Lokalni i sistemski biomarkeri upale u djece s kontroliranom i nekontroliranom astmom

Navratil, Marta (2014) Lokalni i sistemski biomarkeri upale u djece s kontroliranom i nekontroliranom astmom. PhD thesis, Sveučilište u Zagrebu.

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Abstract

BACKGROUND: Over last 15 years there has been increasing interest in the non-invasive assessment of airway inflammation in addition to traditional parameters of asthma control and severity. ----- AIMS: 1) to compare different inflammatory biomarkers (BMs) in children with controlled and uncontrolled asthma, 2) to investigate their relationship with each other and with other clinical indices of asthma control (symptoms, lung function, prn salbutamol use, exacerbations, asthma control test [ACT], quality of life [AQLQ]). ----- MATERIALS AND METHODS: This prospective, observational, parallel-cohort study comprised 103 consecutive patients (age 6-18 years) with controlled ([CA], n=50) and uncontrolled ([UA], n=53) asthma. Measured lung function and BMs included: spirometry, eosinophilic cationic protein (ECP), high-sensitivity C-reactive protein (hs-CRP), blood counts with differentials, exhaled NO (FENO), pH and urates in EBC, and exhaled breath temperature (EBT). ----- RESULTS: EBC urates, EBC pH and EBT showed statistically significant differences between groups (UA vs. CA: EBC urates, median [IQR], μmol/L; 0 [3] vs 37,9 [26], p≤0,0001; EBC pH, mean [SD], 7,2 [0,17] vs. 7,33 [0,16], p=0,002; EBT mean [SD], °C; 34,26 [0,83], vs 33,90 [0,60], p=0,014). Discriminant analysis depicted EBC urates as the best single significant predictor of asthma control (F=57,899; p≤0,0001) with a 79,6% diagnostic accuracy. Serum hs-CRP significantly positively correlated with symptom score, prn salbutamol use, and EBT (r=0,395, p=0,003; r=0,240, p=0,014; r=0,445, p≤0,0001; respectively) and inversely with FEV1 (r=-0,366, p=0,007). EBC urates showed significant association with time from last exacerbation (TLE) and FENO (r=0,558, p≤0,0001; r=0,3839; p=0,005, respectively) in UA, and EBC pH (r=0,379; p≤0,0001), EBT (r=-0,220; p=0,025), FEV1 (as % predicted) (r=0,225, p=0,022), ACT (r=0,665; p≤0,0001), AQLQ (r=0,703, p≤0,0001), prn salbutamol use (r=-0,538; p≤0,0001), and symptom score (r=-0,722; p≤0,0001) in all asthmatics. ----- CONCLUSION: EBC urates were the best single predictor of asthma control. Our results provide the evidence supporting the potential utility of a panel of non-invasive BMs of local and systemic inflammation, as additional tools for monitoring childhood asthma.

Abstract in Croatian

UVOD: Obzirom na manjkavosti tradicionalnih parametara kontrole i težine astme, zadnjih 15-tak godina istraživanja su usmjerena k pronalaženju neinvazivnih biomarkera (BM-a) upale u dišnim putovima. ----- CILJEVI: 1. usporediti različite upalne BM-e u djece s kontroliranom i nekontroliranom astmom, 2. ispitati povezanost BM-a upale međusobno i s drugim pokazateljima aktivnosti bolesti (simptomi, plućna funkcija, potreba za salbutamolom, egzacerbacije, upitnik o kontroli astme [ACT], kvaliteta života [AQLQ]). ----- MATERIJALI I METODE: Opservacijska usporedna studija kohorte paralelnih skupina uključila je 103 djece (dob 6-18 godina) s kontroliranom ([KA], n=50) i nekontroliranom ([NA], n=53) astmom. Mjerena je plućna funkcija i slijedeći BM-i: eozinofilni kationski protein (ECP), C-reaktivni protein velike osjetljivosti (hs-CRP), kompletna krvna slika, izdahnuti NO (FENO), pH i urati u kondenzatu izdaha (KI) i temperatura izdaha (TI). ----- REZULTATI: Koncentracija urata u KI, pH vrijednost KI i TI su se statistički značajno razlikovale između skupina (NA vs. KA: urati u KI, medijan [IQR], μmol/L; 0 [3] vs 37,9 [26], p≤0,0001; pH u KI, srednja vrijednost [SD], 7,2 [0,17] vs. 7,33 [0,16], p=0,002; TI srednja vrijednost [SD], °C; 34,26 [0,83], vs 33,90 [0,60], p=0,014). Diskriminantna analiza je pokazala da su urati u KI najbolji samostalni parametar u razlikovanju kontrolirane od nekontrolirane astme (F=57,899; p≤0,0001) uz dijagnostičku točnost 79,6%. Serumski hs- CRP je bio značajno proporcionalno povezan sa zbirom simptoma potrebom za salbutamolom, TI (r=0,395, p=0,003; r=0,240, p=0,014; r=0,445, p≤0,0001) i obrnuto proporcionalno s FEV1 (r=-0,366, p=0,007). Urati u KI su bili statistički značajno proporcionalno povezani s vremenskom udaljenošću zadnje egzacerbacije (PZE) i FENO-om (r=0,558, p≤0,0001; r=0,3839; p=0,005) u NA, i pH u KI (r=0,379; p≤0,0001), TI (r=-0,220; p=0,025), FEV1 (r=0,225, p=0,022), ACT-om (r=0,665; p≤0,0001), AQLQ (r=0,703, p≤0,0001), potrebom za salbutamolom (r=-0,538; p≤0,0001) i zbirom simptoma (r=-0,722; p≤0,0001) u svih astmatičara. ----- ZAKLJUČAK: Urati u KI su najbolji samostalni parametar u predviđanju kontrole astme. Rezultati ukazuju na moguću vrijednost neinvazivnih BM-a lokalne i sistemske upale kao dodatnih parametara u praćenju kontrole dječje astme.

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