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.

Chronic Obstructive Pulmonary Disease: Epidemiology, Biomarkers, and Paving the Way to Lung Cancer

“…Additionally, serum galectin-3 concentration, as a potential biomarker of acute exacerbation in COPD patients, showed a positive correlation with c-reactive protein and the serum concentration of a prohormone of brain natriuretic peptide [148]. However, in a recent follow-up study, serum galectin-3 concentration showed modest elevation in smokers with COPD and chronic bronchitis but did not differentiate stable COPD patients from those that underwent future exacerbations [149]. Another galectin, galectin-9, was shown to inhibit pathological changes in a PPE (porcine pancreatic elastase) instillation-induced COPD emphysema model via inhibition of neutrophil infiltration and MMP-9 [150].…”

Association between serum galectin-3 and chronic obstructive pulmonary disease: A meta-analysis

“…Accordingly, the full texts of the 26 remaining records were read by two independent authors, and 14 of them were further removed for various reasons, as listed in Figure 1. Finally, 12 observational studies remained and were considered to be suitable for the subsequent quantitative analyses [14][15][16][17][18][19][20][21][22][23][24][25].…”

“…A subsequent preclinical investigation also suggested that exposure to cigarette smoke might trigger the release of galectin-3 in cultured airway epithelial cells, potentially contributing to the development of COPD [13]. However, previous studies examining changes in serum levels of galectin-3 among COPD patients have yielded conflicting findings [14][15][16][17][18][19][20][21][22][23][24][25]. While some studies reported higher serum levels of galectin-3 compared to healthy controls [18,20,[23][24][25], others did not observe this difference [14,17,21,22].…”

“…However, previous studies examining changes in serum levels of galectin-3 among COPD patients have yielded conflicting findings [14][15][16][17][18][19][20][21][22][23][24][25]. While some studies reported higher serum levels of galectin-3 compared to healthy controls [18,20,[23][24][25], others did not observe this difference [14,17,21,22]. Given these uncertainties we aim to investigate the link between serum levels of galectn-3 and COPD through a meta-analysis.…”

Insights into the Role of Galectin-3 as a Diagnostic and Prognostic Biomarker of Atrial Fibrillation

“…Based on multiple clinical and preclinical studies demonstrating an association between altered peripheral Gal-3 levels and interstitial fibrosis and inflammation, with consequent organ (mainly heart and lung) failure [ 35 – 37 ], in the 2017 guidelines, the American Heart Association recommended Gal-3 measurement for the prognosis of HF [ 38 ], and circulating Gal-3 levels were suggested as biomarkers of cardiovascular diseases (CVDs) and non-CVDs [ 39 – 41 ]. Moreover, recent studies have proposed serum Gal-3 levels as strictly associated with atrial remodeling, including the extent of atrial fibrosis [ 42 ].…”