abstract: ABSTRACT Asthma is a high-stress, chronic medical condition; 1 in 12 adults in the United States combat the bronchoconstriction from asthma. However, there are very few strong studies indicating any alternative therapy for asthmatics, particularly following a cold incidence. Vitamin C has been proven to be effective for other high-stress populations, but the asthmatic population has not yet been trialed. This study examined the effectiveness of vitamin C supplementation during the cold season on cold incidence and asthmatic symptoms. Asthmatics, otherwise-healthy, who were non-smokers and non-athletes between the ages of 18 and 55 with low plasma vitamin C concentrations were separated by anthropometrics and vitamin C status into two groups: either vitamin C (500 mg vitamin C capsule consumed twice per day) or control (placebo capsule consumed twice per day). Subjects were instructed to complete the Wisconsin Upper Respiratory Symptom Survey-21 and a short asthma symptoms questionnaire daily along with a shortened vitamin C Food Frequency Questionnaire and physical activity questionnaire weekly for eight weeks. Blood samples were drawn at Week 0 (baseline), Week 4, and Week 8. Compliance was monitored through a calendar check sheet. The vitamin C levels of both groups increased from Week 0 to Week 4, but decreased in the vitamin C group at Week 8. The vitamin C group had a 19% decrease in plasma histamine while the control group had a 53% increase in plasma histamine at the end of the trial, but this was not statistically significant (p>0.05). Total symptoms recorded from WURSS-21 were 129.3±120.7 for the vitamin C and 271.0±293.9, but the difference was not statistically significant (p=0.724). Total asthma symptoms also slightly varied between the groups, but again was not statistically significant (p=0.154). These results were hindered by the low number of subjects recruited. Continued research in this study approach is necessary to definitively reject or accept the potential role of vitamin C in asthma and cold care. / Dissertation/Thesis / Masters Thesis Nutrition 2015

Disturbed sleep is common in asthma and impairs quality of life in these patients. Melatonin has sleep-inducing activity and reportedly affects smooth muscle tone and inflammation. The aim of this study was to evaluate the effect of melatonin on sleep in female patients with stable mild and moderate asthma. Twenty consecutive patients were recruited into the study. After a two-week run-in period, they were randomized to receive melatonin 3 mg (n= 10) or placebo for four weeks. Sleep quality and daytime somnolence were assessed by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, respectively. Pulmonary function was assessed by spirometry. Use of relief medication, asthma symptoms and morning and evening peak expiratory flow rate (PEFR) were recorded daily. Melatonin treatment, but not placebo, significantly improved subjective quality of sleep (p = 0,034), sleep latency (p = 0.031), sleep duration (p = 0,034), sleep disturbances (p = 0,034), daytime dysfunction (p = 0,025) and subjective daytime somnolence (p = 0,028). No significant difference in asthma symptoms, use of relief medication and daily PEFR was found between the two groups. We conclude that melatonin can improve sleep in patients with asthma without significantly affecting pulmonary function or asthma symptoms. Further studies looking into long-term effects of melatonin on airway inflammation and bronchial hyperresponsiveness are needed before melatonin can be safely recommended in asthmatic patients. / AlteraÃÃes do sono sÃo comuns na asma, dificultando o manuseio desta condiÃÃo e reduzindo a qualidade de vida dos seus portadores. A melatonina (MLT) possui aÃÃo indutora do sono e apresenta baixa incidÃncia de efeitos adversos. Existem relatos de que a MLT tambÃm possui aÃÃo sobre o tÃnus da musculatura lisa e exerce atividade imunomoduladora, potencialmente Ãteis no tratamento da asma. O objetivo principal deste estudo foi avaliar os efeitos da administraÃÃo noturna da MLT sobre o sono e a funÃÃo pulmonar de pacientes com asma persistente leve e moderada. O estudo foi um ensaio clÃnico randomizado, duplo-cego, controlado por placebo e duraÃÃo total de seis semanas. Vinte pacientes do sexo feminino foram submetidas a um perÃodo de prÃ-tratamento de duas semanas com beclometasona na dose de 1000 mcg/dia e salbutamol quando necessÃrio, ambos por via inalatÃria. ApÃs esse perÃodo, foram randomizadas para receber MLT na dose de 3 mg (n= 10) ou placebo (n= 10) duas horas antes do horÃrio habitual de sono, por quatro semanas. A qualidade do sono e a sonolÃncia diurna foram avaliadas pelo Ãndice de Qualidade de Sono de Pittsburgh (IQSP) e pela Escala de SonolÃncia de Epworth (ESE) respectivamente, enquanto a funÃÃo pulmonar foi avaliada