Title Mogućnosti rane dijagnostike kronične opstruktivne plućne bolesti u populaciji pod rizikom Title (english) Possibilities of early diagnosis of chronic obstructive pulmonary disease in the population at risk Author Žarko Vrbica Mentor Davor Plavec (mentor)Committee member Suzana Mladinov (predsjednik povjerenstva)Committee member Miroslav Samaržija (član povjerenstva)Committee member Mislav Radić (član povjerenstva)Granter University of Split Defense date and country 2024-11-27, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 616 - Pathology. Clinical medicine Abstract Uvod: Pušenje je glavni uzrok nastanka KOPB-a, ali samo oko 1/3 pušača razviju KOPB tijekom života. Progresivni tijek KOPB-a uz značajan morbiditet i mortalitet indiciraju potrebu za što ranijim otkrivanjem bolesti kako bi se što prije započelo s liječenjem. Metode: MARKO projekt je multicentrično prospektivno kohortno istraživanje koje uključuje 500 ispitanika s rizikom za nastanak KOPB-a (pušači/bivši pušači ≥20 pušačkih godina u dobi od 40-65 godina, oba spola, bez prije postavljene dijagnoze KOPB-a). Ispitivanje je planirano u dvije faze: (1) presječno istraživanje: razvoj i validacija novog upitnika uz evaluaciju učinkovitosti ručnog COPD-6™ spirometra u ordinaciji obiteljske medicine u pronalaženju bolesnika s KOPB-om u rizičnoj populaciji; i (2) prospektivno istraživanje: praćenje kohorte ispitanika iz populacije pod rizikom za nastanak KOPB-a. Ispitanici su uključeni iz 25 ambulanti obiteljske medicine i pregledani od strane pulmologa u 7 bolničkih centara prema predefiniranom protokolu: upitnicima za s bolesti povezanom kvalitetom života, anamnezom, fizikalnim pregledom, uzimanjem uzoraka krvi, mjerenjem temperature izdahnutog zraka, mjerenjem plućne funkcije i šestominutnim testom hoda. Ispitanici kod kojih nije postavljena dijagnoza KOPB-a kao i oni s KOPB-om prvog stupnja po GOLD-u su uključeni u dalje praćenje i procjenu progresije bolesti nakon dvije godine, a planira se i ponovna evaluacija nakon 5 godina praćenja. Rezultati: U prvoj fazi, KOPB je dijagnosticiran kod 43 ispitanika (18,9% od ispitanika s rizikom) što indicira poboljšanje postupaka za pronalaženje oboljelih unutar populacije s rizikom za KOPB. Portabilni COPD-6™ spirometar je pokazao visoku specifičnost i nisku osjetljivost za postavljanje dijagnoze KOPB-a, ali smo dokazali kako se uporabom dvije različite granične vrijednosti ispitanici mogu podijeliti u dvije skupine: skupinu s dokazanim KOPB-om (FEV1/FEV6 < 0.7) i skupinu kod koje je isključeno postojanje KOPB-a (FEV1/FEV6>0.85) što ostavlja samo manji broj nedefiniranih bolesnika između ove dvije vrijednosti, a kod kojih je indicirana dalja dijagnostička obrada. Na temelju psihometrijske analize i visoke podudarnosti s validiranim upitnicima za procjenu kvalitete života, MARKO upitnik pokazao se pouzdanim kao kratki alat za samoprocjenu ispitanika. U drugoj fazi nakon dvije godine praćenja, našli smo učestalost novonastalog KOPB-a od 4.911/100 osoba-godina (95% CI [3.436–6.816]). Analizom eksploratornih čimbenika MARKO upitnika izolirane su tri odvojene domene (zaduha i umor, “egzacerbacije”, kašalj uz iskašljavanje). Pitanja o zadusi i egzacerbacijama kao i muški spol su bili prediktivni čimbenici za nastanak KOPB-a u rizičnoj populaciji nakon dvije godine praćenja (AUC 0.79, 95% CI [0.74–0.84], p < 0.001). Promjena temperature izdahnutog zraka nakon pušenja cigarete (ΔEBT) pri inicijalnoj obradi je bila značajno prediktivna za progresiju bolesti (p < 0.05) uz AUC od 0.859 (p=0.011) osjetljivost od 66.7% i specifičnost od 98.1% za novo dijagnosticirani KOPB uz uporabu LLN kriterija. Zaključak: Ovo je jedno od prvih kohortnih ispitivanja koje pokušava ustanoviti incidenciju KOPB a kod pre-simptomatskih ispitanika iz rizične skupine prije nastanka značajnog oštećenja ciljnih organa. Rezultati našeg ispitivanja upućuju na potrebu uvođenja aktivnog traženja oboljelih u populaciji s rizikom (nađeno je skoro 20% nedijagnosticiranih bolesnika s KOPB-om). Testiranje plućne funkcije s COPD-6™ može zamijeniti spirometriju ukoliko ona nije lako dostupna. Rezultati MARKO upitnika u kombinaciji s ΔEBT mogu potencijalno poslužiti kao rani biljeg budućeg razvoja KOPB-a kod rizičnih pušača. Registracija ispitivanja: Clinicaltrial.gov NCT01550679 retrospektivno registrirano 28. veljače 2012.
