Systemic Galectin-3 in Smokers with Chronic Obstructive Pulmonary Disease and Chronic Bronchitis: The Impact of Exacerbations

Abstract

Purpose

The carbohydrate-binding protein Galectin-3 is increased in several inflammatory diseases and has recently been forwarded as a systemic biomarker in chronic obstructive pulmonary disease (COPD). In this longitudinal study, we characterized the level of systemic Galectin-3 using blood from smokers with a history of COPD and chronic bronchitis (COPD-CB), during stable clinical conditions and exacerbations.

Patients and Methods

The study population comprised 56 long-term smokers with COPD-CB, 10 long-term smokers without lung disease (LTS) and 10 clinically healthy never-smokers (HNS). Blood samples were analyzed for levels of Galectin-3, leukocyte populations and C-reactive protein (CRP). In addition, sputum samples from the COPD-CB group were analyzed for bacterial growth.

Results

When comparing stable clinical conditions and exacerbations in the COPD-CB group, we found that the level of Galectin-3, just like that of CRP, leukocytes and neutrophils, respectively, was increased during exacerbations. However, this exacerbation-associated increase of Galectin-3 was modest. During stable clinical conditions of COPD-CB, the level of Galectin-3 was not elevated in comparison with HNS or LTS. Nor did this level of Galectin-3 distinguish patients that remained in a clinically stable condition throughout the study to those that developed an exacerbation. In addition, neither during stable clinical conditions nor during exacerbations, did the presence of bacterial growth in sputum alter Galectin-3 levels. In contrast to Galectin-3, the level of CRP, leukocytes and neutrophils, respectively, were increased during clinical stable conditions in the COPD-CB group compared with the other groups and were further enhanced during exacerbations.

Conclusion

Systemic Galectin-3 is increased in a reproducible but modest manner during exacerbations in smokers with COPD-CB. During stable clinical conditions, the level of systemic Galectin-3 does not distinguish patients that remain clinically stable from those that develop exacerbations. This makes it less likely that systemic Galectin-3 may become a clinically useful biomarker in the current setting.

Keywords:

• COPD
• CRP
• airflow limitation
• exacerbation

Abbreviations

CB, chronic bronchitis; COPD, chronic obstructive pulmonary disease; COPD-CB, chronic obstructive pulmonary disease and chronic bronchitis; CRP, C-reactive protein; DLCO, gas diffusion capacity for carbon monoxide; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; GOLD, Global initiative for Chronic Obstructive Lung Disease; IQR, interquartile range; LTS, long-term smokers without COPD; HNS, healthy never-smokers.

Ethics Approval and Informed Consent

This study was conducted in accordance with the World Medical Association (the declaration of Helsinki) and approved by the regional ethics committee for medical research at the University of Gothenburg (S 233-03, T 286-04 and T 521-06). Thus, all participants were included after oral and written informed consent.

Acknowledgments

The highly professional monitoring of study subjects and sample collection by Barbro Balder, B.Sc., at the Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, is gratefully acknowledged posthumously.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article was submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no financial or non-financial conflicts of interest for this work.

Additional information

Funding

The study was supported by project funding from the Magnus Bergwall foundation (MS), the Rådman and Mrs Ernst Colliander foundation (MS), the Rune and Ulla Almlövs Foundation (MS), IFs foundation and Elisabeth and Alfred Ahlqvist’s foundation – Swedish pharmacy Society (MS), the Swedish Medical Research Council (JB, AK and AL), federal funding under the ALF agreement for Region Västra Götaland (AK and AL), federal funding under the ALF agreement for Region Stockholm (AL), the Arne and Inga-Britt Lundberg foundation (AK), the Swedish Heart-Lung Foundation (JB, AK and AL), the King Gustaf V 80-years foundation (AK), the King Gustaf V’s and Queen Victoria’s Freemason Research Foundation (AL) and by federal funding from Karolinska Institutet (AL). The study sponsors were not involved in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No funding was obtained from the tobacco industry.