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

Njira Lugogo, Dave Francisco, Kenneth J. Addison, Akarsh Manne, William Pederson, Jennifer L. Ingram, Cynthia L. Green, Benjamin T. Suratt, James J. Lee, Mary E. Sunday, Monica Kraft, Julie G. Ledford

Eosinophils are prominent in some individuals with asthma and are elevated in the submucosa in a subgroup of obese asthmatics. Surfactant protein-A (SP-A) modulates host responses to infectious and environmental insults. To determine if SP-A levels are altered in obese asthma patients compared to a control group and to determine the implications of these alterations in SP-A levels in asthma. Bronchoalveolar lavage fluid from 23 lean, 12 overweight and 20 obese subjects were examined for SP-A. Mouse tracheal epithelial cells (MTECs) 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 the lung parenchyma by immunostaining. Significantly less SP-A (p=0.002) was detected in samples from obese asthmatics compared to the control group. A univariable regression model found SP-A was significantly negatively correlated with BMI (r= -0.33; p=0.014), while multivariable modeling demonstrated the correlation depended both on asthma status (p=0.017) and the interaction of asthma and BMI (p=0.008). Addition of exogenous TNF-α to MTECs 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 to mice receiving vehicle. SP-A functions as an important mediator in resolving tissue and lavage eosinophilia in allergic mouse models. Decreased levels of SP-A in obese asthmatics, which could be due to increased local TNF-α, may lead to impaired eosinophil resolution and could contribute to the eosinophilic asthma phenotype.