por espirometria. Foram realizadas medidas domiciliares diurnas e noturnas do pico de fluxo expiratÃrio. Um registro diÃrio de sintomas de asma e de uso de broncodilatador inalatÃrio foi mantido durante todo o perÃodo. ApÃs a fase de tratamento, a qualidade do sono, a sonolÃncia diurna e a funÃÃo pulmonar foram reavaliadas. Os resultados demonstram que o grupo que utilizou a MLT, ao contrÃrio do grupo placebo, apresentou melhora da qualidade subjetiva do sono (p= 0,034), da latÃncia do sono (p= 0,031), da duraÃÃo do sono (p= 0,034), dos distÃrbios do sono (p= 0,034), das disfunÃÃes diurnas (p= 0,025) e do grau de sonolÃncia diurna subjetiva (p= 0,028). Nenhuma diferenÃa estatisticamente significante foi observada nos sintomas de asma, no uso de broncodilatador para alÃvio de sintomas e nas medidas diÃrias de PFE entre os grupos MLT e placebo. Em conclusÃo, a MLT melhora a qualidade do sono e reduz a sonolÃncia diurna em pacientes com asma persistente leve e moderada, sem produzir efeitos detectÃveis sobre sintomas ou sobre a funÃÃo pulmonar. Estudos adicionais sobre os efeitos a longo prazo da MLT na inflamaÃÃo das vias aÃreas e na hiper-responsividade brÃnquica, sÃo necessÃrios antes que esta substÃncia possa ser recomendada com seguranÃa em pacientes asmÃticos.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / A presente pesquisa visou determinar a contratilidade do mÃsculo liso traqueal de ratos submetidos a exercÃcio leve de curto prazo, ou seja, treinados 1h ou prÃ-treinados e posteriormente exercitados por 1, 5 e 10 hs (PT1, PT5 e PT10, respectivamente), bem como de animais sensibilizados com OVA, submetidos ao exercÃcio por 5hs e posteriormente desafiados, com o objetivo de verificar as alteraÃÃes causadas pelo exercÃcio neste mÃsculo determinando tambÃm a interferÃncia da broncoprovocaÃÃo antigÃnica sobre a contratilidade traqueal de animais previamente exercitados. Para a realizaÃÃo da pesquisa, ratos machos (250-350g) foram submetidos a diferentes protocolos de nado, por 1, 5 e 10hs, sendo um grupo submetido à sensibilizaÃÃo com OVA e, 21 dias depois, desafiados em intervalos de 15 minutos atravÃs da inalaÃÃo do antÃgeno sensibilizante (grupo S/D). No grupo sensibilizado e submetido ao exercÃcio, este Ãltimo foi realizado durante 5 dias antes do desafio (grupo S/E prà desafio). O sacrifÃcio dos animais ocorreu 30 min apÃs a sessÃo de nado ou 24 horas apÃs o desafio antigÃnico no caso dos animais submetidos ao modelo de asma. Os ratos sedentÃrios nÃo foram submetidos a nenhum treino. Os controles do grupo asma inalaram apenas o veÃculo (NaCl 0,9%). Para os experimentos in vitro a traquÃia foi removida e montada em cuba para ÃrgÃo isolado contendo 5ml de soluÃÃo Tyrod (mantida a 37  0,5 ÂC) e aerada com mistura de O2. Foram confeccionadas curvas concentraÃÃo-efeito (CCE) para carbacol e cloreto de potÃssio. Os resultados mostraram que o pD2 nÃo apresentou valores significativos nos grupos em estudo, exceto em PT5 e PT10, ambos em relaÃÃo ao grupo PT1. A resposta mÃxima (%) apresentou valores significativamente crescentes e maiores nos grupos PT1 (107,62  3,57),PT5 (116,35  0,54) e PT10 (123,50  2,59) em relaÃÃo ao grupo sedentÃrio (82,70  5,90), quando o carbacol foi utilizado como estÃmulo contrÃtil. SituaÃÃo semelhante ocorreu nos grupos PT1 (105,19 Â1,12), PT5 (112,02  1,44) e PT10 (119,56  0,95) em relaÃÃo ao grupo sedentÃrio (90,45  2,22), para o potÃssio e nos grupos S/D (100,74  4,79) e S/E prÃ-desafio (109,09 Â3,68) em relaÃÃo ao grupo sensibilizado (82,69 Â5,90) para o carbacol, e nos grupos S/D (105,50  2,37) e S/E prÃ-desafio (115,05  1,96) em relaÃÃo ao grupo sensibilizado (93,11  3,58). Para verificar a participaÃÃo do Ãxido nÃtrico, acetilcolina e estresse oxidativo no mecanismo da aÃÃo prÃcontrÃtil da musculatura lisa traqueal induzida pelo exercÃcio foram determinados, respectivamente os nÃveis de nitrito, atividade da acetilcolinesterase (AChE) e espÃcies reativas ao Ãcido tiobarbitÃrico (TBARs) como uma maneira de determinar a peroxidaÃÃo lipÃdica. Os valores de nitrito foram significativos para o grupo PT5 em relaÃÃo aos grupos sedentÃrio e treinado 1h. Nos animais submetidos ao protocolo da asma ocorreu queda significativa dos nÃveis de nitrito nos grupos S/D e S/E prÃ-desafio. Ocorreu aumento da peroxidaÃÃo lipÃdica nos grupos PT1, PT5 e PT10 em relaÃÃo ao grupo sedentÃrio. Jà no grupo asmÃtico, os valores foram significativamente maiores nos grupos S/D e S/E prÃdesafio em relaÃÃo ao grupo controle. A atividade da AChE apresentou reduÃÃo significativa nos grupos PT1, PT5 e PT10 em relaÃÃo aos grupos sedentÃrio e treinado 1h. No grupo asmÃtico, tambÃm ocorreu reduÃÃo na atividade da AChE nos grupos S/D e S/E prÃ-desafio. Portanto, os resultados mostram que o exercÃcio a curto prazo aumenta a contratilidade da musculatura lisa traqueal isolada