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Upper Airway Mucosal Inflammation: Proteomic Studies after Exposure to Irritants and Microbial Agents
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

People are, in their daily lives, exposed to a number of airborne foreign compounds that do not normally affect the body. However, depending on the nature of these compounds, dose and duration of exposure, various airway symptoms may arise. Early symptoms are often manifested as upper airway mucosal inflammation which generates changes in protein composition in the airway lining fluid.

This thesis aims at identifying, understanding mechanisms and characterizing protein alterations in the upper airway mucosa that can be used as potential new biomarkers for inflammation in the mucosa. The protein composition in the mucosa was studied by sampling of nasal lavage fluid that was further analyzed with a proteomic approach using twodimensional gel electrophoresis and mass spectrometry. Additionally, by studying factors on site through environmental examination, health questionnaires and biological analyses, we have tried to understand the background to these protein alterations and their impact on health.

Respiratory symptoms from the upper airways are common among people who are exposed to irritative and microbial agents. This thesis have focused on personnel in swimming pool facilities exposed to trichloramine, metal industry workers exposed to metalworking fluids, employees working in damp and moldy buildings and infants diagnosed with respiratory syncytial virus infection. The common denominator in these four studies is that the subjects experience upper airway mucosal inflammation, which is manifested as cough, rhinitis, phlegm etc. In the three occupational studies, the symptoms were work related. Notably, a high prevalence of perceived mucosal symptoms was shown despite the relatively low levels of airborne irritants revealed by the environmental examination. Protein profiling verified an ongoing inflammatory response by identification of several proteins that displayed altered levels. Interestingly, innate immune proteins dominated and four protein alterations occurred in most of the studies; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin. Similarly, these proteins were also found in nasal fluid from children with virus infection and in addition a truncated form of SPLUNC1 and two other S100 proteins (S100A7-like 2 and S100A16), not previously found in nasal secretion, were identified.

Altogether, the results indicate the potential use of a proteomic approach for identifying new biomarkers for the upper respiratory tract at an early stage in the disease process after exposure to irritant and microbial agents. The results indicate an effect on the innate immunity system and the proteins; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin are especially promising new biomarkers. Moreover, further studies of these proteins may help us to understand the molecular mechanisms involved in irritant-induced airway inflammation.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. , 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1453
National Category
Environmental Health and Occupational Health Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-117343DOI: 10.3384/diss.diva-117343ISBN: 978-91-7519-129-4 (print)OAI: oai:DiVA.org:liu-117343DiVA: diva2:807423
Public defence
2015-05-21, Hälsans hus, Campus US, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-04-23 Created: 2015-04-23 Last updated: 2015-04-23Bibliographically approved
List of papers
1. Innate immunity proteins and a new truncated form of SPLUNC1 in nasopharyngeal aspirates from infants with respiratory syncytial virus infection
Open this publication in new window or tab >>Innate immunity proteins and a new truncated form of SPLUNC1 in nasopharyngeal aspirates from infants with respiratory syncytial virus infection
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2011 (English)In: PROTEOMICS CLINICAL APPLICATIONS, ISSN 1862-8346, Vol. 5, no 9-10, 513-522 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: Respiratory syncytial virus (RSV) is the most common cause of severe respiratory tract infection in infants. The aim was to identify host defence components in nasopharyngeal aspirate (NPA) from infants with RSV infection and to study the expression of the novel 25 kDa innate immunity protein SPLUNC1. less thanbrgreater than less thanbrgreater thanExperimental design: NPAs from infants were analyzed with 2-DE and MS in a pilot study. The levels of SPLUNC1 were analyzed with immunoblotting in 47 NPAs, admitted for RSV diagnosis. less thanbrgreater than less thanbrgreater thanResults: Totally, 35 proteins were identified in NPA, including several innate immunity proteins such as group X phospholipase A(2), different S100 proteins and SPLUNC1. In addition, a new truncated 15 kDa form of SPLUNC1 was identified that was detected in about 50% of the aspirates admitted for RSV diagnosis. RSV-positive boys had significantly less 25 kDa SPLUNC1 than RSV-negative boys while there were no significant differences among girls. less thanbrgreater than less thanbrgreater thanConclusions and clinical relevance: Several important innate immunity proteins were identified in NPA. Notably, a new truncated form of the newly suggested anti-bacterial protein SPLUNC1 was found. It is possible that a decrease in SPLUNC1 in the upper airways may increase the risk for severe pneumonia in boys.

