Asthma is a chronic disease of the airways and affects many people regardless of their age, gender, race and socioeconomic status. Since asthma is recognised as one of the major causes of morbidity and mortality in people and especially in South Africa, the prescribing patterns, prevalence and medication cost of asthma in South Africa are saliently important and need to be investigated. A non-experimental, quantitative retrospective drug utilisation review was conducted on medicine claims data of a pharmaceutical benefit management company in a section of the private health care sector of South Africa. The study period was divided into four annual time periods (1 January 2008 to 31 December 2008, 1 January 2009 to 31 December 2009, 1 January 2010 to 31 December 2010 and 1 January 2011 to 31 December 2011). The prescribing patterns and cost of asthma medication were investigated and stratified according to province, age and gender. Patients were included if the prescriptions which were provided by the health care practitioners matched the Chronic Disease List (CDL) of South Africa and the International Classification of Disease (ICD-10) coding for asthma and chronic obstructive pulmonary disease (COPD). Data analysis was conducted by means of the SAS 9.3® computer package. Asthma patients were divided according to different age groups (there were five different age groups for this study), gender and geographical areas of South Africa. The study indicated a steady increase in the prevalence of asthma patients from 0.82% (n = 7949) in 2008 to 1.18% (n = 15 423) in 2009 and reached a minimum of 0.79% (n = 8554) in 2011. Analysis of the prevalence regarding geographical areas in South Africa suggested that Gauteng had the highest number [n = 17 696, (0.85%)] of asthma patients throughout the study period, followed by KwaZulu Natal [n = 8 628, 1.16%)] and the Western Cape [(n = 8513, 0.97%) (p < 0.05)]. The prevalence of asthma in female patients [0.89% (n = 26 588)] was higher than in their male counterparts [0.79% (n = 19 244)] (p > 0.05). The results showed that asthma was not as common chronic disease in children. The total number of asthma patients younger than 7 years represented 0.64% (n = 2 909). It was found that patients over 65 years of age showed the highest prevalence of the five age groups [1.94% (n = 13 403) (p < 0.05)]. The average number of asthma prescriptions per patient per year was 8.28 (95% CI, 8.16- 8.40) and 5.15 (95% CI, 5.06-5.23) in 2008 and 2011, respectively. The number of asthma items per prescription varied from 1.55 (95% CI, 1.55-1.56) in 2008 to 1.40 (95% CI, 1.39- 1.40) in 2011. Medication from the MIMS® pharmacological group (anti-asthmatics and bronchodilators) was used to identify asthma medication. The top three asthma medication with the highest prevalence in the study period were the anti-inflammatory inhaler of fluticasone (n = 39 721) followed by the single item combination product of budesonide/ formoterol (n = 25 121) and salbutamol (n = 24 296). The influence of COPD on asthma treatment and the costimplication thereof were investigated. Medication from the MIMS® pharmacological group (anti-asthmatics and bronchodilators) was used to identify COPD medication. This study also showed that COPD had an influence in the economic burden of the South African asthma population. The cost of medication is responsible for the single largest direct cost involved in the economic burden of asthma. This study showed that asthma represented 0.88% of the direct medication cost in the study (excluding hospitalisation and indirect cost). The average cost per prescription and average cost per asthma item both increased throughout the study period. The prescribing patterns for the different medication used in the treatment of asthma were investigated and recommendations for further research in this field of study were made. / MPharm (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

<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>

Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease, characterized by progressive and largely irreversible airflow limitation due to alveolar destruction (emphysema), small airway narrowing, and chronic bronchitis. It is one of the leading causes of morbidity and mortality worldwide and in the UK, it may affect approximately 1.5 per cent of the population; and up to one in eight emergency admissions may be due to COPD,corresponding to over one million bed days, with some 24160 people in the UK dying as a result of COPD in 2005 (Burden of Lung Disease 2nd Edition,British Thoracic Society 2006). Most cases of COPD are triggered by chronic inhalation of cigarette smoke.However, some people do not suffer from COPD even if they smoke