Airway surfactant protein D deficiency in adults with severe asthma

Abstract

Background: Surfactant protein D (SP-D) is an essential component of the innate immune defence against pathogens within the airways. In addition SP-D regulates allergic inflammation and promotes the removal of apoptotic cells. SP-D dysregulation is evident in several pulmonary diseases. Our aim was to investigate whether airway and serum levels of SP-D are altered in treatment-resistant severe asthma.

Methods: SP-D concentrations were measured in matched serum and bronchoalveolar lavage (BAL) samples collected from 10 healthy controls (HC) and 50 asthmatics (22 mild [MA] and 28 severe [SA]). These samples were also evaluated by Western blots to investigate variations in SP-D size.

Results: SP-D levels in BAL were significantly lower in SA compared to HC and MA (P < .001) and inversely correlated with BAL eosinophil cationic protein (ECP) concentrations in severe asthma (P < .01). Serum SP-D was significantly increased in SA when compared to HC and MA (P < .001), BAL/serum ratios were significantly lower in SA compared to HC and MA (P < .001). Reduced SP-D levels in in BAL with concomitant rises in serum in SA were associated with degraded fragments of SP-D in the serum and increased BAL neutrophils and lipopolysaccharide levels.

Conclusions: These findings suggest defective innate immunity within the airways in severe asthma, as reflected by low BAL SP-D concentrations and altered bacterial presence with airway neutrophilia. Furthermore, BAL SP-D leakage into the serum in severe asthmatics may provide a peripheral blood biomarker reflecting increased epithelial damage and/or epithelial permeability within the peripheral airways.

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Identifiers

ORCID for R-M. Mackay: orcid.org/0000-0002-9493-9654

ORCID for C. Barber: orcid.org/0000-0001-5335-5129

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