Chest
Volume 137, Issue 4, April 2010, Pages 812-822
Journal home page for Chest

Original Research
COPD
Serum IP-10 as a Biomarker of Human Rhinovirus Infection at Exacerbation of COPD

https://doi.org/10.1378/chest.09-1541Get rights and content

Background

Human rhinovirus (HRV) is the most frequent virus associated with COPD exacerbations. Viral infections increase exacerbation severity and likelihood of hospitalization. As ease of sampling blood makes serum a more practical marker than sputum, we investigated whether changes in serum interferon-γ-inducible protein 10 (IP-10) from baseline to exacerbation were higher in airway HRV-positive exacerbations and whether IP-10 levels related to HRV load.

Methods

One hundred thirty-six patients with COPD and 70 controls were included over 2 years and 72 exacerbations sampled. HRV positivity and load were determined by reverse transcriptase-polymerase chain reaction in nasopharyngeal swabs and/or sputum at baseline and exacerbation. IP-10 was measured by enzyme-linked immunosorbent assay in serum and compared with HRV load.

Results

At baseline, serum IP-10 was higher in patients with COPD than controls; medians were 149.4 pg/mL (103-215) and 111.7 pg/mL (82-178), P = .02. The presence of HRV at baseline did not increase IP-10: patients with COPD, 166.9 pg/mL (110-240) and 149.4 pg/mL (103-215), P = .30; controls, 136.4 pg/mL (77-204) and 111.7 pg/mL (82-178), P = .53. IP-10 increased significantly from baseline to exacerbation in HRV-positive exacerbations: 154.9 pg/mL (114.0-195.1) to 207.5 pg/mL (142.1-333.5), P = .009. There was no change in IP-10 between baseline and exacerbation in HRV-negative exacerbations: 168.3 pg/mL (94.3-249.8) and 175.6 pg/mL (107.2-290.4), P = .49. At exacerbation, IP-10 correlated with sputum viral load: rho = 0.48; P = .02. In receiver operating characteristics analysis, the combination of IP-10 and coryzal symptoms gave an area under the curve of 0.82 (95% CI, 0.74-0.90).

Conclusions

IP-10 increases from baseline to exacerbation in HRV-positive exacerbations and correlates with sputum HRV load. Serum IP-10 may be useful as a novel marker for these events.

Section snippets

Patient Recruitment

One hundred thirty-six patients were studied between April 1, 2006, and May 31, 2008. Seventy smoking and nonsmoking control subjects of similar age but without COPD were recruited from a primary care practice. The recruitment and monitoring of patients in the London COPD study has previously been described2, 4, 12, 13, 14 and further details are available in the online supplement. This study was approved by the Royal Free Hospital Research Ethics Committee and patients gave written informed

Baseline Patient Characteristics

One hundred thirty six patients with COPD were studied (83 men and 53 women). The baseline characteristics of the cohort are reported in Table 1. The patients had a mean FEV1 of 1.16 l or 53.9% predicted.

Seventy control subjects were studied (28 men and 42 women). The baseline characteristics are reported in Table 2. The control subjects had a mean FEV1 of 2.63 L or 112.1% predicted. There were significant differences in age, smoking history, and oxygen saturations between the control subjects

Discussion

We have shown for the first time that serum IP-10 increases from baseline to exacerbation in COPD specifically in exacerbations positive for HRV. Serum IP-10 has previously been shown to increase in virus-triggered acute asthma exacerbations,19 and we have now shown that in COPD exacerbations, sputum HRV load determined by quantitative RT-PCR correlates with IP-10 levels in the blood. Although HRV infection in most individuals is mild and self-limiting, in patients with COPD viral infection not

Acknowledgments

Author contributions: Dr Quint: contributed to the conception and design of the study, the acquisition of samples, ELISA processing, data analysis and interpretation, writing the first draft of the manuscript, and editing and revising the manuscript.

Dr Donaldson: contributed to the conception and design of the study, data analysis and interpretation, and editing and revising the manuscript.

Dr Goldring: contributed to acquisition of samples and editing and revising the manuscript.

Dr

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Funding/Support: This work was supported by the National Institutes of Health [Grant RO1 HL082578].

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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