Skip to main content
Top
Published in: Respiratory Research 1/2019

Open Access 01-12-2019 | Expectoration | Letter to the Editor

Systemic inflammatory response to inhaled endotoxin does not correlate with airway response

Authors: Amika K. Sood, Allison J. Burbank, Michael Lawson, Haibo Zhou, Heather B. Wells, David B. Peden, Michelle L. Hernandez

Published in: Respiratory Research | Issue 1/2019

Login to get access

Abstract

Background

Endotoxin is a component of particulate matter linked to respiratory disease. Our group has shown that experimental endotoxin inhalation challenge reproducibly triggers neutrophilic inflammation in the airways and in peripheral blood. Sputum induction is currently the only available method for assessing airway neutrophilia but is laborious and time-consuming. This analysis examined the correlation between systemic and airway inflammatory responses to endotoxin to determine if peripheral blood could serve as a surrogate marker for neutrophilic airway inflammation.

Methods

We conducted a retrospective study of 124 inhaled endotoxin challenges conducted at our center using 20,000 endotoxin units (EU) of Clinical Center Reference Endotoxin (CCRE). Venipuncture and induced sputum samples were obtained at baseline and 6 hours after completion of endotoxin challenge. The relationship between change in sputum neutrophils (post-challenge – baseline) and change in peripheral blood neutrophils (post-challenge – baseline) was assessed using Spearman’s correlation analyses.

Results

Inhaled endotoxin induced a significant increase in mean sputum percent neutrophils and peripheral blood absolute neutrophil counts in healthy adults with or without mild asthma, but no significant correlation was found between airway and systemic neutrophilia (r = 0.13, p = 0.18). Stratification by degree of airway neutrophil response and by atopic or asthmatic status did not change the results.

Conclusions

Inhalation challenge with endotoxin safely and effectively induces airway neutrophilic inflammation in most individuals. Increases in endotoxin-induced peripheral blood neutrophils do not correlate well with airway responses and should not be used as a surrogate marker of airway inflammation.
Literature
1.
go back to reference Zielen S, Trischler J, Schubert R. Lipopolysaccharide challenge: immunological effects and safety in humans. Expert Rev Clin Immunol. 2015;11(3):409–18.PubMedCrossRef Zielen S, Trischler J, Schubert R. Lipopolysaccharide challenge: immunological effects and safety in humans. Expert Rev Clin Immunol. 2015;11(3):409–18.PubMedCrossRef
2.
go back to reference Thorne PS, Mendy A, Metwali N, Salo P, Co C, Jaramillo R, et al. Endotoxin exposure: predictors and prevalence of associated asthma outcomes in the United States. Am J Respir Crit Care Med. 2015;192(11):1287–97.PubMedPubMedCentralCrossRef Thorne PS, Mendy A, Metwali N, Salo P, Co C, Jaramillo R, et al. Endotoxin exposure: predictors and prevalence of associated asthma outcomes in the United States. Am J Respir Crit Care Med. 2015;192(11):1287–97.PubMedPubMedCentralCrossRef
3.
go back to reference Dillon MA, Harris B, Hernandez ML, Zou B, Reed W, Bromberg PA, et al. Enhancement of systemic and sputum granulocyte response to inhaled endotoxin in people with the GSTM1 null genotype. Occup Environ Med. 2011;68(10):783–5.PubMedCrossRef Dillon MA, Harris B, Hernandez ML, Zou B, Reed W, Bromberg PA, et al. Enhancement of systemic and sputum granulocyte response to inhaled endotoxin in people with the GSTM1 null genotype. Occup Environ Med. 2011;68(10):783–5.PubMedCrossRef
4.
go back to reference Kobernick AK, Peden DB, Zhou H, Zhou Q, Dillon MA, Alexis NE. Reproducibility of the inflammatory response to inhaled endotoxin in healthy volunteers. J Allergy Clin Immunol. 2016;138(4):1205–7.PubMedPubMedCentralCrossRef Kobernick AK, Peden DB, Zhou H, Zhou Q, Dillon MA, Alexis NE. Reproducibility of the inflammatory response to inhaled endotoxin in healthy volunteers. J Allergy Clin Immunol. 2016;138(4):1205–7.PubMedPubMedCentralCrossRef
5.
go back to reference Janssen O, Schaumann F, Holz O, Lavae-Mokhtari B, Welker L, Winkler C, et al. Low-dose endotoxin inhalation in healthy volunteers--a challenge model for early clinical drug development. BMC Pulm Med. 2013;13:19.PubMedPubMedCentralCrossRef Janssen O, Schaumann F, Holz O, Lavae-Mokhtari B, Welker L, Winkler C, et al. Low-dose endotoxin inhalation in healthy volunteers--a challenge model for early clinical drug development. BMC Pulm Med. 2013;13:19.PubMedPubMedCentralCrossRef
6.
go back to reference Alexis NE, Lay JC, Zhou H, Kim CS, Hernandez ML, Kehrl H, et al. The glutathione-S-transferase mu 1 (GSTM1) null genotype and increased neutrophil response to low-level ozone (0.06 ppm). J Allergy Clin Immunol. 2013;131(2):610–2.PubMedCrossRef Alexis NE, Lay JC, Zhou H, Kim CS, Hernandez ML, Kehrl H, et al. The glutathione-S-transferase mu 1 (GSTM1) null genotype and increased neutrophil response to low-level ozone (0.06 ppm). J Allergy Clin Immunol. 2013;131(2):610–2.PubMedCrossRef
7.
go back to reference Korevaar DA, Westerhof GA, Wang J, Cohen JF, Spijker R, Sterk PJ, et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. Lancet Respir Med. 2015;3(4):290–300.PubMedCrossRef Korevaar DA, Westerhof GA, Wang J, Cohen JF, Spijker R, Sterk PJ, et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. Lancet Respir Med. 2015;3(4):290–300.PubMedCrossRef
8.
go back to reference Esther CR Jr, Olsen BM, Lin FC, Fine J, Boucher RC. Exhaled breath condensate adenosine tracks lung function changes in cystic fibrosis. Am J Physiol Lung Cell Mol Physiol. 2013;304(7):L504–9.PubMedPubMedCentralCrossRef Esther CR Jr, Olsen BM, Lin FC, Fine J, Boucher RC. Exhaled breath condensate adenosine tracks lung function changes in cystic fibrosis. Am J Physiol Lung Cell Mol Physiol. 2013;304(7):L504–9.PubMedPubMedCentralCrossRef
Metadata
Title
Systemic inflammatory response to inhaled endotoxin does not correlate with airway response
Authors
Amika K. Sood
Allison J. Burbank
Michael Lawson
Haibo Zhou
Heather B. Wells
David B. Peden
Michelle L. Hernandez
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2019
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-019-1227-3

Other articles of this Issue 1/2019

Respiratory Research 1/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine