title: Airway Surfactant Protein D Deficiency in Adults With Severe Asthma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK. Electronic address: r.a.mackay@soton.ac.uk.
authors.forename: Rose-Marie A
authors.initials: RM
authors.lastname: Mackay
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK; Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Grainge
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Laurie C
authors.initials: LC
authors.lastname: Lau
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK; Southampton NIHR Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Clair
authors.initials: C
authors.lastname: Barber
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK; Southampton NIHR Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Howard W
authors.initials: HW
authors.lastname: Clark
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK; Southampton NIHR Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Howarth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D047150:Eosinophil Cationic Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D009195:Peroxidase / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology / Q000378:metabolism*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; D037663:Pulmonary Surfactant-Associated Protein D; D009195:Peroxidase; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human; D019272:Leukocyte Elastase
keywords: asthma; biomarkers; bronchoalveolar lavage; eosinophilic inflammation; immunology (lung); immunology asthma; neutrophilic inflammation; severe asthma; surfactant protein D
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