Dissertation committee:
Παπαευαγγέλου Βασιλική, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Παπαδημητρίου Αναστάσιος, Καθηγητής, Ιατρική, ΕΚΠΑ
Πρίφτης Κωνσταντίνος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Μπενέτου Βασιλική, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
Καδίτης Αθανάσιος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Λουκίδης Στυλιανός, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Αττιλάκος Αχιλλέας, Επίκουρος Καθηγητής, Ιατρική, ΕΚΠΑ
Summary:
Introduction: There is accumulated evidence supporting a beneficial role of Mediterranean diet (MD) in the control of asthma symptoms. The aim of this study was to delve into the mechanisms through which MD exerts its beneficial effects on asthma, in children. In order to do so, we examined the relationships between adherence to MD and serum levels of certain cytokines namely, interleukin (IL)-4, IL-33, and IL-17, known to have a pivotal role in the airway changes associated with asthma. Material –Methods: Two groups of children, 5 – 15 years old, were recruited for the study. The first group (patients) consisted of 44 children diagnosed with intermittent or mild persistent asthma who attended the Children’s Respiratory & Allergy Unit of “Attikon” General University Hospital, all treatment naive for at least 1 month before entering the study. The second group (controls) consisted of 26 healthy children. Children with any kind of chronic inflammatory disease were excluded from the study in order to avoid conditions that could potentially affect cytokines levels. All children were required to be clinically stable for at least 4 weeks before blood sampling. All children underwent complete physical examination and measurement of body weight and height. Spirometry and skin prick tests to 14 of the most common aeroallergens in Greece were performed on the same day of blood collection. Laboratory tests were carried out for all enrolled subjects including complete blood count, liver and renal function, lipid profile analysis, insulin, cortisol, IgA, Ig G, IgM, Ig E, C3, C4, eosinophils, neutrophils. Isolated serum samples were used for the analysis of IL-4, IL-17, and IL-33. Measurements of serum levels of IL-17 were done with the use of Human IL-17 Quantikine ELISA Kits (R&D Systems, Minneapolis, MN, USA; Catalog Number: D1700). IL-4 and IL-33 serum levels were measured with Human IL-4 and IL-33 PicoKine ELISA Kits (Boster Biological Technology, Pleasanton CA, USA, Catalog Numbers: EK0404 and EK0929, respectively). The tests procedures were performed according to the manufacturers’ directions. Adherence to the MD was evaluated with the use of the Mediterranean Diet Quality Index for children and adolescents (KIDMED). The parents were invited to complete a questionnaire incorporating questions related to socioeconomic status, education level, lifestyle factors and physical activity, a Food Frequency Questionnaire (FFQ) and a questionnaire that included questions on the child’s respiratory and allergic symptoms (modified ISAAC questionnaire, translated into greek).Children in the asthma group underwent a Childhood Asthma Control Test. Continuous parameters were expressed as mean ± standard deviation (SD). Coefficient of variation (CV) was used to express dispersion of values. Univariate analysis was performed with chi-square, Student’s t-test, and Pearson’s correlation coefficient (r). Multivariate analysis was performed with three consecutive linear regression models. The three models were first applied to the whole study population and then only to the group of asthmatic children. In order to obtain a meaningful comparison between the different regression models, we choose to express the results as standardized regression coefficients (Beta). Results: The mean (SD) KIDMED score of our study population was 5.70 (1.94), and the CV was 34.0%. Both groups had, on average, moderate adherence to MD, and KIDMED scores were similar between the two groups. KIDMED score was not associated with BMI z-score (p 0.20).The asthmatic kids with better control of their asthma symptoms (ACT score >19) had higher KIDMED score (6.92±1.81) regarding those with poor control of their asthma (ACT <19; 4.96±1.68), showing a better adherence to the Mediterranean diet (p 0.0014). IL-4 was correlated with IL-33, in the whole study population as well as, in the asthmatics’ group (r=0.51, p<0.001; r=0.53, p 0.003, respectively). No correlation was found between IL-17 and the other two measured cytokines. When we applied the three multivariate models in the whole study populations, the only statistically significant association we identified was that of IL-17 with the presence of asthma (Beta: 0.52, p 0.010). However, when the analysis was restricted to the group of asthmatic children, KIDMED score was found to be correlated with IL-4, IL-33, and IL-17 (Beta: -0.56, p 0.007; Beta: 0.57, p 0.010; Beta:-0.62, p 0.017, respectively). Discussion: Our results largely corroborated our hypothesis by showing a clear relationship of MD with IL-4, IL-33, and IL-17. The negative association of IL-4 with KIDMED score in asthmatic children implies an inhibiting role of MD on the IL-4 production. In our study, IL-17 showed a negative correlation with KIDMED score implying that MD exerts an anti-inflammatory effect by lowering the levels of IL-17 in asthmatic patients. KIDMED was positively associated with IL-33 in asthmatic children implying that adherence to MD promotes the production of IL-33. The role of IL-33 in airway inflammation is not univocal, showing an important role in the resolution of inflammation and repair of tissue damage. The opposite effect of IL‑33 in asthma may arise from a failure of IL‑33‑driven regulatory and reparative responses (involving Treg cells, ILC2s or M2 macrophages) to successfully counter the ongoing tissue damage. In conclusion, our results indicate that MD can modulate the production of main inflammatory mediators of asthma demonstrating a protective effect and may be the ideal dietary pattern for these patients.
