Cargando…
Phenotypic characteristics of asthma and morbidity are associated with distinct longitudinal changes in L-arginine metabolism
BACKGROUND: The L-arginine metabolome is dysregulated in asthma, though it is not understood how longitudinal changes in L-arginine metabolism differ among asthma phenotypes and relate to disease outcomes. OBJECTIVES: To determine the longitudinal associations between phenotypic characteristics with...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254613/ https://www.ncbi.nlm.nih.gov/pubmed/37270184 http://dx.doi.org/10.1136/bmjresp-2023-001683 |
_version_ | 1785056684241059840 |
---|---|
author | Althoff, Meghan Dolan Peterson, Ryan McGrath, Max Jin, Ying Grasemann, Hartmut Sharma, Sunita Federman, Alex Wisnivesky, Juan Pablo Holguin, Fernando |
author_facet | Althoff, Meghan Dolan Peterson, Ryan McGrath, Max Jin, Ying Grasemann, Hartmut Sharma, Sunita Federman, Alex Wisnivesky, Juan Pablo Holguin, Fernando |
author_sort | Althoff, Meghan Dolan |
collection | PubMed |
description | BACKGROUND: The L-arginine metabolome is dysregulated in asthma, though it is not understood how longitudinal changes in L-arginine metabolism differ among asthma phenotypes and relate to disease outcomes. OBJECTIVES: To determine the longitudinal associations between phenotypic characteristics with L-arginine metabolites and their relationships with asthma morbidity. METHODS: This is a prospective cohort study of 321 patients with asthma followed semiannually for over 18 months with assessments of plasma L-arginine metabolites, asthma control, spirometry, quality of life and exacerbations. Metabolite concentrations and ratios were transformed using the natural logarithm. RESULTS: There were many differences in L-arginine metabolism among asthma phenotypes in the adjusted models. Increasing body mass index was associated with increased asymmetric dimethylarginine (ADMA) and depleted L-citrulline. Latinx was associated with increased metabolism via arginase, with higher L-ornithine, proline and L-ornithine/L-citrulline levels, and was found to have higher L-arginine availability compared with white race. With respect to asthma outcomes, increasing L-citrulline was associated with improved asthma control and increasing L-arginine and L-arginine/ADMA were associated with improved quality of life. Increased variability in L-arginine, L-arginine/ADMA, L-arginine/L-ornithine and L-arginine availability index over 12 months were associated with increased exacerbations, OR 4.70 (95% CI 1.35 to 16.37), OR 8.69 (95% CI 1.98 to 38.08), OR 4.17 (95% CI 1.40 to 12.41) and OR 4.95 (95% CI 1.42 to 17.16), respectively. CONCLUSIONS: Our findings suggest that L-arginine metabolism is associated with multiple measures of asthma control and may explain, in part, the relationship between age, race/ethnicity and obesity with asthma outcomes. |
format | Online Article Text |
id | pubmed-10254613 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-102546132023-06-10 Phenotypic characteristics of asthma and morbidity are associated with distinct longitudinal changes in L-arginine metabolism Althoff, Meghan Dolan Peterson, Ryan McGrath, Max Jin, Ying Grasemann, Hartmut Sharma, Sunita Federman, Alex Wisnivesky, Juan Pablo Holguin, Fernando BMJ Open Respir Res Asthma BACKGROUND: The L-arginine metabolome is dysregulated in asthma, though it is not understood how longitudinal changes in L-arginine metabolism differ among asthma phenotypes and relate to disease outcomes. OBJECTIVES: To determine the longitudinal associations between phenotypic characteristics with L-arginine metabolites and their relationships with asthma morbidity. METHODS: This is a prospective cohort study of 321 patients with asthma followed semiannually for over 18 months with assessments of plasma L-arginine metabolites, asthma control, spirometry, quality of life and exacerbations. Metabolite