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The Bronchoalveolar Lavage Proteome- Phenotypic associations to smoking and divergence towards development of COPD

Plymoth, Amelie LU (2006) In Lund University Faculty of Medicine Doctoral Dissertation Series 2006:150.
Abstract
Proteomic analysis of bronchoalveolar lavage (BAL) fluid from smokers at risk of developing chronic obstructive pulmonary disease (COPD) and never smokers is described. COPD is currently the world's fourth leading cause of death and its prevalence is increasing. The leading cause of COPD is smoking and an estimated 600 million people in the world suffer from COPD which makes it the world's most common chronic disease. The aim of this thesis was to explore and characterize the BAL proteome of never smokers and smokers. The hypotheses were that the BAL proteome reflect smoking habits in subjects, and that smokers susceptible to COPD development have a specific proteome. In order to relate the measurement of protein expression with clinical... (More)
Proteomic analysis of bronchoalveolar lavage (BAL) fluid from smokers at risk of developing chronic obstructive pulmonary disease (COPD) and never smokers is described. COPD is currently the world's fourth leading cause of death and its prevalence is increasing. The leading cause of COPD is smoking and an estimated 600 million people in the world suffer from COPD which makes it the world's most common chronic disease. The aim of this thesis was to explore and characterize the BAL proteome of never smokers and smokers. The hypotheses were that the BAL proteome reflect smoking habits in subjects, and that smokers susceptible to COPD development have a specific proteome. In order to relate the measurement of protein expression with clinical phenotypes we have developed and utilized an interdisciplinary toolbox that includes protein separation (two-dimensional gel electrophoresis and liquid chromatography), mass spectrometry identification and statistical methods for multivariate analysis. The study material used in this thesis consisted of age matched men all born in 1933, living in one city differing by lifelong smoking history. These were compared by clinical function measurements and histological assessment at the same relative time points. A follow up study after 6-7 years identified a group of subjects who had progressed to COPD GOLD stage 2. Those with COPD shared a distinct protein expression profile in the baseline BAL sample which could be identified using multivariate analysis. This pattern was not observed in BAL samples of asymptomatic smokers free of COPD at the 6-7 year follow-up. The results suggest that specific patterns of protein expression occur in the airways of smokers susceptible to COPD disease progression, before the disease is clinically measurable. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Kroniskt Obstruktiv Lungsjukdom (KOL) är idag världens fjärde vanligaste dödsorsak vars dödlighetsfrekvens ökar. KOL är en lungsjukdom som nästan alltid beror på rökning och i hela världen är cirka 600 miljoner människor drabbade av sjukdomen. Detta gör KOL till världens vanligaste kroniska sjukdom. I Sverige beräknas sjukvårdskostnaderna för KOL att uppgå till ca 9,1 miljarder SEK per år (2002). Trots att KOL är en vanlig sjukdom är vår förståelse för dess bakomliggande biologiska mekanismer begränsade.



Denna avhandling syftar till att studera och karakterisera proteinerna i bronksköljvätskan från personer som aldrig har rökt och kroniska rökare. Vår hypotes var att... (More)
Popular Abstract in Swedish

Kroniskt Obstruktiv Lungsjukdom (KOL) är idag världens fjärde vanligaste dödsorsak vars dödlighetsfrekvens ökar. KOL är en lungsjukdom som nästan alltid beror på rökning och i hela världen är cirka 600 miljoner människor drabbade av sjukdomen. Detta gör KOL till världens vanligaste kroniska sjukdom. I Sverige beräknas sjukvårdskostnaderna för KOL att uppgå till ca 9,1 miljarder SEK per år (2002). Trots att KOL är en vanlig sjukdom är vår förståelse för dess bakomliggande biologiska mekanismer begränsade.



Denna avhandling syftar till att studera och karakterisera proteinerna i bronksköljvätskan från personer som aldrig har rökt och kroniska rökare. Vår hypotes var att proteinerna i bronksköljvätskan speglar en persons rökvanor och att det hos de rökare som kommer att utveckla KOL finns karakteristiska proteinmönster. Vi valde att studera bronksköljvätska eftersom proteiner från de centrala luftvägarna och de nedre luftvägarna återfinns i denna biologiska vätska. En stor fördel med att studera bronksköljvätska är att denna biologiska vätska erhålls från platsen för inflammationen, d.v.s. från luftvägarna.



För att studera proteinerna i bronksköljvätskan har vi utvecklat analytiska metoder för tvådimensionella geler och vätskekromatografi. Därefter har proteinerna identifierats med hjälp av masspektrometri. För att kunna dra slutsatser om proteinerna i bronksköljvätskan speglar en persons rökvanor och om det hos de personer som kommer att utveckla KOL finns karakteristiska proteinmönster utvecklades statistiska modeller.



