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

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


Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Airway Remodeling / drug effects*
  • Animals
  • Asthma, Aspirin-Induced / blood*
  • Asthma, Aspirin-Induced / drug therapy
  • Eosinophils / drug effects
  • Eosinophils / immunology*
  • Female
  • Humans
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Leukotriene E4 / pharmacology
  • Leukotriene E4 / urine
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Pulmonary Surfactant-Associated Protein D / blood
  • Pulmonary Surfactant-Associated Protein D / genetics
  • Pulmonary Surfactant-Associated Protein D / pharmacology*
  • Pulmonary Surfactant-Associated Protein D / therapeutic use
  • Respiratory System / pathology*


  • Indoles
  • Pulmonary Surfactant-Associated Protein D
  • Leukotriene E4
  • nintedanib