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

Abstract

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. 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. 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. Significantly less SP-A (P=.002) was detected in samples from OAs compared with those from control subjects. Aunivariable 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. SP-A functions as an important mediator in resolving tissue and lavage fluid eosinophilia in allergic mousemodels. Decreased levels of SP-A in OAs, which could bedue to increased local TNF-α levels, might lead to impairedeosinophil resolution and could contribute to the eosinophilic asthma phenotype.