Lau Yin Kei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 58-79). / Abstracts in English and Chinese. / Acknowledgement --- p.I / Abstract --- p.IV / Abstract in Chinese --- p.VI / Abbreviations --- p.VIII / Introduction --- p.1 / Chapter 1.1 --- Prevalence of COPD and asthma in Hong Kong --- p.1 / Chapter 1.2 --- Players in pathogenesis of COPD --- p.2 / Chapter 1.3 --- Players in pathogenesis of asthma --- p.4 / Chapter 1.4 --- The use of exhaled breath condensate in previous studies --- p.6 / Chapter 1. 5 --- Brief overview of chemokines --- p.8 / Chapter 1.6 --- Objective of this study --- p.12 / Materials and methods --- p.14 / Chapter 2.1 --- Study population --- p.14 / Chapter 2.1.1 --- Patients with COPD and control subjects --- p.14 / Chapter 2.1.2 --- Patients with asthma and control subjects --- p.15 / Chapter 2.2 --- Lung function --- p.15 / Chapter 2.3 --- Dyspnoea score measurement of patients with COPD --- p.16 / Chapter 2.4 --- Classification of patients and asthma severity --- p.16 / Chapter 2.5 --- Skin prick test and blood tests --- p.16 / Chapter 2.6 --- Collection of exhaled breath condensate --- p.17 / Chapter 2.7 --- Measurement of constituent in EBC --- p.17 / Chapter 2.7.1 --- "Measurement of 8-isoprostane, MCP-1 and GROα in patients with COPD and the corresponding control subjects" --- p.17 / Chapter 2.7.2 --- Measurement of eotaxin and MDC of patients with asthma and the corresponding control subjects --- p.18 / Chapter 2.8 --- Reproducibility of exhaled breath constituent --- p.18 / Chapter 2.8.1 --- "Assessment of reproducibility of the exhaled MCP-1, GROα and8- isoprostane measurements" --- p.19 / Chapter 2.8.2 --- Assessment of reproducibility of the exhaled eotaxin and MDC measurement --- p.19 / Chapter 2.9 --- Statistical analysis --- p.19 / Results --- p.21 / Chapter 3.1 --- Patients with COPD and corresponding control subjects --- p.21 / Chapter 3.2 --- Patients with asthma and corresponding control subjects --- p.28 / Discussion --- p.36 / Chapter 4.1 --- "Exhaled 8-isoprostane, GRO-α and MCP-1 of patients with COPD and corresponding control subjects" --- p.36 / Chapter 4.2 --- Exhaled eotaxin and MDC from patients with asthma and corresponding control subjects --- p.43 / Chapter 4.3 --- Technical aspects of EBC assessment --- p.49 / Future prospect --- p.54 / Conclusion --- p.56 / References --- p.58 / Tables and Figures / Table 1. Demographics of the COPD and control subjects --- p.22 / Figure 1. The level of 8-isoprostane in the exhaled breath condensate of COPD and control subjects --- p.23 / Figure 2. The level of GROa in the exhaled breath condensate of COPD and control subjects --- p.25 / "Figure 3 Bland and Altman's Plot of the repeatability of 8-isoprostane, GROa and MCP-1 in the exhaled breath condensate of normal controls" --- p.27 / Table2. Clinical and physiological details of the subjects --- p.29 / Figure 4. Level of eotaxin in exhaled breath condensate of asthma and control subjects --- p.30 / Figure 5 Level of MDC in exhaled breath condensate of asthma and control subjects --- p.31 / Table 3. Levels of eotaxin and MDC in exhaled breath condensate of asthma subjects on different dose of inhaled corticosteroids --- p.33 / Figure 6. Relationship between exhaled breath condensate level of MDC and total serum IgE level --- p.35

Diss. (sammanfattning) Umeå : Umeå universitet, 2010.

