the exhaled NO test to children attending summer camps, we recently found that ambient ozone produces an acute inflammatory response in children from levels slightly lower than current air quality guidelines. In a study exploring the links between atopy, asthma, and exposure to chlorination products in indoor pools, we also found that the exhaled NO test can serve to detect the chronic airway inflammation associated with excessive exposure to trichloramine. Lung-specific proteins measurable in serum and markers in exhaled air represent sensitive tools that can be used to assess non-invasively the effects of air pollutants on the respiratory tract of children. D 2005 Elsevier Inc. All rights reserved. Keywords: Ozone; Chlorine; Nitrogen trichloride; Nitric oxide; Trichloramine; Lung inflammation; Swimming pool; Swimming baby; Children Clara cell protein; Surfactant-associated proteins; Non-invasive tests Introduction During the last decades, a number of epidemiological studies have documented the acute and chronic effects of air pollutants on the respiratory tract. These studies carried out on virtually all segments of the general population have clearly shown that adverse effects may occur at exposure levels commonly encountered in episodes of air pollution. In adults, these adverse effects have been evidenced using a variety of indicators and tests, including very invasive tests such as bronchoalveolar lavage and bronchial biopsy. By contrast, the assessment of the respiratory toxicity of air pollutants in children has proved to be a much more delicate task, both for ethical and practical reasons, as methods applied to children not only have to remain non-invasive but also are difficult to apply when they require the child’s active participation as in the case of traditional lung function tests (Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society, 1996; Schwartz, 2004; Weaver et al., 1998). Current research in the biomarkers field is opening new perspectives with the development of molecular tools measuring non-invasively the extent of lung inflammation or damage without any major restriction related to the exposure conditions, the age, or the health status of 0041-008X/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.taap.2004.10.022 T Corresponding author. E-mail address: bernard@toxi.ucl.ac.be (A. Bernard). Toxicology and Applied Pharmacology 206 (2005) 185– 190 www.elsevier.com/locate/ytaap