Abstract
BackgroundPulmonary surfactant protein D (SP-D) is considered as a candidate biomarker for the functional integrity of the lung and for disease progression, which can be detected in serum. The origin of SP-D in serum and how serum concentrations are related to pulmonary concentrations under inflammatory conditions is still unclear.MethodsIn a cross-sectional study comprising non-smokers (n = 10), young - (n = 10), elderly smokers (n = 20), and smokers with COPD (n = 20) we simultaneously analysed pulmonary and serum SP-D levels with regard to pulmonary function, exercise, repeatability and its quaternary structure by native gel electrophoresis. Statistical comparisons were conducted by ANOVA and post-hoc testing for multiple comparisons; repeatability was assessed by Bland-Altman analysis.ResultsIn COPD, median (IQR) pulmonary SP-D levels were lower (129(68) ng/ml) compared to smokers (young: 299(190), elderly: 296(158) ng/ml; p < 0.01) and non-smokers (967(708) ng/ml; p < 0.001). The opposite was observed in serum, with higher concentrations in COPD (140(89) ng/ml) as compared to non-smokers (76(47) ng/ml; p < 0.01). SP-D levels were reproducible and correlated with the degree of airway obstruction in all smokers. In addition, smoking lead to disruption of the quaternary structure.ConclusionsPulmonary and serum SP-D levels are stable markers influenced by smoking and related to airflow obstruction and disease state. Smaller subunits of pulmonary SP-D and the rapid increase of serum SP-D levels in COPD due to exercise support the translocation hypothesis and its use as a COPD biomarker.Trial registrationno interventional trial
Highlights
Chronic obstructive pulmonary diseases (COPD) is a multi-component disease
In smokers with COPD, lung function was lowest and pack years were highest compared to all other groups
Patients with COPD and elderly smokers were matched for gender, while females dominated in the healthy nonsmoking group and males were more prevalent in the group of young smokers
Summary
Chronic obstructive pulmonary diseases (COPD) is a multi-component disease. It is characterized by airflow limitation that is not fully reversible when treated with bronchodilators. SP-D is synthesized in type II pneumocytes and Clara cells It is composed of monomers (43 kDa), which assemble into trimers via disulfid crosslinking and undergo further multimerization to higher order such as dodecamers and oligomers (~ 1 MDa) [3]. The integrity of the quaternary structure is important for functions such as in pulmonary surfactant and lipid homeostasis [4], innate immunity [3], regulation of cellular clearance as well as inflammatory and immune responses [5]. Destruction of the quaternary structure leads to reduced binding affinity of the CRD to pathogens or allergens [6,7] and can promote a switch towards pro-inflammatory signalling [8,9]. The origin of SP-D in serum and how serum concentrations are related to pulmonary concentrations under inflammatory conditions is still unclear
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