ELASTIN BREAKDOWN PRODUCTS DURING PULMONARY EXACERBATIONS IN CF

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Progressive degradation of lung parenchyma is a key pathologic feature of cystic fibrosis (CF). Measures of lung degradation would be useful in clinical and research settings. The destruction of the fibrous network of the lung results in the formation of the elastin breakdown products desmosine and isodesmosine (DESX). Although DESX are elevated in CF, their clinical and research utility is not validated. We have hypothesized that sensitive determination of DESX in urine, sputum and plasma will provide useful markers of this degradation. We further hypothesize that pulmonary exacerbation in CF patients results in a direct increase in the levels of DESX in urine, sputum and plasma and that standard-of-care inpatient treatment will result in a significant decrease in these same levels. To begin to validate the use of DESX in CF, we therefore propose the following specific aims: (1) To determine change in levels of DESX in urine, sputum and plasma during inpatient treatment of a pulmonary exacerbation in CF patients, and (2) To validate the use of DESX as biomarkers of positive response to therapy for a pulmonary exacerbation through correlation of these levels with known markers of improvement such as pulmonary function and markers of infection and inflammation. We propose to improve utility of DESX determination compared to previous studies through examining new matrices (sputum, plasma), employing mass spectrometry detection and applying a strict internal standard. Our long term objective is the validation of a non-invasive, assay of parenchymal lung destruction useful in prediction of lung function decline, early detection of exacerbation, and evaluation of response to therapy.