Serum Surfactant Protein D during Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Abstract

Background: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations. Objectives: To determine whether or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease. Study design: case control study. Methods: We measured serum SP-D levels from patients with stable COPD (n = 14), patients experiencing acute exacerbations (n = 13) and in control subjects (n = 54) using a specific immunoassay and compared the levels using analysis of variance. Results: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 ± 120 ng/mL) compared to patients with stable disease (151 ± 83 ng/mL) or control subjects (128 ± 65 ng/mL; p = 0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV1/FVC% predicted. Conclusions: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations.

SP-D Polymorphisms and the Risk of COPD

“…Our study supports the previous studies correlating age [29], body mass index [31,32], corticosteroid intake [33] and rs721917 [29,31,39] with systemic SP-D levels. We have previously reported on significantly raised serum SP-D levels in COPD exacerbations [34]. In the current study we confirm those findings using a larger sample size (n = 153) and a more comprehensive regression model incorporating genetic markers (rs3088308 and rs721917) as covariates.…”

“…Thus we show that even when genetic factors are considered, exacerbation remains a significant determinant of systemic SP-D levels. These data highlight the potential utility of serum SP-D as a biomarker for exacerbations as previously reported [34]. A study by Sims et al [35] reports on decreased SP-D levels in broncho-alveolar lavage fluid (BALF) of COPD patients and that these levels increased after corticosteroid therapy.…”

Eosinophil-Associated Lung Diseases. A Cry for Surfactant Proteins A and D Help?

“…In patients with COPD, sputum SP-A/-D (101) and serum SP-D levels associate with lung function and with health status (102) and increase significantly during COPD exacerbations (103), suggesting that SP-D may be a biomarker of disease severity for COPD. In a recent candidate gene association study by Kim and colleagues, SP-D was identified as one of two risk loci for COPD from among circulating COPD biomarkers measured in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (104).…”

The Expanding Role of Biomarkers in the Assessment of Smoking-Related Parenchymal Lung Diseases

“…67 CRP is also useful in confi rming the diagnosis of COPD exacerbation when combined with the presence of at least one major exacerbation symptom. 61 Other potential biomarkers include SP-D, whose levels are increased during exacerbations, 35,62 and CXC chemokine ligand-10, which helps differentiate between bacterial-, viral-, and eosinophilic-associated exacerbations. 57 Similarly, MMP-9, 11 IL-8, TNF-a , IL-6, and myeloid progenitor inhibitory factor-1 may have a potential role in identifying COPD exacerbations.…”

“…Assessment of COPD exacerbations relies mostly on clinical 43,44,[58][59][60] ; MMP 5 matrix metalloproteinase 11,40,[49][50][51]53 ; MPIF-1 5 myeloid progenitor inhibitory factor-1 61 ; S100A12 53 ; SP 5 surfactant protein 10,[34][35][36][37]46,48,62,[58][59][60] ; TNF-a 5 tumor necrosis factor-a 10,26 ; TNFRSF1A 5 tumor necrosis factor receptor superfam ily, member 1A 51 ; VCAM-1 5 vascular cell adhesion moledule-1 53 ; YKL-40. 56 to identify clinical phenotypes such as rapid decliners and frequent exacerbators.…”