<p>Bolesti kardiovaskularnog sistema su vodeći uzrok smrtnosti među pacijentima sa poremećajem plućne funkcije. Poznato je da je plućna hipertenzija i posledična insuficijencija desne srčane komore često pratilac te&scaron;ke hronične opstruktivne bolesti pluća (HOBP). Međutim učestalost insuficijencije leve komore u poslednje vreme je predmet brojnih istraživanja i srčana insuficijencija je jo&scaron; uvek nedovoljno ispitana kod bolesnika sa HOBP. Cilj ove doktorske disertacije je ispitati funkciju leve komore i prisustvo plućne hipertenzije kod bolesnika sa HOBP. Materijal i metode : Istraživanjem je obuhvaćeno 120 ispitanika koji su prema GOLD kriterijumima podeljeni u četiri grupe po 30 bolesnika za svaki od četiri stadijuma bolesti. Svim bolesnicima je urađena spiropletizmografija i ehokardiografija. Rezultati : Analizom dobijenih vrednosti parametara (udarni volumen (SV) i njegov indeks (SVI), ejekciona frakcija (EF), frakcija skraćenja) sistolne funkcije miokarda leve komore dokazali smo da postoji sistolna disfunkcija miokarda leve komore kod bolesnika sa HOBP. Sa napredovanjem bolesti opadaju i vrednosti SV i SVI. Vrednosti ejekcione frakcije takođe opadaju sa porastom stepena HOBP. Analizom parametara dijastolne funkcije kod bolesika sa HOBP dokazali smo sa postoji dijastolna disfunkcija leve komore. Ispitivanjem transmitranog protoka i kontinuiranim i tkivnim doplerom registruju se smanjene srednje vrednosti vrednosti E/A i E&#39;/ A&#39;odnosa i u svim stadijumima bolesti. Ispitivanjem prisustva plućne hipertenzije dokazali smo da je sistolni pritisak u desnoj komori (RVSP) bio najniži u početnim stadijumima HOBP, postepeno raste sa težinom bolesti i najveći vrednosti se beleže u četvrtom stadijumu bolesti. Visoka prevalenca funkcionalnih promena na srcu koje smo dokazali u na&scaron;em istraživanju treba da ukaže na potrebu ehokardiografije u otkrivanju ovih poremećaja u HOBP.</p> / <p>Cardiovascular diseases are the leading cause of death among patients with impaired lung function. It is known that pulmonary hypertension and right heart failure are often companion of severe chronic obstructive pulmonary disease (COPD). Left ventricular dysfunction is still not well studied and it is the subject of numerous studies in patients with COPD in recent years. The aim of this dissertation is to examine the function of left ventricle and the presence of pulmonary hypertension in patients with COPD. Materials and Methods: The study included 120 patients who meet the GOLD criteria for COPD. They were divided into four groups of 30 patients for each of the four stages of the disease. All patients underwent echocardiography and spiropletismography. Results: Analysis of the obtained values of the systolic function parameters (stroke volume (SV) and it&rsquo;s index (SVI), ejection fraction (EF), fractional shortening) show impaired systolic left ventricular function in patients with COPD. With disease progression SV and SVI decrease. With increased severity of COPD the values of ejection fraction decreases. We showed diastolic dysfunction of the left ventricle in COPD patients. Transmitral continuous flow Doppler and tissue Doppler recorded reduced values of the mean E / A and E &#39;/ A&#39; in all stages of the disease. Examining the presence of pulmonary hypertension, we have shown that the systolic pressure in the right ventricle (RVSP) was the lowest in the early stages of COPD, gradually increases with the severity of disease and the highest value was recorded in the fourth stage of the disease. The high prevalence of functional changes in the heart that we have proved in our research highlights the need for echocardiography in the detection of these disorders in COPD.</p>

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 5 uppsatser.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Present study had examined the influence of the sympathetic modulation of the hypoxic respiratory pattern in patients with chronic obstructive pulmonary disease (COPD). 12 were evaluated with the disease and, for comparative purposes, 10 healthy patients also participated. The subjects were assessed for Heart Rate Variability (HRV) through Finapress, and concurrently monitored oxygen saturation and respiratory rate, for 5 minutes at rest. After this evaluation, spirometry was performed on each patient, resulting in the forced expiratory volume values in one second (FEV1) and the FEV1 and the Forced Vital Capacity (FVC). When correlated the levels of Oxygen Saturation (SpO2) and Tiffeneau index, there is direct variation between spirometric index and SpO2 (ρ = 0.45). The reverse occurs between systolic blood pressure (SBP) and SpO2 and FEV1 and band Lf SAP (ρ = -0.65). When analyzed HRV in the time domain, a statistically significant difference between groups for the band Lf (p = 0.01) and LF / HF ratio (p = 0.02). It was seen that, when compared to healthy subjects, patients with COPD had lower values of HRV increased SBP and decrease in oxygen saturation (SpO2) and spirometric indices. Still, the drop in autonomic function seems to be more impaired in patients where FEV1 indexes and the FEV1 / FVC are lower. Apparently, the drop in SpO2, due to the loss in gas exchange, seems to increase the sympathetic modulation, increasing the SBP levels. / O presente estudo analisou os determinantes da modulação simpática nos pacientes com Doença Pulmonar Obstrutiva crônica (DPOC). Foram avaliados 12 pacientes portadores da doença e, para fins comparativos, 10 pacientes saudáveis. Os sujeitos foram submetidos à avaliação da Variabilidade da Frequência Cardíaca (VFC) através do aparelho finapress, sendo concomitantemente monitorada a saturação de oxigênio e frequência respiratória, durante 5 minutos, em seu estado de repouso. Após esta avaliação, foi realizada a espirometria de cada paciente, obtendo-se os valores de Volume Expiratório Forçado no primeiro segundo (VEF1) e a relação entre VEF1 e a Capacidade Vital Forçada (CVF). Quando correlacionados os índices de Saturação de Oxigênio (SatO2) e índice de Tiffenau, observa-se variação direta entre o índice espirométrico e a SatO2 (ρ = 0,45). O inverso ocorre entre a Pressão arterial sistólica (PAS) e SatO2 e VEF1 e banda de baixa frequência (Lf) da PAS (ρ = -0,65). Ao analisar-se a VFC no domínio da frequência, houve diferença estatisticamente significante entre os grupos para a banda Lf (p = 0,01) e no balanço simpato-vagal (p=0,02). Quando comparados aos sujeitos saudáveis, pacientes com DPOC apresentaram menores valores de VFC, aumento da PAS, bem como queda na Saturação de Oxigênio (SatO2) e nos índices espirométricos. Ainda, a queda na função autonômica parece estar relacionada aos índices de VEF1 e a relação VEF1/CVF, quando do decréscimo destes. Ainda, ao que parece, a queda na SatO2, decorrente do prejuízo nas trocas gasosas, parece aumentar a modulação simpática, elevando os níveis de PAS.

