الفهرس 
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Abstract
Asthma is a heterogeneous disease, characterized by chronic airway inflammation which is defined by the history of respiratory symptoms that vary over time and in intensity, together with variable expiratory airflow limitation. Airway inflammation plays a crucial role in the pathophysiology of asthma and involves many cell types and multiple mediators.
The parallel increase in asthma and obesity prevalence has led to several studies examining the possible relationship between the two conditions. An association between obesity and asthma is now well described, although the mechanisms underlying this association are incompletely understood. Obesity is associated with increased asthma incidence, and severity, and obese patients with asthma have a poor response to standard asthma therapy.Thus, understanding the mutual influence between asthma and obesity is essential for more efficient diagnosis and more optimal treatment to obese asthmatics.
Exercise is one the most common triggers of bronchoconstriction in patients with asthma, particularly in children. Exercise-induced bronchoconstriction (EIB) is a clinical condition where a brief period of vigorous exercise or increase in ventilation triggers acute transient lower airway narrowing that lasts 30 to 90 minutes in the absence of treatment.
The precise mechanism by which airflow limitation develops after an exercise challenge remains an area of controversy. However, the release of inflammatory mediators, especially the bronchoconstrictive eicosanoids (LTs and PGD2), from different cells in the airways was recognized to play an important role. LTs are a group of lipid mediators that play a key role in perpetuating airway inflammation which may lead directly to airflow obstruction and contribute to airway remodeling.
Some studies have reported increased EIB frequency, severity or recovery time among obese individuals, yet, a clear cause and effect relationship between obesity and EIB is still elusive. Notably, a better understanding of this relationship may lead to identification of novel targets for effective prevention and therapy of EIB in obese asthmatics. Both, obesity and EIB, share inflammation as a common denominator, and recent studies suggest an important role for leptin, and its possible effect on LT secretion, in the occurrence of EIB in obese patients. However, leptin-induced effects on LT secretion in the human airway that may affect the pathophysiology of EIB in obese asthmatics have not been clearly demonstrated. So the aim of the present work was to study the possible effect of obesity on the pathophysiology of exercise-induced bronchoconstriction (EIB) in bronchial asthma.
Eighty asthmatic pre-pubertal children 5 to 12 years old (50 males and 30 females) were included in this study. Participants were divided according to their Body Mass Index (BMI) and response to exercise challenge test (ECT) into four groups, group I; included 20 obese exercise-responder patients, group II; 20 normal-weight exercise-responder patients, group III; 20 obese exercise non-responder patients, and group IV; 20 normal-weight exercise non-responder patients.
All studied patients were subjected to detailed history taking and complete physical examination. The anthropometric measurements included height, weight and waist and hip circumferences. A spirometry test was performed using a masterScreen™ Pneumo Spirometer (CareFusion, Hoechberg, Germany), with SentrySuite® software and a calibrated Jaeger™ pneumotachograph. The largest forced vital capacity (FVC), forced expiratory volume in one second (FEV1), the ratio FEV1/FVC% and forced expiratory flow at 25-75% of FVC (FEF25-75%) were recorded and represented as percent of the predicted values (%pred) according to ATS/ERS criteria. An exercise challenge test (ECT) was conducted in accordance with ATS standards and performed by running on a motor-driven treadmill, with the nose clipped using a standardized protocol. Starting at a low speed and grade, both were progressively advanced during the first 2-4 min of exercise until the heart rate was approximately 85% of the predicted maximum (220 – age in years). Treadmill speed and slope were chosen to achieve the target heart rate within 2-4 min, then they were maintained for 4 min with a total duration of exercise of 6-8 min. Spirometry was conducted at baseline (before ECT) and then repeated serially at 1, 5, 10, 15, 20 and 30 minutes after cessation of ECT. The response to exercise was monitored by plotting FEV1 as a percentage of the pre-exercise baseline FEV1, at each post-exercise interval. The maximum percentage fall in FEV1 (MF%FEV1) compared to baseline was used for further analysis. A reduction in FEV1 ≥ 12% from baseline value was considered a positive response.
Leukotriene E4 (LTE4) was quantified in urine 5 minutes before the ECT then 2 hours after the end of the ECT and urinary LTE4 level was expressed as picograms per milligram of creatinine (pg/mg creatinine). Fasting blood samples were collected from all patients and serum leptin was measured using a commercially available enzyme-linked immunosorbent assay. Finally, data were calculated and analyzed using IBM SPSS software package version 17.0.
The main findings of this study demonstrated that obese asthmatic patients had a significantly more severe bronchoconstrictive responseto exercise than normal-weight patients and the post-exercise maximal percentage fall in FEV1 after exercise (MF% FEV1) was positively associated with BMI z-score and waist circumference (WC). Serum leptin levels were significantly higher in obese patients than in normal-weight patients and a strong positive correlation existed between serum leptin level and BMI in exercise-responder patients (r = 0.936, p<0.001). The bronchoconstrictive response to exercise was positively correlated with serum leptin in exercise-responder patients (r = 0.592, p<0.001). Baseline urinary LTE4 (U-LTE4) was significantly higher in obese than in normal-weight asthmatic patients with a positive correlation between baseline U-LTE4 and BMI (r=0.295, p=0.008). U-LTE4 significantly increased after exercise in all exercise-responder patients, and the change in U-LTE4 after exercise was positively associated with the MF% FEV1
(r = 0.615, p<0.001). The post-exercise change in U-LTE4 was significantly higher in obese responder patients compared with their normal-weight counterparts and there had been a positive correlation between the change in U-LTE4 after exercise and both the BMI z-score (r =0.623, p <0.001) and the serum leptin levels (r =0.514, p=0.001) in exercise-responder patients.