Background: Advancements in machine learning (ML) techniques and voice technology offer the potential to harness voice as a new tool for developing decision-support tools in healthcare for the benefit of both healthcare providers and patients. Motivated by technological breakthroughs and the increasing integration of Artificial Intelligence (AI) and Machine Learning (ML) in healthcare, numerous studies aim to investigate the diagnostic potential of ML algorithms in the context of voice-affecting disorders. This thesis focuses on respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD) and explores the potential of a decision support tool that utilizes voice and ML. This exploration exemplifies the intricate relationship between voice and overall health through the lens of applied health technology (AHT. This interdisciplinary nature of research recognizes the need for accurate and efficient diagnostic tools. Objective: The objectives of this licentiate thesis are twofold. Firstly, a Systematic Literature Review (SLR) thoroughly investigates the current state of ML algorithms in detecting voice-affecting disorders, pinpointing existing gaps and suggesting directions for future research. Secondly, the study focuses on respiratory health, specifically COPD, employing ML techniques with a distinct emphasis on the vowel "A". The aim is to explore hidden information that could potentially be utilized for the binary classification of COPD vs no COPD. The creation of a new Swedish COPD voice classification dataset is anticipated to enhance the experimental and exploratory dimensions of the research. Methods: In order to have a holistic view of a research field, one of the commonly utilized methods is to scan and analyze the literature. Therefore, Paper I followed the methodology of an SLR where existing journal publications were scanned and synthesized to create a holistic view in the realm of ML techniques employed to experiment on voice-affecting disorders. Based on the results from the SLR, Paper II focused on the data collection and experimentation for the binary classification of COPD, which was one of the gaps identified in the first study. Three distinct ML algorithms were investigated on the collected datasets through voice features, which consisted of recordings collected through a mobile application from participants 18 years old and above, and the most utilized performance measures were computed for the best outcome.  Results: The summary of findings from Paper I reveals the dominance of Support Vector Machine (SVM) classifiers in voice disorder research, with Parkinson's Disease and Alzheimer's Disease as the most studied disorders. Gaps in research include underrepresented disorders, limited datasets in terms of number of participants, and a lack of interest in longitudinal studies. Paper II demonstrates promising results in COPD classification using ML and a newly developed dataset, offering insights into potential decision support tools for COPD diagnosis. Conclusion: The studies covered in this dissertation provide a comprehensive literature summary of ML techniques used to support decision-making on voice-affecting disorders for clinical outcomes. The findings contribute to understanding the diagnostic potential of using ML on vocal features and highlight avenues for future research and technology development. Nonetheless, the experiment reveals the potential of employing voice as a digital biomarker for COPD diagnosis using ML.

Made available in DSpace on 2016-06-02T20:18:12Z (GMT). No. of bitstreams: 1 2946.pdf: 2432239 bytes, checksum: 38088e144c053efcf31c8e90a089b74f (MD5) Previous issue date: 2010-04-07 / Universidade Federal de Sao Carlos / Patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) present significant exertional dyspnea. The peripheral muscle dysfunction appears to be the greatest impact on the inability to perform physical exercise. Additionally, there is respiratory muscle weakness caused by a limited supply of O2 and alteration of mechanical ventilation. In this context, in order to better understand the manifestations of these disorders and to establish management strategies, we have proposed the development of three studies. The first study was entitled Deep breathing heart rate variability is associated with respiratory muscle weakness in patients with chronic obstructive pulmonary disease . The purpose of the present investigation was to evaluate the influence of respiratory muscle strength on autonomic control of heart rate variability (HRV) in these patients. Ten COPD patients (69±9 years; forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) 59±12% and FEV1 41±11% predicted) and nine age-matched healthy male volunteers (64±5 years) participated in this study. The maximal inspiratory pressure was obtained in the sitting position. Then, electrocardiography signal was obtained in three conditions: 1) lying position for 15 min; 2) lying position during the respiratory sinusal arrhythmia maneuver (RSA-M) for 4 min; and 3) sitting position for 15 min. Data was analyzed by the time (RMSSD and SDNN indexes) and the frequency domains, in total power, low frequency (LF), high frequency (HF) absolute (ab) and normalized (nu) units and LF/HF ratio. Regarding the RSA-M indexes, the expiratory/inspiratory ratio (E/I) and the inspiratory/expiratory difference (&#916;IE) were calculated. The patients with COPD demonstrated significantly impaired cardiac autonomic modulation at rest and during RSA-M when compared with healthy subjects (ratio E/I: 1.1±0.06 vs. 1.2±0.1 e &#916;IE: 7.0±3.5 vs 12.7±4.2, respectively). Moreover, significant and positive correlations between maximal inspiratory pressure (MIP) and the inspiratory-expiratory difference (&#916;IE) (r = 0.60, p<0.01) were found. In conclusion, patients with COPD presented impaired sympathetic-vagal balance at rest and during RSA-M. In addition, cardiac autonomic control of heart rate was associated with inspiratory muscle weakness in chronic obstructive pulmonary disease. Based on this evidence, future research applications of respiratory muscle training may bring to light a potentially valuable target for rehabilitation. The second study was entitled to Deep breathing heart rate variability xviii is able to reflect the respiratory muscle weakness in chronic heart failure . The purpose of the present investigation was to evaluate the influence of respiratory muscle strength on autonomic control in these patients. Ten CHF (62 ± 7 years left ventricle eject fraction of 40 ± 5% and NYHA class I-III) and nine matched-age healthy volunteers (64±5 years) participated in this study. Heart rate variability (HRV) was obtained at rest and during RSA-M by electrocardiograph (as previously described). CHF patients demonstrated impaired cardiac autonomic modulation at rest and during RSA-M when compared with healthy subjects (p<0.05). Moreover, significant and positive correlations between MIP and IE-differences (r: 0.79), E/I ratio (r: 0.83), RMSSD (r: 0.77), SDNN (r: 0.77), LFab (r: 0.77), HFab (r: 0.70) were found during RSA-M. At rest, significant correlations were also found. Patients with CHF presented impaired sympathetic-vagal balance at rest. In addition, cardiac autonomic control of heart rate was associated with inspiratory muscle weakness in CHF. Based