Personerna vars bronksköljvätska studerades, var alla födda i Göteborg 1933 och skiljde sig bara väsentligen åt i avseende på rökvanor. Samtliga personers lungfunktion undersöktes. Vid uppföljning 6-7 år efter det att bronksköljvätskan tagits (eller samlats in), undersöktes personerna igen och det visade sig då att en del av personerna utvecklat KOL. Hos personerna som utvecklat KOL kunde vi med hjälp tidigare utvecklade tekniker för proteinseparation finna att det fanns karakteristiska proteinmönster. Dessa proteinmönster återfanns inte bland rökare som inte utvecklat KOL vid uppföljningen. Sammanfattningsvis pekar resultaten av denna avhandling på att proteinerna i bronksköljvätskan speglar en persons rökvanor och att det hos de personer som kommer att utveckla KOL finns KOL karakteristiska proteinmönster. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Dr. Nilsson, Carol L., National High Magnetic Field Laboratory, Tallahassee, Florida, USA
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Andningsorganen, Respiratory system, mass spectrometry, proteomics, 2-D gel, COPD, bronchoalveolar lavage
in
Lund University Faculty of Medicine Doctoral Dissertation Series
volume
2006:150
pages
182 pages
publisher
IPC, AstraZeneca, Lund, Sweden
defense location
Segerfalksalen, Wallenberg Neurocentrum, BMC, Sölvegatan 17, Lund.
defense date
2006-12-01 13:00:00
ISSN
1652-8220
ISBN
91-85559-70-9
language
English
LU publication?
yes
additional info
Amelie Plymoth, Ziping Yang, Claes-Göran Löfdahl, Ann Ekberg-Jansson, Magnus Dahlbäck, Thomas E. Fehniger, György Marko-Varga and William S. Hancock. 2006. Rapid Proteome Analysis of Bronchoalveolar Lavage Samples of Lifelong Smokers and Never-Smokers by Micro-Scale Liquid Chromatography and Mass Spectrometry Clinical Chemistry, vol 52 pp 671-679. American Association for Clinical Chemistry
Amelie Plymoth, Claes-Göran Löfdahl, Ann Ekberg-Jansson, Magnus Dahlbäck, Henrik Lindberg, Thomas E. Fehniger and Marko-Varga György. . Human bronchoalveolar lavage: biofluid analysis with special emphasis on sample preparation, vol 3 pp 962-972. Wiley-VCH Verlag Gmbh & Co. KGaA, Weinheim
Amelie Plymoth, Claes-Göran Löfdahl, Ann Ekberg-Jansson, Magnus Dahlbäck, Per Broberg, Martyn Foster, Thomas E. Fehniger and György Marko-Varga. 2006. Protein expression patterns associated with chronic obstructive pulmonary disease progression in bronchoalveolar lavage of smokers (submitted)
id
38ca2136-6c09-48e0-888a-9b1ebf0c9d1c (old id 547561)
date added to LUP
2016-04-01 17:02:54
date last changed
2019-05-22 01:48:03
@phdthesis{38ca2136-6c09-48e0-888a-9b1ebf0c9d1c,
  abstract     = {{Proteomic analysis of bronchoalveolar lavage (BAL) fluid from smokers at risk of developing chronic obstructive pulmonary disease (COPD) and never smokers is described. COPD is currently the world's fourth leading cause of death and its prevalence is increasing. The leading cause of COPD is smoking and an estimated 600 million people in the world suffer from COPD which makes it the world's most common chronic disease. The aim of this thesis was to explore and characterize the BAL proteome of never smokers and smokers. The hypotheses were that the BAL proteome reflect smoking habits in subjects, and that smokers susceptible to COPD development have a specific proteome. In order to relate the measurement of protein expression with clinical phenotypes we have developed and utilized an interdisciplinary toolbox that includes protein separation (two-dimensional gel electrophoresis and liquid chromatography), mass spectrometry identification and statistical methods for multivariate analysis. The study material used in this thesis consisted of age matched men all born in 1933, living in one city differing by lifelong smoking history. These were compared by clinical function measurements and histological assessment at the same relative time points. A follow up study after 6-7 years identified a group of subjects who had progressed to COPD GOLD stage 2. Those with COPD shared a distinct protein expression profile in the baseline BAL sample which could be identified using multivariate analysis. This pattern was not observed in BAL samples of asymptomatic smokers free of COPD at the 6-7 year follow-up. The results suggest that specific patterns of protein expression occur in the airways of smokers susceptible to COPD disease progression, before the disease is clinically measurable.}},
  author       = {{Plymoth, Amelie}},
  isbn         = {{91-85559-70-9}},
  issn         = {{1652-8220}},
  keywords     = {{Andningsorganen; Respiratory system; mass spectrometry; proteomics; 2-D gel; COPD; bronchoalveolar lavage}},
  language     = {{eng}},
  publisher    = {{IPC, AstraZeneca, Lund, Sweden}},
  school       = {{Lund University}},
  series       = {{Lund University Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{The Bronchoalveolar Lavage Proteome- Phenotypic associations to smoking and divergence towards development of COPD}},
  url          = {{https://lup.lub.lu.se/search/files/4858805/547562.pdf}},
  volume       = {{2006:150}},
  year         = {{2006}},
}