Abstract (english) Introduction: Main risk factor for the development of chronic obstructive pulmonary disease (COPD) is smoking, but only less than 1/3 of smokers develop clinically manifest COPD. COPD’s progressive nature with high disability and mortality makes it plausible to detect it as early as possible thus allowing for an early intervention. Methods: MARKO project is a multicenter prospective cohort study recruiting 500 subjects at risk for COPD (smokers/ex-smokers ≥20 pack-years, 40–65 years, both sexes, with no prior diagnosis of COPD) in two phases: (1) cross-sectional: development and validation of a new questionnaire and evaluation of the efficacy of the handheld COPD-6™ in GP’s office in case finding of COPD from the population at risk; and (2) prospective: follow-up of a cohort of patients at risk for COPD. Subjects were recruited by 25 GPs and assessed for COPD by dedicated pulmonologists in 7 hospital centers using a predefined protocol: HRQoL, history, physical, blood sampling, exhaled breath temperature (EBT), lung function, 6-min walk test (6MWT). Patients without COPD and those in GOLD stage 1 at initial assessment were reassessed for disease progression by the same pulmonologist after 2 years and are planned to be reassessed again after 5 years. Results: In the phase I, COPD was diagnosed in 43 subjects (18.9 %), which indicate the need for better case finding procedures in the population at risk. The handheld COPD-6™ showed high specificity but low sensitivity for the COPD diagnosis but we found that by using two different cut off values we can stratify the majority of the patients to the two groups: COPD group (FEV1/FEV6 < 0.7) and group without COPD (FEV1/FEV6>0.85) leaving only small number of patients between these two values for further diagnostic workout. Based on psychometric analyses and high convergent validity correlation with already validated QoL questionnaires, the newly developed MARKO questionnaire was shown to be a reliable self-administered short health status assessment tool. In the phase II, after two years of follow up, we have determined a rate for incident COPD that was 4.911/100 person-years (95% CI [3.436–6.816]). Exploratory factor analysis of MARKO questionnaire isolated three distinct domains (breathlessness and fatigue, “exacerbations”, cough, and expectorations). We found out that questions about breathlessness and “exacerbations”, and male sex were predictive of incident COPD after two years follow-up (AUC 0.79, 95% CI [0.74–0.84], p < 0.001). The change in EBT after smoking a cigarette at initial visit (ΔEBT) was significantly predictive for disease progression after 2 years (p < 0.05) with an AUC of 0.859 (p=0.011) with sensitivity of 66.7% and specificity of 98.1% for newly diagnosed COPD using LLN criteria. Conclusion: This is one of the first cohort studies attempting to establish the incidence of COPD in the presymptomatic stage before significant end organ damage. Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD). Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available. The MARKO questionnaire combined with ΔEBT could potentially serve as early markers of future COPD in smokers at risk. Trial registration: Clinicaltrial.gov NCT01550679 retrospectively registered February 28, 2012.
Keywords
Kronična opstruktivna plućna bolest
Keywords (english)
Chronic Obstructive Pulmonary Disease
Language croatian URN:NBN urn:nbn:hr:171:146422 Study programme Title: Biology of Neoplasms Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2024-11-14 09:08:15
