Obese Asthmatics Have Decreased Surfactant Protein-A Levels: Mechanisms and Implications

Publication date: Available online 15 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): 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
BackgroundEosinophils 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.ObjectiveTo 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.MethodsBronchoalveolar 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.ResultsSignificantly 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.ConclusionsSP-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.

Teaser

SP-A secretion by epithelial cells is attenuated by TNF-α, a cytokine increased in obese asthmatics. SP-A plays an important role in resolving tissue eosinophilia, therefore obese asthmatics may have prolonged tissue eosinophilia due to significantly decreased SP-A levels.


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