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

J Allergy Clin Immunol 2018 03 15;141(3):918-926.e3. Epub 2017 Jun 15.

Department of Medicine, University of Arizona, Tucson, Ariz; Department of Immunobiology, University of Arizona, Tucson, Ariz. Electronic address:

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.

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http://dx.doi.org/10.1016/j.jaci.2017.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732097PMC
March 2018
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