Prolonged exercise has been associated with depressed immune function, and hence an increased risk of infection. However, several nutritional supplements may reduce or overcome this problem. Thus, the aims of this thesis were to investigate the effects of some nutritional supplements on athletes immune function. In study 1 (Chapter 3), effects of several vaccine stimulant dose on whole blood culture cytokine production was carried out to determine effective vaccine stimulant dose; which was found to be between a dilution of 4000 (dose 4) and 1000 (dose 6) of the original vaccine. This finding was used for the other studies (Chapter 4 and 5). In addition, the relationship between data obtained from Evidence Investigator analyser and enzyme linked-immuno-sorbent assay (ELISA) for IL-10 was analysed and the results show a positive strong correlation between them. In study 2 (Chapter 4), in vitro effects of various immunomodulatory nutritional compounds on antigen-stimulated whole blood culture cytokine production was investigated and it was found that caffeine and quercetin showed tendency towards decrease cytokine production as the doses were increased. On the other hand, an upward trend was evident with kaloba, where high dose of kaloba seemed to increase the cytokine production. Since kaloba appeared to act as an immunostimulant in vitro, its effects on the immune response to prolonged exercise were examined in study 3 (Chapter 5). However, 7 days kaloba supplementation (20 mg of the root extract) did not alter athletes immune response although prolonged moderate intensity exercise significantly decreased S-IgA secretion rate and concentration post-exercise with the values returning to baseline by 1 h post-exercise. A 14-strain probiotic supplement effects on salivary antimicrobial proteins at rest and in response to an acute bout of prolonged exercise was investigated in study 4 (Chapter 6). Unfortunately, 30 days supplementation of the 14-strain probiotic appeared not enough to induce any significant effects on salivary antimicrobial proteins. Lastly, in study 5 (Chapter 7), the effects of a Lactobacillus probiotic on healthy people, who tend to have a higher than normal incidence of infection due to exercise stress-induced immune impairment was studied. In summary, this 16-week intervention study on 267 athletes found that regular ingestion of the probiotic reduced the extent to which training was negatively affected in endurance athletes when infection was present, and increased both S-IgA concentration and secretion rate over time. But it did not appear to reduce URTI incidence or the duration and severity of URTI episodes. Two major confounding factors, namely the unexpectedly low incidence of URTI during the winter period and the lower baseline S-IgA in the probiotic group may have prevented potential beneficial effects of probiotic supplementation from being identified.

Despite the abundance of research conducted into the effects of exercise on mucosal immunity the results remain controversial. Much of the inconsistencies arise from the exercise protocols, the participants studied and their nutritional status, as well as methodological and analytical differences. The purpose of this thesis was to examine the influence of some of these factors, and to investigate potential means of enhancing the mucosal immune response to exercise. In study 1 (Chapter 3) it was shown that a fed or fasted state 2 h prior to exercise had no effect on the s-IgA concentration or secretion rate during prolonged exercise. However, when participants were fed during exercise (Chapter 4), the secretion rate of salivary antimicrobial proteins lysozyme and a-amylase increased, but sIgA remained unchanged. These changes were likely due to the activation of mechanical and gustatory receptors leading to a reflex stimulation of protein secretion via the autonomic nerves, rather than changes in stress hOnliones, since cortisol did not change significantly during exercise. Study 3 (Chapter 5) extended these findings where it was demonstrated that chewing flavoured gum during exercise enhanced lysozyme and a-amylase secretion but resulted in a small reduction in s-IgA secretion rate. Salivary antimicrobial proteins are affected by the exercise intensity since both s-IgA and lysozyme secretion rate increased post -exercise following an incremental test to exhaustion, but not after exercise at 50% Y02max. Moreover, lysozyme secretion rate was also elevated following exercise at 75% Y02mru<, whereas s-IgA remained unchanged. These effects are thought to be mediated by increased sympathetic nervous system activity reflected by the concomitant increases in (lamylase and chromogranin A, rather than the hypothalamic-pituitary-adrenal axis. Resting mucosal immunity exhibits significant gender differences. In study 1 (Chapter 3) s-IgA concentration, secretion rate and osmolality were found to be lower in females than in males at rest. In addition, saliva flow rate was found to be lower in females compared with males in study 5 (Chapter 7). However, these differences did not appear to influence the salivary responses to acute exercise or exercise training. Chronic exercise training in elite male and female swimmers resulted in lower levels of s-IgA secretion rate following periods of intense training prior to competition compared with post-competition (Chapter 7), but these levels were not directly associated with reported episodes of respiratory illness.