concentrations and ratios were transformed using the natural logarithm. RESULTS: There were many differences in L-arginine metabolism among asthma phenotypes in the adjusted models. Increasing body mass index was associated with increased asymmetric dimethylarginine (ADMA) and depleted L-citrulline. Latinx was associated with increased metabolism via arginase, with higher L-ornithine, proline and L-ornithine/L-citrulline levels, and was found to have higher L-arginine availability compared with white race. With respect to asthma outcomes, increasing L-citrulline was associated with improved asthma control and increasing L-arginine and L-arginine/ADMA were associated with improved quality of life. Increased variability in L-arginine, L-arginine/ADMA, L-arginine/L-ornithine and L-arginine availability index over 12 months were associated with increased exacerbations, OR 4.70 (95% CI 1.35 to 16.37), OR 8.69 (95% CI 1.98 to 38.08), OR 4.17 (95% CI 1.40 to 12.41) and OR 4.95 (95% CI 1.42 to 17.16), respectively. CONCLUSIONS: Our findings suggest that L-arginine metabolism is associated with multiple measures of asthma control and may explain, in part, the relationship between age, race/ethnicity and obesity with asthma outcomes. BMJ Publishing Group 2023-06-02 /pmc/articles/PMC10254613/ /pubmed/37270184 http://dx.doi.org/10.1136/bmjresp-2023-001683 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Asthma Althoff, Meghan Dolan Peterson, Ryan McGrath, Max Jin, Ying Grasemann, Hartmut Sharma, Sunita Federman, Alex Wisnivesky, Juan Pablo Holguin, Fernando Phenotypic characteristics of asthma and morbidity are associated with distinct longitudinal changes in L-arginine metabolism |
title | Phenotypic characteristics of asthma and morbidity are associated with distinct longitudinal changes in L-arginine metabolism |
title_full | Phenotypic characteristics of asthma and morbidity are associated with distinct longitudinal changes in L-arginine metabolism |
title_fullStr | Phenotypic characteristics of asthma and morbidity are associated with distinct longitudinal changes in L-arginine metabolism |
title_full_unstemmed | Phenotypic characteristics of asthma and morbidity are associated with distinct longitudinal changes in L-arginine metabolism |
title_short | Phenotypic characteristics of asthma and morbidity are associated with distinct longitudinal changes in L-arginine metabolism |
title_sort | phenotypic characteristics of asthma and morbidity are associated with distinct longitudinal changes in l-arginine metabolism |
topic | Asthma |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254613/ https://www.ncbi.nlm.nih.gov/pubmed/37270184 http://dx.doi.org/10.1136/bmjresp-2023-001683 |
work_keys_str_mv | AT althoffmeghandolan phenotypiccharacteristicsofasthmaandmorbidityareassociatedwithdistinctlongitudinalchangesinlargininemetabolism AT petersonryan phenotypiccharacteristicsofasthmaandmorbidityareassociatedwithdistinctlongitudinalchangesinlargininemetabolism AT mcgrathmax phenotypiccharacteristicsofasthmaandmorbidityareassociatedwithdistinctlongitudinalchangesinlargininemetabolism AT jinying phenotypiccharacteristicsofasthmaandmorbidityareassociatedwithdistinctlongitudinalchangesinlargininemetabolism AT grasemannhartmut phenotypiccharacteristicsofasthmaandmorbidityareassociatedwithdistinctlongitudinalchangesinlargininemetabolism AT sharmasunita phenotypiccharacteristicsofasthmaandmorbidityareassociatedwithdistinctlongitudinalchangesinlargininemetabolism AT federmanalex phenotypiccharacteristicsofasthmaandmorbidityareassociatedwithdistinctlongitudinalchangesinlargininemetabolism AT wisniveskyjuanpablo phenotypiccharacteristicsofasthmaandmorbidityareassociatedwithdistinctlongitudinalchangesinlargininemetabolism AT holguinfernando phenotypiccharacteristicsofasthmaandmorbidityareassociatedwithdistinctlongitudinalchangesinlargininemetabolism |