Inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers
Abstract Particles in exhaled air (PEx) are generated when collapsed small airways reopen during breathing. PEx can be noninvasively collected by particle impaction, allowing the analysis of undiluted epithelial lining fluid (ELF). We used the endotoxin (LPS) challenge model to proof the concept tha...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-09399-z |
| _version_ | 1819045644107513856 |
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| author | Olaf Holz Meike Müller Saskia Carstensen Anna-Carin Olin Jens M. Hohlfeld |
| author_facet | Olaf Holz Meike Müller Saskia Carstensen Anna-Carin Olin Jens M. Hohlfeld |
| author_sort | Olaf Holz |
| collection | DOAJ |
| description | Abstract Particles in exhaled air (PEx) are generated when collapsed small airways reopen during breathing. PEx can be noninvasively collected by particle impaction, allowing the analysis of undiluted epithelial lining fluid (ELF). We used the endotoxin (LPS) challenge model to proof the concept that PEx can be used to monitor inflammatory changes in the lung. In this pilot study PEx were collected from ten healthy nonsmoking subjects using the PExA® instrument twice before and twice after a segmental LPS challenge (5, 21 h). Following a 4-week washout period, PEx were collected during the week before and 5 h after a whole lung LPS inhalation challenge. PEx biomarkers were compared to blood, bronchoalveolar lavage (BAL) following segmental challenge and induced sputum (ISP) following inhalation challenge. A clear LPS-induced inflammatory response was detectable in BAL fluid, ISP and blood. Albumin and surfactant–protein D were detectable in all PEx samples. While most baseline cytokines were close to or below the detection limit, the median (IQR) IL-6 and IL-8 concentrations in PEx increased significantly after segmental (0.04 (0.03; 0.06) fg/ng PEx; 0.10 (0.08; 0.17) fg/ng PEx) and inhalation LPS challenge (0.19 (0.15; 0.23) fg/ng PEx; 0.32 (0.23; 0.42) fg/ng PEx). Using a highly sensitive analysis platform, we were able to detect a cytokine response in PEx during the early phase of LPS-induced inflammation. This will broaden the spectrum of applications for this noninvasive method to monitor inflammatory processes in the lung, including its use in clinical trials for respiratory drug development. Trial registration: The study has been registered on 07.02.2017 at Clinicaltrials.gov (NCT03044327). |
| first_indexed | 2024-12-21T10:31:51Z |
| format | Article |
| id | doaj.art-b2bc9773bb434ad0964f4fca1ebda65e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-21T10:31:51Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b2bc9773bb434ad0964f4fca1ebda65e2022-12-21T19:07:10ZengNature PortfolioScientific Reports2045-23222022-04-011211810.1038/s41598-022-09399-zInflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteersOlaf Holz0Meike Müller1Saskia Carstensen2Anna-Carin Olin3Jens M. Hohlfeld4Department of Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine ITEMDepartment of Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine ITEMDepartment of Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine ITEMOccupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Gothenburg UniversityDepartment of Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine ITEMAbstract Particles in exhaled air (PEx) are generated when collapsed small airways reopen during breathing. PEx can be noninvasively collected by particle impaction, allowing the analysis of undiluted epithelial lining fluid (ELF). We used the endotoxin (LPS) challenge model to proof the concept that PEx can be used to monitor inflammatory changes in the lung. In this pilot study PEx were collected from ten healthy nonsmoking subjects using the PExA® instrument twice before and twice after a segmental LPS challenge (5, 21 h). Following a 4-week washout period, PEx were collected during the week before and 5 h after a whole lung LPS inhalation challenge. PEx biomarkers were compared to blood, bronchoalveolar lavage (BAL) following segmental challenge and induced sputum (ISP) following inhalation challenge. A clear LPS-induced inflammatory response was detectable in BAL fluid, ISP and blood. Albumin and surfactant–protein D were detectable in all PEx samples. While most baseline cytokines were close to or below the detection limit, the median (IQR) IL-6 and IL-8 concentrations in PEx increased significantly after segmental (0.04 (0.03; 0.06) fg/ng PEx; 0.10 (0.08; 0.17) fg/ng PEx) and inhalation LPS challenge (0.19 (0.15; 0.23) fg/ng PEx; 0.32 (0.23; 0.42) fg/ng PEx). Using a highly sensitive analysis platform, we were able to detect a cytokine response in PEx during the early phase of LPS-induced inflammation. This will broaden the spectrum of applications for this noninvasive method to monitor inflammatory processes in the lung, including its use in clinical trials for respiratory drug development. Trial registration: The study has been registered on 07.02.2017 at Clinicaltrials.gov (NCT03044327).https://doi.org/10.1038/s41598-022-09399-z |
| spellingShingle | Olaf Holz Meike Müller Saskia Carstensen Anna-Carin Olin Jens M. Hohlfeld Inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers Scientific Reports |
| title | Inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers |
| title_full | Inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers |
| title_fullStr | Inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers |
| title_full_unstemmed | Inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers |
| title_short | Inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers |
| title_sort | inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers |
| url | https://doi.org/10.1038/s41598-022-09399-z |
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