on this evidence, recommendations for future research applications of respiratory muscle training can bring to light a potentially valuable target for rehabilitation. Finally, the third study: "Behavior of heart rate on determination of anaerobic threshold in healthy men: comparison with cardiopulmonary exercise testing and near-infrared spectroscopy" aimed to identify the anaerobic threshold (AT) obtained from the V-slope method , visual method on oxihemoglobin (O2Hb) and deoxihemoglobin (HHb) and compare the method with heteroscedastic (HS) applied to VCO2, HR and HHb data. Secondly, to assess the degree of agreement between the methods for determination of AT. Fourteen healthy men were subjected to incremental cardiopulmonary test (CPT) in the electromagnetic cycle-ergometer until physical exhaustion. At the same time they obtained the following biological signals: (i) ventilatory and metabolic variables - a breath to breath - measured by the Cardio2 System (Medical Graphics Corporation, St. Paul, MO, USAI), (ii) spectroscopy, quasiinfrared rays - NIRS (NIRO 300 - Hamamatsu Photonics, Japan), and (iii) heart rate through cardiofrequencymeter (Polar S810i). We observed temporal equivalence and similar values of power (W), absolute O2 consumption (mL/min) and relative O2 consumption (mL/kg/min) and HR (bpm) on determination of AT by the methods performed. In addition, by the Bland-Altman plot, HR (bpm) confirmed the good agreement between the methods with biases between -1.3 and 3.5. In conclusion: (i) all methods were sensitive in identifying the AT1, including the HS applied to FC, and (ii) the methods showed a good correlation in the identification of AT1. Thus the xix results support the FC, a methodology that is simple and economically feasible, seems to be a valid parameter in determining the AT of the individuals in our study. Therefore it remains to be clarified if these results can be replicated in patients with chronic cardiopulmonary disorders, contributing in safe, individualized and adequate prescribing physical exercise in rehabilitation programs. / Pacientes com insuficiência cardíaca crônica (ICC) e doença pulmonar obstrutiva crônica (DPOC) apresentam significativa dispnéia exercional. A disfunção muscular periférica parece ser a causa de maior impacto na incapacidade de realização de exercício físico. Adicionalmente, pode coexistir a fraqueza muscular respiratória provocada pela limitada oferta de O2 e a alteração da mecânica ventilatória. Neste contexto, com intenção de compreender melhor as manifestações dessas disfunções e estabelecer estratégias de manejo, foi proposto o desenvolvimento de três estudos. O primeiro intitulado por Deep breathing heart rate variability is associated with respiratory muscle weakness in patients with chronic obstructive pulmonary disease teve como objetivo, avaliar a influência da fraqueza muscular inspiratória sobre a o controle autonômico da frequência cardíaca (FC) de homens com DPOC. Foram estudados 10 pacientes (69±9 anos; FEV1/FVC 59±12% and FEV1 41±11% do predito) e 9 homens saudáveis (64±5 anos). Na posição sentada, foi medida a pressão inspiratória máxima (PIMax) dos voluntários. Na sequência, em repouso, o sinal eletrocardiográfico foi obtido em três situações: 1) 15 min na posição supina; 2) quatro min durante a manobra de acentuação da arritmia sinusal respiratória (MASR) na posição supina; e 3) 15 min na posição sentada. Os dados foram analisados no domínio do tempo (índices RMSSD e SDNN) e da freqüência, pela densidade espectral total (DET), bandas de baixa (BF) e alta freqüências (AF) - absolutas (ab) e normalizadas (un), e a razão BF/AF. Durante M-ASR foram calculadas a razão expiração/inspiração (E/I) e a diferença inspiração/expiração (&#916;IE). Os pacientes com DPOC apresentaram valores significativamente menores da variabilidade da frequência cardíaca (VFC) quando comparados ao grupo controle em repouso e durante a M-ASR (razão E/I: 1,1±0,06 vs. 1,2±0,1 e &#916;IE: 7,0±3,5 vs 12,7±4,2, respectivamente). Adicionalmente, foi observado correlação positiva entre PIMax e &#916;IE (r = 0.60, p<0.01). Em conclusão: (i) pacientes com DPOC apresentam prejuízos da modulação autonômica da FC em repouso e durante a M-ASR; e (ii) a fraqueza muscular inspiratória parece influenciar no desbalanço simpato-vagal desses pacientes. Em similaridade, no segundo estudo, intitulado com Deep breathing heart rate variability is able to reflect the respiratory muscle weakness in chronic heart failure o objetivo foi avaliar a influência da PIMax no controle autonômico da FC de pacientes com ICC. Foram estudados 10 pacientes com ICC xv (62±7 anos Fração de Ejeção do ventrículo esquerdo de 40 ± 5% e classificação IIII da NYHA). Seguindo a metodologia descrita no estudo anterior, os resultados mostraram que os pacientes com ICC também apresentaram menores valores da VFC em repouso e durante a M-ASR e correlações positivas e significativas entre PIMax e diferença expiração-inspiração (r: 0,79), razão expiração/inspiração (r: 0,83), RMSSD (r: 0,77), SDNN (r: 0,77), BF (r: 0,77), AF (r: 0,70). Em conclusão: (i) pacientes com ICC apresentam prejuízos da modulação autonômica da FC em repouso e durante a M-ASR; e (ii) a fraqueza muscular inspiratória parece influenciar no desbalanço simpato-vagal desses pacientes. Por fim, o terceiro estudo: Comportamento da frequência cardíaca na determinação do limiar de anaerobiose em homens saudáveis: análise comparativa com o teste cardiopulmonar e a espectroscopia por raios quasi-infravermelhos objetivou identificar do limiar de anaerobiose (LA) obtido pelo método padrão-ouro, método visual pelo comportamento da oxihemoglobina (O2Hb) e deoxihemoglobina (HHb) e comparar com o método heteroscedástico (HS) aplicado aos dados de VCO2, HHb e da FC. Secundariamente, avaliar o grau de concordância entre os métodos de determinação do limiar de LA. Quatorze homens saudáveis foram submetidos ao teste cardiopulmonar (TCP) incremental em cicloergômetro de frenagem eletromagnética até a exaustão física. Concomitantemente foram obtidos os seguintes sinais biológicos: (i) variáveis ventilatórias e metabólicas respiração a respiração - medida pelo sistema CardiO2 System (Medical Graphics Corporation, St. Paul, MO, USAi); (ii) espectroscopia por raios quasi-infravermelhos - NIRS (NIRO 300 Hamamatsu Photonics, Japan); e (iii) frequência cardíaca por meio do cardiofreqüencímetro (Polar S810i). Foram observadas equivalências temporais e das variáveis potência (W), consumo de O2 absoluto (mL/min) e relativo (mL/kg/min) e FC (bpm) na determinação do LA pelos métodos empregados. Em adição, pela análise de Bland-Altman, a FC (bpm) confirmou a boa concordância entre os médotos com viéses entre -1,3 e 3,5. Em conclusão: (i) todos os métodos mostraram-se sensíveis na identificação do LA1, inclusive o HS aplicado a FC; e (ii) os médotos apresentaram boa correlação na identificação do LA1. Assim os resultados suportam que a FC, uma metodologia mais simples e economicamente viável, parece ser um parâmetro válido na determinação do LA dos indivíduos do nosso estudo. Agora, basta saber se estes resultados podem ser replicados em pacientes com disfunções cardiorrespiratórias crônicas, contribuíndo na prescrição xvi segura, individualizada e adequada de exercício físico em programas de reabilitação.

