Modularea răspunsului imun în infecții respiratorii virale la pacienții atopici: corelarea cu nivelul vitaminei D

Abstract

In children, the prevalence of vit D deficiency and insufficiency even in a sunny region is high. In addition, there are seasonal variations, with normal serum levels of 25(OH)D in the sunny months and low levels in the less sunny months. Our data suggest that the use of sunscreen products during the summer allows the skin to receive enough sunlight permitting the production of vit D at a level capable of maintaining serum levels of 25(OH)D within normal limits in the sunny months. According to our study, the use of sunscreen products in the summer months is not a risk factor for vit D deficiency and should be encouraged. The results of study 2 support a link between vit D status and different types of inflammation, allergic or infectious. Vit D deficiency is associated with atopy defined as an increase in age-appropriate IgE levels, and the mean vit D level is only slightly lower in asymptomatic atopic children compared to healthy children. During the pandemic, under unprecedented circumstances in the absence of other infections, serum vit D levels were higher and fewer children were more likely to be deficient, more probably due to reduced demand for vit D in the process of immunomodulation. Vit D deficiency may not be a risk factor, but rather a consequence of inflammation, caused by atopy or viral infections, due to the fact that it is used by macrophages, T and B lymphocytes in immunomodulatory processes. In atopic asymptomatic children, vit D levels should be measured and, if deficient, should be corrected in order to change the natural course of allergic inflammation. This hypothesis could be important for the development of strategies for the prevention of allergic diseases in children. Study 3 showed that in children aged 4-16 years with RTI, muscle pain was more common in those with influenza infection, while diarrhea, nasal congestion and tachycardia were more common in children with non-influenza infections. The symptom present in all children was fever, which in those with influenza was higher. Significantly altered haematological parameters were lymphocytes, monocytes, eosinophils and platelets as well as the neutrophils-to-lymphocytes ratio (NLR) and platelets-to-neutrophils ratio (PNR). Viral RTIs in children could probably reduce the size of platelets by suppressing platelet activation in the first 48 hours of illness. MPV was also found to act positively as an acute phase reagent in children with influenza RTI, and MPV levels were significantly increased in these children. This response is associated with low vit D levels, which are likely to alter the virus-platelet-immune / inflammatory response. Among the inflammatory factors, only CPR and IL-10 are significantly altered in RTI, while vit D levels were low towards reaching statistical significance. Asymptomatic atopy appears to predispose to viral respiratory infections. Study 4 aimed to identify those infants with recurrent wheezing who are at increased risk of subsequent recurrences. Vit D deficiency appears to be a factor associated with the presence of recurrent wheezing in children, therefore determination of serum 25(OH)D is recommended. Furthermore, we believe that the measurement of serum vit D levels should be included in the routine assessment of children with recurrent wheezing and should be corrected in case of deficiency. Immune modulation, as measured by IL-10 and IL-31 levels, depends on the type of wheezing as well as the acute phase of the disease or general health status. However, more studies are needed to confirm our results

