الفهرس 
NON CYSTIC FIBROSIS BRONCHIECTASISOnly 14 pages are availabe for public view
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Abstract
B
ronchiectasis is a chronic debilitating respiratory disease, most often secondary to an infectious process, that results in the abnormal and permanent distortion of one or more of the conducting bronchi or airways. First described by Laennec in 1819, later detailed by Sir William Osler in the late 1800s, and further defined by Reid in the 1950s, bronchiectasis has undergone significant changes as regards its prevalence, etiology, presentation, and treatment.
Bronchiectasis most commonly presents as a focal process involving a lobe, segment, or sub-segment of the lung. Far less commonly, it may be a diffuse process involving both lungs; these cases most often occur in association with systemic illnesses, such as cystic fibrosis (CF), sino-pulmonary disease, or both.
Cystic fibrosis (CF) is autosomal recessive disease involving mucus and sweat producing cells affecting multiple organs with lungs most severely affected. A mutation in Cystic fibrosis trans-membrane conductance regulator (CFTR) gene changes a protein (a regulated chloride channel), which regulate the activity of other chloride and sodium channels at the cell surface epithelium.
Lipoxins are a metabolite of the arachidonic acid pathways, Arachidonic acid pathways play an important role in inflammation, producing several anti-inflammatory molecules. Lipoxins can be synthesized by two major routes from arachidonic acid. Additionally, lipoxin epimers can be formed under the influence of aspirin treatment.
Lipoxin A4 exerts its anti-inflammatory effects in several inflammatory diseases, such as nephritis, periodontitis, bronchiectasis, arthritis and inflammatory bowel disease.
Arachidonic acid is metabolized by three families of enzymes, namely cyclooxygenases, lipoxygenases and cytochrome P450 monooxygenases, Lipoxygenases (LOXs) are non heme-iron containing dioxygenases that catalyze the stereospecific oxygenation of polyunsaturated fatty acids in lipids.There are six known functional LOX genes in humans (ALOX5, ALOX12, ALOX12B, ALOX15, ALOX15B, ALOXE3).
The human reticulocyte type 15-LOX1 (ALOX15) produces predominantly 15(S)-HETE and only little amounts of 12(S)-HETE (ratio of 9:1), Both these enzymes share 73% amino acid similarity, a similar expression pattern and largely overlap in their known biological effects. Recently, it has been suggested that various LOX isoforms should be named according to their encoding genes, such as all 12/15-LOX orthologs from different species should be called as ALOX15.
In the present study we aimed to investigate the effect of ALOX-15 polymorphism on BAL lipoxin A4 level in children with bronchiectasis and to detect the association between the inflammatory genotype with clinical and radiological phenotype in those children.
60 patients were recruited to this study and was categorized in three groups: A group of 15 patients with CF bronchiectasis, 15 patients with non-CF bronchiectasis and a control group of 30 patients with no relevant medical history of respiratory disease or chronic illness.
The patient underwent full clinical assessment and the clinical data were collected simultaneously with radiological data, Measuremet of lipoxin A4 and genotyping of ALOX-15 in BAL samples, and all of these data underwent statistical analysis.
The results of this study could be summarized as follow
• Regarding demographic data, age of onset and course of the disease there was highly significant difference between bronchiectasis, CF cases and control group as regards age and sex (p<0.01), and there was highly significant difference between bronchiectasis and CF cases as regards onset of the disease (p<0.01) suggesting that CF starts earlier in life.
• Regarding anthropoemetry and clinical examination, there was no statistically significant difference between CF, Bronchiectasis cases and control group as regards clinical examination, there was significant difference between bronchiectasis and CF cases as regards weight for age and BMI for age (p<0.05). being lower in CF cases.
• Regarding laboratory investigations, there was no significant difference between bronchiectasis and CF patients as regards laboratory investigations, BAL examination in the studied cases showed higher affection by pseudomonas (36.7% of cases) followed by MRSA (13.3% of cases).
• Regarding radiological examination there was no significant difference between bronchiectasis and CF groups (p>0.05).
• Regarding BAL lipoxin A4 level, there was significant difference between studied cases and control group as regards BAL Lipoxin A4 level (p<0.05), cases have lower level than control, and the best cutoff value of BAL Lipoxin A4 level as a marker of severity was <2353 ng/dl, sensitivity 100%, specificity 40%, PPV 76.9% and NPV 100%.
• Regarding ALOX-15 C292T gene polymorphism, there was no significant difference between study groups as regards genotype.
• This study showed significant positive correlation between BAL lipoxin A4 and RR and number of hospital admissions.
• There was significant positive correlation between lipoxin A4, FEV1 and FVC.
• There was significant relation between Lipoxin A4 level, genotypes and disease severity, lowest level of BAL Lipoxin A4 was related to severe cases and TT genotype.
CONCLUSION
D
ecreased Lipoxin A4 level as endogenous anti-inflammatory marker in BAL of children with bronchiectasis was correlated with clinical and radiological severity.
ALOX-15 gene expression (homozygous TT) genotype was associated with increased disease severity which signify the genetic susceptibility of some children with bronchiectasis to worse clinical outcome.
RECOMMENDATIONS
1. Clinical trials using medications increasing levels of Lipoxin A4 as Aspirin may be needed to study its effect on disease severity and progression in differen stages of disease process.
2. More studies about other endogenous anti-inflammatory agents as prognostic markers for severity of bronchiectasis should be considered.
3. Genetic susceptibility to severe form of chronic pulmonary diseases as bronchiectasis may be of value in the era of gene modulators.
4. Assessment of effect of Lipoxin A4 level on bronchiectasis exacerbations should be further studied.
5. Larger multicentric study on Egyptian children with bronchiectasis is needed to confirm the results of this study among the Egyptian bronchiectasis children.