Inflammation, genotoxicity and cell proliferation and nasal epithelium of people exposed to urban pollution [Elektronische Ressource] / vorgelegt von Dünya Polat

Sujets

• Gesundheit

Informations

• Publié par: heinrich-heine-universitat_dusseldorf
• Publié le: 01 janvier 2001
• Nombre de lectures: 16
• Langue: English

Extrait

Aus dem Medizinischen Institut für Umwelthygiene
an der Heinrich-Heine-Universität Düsseldorf
Direktor: Prof. Dr. J. Krutmann
INFLAMMATION, GENOTOXICITY AND CELL PROLIFERATION
IN NASAL LAVAGE AND NASAL EPITHELIUM OF PEOPLE
EXPOSED TO URBAN POLLUTION
DISSERTATION
Zur Erlangung des Grades eines Doktors der Medizin
Der Medizinischen Fakultät der
Heinrich-Heine-Universität Düsseldorf
vorgelegt von
Dünya Polat
2001In Liebe an Aydin, Mehmet und meinen Eltern gewidmet.
Als Inauguraldissertation gedruckt mit Genehmigung der
Medizinischen Fakultät der Heinrich-Heine-Universität Düsseldorf
Gez:
Dekan: Prof. Dr. Raab
Referent: Prof. Dr. Borm
Koreferent: Prof. Dr. KahlContents
List of Abbreviations: _______________________________________________________
CHAPTER 1 __________________________________________________________5
1 Genaral Introduction_____________________________________________________ 5
1.1 Ambient exposure and adverse health effects _____________________________________ 5
1.1.1 The effects of air pollution on children 8
1.1.2 Airway Inflammation and Ambient Exposure_______________________________ 12
1.1.2.1 Ozone ___________________________________________________________ 12
1.1.2.2 Particulate matter (PM)______________________________________________ 16
1.1.2.2.1 Diesel exhaust ____________________________________________________ 17
1.1.2.2.2 Ultrafine particles__________________________________________________ 19
1.1.3 Inflammation, Genotoxicity and Proliferation_______________________________ 21
1.2 The nose as a target organ for environmental exposure ______________________________ 23
1.2.1 Nasal functional anatomy _________________________________________________ 23
1.2.2 Nasal sampling techniques ________________________________________________ 26
1.2.2.1 Blown secretions 26
1.2.2.2 Nasal smears _______________________________________________________ 27
1.2.2.3 Imprints ___________________________________________________________ 27
1.2.2.4 Nasal brush ________________________________________________________ 27
1.2.2.5 Nasal scrapings _____________________________________________________ 28
1.2.2.6 Nasal biopsies ______________________________________________________ 28
1.2.3 Nasal Lavage as a tool to detect inflammatory effects ________________________ 29
1.2.4 Biomarkers measured in NAL _____________________________________________ 31
1.3 Study aims and design 38
1.4 References ________________________________________________________________ 40
CHAPTER 2 _________________________________________________________58
2 Ambient exposure and nasal inflammation in adults and children_______________ 58
2.1 Abstract___________________________________________________________________ 58
2.2 Introduction _______________________________________________________________ 59
2.3 Methods __________________________________________________________________ 60
2.4 Results 61
2.4.1 Exposure ___________________________________________________________ 61
2.4.2 Nasal Lavage ________________________________________________________ 61
2.5 Discussion_________________________________________________________________ 63
2.6 References ________________________________________________________________ 65CHAPTER 3 _________________________________________________________72
Oxidative DNA damage and proliferation in nasal epithelium in relation to nasal
inflammation ____________________________________________________________ 72
3.1 Abstract___________________________________________________________________ 72
3.2 Introduction _______________________________________________________________ 73
3.3 Methods __________________________________________________________________ 74
3.3.1 Chemicals __________________________________________________________ 74
3.3.2 Study population _____________________________________________________ 74
3.3.3 Nasal lavage and nasal brush____________________________________________ 75
3.3.4 8-Hydroxydeoxyguanosine analysis ______________________________________ 75
3.3.5 Immunnohistochemical staining and analysis of Ki-67________________________ 76
3.3.6 Statistical analysis ____________________________________________________ 76
3.4 Results ___________________________________________________________________ 78
3.4.1 Characteristics of selected subjects _______________________________________ 78
3.4.2 Quantification of 8-OHdG immunnohistochemical staining ____________________ 78