Place, publisher, year, edition, pages
Wiley-VCH Verlag Berlin, 2011
Keyword
MS, Nasopharynx, PLUNC, Respiratory syncytial virus, Two-dimensional gel electrophoresis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-72142 (URN)10.1002/prca.201100016 (DOI)000296418400005 ()
Note
Funding Agencies|The Research Council of South East Sweden|FORSS-36761- 8505|Available from: 2011-11-18 Created: 2011-11-18 Last updated: 2015-04-23
2. Airway irritation among indoor swimming pool personnel: trichloramine exposure, exhaled NO and protein profiling of nasal lavage fluids
Open this publication in new window or tab >>Airway irritation among indoor swimming pool personnel: trichloramine exposure, exhaled NO and protein profiling of nasal lavage fluids
2013 (English)In: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 86, no 5, 571-580 p.Article in journal (Refereed) Published
Abstract [en]

Purpose

Occurrence of airway irritation among indoor swimming pool personnel was investigated. The aims of this study were to assess trichloramine exposure levels and exhaled nitric oxide in relation to the prevalence of airway symptoms in swimming pool facilities and to determine protein effects in the upper respiratory tract.

Methods

The presence of airway symptoms related to work was examined in 146 individuals working at 46 indoor swimming pool facilities. Levels of trichloramine, as well as exhaled nitric oxide, were measured in five facilities with high prevalence of airway irritation and four facilities with no airway irritation among the personnel. Nasal lavage fluid was collected, and protein profiles were determined by a proteomic approach.

Results

17 % of the swimming pool personnel reported airway symptoms related to work. The levels of trichloramine in the swimming pool facilities ranged from 0.04 to 0.36 mg/m3. There was no covariance between trichloramine levels, exhaled nitric oxide and prevalence of airway symptoms. Protein profiling of the nasal lavage fluid showed that the levels alpha-1-antitrypsin and lactoferrin were significantly higher, and S100-A8 was significantly lower in swimming pool personnel.

Conclusions

This study confirms the occurrence of airway irritation among indoor swimming pool personnel. Our results indicate altered levels of innate immunity proteins in the upper airways that may pose as potential biomarkers. However, swimming pool facilities with high prevalence of airway irritation could not be explained by higher trichloramine exposure levels. Further studies are needed to clarify the environmental factors in indoor swimming pools that cause airway problems and affect the immune system.

Place, publisher, year, edition, pages
Springer, 2013
Keyword
Innate immunity, Occupational medicine, roteomics, Upper respiratory tract
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-86713 (URN)10.1007/s00420-012-0790-4 (DOI)000320394300008 ()22729567 (PubMedID)
Available from: 2012-12-25 Created: 2012-12-25 Last updated: 2017-12-06Bibliographically approved
3. Airway symptoms and biological markers in nasal lavage fluid in subjects exposed to metalworking fluids
Open this publication in new window or tab >>Airway symptoms and biological markers in nasal lavage fluid in subjects exposed to metalworking fluids
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, e83089- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUNDS: Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in nasal mucous membranes, and evaluate preventive actions.

METHODS: The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach.

RESULTS: Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and β2-microglobulin among workers with airway symptoms.

CONCLUSIONS: This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted.

Place, publisher, year, edition, pages
Public Library of Science, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103739 (URN)10.1371/journal.pone.0083089 (DOI)000329325200035 ()24391738 (PubMedID)
Available from: 2014-01-24 Created: 2014-01-24 Last updated: 2017-12-06Bibliographically approved
4. Protein profiles of nasal lavage fluid from individuals with work-related upper airway symptoms associated to moldy and damp buildings
Open this publication in new window or tab >>Protein profiles of nasal lavage fluid from individuals with work-related upper airway symptoms associated to moldy and damp buildings
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2016 (English)In: Indoor Air, ISSN 0905-6947, E-ISSN 1600-0668, Vol. 26, no 5, 743-754 p.Article in journal (Refereed) Published
Abstract [en]

Upper airway irritation is common among individuals working in moldy and damp buildings. The aim was to investigate effects on the protein composition of the nasal lining fluid. The prevalence of symptoms in relation to work was examined in 37 individuals working in two damp buildings. Microbial growth was confirmed in one of the buildings. Nasal lavage fluid was collected from 29 exposed subjects and 13 controls. Protein profiles were investigated with a proteomic approach and evaluated by multivariate statistical models. Subjects from both workplaces reported upper airway and ocular symptoms. Based on protein profiles, symptomatic subjects in the two workplaces were discriminated from each other and separated from healthy controls. The groups differed in proteins involved in inflammation and host defense. Measurements of innate immunity proteins showed a significant increa e of protein S100-A8 and decrease of SPLUNC1 in subjects from one workplace while alpha-1-antitrypsin was elevated in subjects from the other workplace, compared to healthy controls. The results show that protein profiles in nasal lavage fluid can be used to monitor airway mucosal effects in personnel working in damp buildings and indicate that the profile may be separate when the dampness is associated with the presence of molds.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keyword
Sick building syndrome, proteomics, nasal mucosa, SPLUNC1, alpha-1-antitrypsin, protein S100-A8
National Category
Environmental Health and Occupational Health Infectious Medicine
Identifiers
urn:nbn:se:liu:diva-117339 (URN)10.1111/ina.12257 (DOI)000387348500009 ()
Note

Funding agencies: Research Council of South East Sweden [FORSS-222751, FORSS-389061]; Cancer and Allergy Foundation [150441]

Available from: 2015-04-23 Created: 2015-04-23 Last updated: 2017-05-02Bibliographically approved

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