Airway Surfactant Protein D Deficiency in Adults With Severe Asthma

Chest. 2016 May;149(5):1165-72. doi: 10.1016/j.chest.2015.11.012. Epub 2016 Jan 13.

Abstract

Background: Surfactant protein D (SP-D) is an essential component of the innate immune defense against pathogens within the airways. SP-D also 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 BAL samples collected from 10 healthy control subjects (HC) and 50 patients with asthma (22 with mild asthma [MA] and 28 with severe asthma [SA]). These samples were also evaluated by using Western blot analysis to investigate variations in SP-D size.

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

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

Keywords: asthma; biomarkers; bronchoalveolar lavage; eosinophilic inflammation; immunology (lung); immunology asthma; neutrophilic inflammation; severe asthma; surfactant protein D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asthma / immunology
  • Asthma / metabolism*
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid / chemistry
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Eosinophil Cationic Protein / metabolism
  • Female
  • Humans
  • Immunity, Innate / immunology
  • Leukocyte Count
  • Leukocyte Elastase / metabolism
  • Lipopolysaccharides / metabolism
  • Male
  • Middle Aged
  • Neutrophils
  • Peroxidase / metabolism
  • Pulmonary Surfactant-Associated Protein D / immunology
  • Pulmonary Surfactant-Associated Protein D / metabolism*
  • Severity of Illness Index
  • Young Adult

Substances

  • Lipopolysaccharides
  • Pulmonary Surfactant-Associated Protein D
  • Peroxidase
  • Eosinophil Cationic Protein
  • RNASE3 protein, human
  • Leukocyte Elastase