0
Correspondence |

d-ROMs Test Detects Ceruloplasmin, Not Oxidative Stress FREE TO VIEW

Mehmet Ibrahim Harma, MD; Muge Harma, MD; Ozcan Erel, MD
Author and Funding Information

Affiliations: Harran University Medical School, Sanliurfa, Turkey,  University Hospital of Larissa, Larissa, Greece

Correspondence to: Mehmet Ibrahim Harma, MD, 6 Sokak, 2/9, Bahcelievler, 06500 Ankara, Turkey; e-mail: mehmetharma@superonline.com



Chest. 2006;130(4):1276-1277. doi:10.1378/chest.130.4.1276
Text Size: A A A
Published online

To the Editor:

We read with interest the article by Papageorgiou et al (November 2005)1 reporting that the measurement of oxidative stress levels with a rapid commercially available method (d-ROMs test; Diacron; Grosseto, Italy) was highly repeatable in the patients studied and may serve as a marker for differentiation between exudates and transudates in clinical practice.

Unfortunately, the basic principle of the d-ROMs test is invalid. In this method, overall oxidative stress is measured indirectly by measuring the level of total hydroperoxides. However, the alchilamine used as a chromogen in this method is also a substrate for the ceruloplasmin (ferroxidase) enzyme, which is abundantly present in serum; the type of buffer used and its pH are more appropriate for ferroxidase activity. This is borne out by the fact that a significant positive correlation between the assay results and ferroxidase activity has been found (r = 0.911; p < 0.001; n = 100) [Table 1, Fig 6 in the article by Erel2]. Also, this assay is inhibited by sodium azide (Fig 3 in the article by Erel2); no response was observed during copper-induced lipoprotein autooxidation (Fig 8 in the article by Erel2). Also, there were no appropriate linear responses for H2O2, t-butyl hydroperoxide, or cumene hydroperoxide solutions. Further, there was a lack of response during copper-induced lipoprotein autooxidation (Fig 8 in the article by Erel,2).2

In a study by Calikoglu et al,3 it was shown that acute-phase reactants, especially ceruloplasmin, have a high sensitivity, specificity, and area under the receiving operator characteristic curve (92%, 85%, and 0.98, respectively) in the discrimination of exudative pleural effusions. These values are very similar to the findings of Papageorgiou et al1 (96%, 96%, and 0.99, respectively). Moreover, the significance of the ceruloplasmin values between exudates and transudates (Table 2 in the article by Calikoglu et al3) were surprisingly similar to the findings of Papageorgiou et al1 for these two groups.3 It is apparent that the results published by Papageorgiou et al1 essentially reflect ceruloplasmin activity and not oxidative stress.

The authors 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.

None of the authors have a conflict of interest to disclose.

Papageorgiou, E, Kostikas, K, Kiropoulos, T, et al (2005) Increased oxidative stress in exudative pleural effusions: a new marker for the differentiation between exudates and transudates?Chest128,3291-3297. [CrossRef] [PubMed]
 
Erel, O A new automated colorimetric method for measuring total oxidant status.Clin Biochem2005;38,1103-1111. [CrossRef] [PubMed]
 
Calikoglu, M, Sezer, C, Unlu, A, et al Use of acute phase proteins in pleural effusion discrimination.Tuberk Toraks2004;52,122-129. [PubMed]
 
To the Editor:

We appreciate Dr. Harma’s comments regarding our article on oxidative stress levels in pleural effusions as a marker for the differentiation between exudates and transudates.1The d-ROMs test (Diacron; Grosseto, Italy) may indeed measure ceruloplasmin oxidase activity besides the total level of hydroperoxides, and this is known from the initial study2 that has validated the d-ROMs method. However, the contribution of ceruloplasmin oxidase activity to the typical change of absorbance at the 505 nm of the d-ROMs test, although not negligible, is relatively small, especially due to the fact that in the d-ROMs method for the serum the sample is 100-fold diluted.2 The same probably applies for the pleural fluid samples, as we have used the same dilutions.