Limited data exists describing the long-term prognosis of patients with acute decompensated heart failure (ADHF) further stratified according to currently recommended ejection fraction (EF) findings. In addition, little is known about the magnitude of, and factors associated with, long-term prognosis for these patients. Based on previously validated and clinically relevant criteria, we defined HF-REF as patients with an EF value ≤40%, HF-PEF was defined as an EF value > 50%, and HF-BREF was defined as patients with an EF value during their index hospitalization between 41 and 49%. The hospital medical records of residents of the Worcester (MA) metropolitan area who were discharged after ADHF from all 11 medical centers in central Massachusetts during the 5 study years of 1995, 2000, 2002, 2004, and 2006 were reviewed. Follow-up was completed through 2011 for all patient cohorts. The average age of this population was 75 years, the majority was white, and 44% were men. Patients with HF-PEF experienced higher post discharge survival rates than patients with either HF-REF or HF-BREF at 1, 2, and 5-years after discharge. Advanced age and lower estimated glomerular filtration rate findings at the time of hospital admission were important predictors of 1-year death rates, irrespective of EF findings. Previously diagnosed chronic obstructive pulmonary disease, chronic kidney disease, and atrial fibrillation were associated with a poor prognosis in patients with PEF and REF whereas a history of diabetes was an important prognostic factor for patients with REF and BREF. In conclusion, although improvements in 1-year post-discharge survival were observed for patients in each of the 3 EF groups examined to varying degrees, the post- 7 discharge prognosis of all patients with ADHF remains guarded. In addition, we observed differences in several prognostic factors between patients with ADHF with varying EF findings, which have implications for more refined treatment and surveillance plans for these patients.

<p>Uvod: Iz rezultata brojnih randomiziranih kliničkih studija proizi&scaron;le su smernice u koijma se navodi da je upotreba neinvazivne ventilacije (NIV), uz farmakolo&scaron;ku terapiju, indikovana kod svih bolesnika sa te&scaron;kom egzacerbacijom hronične opstruktivne bolesti pluća (HOBP), i to sa najvi&scaron;im nivoom preporuke. Dokazano je da se upotrebom NIV-a smanjuje broj intubacija, uz smanjenje mortaliteta ali i skraćenje dužine bolničkog lečenja. S obzirom da je nekada ventilatorna potpora bila pružana isključivo u jedinicama intenzivne nege, a da je kapacitet ovakvih odeljenja gotovo stalno popunjen, postavlja se pitanje adekvatnog okruženja unutar bolnice gde se bezbedno i efikasno može primeniti neinvazivna ventilacija, ali gde se i na vreme mogu prepoznati rani znakovi njene neuspe&scaron;ne primene, nakon čega trebaobezbediti pravovremenu endotrahealnu intubaciju. Stoga su rađene brojne studije u cilju izdvajanja ranih prediktora ishoda neinvazivne ventilacije - kako u cilju ranog prepoznavanja neuspeha NIV-a i omogućavanja pravovremene intubacije, tako i u cilju stratifikacije pacijenata sa različitim stepenom rizika za neuspeh, uz obezbeđivanje adekvatnog nivoa nege i monitoringa za sve bolesnike. Ciljevi: Ciljevi istraživanja su da se utvrdi koji pokazatelji koreliraju sa neuspe&scaron;nim ishodom primene neinvazivne mehaničke ventilacije kod bolesnika sa te&scaron;kom egzacerbacijom hronične opstruktivne bolesti pluća, kako bi se kreirao prognostički model ishoda lečenja, te da se se na osnovu prognostičkog modela stratifikuju bolesnici prema stepenu rizika za neuspeh NIV-a i u skladu sa njim predloži adekvatan stepen monitoringa, odnosno kliničko okruženje za bezbedno i efikasno pružanje ventilatorne potpore. Metodologija: U Institutu za plućne bolesti Vojvodine u Sremskoj Kamenici sprovedeno je prospektivno opservaciono istraživanje u trajanju od 39 meseci, u koje je uključeno 250 konsekutivnih bolesnika hospitalizovanih zbog te&scaron;ke egzacerbacije HOBP-a sa respiratornom acidozom. NIV je primenjen u modu pritiskom podržane ventilacije ventilatorima marke Covidien tipa Airox Supportair, uz upotrebu oronazalne maske. Početni parametri su podrazumevali upotrebu ekspiratornog pozitivnog pritiska u disajnim putevima - EPAP-a od 5 cm H2O i inspiratornog pozitivnog pritiska u disajnim putevima IPAPa od 12 cm H20, koji su u potom titrirani ka ciljnim vrednostima IPAPa od 15-20 cmH2O, a u skladu sa kliničkim odgovorom. Za svakog bolesnika evidentirani su: pol, starost, ranija primena dugotrajne oksigenoterapije u kućnim uslovima, primena NIV-a tokom prethodnih hospitalizacija, komorbiditeti preko Charlson indeksa, vreme proteklo od početka hospitalizacije do započinjanja NIV-a, vrednosti pH, bikarbonata, PaCO2 i PaO2 u gasnim analizama arterijske krvi pre započinjanja NIV-a, inicijalna SpO2 i odnos PaO2/FiO2, zatim promena vrednosti pH, PaCO2 i PaO2 u gasnim analizama arterijske krvi sat vremena nakon početka primene NIV-a, inicijalni vitalni parametri - srčana frekvenca, respiratorna frekvenca, stanje svesti procenjeno Glazgov koma skalom (GCS), telesna temperatura, sistolni arterijski pritisak, diureza, a potom zbirni modifikovani ranoupozoravajući bodovni skor (MEWS-modified early warning score), prisustvo i opseg konsolidacija na radiogramu grudnog ko&scaron;a, saradnja bolesnika, te mesto primene NIV-a. Kao primarni ishod istraživanja definisan je neuspeh neinvazivne mehaničke ventilacije: intubacija ili smrtni ishod u toku hospitalizacije uzrokovan respiratornom insuficijencijom. Svaki potencijalni prediktor neuspeha je prvo evaluiran uz pomoć univarijantne analize, a potom su svi faktori rizika za koje je univarijantnom analizom utvrdjena statistička značajnost analizirani uz pomoć multivarijantne logističke regresije, u cilju utvrdjivanja adekvatnih statističkih modela. Rezultati: Od ukupno 250 bolesnika NIV je uspe&scaron;no primenjen kod 164 bolesnika (65.6%). Ukupno 139 (59.3%) bolesnika bilo je mu&scaron;kog pola, a prosečna starost svih ispitanika bila je 67 godina. Bolesnici sa neuspe&scaron;nim ishodom NIV-a imaju, prema univarijantnoj analizi: statistički značajno veće vrednosti Charlson indexa (p=0.002, OR 1.293, 95%CI 1.103-1.516), konsolidacije u &ge;2 kvadranata (p=0.000, OR 5.384, 95%CI 2.487-11.655), duže vreme od početka hospitalizacije do započinjanja NIV-a (p=0.0034, OR 1.005, 95%CI 1.000-1.009), tahikardiju (p=0.031, OR 2.292, 95%CI 1.080-4.864), vrednost GCS &le;11 (p=0.042, OR 1.000, 95%CI 0.165-0.969), veći MEWS skor (p=0.000, OR 1.708, 95%CI 1.410-2.068), niže vrednosti inicijalnog pH (p=0.004, OR 0.002, 95%CI 0.000-0.147), slabiju saradnju (p=0.000, OR 2.102, 95%CI 0.145-0.339). Mesto gde je sprovedena NIV