<p>Astma i hronična opstruktivna bolest pluća (HOBP) su najče&scaron;će hronične nezarazne bolesti respiratornog sistema i predstavljaju značajan zdravstveni problem. U dijagnostici i proceni stepena poremećaja disajne funkcije u ovih bolesnika najče&scaron;će se koriste spirometrija i telesna pletizmografija. Impulsna oscilometrija predstavlja novu metodu u dijagnostici poremećaja plućne funkcije. Ova metoda je jednostavna za izvođenje i minimalno zavisi od saradnje pacijenta.Osnovni cilj ove doktorske disertacije bio je da se uporede parametri dobijeni impulsnom oscilometrijom, spirometrijom i telesnom pletizmografijom kod pacijenata sa astmom i hroničnom opstruktivnom bolesti pluća, utvrdi senzitivnost navednih metoda u detekciji opstruktivnog poremećaja ventilacije kao i povezanost parametara impulsne oscilometrije, spirometrije i telesne pletizmografije i stepena težine dispnoičnih tegoba kod odraslih pacijenata sa astmom i HOBP. Korelacijom parametara dobijenih impulsnom oscilometrijom i spirometrijom dobijena je umerena negativna korelacija vrednosti R5 sa FEV1 kod pacijenata sa astmom (r= -0.47, r&lt;0.001) i HOBP (r= -0.50, r&lt;0.001), kao i umerena pozitivna korelacija X5 sa FEV1 (r= 0.54, r&lt;0.001, kod pacijenata sa astmom; r= 0.56, r&lt;0.001 kod pacijenata sa HOBP). Registrovana je dobra korelacija Rt sa vrednostima R5 (r=0.63, r&lt;0.001) i H5 (r= -0.55, r&lt;0.001) kod pacijenata sa astmom, kao dobra korelacija Rt sa R5 (r=0.73, r&lt;0.001) i H5 (r= -0.74, r&lt;0.001) kod pacijenata sa HOBP. Kod pacijenata sa astmom nije registrovana razlika između tri metode u detekciji opstruktivnog poremećaja ventilacije kod pacijenata sa simptomima bolesti, dok se upotrebom sve tri metode povećala se senzitivnost. Sve tri metode bile su u slaboj korelaciji sa stepenom dispnoičnih tegoba kod pacijenta sa astmom. Svi HOBP pacijenti imali su spirometrijski registrovanu opstrukciju disajnih puteva. Senzitivnost impusne oscilometrije raste sa stepenom opstrukcije disajnih puteva, te je sposobnost detekcije opstruktivnog poremećaja ventilacije kod pacijenata sa FEV1%&lt;80 % iznosila 55%, 95% CI 43-67 %, a kod pacijenata sa FEV1%&lt;70 % 61%, 95% CI 47-73%. Registrovana je statistički značajna razlika vrednosti oscilometrijskih parametara u odnosu na spirometrijski stadijum HOBP. Kod pacijenata sa HOBP, sve tri metode bile su u umerenoj korelaciji sa stepenom dispnoičnih tegoba. Zaključujemo da postoji umerena korelacija impulsne oscilometrije sa spirometrijom i telesnom pletizmografijom kod pacijenta sa astmom i HOBP. Impulsna oscilometrija bolje korelira sa telesnom pletizmografijom u poređenju sa spirometrijom. Korelacija tri metode raste sa stepenom opstrukcije disajnih puteva. Komplementarna upotreba tri metode daje sveobuhvatniju sliku respiratorne funkcije kod pacijenata sa astmom i HOBP.</p> / <p>Asthma and chronic obstructive pulmonary disease (COPD) are most common chronic noninfectious diseases of the respiratory system, representing a major health issue. Spirometry and body plethysmography are the procedures which are most often performed to diagnose these diseases and evaluate the lung function impairment of the affected patients. Impulse oscillometry is a novel procedure to establish the lung function impairment. It is easy to perform, and minimally depends on a patient&#39;s cooperation. The major objective of this Ph. D. thesis is to compare the parameters obtained by impulse oscillometry, spirometry and body plethysmography in patients with asthma and COPD, establish the sensitivity of these procedures in detecting an obstructive ventilation disorder, and correlate the parameters of impulse oscillometry, spirometry and body plethysmpography to the severity of dyspneic symptoms in adult asthma and COPD patients. Correlating the parameters obtained by impulse oscillometry and spirometry, a moderate negative correlation of R5 values to FEV1 in asthma (r= -0.47, р&lt;0.001) and COPD patients (r= -0.50, р&lt;0.001) has been obtained, as well as a moderate positive correlation of X5 to FEV1 (r= 0.54, р&lt;0.001, in asthmatics; r= 0.56, р&lt;0.001 in COPD patients). A good correlation of Rt to R5 (r=0.63, р&lt;0.001) and Х5 values (r= -0.55, р&lt;0.001) has been registered in asthmatics, as well as a good correlation of Rt to R5 (r=0.73, р&lt;0.001) and Х5 (r= -0.74, р&lt;0.001) in COPD patients. In asthma patients, the three analysed procedures exhibited no difference in detecting an obstructive ventilation disorder in the patients with manifested symptoms, while the sensitivity improved when the procedures were complementary performed. Any of the three procedures correlated poorly to the severity of dyspneic symptoms in asthma patients. All COPD patients had a spirometry-registered airway obstruction. The sensitivity of impulse oscillometry increased with the severity of the airway obstruction, so its capacity to detect an