期刊
CHEST
卷 149, 期 5, 页码 1165-1172出版社
AMER COLL CHEST PHYSICIANS
DOI: 10.1016/j.chest.2015.11.012
关键词
asthma; biomarkers; bronchoalveolar lavage; eosinophilic inflammation; immunology asthma; immunology (lung); neutrophilic inflammation; severe asthma; surfactant protein D
资金
- Wessex Severe Asthma Cohort Medical Research Council [G0800649]
- A Life Course Approach to Investigating Asthma Pathogenesis and Progression Medical Research Council [G0900453]
- Medical Research Council [G0900453, G0400473, G0800649, G0800766] Funding Source: researchfish
- MRC [G0800649, G0900453, G0400473] Funding Source: UKRI
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.
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