Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells?
BACKGROUND:Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath. METHODS:Thirty-seven smokers undergoing lung resection for primary lung cancer...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4466526?pdf=render |
_version_ | 1811243377887281152 |
---|---|
author | Yvonne Nussbaumer-Ochsner Jan Stolk Luiz F Ferraz da Silva Annemarie van Schadewijk Ronald C de Jeu Frans A Prins Thais Mauad Klaus F Rabe Pieter S Hiemstra |
author_facet | Yvonne Nussbaumer-Ochsner Jan Stolk Luiz F Ferraz da Silva Annemarie van Schadewijk Ronald C de Jeu Frans A Prins Thais Mauad Klaus F Rabe Pieter S Hiemstra |
author_sort | Yvonne Nussbaumer-Ochsner |
collection | DOAJ |
description | BACKGROUND:Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath. METHODS:Thirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test), measurement of fractional exhaled nitric oxide (FeNO) and pH/8-isoprostane in exhaled breath condensate (EBC). Lung tissue sections containing cancer-free large (LA) and small airways (SA) were stained for inflammatory cells. Mucosal (MCT) respectively connective tissue mast cells (MCTC) and interleukin-17A (IL-17A) expression by mast cells was analysed using a double-staining protocol. RESULTS:The median number of neutrophils, macrophages and mast cells infiltrating the lamina propria and adventitia of SA was higher than in LA. Both MCTC and MCT were higher in the lamina propria of SA compared to LA (MCTC: 49 vs. 27.4 cells/mm2; MCT: 162.5 vs. 35.4 cells/mm2; P<0.005 for both instances). IL-17A expression was predominantly detected in MCTC of LA. Significant correlations were found for the slope of phase III % pred. of the sb-N2-test (rs= -0.39), for the FEV1% pred. (rs= 0.37) and for FEV1/FVC ratio (rs=0.38) with MCT in SA (P<0.05 for all instances). 8-isoprostane concentration correlated with the mast cells in the SA (rs=0.44), there was no correlation for pH or FeNO with cellular distribution in SA. CONCLUSIONS:Neutrophils, macrophages and mast cells are more prominent in the SA indicating that these cells are involved in the development of small airway dysfunction in smokers. Among these cell types, the best correlation was found for mast cells with lung function parameters and inflammatory markers in exhaled breath. Furthermore, the observed predominant expression of IL-17A in mast cells warrants further investigation to elucidate their role in smoking-induced lung injury, despite the lack of correlation with lung function and exhaled breath parameters. |
first_indexed | 2024-04-12T14:06:24Z |
format | Article |
id | doaj.art-64b26d2871b14713bfee5f0f763fe6b6 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-12T14:06:24Z |
publishDate | 2015-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-64b26d2871b14713bfee5f0f763fe6b62022-12-22T03:30:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e012942610.1371/journal.pone.0129426Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells?Yvonne Nussbaumer-OchsnerJan StolkLuiz F Ferraz da SilvaAnnemarie van SchadewijkRonald C de JeuFrans A PrinsThais MauadKlaus F RabePieter S HiemstraBACKGROUND:Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath. METHODS:Thirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test), measurement of fractional exhaled nitric oxide (FeNO) and pH/8-isoprostane in exhaled breath condensate (EBC). Lung tissue sections containing cancer-free large (LA) and small airways (SA) were stained for inflammatory cells. Mucosal (MCT) respectively connective tissue mast cells (MCTC) and interleukin-17A (IL-17A) expression by mast cells was analysed using a double-staining protocol. RESULTS:The median number of neutrophils, macrophages and mast cells infiltrating the lamina propria and adventitia of SA was higher than in LA. Both MCTC and MCT were higher in the lamina propria of SA compared to LA (MCTC: 49 vs. 27.4 cells/mm2; MCT: 162.5 vs. 35.4 cells/mm2; P<0.005 for both instances). IL-17A expression was predominantly detected in MCTC of LA. Significant correlations were found for the slope of phase III % pred. of the sb-N2-test (rs= -0.39), for the FEV1% pred. (rs= 0.37) and for FEV1/FVC ratio (rs=0.38) with MCT in SA (P<0.05 for all instances). 8-isoprostane concentration correlated with the mast cells in the SA (rs=0.44), there was no correlation for pH or FeNO with cellular distribution in SA. CONCLUSIONS:Neutrophils, macrophages and mast cells are more prominent in the SA indicating that these cells are involved in the development of small airway dysfunction in smokers. Among these cell types, the best correlation was found for mast cells with lung function parameters and inflammatory markers in exhaled breath. Furthermore, the observed predominant expression of IL-17A in mast cells warrants further investigation to elucidate their role in smoking-induced lung injury, despite the lack of correlation with lung function and exhaled breath parameters.http://europepmc.org/articles/PMC4466526?pdf=render |
spellingShingle | Yvonne Nussbaumer-Ochsner Jan Stolk Luiz F Ferraz da Silva Annemarie van Schadewijk Ronald C de Jeu Frans A Prins Thais Mauad Klaus F Rabe Pieter S Hiemstra Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells? PLoS ONE |
title | Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells? |
title_full | Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells? |
title_fullStr | Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells? |
title_full_unstemmed | Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells? |
title_short | Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells? |
title_sort | association of lung inflammatory cells with small airways function and exhaled breath markers in smokers is there a specific role for mast cells |
url | http://europepmc.org/articles/PMC4466526?pdf=render |
work_keys_str_mv | AT yvonnenussbaumerochsner associationoflunginflammatorycellswithsmallairwaysfunctionandexhaledbreathmarkersinsmokersisthereaspecificroleformastcells AT janstolk associationoflunginflammatorycellswithsmallairwaysfunctionandexhaledbreathmarkersinsmokersisthereaspecificroleformastcells AT luizfferrazdasilva associationoflunginflammatorycellswithsmallairwaysfunctionandexhaledbreathmarkersinsmokersisthereaspecificroleformastcells AT annemarievanschadewijk associationoflunginflammatorycellswithsmallairwaysfunctionandexhaledbreathmarkersinsmokersisthereaspecificroleformastcells AT ronaldcdejeu associationoflunginflammatorycellswithsmallairwaysfunctionandexhaledbreathmarkersinsmokersisthereaspecificroleformastcells AT fransaprins associationoflunginflammatorycellswithsmallairwaysfunctionandexhaledbreathmarkersinsmokersisthereaspecificroleformastcells AT thaismauad associationoflunginflammatorycellswithsmallairwaysfunctionandexhaledbreathmarkersinsmokersisthereaspecificroleformastcells AT klausfrabe associationoflunginflammatorycellswithsmallairwaysfunctionandexhaledbreathmarkersinsmokersisthereaspecificroleformastcells AT pietershiemstra associationoflunginflammatorycellswithsmallairwaysfunctionandexhaledbreathmarkersinsmokersisthereaspecificroleformastcells |