| Abstract | CILJ: Slijedeći eksperimentalne dokaze o pojačanom stvaranju i patofiziološkoj ulozi ET-1 u astmi, cilj je ovog rada bio istražiti koncentraciju ET-1 u induciranom iskašljaju (IS) i plazmi te procijeniti njegovu vrijednost u razlučivanju zdravih ispitanika i astmatičnih bolesnika te bolesnika tijekom stabilne i pogoršane bolesti. Također, cilj je bio procijeniti sigurnost upotrijebljene metode indukcije iskašljaja u astmatičnih bolesnika tijekom pogoršanja bolesti s obzirom na njezin poznati neizravni bronhoprovokacijski učinak. ----- ISPITANICI I METODE: Istraživanje je provedeno u 26 bolesnika sa stabilnom astmom koji su u ispitivanom razdoblju imali pogoršanje – egzacerbaciju – bolesti i u 21 zdravog kontrolnog ispitanika. Najvažniji kriterij za isključivanje bolesnika iz istraživanja bio je izostanak pogoršanja bolesti u ispitivanom razdoblju, a za sve ispitanike neuspješnost indukcije iskašljaja. Sigurnost metode indukcije iskašljaja u bolesnika s astmom procijenjena je na temelju spirometrijskih nalaza i subjektivnih tegoba. U uzorcima IS i venske krvi imunokemijski je izmjerena koncentracija ET-1 i ECP-a, a u IS također i koncentracija ukupnih bjelančevina i albumina. ----- REZULTATI: Izmjerene koncentracije ET-1 i ECP u IS bile su višestruko više nego u venskoj krvi. U IS i venskoj krvi nije se ET-1 statistički bitno razlikovao između zdravih ispitanika i bolesnika, a ni između stabilne i pogoršane bolesti. Nasuprot tome ECP u IS bitno se razlikovao između bolesnika i zdravih ispitanika (p<0.001), te između stabilne i pogoršane bolesti (p= 0.024). ECP u venskoj krvi statistički se bitno razlikovao samo između stabilne i pogoršane bolesti (p= 0,048). U bolesnika tijekom stabilne bolesti nađena je bitna negativna korelacija između ET-1 i ECP u IS (ρ = -0.473, p= 0.026), te između ET-1 i albumina u IS (ρ= -0.508, p= 0.016). Kada je ET-1 u IS izražen u odnosu na albumine u IS, nađena je neočekivano statistički bitno niža koncentracija u bolesnika tijekom pogoršanja bolesti nego u kontrolnih ispitanika (p= 0.009). ET-1 izražen u odnosu na albumine korelirao je bitno s koncentracijom ET-1 u venskoj krvi u bolesnika tijekom stabilne bolesti (ρ= 0.436, p= 0.030) i s ECP-om u IS u svim ispitivanim skupinama. Nije nađena statistički bitna povezanost između koncentracije ET-1 u IS i venskoj krvi sa spirometrijskim pokazateljima ni za jednu ispitivanu skupinu. Nasuprot tome, ECP u IS korelirao je bitno s osnovnim FEV1 (ρ= -0.429, p= 0.041) i PEF (ρ= -0.430, p= 0.041) u bolesnika tijekom pogoršanja bolesti. Nije nađena bitna povezanost ET-1 i ECP-a sa simptomima bolesti ni u stabilnoj niti u pogoršanoj bolesti. Metoda indukcije iskašljaja procijenjena je jednako sigurnom u pogoršanju bolesti kao i tijekom stabilne bolesti. Spirometrijski nalazi nakon postupka indukcije iskašljaja nisu se bitno razlikovali između stabilne i pogoršane bolesti za FEV1 (p= 0,115), PEF (p= 0,808) i FEF50 (p= 0,088). Također, nalazi nakon indukcije iskašljaja, tijekom stabilne bolesti nisu se bitno razlikovali od osnovnih nalaza za FEV1 (p= 0,105), i FEF50 (p= 0,580), a tijekom pogoršanja bolesti za FEV1 (p= 0,622), PEF (p= 0,899) i FEF50 (p= 0,160). Pogoršanje simptoma tijekom indukcije iskašljaja bitno je koreliralo s pogoršanjem plućne funkcije i to za sva tri pokazatelja, i tijekom stabilne bolesti: FEV1 (ρ= -0.665; p= 0.001), PEF (ρ= -0.772; p<0.001) i FEF50 (ρ= -0.578; p= 0.004) i tijekom pogoršane bolesti: FEV1 (ρ= -0.434: p= 0.039), PEF (ρ= -0.529; p= 0.009) i FEF50 (ρ= -0.444; p= 0.034). ----- ZAKLJUČAK: Koncentracija ET-1 u IS i venskoj krvi nije se pokazala vrijednom metodom u razlučivanju ispitivanih astmatičnih bolesnika od kontroliranih ispitanika, kao i razlučivanju stanja stabilne i pogoršane bolesti. Nađena je velika varijabilnost nalaza u IS bolesnika koja ukazuje na složene i neujednačene promjene u pogledu stvaranja tog medijatora u astmi. Neočekivano niska koncentracija ET-1 u IS bolesnika tijekom pogoršanja bolesti kao i bitna negativna povezanost s albuminima u IS upućuje na mogućnost da albumini ili pridruženi čimbenici u pogoršanju bolesti i/ili postupku indukcije iskašljaja utječu na niske izmjerene vrijednosti. Metoda indukcije iskašljaja, uz pridržavanje mjera sigurnosti, u bolesnika s astmom pokazala se jednako sigurnom tijekom pogoršanja kao i tijekom stabilne bolesti. |