for many years. COPD cannot be cured, and patients usually live with poor life quality. Treatments include giving up smoking, medication and oxygen therapy. Genetic factors contribute to the development of COPD. In Northern Europe,Z-AT homozygotes (342Glu Lys) develop emphysema in their third or forth decade. One explanation is AT deficiency because they form inactive polymers. However, this cannot explain why bronchoalveolar lavage fluid (BALF) from Z-AT homozygotes with emphysema contains more neutrophils than BALF from individuals with emphysema and normal AT (M-AT). Inhaling pollutants which include smoking (cigarettes, pipes, cigars, etc.) and other fumes such as those found in many industrial work environments probably also plays a role in an individual’s development of COPD. Previously, it has been shown that the polymeric conformer of AT is present in BALF from Z-AT homozygotes and that it is a chemoattractant for neutrophils in vitro (Parmar JS, 2002). These findings have been confirmed by others (Mulgrew AT, 2004). However, it is unknown where the polymers form and if 4 they are chemotactic in vivo. My colleague Dr Carl Atkison† showed that polymers of Z 1-AT are present in the alveolar wall of Z-AT homozygotes with emphysema, which accounts for 20% of the total AT from lung homogenates.These Z-AT individuals also have an excess of neutrophils in the alveolar wall compared with M-AT homozygotes. Furthermore, neutrophils and polymeric AT co-localize in the alveolar wall (Mahadeva R, 2005). To investigate whether there was a direct relationship between polymers of Z-AT and the excess neutrophils, polymers of AT were instilled into the lungs of wild-type mice (Mahadeva R, 2005). This produced a significant increase in neutrophil influx into the lungs compared with instillation of the native protein.Examination of the time course demonstrated that the influx of neutrophils was closely linked to the presence of polymeric AT. The mechanism of neutrophil recruitment in this mouse model was subsequently shown to be a direct chemotactic effect rather than stimulation of IL-8 homologues or other CXC chemokines. Oxidized AT (Ox-AT) promotes release of human monocyte chemoattractant protein-1 (MCP-1) and IL-8 from human lung type epithelial cells (A549) and normal human bronchial epithelial (NHBE) cells. Native, cleaved, polymeric AT and secretory leukoproteinase inhibitor (SLPI) and oxidized conformations of cleaved, polymeric AT and SLPI did not have any significant effect on MCP-1 and IL-8 secretion. These findings were supported by the fact that instillation of Ox-AT into murine lungs resulted in an increase in JE (mouse MCP-1) and increased macrophage numbers in the bronchoalveolar lavage fluid. The effect of Ox-AT was dependent on NF- B and activator protein-1 (AP-1)/JNK. These findings have important implications. They demonstrate that the oxidation of methionines in AT by oxidants released by cigarette smoke or inflammatory cells not only reduces the anti-elastase lung protection, but also converts AT into a proinflammatory stimulus. Ox-AT generated in the airway † My colleagues’ contributions are acknowledged in future text where appropriate by the following superscripts: (a) Dr Sam Alam, (b) Dr Jichun Wang, (c) Dr Carl Atkinson, (d) Dr Sabina Janciauskiene. 5 interacts directly with epithelial cells to release chemokines IL-8 and MCP-1,which in turn attracts macrophages and neutrophils into the airways. The release of oxidants by these inflammatory cells oxidizes AT, perpetuating the cycle, potentially contributing to the pathogenesis of COPD. Furthermore, this demonstrates that molecules such as oxidants, anti-proteinases, and chemokines, rather than acting independently, collectively interact to cause emphysema (Li Z, 2009). To investigate the molecular basis for the interaction between Z-AT and Ox-AT associated with cigarette smoking, female mice transgenic for normal (MAT)or Z-AT on CBA background were exposed to cigarette smoke (CS). Transgenic mice for Z-AT developed a significant increase in pulmonary polymers following acute CS exposure. Increased levels of neutrophils in CSZ lungs were tightly correlated with polymer concentrations. Oxidation of human plasma Z-AT by CS or -chlorosuccinimide greatly accelerated polymerization, which could be abrogated by antioxidants. The results showed that cigarette smoke accelerated polymerization of Z-AT by oxidative modification, which in so doing further reduced pulmonary defense and increased neutrophil influx into the lungs. These novel findings provided a molecular explanation for the striking observation of premature emphysema in ZZ homozygote smokers, and raised the prospect of anti-oxidant therapy in ZAT related COPD (Alam S, 2011).

