Background: Cystic fibrosis (CF) lung disease is characterized by structural changes in the airways and parenchyma. No sputum biomarker exists to measure the degree of active structural destruction during pulmonary exacerbation in patients with CF. The noninvasive measurement of desmosine, a breakdown product of elastin, may reflect ongoing lung injury and serve as a biomarker of short-term damage. Our objectives were to measure desmosine in the sputum of patients with CF hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine levels and other markers of clinical improvement, including lung function and inflammatory mediators, following hospitalization. Methods: Sputum and blood samples collected and lung function measurements were made at multiple time points during hospitalization. We used a repeated measures model, adjusted for age and time between measurements, to compare log-transformed sputum desmosine levels across multiple time points and to correlate those levels with related variables. Results: Desmosine levels were measured by radioimmunoassay in 71 expectorated sputum samples from 19 patients with CF hospitalized for 26 pulmonary exacerbations (range of results, 0 to 200 pmol/L desmosine/mL). Sputum desmosine levels decreased significantly during the first week of hospitalization (p= 0.04). Desmosine levels were positively associated with plasma C-reactive protein (ρ= 0.59; p=0.03), sputum interleukin-8 (ρ=0.86; p < 0.01), and sputum neutrophil elastase (ρ=0.78; p < 0.01). Conclusions: Sputum desmosine, a novel measure of acute structural lung injury, may serve as a marker of structural lung damage occurring during exacerbations of lung disease in CF.
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Financial/nonfinancial disclosures: Dr. Laguna has received grant support from the American Thoracic Society and the Cystic Fibrosis Foundation. She has provided an educational symposium sponsored by Hill-Rom. Dr. Sagel has received grant support from the University of Colorado Clinical Translational Science Award, the Cystic Fibrosis Foundation, and the National Institutes of Health. He has also received industry funding from Yasoo Health, Incorporated, and Vertex Pharmaceuticals, Incorporated. Dr. Regelmann has received grant support from the Cystic Fibrosis Foundation and the Cystic Fibrosis Foundation Therapeutic Development Network. He serves as an advisor for the National Epidemiologic Study of Cystic Fibrosis sponsored by Genentech. Dr. Accurso has received grant support from the National Institutes of Health and the Cystic Fibrosis Foundation. He has served as a consultant to Inspire Pharmaceuticals, Inc, in the last 3 years. He has participated in industry studies through the Cystic Fibrosis Foundation Therapeutic Development Network (Gilead Sciences, Inc; Targeted Genetics, Inc; PTC Therapeutics, Inc; Vertex Pharmaceuticals, Inc; Altus Biologics, Inc; Digestive Care, Inc; KalobBios Pharmaceuticals, Inc). Dr. Wagner, Ms. Luckey, and Ms. Mann have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.