Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr 27;10(2):159-169.
doi: 10.15326/jcopdf.2022.0375.

Airway and Systemic Prostaglandin E2 Association with COPD Symptoms and Macrophage Phenotype

Vickram Tejwani  1   2 , Andres F Villabona-Rueda  2 , Pratik Khare  3 , Cissy Zhang  4 , Anne Le  4   5 , Nirupama Putcha  2 , Franco D'Alessio  2 , Neil E Alexis  6 , Nadia N Hansel  2 , Ashraf Fawzy  2
Affiliations

Airway and Systemic Prostaglandin E2 Association with COPD Symptoms and Macrophage Phenotype

Vickram Tejwani et al. Chronic Obstr Pulm Dis. .

Abstract

Background: Polymorphisms and products of the cyclooxygenase (COX) pathway have been associated with the development of chronic obstructive pulmonary disease (COPD) and adverse outcomes. COX-produced prostaglandin E2 (PGE-2) may play a role in the inflammation observed in COPD, potentially through deleterious airway macrophage polarization. A better understanding of the role of PGE-2 in COPD morbidity may inform trials for therapeutics targeting the COX pathway or PGE-2.

Methods: Urine and induced sputum were collected from former smokers with moderate-severe COPD. The major urinary metabolite of PGE-2 (PGE-M) was measured, and ELISA was performed on sputum supernatant for PGE-2 airway measurement. Airway macrophages underwent flow cytometry phenotyping (surface CD64, CD80, CD163, CD206, and intracellular IL-1β, TGF-β1). Health information was obtained the same day as the biologic sample collection. Exacerbations were collected at baseline and then monthly telephone calls.

Results: Among 30 former smokers with COPD (mean±SD age 66.4±8.88 years and forced expiratory volume in 1 second [FEV1] 62.4±8.37 percent predicted), a 1 pg/mL increase in sputum PGE-2 was associated with higher odds of experiencing at least one exacerbation in the prior 12 months (odds ratio 3.3; 95% confidence interval: 1.3 to15.0), worse respiratory symptoms and health status. PGE-M was not associated with exacerbations or symptoms. Neither airway PGE-2 nor urinary PGE-M was uniformly associated with an M1 or M2 polarization.

Conclusions: Elevated levels of sputum PGE-2, rather than systemic PGE-2, is associated with increased respiratory symptoms and history of exacerbation among individuals with COPD. Additional studies focused on mechanism of action are warranted.

Keywords: COPD; macrophage; prostaglandin.

PubMed Disclaimer

Conflict of interest statement

Dr. Tejwani, Dr. Villabona-Rueda, Mr. Khare, Ms. Zhang, Dr. Le, Dr. Putcha, Dr. D’Alessio, Dr. Alexis, and Dr. Fawzy have nothing to disclose. Dr. Hansel reports grants and personal fees from AstraZeneca, grants and personal fees from GSK, grants from Boehringer Ingelheim, grants from the COPD Foundation, and personal fees from Mylan, all outside the submitted work.

References

    1. Pietras T,Szemraj J,Panek M,et al. Functional polymorphism of cyclooxygenase-2 gene (G-765C) in chronic obstructive pulmonary disease patients. Mol Biol Rep. 2012;39(3):2163-2167. doi: https://doi.org/10.1007/s11033-011-0964-2 - PubMed
    1. Dagouassat M,Gagliolo JM,Chrusciel S,et al. The cyclooxygenase-2-prostaglandin E2 pathway maintains senescence of chronic obstructive pulmonary disease fibroblasts. Am J Respir Crit Care Med. 2013;187(7):703-714. doi: https://doi.org/10.1164/rccm.201208-1361OC - PubMed
    1. Mitchell JA,Warner TD. COX isoforms in the cardiovascular system: understanding the activities of non-steroidal anti-inflammatory drugs. Nat Rev Drug Discov. 2006;5(1):75-86. doi: https://doi.org/10.1038/nrd1929 - PubMed
    1. Ricciotti E,FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986-1000. doi: https://doi.org/10.1161/ATVBAHA.110.207449 - PMC - PubMed
    1. Davì G,Basili S,Vieri M,et al. Enhanced thromboxane biosynthesis in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1997;156(6):1794-1799. doi: https://doi.org/10.1164/ajrccm.156.6.9706026 - PubMed