Download - THE ROLE OF MONOCYTE INFLAMMATION AND OXIDANT STRESS IN THE ETIOPATHOGENESIS OF CYSTIC FIBROSIS
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THE ROLE OF THE ROLE OF MONOCYTE INFLAMMATION MONOCYTE INFLAMMATION
AND OXIDANT STRESSAND OXIDANT STRESS IN THE ETIOPATHOGENESIS OF IN THE ETIOPATHOGENESIS OF
CYSTIC FIBROSISCYSTIC FIBROSIS
Z.S. Uyan*, G. Ünlügüzel**, G. Haklar**, E. Çakır*, R. Ersu*, F. Karakoç*, E. Dağlı*
*Division of Pediatric Pulmonology, Marmara University, Istanbul, TURKEY**Department of Biochemistry, Marmara University, Istanbul, TURKEY
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INTRODUCTIONINTRODUCTION
Cystic fibrosis (CF) is the most common recessively inherited lethal disease of Caucasians
CF occurs due to mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a transmembrane chloride channel expressed in the epithelium of multiple organs
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INTRODUCTIONINTRODUCTION
Although the organs affected in CF also include the pancreas, gut, liver and reproductive tract, the clinical picture is dominated by pulmonary involvement, with recurrent cycles of infection leading to inflammation and bronchiectasis
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INTRODUCTIONINTRODUCTION
The lung disease of cystic fibrosis is associated with a chronic inflammatory reaction and an overabundance of oxidants relative to antioxidants
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INTRODUCTIONINTRODUCTION
Chronic bacterial colonisation of lungs leads to infection and inflammation in CF
Increased free radicle formation is seen in CF due to infectious pathology and this increases tendency of CF patients to oxidative damage
In CF, patients have tendency to oxidative stress due to both reduction of antioxidant mechanisms and increased free radicle formation
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AIMAIM
To investigate; the inflammatory status of CF patients the intensity of oxidative stress and free
radical damage that CF patients were exposed to
compared to non-CF bronchiectasis patients
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METHODMETHOD
Children with CF and non-CF bronchiectasis not receiving any steroids for at least two months were enrolled
Previous sputum culture results of both CF and non-CF bronchiectasis patients were reviewed
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METHODMETHOD
To evaluate oxidative damage intensity, we measured plasma concentrations of malondialdehyde (MDA)
To evaluate inflammatory status, we measured hs-CRP levels and oxidative burst of monocytes
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METHODMETHOD
Blood samples were taken for hs-CRP MDA monocyte respiratory burst measurement
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METHODMETHOD
MDA measurements were done with HPLC and hs-CRP immunoturbidometrically
Respiratory burst of monocytes were measured by luminol-enhanced chemiluminescence before and after phorbol-myristate acetate (PMA) induction
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RESULTSRESULTS
Twenty-six CF cases and eight non-CF bronchiectasis controls were enrolled
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Table 1. Demographic properties of cystic fibrosis and non-cystic fibrosis bronchiectasis patients
3,3 + 2,811,6 + 1,837,5 / 62,5Bronchiectasis
5,3 + 3,410,9 + 2,973 / 27Cystic Fibrosis
Duration of follow-up
(years)
Age
(years)
Gender (%)
(Female / Male)
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Figure 1. Etiology of non-cystic fibrosis bronchiectasis patients
Postinfectious
Immunodeficiency
Asthma
Primary ciliarydyskinesia
12,5%37,5%
25%
25%
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Figure 2. Previous sputum culture results of cystic fibrosis and non-cystic fibrosis bronchiectasis patients
culture positive
culture negative
46% 54%
culture positive
culture negative
62,5% 37,5%
Patients with cysric fibrosis
Patients with non-cystic fibrosis bronchiectasis
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Figure 3. Microorganisms recovered from previous sputum samples of cystic fibrosis patients
P. aeruginosa
S. aureus
H. influenza
M. abscessus
27% of CF patients had more than one microorganism in their sputum cultures
42%
27%
20%
4%
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Figure 4. Microorganisms recovered from previous sputum samples of non-cystic fibrosis bronchiectasis patients
37,5% of non-CF bronchiectasis patients had H. influenza in their previous sputum cultures
H. influenza
culture negative
62,5%
37;5%
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Figure 5. Mean respiratory function test results of cystic fibrosis and non-cystic fibrosis bronchiectasis patients
0
20
40
60
80
100
FVC FEV1 PEF FEF25-75
CF
Non-CF BE
% of predicted
valuep>0,5
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RESULTSRESULTS
Monocyte respiratory burst (PMA induction - basal) activations were significantly increased in CF group compared to the non-CF bronchiectasis cases (5.290.84 vs. 4.60.83 log AUC/mL, p<0.01)
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Figure 6. Monocyte respiratory burst results of cystic fibrosis and non-cystic fibrosis bronchiectasis patients
0
1000000
2000000
3000000
4000000
5000000
6000000
ΔAUC/ml
Cystic fibrosis Bronchiectasis
p<0,01
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RESULTSRESULTS
Plasma MDA concentrations were also elevated in CF patients compared to non-CF bronchiectasis cases
hs-CRP measurements were not different
between the two groups
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CONCLUSIONCONCLUSION
Oxidative stress is more pronounced in CF patients compared to non-CF bronchiectasis cases
This could be attributed to systemic nature of the disease
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CONCLUSION CONCLUSION
This is a preliminary study Patients with CF and non-CF bronchiectasis
are still enrolled into the study Sputum samples of patients are collected to
study cytokines in the sputum
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CONCLUSIONCONCLUSION
There are few studies about antiinflammatory and antioxidant treatment regimens in CF.
It is thought that studies like this which are about the etiopathogenesis of CF can guide for studies about treatment of CF.
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THANK YOU FOR YOUR ATTENTION…THANK YOU FOR YOUR ATTENTION…