| Abstract (english) | AIM: Following the experimental proofs of the increased formation and pathophysiological role of ET-1 in asthma, the aim of this study was to examine the concentration of ET-1 in the induced sputum (IS) and in plasma, and to evaluate its level in differentiation between healthy examinees and patients with asthma, as well as between the patients during stable and exacerbated disease. The other aim was to evaluate the security of the applied method of induced sputum in patients with asthma during exacerbation of a disease in regard of its known indirect bronchoprovocational effect. ----- EXAMINEES AND METHODS: The study included 26 patients with stable asthma who had deterioration i.e. exacerbation of a disease during the study period and 21 healthy examinees. The most important criterion for excluding the examinees from the study was the absence of disease deterioration during the study period in patients and failure of sputum induction in healthy subjects. Reliability of sputum induction method in patients with asthma was evaluated according to spirometry findings and individual disorders during the procedure. Concentration of ET-1 and ECP were measured immunochemically in IS samples and venous blood. Concentration of total proteins and albumins was also measured in IS samples. ----- RESULTS: Measured concentrations of ET-1 and ECP in IS were manifold higher than in venous blood. ET-1 in IS and venous blood were not significantly different between healthy examinees and patients, nor between stable and exacerbated disease. Conversely, ECP in IS was significantly different between patients and healthy examinees (p<0.001), and between stable and exacerbated disease (p=0.024). The level of ECP in venous blood was significantly different between stable and exacerbated disease (p=0.048). In patients with stable disease significant negative correlation between ET-1 and ECP in IS was found (r = - 0.473, p= 0.026), and between ET-1 and albumins in IS (r = - 0.508, p= 0.016). When ET-1 in IS is expressed compared to albumins in IS, unexpected statistically significant lower concentration was found in patients during disease exacerbation than in the control group of examinees (p=0.009). ET-1 expressed in comparison to albumins correlated significantly with ET-1 concentration in venous blood in patients during stable disease (r = 0.436, p = 0.030) and with ECP in IS in all groups of examinees. No statistically significant correlation between concentrations of ET-1 in IS and venous blood, and spirometric indicators has been found in any of the investigated groups. Conversely, ECP in IS correlated significantly with basic FEV1 (r = - 0.429, p = 0.041 and PEF (r= -0.430, p=0.041) in patients during exacerbation of a disease. No significant correlation of ET-1 and ECP and disease symptoms has been found in stable or in exacerbated disease. Method of induced sputum has been evaluated equally reliable in disease exacerbation and during stable disease. Spirometric findings after induced sputum did not differ significantly between stable and exacerbated disease for FEV1 (p= 0.115), PEF (p=0.808) and FEF 50 (p= 0.088). Findings after sputum induction during stable disease didn't differ significantly from basic findings for FEV1 (p=0.105) and FEF50 (p=0.580), and during exacerbation for FEV1 (p=0.622), PEF (0.899) and FEF50 (p=0.160). Exacerbation of symptoms during sputum induction significantly correlated to deterioration of pulmonary function for all three indicators, both during stable disease: FEV1 (r=-0.665; p=0.001), PEF (r=-0.772; p<0.001) and FEF50 (r=-0.578; p=0.004) and during disease exacerbation: FEV1 (r=-0.434; p=0.039), PEF (r=-0.529; p=0.009) and FEF50 (r=-0.444; p=0.034). ----- CONCLUSION: Concentration of ET-1 in IS and in venous blood has not been found a worthy method in distinguishing patients with asthma from control group of examinees, nor in distinguishing stable condition and exacerbated disease. A great variability of findings in IS patients suggesting complex and uneven changes concerning creation of this mediator in asthma has been found. Unexpectedly low concentration in IS patients during disease exacerbation and significant negative correlation to albumins in IS, suggest the possibility that albumins or associated factors in disease deterioration and/or procedure of sputum induction influence low values. Method of sputum induction, considering security measures requirements, in patients with asthma was equally safe during disease deterioration and during stable disease. |
