Complex Evaluation of Surfactant Protein A and D as Biomarkers for the Severity of COPD

Abstract

Purpose

Pulmonary surfactant proteins A (SP-A) and D (SP-D) are lectins, involved in host defense and regulation of pulmonary inflammatory response. However, studies on the assessment of COPD progress are limited.

Patients and Methods

Pulmonary surfactant proteins were obtained from the COPD mouse model induced by cigarette and lipopolysaccharide, and the specimens of peripheral blood and bronchoalveolar lavage (BALF) in COPD populations. H&E staining and RT-PCR were performed to demonstrate the successfully established of the mouse model. The expression of SP-A and SP-D in mice was detected by Western Blot and immunohistochemistry, while the proteins in human samples were measured by ELISA. Pulmonary function test, inflammatory factors (CRP, WBC, NLR, PCT, EOS, PLT), dyspnea index score (mMRC and CAT), length of hospital stay, incidence of complications and ventilator use were collected to assess airway remodeling and progression of COPD.

Results

COPD model mice with emphysema and airway wall thickening were more prone to have decreased SP-A, SP-D and increased TNF-α, TGF-β, and NF-kb in lung tissue. In humans, SP-A and SP-D decreased in BALF, but increased in serum. The serum SP-A and SP-D were negatively correlated with FVC, FEV1, FEV1/FVC, and positively correlated with CRP, WBC, NLR, mMRC and CAT scores (P < 0.05, respectively). The lower the SP-A and SP-D in BALF, the worse the lung function and the increased probability of complications and ventilator use. Moreover, the same trend emerged in COPD patients grouped according to GOLD severity grade (Gold 1–2 group vs Gold 3–4 group). The worse the patient’s condition, the more pronounced the change.

Conclusion

This study suggests that SP-A and SP-D may be related to the progression and prognostic evaluation of COPD in terms of airway remodeling, inflammatory response and clinical symptoms, and emphasizes the necessity of future studies of surfactant protein markers in COPD.

Keywords:

• COPD
• pulmonary surfactant protein A and D
• airway remodeling

Data Sharing Statement

The data/documents could be obtained from the corresponding author.

Ethics Approval

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the institutional ethics committee of the Fourth Affiliated Hospital of Harbin Medical University (2022-SCILLSC-01) and was conducted according to the Declaration of Helsinki and informed consent was given by all patients.

Informed Consent

The information involved in the article has obtained all the patient’s oral informed consent.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81670028) and the Graduate Practice Innovation Project Fund of Harbin Medical University (2018182).

Disclosure

The authors report no conflicts of interest in this work.