Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotype

Aims Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obese-allergen sensitized mice. Main methods Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1 +) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression. Key findings Obesity and allergen-sensitization together increased the number of LYVE-1 + lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues. Significance The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.

Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotype

Aims: Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obeseallergen sensitized mice. Main methods: Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1+) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression. Key findings: Obesity and allergen-sensitization together increased the number of LYVE-1+ lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues. Significance: The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.

Qualidade de vida relacionada com o exerc��cio em indiv��duos com asma: revis��o sistem��tica

Background: A asma condiciona o dia-a-dia do indiv��duo asm��tico do ponto de vista cl��nico e emocional demonstrando-se muitas vezes como um subtractivo da qualidade de vida (QV). Alguns estudos, com particular incid��ncia nos ��ltimos dez anos, para al��m de demonstrarem os benef��cios da actividade f��sica na componente cl��nica da doen��a, t��m analisado o seu efeito na QV dos asm��ticos. Objectivo: Analisar os efeitos da actividade f��sica na QV de indiv��duos com asma tendo por base uma revis��o da literatura actual. M��todos: Foi conduzida uma pesquisa dos randomized controlled trials (RCT) compreendidos entre Janeiro de 2000 e Agosto de 2010, bem como as cita����es e as refer��ncias bibliogr��ficas de cada estudo nas principais bases de dados de ci��ncias da sa��de (Academic Search Complete, DOAJ, Elsevier ��� Science Direct, Highwire Press, PubMed, Scielo Global, Scirus, Scopus, SpringerLink, Taylor & Francis e Wiley Interscience) com as palavras-chave: asthma, quality of life, QoL, physical activity, exercise, breathing, training e programme em todas as combina����es poss��veis. Os estudos foram analisados independentemente por dois revisores quanto aos crit��rios de inclus��o e qualidade dos estudos. Resultados: Dos 1075 estudos identificados apenas onze foram inclu��dos. Destes, seis apresentaram um score 5/10, tr��s 6/10 e dois 7/10 segundo a escala PEDro. Cinco destes estudos foram realizados em crian��as entre os 7 e os 15 anos e os restantes em adultos. Os programas de interven����o dividiram-se em programas de treino aer��bio e programas de exerc��cios respirat��rios. Todos programas de treino aer��bio apresentaram melhorias na QV demonstrando uma influ��ncia positiva do treino aer��bio na asma. Principais conclus��es: H�� uma tend��ncia not��ria do benef��cio dos programas de treino aer��bio na QV dos indiv��duos asm��ticos. Os programas de exerc��cios respirat��rios foram poucos e heterog��neos impossibilitando uma conclus��o positiva quanto �� sua recomenda����o para a melhoria da QV nesta patologia. H�� uma grande necessidade de mais RCT com rigor metodol��gico.

Linfangiog��nese no tecido adiposo em modelos de doen��a inflamat��ria cr��nica (asma e obesidade): uma abordagem por imunohistoqu��mica e lipid��mica

O tecido adiposo �� um ��rg��o end��crino din��mico, secretando factores importantes na regula����o do metabolismo, fluxo vascular sangu��neo e linf��tico, e fun����o imunol��gica, entre outros. Em caso de acumula����o de tecido adiposo por ingest��o de uma dieta gorda, ou por disfun����o metab��lica, os adip��citos podem desencadear uma reac����o inflamat��ria por falha na drenagem linf��tica, acumulando-se mediadores inflamat��rios, os quais potenciam a propaga����o da reac����o. Assim, questiona-se uma potencial associa����o entre o aumento de tecido adiposo na obesidade, hip��xia adipocit��ria e estimula����o da linfangiog��nese. Al��m disso, a express��o de adipocinas varia de acordo com a distribui����o do tecido adiposo (subcut��neo, TAS e visceral, TAV). Deste modo, pretende-se com este estudo contribuir para o aumento do conhecimento sobre os complexos mecanismos moleculares subjacentes �� linfangiog��nese. Ensaios com ratinhos da estirpe C57Bl/6J (modelo de obesidade) e BALB/c (modelo de asma e obesidade), divididos em grupos submetidos a dieta normal e dieta rica em gordura. Avalia����o semi-quantitativa da express��o tecidular de LYVE-1 (marcador da linfangiog��nese) por imunohistoqu��mica em material embebido em parafina, no TAS e TAV, e cromatografia l��quida de ultra-performance acoplada de espectrometria de massa (UPLC-MS) para an��lise da express��o plasm��tica de ceramida e esfingosina-1-fosfato (S1P). No modelo de obesidade observou- -se diminui����o do n��mero de vasos linf��ticos e express��o de LYVE-1 ao longo do tempo no TAV, e aumento de ambos os par��metros e hipertrofia adipocit��ria no TAS. As concentra����es de ceramida e S1P corroboram a exist��ncia de um processo inflamat��rio nos ratinhos em estudo, ainda que numa fase muito inicial. No modelo de asma e obesidade, ap��s 17 semanas de tratamento, observou-se incremento da linfangiog��nese no TAV, mas n��o no TAS. A resposta inflamat��ria avaliada atrav��s dos diferentes par��metros permite afirmar que num estadio inicial de obesidade a prolifera����o linf��tica poder�� estar a ser retardada pela hipertrofia adipocit��ria. A liberta����o de adipocinas ser�� observada apenas numa fase posterior, desencadeando todo o processo inflamat��rio que incrementar�� a prolifera����o linf��tica. Adicionalmente, �� poss��vel sugerir que a maior press��o �� qual o TAV se encontra sujeito n��o favorece a prolifera����o linf��tica, pelo menos num estadio incial.