Στα παιδιά, ο επιπολασμός της ανεπάρκειας και της έλλειψης βιταμίνης D είναι υψηλός ακόμη και σε περιοχές με έντονη ηλιοφάνεια. Επιπλέον, παρατηρούνται εποχικές διακυμάνσεις, με φυσιολογικά επίπεδα ορού 25(OH)D κατά τους ηλιόλουστους μήνες και χαμηλά επίπεδα κατά τους λιγότερο ηλιόλουστους μήνες. Τα δεδομένα μας υποδηλώνουν ότι η χρήση αντηλιακών προϊόντων κατά τη διάρκεια του καλοκαιριού επιτρέπει στο δέρμα να δέχεται επαρκή ηλιακή ακτινοβολία, ώστε να επιτυγχάνεται παραγωγή βιταμίνης D σε επίπεδο ικανό να διατηρεί τα επίπεδα ορού 25(OH)D εντός φυσιολογικών ορίων στους ηλιόλουστους μήνες. Σύμφωνα με τη μελέτη μας, η χρήση αντηλιακών προϊόντων κατά τους θερινούς μήνες δεν αποτελεί παράγοντα κινδύνου για ανεπάρκεια βιταμίνης D και θα πρέπει να ενθαρρύνεται. Τα αποτελέσματα της μελέτης 2 υποστηρίζουν τη σύνδεση μεταξύ της κατάστασης της βιταμίνης D και διαφορετικών τύπων φλεγμονής, αλλεργικής ή λοιμώδους. Η ανεπάρκεια βιταμίνης D σχετίζεται με ατοπία, όπως αυτή ορίζεται από την αύξηση των κατάλληλων για την ηλικία επιπέδων IgE, ενώ το μέσο επίπεδο βιταμίνης D είναι μόνο ελαφρώς χαμηλότερο στα ασυμπτωματικά ατοπικά παιδιά σε σύγκριση με τα υγιή παιδιά. Κατά τη διάρκεια της πανδημίας, υπό πρωτοφανείς συνθήκες και απουσία άλλων λοιμώξεων, τα επίπεδα βιταμίνης D στον ορό ήταν υψηλότερα και λιγότερα παιδιά εμφάνιζαν ανεπάρκεια, πιθανότατα λόγω μειωμένης ανάγκης για βιταμίνη D στη διαδικασία της ανοσορρύθμισης. Η ανεπάρκεια βιταμίνης D ενδέχεται να μην αποτελεί παράγοντα κινδύνου, αλλά μάλλον συνέπεια της φλεγμονής, που προκαλείται από ατοπία ή ιογενείς λοιμώξεις, δεδομένου ότι η βιταμίνη D χρησιμοποιείται από τα μακροφάγα και τα Τ και Β λεμφοκύτταρα στις ανοσορρυθμιστικές διεργασίες. Στα ασυμπτωματικά ατοπικά παιδιά, τα επίπεδα βιταμίνης D θα πρέπει να μετρώνται και, εφόσον διαπιστώνεται ανεπάρκεια, να διορθώνονται, προκειμένου να μεταβληθεί η φυσική πορεία της αλλεργικής φλεγμονής. Η υπόθεση αυτή θα μπορούσε να είναι σημαντική για την ανάπτυξη στρατηγικών πρόληψης των αλλεργικών νοσημάτων στα παιδιά .Η μελέτη 3 έδειξε ότι σε παιδιά ηλικίας 4–16 ετών με λοιμώξεις του αναπνευστικού (RTI), ο μυϊκός πόνος ήταν συχνότερος σε εκείνα με λοίμωξη από ιό της γρίπης, ενώ η διάρροια, η ρινική συμφόρηση και η ταχυκαρδία ήταν συχνότερες σε παιδιά με μη γριππώδεις λοιμώξεις. Το σύμπτωμα που παρουσίασαν όλα τα παιδιά ήταν ο πυρετός, ο οποίος στα παιδιά με γρίπη ήταν υψηλότερος. Σημαντικά μεταβαλλόμενες αιματολογικές παράμετροι ήταν τα λεμφοκύτταρα, τα μονοκύτταρα, τα ηωσινόφιλα και τα αιμοπετάλια, καθώς και ο λόγος ουδετερόφιλων προς λεμφοκύτταρα (NLR) και ο λόγος αιμοπεταλίων προς ουδετερόφιλα (PNR). Οι ιογενείς λοιμώξεις του αναπνευστικού στα παιδιά ενδέχεται να μειώνουν το μέγεθος των αιμοπεταλίων μέσω καταστολής της ενεργοποίησής τους κατά τις πρώτες 48 ώρες της νόσου. Η μέση τιμή όγκου αιμοπεταλίων (MPV) βρέθηκε επίσης να δρα θετικά ως δείκτης οξείας φάσης σε παιδιά με γριππώδη λοίμωξη του αναπνευστικού, με τα επίπεδα MPV να είναι σημαντικά αυξημένα σε αυτά τα παιδιά. Η αντίδραση αυτή σχετίζεται με χαμηλά επίπεδα βιταμίνης D, τα οποία είναι πιθανό να τροποποιούν την αλληλεπίδραση ιού–αιμοπεταλίων–ανοσολογικής/φλεγμονώδους απόκρισης. Από τους φλεγμονώδεις παράγοντες, μόνο η CRP και η IL-10 εμφανίστηκαν σημαντικά μεταβαλλόμενες στις λοιμώξεις του αναπνευστικού, ενώ τα επίπεδα βιταμίνης D ήταν χαμηλά, πλησιάζοντας τη στατιστική σημαντικότητα. Η ασυμπτωματική ατοπία φαίνεται να προδιαθέτει σε ιογενείς λοιμώξεις του αναπνευστικού. Η μελέτη 4 είχε ως στόχο να εντοπίσει εκείνα τα βρέφη με υποτροπιάζον συριγμό που διατρέχουν αυξημένο κίνδυνο για μελλοντικές υποτροπές. Η ανεπάρκεια βιταμίνης D φαίνεται να αποτελεί παράγοντα που σχετίζεται με την παρουσία υποτροπιάζοντος συριγμού στα παιδιά· επομένως, συνιστάται ο προσδιορισμός των επιπέδων ορού 25(OH)D. Επιπλέον, θεωρούμε ότι η μέτρηση των επιπέδων βιταμίνης D στον ορό θα πρέπει να εντάσσεται στη ρουτίνα αξιολόγησης των παιδιών με υποτροπιάζον συριγμό και να διορθώνεται σε περίπτωση ανεπάρκειας. Η ανοσορρύθμιση, όπως αυτή εκτιμάται μέσω των επιπέδων IL-10 και IL-31, εξαρτάται από τον τύπο του συριγμού, καθώς και από την οξεία φάση της νόσου ή τη γενική κατάσταση υγείας. Ωστόσο, απαιτούνται περισσότερες μελέτες για την επιβεβαίωση των αποτελεσμάτων μας.