obstructive ventilation disorder in the patients with FEV1%&lt;80 % was 55%, 95% CI 43-67 %, and in the patients with FEV1%&lt;70 %, it amounted to 61%, 95% CI 47-73%. A statistically significant difference in the values of all oscillometry parameters was registered depending on the spirometric COPD stage. In COPD patients, all the three procedures were moderately correlated to the severity of dyspenic symptoms. In conclusion, there is a moderate correlation of impulse oscillometry to spirometry and body plethysmography in asthma and COPD patients. Impulse oscillometry correlates better to body plethysmography than to spirometry. The correlation of the three procedures increases with the severity of the airway obstruction. The complementary application of these three procedures provides a more accurate assessment of the respiratory function in asthma and COPD patients.</p>

<p>Hronične inflamatorne bolesti disajnih organa su&nbsp;jedan od vodećih uzroka morbiditeta i mortaliteta&nbsp;&scaron;irom sveta. I pored stalnog napretka u naučnim&nbsp;istraživanjima, u otkrivanju molekularnih i ćelijskihmehanizama koji doprinose progresiji bolesti, uvođenju novih prognostičkih biomarkera, novim&nbsp;metodama detektovanja infektivnih uzročnika,&nbsp;primeni novih moćnih bronhodilatatornih,&nbsp;antiniflamatornih i antiinfektivnih lekova, hronične&nbsp;plućne bolesti i danas u dvadeset prvom veku beleže&nbsp;stalan porast broja obolelih i umrlih. Prema savremenom tumačenju HOBP je&nbsp; heterogena bolest koja je udružena sa brojnim komorbiditetima i&nbsp;sistemskim manifestacijama. Zajednički faktori rizika&nbsp;su osnova za javljanje udruženih hroničnih bolesti. Komorbiditeti i akutne egzacerbacije doprinose&nbsp;ukupnoj težini bolesti . S obzirom da se HOBP&nbsp;manifestuje i izvan pluća kod svakog pacijenta je&nbsp;potrebno proceniti postojanje sistemskih&nbsp;manifestacija&nbsp; i tragati za komorbiditetima. U reviziji&nbsp;&bdquo;Globalne strategije za dijagnozu, lečenje i prevenciju hronične opstruktivne bolesti pluća H GOLD&ldquo;&nbsp; iz 2011. godine navedene sledeće pridružene bolesti za&nbsp;kojima je potrebno aktivno tragati: kardiovaskularne&nbsp;bolesti, disfunkcija skeletnih mi&scaron;ića, metabolički&nbsp;sindrom, osteoporoza, depresija i karcinom pluća.&nbsp;Bronhiektazije sepredstavljaju hronično oboljenje&nbsp;pluća koje se karakteri&scaron;e abnormalnim pro&scaron;irenjem&nbsp;lumena bronha koje je uzrokovano slabljenjem ili&nbsp;destrukcijom mi&scaron;ićnih i elastičnih komponenti&nbsp;bronhijalnog zida, smanjenim klirensom mukusa i&nbsp;čestim infekcijama respiratornog trakta. Bronhiektazije se nekim svojim&nbsp; kliničkim&nbsp;karakteristikama preklapaju&nbsp; sa hroničnom opstruktivnom bolesti pluća. Metabolički sindrom&nbsp;predstavlja skup metaboličkih poremećaja koji&nbsp;povećavaju rizik za razvoj kardiovaskularnih bolesti i tipa 2 &scaron;ećerne bolesti. Za na&scaron;e istraživanje smo&nbsp;koristili definiciju NCEPHATPIII prema kojoj se metabolički sindrom zasniva na prisustvu tri od pet&nbsp;komponenti: Abdominalna gojaznost (obim struka&nbsp;preko 102 cm za&nbsp; mu&scaron;karce i preko 88 cm za žene),&nbsp;povi&scaron;ene vrednosti triglicerida na&scaron;te preko 1,7 mmol/l ili od ranije lečen poremećaj, snižen nivo HDL&nbsp;holesterola manje od 1,03 mmol/l za mu&scaron;karce i&nbsp;manje od 1,29 mmol/l za žene ili već lečen&nbsp;poremećaj, povi&scaron;en sistolni krvni pritisak preko 130 mmHg i/ili dijastolni preko 85 mmHg ili već lečena&nbsp;hipertenzija, povi&scaron;en nivo glukoze na&scaron;te preko 5,6 mmol/l ili već postojeći tip 2 &scaron;ećerne bolesti.&nbsp;Istraživenje je sprovedeno u Institutu za plućne&nbsp;bolesti Vojvodine u Sremskoj Kamenici. Cilj je bio&nbsp;da se utvrdi učestalost metaboličkog sindroma i&nbsp;komponenti među bolesnicima sa HOBP i&nbsp;bronhiektazijama. Sledeći cilj je bio da analizira&nbsp;i uporedi&nbsp; zastupljenosti metaboličkog sindroma i pojedinih komponenti među ispitivanim grupama u&nbsp;odnosu na pol, starost bolesnika i dužinu lečenja&nbsp;HOBP. Bilo je uključeno ukupno 193 ispitanika. Od&nbsp;ovog broja 163 su činili bolesnici od HOBP i&nbsp;bronhiektazija&nbsp; koji su bili podeljeni u tri grupe:&nbsp;pacijenti oboleli od hronične opstruktivne bolesti&nbsp;pluća (n=55, grupa 1), pacijenti oboleli od bronhiektazija (n=50, grupa 2) i pacijenti sa&nbsp;udruženom hroničnom opstruktivnom bolesti pluća i&nbsp;bronhiektazijama (n=58, grupa 3). Kontrolna grupa,&nbsp;koja je označena kao grupa 4, formirana je od 30&nbsp;ispitanika bez bronhiektazija i hronične opstruktivne bolesti pluća, tako da je ukupan broj ispitanika u&nbsp;istraživanju bio 193. Učestalost metaboličkog&nbsp;sindroma prema kriterijumuma NCEP/ATP III kod&nbsp;bolesnika hroničnim bolestima respiratornog sistema&nbsp;(hroničnom opstruktivnom bolesti pluća,&nbsp;bronhiektazijama i udružena ova dva oboljenja) je&nbsp;iznosila