Cargando…
The Complex Relationship Between Inflammation And Lung Function In Severe Asthma
Asthma is a common respiratory disease affecting approximately 300 million people worldwide. Airway inflammation is thought to contribute to asthma pathogenesis, but the direct relationship between inflammation and airway hyperresponsiveness remains unclear. This study investigates the role of infla...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138304/ https://www.ncbi.nlm.nih.gov/pubmed/24549277 http://dx.doi.org/10.1038/mi.2014.8 |
_version_ | 1782331215471181824 |
---|---|
author | Manni, Michelle L. Trudeau, John B. Scheller, Erich V. Mandalapu, Sivanarayana Elloso, M. Merle Kolls, Jay K. Wenzel, Sally E. Alcorn, John F. |
author_facet | Manni, Michelle L. Trudeau, John B. Scheller, Erich V. Mandalapu, Sivanarayana Elloso, M. Merle Kolls, Jay K. Wenzel, Sally E. Alcorn, John F. |
author_sort | Manni, Michelle L. |
collection | PubMed |
description | Asthma is a common respiratory disease affecting approximately 300 million people worldwide. Airway inflammation is thought to contribute to asthma pathogenesis, but the direct relationship between inflammation and airway hyperresponsiveness remains unclear. This study investigates the role of inflammation in a steroid-insensitive, severe allergic airway disease model and in severe asthmatics stratified by inflammatory profile. First, we utilized the T(H)17 cell adoptive transfer mouse model of asthma to induce pulmonary inflammation, which was lessened by TNFα neutralization or neutrophil depletion. While decreased airspace inflammation following TNFα neutralization and neutrophil depletion rescued lung compliance, neither intervention improved airway hyperresponsiveness to methacholine, and tissue inflammation remained elevated when compared to control. Further, sputum samples were collected and analyzed from 41 severe asthmatics. In severe asthmatics with elevated levels of sputum neutrophils, but low levels of eosinophils, increased inflammatory markers did not correlate with worsened lung function. This subset of asthmatics also had significantly higher levels of T(H)17-related cytokines in their sputum compared to other severe asthmatics with other inflammatory phenotypes. Overall, this work suggests that lung compliance may be linked with cellular inflammation in the airspace, while T cell-driven airway hyperresponsiveness may be associated with tissue inflammation and other pulmonary factors. |
format | Online Article Text |
id | pubmed-4138304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-41383042015-03-01 The Complex Relationship Between Inflammation And Lung Function In Severe Asthma Manni, Michelle L. Trudeau, John B. Scheller, Erich V. Mandalapu, Sivanarayana Elloso, M. Merle Kolls, Jay K. Wenzel, Sally E. Alcorn, John F. Mucosal Immunol Article Asthma is a common respiratory disease affecting approximately 300 million people worldwide. Airway inflammation is thought to contribute to asthma pathogenesis, but the direct relationship between inflammation and airway hyperresponsiveness remains unclear. This study investigates the role of inflammation in a steroid-insensitive, severe allergic airway disease model and in severe asthmatics stratified by inflammatory profile. First, we utilized the T(H)17 cell adoptive transfer mouse model of asthma to induce pulmonary inflammation, which was lessened by TNFα neutralization or neutrophil depletion. While decreased airspace inflammation following TNFα neutralization and neutrophil depletion rescued lung compliance, neither intervention improved airway hyperresponsiveness to methacholine, and tissue inflammation remained elevated when compared to control. Further, sputum samples were collected and analyzed from 41 severe asthmatics. In severe asthmatics with elevated levels of sputum neutrophils, but low levels of eosinophils, increased inflammatory markers did not correlate with worsened lung function. This subset of asthmatics also had significantly higher levels of T(H)17-related cytokines in their sputum compared to other severe asthmatics with other inflammatory phenotypes. Overall, this work suggests that lung compliance may be linked with cellular inflammation in the airspace, while T cell-driven airway hyperresponsiveness may be associated with tissue inflammation and other pulmonary factors. 2014-02-19 2014-09 /pmc/articles/PMC4138304/ /pubmed/24549277 http://dx.doi.org/10.1038/mi.2014.8 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Manni, Michelle L. Trudeau, John B. Scheller, Erich V. Mandalapu, Sivanarayana Elloso, M. Merle Kolls, Jay K. Wenzel, Sally E. Alcorn, John F. The Complex Relationship Between Inflammation And Lung Function In Severe Asthma |
title | The Complex Relationship Between Inflammation And Lung Function In Severe Asthma |
title_full | The Complex Relationship Between Inflammation And Lung Function In Severe Asthma |
title_fullStr | The Complex Relationship Between Inflammation And Lung Function In Severe Asthma |
title_full_unstemmed | The Complex Relationship Between Inflammation And Lung Function In Severe Asthma |
title_short | The Complex Relationship Between Inflammation And Lung Function In Severe Asthma |
title_sort | complex relationship between inflammation and lung function in severe asthma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138304/ https://www.ncbi.nlm.nih.gov/pubmed/24549277 http://dx.doi.org/10.1038/mi.2014.8 |
work_keys_str_mv | AT mannimichellel thecomplexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT trudeaujohnb thecomplexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT schellererichv thecomplexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT mandalapusivanarayana thecomplexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT ellosommerle thecomplexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT kollsjayk thecomplexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT wenzelsallye thecomplexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT alcornjohnf thecomplexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT mannimichellel complexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT trudeaujohnb complexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT schellererichv complexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT mandalapusivanarayana complexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT ellosommerle complexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT kollsjayk complexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT wenzelsallye complexrelationshipbetweeninflammationandlungfunctioninsevereasthma AT alcornjohnf complexrelationshipbetweeninflammationandlungfunctioninsevereasthma |