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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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