Introduction. Les mécanismes physiopathologiques du remodelage vasculaire pulmonaire chez le patient BPCO sont encore mal élucidés. L'inflammation pourrait jouer un rôle déterminant.Objectifs. Déterminer le rôle de l'interleukine 6 (IL6) dans la physiopathologie de l'hypertension pulmonaire (HTP) associée à la BPCO.Méthodes. Nous avons étudié le lien entre l'IL6 et l'HTP sur une population de patients atteints de BPCO, l'effet de l'hypoxie sur le développement d'une HTP chez des souris IL6-/- et l'effet in vitro de l'IL6 sur les cellules endothéliales et les cellules musculaires lisses d'artère pulmonaire humaine.Résultats. Les patients BPCO avec HTP présentaient un taux plasmatique d'IL6 circulante plus élevé. Le génotype GG de l'IL6 était corrélé à un risque plus élevé de développer une HTP. L'IL6 est produite par tous les acteurs cellulaires impliqués dans la physiopathologie du remodelage vasculaire pulmonaire et en particulier la cellule musculaire lisse. Sa synthèse, ainsi que celle de ses récepteurs, est très nettement stimulée par l'hypoxie aigue et chronique. L'IL6 participe probablement à l'entretien de la dysfonction endothéliale, à la migration des cellules musculaires lisses et au recrutement des cellules inflammatoires. Les souris IL6-/- sont partiellement protégées de l'hypertension pulmonaire hypoxique et présentent un moindre recrutement pulmonaire de cellules inflammatoires induit par l'hypoxie. Le taux d'IL6 est corrélé à une longueur télomérique plus courte chez les patients BPCO, témoignant d'un processus de vieillissement biologique accéléré. L'HTP associée à la BPCO ou à l'hypoxie chronique pourrait résulter d'une accentuation du processus de sénescence des cellules vasculaires pulmonaires, favorisé par l'inflammation.Conclusion. L'inflammation et plus particulièrement l'IL6 semblent fortement impliquées dans la physiopathologie du remodelage vasculaire pulmonaire chez le patient BPCO. / Introduction. The pathophysiological mechanisms responsible for pulmonary vascular remodeling in COPD remain poorly understood. Inflammation may play a major role.Objectives. To study the role of interleukin-6 (IL6) in the pathophysiology of pulmonary hypertension associated with COPD.Methods. We studied the relationship between IL6 and PH in a population of patients with COPD, the effect of hypoxia on the development of PH in mice IL6-/- and the effect of IL-6 on endothelial cells and smooth muscle cells of human pulmonary artery in vitro.Results. COPD patients with PH were characaterised by a more pronounced hypoxia and higher plasma levels of circulating IL-6. The GG genotype of IL-6 also correlated with a higher risk of developing PH in these patients. Each of the different cellular elements that promote pulmonary vascular remodeling are known to produce IL-6, with smooth muscle cells known to be a particularly important source of this cytokine In addition, synthesis of IL-6 and its associated receptors is increased in response to acute and chronic hypoxia. It is likely that IL-6 contributes to endothelial dysfunction, the migration and, indirectly, proliferation of smooth muscle cells, and recruitment of inflammatory cells. Indeed, IL6-/- mice are partially protected from hypoxia-associated pulmonary hypertension and demonstrate attenuated hypoxia-induced lung recruitment of inflammatory cells. Levels of IL-6 also correlate with shorter telomere length in patients with COPD, indicating a process of accelerated biological aging. This suggests that pulmonary hypertension secondary to COPD or chronic hypoxia may be due to inflammation-associated acceleration of normal pulmonary vascular cell sénescence.Conclusion. Inflammation in general, and IL-6 in particular, appear to be strongly involved in the pathophysiology of pulmonary vascular remodeling in patients with COPD

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelinesare used to guide clinical practices for treating Chronic Obstructive Pulmonary Disease (COPD). GOLD focuses heavily on stable COPD patients, limiting its use fornon-stable COPD patients such as those with severe, acute exacerbations of COPD (AECOPD) that require hospitalization. Although AECOPD can be heterogeneous, it can lead to deterioration of health and early death. Electronic health records (EHRs) can be used to analyze patient data for understanding disease progression and generating guideline evidence for AECOPD patients. However, because of its structure and representation, retrieving, analyzing, and properly interpreting EHR data can be challenging, and existing tools do not provide granular analytic capabil-ities for this data.