je kod 37,3 % . Metabolički sindrom je bio&nbsp;učestaliji kod ispitanika sa hroničnim opstruktivnom<br />bolesti pluća i/ili bronhiektazijama u odnosu na&nbsp;ispitanike iz kontrolne grupe bez&nbsp; hroničnih bolesti&nbsp;respiratornog trakta. Kod bolesnika sa hroničnom&nbsp;opstruktivnom bolesti pluća dokazano je prisustvo&nbsp;metaboličkog sindroma kod 38,2%&nbsp; ispitanika, kod&nbsp;bolesnika sa bronhiektazijama kod 54% ispitanika i&nbsp;IV kod pacijenata sa udruženom hroničnom&nbsp;opstruktivnom bolesti pluća i bronhiektazijama kod&nbsp;36,2% ispitanika. Prosečan broj komponenti&nbsp;metaboličkog sindroma kod bolesnika sa hroničnom&nbsp;opstruktivnom bolesti pluća je iznosio 2,18, kod&nbsp;bolesnika sa bronhiektazijama je bio 2,56, a kod&nbsp;bolesnika sa udružena ova dva oboljenja 2,1.<br />Komponente metaboličkog sindroma nisu učestalije i&nbsp;nisu statistički vi&scaron;e kod bolesnika sa udruženom&nbsp;hroničnom opstruktivnom bolesti pluća i&nbsp;bronhiektazijama u odnosu na obolele sa HOBP i&nbsp;bronhiektazijama kao samostalnim oboljenjima.<br />Razlika u pojedinačnim vrednostima komoponenti&nbsp;metaboličkog sindroma i učestalosti pojedinih&nbsp;komponenti među posmatranim grupama bolesnika sa<br />hroničnim plućnim bolestima nije statistički značajna.&nbsp;Učestalost metaboličkog sindroma kod bolesnika sa&nbsp;hroničnim bolestima respiratornog sistema nije u vezi sa polom i ne zavisi od starosti ispitanika. Nije&nbsp;dokazano da je metabolički sindrom učestaliji kod&nbsp;mu&scaron;karaca i i nije dokazano da je učestaliji kod&nbsp;ispitanika koji imaju vi&scaron;e od &scaron;esdeset i pet godina&nbsp;u odnosu na mlađe bolesnike među ispitivanim.&nbsp;Učestalost metaboličkog sindroma kod ispitanika sa&nbsp;hroničnom opstruktivnom bolesti pluća ne zavisi od&nbsp;dužine lečenja hronične opstruktivne bolesti pluća.&nbsp;Dokazano je da učestalost&nbsp; metaboličkog sindoma&nbsp;nije veća kod bolesnika kojima je dijagnoza bolesti postavljena pre vi&scaron;e od pet godina i koji se od HOBP&nbsp;leče duže od pet godina. Na osnovu rezultata koje&nbsp;smo dobili u na&scaron;em istraživanju zaključili smo da&nbsp;hronične plućne bolesti, bronhiektazije i hronična&nbsp;opstruktivna bolest pluća, predstavljaju stanja sa povi&scaron;enim kardiometaboličkim rizikom.</p><p>&nbsp;</p> / <p>Chronic inflammatory diseases of the respiratory&nbsp;organs are one of the leading morbidity and&nbsp;mortality causes all over the world. Despite the&nbsp;steady advance in scientific research, discovery&nbsp;of&nbsp; the disease-progression-contributing molecular<br />and cellular mechanisms, introduction of novel&nbsp;prognostic biomarkers, new detection methods of&nbsp;infectious agents, application of&nbsp; new, potent&nbsp;bronchodilation, anti-inflammatory and anti-infectious drugs,&nbsp; a constant&nbsp; increase in&nbsp; the&nbsp;number of the affected and deceased from chronic&nbsp;pulmonary diseases has still been permanently<br />evidenced in the 21st century. In a modern&nbsp;concept, the chronic obstructive pulmonary<br />disease (COPD) is understood as a heterogenous&nbsp;disorder associated with numerous comorbidities&nbsp;and systemic manifestations. Common risk factors&nbsp;represent the basis for concomitant chronic&nbsp;diseases to develop. Comorbidities and acute&nbsp;exacerbations contribute to the overall disease&nbsp;severity. As a COPD may develop extrapulmonary manifestations as well, each&nbsp;patient should be evaluated for systemic&nbsp;manifestations and comorbidities. The 2011&nbsp;update of the &bdquo;Global Strategy for Chronic&nbsp;Obstructive Lung Disease Diagnosis,&nbsp;Management, and Prevention &ndash;GOLD&rdquo; lists the&nbsp;following comorbidities to be actively searched&nbsp;for: cardiovascular diseases, skeletal muscle<br />dysfunction, metabolic syndrome, osteoporosis,&nbsp;depression, and lung cancer. Bronchiectases&nbsp;represent a chronic lung disorder marked by&nbsp;VII excessively dilated bronchial lumen&nbsp; induced by&nbsp;weakened or destructed muscular and elastic&nbsp;components of the bronchial wall, reduced mucus&nbsp;clearance, and recurrent respiratory infections.