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Allergy. 2019 Jan;74(1):78-88. doi: 10.1111/all.13458. Epub 2018 Oct 22.

Surfactant protein D alleviates eosinophil-mediated airway inflammation and remodeling in patients with aspirin-exacerbated respiratory disease.

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Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
Department of Biomedical Science, Graduate School of Ajou University, Suwon, Korea.
Clinical Trial Center, Ajou University Medical Center, Suwon, Korea.



Surfactant protein D (SPD) is a member of the collectin family that lines the airway epithelial cells with host defense. However, the role of SPD in the pathogenesis of aspirin-exacerbated respiratory disease (AERD) is still unclear.


The serum SPD level was measured in patients with AERD (n = 336), those with aspirin-tolerant asthma (ATA, n = 442), and healthy controls (HC, n = 104). Polymorphisms of SFTPD in the study subjects were analyzed. The effect of LTE4 on SPD production through eosinophil infiltration was investigated in BALB/c mice. The protective function of SPD against eosinophils inducing inflammation and remodeling was assessed in vitro/vivo. The potential efficacy of nintedanib against airway remodeling through the production of SPD was evaluated.


The serum SPD level was significantly lower (P < .001) in AERD compared with ATA patients, and negatively correlated with fall in FEV1 (%) after lysine-aspirin bronchoprovocation test and/or the urinary LTE4 level. In addition, polymorphism of SFTPD at rs721917 was significantly different in the study subjects (odds ratio, 1.310; 95% confidence intervals, 2.124-3.446; P = .002). LTE4-exposed mice showed an increased eosinophil count with a decreased SPD level in bronchoalveolar lavage fluid. Eosinophils increased α-smooth muscle actin expression in airway epithelial cells, which was attenuated by SPD treatment. Furthermore, nintedanib protected the airway epithelial cells against eosinophils by enhancing the production of SPD.


The decreased level of SPD in AERD was associated with airway inflammation/remodeling under the eosinophilic condition, suggesting that modulation of SPD may provide a potential benefit in AERD.


aspirin-exacerbated respiratory disease; eosinophils; inflammation; remodeling; surfactant protein D


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