Morphological Characteristics of Chronic Obstructive Pulmonary Disease (COPD) Affected Lung Tissue

Research output: Types of ThesisDoctoral Thesis

Abstract

Chronic obstructive pulmonary disease (COPD) is a potentially preventable and treatable disease characterized by progressive airway disorders. Under the influence of various risk factors,
oxidative stress and chronic inflammation develop, which determines the formation and course of practically all other processes (for example, local fibrosis). Even with the maximal elimination of risk factors, inflammation in COPD persists and even continues. In general, COPD morphopathogenesis is characterized by oxidative stress, chronic inflammation, remodeling, as well as impaired antimicrobial and other locally realized tissue protective responses.
The aim of the study was to determine and evaluate the morphological characteristics of bronchial tissues affected by COPD and analyze the tissue distribution of markers relevant to
chronic inflammation, changes in tissue remodeling and local protective mechanisms. Also, these markers were evaluated in ontogenesis perspective.
The study included 40 COPD and 49 relatively healthy control patients. Tissue material from COPD patients was collected during bronchoscopy. Tissue material from the control group was obtained by autopsy from individuals of different ages who died of accidents and from diseases not affecting respiratory system, as well as from / or during lung surgery. IL-1α (interleukin-1 alpha), IL-4 (interleukin-4), IL-6 (interleukin-6), IL-7 (interleukin-7), IL-8 (interleukin-8), IL-10 (interleukin-10), IL-12 (interleukin-12), TNF-α (tumour necrosis factor-alpha), TGF-β1 (transforming growth factor-beta 1), MMP-2 (matrix metalloproteinase-2), TIMP-2 (matrix metalloproteinase-2 tissue inhibitor), Hsp-70 (heat shock protein-70), hBD-2 (human beta defensin-2), hBD-3 (human beta defensin-3), hBD-4 ( human beta defensin-4) immunoreactive cell counts were determined by immunohistochemistry in eight different tissue groups and lung
localizations in control and COPD patients, and also compared. The immunohistochemical findings were also analyzed in terms of ontogenesis or aging.
In the lung tissues of the control group, we found a mild to moderate increase in the number of immunoreactive cells of all studied factors at different localizations, indicating low, persistent, continuous and adaptive “baseline” level for various factors.
Lung tissue in COPD patients is characterized by variable and various localized changes with chronic inflammation and tissue remodeling including inflammatory cell infiltration, granulation tissue, thickened basement membrane, bronchial gland and smooth muscle hypeplasia and hypertrophy, also thickened vascular fibrosis, moreover, fibrosis and epithelial metaplasia.
The most pronounced finding of the studied tissue factors was in bronchial epithelium, mucosal connective tissue and blood vessels of COPD patients, which proves the significant involvement and role of these structures in COPD morphopathogenesis. Overall, COPD morphopathogenesis is characterized by increased IL-1α, IL-4, IL-6, IL-8, TNF-α, IL-7, IL-10, IL-12, TGF-β1, MMP-2, TIMP-2, hBD-2 and hBD-3 immunoreactive cell counts, as
well as reduced Hsp-70 and hBD-4-containing cell counts, indicating high activity of persistent complex cytokine pleiade, tissue remodeling and total tissue antimicrobial protection.
Ontogenesis dependent changes, including in terms of aging, within the lungs of relatively healthy individuals are associated with mild inflammation, aging of immune system cells and
disorder of immune system regulation. Age changes in the relatively healthy lungs are individual, even different for individuals in different age groups, as well as mostly
characterized by a lack to maintain inflammation, also, reduced number of immune cells are found.
In elderly COPD patients within ontogenesis, we detected an increase in the numbers of IL-1α, IL-4, IL-6, IL-10, IL-12, MMP-2, hBD-4 immunoreactive cells, but decreased numbers of
IL-7, IL-8, TNF-α, TIMP-2, TGF-β1, Hsp-70, hBD-2, hBD-3 immunoreactive cells with age, as well as chronic bronchitis, epithelial metaplasia, granulation tissue and poorer functional
parameters. In the case of COPD, aging is associated with the worsening of the disease, as well as persistence and altered remodeling of inflammatory cytokines otherwise characteristic of
COPD.
Translated title of the contributionMorphological Characteristics of Chronic Obstructive Pulmonary Disease (COPD) Affected Lung Tissue
Original languageLatvian
Supervisors/Advisors
  • Pilmane, Māra, First/Primary/Lead supervisor
  • Babjoniševa, Aurika, Consultant/Advisor
Place of PublicationRīga
Publisher
DOIs
Publication statusPublished - 2020

Keywords

  • histoloģija
  • citoloģija
  • hroniska obstruktīva plaušu slimība
  • plaušu audi

Field of Science

  • 3.1 Basic medicine

Publication Type

  • 4. Doctoral Thesis

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