je značajno uticalo na ishod &ndash; &scaron;anse za neuspe&scaron;an ishod su bile dvostruko veće kod bolesnika ventiliranih na op&scaron;tem odeljenju (p=0.006, OR 2.102, 95%CI 1.236-3.574). Kao nezavisni prediktori neuspeha nakon multivarijantne logističke regresije pokazali su se vrednosti Charlson-ovog indexa (p=0.043, OR 1.246, 95%CI 1.007-1.541), MEWS skora (p=0.010, OR 1.394, 95%CI 1.083-1.795), inicijalne vrednosti pH (p=0.030, OR 0.642, 95%CI 0.430-0.958) i stepena saradnje (p=0.000, OR 0.230, 95%CI 0.141-0.376). Zaključci: Bolesnici sa visokim vrednostima Charlson-ovog indeksa (preko 6 bodova) i MEWS-ovog skora (preko 4 boda), te niskom inicijalnom pH vredno&scaron;ću arterijske krvi (ispod 7.29) i niskim stepenom saradnje (manjim od 4) su bolesnici koji imaju povi&scaron;en stepen rizika za neuspe&scaron;an ishod primene neinvazivne ventilacije. Bolesnici visokog stepena rizika treba da se zbrinjavaju i neinvazivno ventiliraju na odeljenjima poluintenzivne i intenzivne nege, dok se bolesnici sa manjim stepenom rizika mogu inicijalno neinvazivno ventilirati i na op&scaron;tim odeljenjima, uz adekvatan monitoring i nadzor obučenog osoblja.</p> / <p>Introduction: Clinical guidelines that have evolved from the results of numerous randomized clinical trials state that the use of non-invasive ventilation (NIV), in addition to pharmacological therapy, is necessary in all patients wih severe exacerbation of chronic obstructive pulmonary disease (COPD) - at the highest level of recommendation. It has been proven that the use of NIV leeds to reduction in mortality, intubation rates, and the length of stay in hospitals. Since ventilatory support in past was only delivered in intensive care units, and bearing in mind that their capacities are limited, there is a question of an adequate setting within a hospital where NIV can be used safely and efficiently, and where potential early signs of failure will be timely recognized and patient intubated, if necessary. Consequently, the studies were performed in order to identify early predictors of NIV outcome &ndash; in order to recognize NIV failure and necessity for transition towards invasive ventilation, but also in order to stratify the patients according to the level of risk, which will then dictate the necessary level of care and monitoring. Goals: This research is aimed at identification of parameters that correlate with failure of non-invasive ventilation in patients with severe exacerbation of COPD, in order to create prognostic model of outcome, which will then enable stratification of patients according to the risk of NIV failure. The model is to be used in order to determine adequate level of care and monitoring, that is, a setting within a hospital, for provision of efficent and safe ventilatory support for all patients. Methods: This 39-month prospective observational study was performed at the Institute for Pulmonary Diseases of Vojvodina in Sremska Kamenica, which included 250 consecutive patients hospitalized due to severe exacerbation of COPD with respiratory acidosis. NIV was applied as pressure support mode of ventilation with the ventilators brand Covidien, type Airox Supportair, with oro-nasal mask. Initial parameters were: expiratory positive airway pressure &ndash; EPAPof 5 cm H2O and inspiratory positive airway pressure - IPAP of 12 cm H20, which were further adjusted towards the IPAP of 15-20 cmH2O, or according to the clinical response. The following data were recorded for each patient: sex, age, earlier longterm oxygen therapy, NIV episode during the previous hospitalizations, co-morbidities through Charlson index, time elapsed from admission to NIV initiation, initial blood gas values: pH, bicarbonates, PaCO2 and PaO2, initial SpO2 and PaO2/FiO2, the subsequent changes inthe blood gas values after one hour: pH, PaCO2 and PaO2, initial vital signs - heart rate, respiratory rate, consciousness level by Glasgow coma scale (GCS), body temperature, sistolic blood pressure, urine output, and then modified early warning score - MEWS, presence of consolidation on chest X-ray, tolerance, setting where NIV was applied. Primary outcome was NIV failure defined as endotracheal intubation or death during hospitalization caused by respiratory failure. All variables were first tested with univariate analysis, and those with statistical significance were further subjected to multivariate logistic regression, in order to generate an adequate statistical model. Results: Amongst the total of 250 patients, NIV was successfully applied in 164 patients (65.6 %). There were 139 (59.3%) male patients, and average age was 67. According to the univariate analysis, patients with NIV failure had: higher Charlson index (p=0.002, OR 1.293, 95%CI 1.103-1.516), consolidation in &ge;2 quadrants (p=0.000, OR 5.384, 95%CI 2.487-11.655), longer time from admission to NIV initiation (p=0.0034, OR 1.005, 95%CI 1.000-1.009), increased heart rate (p=0.031, OR 2.292, 95%CI 1.080-4.864), GCS &le;11 (p=0.042, OR 1.000, 95%CI 0.165-0.969), higher MEWS score (p=0.000, OR 1.708, 95%CI 1.410-2.068), lower initial pH (p=0.004, OR 0.002, 95%CI 0.000-0.147), poorer tolerance (p=0.000, OR 2.102, 95%CI 0.145-0.339). The setting were NIV was applied influenced the outcome &ndash; odds for NIV failure were twice as high for the patients on general wards (p=0.006, OR 2.102, 95%CI 1.236-3.574). After the multivariate logistic regression, the following variables were identified as independent predictors of outcome: Charlson index (p=0.043, OR 1.246, 95%CI 1.007- 1.541), MEWS score (p=0.010, OR 1.394, 95%CI 1.083-1.795), initial pH (p=0.030, OR 0.642, 95%CI 0.430-0.958) and tolerance (p=0.000, OR 0.230, 95%CI 0.141-0.376). Conclusions: Patients with higher Charlson index (&gt; 6 points) and MEWS score (&gt;4 points), lower initial pH (&lt;7.29) and tolerance (&lt;4) are at a higher risk for nonivasive ventilation failure. High-risk patients should be admitted and ventilated at high dependency or intensive care units, while the low-risk patients may receive non-invasive ventilatory support on general wards, with adequate monitoring and under the trained staff supervision.</p>