La copii, prevalența deficitului și insuficienței de vit D chiar într-o regiune însorită este ridicată și prezintă variații sezoniere, cu niveluri serice normale de 25(OH)D în lunile însorite și niveluri scăzute în lunile mai puțin însorite. Datele noastre sugerează că utilizarea produselor de protecție solară în timpul verii permite ca pielea să primească o cantitate suficientă de lumină solară pentru a permite producerea de vit D la un nivel capabil să mențină nivelurile serice de 25(OH)D în limite normale în lunile însorite. Utilizarea produselor de protecție solară în lunile de vară trebuie încurajată, deoarece, conform studiului nostru, nu reprezintă un factor de risc pentru deficiența vit D. Rezultate studiului 2 susțin o legătură între statusul vit D și diferite tipuri de inflamații, mai concret alergice sau infecțioase. Deficitul de vit D este asociat cu atopia definită ca și creșterea nivelului de IgE corespunzător vârstei, iar nivelul mediu de vit D este doar ușor scăzut la copiii atopici asimptomatici, comparativ cu copiii sănătoși. În timpul pandemiei, în circumstanțe fără precedent care constau în absența altor infecții, nivelurile serice de vit D au fost mai mari și mai puțini copii au fost predispuși să aibă un status deficient, datorită mai probabil unei cereri reduse de vit D în procesele de imunomodulare. Deficitul de vit D poate să nu fie un factor de risc, ci mai degrabă o consecință a inflamației, cauzată de atopie sau infecții virale, datorită faptului că este folosită de macrofage, limfocitele T și B în procesele de imunomodulare. La copiii asimptomatici atopici, nivelul vit D trebuie măsurat și, dacă este deficitar, trebuie corectat pentru a încerca schimbarea evoluției naturale a inflamației alergice. Această ipoteză ar putea fi importantă pentru dezvoltarea strategiilor de prevenție a bolilor alergice la copii. Studiul 3 a arătat că la copiii de 4-16 ani cu ITR, durerile musculare au fost mai frecvente la cei cu infecție gripală, în timp ce diareea, congestia nazală și tahicardia, au fost mai frecvente la copiii cu infecții non-gripale. Simptomul prezent la toți copiii a fost febra, care la cei cu gripă a fost mai înaltă. Parametrii hematologici modificați semnificativ au fost limfocitele, monocitele, eozinofilele și trombocitele precum și raportul dintre neutrofile și limfocite (NLR) și cel dintre trombocite și neutrofile (PNR). ITR virale la copii pot diminua dimensiunea trombocitelor probabil prin suprimarea activării trombocitelor, încă din primele 48 de ore de boală. De asemenea, s-a constatat că MPV a acționat pozitiv ca un reactiv în fază acută la copiii cu ITR gripală, iar nivelurile MPV au fost semnificativ crescute la acești copii. Acest răspuns este asociat cu niveluri scăzute de vit D, care probabil modifică interacțiunea virus-trombocite-răspuns imun/inflamator. Dintre factorii inflamatori, numai PCR și IL-10 sunt modificate semnificativ în ITR, în timp ce vit D este scăzută la limita semnificației. Se pare ca atopia asimptomatică predispune la infecții respiratorii virale. Studiul 4 a avut ca și obiectiv, identificarea acelor sugari cu wheezing recurent care prezintă risc crescut de recidive ulterioare. Deficiența vit D se pare a fi un factor asociat cu prezenta wheezing-ului recurent la copii, prin urmare determinarea nivelului seric de 25(OH)D este recomandată. Mai mult, considerăm că măsurarea nivelului seric de vit D ar trebui inclusă în evaluarea de rutină a copiilor cu wheezing recurent, iar în caz de deficiență aceasta trebuie corectată. Modularea imună, măsurată prin nivelurile de IL-10 și IL-31 depinde de fenotipul de wheezing, precum și de faza acută a bolii sau de statusul general al sănătății. Sunt necesare însă studii mai ample pentru a confirma rezultatele noastre.