TITLE

A disintegrin and metalloprotease 33 and chronic obstructive pulmonary disease pathophysiology

AUTHOR(S)
Gosman, Margot M. E.; Boezen, H. Marike; Van Diemen, Cleo C.; Snoeck-Stroband, Jiska B.; Slapperre, Thérëse; Hiemsfra, Pieter S.; Ten Hacken, Nick H. T.; Stolk, Jan; Postma, Dirkje S.
PUB. DATE
March 2007
SOURCE
Thorax;Mar2007, Vol. 62 Issue 3, p242
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Chronic obstructive pulmonary disease (COPD) is a respiratory disorder with increasing prevalence and mortality. It is associated with airway obstruction, increased airway hyper-responsiveness (AHR), and ongoing airway and lung inflammation dominated by CD8 lymphocytes and neutrophils. Single- nucleotide polymorphisms (SNPs) in a disintegrin and metalloprotease 33 (ADAM33) gene have been associated with AHR and COPD. Objective: To assess whether SNPs in ADAM33 are associated with the severity of AHR and airway inflammation in COPD. Methods: Eight SNPs in ADAM33 (F+1, Q-1, S̱1, S̱2, ST+5, Ṯ1, Ṯ2, V̱4) were genotyped in 11 patients with COPD (96 males, 69 current smokers, mean (standard deviation (SD)), aged 62 (8) years, median pack-years 42 (IQR 31-55), mean postbronchodilator forced expiratory volume in i s (FEV1)% predicted 63 (9). Provocative concentration of methacholine causing a decrease in FEV1 of 20% (PC20 methacholine), sputum and bronchial biopsies were collected. Results: Patients with the ST+5 AA genotype had more severe AHR, higher numbers of sputum inflammatory cells and CD8 cells in bronchial biopsies than patients with the GG genotype (p=0.03, 0.05 and 0.01, respectively). CD8 cell numbers were lower in patients carrying the minor allele of SNP Ṯ1 and Ṯ2, and homozygotic minor variants of SNP S̱2 compared with the wild type (p = 0.02, 0.01 and 0.02, respectively). Conclusions: This is the first study revealing that SNPs in a gene that confers susceptibility to COPD in the general population—that is, ADAM33—are associated with AHR and airway inflammation in COPD. These findings constitute an important step forward in linking gene polymorphisms with COPD pathophysiology, thereby possibly contributing to better treatments for this progressive and disabling disease in the future.
ACCESSION #
24626230

 

Related Articles

  • A novel tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphism associated with asthma in Australian women. Lose, F.; Thompson, P. J.; Duffy, D.; Stewart, G. A.; Kedda, M.-A. // Thorax;Aug2005, Vol. 60 Issue 8, p623 

    Background: Airway remodelling is a characteristic feature of chronic asthma and there is evidence that an airway imbalance between levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) is associated with airway remodelling. On this basis, we...

  • Genetic association between human chitinases and lung function in COPD. Aminuddin, F.; Akhabir, L.; Stefanowicz, D.; Paré, P.; Connett, J.; Anthonisen, N.; Fahy, J.; Seibold, M.; Burchard, E.; Eng, C.; Gulsvik, A.; Bakke, P.; Cho, M.; Litonjua, A.; Lomas, D.; Anderson, W.; Beaty, T.; Crapo, J.; Silverman, E.; Sandford, A. // Human Genetics;Jul2012, Vol. 131 Issue 7, p1105 

    Two primary chitinases have been identified in humans-acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and...

  • Adam33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers. Sadeghnejad, Alireza; Ohar, Jill A.; Zheng, Siqun L.; Sterling, David A.; Hawkins, Gregory A.; Meyers, Deborah A.; Bleecker, Eugene R. // Respiratory Research;2009, Vol. 10, p1 

    Background: Variation in ADAM33 has been shown to be important in the development of asthma and altered lung function. This relationship however, has not been investigated in the population susceptible to COPD; long term tobacco smokers. We evaluated the association between polymorphisms in...

  • LUNG FUNCTION TEST WITH BODY-PLETISMOGRAPH AND DIFFUSION MEASUREMENT IN DIAGNOSIS OF OCCUPATIONAL LUNG DISEASES. SZASZ, Zsuzsanna; SZASZ, Lorand; MOLDOVAN, Horatiu // Studia Universitatis Vasile Goldis Seria Stiintele Vietii (Life ;2010, p17 

    Lung function test using the body-plethysmograph in a 17 patients study group from professional environment with exposure to irritant gases and vapours found significant changes in residual volume and airway resistance to flow. These changes are also accompanied by abnormal alveolo-capillary...

  • Relationship between improved airflow limitation and changes in airway calibre induced by inhaled anticholinergic agents in COPD. M Hasegawa // Thorax;Apr2009, Vol. 64 Issue 4, p332 

    BACKGROUND: Although airflow limitation improved by inhaled anticholinergic drugs varies among individuals with chronic obstructive pulmonary disease (COPD), the relationship between actual bronchodilation and improved pulmonary function and where in the lung such bronchodilation occurs remains...

  • What Happens with Airway Resistance (RAW) in Asthma and COPD exacerbation. Jalusic-Gluncic, Tajana // Medicinski Arhiv;2011, Vol. 65 Issue 5, p270 

    Background: To show that during the exarcerbration of asthma and COPD, increased airway resistance is accompanied with decreased spirometry values (FVC, FEV1, FEF50, and PEF) also comes increasing of airway resistance (RAW). Patients and methods: This research included 74 patients, in...

  • Obstructive Airway Disease and Obstructive Sleep Apnea: Effect of Pulmonary Function. Sharma, Bhavneesh; Feinsilver, Steven; Owens, Robert L.; Malhotra, Atul; McSharry, David; Karbowitz, Stephen // Lung;Feb2011, Vol. 189 Issue 1, p37 

    This study sought to determine whether reduced pulmonary function in obstructive airway disease (OAD) is an independent risk factor for obstructive sleep apnea (OSA). This was a prospective observational study conducted at an outpatient pulmonary clinic. Adults with a known diagnosis of...

  • Accelerated decline in lung function in smoking women with airway obstruction: SAPALDIA 2 cohort study. Downs, Sara H.; Brändli, Otto; Zellweger, Jean-Pierre; Schindler, Christian; Künzli, Nino; Gerbase, Margaret W.; Burdet, Luc; Bettschart, Robert; Zemp, Elisabeth; Frey, Martin; Keller, Roland; Tschopp, Jean-Marie; Leuenberger, Philippe; Ackermann-Liebrich, Ursula // Respiratory Research;2005, Vol. 6, p45 

    Background: The aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women. Methods: In a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults) current smokers in 1991 (18 - 60 yrs) were...

  • Measurement of physiological recovery from exacerbation of chronic obstructive pulmonary disease using within-breath forced oscillometry. Johnson, Martin K.; Birch, Malcolm; Carter, Roger; Kinsella, John; Stevenson, Robin D. // Thorax;Apr2007, Vol. 62 Issue 4, p299 

    Background: Within-breath reactance from forced oscillometry estimates resistance via its inspiratory component (Xrs,insp) and flow limitation via its expiratory component (Xrs,exp). Aim: To assess whether reactance can detect recovery from an exacerbation of chronic obstructive pulmonary...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics