Chest
Volume 137, Issue 3, March 2010, Pages 635-641
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Original Research
Biomarkers
Sputum Trace Metals Are Biomarkers of Inflammatory and Suppurative Lung Disease

https://doi.org/10.1378/chest.09-1047Get rights and content

Background

Induced sputum cytology and protein biomarkers can be used to assess airways inflammation. Increases in sputum iron have been described in inflammatory lung disease. We hypothesized that other sputum metals may be affected by airways inflammation and investigated their potential value as biomarkers.

Methods

Sputum was obtained from 20 healthy control subjects and from patients with inflammatory pulmonary diseases (23 with cystic fibrosis [CF], 16 with bronchiectasis, 17 with asthma, and 23 with COPD), and iron, zinc, manganese, and copper were measured. Fourteen patients with CF were also studied through an exacerbation cycle.

Results

Sputum zinc and iron were elevated in CF and non-CF bronchiectasis vs controls (P < .001, zinc; P < .01 iron). Manganese was elevated in asthma (P < .01) and bronchiectasis (P < .05) vs controls. Copper was elevated in CF vs controls (P < .05). Zinc decreased (P < .01) following treatment of CF exacerbation. In subjects with CF zinc levels correlated with other biomarkers.

Conclusions

These results suggest a relationship of high concentrations of total zinc and iron with airways inflammation in CF and non-CF bronchiectasis, with longitudinal changes being observed in CF. Further work is required to elucidate potential inflammatory mechanisms related to these observations.

Section snippets

Subjects

Induced sputum was obtained from patients attending the Respiratory Unit at the Western General Hospital, Edinburgh. Approval was obtained from the local regional ethics committee. Twenty-three patients with CF, 16 with non-CF bronchiectasis, 17 with asthma, 23 with COPD, and 20 healthy controls were studied. In order to monitor the effects of a changing state of inflammation, sputum samples were obtained from 14 additional patients with CF during CF exacerbation. Exacerbation samples were

Subject Demographics

The demographic profiles and sputum cytology of each group are shown in Table 1. The CF group was younger than the control and other disease groups (P < .01). Of the COPD group 10 were current smokers, nine ex-smokers, and four gave no information on current smoking status. Of the patients with CF, 14 were colonized with P aeruginosa, the other patients being colonized by a variety of organisms, including Stenotrophomonas maltophilia and Burkholderia cenocepacia species.

Assay Reproducibility

Pooled samples of five

Discussion

Total elemental zinc and iron concentrations are elevated in sputum from subjects with CF and non-CF bronchiectasis compared with healthy control subjects. There is a small degree of overlap between the CF and control groups, but this may be explained by the finding that patients with CF in this small subgroup had better lung function and thus less severe lung disease (data not shown). Sputum zinc levels were also significantly higher in CF and non-CF bronchiectasis compared with COPD. Sputum

Acknowledgments

Author contributions: Dr Gray: contributed to the original concept and design of the study, manuscript writing and preparation, and collecting, processing, and analyzing samples.

Dr Duncan: contributed to overseeing trace element analysis and providing intellectual input to the manuscript.

Dr Noble: contributed to collecting, processing, and analyzing samples.

Ms Imrie: contributed to collecting, processing, and analyzing samples.

Dr O'Reilly: contributed to overseeing trace element analysis and

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Funding/Support: This study was funded by the Cystic Fibrosis Trust (R.D.G. and A.C.B.). R.D.G. was supported in part by the Medical Research Council (Programme Grant G9313618). D.N. was supported by an unrestricted grant from GlaxoSmithKline.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).

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