3.4.3 8-Hydroxydeoxyguanosine analysis in relation to inflammation ________________ 79
3.4.4 Ki-67 in relation to inflammation ________________________________________ 79
3.4.5 DNA damage in relation to cell proliferation _______________________________ 81
3.5 Discussion_________________________________________________________________ 82
3.6 References ________________________________________________________________ 86
3.7 Tables and Figures __________________________________________________________ 88
CHAPTER 4 _________________________________________________________97
4.1 Summary and general discussion ________________________________________ 97
4.2 References _______________________________________________________________ 102
5 Danksagungen _____________________________________________________104
6 Curriculum vitae ___________________________________________________106
7 List of publications__________________________________________________107
Index of Tables ______________________________________________________110
Index of Figures111List of Abbreviations:
NAL Nasal Lavage
NALF Nasal Lavage Fluid
PMN Polymorphonuclear leucocytes
IL-8 Interleukin -8
IL-6 Interleukin- 6
Interleukin 1 ßetaIL-1β
IL-5 Interleukin 5
LTC Leukotriene C4 4
LTD Leukotriene D4 4
LTE Leukotriene E4 4
PGE Prostaglandin E2 2
Tumor Necrosis Factor AlphaTNF-α
TXB Thromboxane B2 2
URI Upper respiratory illness
FEV Forced expired volume in 1 second1
FVC Forced vital capacity
PEF Peak expiratory flow
DEP Diesel Exhaust Particles
PM Particulate matter
PM Particulate matter with 50% cut-off aerodynamic diameter of ≤ 10 µm10
PM Fine particulate matter2.5
PM Ultra fine particulate matter0.1
MMAD Mass median aerodynamic diameter
NAAQS National Ambient Air Quality Standards (in USA)CHAPTER 1
1 Genaral Introduction
1.1 Ambient exposure and adverse health effects
A complex mixture of chemicals and particulate matter is present in the ambient air of
both rural and industrial areas. There is increasing concern about adverse effects on the
cardiopulmonary and host defence systems resulting from chronic exposures to air
pollutants. Epidemiological studies strongly suggest that children and adults have
increased mortality and morbidity from photochemical smog and particulate air
pollution (Brunekreef et al., 2000; Roemer et al., 2000; Hiltermann et al., 1997; Pope et
al., 1999; Dockery et al., 1992,1993).
One of the most dramatic examples of the effects of air pollution on health was seen in
an episode that started on 4 December 1952 in London and resulted in 4000 excess
deaths in that month (HMSO, 1954; Logan, 1953). It was public concern about this,
rather than pressure from the medical profession, that led to the first clean air legislation
in Britain (Bates, 1994). Since then drastic efforts have been made to reduce air
pollution.
The main air pollutants measured in the earlier years were sulphur dioxide (SO ) and2
particulate matter (PM) in the form of black smoke from the burning of domestic coal.
Early animal-based studies investigated the effects of relatively high doses (e.g. 50-400
ppm) of inhaled SO on airway epithelium and demonstrated ulceration of large airway2
epithelium, increases of epithelial cell mitoses, and a goblet cell hyperplasia and
increase in gland size which mimicked the changes observed in human bronchitis
(Lamb and Reid, 1968). However as a result of national and international measures
directed to control the most important sources of emission (i.e. power stations and
refineries), SO levels have decreased in several countries in Europe. Instead, in2
developed countries a new form of pollution has emerged resulting from increased use
of liquid petroleum gas or kerosine in industry and increased use of motor vehicles. In
5these settings ozone and respirable particular matter (e.g.PM ) often exceed10
recommended standards and new threats include, nitrogen (NO ) and diesel exhaust.x
World-wide, about 480 million people are being exposed to increased levels of ozone
(Schwela, 1996), of which at least 150 million are in Europe (Sivertsen and Clench-Aas,
1996). Air pollution in Western Europe is mainly traffic-related, and therefore ozone
and NO are particularly important. In Eastern Europe pollution is mainly related to thex
combustion of fossil fuels, and so PM and SO are the key constituents.2
The US Environmental Protection Agency cited in the 1987 revision of the particulate
air pollution standards, the results of three epidemiological studies as providing the key
supporting evidence for the proposed particle standard (US-EPA, 1987). Since then
there has been a burst of epidemiologic studies of the health effects of particulate air
pollution in the succeeding ten years and the Environmental Prot