<div><br></div><div>This dissertation presents, develops, and implements a novel approach that systematically captures the effect of interventions during patient medical encounters, and hence may support evidence generation for clinical guidelines in a systematic and principled way. A conceptual framework that structures components, such as data storage, aggregation, extraction, and visualization, to support EHR data analytics for granular analysis is introduced. We develop a software framework in Python based on these components to create longitudinal representations of raw medical data extracted from the Medical Information Mart for Intensive Care (MIMIC-III) clinical database. The software framework consists of two tools: Patient Aggregated Care Events (PACE), a novel tool for constructing and visualizing entire medical histories of both individual patients and patient cohorts, and Mark SIM, a Markov Chain Monte Carlo modeling and simulation tool for predicting clinical outcomes through probabilistic analysis that captures granular temporal aspects of aggregated, clinicaldata.<br></div><div><br></div><div>We assess the efficacy of antibiotic treatment and the optimal time of initiationfor in-hospitalized AECOPD patients as an application to probabilistic modeling. We identify 697 AECOPD patients of which 26.0% were administered antibiotics. Our model simulations show a 50% decrease in mortality rate as the number of patients administered antibiotics increase, and an estimated 5.5% mortality rate when antibiotics are initially administrated after 48 hours vs 1.8% when antibiotics are initially administrated between 24 and 48 hours. Our findings suggest that there may be amortality benefit in initiation of antibiotics early in patients with acute respiratory failure in ICU patients with severe AECOPD.<br></div><div><br></div><div>Thus, we show that it is feasible to enhance representation of EHRs to aggregate patients’ entire medical histories with temporal trends and support complex clinical questions to drive clinical guidelines for COPD.<br></div>

O exercício aeróbio foi recentemente descrito como capaz de reduzir a função pulmonar e diminuir o risco de desenvolver DPOC entre fumantes ativos. A plausibilidade biológica da influência da atividade física sobre o declínio da função pulmonar está relacionada aos efeitos anti-inflamatórios efeitos da atividade física, que tem sido descritos em estudos experimentais. A hipótese é que haveria uma interação entre exercício aeróbio e o desenvolvimento da doença. A fim de explorar mais a fisiopatologia da DPOC induzida pela exposição à fumaça de cigarro e os efeitos do exercício no desenvolvimento do enfisema, utilizamos um modelo experimental de DPOC. C57Bl6 foram divididos em quatro grupos: Controle, Fumo, Exercício e Fumo/Exercício. Os animais dos grupos Fumo foram expostos à fumaça de cigarro por 30 minutos por dia, 5 dias por semana, durante 24 semanas. Os animais dos grupos Exercício foram treinados em intensidade moderada durante 60 minutos por dia, 5 dias por semana durante 24 semanas. Os resultados demonstraram que o treinamento físico aeróbio regular de intensidade moderada inibiu o desenvolvimento de enfisema, o aumento do total de células inflamatórias e a produção de espécies reativas de oxigênio no LBA, além do aumento na geração de óxido nítrico exalado, induzido pela exposição à fumaça do cigarro, e inibiu o aumento de 8-isoprostano e MCP1, além de aumentar a expressão da GPx, SODCuZn, TIMP1 e IL-10 por células inflamatórias na parede alveolar. O estudo também mostrou que o treinamento físico aeróbio foi capaz de inibir a diminuição da elastância pulmonar induzida pela exposição à fumaça de cigarro, mas não reduziu o aumento de colágeno no parênquima pulmonar. Estes resultados sugerem que o treinamento físico regular aeróbico de intensidade moderada pode desempenhar um papel importante durante a instalação da doença devido ao seu efeito antioxidante e antiinflamatório / Aerobic exercise was recently described as capable to reduce lung function decline and risk of developing COPD among active smokers. The biological plausibility of the influence of physical activity on the decline of lung function relies on the anti-inflammatory effects of physical activity, which have been described in experimental studies. We hypothesized there would be an interaction between aerobic exercise and development of disease. In order to further explore the physiopathology of COPD induced by exposure to cigarette smoke and the effects of exercise in development of emphysema, we used an experimental model of DPOC. C57Bl6 were divided in four groups: Control, Smoke, Exercise and Smoke/Exercise. Smoke groups were exposed to cigarette smoke for 30 minutes a day, 5 days a week, for 24 weeks. Exercise groups were trained at moderate