&nbsp;Bronchiectases and COPD have some clinical&nbsp;features in common. The metabolic syndrome is a&nbsp;group of metabolic disorders which increase the&nbsp;risk of&nbsp; cardiovascular diseases and type 2&nbsp;diabetes. In our investigation, we utilized the&nbsp;NCEP HATPIII definition of the metabolic&nbsp;syndrome based on the presence of three of five&nbsp;components: abdominal obesity (&gt; 102 cm and &gt;<br />88 cm waist&nbsp; measure for males and females&nbsp;respectively), elevated (&gt;1.7 mmol/l) triglyceride&nbsp;levels on an empty stomach, or a former history of&nbsp;the disorder treatment, reduced&nbsp; HDL cholesterol&nbsp;(&lt; 1.03 mmol/l and &lt;1.29 mmol/l for males and&nbsp;females respectively), or a former history of the&nbsp;disorder treatment, elevated systolic blood<br />pressure of &gt;130 mmHg and/or diastolic blood&nbsp;pressure of &gt; 85 mmHg, or a former history of&nbsp;treated hypertension, elevated glucose levels&nbsp; (&gt;5.6 mmol/l), or already existing type 2 diabetes&nbsp;mellitus. The investigation has been carried out in<br />the Institute for Pulmonary Diseases of&nbsp;Vojvodina, Sremska Kamenica, aimed at 1)<br />establishing the frequency of the metabolic&nbsp;syndrome and its components among the patients&nbsp;with COPD and bronchiectases; 2) analyze and&nbsp;compare the frequency of metabolic syndrome&nbsp;and its components in the examined groups related&nbsp;to the patients&rsquo; sex, age, and COPD treatment&nbsp;length. The study included 193 subjects, 163 of&nbsp;whom suffered from COPD and bronchiectases,&nbsp;classified into three groups: COPD patients (n=55,&nbsp;Group 1), patients with bronchiectases (n=50,&nbsp;Group 2), and patients with concurrent COPD and&nbsp;bronchiectases (n=58, Group 3). The control&nbsp;group, designated as Group 4, included 30&nbsp;subjects&nbsp; free of bronchiectases and COPD, so the&nbsp;total of 193 subjects were included in the&nbsp;investigation. The NCEP/ATP III criteria<br />established metabolic syndrome frequency among&nbsp;the patients with chronic respiratory diseases&nbsp;(COPD, bronchiectases, and concomitant COPD&nbsp;and bronchiectases) amounted to 37.3 % . The&nbsp;metabolic syndrome was more frequent in the&nbsp;patients with COPD and/or bronchiectases than in&nbsp;the control group patients free of any chronic&nbsp;respiratory disease. The metabolic syndrome was&nbsp;VIII confirmed in 38.2% of COPD patients, 54% of the&nbsp;patients with bronchiectases, and in 36.2% of the<br />patients with&nbsp; concomitant COPD and&nbsp;bronchiectases. The mean number of the<br />metabolic syndrome components was&nbsp; 2.18 in&nbsp;COPD patients,&nbsp;&nbsp; 2.56 in patients with<br />bronchiectases, and 2.1 in patients with&nbsp;concomitant COPD and bronchiectases. The<br />metabolic syndrome components were neither&nbsp;more frequent, nor statistically higher in the&nbsp;patients with concomitant COPD and&nbsp;bronchiectases as compared to the patients with a&nbsp;single presence of any of the two diseases. The&nbsp;difference in the single values of the metabolic&nbsp;syndrome components and the frequency of&nbsp;certain components in the examined groups of the&nbsp;patients with chronic pulmonary diseases was not&nbsp;statistically significant. Among the patients with&nbsp;chronic respiratory diseases, no correlation was&nbsp;observed between the metabolic syndrome&nbsp;frequency and the patients&rsquo; sex or age. The&nbsp;metabolic syndrome was not confirmed to be&nbsp;more frequent in males, or in&nbsp;&nbsp; &gt;65 yr old patients,&nbsp;as compared to younger patients. Among COPD<br />patients, no correlation was registered between the&nbsp;metabolic syndrome frequency and&nbsp;&nbsp; COPD&nbsp;treatment duration. It was confirmed that the&nbsp;metabolic syndrome frequency was not higher in&nbsp;the patients with &lt;5Hyear long COPD treatment<br />than in those treated for COPD longer. On the&nbsp;basis of the results obtained in our investigation,&nbsp;we conclude that chronic respiratory diseases,&nbsp;COPD and &nbsp;bronchiectases, are the conditions with&nbsp;a higher cardiometobolic risk.</p>

<p>Hronična opstruktivna bolest pluća (HOBP) je rastući zdravstveni problem radno sposobne populacije. Akutne egzacerbacije hronične opstruktivne bolesti pluća (AEHOBP) značajno doprinose pogor&scaron;anju bolesti i sa aspekta kvaliteta života bolesnika i sa aspekta tro&scaron;kova. Cilj istraživanja je bila identifikacija faktora visokih tro&scaron;kova lečenja AEHOBP koja može pomoći u definisanju strategija smanjenja HOBP egzacerbacija ove bolesti i analiza podataka o prehospitalnom lečenju obolelih od HOBP. Materijal i metode: Istraživanjem je obuhvaćeno 130 pacijenata koji su ispunjavali uključujuće kriterijume studije. Rezultati: Ukupni godi&scaron;nji direktni tro&scaron;kovi hospitalizacija usled AEHOBP čine17,3% od tro&scaron;kova svih hospitalizovanih pacijenata. Prosečna dužina hospitalizacije je bila duža kod pacijenata sa te&scaron;kom AEHOBP u odnosu na srednje te&scaron;ku, razlika je statistički značajna (p = 0,044). Prema rezultatima istraživanja o potro&scaron;nji lekova godinu dana pre hospitalizacije, adekvatnu terapiju je koristilo 41,7% pacijenata, a neadekvatnu 58,3% pacijenata i postojala je negativna korelacija između adekvatnosti lečenja i stepena težine akutne egzacerbacije. Multivarijantnom logističkom regresijom dobijena je formula za predikciju ukupnih tro&scaron;kova. Zaključak: Nezavisni prediktori direktnih tro&scaron;kova lečenja su: mu&scaron;ki pol, pu&scaron;ačka navika, te&scaron;ka AEHOBP, postojanje acidoze, primena neadekvatne ili adekvatne terapije trajanja kraćeg od devet meseci tokom godine koja je prethodila hospitalnom lečenju egzacerbacije.