Firstly, the aims of the study were to investigate the influences of various factors, sex differences, Cytomegalovirus/Epstein-Barr virus (CMV/EBV) serostatus and vitamin D concentrations on respiratory illness incidence and immune function during the winter months in a student cohort of endurance athletes. In Chapter 3, the findings of the study concur with recent reports of illness incidence at major competitive games which indicate that female athletes may be more susceptible than their male counterparts to upper respiratory tract illness (URTI) symptoms and that lower oral-respiratory mucosal immunity may, in part, account for this. It was also found that previous coinfection with CMV and EBV might promote protective immune surveillance to lower the risk of URTI. In addition, it can be concluded that athletes with low plasma vitamin D concentrations may have a higher risk of URTI and suffer more severe symptoms when URTI is present. This may be due to impaired mucosal and systemic immunity as secretory immunoglobulin A (SIgA) secretion, cathelicidin levels and antigen-stimulated pro-inflammatory cytokine production appear to be increased by vitamin D-dependent mechanisms. A series of follow-up studies were also conducted to examine the effect of vitamin D on mucosal and systemic immunity in athletes. In Chapter 4, it was reported that the influence of vitamin D on circulating cytokines might be different in athletes compared with non-athletes and that both pro-inflammatory and anti-inflammatory cytokine production by multi-antigen stimulated whole blood culture were not influenced by 1,25-dihydroxy vitamin D (1, 25(OH)2D) iconcentrations within the normal healthy range. In Chapter 5, it was found that 5000 IU of vitamin D3 supplementation daily appears to have a beneficial effect in up-regulating the expression of SIgA and cathelicidin in athletes during a winter training period. Nevertheless, the findings reported in Chapter 6 showed that there were no significant effects of vitamin D status and a 4-week period of daily high does vitamin D3 supplementation on salivary antimicrobial protein (AMP) responses to prolonged exercise. In conclusion, a series of studies in this thesis have demonstrated the influence of various factors (sex differences, CMV/EBV serostatus and vitamin D concentrations) on susceptibility to URTI among athletes. Moreover, it was suggested that vitamin D3 supplementation could have a positive effect on immune function and lead to decreased incidence of respiratory infections.

Orientador: Norma Sueli Pinheiro Módolo / Resumo: Justificativa e Objetivos: a diferença na incidência de eventos adversos perioperatórios (EAPs) entre tubo traqueal (TT), máscara laríngea (ML) e máscara facial (MF) ainda é questão controversa no tocante à anestesia em crianças com infecção de vias aéreas superiores (IVAS). O objetivo desta revisão sistemática foi comparar o risco de EAPs entre os dispositivos de via aérea após anestesia em pacientes pediátricos com IVAS. Métodos: foi conduzida revisão sistemática de acordo com as recomendações da Colaboração Cochrane e declaração PRISMA. A estratégia de busca foi realizada nas principais bases de dados eletrônicas (PubMed, EMBASE, Cochrane CENTRAL, Lilacs, Scielo, Scopus e Web of Science) e a última pesquisa foi realizada em 30 de junho de 2015. Não houve restrições quanto a idioma, data, revista ou publicação. Foram incluídos somente estudos avaliando EAPs em pacientes com IVAS submetidos à anestesia e cujas vias aéreas tenham sido manejadas com MF, ML ou TT. Dados de cada ensaio clínico randomizado (ECR) foram combinados utilizando o modelo de efeito randômico para cálculo do risco relativo (RR). Resultados: dos 680 estudos identificados, 5 eram ECRs e foram incluídos na análise final. Não houve diferença estatisticamente significante entre os diferentes dispositivos estudados com relação a broncoespasmo (RR 0,47, IC 95% 0,04-6,25, p=0,57), laringoespasmo (RR 0,84, IC 95% 0,56-1,27, p=0,41), dessaturação arterial de oxigênio (RR 0,66, IC 95% 0,38-1,16, p=0,15), apneia (RR... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: rate of perioperative adverse events (PAEs) among tracheal tube (TT), laryngeal mask airway (LMA), and facemask (FM) remains a controversial issue during anesthesia in children with an upper respiratory tract infection (URTI). The aim of the present study was to compare the risk of PAEs among the different airway devices after anesthesia in pediatric patients with an URTI. Methods: a systematic review according to the Cochrane Handbook and PRISMA guidelines was conducted. The search was performed in the main electronic databases (PubMed, EMBASE, Cochrane CENTRAL, Lilacs, Scielo, Scopus and Web of Science) and the last one was carried out in June 30, 2015. There were no language, year of publication, or publication status restriction. Only randomized clinical trial evaluating anesthesia in children with URTI and who were submitted to either of the airway devices were included. Data from each trial was combined using the random effects models to calculate the pooled relative risk (RR) and 95% confidence intervals. Results: from 680 studies identified, 5 randomized clinical trials were included in the final analysis. There were no statistical difference with regard to bronchospasm (RR 0.47, CI 95% 0.04-6.25, p=0.57), laryngospasm (RR 0.84, CI 95% 0.56-1.27, p=0.41), arterial oxygen desaturation (RR 0.66, CI 95% 0.38-1.16, p=0.15), apnea or breath holding (RR 0.91, CI 95% 0.49-1.67, p=0.75), sore throat (RR 0.87, CI 95% 0.39-1.96, p=0.74), and hospital readmission (RR... (Complete abstract click electronic access below) / Doutor

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No. of bitstreams: 1 carvalho_alr_dr_bot.pdf: 1510567 bytes, checksum: 016ef353508cc1d168cdef1d8cf5cea3 (MD5) Previous issue date: 2016-02-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Justificativa e Objetivos: a diferença na incidência de eventos adversos perioperatórios (EAPs) entre tubo traqueal (TT), máscara laríngea (ML) e máscara facial (MF) ainda é questão controversa no tocante à anestesia em crianças com infecção de vias aéreas superiores (IVAS). O objetivo desta revisão sistemática foi comparar o risco de EAPs entre os dispositivos de via aérea após anestesia em pacientes pediátricos com IVAS. Métodos: foi conduzida revisão sistemática de acordo com as recomendações da Colaboração Cochrane e declaração PRISMA. A estratégia de busca foi realizada nas principais bases de dados eletrônicas (PubMed, EMBASE, Cochrane CENTRAL, Lilacs, Scielo, Scopus e Web of Science) e a última pesquisa foi realizada em 30 de junho de 2015. Não houve restrições quanto a idioma, data, revista ou publicação. Foram incluídos somente estudos avaliando EAPs em pacientes com IVAS submetidos à anestesia e cujas vias aéreas tenham sido manejadas com MF, ML ou TT. Dados de cada ensaio clínico randomizado (ECR) foram combinados utilizando o modelo de efeito randômico para cálculo do risco relativo (RR). Resultados: dos 680 estudos identificados, 5 eram ECRs e foram incluídos na análise final. Não houve diferença estatisticamente significante entre os diferentes dispositivos estudados com relação a broncoespasmo (RR 0,47, IC 95% 0,04-6,25, p=0,57), laringoespasmo (RR 0,84, IC 95% 0,56-1,27, p=0,41), dessaturação arterial de oxigênio (RR 0,66, IC 95% 0,38-1,16, p=0,15), apneia (RR 0,91, IC 95% 0,49-1,67, p=0,75), dor de garganta (RR 0,87, IC 95% 0,39-1,96, p=0,74) e taxa de readmissão hospitalar (RR 0,76, IC 95% 0,17-3,33, p=0,71). O uso de ML resultou em significante redução da incidência de tosse (RR 0,63, IC 95% 0,45-0,89, p=0,009) comparado aos outros dispositivos de via aérea. Notou-se, também, tendência à redução da incidência de vômito com o uso da ML quando comparado ao TT e MF, embora sem significância estatística (RR 0,57, IC 95% 0,33-1,00, p=0,05). Conclusões: o manejo ideal das vias aéreas em crianças com IVAS permanece incerto. Esta revisão sistemática demonstra que o uso da ML durante anestesia em crianças com IVAS não resultou na diminuição dos mais temidos EAPs. Entretanto, o uso da ML foi mais eficaz em reduzir a incidência de tosse comparado aos outros dispositivos de via aérea. Além disso, houve tendência da ML em reduzir a incidência de vômito. / Background: rate of perioperative adverse events (PAEs) among tracheal