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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)918-926.e3
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Pulmonary Surfactant-Associated Protein A
Asthma
Eosinophils
Eosinophilia
Allergens
Body Mass Index
Epithelial Cells
Therapeutic Irrigation
Bronchoalveolar Lavage Fluid

Keywords

  • asthma
  • eosinophils
  • eotaxin
  • epithelial cells
  • IL-6
  • lung function
  • obesity
  • Surfactant
  • surfactant protein A
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lugogo, N., Francisco, D., Addison, K. J., Manne, A., Pederson, W., Ingram, J. L., ... Ledford, J. G. (2018). Obese asthmatic patients have decreased surfactant protein A levels: Mechanisms and implications. Journal of Allergy and Clinical Immunology, 141(3), 918-926.e3. https://doi.org/10.1016/j.jaci.2017.05.028

Obese asthmatic patients have decreased surfactant protein A levels : Mechanisms and implications. / Lugogo, Njira; Francisco, Dave; Addison, Kenneth J.; Manne, Akarsh; Pederson, William; Ingram, Jennifer L.; Green, Cynthia L.; Suratt, Benjamin T.; Lee, James J.; Sunday, Mary E.; Kraft, Monica; Ledford, Julie G.

In: Journal of Allergy and Clinical Immunology, Vol. 141, No. 3, 01.03.2018, p. 918-926.e3.

Research output: Contribution to journalArticle

Lugogo, N, Francisco, D, Addison, KJ, Manne, A, Pederson, W, Ingram, JL, Green, CL, Suratt, BT, Lee, JJ, Sunday, ME, Kraft, M & Ledford, JG 2018, 'Obese asthmatic patients have decreased surfactant protein A levels: Mechanisms and implications', Journal of Allergy and Clinical Immunology, vol. 141, no. 3, pp. 918-926.e3. https://doi.org/10.1016/j.jaci.2017.05.028
Lugogo, Njira ; Francisco, Dave ; Addison, Kenneth J. ; Manne, Akarsh ; Pederson, William ; Ingram, Jennifer L. ; Green, Cynthia L. ; Suratt, Benjamin T. ; Lee, James J. ; Sunday, Mary E. ; Kraft, Monica ; Ledford, Julie G. / Obese asthmatic patients have decreased surfactant protein A levels : Mechanisms and implications. In: Journal of Allergy and Clinical Immunology. 2018 ; Vol. 141, No. 3. pp. 918-926.e3.
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abstract = "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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AU - Francisco, Dave

AU - Addison, Kenneth J.

AU - Manne, Akarsh

AU - Pederson, William

AU - Ingram, Jennifer L.

AU - Green, Cynthia L.

AU - Suratt, Benjamin T.

AU - Lee, James J.

AU - Sunday, Mary E.

AU - Kraft, Monica

AU - Ledford, Julie G.

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N2 - 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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KW - obesity

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KW - surfactant protein A

KW - TNF-α

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