Validation of Lung Surfactant Protein Type B Levels As a Diagnostic and Prognostic Marker in Heart Failure Progression

Pulmonary surfactant is a highly surface-active lipoprotein complex that forms a thin film lining the alveolar and terminal airway surfaces. Its primary physiological function is to reduce surface tension at the air-liquid interface, stabilizing the alveoli and preventing their collapse at the end of expiration. Both the lipid and protein fractions of surfactant are synthesized by type II pneumocytes and stored in lamellar bodies-intracellular organelles where surfactant is secreted through the fusion of their outer membrane with the apical plasma membrane of the cell, releasing surfactant into the alveolar space.

The surface-active properties of pulmonary surfactant at the liquid-gas interface of the alveoli are primarily attributed to its lipid component (90%), particularly phospholipids. Although accounting for less than 10% of the surfactant, the protein fraction-composed of SP-A, SP-B, SP-C, and SP-D-plays a crucial role. SP-B, along with SP-C, is essential for the lipid fraction's ability to exert its surface-active function. The absence of SP-B is associated with severe respiratory failure, which can be fatal. SP-A and SP-D are less directly involved in surfactant's surface activity but appear to have significant anti-infective functions in the lungs.

Human SP-B is a small amphipathic peptide of 79 amino acids (8 kDa), produced through proteolytic processing from a 381-amino acid precursor (42 kDa). It is encoded by a single gene (SFTPB) located on chromosome 2. SP-B is predominantly produced by type II alveolar epithelial cells, initially synthesized as a glycosylated precursor that is transported from the endoplasmic reticulum to the Golgi apparatus, then to multivesicular bodies, and finally packaged into lamellar bodies. The proteolytic maturation of SP-B occurs during its transfer from multivesicular bodies to lamellar bodies, where active SP-B is stored together with SP-C and phospholipids. The contents of lamellar bodies are secreted into the airway space, where SP-A facilitates surfactant film formation over the alveolar surface.

Extracellular SP-B plays a fundamental role in surfactant homeostasis by promoting lipid absorption into the surface film and enhancing its stability during the compression and expansion cycles of respiration.

Recent studies have shown that in heart failure (HF) patients, plasma SP-B levels are significantly elevated, likely due to increased pulmonary microvascular pressure, which may compromise alveolar-capillary barrier integrity, leading to SP-B release into circulation. Plasma levels of immature SP-B, a surfactant protein isoform, increase in HF patients and strongly correlate with functional indicators of pulmonary impairment (peak oxygen uptake, VO2, lung diffusion, DLco) and New York Heart Association (NYHA) classification, establishing SP-B as a specific marker of disease severity linked to organ damage. More importantly, our studies indicate that SP-B is a circulating prognostic marker for hospitalization in HF patients, with superior predictive ability compared to functional parameters. Furthermore, SP-B also emerges as a marker of therapeutic efficacy.