Avalia����o de um programa de sa��de sobre asma em meio escolar

Objectivos: Avaliar o efeito de um programa sobre asma em estudantes Metodologia: Estudo quase-experimental numa amostra de 44 estudantes (12,48��0,698 anos). O grupo experimental (n= 23) foi sujeito a uma sess��o de educa����o sobre asma e grupo controlo (n= 21) n��o. Ambos foram avaliados atrav��s de um question��rio na baseline do estudo e reavaliados uma semana ap��s relativamente a conhecimentos e procedimentos. Resultados: Obtiveram-se diferen��as estatisticamente significativas entre grupos relativamente aos conhecimentos (p<0.001) e comportamentos (p<0.001) sendo estes mais elevados no grupo experimental. Conclus��o: O programa teve efeitos positivos na mudan��a de comportamentos e conhecimentos

Estudo da transfer��ncia das cloraminas da ��gua para o ar duma piscina coberta

Mestrado em Engenharia Qu��mica

Influence of environmental temperature and humidity on the acute ventilatory response to exercise in asthmatic adolescents

Asthma is a chronic inflammatory disorder of the respiratory airways affecting people of all ages, and constitutes a serious public health problem worldwide (6). Such a chronic inflammation is invariably associated with injury and repair of the bronchial epithelium known as remodelling (11). Inflammation, remodelling, and altered neural control of the airways are responsible for both recurrent exacerbations of asthma and increasingly permanent airflow obstruction (11, 29, 34). Excessive airway narrowing is caused by altered smooth muscle behaviour, in close interaction with swelling of the airway walls, parenchyma retractile forces, and enhanced intraluminal secretions (29, 38). All these functional and structural changes are associated with the characteristic symptoms of asthma ��� cough, chest tightness, and wheezing ���and have a significant impact on patients��� daily lives, on their families and also on society (1, 24, 29). Recent epidemiological studies show an increase in the prevalence of asthma, mainly in industrial countries (12, 25, 37). The reasons for this increase may depend on host factors (e.g., genetic disposition) or on environmental factors like air pollution or contact with allergens (6, 22, 29). Physical exercise is probably the most common trigger for brief episodes of symptoms, and is assumed to induce airflow limitations in most asthmatic children and young adults (16, 24, 29, 33). Exercise-induced asthma (EIA) is defined as an intermittent narrowing of the airways, generally associated with respiratory symptoms (chest tightness, cough, wheezing and dyspnoea), occurring after 3 to 10 minutes of vigorous exercise with a maximal severity during 5 to 15 minutes after the end of the exercise (9, 14, 16, 24, 33). The definitive diagnosis of EIA is confirmed by the measurement of pre- and post-exercise expiratory flows documenting either a 15% fall in the forced expiratory volume in 1 second (FEV1), or a ���15 to 20% fall in peak expiratory flow (PEF) (9, 24, 29). Some types of physical exercise have been associated with the occurrence of bronchial symptoms and asthma (5, 15, 17). For instance, demanding activities such as basketball or soccer could cause more severe attacks than less vigorous ones such as baseball or jogging (33). The mechanisms of exercise-induced airflow limitations seem to be related to changes in the respiratory mucosa induced by hyperventilation (9, 29). The heat loss from the airways during exercise, and possibly its post-exercise rewarming may contribute to the exercise-induced bronchoconstriction (EIB) (27). Additionally, the concomitant dehydration from the respiratory mucosa during exercise leads to an increased interstitial osmolarity, which may also contribute to bronchoconstriction (4, 36). So, the risk of EIB in asthmatically predisposed subjects seems to be higher with greater ventilation rates and the cooler and drier the inspired air is (23). The incidence of EIA in physically demanding coldweather sports like competitive figure skating and ice hockey has been found to occur in up to 30 to 35% of the participants (32). In contrast, swimming is often recommended to asthmatic individuals, because it improves the functionality of respiratory muscles and, moreover, it seems to have a concomitant beneficial effect on the prevalence of asthma exacerbations (14, 26), supporting the idea that the risk of EIB would be smaller in warm and humid environments. This topic, however, remains controversial since the chlorified water of swimming pools has been suspected as a potential trigger factor for some asthmatic patients (7, 8, 20, 21). In fact, the higher asthma incidence observed in industrialised countries has recently been linked to the exposition to chloride (7, 8, 30). Although clinical and epidemiological data suggest an influence of humidity and temperature of the inspired air on the bronchial response of asthmatic subjects during exercise, some of those studies did not accurately control the intensity of the exercise (2, 13), raising speculation of whether the experienced exercise overload was comparable for all subjects. Additionally, most of the studies did not include a control group (2, 10, 19, 39), which may lead to doubts about whether asthma per se has conditioned the observed results. Moreover, since the main targeted age group of these studies has been adults (10, 19, 39), any extrapolation to childhood/adolescence might be questionable regarding the different lung maturation. Considering the higher incidence of asthma in youngsters (30) and the fact that only the works of Amirav and coworkers (2, 3) have focused on this age group, a scarcity of scientific data can be identified. Additionally, since the main environmental trigger factors, i.e., temperature and humidity, were tested separately (10, 28, 39) it would be useful to analyse these two variables simultaneously because of their synergic effect on water and heat loss by the airways (31, 33). It also appears important to estimate the airway responsiveness to exercise within moderate environmental ranges of temperature and humidity, trying to avoid extreme temperatures and humidity conditions used by others (2, 3). So, the aim of this study was to analyse the influence of moderate changes in air temperature and humidity simultaneously on the acute ventilatory response to exercise in asthmatic children. To overcome the above referred to methodological limitations, we used a 15 minute progressive exercise trial on a cycle ergometer at 3 different workload intensities, and we collected data related to heart rate, respiratory quotient, minute ventilation and oxygen uptake in order to ensure that physiological exercise repercussions were the same in both environments. The tests were done in a ���normal��� climatic environment (in a gymnasium) and in a hot and humid environment (swimming pool); for the latter, direct chloride exposition was avoided.