intensity exercise for 60 minutes/day, 5 days/week for 24 weeks. The results demonstrated that regular aerobic physical training of moderate intensity inhibited alveolar distension, the increase of total inflammatory cells and production of reactive oxygen species in BAL and the increase in the generation of exhaled nitric oxide induced by exposure to cigarette smoke, and reduced the expression of 8-isoprostane and MCP1 and increased the expression of GPx, SODCuZn, TIMP1 and IL-10 by inflammatory cells in the alveolar wall. The study also showed that aerobic physical training was able to inhibit the decrease in lung elastance induced by exposure to cigarette smoke, but not the content in collagen fibers. These results suggest that regular aerobic physical training of moderate intensity may play an important role during the installation of disease due to its antioxidant and antiinflammatory effects

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: Os pacientes com asma crônica podem compartilhar similaridades clínicas e fisiológicas com pacientes com doença pulmonar obstrutiva crônica, tal como reversibilidade parcial ao broncodilatador ou pouca obstrução persistente do fluxo expiratório. Entretanto, não existem estudos comparando a patologia destas duas doenças em pacientes com idade similares e mesma gravidade da doença. MÉTODOS: Nós comparamos as dimensões das grandes e pequenas vias aéreas de 12 pacientes adultos (média±erro padrão, 32±3 anos) e 15 pacientes idosos e pré-idosos idosos (65±1 ano) não tabagista que foram a óbito por asma fatal com 14 pacientes tabagistas crônicos que foram a óbito por DPOC grave (71± 1 ano) e 19 pacientes-controle (56±1 ano). Usando a coloração de Movat e H&E, e a técnica de análise de imagens, nós quantificamos a espessura da membrana basal (MB) (valores expressos em ?m) a área de glândula submucosa nas grandes vias aéreas. Nas grandes e pequenas vias aéreas quantificamos a área de camada interna, a área de músculo liso e a área de camada externa. As áreas foram normalizadas pelo perímetro da MB (?m/?m2). RESULTADOS: os pacientes asmáticos adultos apresentaram a MB, área de músculo liso e a área da camada externa nas grandes e pequenas vias aéreas mais espessas, quando comparadas com os controles com idade similar com DPOC grave. Nos pacientes idosos e pré-idosos com asma, houve uma sobreposição na espessura da MB e na área da glândula submucosa, enquanto que nas pequenas e grandes vias aéreas a área de músculo liso foi mais espessa quando comparados com os controles com idade similar com pacientes com DPOC grave. Os pacientes com DPOC apresentaram nas pequenas e grandes vias aéreas as áreas de músculo liso menor quando comparada aos controles com idade similar. Os asmáticos adultos apresentaram a área de músculo liso maior quando comparada aos asmáticos idosos. CONCLUSÃO: Nossos dados fornecem novas informações sobre as mudanças patológicas que podem nos ajudar a entender melhor as similaridades e diferenças patológicas no pacientes adultos e idosos com asma comparados ao DPOC / Background: In some patients with chronic asthma, clinical and physiological similarities with chronic obstructive pulmonary disease may co-exist, such as partial reversibility to bronchodilators despite persistent expiratory airflow obstruction. However, pathologic analyses comparing both diseases in patients of similar age and disease severity are scarce. Methods: We compared the large and small airway dimensions in 12 younger (mean±SD, age 32 yr±3 yr) and 15 older (65 yr±1 yr) non-smoking fatal asthmatics with 14 chronic smokers with severe, fatal COPD (71 yr±1 yr) and 19 control patients (56 yr±1 yr). Using H&E, Movat\'s pentachrome staining and image analysis, we quantified large airway basement membrane (BM) thickness (?m); submucosal gland area; and large and small airway inner wall, smooth muscle and outer wall areas. Areas were normalized by BM perimeter (?m2/?m). Results: Younger adult fatal asthmatics had thicker BM, smooth muscle, and outer wall areas in both small and large airways when compared to agematched controls and fatal COPD patients. In older asthmatics, there was an overlap in BM thickness and submucosal gland area, whereas both large and small airway smooth muscle areas were thicker compared to age-matched controls and fatal COPD patients. COPD patients had thinner large and small airway smooth muscle areas compared to age-matched controls. Younger asthmatics had thicker small airway smooth muscle area compared to older asthmatics. Conclusion: Our data provide novel pathological substrate changes that may help us better understand physiological similarities and differences in younger and older patients with asthma compared to COPD.