<p>Uvod: Astma i hronična opstruktivna bolest pluća (HOBP) najče&scaron;će su hronične respiratorne bolesti u čijoj terapiji prednost imaju inhalatorni lekovi. Pacijenti na inhalatornoj terapiji imaju povećan rizik od nastanka dentalnih erozija i karijesnih lezija, usled promena u količini lučenja pljuvačke i njene pH vrednosti. Cilj: Cilj ovog istraživanja je verifikacija dentalnih erozija i karijesnih lezija kod pacijenata s astmom i hroničnom opstruktivnom bolesti pluća, koji koriste inhalatornu terapiju. Materijal i metode rada: Istraživanjem je obuhvaćeno 80 ispitanika, životne dobi od 18 do 65 godina. Eksperimentalnu grupu sačinjavalo je 40 ispitanika, s dijagnostikovanom astmom ili hroničnom opstruktivnom bolesti pluća, koji uzimaju inhalatornu terapiju duže od 5 godina. Kontrolnu grupu činilo je 40 zdravih ispitanika istog godi&scaron;ta i pola kao u eksperimentalnoj grupi. Upitnik se koristio za prikupljanje podataka o osnovnom oboljenju, simptomima koji se mogu javiti kao nuspojave inhalatornih lekova, navikama, ishrani i održavanju oralne higijene. Kliničkim stomatolo&scaron;kim pregledom određeni su erozivni indeks, KEP indeks, indeks krvarenja iz interdentalne gingive i indeks mekih naslaga na zubima. Laboratorijskim ispitivanjem određeni su količina izlučene nestimulisane pljuvačke, te pH vrednost i koncentracije kalcijuma i fosfata u pljuvački. Rezultati: Kod pacijenata na inhalatornoj terapiji ustanovljena je vi&scaron;a prevalencija dentalnih erozija i karijesnih lezija, te vi&scaron;e vrednosti indeksa krvarenja iz interdentalne gingive i indeksa mekih naslaga na zubima, u odnosu na ispitanike kontrolne grupe. U eksperimentalnoj grupi ispitanika količina i pH vrednosti nestimulisane pljuvačke su statistički značajno niže u odnosu na ista obeležja kontrolne grupe. Vrednosti koncentracije kalcijuma u pljuvački između ispitivanih grupa se ne razlikuju statistički značajno. Vrednosti koncentracije fosfata u eksperimentalnoj grupi ispitanika su statistički značajno vi&scaron;e nego u kontrolnoj grupi ispitanika. Zaključak: Pacijenti na inhalatornoj terapiji spadaju u grupu osoba s visokim rizikom od nastanka dentalnih erozija i karijesnih lezija. Uvođenje lokalne strategije preventivnih mera, te uspostavljanje međusobne saradnje stomatologa i lekara &ndash; pulmologa, dovelo bi do očuvanja i unapređenja zdravlja zuba kod pacijenata na inhalatornoj terapiji.</p> / <p>Introduction: Asthma and chronic obstructive pulmonary disease (COPD) are predominant chronic respiratory diseases in whose treatment a priority is given to inhalation drugs. The patients receiving inhalation therapy are at an increased risk of dental erosion and caries lesions due to changes in the amount of salivary flow rate and its pH value. Objective: The study objective was to investigate the prevalence of dental erosion and caries lesions in patients with asthma and chronic obstructive pulmonary disease who use inhalation therapy. Materials and methods: The study included 80 participants between the age of 18 and 65. The experimental group comprised of 40 participants previously diagnosed with asthma or chronic obstructive pulmonary disease undergoing inhalation therapy for more than 5 years. The control group involved 40 healthy participants of the same age and gender status as those in the experimental group. The questionnaire was designed to collect informations on underlying disease, symptoms that can occur as side effects of inhaled drugs, habits, dietary and oral hygiene habits. The clinical dental examination established the basic erosive wear examination (BEWE index), DMFT index, papilla bleeding index (PBI) and dental plaque index. The laboratory investigation comprised measurements of the salivary flow rates of non-stimulated saliva, pH value and calcium and phosphate concentrations in the saliva. Results: The subjects receiving inhalation therapy were found to have a higher prevalence of dental erosion and caries lesion as well as higher mean papilla bleeding index scores and mean plaque index scores in comparison to the control group. In the experimental group, the mean value of the salivary flow rate and pH value were lower as compared to the control group. Calcium concentrations in the saliva were similar in both groups, but the results were not statistically significant. However, phosphate concentration was statistically significantly higher in the experimental group than in the control group. Conclusion: The patients undergoing inhalation therapy have a high risk of dental erosion and caries lesion. The introduction of local strategy of preventive dental care and establishing mutual cooperation between dentists and pulmonary specialists would contribute to the promotion and preservation of the dental health in the patients on inhalation therapy.</p>

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Student: Terezie Poláková Supervisor of master thesis: PharmDr. Miroslav Kovařík, Ph.D. Title of master thesis: Assessment of energy metabolism in patients with chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease (COPD) is the name for lung disease with systemic consequences. Besides the respiratory symptoms there are also described changes in body metabolism, which could lead to the development of serious metabolic syndrome called cachexia. The main aim of this study was to compare the resting energy expenditure (REE) and nutrition substrate utilization in 12 patients with advanced form of COPD from the Czech Multicentre Research Database of COPD (5 females and 7 males, mean age 68 ± 6 years) and in 9 patients of control group without respiratory impairment (5 females and 4 males, 62 ± 4 years). Assessment of body metabolism was determined by method of indirect calorimetry. Measured REE was then compared with prediction based on Harris-Benedict equation. The utilization of main nutrition substrates was determined from the respiratory quotient and urea nitrogen loss in urine. We found that measured REE in COPD patients was about 20 % higher than in control group....

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Student: Magdaléna Doleželová Supervisor of master thesis: PharmDr. Miroslav Kovařík, Ph.D. Title of master thesis: Body composition parameters in dependence on the metabolism degrese in patiens with COPD Chronic Obstructive Pulmonary Disease (COPD) is a very serious illness characterized by incompletely reversible airflow obstruction and lung emphysema. Contributes to its overall severity are extrapulmonary manifestations, especially cachexia and loss of lean tissue mass. Chronic inflammation of the respiratory airways and increased respiratory effort cause the hypermetabolic state to some patients with COPD. This thesis investigates the impact of increased metabolism on body composition in patients with COPD. Our study included 50 COPD patients (38 men, 12 women) who were examined by bioelectrical impedance. In this study, we compared the parameters of body composition of men with resting energy expenditure REE > 130% (hereinafter Men over 130%) (n = 9) and the group of men with REE < 130 % (hereinafter Men below 130 %) (n = 29). In the group of Men over 130 % we found a lower average value of body weight by 18 % compared to Men below 130 %. Total body and intracellular water were 12 %...