Efeito de um programa de exerc��cios segundo Pilates em indiv��duos com asma controlada ��� controlo motor vs. fun����o ventilat��ria

Introdu����o: Embora existam estrat��gias para coordenar as fun����es postural e ventilat��ria numa situa����o normal, isto pode n��o ser verdade quando a necessidade para uma das fun����es est�� aumentada, como por exemplo em patologia respirat��ria (asma) ou no exerc��cio f��sico, em que subsistem maiores necessidades ventilat��rias. O m��todo Pilates, que foca a rela����o entre o corpo e a disciplina mental, visa prosperar a sa��de e o bem-estar pelo enfatizar da boa postura, do alinhamento corporal e da coordena����o da ventila����o com o movimento. Objectivo: Comparar caracter��sticas de controlo motor e par��metros ventilat��rios em asm��ticos controlados e indiv��duos sem patologia, e verificar o efeito de um programa de exerc��cios segundo Pilates nesses outcomes em indiv��duos com asma controlada. M��todos: Estudo quasi-experimental, com uma amostra constitu��da por 21 estudantes volunt��rios, 7 pertencentes ao ���grupo sem patologia���, 7 ao ���grupo controlo asm��tico��� e 7 ao ���grupo experimental asm��tico���. Para avalia����o do timing de ativa����o e do padr��o de recrutamento muscular no movimento r��pido do membro superior foi utilizada eletromiografia de superf��cie do Diafragma, Eretor da Coluna, Mult��fidos, Obl��quo Externo, Reto Anterior e Transverso Abdominal/Obl��quo Interno. Foram tamb��m avaliados par��metros de fun����o ventilat��ria: a percentagem de volume expirat��rio for��ado no primeiro segundo do previsto, o d��bito expirat��rio m��ximo instant��neo, a ventila����o m��xima volunt��ria, a press��o inspirat��ria m��xima e a press��o expirat��ria m��xima. As avalia����es decorreram antes e ap��s 8 semanas da aplica����o de um programa de exerc��cios segundo Pilates no grupo experimental asm��tico, com exce����o do grupo sem patologia que realizou apenas o primeiro momento de avalia����o. Resultados: O grupo controlo asm��tico apresentou um timing de ativa����o significativamente maior do Transverso Abdominal/Obl��quo Interno e do Diafragma, em rela����o ao grupo sem patologia. Nos par��metros ventilat��rios, o grupo controlo asm��tico apresentou menores valores de percentagem de volume expirat��rio no primeiro segundo do previsto, de d��bito expirat��rio m��ximo instant��neo e de press��o expirat��ria m��xima. Ap��s a realiza����o do programa de exerc��cios segundo Pilates verificaram-se altera����es significativas no timing de activa����o do Eretor da Coluna, do Mult��fidos, do Transverso/Obl��quo Interno e do Diafragma, tendo ambos diminu��do no grupo experimental asm��tico. Ainda, o grupo experimental asm��tico, em rela����o aos par��metros ventilat��rios, apresentou diferen��as significativas no d��bito expirat��rio m��ximo instant��neo, na ventila����o m��xima volunt��ria e na press��o expirat��ria m��xima, tendo ambos aumentado estes valores. Conclus��o: Os asm��ticos controlados parecem possuir caracter��sticas de controlo motor, especificamente no timing de ativa����o, e valores de par��metros ventilat��rios diferentes em compara����o aos indiv��duos sem patologia. O programa de exerc��cios segundo Pilates, implementado no grupo experimental asm��tico, parece ter influenciado positivamente esses outcomes.