tube (TT), laryngeal mask airway (LMA), and facemask (FM) remains a controversial issue during anesthesia in children with an upper respiratory tract infection (URTI). The aim of the present study was to compare the risk of PAEs among the different airway devices after anesthesia in pediatric patients with an URTI. Methods: a systematic review according to the Cochrane Handbook and PRISMA guidelines was conducted. The search was performed in the main electronic databases (PubMed, EMBASE, Cochrane CENTRAL, Lilacs, Scielo, Scopus and Web of Science) and the last one was carried out in June 30, 2015. There were no language, year of publication, or publication status restriction. Only randomized clinical trial evaluating anesthesia in children with URTI and who were submitted to either of the airway devices were included. Data from each trial was combined using the random effects models to calculate the pooled relative risk (RR) and 95% confidence intervals. Results: from 680 studies identified, 5 randomized clinical trials were included in the final analysis. There were no statistical difference with regard to bronchospasm (RR 0.47, CI 95% 0.04-6.25, p=0.57), laryngospasm (RR 0.84, CI 95% 0.56-1.27, p=0.41), arterial oxygen desaturation (RR 0.66, CI 95% 0.38-1.16, p=0.15), apnea or breath holding (RR 0.91, CI 95% 0.49-1.67, p=0.75), sore throat (RR 0.87, CI 95% 0.39-1.96, p=0.74), and hospital readmission (RR 0.76, CI 95% 0.17-3.33, p=0.71). The use of LMA produced a significant reduction of cough (RR 0.63, CI 95% 0.45- 0.89, p=0.009) compared with other airway devices. Also, LMA tended toward a reduction of vomiting compared with other forms of airway management but did not reach statistical significance (RR 0.57, CI 95% 0.33-1.00, p=0.05). Conclusions: the ideal airway management in children with URTI remains obscure. This systematic review demonstrates that the use of LMA during anesthesia for surgery in children with URTI did not result in decrease of the most feared PAEs. However, the use of LMA was better than other airway devices in reducing cough and tended toward a protective effect against vomiting.

Background: Humanmilk oligosaccharides (HMOs) support and concurrently shape the neonatal immune system through various mechanisms. Thereby, they may contribute to lower incidence of infections in infants. However, there is limited evidence on the role of individual HMOs in the risk of otitis media (OM), as well as lower and upper respiratory tract infections (LRTI and URTI, respectively) in children up to 2 years. Objective: To investigate whether individual HMO concentrations measured at 6 weeks of lactation were associated with risk of OM, LRTI or URTI up to 2 years in breastfed infants. Associations with OM, LRTI and URTI were determined for the most prominent human milk oligosaccharides including 13 neutral, partly isomeric structures (trioses up to hexaoses), two acidic trioses, and lactose. Design: HMO measurements and physician reported data on infections were available from human milk samples collected at 6 weeks postpartum (n = 667). Associations of HMOs with infections were assessed in crude and adjusted models using modified Poisson regression. Results: Absolute concentrations (median [min, max], in g/L) of 2′-fucosyllactose (2′-FL) tended (p = 0.04) to be lower, while lacto-N-tetraose (LNT) was higher in the milk for infants with OM in the 1st year of life (p = 0.0046). In the milk of secretor mothers, LNT was significantly higher in the milk for infants with OM (RR [95% CI]: 0.98 [0.15, 2.60]) compared to infants without OM (RR [95% CI]: 0.76 [0.14, 2.90]) at 1 year (p = 0.0019). No statistically significant milk group differences and associations were observed for OM, LRTI, and URTI (p > 0.0031). Conclusion: Our findings suggest that neither prominent neutral individual HMOs (ranging from 2′-FL to LNDFHs) nor acidic human milk sialyllactoses or lactose are significantly associated with a reduced or increased risk of infections in infants up to 2 years of age. Further research is needed to determine whether specific HMOs could potentially reduce the incidence or alleviate the course of distinct infections in early life.