</p> / <p>Chronic obstructive pulmonary disease (COPD) is a rising health issue of working population. Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are significantly contributing to worsening of the disease prognosis, consequently leading to decline of patient&rsquo;s quality of life and increasing costs of treatment. Objective of the study was identification of factors for high AECOPD treatment costs, which can help in defining strategy for decreasing COPD exacerbations and data analysis of prehospital treatment of COPD patients. Material and Methods: The study included 130 patients who fulfilled including criteria of the study. Results: Total direct costs of AECOPD hospitalizations demonstrated 17.3% of all hospitalized patients costs. Average length of hospitalization was longer in patients with severe AECOPD compared to patients with moderate AEHOBP, there was statistically significant difference (p= 0,044). According to research results of medication usage one year before the hospitalization, adequate treatment used 41.7% of patients, and inadequate 58.3%; there was negative correlation between adequate treatment and level of severance of acute exacerbations. Multivariate logistic regression was used for obtaining total costs predictions formula. Conclusion: Independent predictors of direct treatment costs were: male patients, smokers, prehospital treatment, inadequate or adequate, not longer than nine months per year.</p>

Camundongos Balb/c receberam instilação intranasal de 50 l de papaína (20 mg/ml) ou solução salina. A instilação de papaína resultou em uma diminuição significativa de Ers (p=<0,001), Gtis (p=0,030) e Htis (p=0,012). Houve um aumento de k, uma constante medida na curva PV. Não observamos diferença estatística nos parâmetros R e E na mecânica do parênquima pulmonar quando comparamos os diferentes grupos. Os camundongos instilados com papaína apresentaram valores aumentados do diâmetro alveolar médio no tecido pulmonar e aumento na proporção de fibras de colágeno, comparados aos que receberam salina (p<0,001 e p=0,004, respectivamente). As medidas in vivo detectaram alterações pulmonares em camundongos enfisematosos. Entretanto, as medidas in vitro, na mecânica do parênquima pulmonar, não foram capazes de detectar essas alterações. / Male Balb/c mice received a nasal drop of 50 l of papain (20 mg/ml) or normal saline. After 28 days of instillation, lungs from papain-treated mice showed a significant decrease in mean values of Ers (P=<0,001),Gtis (P=0.030) and Htis (P=0.012). There was an increase in mean values of k, a constant measured in P-V curve. We did not observe a significant difference between the groups in R and E in lung tissue strips. Papain instillation presented greater values of mean linear intercept and increase in the density of collagen fibers in alveolar septa in pulmonary tissue than saline-treated mice (P<0.001 and P=0.004, respectively). We conclude that in vivo measurements of pulmonary mechanics detected pulmonary emphysematous changes in mice. In contrast, in vitro measurements in lung strips with oscillatory mechanics did not detect these changes

Introdução: Demonstramos previamente que em modelo experimental de enfisema pulmonar induzido por instilação de elastase, o inibidor de serinoprotease rBmTI-A promoveu a melhora da destruição tecidual em camundongos. Considerando que o tabagismo é o principal fator de risco para o desenvolvimento da Doença Pulmonar Obstrutiva Crônica (DPOC) e que o modelo de exposição à fumaça de cigarro é considerado o que melhor mimetiza esta doença em humanos, este estudo teve por objetivo verificar a ação do inibidor para serinoproteases rBmTI-A sobre os processos fisiopatológicos envolvidos no desenvolvimento do enfisema pulmonar, em modelo de exposição ao tabaco. Métodos: Para a indução do enfisema pulmonar, os animais foram expostos à fumaça de cigarro (duas vezes ao dia/ 30 minutos/ 5 dias por semana/ durante 12 semanas), e os animais controle permaneceram expostos ao ar ambiente. Dois protocolos de tratamento com o inibidor rBmTI-A foram realizados. No primeiro, os animais receberam duas administrações do inibidor rBmTI-A ou de seu veículo (Solução Salina 0,9%) por via intranasal, sendo a primeira após 24h do término das exposições ao cigarro e outra, 7 dias após à primeira instilação do inibidor. No segundo protocolo, os animais receberam 3 administrações do inibidor rBmTI-A, durante o tempo de exposição (1ª dose: 24h antes do início da exposição à fumaça de cigarro; 2ª dose: um mês após o início da exposição; 3ª dose: dois meses após o início). Após o término dos protocolos de exposição e tratamento, os animais foram submetidos aos procedimentos para coleta dos dados de mecânica respiratória e avaliação do Intercepto