Molekularni obrasci povezani s oštećenjem tkiva kao medijatori upale u kroničnoj opstrukcijskoj plućnoj bolesti

master's thesis

• Title (english): Damage-associated molecular patterns as mediators of inflammation in chronic obstructive pulmonary disease
• Author: Višnja Rešić
• Mentor: Anita Somborac Bačura (mentor)
• Committee member: Anita Somborac Bačura (predsjednik povjerenstva)
• Committee member: Andrea Hulina Tomašković (član povjerenstva)
• Committee member: Sandra Šupraha Goreta (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2021-04-01, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Kronična opstrukcijska plućna bolest (KOPB) je jedan od vodećih uzročnika smrti u svijetu, što predstavlja veliki javnozdravstveni izazov. Pušenje cigareta je najčešći okolišni čimbenik rizika za razvoj KOPB-a. Budući da se dijagnosticira u relativno kasnom stadiju bolesti, postavlja se pitanje potencijalnih ranijih biljega bolesti. Dim cigarete može uzrokovati oštećenje rezidentnih stanica u plućima i dovesti do oslobađanja različitih molekularnih obrazaca povezanih s oštećenjem tkiva (DAMP molekule ili alarmini) u izvanstanični prostor, a koje je moguće mjeriti u tjelesnim tekućinama. Dokazano je da otpuštanje DAMP molekula potaknuto dimom cigarete može dovesti do neprikladnih upalnih reakcija kakve se eksprimiraju kod bolesnika s ovom bolešću. Ovaj diplomski rad daje pregled najnovijih saznanja o DAMP molekulama kao upalnih medijatora kod bolesnika s KOPB-om, čije su se vrijednosti u serumu / plazmi / BAL tekućini/ sputumu/ mokraći pokazale znatno različitima od onih kod zdravih pušača, ili nepušača. Pojedini alarmini (HSP27, HSP70, S100 proteini, galektini, LL-37, mokraćna kiselina, HMGB1, mtDNA i eATP) pokazuju korelaciju s različitim parametrima plućne funkcije i težinom bolesti, kao i serumskim biomarkerima za procjenu egzacerbacija KOPB-a i komorbiditeta. Nadalje, kalprotektin se pokazao potencijalnim biomarkerom diferencijacije KOPB-a i astme, dok se pomoću S100A8 mogu razlikovati KOPB i sindrom preklapanja astme i KOPB-a. U budućnosti bi klasifikacija bolesnika mogla biti olakšana budući da pojedine DAMP molekule mogu razlikovati svaku skupinu bolesnika s obzirom na GOLD ABCD klasifikaciju (težinu simptoma i povijest egzacerbacija) kao i samo prema GOLD stadijima (2 – 4 stupanj), no potrebna su daljnja istraživanja.

Abstract (english)

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world and represents a major public health challenge. Cigarette smoking is the most common environmental risk factor for developing COPD. Given the fact that it is diagnosed at a relatively late stage of the disease, the question of potential earlier markers of the disease arises. Cigarette smoke can cause damage to resident cells in the lungs, leading to the release of various damage associated molecular patterns (DAMP molecules or alarmins) in the extracellular space, which can be measured in body fluids. It has been shown that the release of a DAMP molecules by cigarette smoke can lead to inappropriate inflammatory reactions such as those expressed in COPD patients. This diploma thesis provides an overview of the latest findings on DAMP molecules as inflammatory mediators in patients with COPD, and their values in serum / plasma / BAL fluid / sputum / urine were found significantly different from those in a healthy smokers, or non-smokers. Some of these alarmins (HSP27, HSP70, S100 proteins, galectins, LL-37, uric acid, HMGB1, mtDNA and eATP) show correlation with different lung function parameters and disease severity, as well as with serum biomarkers for the assessment of COPD exacerbations and comorbidities. Furthermore, calprotectin may serve as a valuable biomarker for differentiating COPD and asthma, while S100A8 is a biomarker for differentiating COPD and asthma-COPD overlap syndrome. In the future, patient classification could be facilitated as some DAMP molecules can differentiate each group of patients according to GOLD ABCD classification (severity of symptoms and history of exacerbation) as well as only according to GOLD stages (grade 2-4), but further studies are needed to validate these findings.

• Keywords: kronična opstrukcijska plućna bolest; KOPB; DAMP molekule; alarmini; upala
• Keywords (english): chronic obstructive pulmonary disease; COPD; DAMP molecules; alarmins; inflammation
• Language: croatian
• URN:NBN: urn:nbn:hr:163:977645
• Study programme: Title: Medical biochemistry; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra medicinske biokemije i laboratorijske medicine (magistar/magistra medicinske biokemije i laboratorijske medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2022-04-08
• Created on: 2022-03-03 09:48:02