The correlation between ceruloplasmin oxidase activity and the d-ROMs test has not been shown in clinical practice. In hemodialyzed patients, for instance, the d-ROMs values are increased,3whereas the ceruloplasmin oxidase activity is reduced.4Additionally, d-ROMs have been validated in large populations of healthy subjects, alcohol abusers, and in various disease states. Interestingly, d-ROMs are increased in patients undergoing prolonged hyperbaric oxygen treatment and correlate with malondialdehyde levels, another marker of oxidative stress.5 Therefore, the similarities between the diagnostic performance of d-ROMs and ceruloplasmin for the differentiation between exudative and transudative pleural effusions referred by Harma et al are only speculative, and further research is needed in that direction.

In our study, we used d-ROMs as a marker of overall oxidative stress in the pleural fluid, and we concluded that this method is repeatable and represents an excellent marker for the differentiation of exudates and transudates. We believe that further research is needed for the clarification of the mechanisms of reactive oxygen metabolites production in the pleural cavity and their role in the pathogenesis of pleural effusions.

References
Papageorgiou, E, Kostikas, K, Kiropoulos, T, et al Increased oxidative stress in exudative pleural effusions: a new marker for the differentiation between exudates and transudates?Chest2005;128,3291-3297. [CrossRef] [PubMed]
 
Alberti, A, Bolognini, L, Macciantelli, D, et al The radical cation of N,N-diethyl-para-phenylendiamine: a possible indicator of oxidative stress in biological samples.Res Chem Intermed2000;26,253-267. [CrossRef]
 
Gerardi, GM, Usberti, M, Martini, G, et al Plasma total antioxidant capacity in hemodialyzed patients and its relationship to other biomarkers of oxidative stress and lipid peroxidation.Clin Chem Lab Med2002;40,104-110. [CrossRef] [PubMed]
 
Roxborough, HE, Mercer, C, McMaster, D, et al The ferroxidase activity of caeruloplasmin is reduced in haemodialysis patients.Nephron2000;84,211-217. [CrossRef] [PubMed]
 
Benedetti, S, Lamorgese, A, Piersantelli, M, et al Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen.Clin Biochem2004;37,312-317. [CrossRef] [PubMed]
 

Figures

Tables

References

Papageorgiou, E, Kostikas, K, Kiropoulos, T, et al (2005) Increased oxidative stress in exudative pleural effusions: a new marker for the differentiation between exudates and transudates?Chest128,3291-3297. [CrossRef] [PubMed]
 
Erel, O A new automated colorimetric method for measuring total oxidant status.Clin Biochem2005;38,1103-1111. [CrossRef] [PubMed]
 
Calikoglu, M, Sezer, C, Unlu, A, et al Use of acute phase proteins in pleural effusion discrimination.Tuberk Toraks2004;52,122-129. [PubMed]
 
Papageorgiou, E, Kostikas, K, Kiropoulos, T, et al Increased oxidative stress in exudative pleural effusions: a new marker for the differentiation between exudates and transudates?Chest2005;128,3291-3297. [CrossRef] [PubMed]
 
Alberti, A, Bolognini, L, Macciantelli, D, et al The radical cation of N,N-diethyl-para-phenylendiamine: a possible indicator of oxidative stress in biological samples.Res Chem Intermed2000;26,253-267. [CrossRef]
 
Gerardi, GM, Usberti, M, Martini, G, et al Plasma total antioxidant capacity in hemodialyzed patients and its relationship to other biomarkers of oxidative stress and lipid peroxidation.Clin Chem Lab Med2002;40,104-110. [CrossRef] [PubMed]
 
Roxborough, HE, Mercer, C, McMaster, D, et al The ferroxidase activity of caeruloplasmin is reduced in haemodialysis patients.Nephron2000;84,211-217. [CrossRef] [PubMed]
 
Benedetti, S, Lamorgese, A, Piersantelli, M, et al Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen.Clin Biochem2004;37,312-317. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543