Linear Médio (Lm). Para o segundo protocolo, realizamos também as medidas para quantificação de fibras de colágeno e elástica, da densidade de células positivas para MAC-2, MMP-12 e 9, TIMP-1, Gp91phox e TNFalfa; no parênquima através de imunohistoquímica, contagem de células polimorfonucleares além da expressão gênica de MMP-12 e 9 no pulmão através de RT-qPCR. Resultados e Discussão: O tratamento com o inibidor para serinoprotease rBmTI-A atenuou o desenvolvimento do enfisema pulmonar apenas no segundo protocolo, quando foi administrado durante a exposição à fumaça de cigarro. Embora os grupos Fumo-rBmTIA e Fumo-VE apresentem aumento de Lm comparados aos grupos controles, houve uma redução deste índice no grupo Fumo-rBmTIA comparado ao grupo Fumo-VE. O mesmo comportamento foi observado para as análises de proporção em volume de fibras de elástica e colágeno no parênquima. Além disto, observamos aumento de macrófagos, MMP-12, MMP-9 e TNFalfa; nos grupos expostos à fumaça de cigarro, mas o tratamento com o inibidor rBmTI-A diminuiu apenas a quantidade de células positivas para MMP-12. Na avaliação da expressão gênica para MMP-12 e 9, não observamos diferença entre os grupos experimentais e o mesmo comportamento foi observado para a quantidade de células polimorfonucleares no parênquima. Além disso, observamos aumento de GP91phox e TIMP-1 nos grupos tratados com rBmTIA. Conclusões: Tais resultados sugerem que o inibidor rBmTI-A não foi efetivo como tratamento da lesão após a doença instalada. Entretanto, atenuou o desenvolvimento da doença quando administrado durante a indução do enfisema, possivelmente através do aumento de GP91phox e TIMP-1, acompanhados pela diminuição de MMP-12. / Introduction: We have previously showed that in an elastase-induced model of emphysema, the treatment with a serine protease inhibitor rBmTI-A, resulted in an improvement of tissue destruction in mice. Considering that smoking is the main risk factor for the development of COPD, and the cigarette smoke (CS) exposure is considered the best model to reproduce physiopathologic similarities with such disease in humans, this study aimed to verify the rBmTI-A treatment on the physiopathological processes involved in the development of cigarette smoke-induced emphysema. Methods: To induce pulmonary emphysema, animals were exposed to cigarette smoke (twice a day/ 30 minutes/ 5 days per week/ for 12 weeks) and the control animals were exposed to room air. Two treatment protocols with rBmTI-A inhibitor were performed. In the first one, animals received two administrations of rBmTI-A inhibitor or its vehicle (Saline Solution 0.9%) by nasal instillation, one dose at 24 hours after the end of exposure to tobacco smoke and another one, 7 days after the first instillation of the inhibitor. In the second protocol, animals received 3 rBmTI-A inhibitor administrations during the exposition time (1st dose: 24 hours before the start of exposure to cigarette smoke; 2nd dose: one month after the start of exposure, 3rd dose: two months after the start). After the end of exposure and treatment protocols, animals were submitted to procedures for collection of respiratory mechanics and evaluation of the Mean Linear Intercept (Lm). For the second protocol, we also measured the volume proportion of collagen and elastic fibers, the density of positive cells for MAC-2, MMP-12 and -9, TIMP-1, GP91phox and TNF-alfa in lung parenchyma by immunohistochemistry. Also, we evaluated the measurement of polymorphonuclear cells and the lung gene expression for MMP-12 and 9 by RT-qPCR. Results and Discussion: Treatment with the serine protease inhibitor rBmTI-A attenuated the development of emphysema only in the second protocol, when it was administered during exposure to cigarette smoke. Although Smoke-rBmTIA and Smoke-VE groups showed an increase of Lm measure compared to Control groups, there were a decrease in the Smoke-rBmTIA group compared to Smoke-VE group. The same response was observed for the analysis of volume proportion of elastic and collagen fibers in parenchyma. In addition, we observed an increase of macrophages, MMP-12, MMP-9 and TNF-alfa; in groups exposed to cigarette smoke, but treatment with rBmTI-A inhibitor only decreased the number of positive cells for MMP-12. We did not observed difference between the experimental groups in lungs gene expression for MMP- 12 and 9, and the same behavior was observed for the amount of polymorphonuclear cells in parenchyma. Moreover, we observed an increase of GP91phox and TIMP-1 in groups treated with rBmTI-A. Conclusions: These results suggest that rBmTI-A inhibitor was not effective for treatment of parenchymal lesions after established disease. However, this inhibitor attenuated the development of disease when administered during the induction of emphysema, possibly by an increase of GP91phox and TIMP-1, accompanied by a decrease of MMP-12