Analysis of the respiratory dynamics during normal breathing by means of pseudo phase plots and pressure-volume loops

This paper reports on the analysis of tidal breathing patterns measured during noninvasive forced oscillation lung function tests in six individual groups. The three adult groups were healthy, with prediagnosed chronic obstructive pulmonary disease, and with prediagnosed kyphoscoliosis, respectively. The three children groups were healthy, with prediagnosed asthma, and with prediagnosed cystic fibrosis, respectively. The analysis is applied to the pressure���volume curves and the pseudophaseplane loop by means of the box-counting method, which gives a measure of the area within each loop. The objective was to verify if there exists a link between the area of the loops, power-law patterns, and alterations in the respiratory structure with disease. We obtained statistically significant variations between the data sets corresponding to the six groups of patients, showing also the existence of power-law patterns. Our findings support the idea that the respiratory system changes with disease in terms of airway geometry and tissue parameters, leading, in turn, to variations in the fractal dimension of the respiratory tree and its dynamics.

Fractional-order impulse response of the respiratory system

This paper presents the measurement, frequency-response modeling and identification, and the corresponding impulse time response of the human respiratory impedance and admittance. The investigated adult patient groups were healthy, diagnosed with chronic obstructive pulmonary disease and kyphoscoliosis, respectively. The investigated children patient groups were healthy, diagnosed with asthma and cystic fibrosis, respectively. Fractional order (FO) models are identified on the measured impedance to quantify the respiratory mechanical properties. Two methods are presented for obtaining and simulating the time-domain impulse response from FO models of the respiratory admittance: (i) the classical pole-zero interpolation proposed by Oustaloup in the early 90s, and (ii) the inverse discrete Fourier Transform (DFT). The results of the identified FO models for the respiratory admittance are presented by means of their average values for each group of patients. Consequently, the impulse time response calculated from the frequency response of the averaged FO models is given by means of the two methods mentioned above. Our results indicate that both methods provide similar impulse response data. However, we suggest that the inverse DFT is a more suitable alternative to the high order transfer functions obtained using the classical Oustaloup filter. Additionally, a power law model is fitted on the impulse response data, emphasizing the intrinsic fractal dynamics of the respiratory system.

Is multidimensional scaling suitable for mapping the input respiratory impedance in subjects and patients?

This paper presents the application of multidimensional scaling (MDS) analysis to data emerging from noninvasive lung function tests, namely the input respiratory impedance. The aim is to obtain a geometrical mapping of the diseases in a 3D space representation, allowing analysis of (dis)similarities between subjects within the same pathology groups, as well as between the various groups. The adult patient groups investigated were healthy, diagnosed chronic obstructive pulmonary disease (COPD) and diagnosed kyphoscoliosis, respectively. The children patient groups were healthy, asthma and cystic fibrosis. The results suggest that MDS can be successfully employed for mapping purposes of restrictive (kyphoscoliosis) and obstructive (COPD) pathologies. Hence, MDS tools can be further examined to define clear limits between pools of patients for clinical classification, and used as a training aid for medical traineeship.

Analysis of the Respiratory Dynamics During Normal Breathing by Means of Pseudophase Plots and Pressure���Volume Loops

This paper reports on the analysis of tidal breathing patterns measured during noninvasive forced oscillation lung function tests in six individual groups. The three adult groups were healthy, with prediagnosed chronic obstructive pulmonary disease, and with prediagnosed kyphoscoliosis, respectively. The three children groups were healthy, with prediagnosed asthma, and with prediagnosed cystic fibrosis, respectively. The analysis is applied to the pressure-volume curves and the pseudophase-plane loop by means of the box-counting method, which gives a measure of the area within each loop. The objective was to verify if there exists a link between the area of the loops, power-law patterns, and alterations in the respiratory structure with disease. We obtained statistically significant variations between the data sets corresponding to the six groups of patients, showing also the existence of power-law patterns. Our findings support the idea that the respiratory system changes with disease in terms of airway geometry and tissue parameters, leading, in turn, to variations in the fractal dimension of the respiratory tree and its dynamics.