Chronic inflammation is a critical feature of chronic obstructive obtained was analyzed for the content of markers of inflampulmonary disease, cystic fibrosis, and asthma. This inflammation mation and oxidative stress such as hydrogen peroxide, leuis associated with the increased production of reactive oxygen spekotrienes, thiobarbituric acid-reactive substances, and isocies or oxidative stress in the lungs. Oxidative stress may have prostanes. several adverse effects and may amplify the

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... atory process; The development of noninvasive methods of assessment however, monitoring oxidative stress is difficult and may not be of inflammation and oxidative stress may provide a means reflected by changes in blood markers. We have therefore develof monitoring disease progress and response to therapy. oped several noninvasive markers in the exhaled breath that may indicate oxidative stress in the lungs, and we studied these in rela-CO tionship to the severity of chronic inflammatory lung diseases. We analyzed the exhaled breath for the content of nitric oxide as a CO is produced endogenously from the stress protein heme marker of inflammation, carbon monoxide as a marker of oxidative oxygenase (HO)-1, which is induced by oxidants, inflammatory stress, and ethane, which is one of the end products of lipid peroxicytokines, and other forms of cellular stress in a variety of cell dation. In addition, we measured the concentration of markers of types. HO-1 plays an important role in the response to oxidative oxidative stress such as isoprostanes in exhaled breath condensate. stress (4). HO-1 converts heme and hemin to biliverdin with the Our results confirm that there are increased inflammation, oxidative formation of CO. Biliverdin is rapidly converted to bilirubin, stress, and lipid peroxidation in lung disease, as shown by elevated which is a potent antioxidant. CO may also be produced by the levels of nitric oxide, carbon monoxide, and ethane, respectively. activity of HO-2, a constitutive enzyme highly expressed in the The finding of lower levels of these gases in patients on steroid brain and testes. treatment and of higher levels in those with more severe lung The precise mechanisms for antioxidant protection are not disease, as assessed by lung function tests and clinical symptoms, fully understood, but both the degradation of heme with removal reinforces the hypothesis that the noninvasive measurement of of iron and induction of ferritin and the generation of bilirubin exhaled gases maybe useful in monitoring the underlying patho-(an antioxidant) may be involved. There is evidence that the logic pathways of lung disease. Longitudinal studies are required to assess the clinical usefulness of these measurements in the moni-deleterious effects of reactive oxygen species, such as superoxide toring of chronic inflammatory lung disease. and hydrogen peroxide, are dependent on the presence of iron. The intracellular pool of free iron can react with both hydrogen Keywords: oxidative stress; noninvasive assessment peroxide and superoxide, giving rise to the hydrogen oxide radical via the Fenton reaction. The free iron that is not metabolized