O objetivo deste trabalho foi avaliar se a proteína bifuncional de planta, CrataBL, que tem lectina e as propriedades inibidoras de enzima, modula alterações de mecânica pulmonar, inflamatórias e remodelamento induzidas por elastase intratraqueal em camundongos. Métodos: 36 camundongos C57BL6 receberam elastase (0,025 mg) por instilação intratraqueal (grupo ELA e ELA-CrataBL). Os grupos controles receberam salina (grupo SAL e SAL-CrataBL). Os camundongos foram tratados com instilação intraperitoneal de CrataBL (2mg/kg) nos dias 1, 14 e 21 após a instilação intratraqueal de elastase (grupo SAL-CrataBL e ELA-CrataBL) os animais controle receberam salina no mesmo volume. No dia 28, os camundongos foram anestesiados, ventilados mecanicamente e foram analisados a resistência e elastância do sistema respiratório (Ers e Rrs), elastância e resistência tecidual (Htis e Gtis), resistência das vias aéreas (Raw) e óxido nítrico exalado (NOex). Após, o lavado broncoalveolar (LBA) foi realizado, os pulmões foram retirados e por morfometria, e foram quantificados o intercepto linear médio (Lm), a quantidade de neutrófilos, células positivas para TNF-alfa, fibras colágenas, elásticas, células positivas para MMP-9, MMP-12, TIMP-1, eNOS e iNOS e isoprostano no parênquima pulmonar e vias aéreas. No parênquima foram avaliados os macrófagos nos septos alveolares e nas vias aéreas, foram também avaliadas as células para MUC-5. Resultados: No grupo ELA houve um aumento na Ers, Raw, Gtis, Htis, Lm, NOex, nas células totais, macrófagos, neutrófilos, eosinófilos e linfócitos no LBA em relação aos controles (p < 0,05), sendo que Raw, diminuiu também nos grupos SAL-CrataBL e ELA-CrataBL. Nos grupos tratados com CrataBL houve uma diminuição de Ers (37,0±2,2 cmH2O/L), Htis (37,9±3,5 cmH2O/ml/s), ENO (14,7±0,7 ppb), comparativamente ao grupo ELA (p < 0,05). No LBA houve atenuação de neutrófilos (0,003±0,001 104células/ml), linfócitos (0,003±0,001 104células/ml) e de Lm (54,6±6,0 mm). Complementando a avaliação, no grupo que recebeu elastase houve um aumento no número de macrófagos (22,88 +- 2,24 células/104um2), neutrófilos (1,18 +- 0,15 células/10 4um2), células positivas para TNF-ala (12,52 +- 0,42 células/104um2) no parênquima pulmonar. Nas alterações de remodelamento no parênquima pulmonar, houve um aumento da proporção de volume de fibras colágenas (11,5 +- 0,11%), elásticas (0,5 +- 0,03%), na quantidade de células positivas para MMP-9 (18,59 +- 1,87 células/104?m2), MMP-12 (20,17 +- 1,92 células/104?m2), TIMP-1 (14,42 +- 2,05 células/104um2) em comparação com os controlos (p < 0,001). No estresse oxidativo, houve um aumento de eNOS (13,15 +- 0,40 células/104um2), iNOS (10,49 +- 0,65 células/104um2) e isoprostano (18,11 =- 5,38%). O tratamento CrataBL (grupo ELA-CrataBL) reduziu no parênquima pulmonar a quantidade de macrófagos (9,58 +- 1,36 células/104um2), neutrófilos (0,75 +- 0,1 células/104um2), células positivas para TNF-alfa (10.4±0,49 células/104?m2), fibras colágenas (10,8 +- 0,13%), elásticas (0,3 +- 0,02%), a quantidade de células positivas para a MMP-9 (10,35±0,65 células/104um2), MMP-12 (14,15±0,59 células/104um2), TIMP-1 (9,89 +- 2,79 células/104um2), MUC-5 (3,56 +- 0,54 células/104um2), eNOS (6.98 +- 0.32 células/104um2) e iNOS (6,21 +- 0,42 células/104um2) e isoprostano (8,96 +- 3,08 %) em relação ao grupo ELA (p < 0,001). Nas vias aéreas também ocorreu um aumento significativo de neutrófilos (5,97 +- 1,03 células/104um2), células positivas para TNF-alfa (15,82 +- 1,03 células/104um2). Nas alterações de remodelamento pulmonar nas vias aéreas também ocorreu um aumento da proporção de volume de fibras colágenas (8,73 +- 2,59%), elásticas (2,56 +- 0,18%), na quantidade de células positivas para MMP-9 (14,86 +- 1,77 células/104um2), MMP-12 (18,56 +- 1,79 células/104um2), TIMP-1 (1,31 +- 0,12 células/104um2) e MUC-5 (7,09 +- 1,71 células/104um2) em comparação com os controlos (p < 0,001). No estresse oxidativo, houve um aumento de células positivas para eNOS (3,09 +- 0,08 células/104um2), iNOS (5,4 +- 0,3 células/104um2) e isoprostano (18,11 +- 5,38%) em comparação com os controlos (p < 0,001). O tratamento CrataBL (grupo ELA-CrataBL) reduziu nas vias aéreas a quantidade de neutrófilos (4,62 +- 0,61 células/104um2), TNF- alfa (14,30 +- 1,28 células/104um2), fibras colágenas (7,80 +- 1,37%), elásticas (1,4 +- 0,13%), a quantidade de células positivas para a MMP-9 (9,93 +- 1,39 células/104um2), MMP-12 (12,06 +- 1,15 células/104um2), TIMP-1 (0,73 +- 0,05 células/104?m2), MUC-5 (3,56 +- 0,54 células/104um2), eNOS (1,89 +- 0,16 células/104um2) e iNOS (4,3 +- 0,31 células/104um2), isoprostano (7,34 +- 2,31%) em relação ao grupo ELA (p < 0,001). Conclusão: CrataBL atenua as alterações de mecânica pulmonar, lavado bronco alveolar, responsividade inflamatória, controle do remodelamento e estresse oxidativo induzidas pela elastase. Embora mais estudos devam ser realizados, esta proteína bifuncional pode contribuir como potencial ferramenta terapêutica para o tratamento da DPOC / The aim of this study was to evaluate whether the bifunctional protein plant, CrataBL, which has lectin and enzyme inhibitory properties, modulates changes in lung mechanics, inflammatory and remodeling induced by intratracheal elastase in mice.Methods : 36 C57/Bl6 mice received elastase (0.025 mg) by intratracheal (group ELA and ELA-CrataBL). Control groups received saline (group SAL and SAL-CrataBL).The mice were treated with intraperitoneal instillation of CrataBL (2mg/kg) on days 1, 14 and 21 after intratracheal instillation of elastase (group SAL-CrataBL and ELA-CrataBL), control animals received saline in the same volume. On day 28, the mice were anesthetized and mechanically ventilated were analyzed resistance and respiratory system elastance (Ers and Rrs), elastance and tissue resistance (Htis and Gtis), airway resistance (Raw) and exhaled nitric oxide (ENO). After the bronchoalveolar lavage (BAL) was performed, the lungs were removed and morphometry were quantified and the linear intercept mean (Lm), the number of neutrophils, positive cells for TNF-alfa, collagen fibers, positive cells for MMP-9, MMP-12, TIMP-1, eNOS, iNOS and isoprostane in lung parenchyma and airways. Parenchyma was also evaluated macrophages in the alveolar septa. Airway was also evaluated MUC-5 cells. Results: In group ELA was an increase in Ers, Raw, Gtis, Htis, Lm, ENO, in total cells, macrophages, neutrophils, eosinophils and lymphocytes in BAL compared to controls (p < 0.05), and Raw, decreased in both groups SAL-CrataBL and ELA-CrataBL. In the groups treated with CrataBL there was a decrease in Ers (37.0±2.2 cmH2O/L) Htis (37 9±3.5 cmH2O/ml/s) and ENO (14.7±0.7 ppb) compared to the ELA group (p < 0.05). In BAL there was attenuation of neutrophils (0.003±0.001 104cells/ml), lymphocytes (0.003±0.001 104cells/ml) and Lm (54.6±6.0 mm). Complementing the assessment, the group that received elastase was an increase in the number of macrophages (22.88±2.24 cells/104um2), neutrophils (1.18±0.15 cells/104um2), positive TNF-alfa cells (12.52±0.42 cells/104um2) in the lung parenchyma. In remodeling changes in lung parenchyma, there was an increase in the volume ratio of collagen fibers (11.5 ± 0.11%), elastic (0.5±0.03%), the number of positive MMP-9 cells (18.59±1.87 cells/104um2), MMP-12 (20.17 ± 1.92 cells/104um2) TIMP-1 (14.42±2.05 cells/104um2) compared to controls (p < 0.001). Oxidative stress, was an increased of eNOS (13.15±0.40 cells/104um2), iNOS (10.49 ± 0.65 cells/104um2) and isoprostane (18.11±5.38%). Treatment CrataBL (ELA-CrataBL group) reduced the amount of parenchymal lung macrophages (9.58±1.36 cells/104um2), neutrophils (0.75±0.1 cells/104um2), positive TNF-alfa cells (10.4±0.49 cells/104um2), collagen (10.8±0.13%), elastic (0.3±0.02%), the number of positive MMP-9 cells (10.35±0.65 cells/104?m2), MMP-12 (14.15±0.59 cells/104um2), TIMP-1 (9.89±2.79 cells/104um2) MUC-5 (3.56±0.54 cells/104um2), eNOS (6.98±0:32 cells/104um2) and iNOS (6.21±0.42 cells/104um2) and isoprostane (8.96 ± 3.08%) compared to group ELA (p < 0.001). Airway was also a significant increase in neutrophils (5.97±1.03 cells/104um2), positive TNF-alfa cells (15.82±1.03 cells/104um2). Changes in lung airway remodeling also occurred an increase in the volume ratio of collagen fibers (8.73±2.59%), elastic (2.56±0.18%), the number of positive MMP-9 cells (14.86±1.77 cells/104um2), MMP-12 (18.56±1.79 cells/104um2) TIMP-1 (1.31±0.12 cells/104um2) and MUC-5 (7.09±1.71 cells/104um2) compared to controls (p < 0.001). Oxidative stress, an increase of eNOS (3.09 ± 0.08 cells/104um2), iNOS (5.4±0.3 cells/104um2) and isoprostane (18.11±5.38%) compared to controls (p < 0.001). Treatment CrataBL (ELA-CrataBL group) reduced the amount airway neutrophils (4.62±0.61 cells/104um2), TNF-alfa (14.30 ± 1.28 cells/104um2), collagen fibers (7 80±1.37%), elastic (1.4±0.13%), the number of positive MMP-9 cells (9.93±1.39 cells/104um2), MMP-12 (12.06±1.15), TIMP-1 (0.73±0.05 cells/104um2), MUC-5 (3.56±0.54 cells/104um2), eNOS (1.89±0,16 cells/104um2) and iNOS (4.3±0.31 cells/104um2), isoprostane (7.34±2.31%) compared to group ELA (p < 0.001). Conclusion: CrataBL attenuates changes in lung mechanics, broncho alveolar inflammatory responsiveness, control remodeling and oxidative stress induced by elastase. Although more studies should be conducted, this bifunctional protein may contribute as a potential therapeutic tool for the treatment of COPD

Introdução: A DPOC é uma doença respiratória prevenível e tratável, caracterizada por limitação persistente ao fluxo aéreo, hiperinsuflação e aprisionamento aéreo. A dispneia e a intolerância aos esforços, decorrentes destas alterações fisiopatológicas sofre influência de vários fatores. Dentre estes, o recrutamento e a sobrecarga imposta aos músculos inspiratórios e expiratórios são de fundamental importância, porém a participação destes ainda não foi completamente elucidada em diferentes gravidades da doença. Objetivos: O objetivo principal deste estudo foi avaliar a mecânica ventilatória, e o grau de recrutamento da musculatura inspiratória e expiratória na DPOC leve e grave, na condição de repouso e durante um teste máximo de exercício, comparado a um grupo de indivíduos saudáveis. Metodologia: Trata-se de um estudo transversal envolvendo 36 indivíduos, sendo 24 pacientes portadores de DPOC e 12 voluntários sadios. As avaliações foram divididas em 2 visitas. No D1, foram realizadas uma avaliação clínica, avaliação de dispneia (mMRC) e de qualidade de vida (SGRQ), além da prova de função pulmonar completa. Na 2ª visita, realizada com intervalo de 1 semana, foram avaliadas: as pressões respiratórias máximas estáticas por meio de métodos volitivos (PImax, PEmax, SNIP, Pes sniff, Pga sniff e Pdi sniff) e não volitivos (Twitch cervical bilateral e T10); avaliação da sincronia toracoabdominal por pletismografia de indutância; avaliação do recrutamento dos músculos inspiratórios e expiratórios ao repouso pela eletromiografia de superfície; e, posteriormente, um teste de exercício cardiopulmonar incremental para estudo de todas essas variáveis no esforço. Resultados: Foram avaliados 24 pacientes (12 leves e 12 graves) e 12 indivíduos saudáveis da mesma faixa etária. A maioria dos pacientes apresentava comprometimento significativo da qualidade de vida e os pacientes do grupo grave eram mais sintomáticos. A função pulmonar encontrava-se alterada na maioria dos pacientes. Destes, 79,2% apresentavam aprisionamento aéreo e 70,8% tinham redução da DLCO. Tais alterações foram semelhantes nos 2 grupos de pacientes. A força muscular estática medida por métodos volitivos e não volitivos estava reduzida nos 2 grupos e mostrou relação com o VEF1. No exercício, a dispneia foi o principal motivo para interrupção do teste em 70% dos pacientes. A HD esteve presente em 87,5% dos pacientes. O comportamento das pressões respiratórias foi significativamente diferente entre os 3 grupos. Os pacientes com DPOC apresentaram maior atividade diafragmática (Pdi) comparado aos controles e a participação da musculatura expiratória também foi maior neste grupo, principalmente nos graves. Apesar disso, os pacientes com DPOC apresentaram uma eficiência mecânica reduzida, ou seja, esse incremento da força muscular foi insuficiente para manter uma ventilação adequada para uma determinada carga. Com o aumento da demanda ventilatória, houve recrutamento precoce e progressivo dos músculos inspiratórios e expiratórios durante o exercício. O trabalho resistivo e o expiratório foram significativamente diferentes entre os controles e os pacientes com DPOC desde o início do exercício. Como consequência destas alterações, a intensidade da dispneia durante o TECP foi maior nos pacientes com DPOC (leve e grave) para a mesma carga e mesma ventilação-minuto (VE), quando comparada aos indivíduos do grupo-controle. Conclusões: O conjunto destes achados demonstra que o comprometimento dos músculos inspiratórios e expiratórios contribuiu significativamente para a dispneia e a intolerância ao exercício tanto no DPOC leve quanto no DPOC grave. E que este comprometimento pode não ser detectado com os testes máximos de força ao repouso / Introduction: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable respiratory disease characterized by persistent airflow limitation, lung hyperinflation and air trapping. Dyspnea and effort intolerance resulting from these pathophysiological changes are influenced by several factors. Among these, the recruitment and burden to the aspiratory and expiratory muscles are of fundamental importance but their participation has not been fully elucidated in different severities of disease. Objectives: The main