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

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

doi:10.1016/j.jaci.2017.05.028

Cited by 38 publications

(40 citation statements)

References 39 publications

(40 reference statements)

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“…Some studies have shown that increased leptin levels in obese adolescents correlate inversely with FEV1, FVC, and the FEV1/FVC ratio and that visceral fat leptin expression correlates with airway reactivity in adults. Leptin, along with adiponectin, has also been linked to exercise-induced changes in lung function [52][53][54][55][56][57].…”

Section: Pulmonary Systemmentioning

confidence: 99%

Inflammation in Obesity-Related Complications in Children: The Protective Effect of Diet and Its Potential Role as a Therapeutic Agent

et al. 2020

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Obesity is a growing health problem in both children and adults, impairing physical and mental state and impacting health care system costs in both developed and developing countries. It is well-known that individuals with excessive weight gain frequently develop obesity-related complications, which are mainly known as Non-Communicable Diseases (NCDs), including cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome, non-alcoholic fatty liver disease, hypertension, hyperlipidemia and many other risk factors proven to be associated with chronic inflammation, causing disability and reduced life expectancy. This review aims to present and discuss complications related to inflammation in pediatric obesity, the critical role of nutrition and diet in obesity-comorbidity prevention and treatment, and the impact of lifestyle. Appropriate early dietary intervention for the management of pediatric overweight and obesity is recommended for overall healthy growth and prevention of comorbidities in adulthood.

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Section: Pulmonary Systemmentioning

confidence: 99%

Inflammation in Obesity-Related Complications in Children: The Protective Effect of Diet and Its Potential Role as a Therapeutic Agent

et al. 2020

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“…Therapies that aim to minimize eosinophilic inflammation aid in the reduction of symptoms associated with allergic airway disease (14). In addition, studies have shown that obese asthmatics have more severe tissue eosinophilia (15,16) and that they also have decreased levels of SP-A compared with lean normal and lean asthmatic individuals (17). Moreover, in a mouse model of allergic airway inflammation, administration of exogenous SP-A promoted the resolution of tissue eosinophilia (17).…”

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confidence: 99%

Genetic Variation in Surfactant Protein-A2 Delays Resolution of Eosinophilia in Asthma

Arif

Addison

et al. 2019

The Journal of Immunology

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Surfactant protein-A (SP-A) is an important mediator of pulmonary immunity. A specific genetic variation in SP-A2, corresponding to a glutamine (Q) to lysine (K) amino acid substitution at position 223 of the lectin domain, was shown to alter the ability of SPA to inhibit eosinophil degranulation. Because a large subgroup of asthmatics have associated eosinophilia, often accompanied by inflammation associated with delayed clearance, our goal was to define how SPA mediates eosinophil resolution in allergic airways and whether genetic variation affects this activity. Wild-type, SPA knockout (SP-A KO) and humanized (SP-A2 223Q/Q, SP-A2 223K/K) C57BL/6 mice were challenged in an allergic OVA model, and parameters of inflammation were examined. Peripheral blood eosinophils were isolated to assess the effect of SPA genetic variation on apoptosis and chemotaxis. Five days postchallenge, SPA KO and humanized SP-A2 223K/K mice had persistent eosinophilia in bronchoalveolar lavage fluid compared with wild-type and SP-A2 223Q/Q mice, suggesting an impairment in eosinophil resolution. In vitro, human SPA containing either the 223Q or the 223K allele was chemoattractant for eosinophils whereas only 223Q resulted in decreased eosinophil viability. Our results suggest that SPA aids in the resolution of allergic airway inflammation by promoting eosinophil clearance from lung tissue through chemotaxis, independent of SP-A2 Q223K, and by inducing apoptosis of eosinophils, which is altered by the polymorphism.

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“…Additionally, obese asthmatics have been shown to have higher tissue eosinophilia compared to non-obese asthmatics [ 26 , 27 ]. In support of these findings, using allergic mouse models in mice lacking SP-A (SP-A −/− ), we discovered SP-A −/− mice had more severe tissue eosinophilia compared to wild-type mice which was resolved upon treatment with exogenous SP-A [ 25 ].…”

Section: Sp-a and Asthmamentioning

confidence: 85%

“…All data thus far from the field have suggested that an adequate pool of functional SP-A is a necessary contributor for normal lung function, whether during periods of homeostasis, infection or allergen challenge. Decreased levels of SP-A as seen in obese asthmatics [ 25 ] or dysfunctional SP-A as detected in some asthmatics [ 24 ], have both been associated with altered lung function and may result in enhanced airway inflammation in asthma. We provide evidence that genetic variation within SP-A2 alters the ability of SP-A to inhibit eosinophil EPO release, which could lead to worse asthma exacerbations upon pathogen infection in those asthmatics harbouring the minor allele (223K).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we have recently found that in a cohort of patients with mild to moderate asthma when stratified according to body mass index (BMI) into lean, overweight and obese groups, decreased levels of SP-A were detected among obese asthmatics compared to lean normal and lean asthmatic individuals [ 25 ]. Additionally, obese asthmatics have been shown to have higher tissue eosinophilia compared to non-obese asthmatics [ 26 , 27 ].…”

Section: Sp-a and Asthmamentioning

confidence: 99%

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The Emerging Roles of Surfactant Protein-A in Asthma

Tanyaratsrisakul

Voelker

et al. 2018

J Clin Cell Immunol

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Asthma remains one of the most common respiratory diseases in both children and adults affecting up to 10% of the US population. Asthma is characterized by persistent symptoms, airway inflammation, airflow limitation and frequent exacerbations. Eosinophils are a key immune cell present in a large majority of asthmatics and their presence and dysregulation are clinically associated with more severe asthma. Surfactant protein A (SP-A) provides a first-line of defense in pulmonary innate immunity by virtue of its role in pathogen opsonization. SP-A is known to specifically bind to Mycoplasma pneumoniae (Mp), a pathogen associated with asthma exacerbations, and functions to attenuate Mp pathogenicity and abrogate lung inflammation. In addition, SP-A has been shown to inhibit Mp-induced eosinophil peroxidase (EPO) release, a toxic product that can compromise the integrity of the delicate airway epithelia. We have determined that genetic variation in SP-A2 at position 223 that results in a glutamine (Q) to a lysine (K) substitution alters the ability of SP-A to inhibit EPO release and may offer a mechanistic explanation as to why some SP-A extracted from subjects with asthma is unable to carry out normal immune regulatory functions.

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

Cited by 38 publications

References 39 publications

Inflammation in Obesity-Related Complications in Children: The Protective Effect of Diet and Its Potential Role as a Therapeutic Agent

Inflammation in Obesity-Related Complications in Children: The Protective Effect of Diet and Its Potential Role as a Therapeutic Agent

Genetic Variation in Surfactant Protein-A2 Delays Resolution of Eosinophilia in Asthma

The Emerging Roles of Surfactant Protein-A in Asthma

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