Obese asthmatic patients have decreased surfactant protein A levels: Mechanisms and implications.

Published

Journal Article

BACKGROUND: Eosinophils are prominent in some patients with asthma and are increased in the submucosa in a subgroup of obese patients with asthma (OAs). Surfactant protein A (SP-A) modulates host responses to infectious and environmental insults. OBJECTIVE: We sought to determine whether SP-A levels are altered in OAs compared with a control group and to determine the implications of these alterations in SP-A levels in asthmatic patients. METHODS: Bronchoalveolar lavage fluid from 23 lean, 12 overweight, and 20 obese subjects were examined for SP-A. Mouse tracheal epithelial cells grown at an air-liquid interface were used for mechanistic studies. SP-A-/- mice were challenged in allergen models, and exogenous SP-A therapy was given after the last challenge. Eosinophils were visualized and quantitated in lung parenchyma by means of immunostaining. RESULTS: Significantly less SP-A (P = .002) was detected in samples from OAs compared with those from control subjects. A univariable regression model found SP-A levels were significantly negatively correlated with body mass index (r = -0.33, P = .014), whereas multivariable modeling demonstrated that the correlation depended both on asthma status (P = .017) and the interaction of asthma and body mass index (P = .008). Addition of exogenous TNF-α to mouse tracheal epithelial cells was sufficient to attenuate SP-A and eotaxin secretion. Allergen-challenged SP-A-/- mice that received SP-A therapy had significantly less tissue eosinophilia compared with mice receiving vehicle. CONCLUSIONS: SP-A functions as an important mediator in resolving tissue and lavage fluid eosinophilia in allergic mouse models. Decreased levels of SP-A in OAs, which could be due to increased local TNF-α levels, might lead to impaired eosinophil resolution and could contribute to the eosinophilic asthma phenotype.

Full Text

Duke Authors

Cited Authors

  • Lugogo, N; Francisco, D; Addison, KJ; Manne, A; Pederson, W; Ingram, JL; Green, CL; Suratt, BT; Lee, JJ; Sunday, ME; Kraft, M; Ledford, JG

Published Date

  • March 2018

Published In

Volume / Issue

  • 141 / 3

Start / End Page

  • 918 - 926.e3

PubMed ID

  • 28624607

Pubmed Central ID

  • 28624607

Electronic International Standard Serial Number (EISSN)

  • 1097-6825

Digital Object Identifier (DOI)

  • 10.1016/j.jaci.2017.05.028

Language

  • eng

Conference Location

  • United States