objective of this study was to evaluate the mechanics of ventilation and the grade of recruitment of inspiratory and expiratory muscles in patients with mild and severe COPD, at rest and during maximum exercise, compared to a group of healthy individuals. Methods: Cross-sectional study involving 36 subjects, 24 patients with COPD and 12 healthy volunteers. The evaluations were performed in two visits. In the first visit, participants underwent a clinical evaluation, dyspnea (modified Medical Research Council) and quality of life (Saint George Respiratory Questionnaire) assessments, and complete pulmonary function test. In the second visit, which was one week later, the following evaluations were performed: maximum static respiratory pressures through volitional (MIP, MEP, SNIP, sniff Pes, sniff Pga and sniff Pdi) and non-volitional methods (cervical twitch and T10); evaluation of thoraco-abdominal synchrony by inductance plethysmography; evaluation of recruitment of the inspiratory and expiratory muscles at rest by surface electromyography; and then an incremental cardiopulmonary exercise testing to assess all of these variables under exercise conditions. Results: We evaluated 24 patients (12 with mild and 12 with severe COPD) and 12 healthy individuals of the same age group. Most patients had significant impairment of quality of life and those with severe COPD were more symptomatic. The lung function was abnormal in the majority of patients. Among them, 79.2% had air trapping and 70.8% had reduced diffusing lung capacity for carbon monoxide (DLCO). These changes were similar in the 2 patients\' groups. Static muscle strength measured by volitional and non-volitional methods was reduced in both patients\' groups and showed a relationship with forced expiratory volume 1 (FEV1). During exercise, dyspnea was the main reason for interrupting the test in 70% of patients. Dynamic hyperinflation (DH) was present in 87.5% of patients. The behavior of the respiratory pressure was significantly different between the three groups. Patients with COPD had higher diaphragmatic activity (Pdi) compared to controls and the participation of expiratory muscles was also higher in this group, especially in patients with severe COPD. Nevertheless, patients with COPD had reduced mechanical efficiency, i.e., the increase of muscle strength was insufficient to maintain adequate ventilation for a given load. With the increase in ventilatory demand, there was an early and progressive recruitment of inspiratory and expiratory muscles during exercise. The resistive and expiratory work were significantly different between controls and patients with COPD since the beginning of the exercise. As a result, the intensity of dyspnea during the cardiopulmonary exercise test CPET was higher in patients with COPD (mild and severe) for the same charge and minute ventilation (VE), when compared to controls. Conclusions: Taken together, these findings demonstrated that inspiratory and expiratory muscles are compromised in patients with mild and severe COPD and this compromise contributed significantly to dyspnea and exercise intolerance. Furthermore, these alterations could not be properly detected with the simple maximal tests commonly used

Introdução: O desequilibrio protease-antiprotease é fundamental para a fisiopatologia da doença pulmonar obstrutiva crónica (DPOC). No entanto, poucos estudos para a inibição da elastase têm sido investigados. Objetivo: O nosso estudo avaliou a capacidade do inibidor proteinase derivada da planta Bauhinia bauhinioides (BbKI) na modulação da inflamação pulmonar induzida pela elastase. Métodos: Camundongos C57BL receberam instilação intratraqueal de elastase (0,025 mg, ELA n=6) ou solução salina (SAL n=6) e foram tratados por via intraperitoneal com BbKI (2 mg/kg, de ELA-BbKI n=6, SAL-BbKI n=6) nos dias 1, 14 e 21. No dia 28 foram realizadas as seguintes análises: (I) avaliação da mecânica pulmonar (II) medida do óxido nítrico exalado (ENO), (III) a determinação do número de céluas no lavado broncoalveolar (FLBA), e ( IV) coloração imunohistoquímica do fluído pulmonar, (V) intercepto linear médio (Lm), Resultados: Além de diminuir alterações mecânicas e a lesão do septo alveolar (Lm), BbKI reduziu o número de células no fluido de FLBA e diminuiu a expressão celular de TNF-alfa, MMP-9, MMP-12, TIMP-1, eNOS e iNOS em vias aéreas e nas paredes alveolares em comparação com o grupo de ELA (p < 0,05). BbKI diminuiu a proporção de volume de 8-iso-PGF2, as fibras colagenas e as elásticas nas vias aéreas e paredes alveolares em comparação com o grupo de ELA (p < 0,05). Houve redução do número de células para positivas MUC-5 nas paredes das vias aéreas (p < 0,05). Houve redução do número de neutrófilos em vias aereas e parenquima e de macrófagosnas paredes alveolares. Conclusão: BbKI foi eficaz na redução da inflamação pulmonar, mecânica pulmonar e do remodelamento da matriz extracelular induzida por elastase. BbKI pode ser uma ferramenta farmacológica potencial para o tratamento da DPOC; no entanto, são necessárias análises adicionais / Introduction: The protease-antiprotease imbalance is essential to the pathophysiology of chronic obstructive pulmonary disease (COPD). However, few studies for inhibition of elastase have been investigated. Objective: Our study evaluated the ability of proteinase inhibitor derived Bauhinia bauhinioides plant (BbKI) in modulating lung inflammation induced by elastase. Methods: Mice C57BL received intratracheal elastase instillation (0.025 mg, ELA n = 6) or saline (SAL n = 6) and were treated intraperitoneally with BbKI (2 mg/kg of ELA-BbKI n = 6, SAL-BbKI n = 6) on days 1, 14 and 21. On the 28th the following analyzes were performed: (i) assessment of pulmonary mechanics (II) measurement of exhaled nitric oxide (ENO), (III) determining the number of cells in bronchoalveolar lavage fluid (BALF), and (IV) immunohistochemical staining of lung fluid, (V) mean linear intercept (Lm) Results: In addition to reducing mechanical changes and Lm, BbKI reduced the number of cells in BALF fluid and decreased cellular expression of TNF-alfa, MMP-9, MMP-12, TIMP-1, eNOS and iNOS in the airway and alveolar walls compared with ELA group (p < 0.05). BbKI decreased volume proportion of 8-iso-PGF2, collagen fibers and elastic airway and alveolar walls compared with ELA group (p < 0.05). There was a reduction from MUC-5 positive cells in the airway walls (p < 0.05). There was a reduction in the number of neutrophils in airway and alveolar walls (p < 0.005) and a reduction in macrophages in alveolar walls (p < 0.005). Conclusion: BbKI was effective in reducing inflammation, pulmonary mechanics and remodeling of the extracellular matrix induced by elastase. BbKI may be a potential pharmacological agent for the treatment of COPD; however, additional tests are required