الفهرس 
Introduction and aim of the study 1 INTRODUCTION AND AIM OF THE WORK
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Pediatric ILD comprises a heterogeneous group of lung disorders characterized by a wide variety of etiologies and mechanisms. An important feature of the pathologic process observed in chILD is an altered communication between epithelial and mesenchymal pulmonary components. Prolonged denudation of the basement membrane after injury contributes to altered interactions between alveolar epithelial and mesenchymal cells, resulting in profound cell function modifications with the production of polypeptide mediators including cytokines, growth factors, oxidants, and proteases. The aim of this study was to evaluate lung fibrosis by measuring plasma levels of TGF-β1, CCN2 and sFas and lung elastin destruction by measuring UDes/UCr in chILD patients and to correlate the findings with demographic, clinical characteristics and patient’s outcome.
This hospital based study consisted of 56 chILD patients recruited from Pulmonology Unit, Assiut University Children Hospital, Assiut, Egypt, over a 3-yr period (January 2012 to January 2015). The patients were 32 boys and 24 girls, with ages ranging from 0.50 to 16 years. Twenty apparently healthy children and adolescent (13 boys and 7 girls), their ages ranging from 1.5 to 17 years served as healthy control. In all participants, height, weight, and body mass index were measured. ChILD patients were undergoing a comprehensive history taken for the duration, symptoms severity, numbers of hospital admission and family, and occupational histories. Initial pulmonary evaluation included physical examination, calculation of severity of Fan chILD clinical score, routine biochemical investigations, chest roentgenography, and cardiac evaluation. Each patient provided midstream urine and venous blood (5 ml) samples on admission. Plasma levels of TGF–β1; CCN2 and sFas and urinary UDes were measured by ELISA kits. All patients were received their supportive care and therapy. Statistical analysis was made to compare and correlate the obtained results.
The weight, height and BMI, BMI centile of patients were significantly lower than control. Mostly in chILD, age group was >2 -5 years (28.57%). BMI in chILD was mostly healthy (46.40%), then underweight (44.60%), obese (7.10%) and overweight (1.80%). Of chILD patients; 3 (5.40%) patients had positive occupational history, 23 (41.10%) patients had positive animal contact and 9 (16.10%) patients had a positive family history. In patients, presentation was mostly crepitation (100.00%) followed by tachypnea (67.90%), recurrent respiratory tract infection (60.70%), cough (33.90%), cardiomegaly (46.40%), digital clubbing (44.60%), fever (35.70%), hepatomegaly (28.57%), accentuated 2nd heart sound and systolic murmur over pulmonary area (28.57%), cyanosis (28.57%) and wheezes (23.30%). Fan chILD clinical illness score in patients was mostly score (3) (35.70%) then score (5) (28.57%), score (2) (16.10%), score (1) (14.30%) and finally score (4) (5.40%) with significant difference between them (P =0.003). In chILD patient, HRCT were mostly ground glass (44.60%) then reticular (33.90%) and honeycomb appearance (21.40%). The abnormal echocardiographic findings were pulmonary hypertension (28.57%) and right atrium and right ventricular dilatation (5.40%). Only 2 (3.60%) patients made lung biopsy and histopathology reports were non-specific inflammation. Supportive treatments were oxygen supplement (69.60%) and ventilation care (28.57%). Complications were oxygen dependency (14.30%), pulmonary hypertension (25.40%), heart failure (44.60%) and lung lobectomy due to bronchiectasis (3.60%). The mortality rate was 10.70%. Plasma levels of TGF-β1, CCN2 and sFas and urinary UDes/UCr were significantly higher in patients than control (P =0.0001). Plasma TGF-β1 and sFas levels were significantly higher in newly and previously diagnosed patients compared to control (P =0.029, P =0.0001, and =0.016, P =0.003) and were significantly higher in old than newly diagnosed patients (P =0.0001). CCN2 and UDes/UCr levels were significantly higher in previously diagnosed patients compared to control and newly diagnosed patients (P =0.0001). Plasma levels of TGF-β1, CCN2 and sFas and urinary UDes/UCr levels were significantly higher in patients without and with complications compared to control. Pharmacological treatments were antibiotics (96.40%), bronchodilators (21.40%) and steroids (46.40%). In chILD patients, TGF-β1 plasma levels were positively correlated with CCN2 (r =0.368, P =0.005), sFas (r =0.415, P =0.001) and UDes/UCr (r =0.663, P =0.0001). CCN2 plasma levels were positively correlated with sFas (r =0.270, P =0.044) and UDes/UCr (r =0.355, P =0.007). UDes/UCr levels were positively correlated with mortality (r =0.304, P =0.023) and sFas (r =0.281, P =0.036). ChILD Fan clinical illness score was positively correlated with morbidity (r =0.565, P =0.0001). Oxygen saturation was negatively correlated with morbidity (r =-0.285, P =0.033) and chILD Fan clinical illness score (r =-0.527, P =0.0001). Presence of digital clubbing showed positively correlated with plasma level of TGF-β¬1 (r= 0.468, P =0.0001) and morbidity (r= 0.284, P =0.034).
In conclusion, this study demonstrates that there is an increase of markers of fibrosis (TGF-β1, CCN2 and sFas) as well as a marker of elastin destruction (UDes/UCr) in chILD especially in patients with the previously diagnosed disease. So, local blockage of their pathways signal may offer novel therapeutic targets changing the natural course of this serious disease. Also, results of this study demonstrate that chILD cases had decreased probabilities of survival that were associated with an increased in UDes/UCr levels and increased morbidity that was associated with an increased in severity–of–Fan chILD illness score. Owing to the rarity of chILD, multicenter and international collaboration should be encouraged to validate or extend these observations. In this tertiary hospital, the quality of diagnosis can be improved by a multidisciplinary approach of the cases, involving together the pediatric pulmonologist, the radiologist, the pathologist and the thoracic surgeon. This might give the opportunity for a coherent diagnosis and therapeutic approach, and will also increase the expertise of each participant in the multidisciplinary team regarding the chILDs.