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CNAA / Theses / 2009 / June /

Interconnection between environmental factors, pathogenetic mechanisms and clinical course of paediatric asthma

Author: Aramă Marina
Degree:doctor of medicine
Speciality: 14.00.09 - Pediatrics
Scientific adviser: Liubov Vasilos
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Scientific council:


The thesis was presented on the 9 June, 2009
Approved by NCAA on the 1 October, 2009


Adobe PDF document0.46 Mb / in romanian


children, bronchial asthma, air pollution, potable water pollution, risk factors, gastroesophageal reflux, allergic inflammation, cytokine, leukotriene modifier, immunomodulation.


The cohort study is based on an analysis of 854 children residing in areas with varying levels of air and drinking water pollution. Standard protocol screening (ISAAC) revealed symptoms of bronchial asthma in the anamnesis of 11.0±1.1% respondents. This indicator was 1.5 times higher in the compromised zones compared to control, (p<0.05), and 2 times higher in urban settings compared to the rural zones (p<0.001). It was established that the exposure to outdoor air pollutants increases the risk of asthma and contributes to a more severe course in adolescents (RR=3.4; 95%IC: 1.6-7.3; p<0.001); the use of poor quality water, triggers the first step “the atopic march” – eczema, and increases the likelihood of asthma evolution in children before 10 years (RR=6.4; 95%CI: 1.1-35.9; p<0.001).

It is demonstrated that environmental stress in children leads to activation of Th2-pattern immunity: the T-cell immunodeficiency develops (0.97±0.1x109/l, p<0.001) with an increase of Th/Ts (p<0.001), the blood levels of IL-4 increase (30.9±7.1 pg/ml, p<0.05), LTC4 (35.2±5.7 ng/ml, p<0.01) and total IgE (354.8±64.6 IU/ml, versus 164.6±37.2 IU/ml in the control group, p<0.01).

24-h gastroesophageal рН-monitoring revealed pathological reflux in 80.0±10.3% of children with asthma. It was established that the severity of the GERD correlates with the degree of bronchial lability (r=0.55; p<0.01), an was inversely proportional to the markers of allergic inflammation – eosinophillia (r= -0.46; p<0.05) and the blood level of LTC4, (r= -0.64; p<0.001), which justifies the view that GER is a non-imune pathogenetic link of the mecahanism of evolution of asthma in children.

A double blinded placebo-controlled clinical trial demonstrated that inclusion of Montelukast (Zespira®), a leucotriene modifier, in the controller medications for children with moderate asthma ensures an additive anti-inflamatory effect (a 3-fold reduction of blood levels of LTC4, p<0.001; a 2-fold reduction of IL-4, p<0.05; 3-fold increase in the level of γIFN, p<0.01), which allows to achieve controlled asthma in 75.0±6.8% patients (compared to 47.0±7.9% on therapy with 200 µg/kg of Flixotide, p<0.01) and a 50% reduction in the doses of inhaled corticosteroides (p<0.001), thus reducing 2.4 times the financial cost of achieving a unit of effect.

It was demonstrated that a short immunomodulative treatment course with Kipferone, in children with asthma and with frequent episodes of respiratory infections, restores the immunological balance, and significantly reduces the blood level of IL-4 and IL-6 (p<0.001), activates the interferonogenesis (p<0.001), which increases the non-specific immunity and provides protection from asthma exacerbations. The economic effect is 40$/treatment course/patient compared to other schemes of immunocorrection.