Epigenetic changes and immunological features of chronic obstructive pulmonary disease
Background: Chronic obstructive pulmonary disease (COPD) is a heterogenous and chronic inflammatory syndrome with the lungs as its main target organ. Clinically, COPD is characterized by airflow limitation, chronic respiratory symptoms, and many extrapulmonary comorbidities. Tobacco smoke is the mai...
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Umeå universitet, Avdelningen för medicin
2023
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ftumeauniv:oai:DiVA.org:umu-201985 2023-10-09T21:54:38+02:00 Epigenetic changes and immunological features of chronic obstructive pulmonary disease Epigenetiska och immunologiska förändringar vid kroniskt obstruktiv lungsjukdom Eriksson Ström, Jonas 2023 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-201985 eng eng Umeå universitet, Avdelningen för medicin Umeå : Umeå University Umeå University medical dissertations, 0346-6612 2214 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-201985 urn:isbn:978-91-7855-946-6 urn:isbn:978-91-7855-947-3 info:eu-repo/semantics/openAccess COPD immunology epigenetics KOLIN Immunology in the medical area Immunologi inom det medicinska området Respiratory Medicine and Allergy Lungmedicin och allergi Medical Genetics Medicinsk genetik Doctoral thesis, comprehensive summary info:eu-repo/semantics/doctoralThesis text 2023 ftumeauniv 2023-09-22T13:56:38Z Background: Chronic obstructive pulmonary disease (COPD) is a heterogenous and chronic inflammatory syndrome with the lungs as its main target organ. Clinically, COPD is characterized by airflow limitation, chronic respiratory symptoms, and many extrapulmonary comorbidities. Tobacco smoke is the main environmental risk factor, but pollutants and smoke from biomass fuel are also major contributors. Why some, but not all, smokers develop the disease is a key but largely unresolved research question. Genetic factors seem to explain 40—60% of COPD susceptibility, but what additional role epigenetic factors such as DNA methylation might play has not been thoroughly investigated. Immune cells are of vital importance in the COPD pathogenesis. Among airway lymphocytes, cytotoxic CD8+ T cells are the ones most often found to be involved in the disease, but other lymphocyte populations are not as well studied. Among patients with manifest COPD, the rate of decline in lung function differs widely. Smoking cessation decreases the rate, but beyond that, it is not well understood why some patients experience a more rapid and some a much slower disease progression. Rapid decline is associated with a poor prognosis and has been recognized as a separate phenotype of COPD. Aim: The overall aim of this thesis was to examine the immunologic and epigenetic features of COPD with a focus on the rapid decline phenotype, using flow cytometry and measurement of DNA methylation in cells from bronchoalveolar lavage (BAL) fluid together with clinical characteristics such as rate of decline in lung function, use of inhaled corticosteroids and smoking status. The studies included in this thesis were all part of the Respiratory and Cardiovascular Effects in COPD (“KOLIN”) study. Methods: The study population was the same for all studies in this thesis. Subjects were recruited from the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study according to predetermined criteria. OLIN COPD also provided the longitudinal data needed for ... Doctoral or Postdoctoral Thesis Northern Sweden Umeå University: Publications (DiVA) |
institution |
Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
COPD immunology epigenetics KOLIN Immunology in the medical area Immunologi inom det medicinska området Respiratory Medicine and Allergy Lungmedicin och allergi Medical Genetics Medicinsk genetik |
spellingShingle |
COPD immunology epigenetics KOLIN Immunology in the medical area Immunologi inom det medicinska området Respiratory Medicine and Allergy Lungmedicin och allergi Medical Genetics Medicinsk genetik Eriksson Ström, Jonas Epigenetic changes and immunological features of chronic obstructive pulmonary disease |
topic_facet |
COPD immunology epigenetics KOLIN Immunology in the medical area Immunologi inom det medicinska området Respiratory Medicine and Allergy Lungmedicin och allergi Medical Genetics Medicinsk genetik |
description |
Background: Chronic obstructive pulmonary disease (COPD) is a heterogenous and chronic inflammatory syndrome with the lungs as its main target organ. Clinically, COPD is characterized by airflow limitation, chronic respiratory symptoms, and many extrapulmonary comorbidities. Tobacco smoke is the main environmental risk factor, but pollutants and smoke from biomass fuel are also major contributors. Why some, but not all, smokers develop the disease is a key but largely unresolved research question. Genetic factors seem to explain 40—60% of COPD susceptibility, but what additional role epigenetic factors such as DNA methylation might play has not been thoroughly investigated. Immune cells are of vital importance in the COPD pathogenesis. Among airway lymphocytes, cytotoxic CD8+ T cells are the ones most often found to be involved in the disease, but other lymphocyte populations are not as well studied. Among patients with manifest COPD, the rate of decline in lung function differs widely. Smoking cessation decreases the rate, but beyond that, it is not well understood why some patients experience a more rapid and some a much slower disease progression. Rapid decline is associated with a poor prognosis and has been recognized as a separate phenotype of COPD. Aim: The overall aim of this thesis was to examine the immunologic and epigenetic features of COPD with a focus on the rapid decline phenotype, using flow cytometry and measurement of DNA methylation in cells from bronchoalveolar lavage (BAL) fluid together with clinical characteristics such as rate of decline in lung function, use of inhaled corticosteroids and smoking status. The studies included in this thesis were all part of the Respiratory and Cardiovascular Effects in COPD (“KOLIN”) study. Methods: The study population was the same for all studies in this thesis. Subjects were recruited from the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study according to predetermined criteria. OLIN COPD also provided the longitudinal data needed for ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Eriksson Ström, Jonas |
author_facet |
Eriksson Ström, Jonas |
author_sort |
Eriksson Ström, Jonas |
title |
Epigenetic changes and immunological features of chronic obstructive pulmonary disease |
title_short |
Epigenetic changes and immunological features of chronic obstructive pulmonary disease |
title_full |
Epigenetic changes and immunological features of chronic obstructive pulmonary disease |
title_fullStr |
Epigenetic changes and immunological features of chronic obstructive pulmonary disease |
title_full_unstemmed |
Epigenetic changes and immunological features of chronic obstructive pulmonary disease |
title_sort |
epigenetic changes and immunological features of chronic obstructive pulmonary disease |
publisher |
Umeå universitet, Avdelningen för medicin |
publishDate |
2023 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-201985 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Umeå University medical dissertations, 0346-6612 2214 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-201985 urn:isbn:978-91-7855-946-6 urn:isbn:978-91-7855-947-3 |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1779318297243680768 |