em ratos, para o carbacol e o potÃssio dos grupos em estudo; provavelmente com a participaÃÃo do Ãxido nÃtrico, acetilcolina e peroxidaÃÃo lipÃdica neste mecanismo prÃ-contrÃtil. / This work aimed to determine the contractility of tracheal smooth muscle of rats submitted to short-term light exercise, trained for 1h or pre-trained and, then, trained for 1, 5 and 10hs (PT1, PT5 and PT10, respectively), as well as, animals sensitized with OVA, submitted to exercise for 5hs and subsequently challenged, with the objective of verifying the changes caused by exercise in this muscle, also determining the interference of antigen bronchoprovocation on the contractility of tracheal smooth muscle of animals previously exercised. To conduct the study male rats (250-350g) were subjected to different protocols of swimming, by 1, 5 and 10hs, in addition to one group that was subjected to sensitization with OVA and 21 days later, challenged at intervals of 30 min through sensitizing antigen inhalation (group S/D). In the sensitized group submitted to exercise, this latter was held for 5 days before OVA challenge (group S/E pre-challenge). The animals were sacrificed 15 min after the swimming session or 24 hs after antigen challenge, in the case of rats submitted to asthma model. Sedentary rats were not subjected to any training session. Asthma control group inhaled only the vehicle (NaCl 0.9%). For in vitro experiments the trachea was removed and mounted in an isolated organ bath containing 5ml of Tyrode solution (maintained at 37  0.5 ÂC) and aerated with O2. Concentration-effect curves (CEC) were designed for carbachol and potassium chloride. The results showed that the pD2 values were not significant among the groups except in PT5 and PT10, both in relation to group PT1. The maximum response values were significantly increased and higher in the groups PT1 (107,62  3,57), PT5 (116,35  0,54) and PT10 (123,50  2,59) compared to the sedentary group (82.70  5,90), when carbachol was used as the contractile stimulus. A similar situation occurred in the groups PT1 (105,19  1,12), PT5 (112,02  1,44) and PT10 (119,56  0,95) as compared to the sedentary group (90,45  2,22), for potassium and S/D (100,74  4,79) and S/E pre-challenge groups (109,09  3,68) as compared to the sensibilized group (82,69  5,90) for carbachol, as well as, S/D (105,50  2,37) and S/E pre-challenge (115,05  1,96) groups when compared to the sensibilized one for potassium (93,11  3,58). To verify the involvement of nitric oxide, acetylcholine, and oxidative stress on the pro-contractile mechanism of the tracheal smooth muscle induced by exercise, nitrite levels, acetylcholinesterase (AChE) activity and thiobarbituric acid reactive species (TBARS), as a way of determining lipid peroxidation, were determined. Nitrite levels decreased in the PT5 group as compared to sedentary and 1h trained groups. In the animals subjected to the asthma protocol there was a significant decrease in the nitrite levels in the S/D and S/E prechallenge groups. An increase in lipid peroxidation occurred in the groups PT1, PT5 and PT10 in relation to the sedentary one. In the asthmatic group, the TBARS values were significantly higher in S/D and S/E pre-challenge groups as compared to the control one. The AChE activity showed a significant reduction in the groups PT1, PT5 and PT10 in relation to sedentary and 1h trained groups. The groups S/D and S/E pre-challenge also presented a decrease on AChE activity. Therefore, the results showed that short-term light exercise increases the tracheal smooth muscle contractility of the study groups, probably with the participation of nitric oxide, acetylcholine, and lipid peroxidation in this pro-contractile mechanism.

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Problem: Asthma affects one out of every ten children in the United States. It is recommended that children with persistent asthma take long-term controller (LTC) medications to achieve control. However, adherence varies, and many children do not take their LTC medication at all. The average cost for hospitalization of a child with asthma is $8,406. Asthma in children also contributes to school absenteeism and a decrease in quality of life. Objective: A literature review was performed to examine factors that affect adherence to LTC medications used to control asthma in children. Method: A literature review was performed using the CINAHL, ERIC, Medline, Psych Info, and Academic Search Premier databases. Keywords included asthma AND child* OR pediatric* AND adherence OR compliance AND corticosteroid* OR “leukotriene modifier*” OR “mast cell stabilizer*” OR “monoclonal antibod*” OR “long-acting beta agonist.*” After applying exclusion criteria 35 articles were included in this review. Results: A variety of factors that affect adherence were identified. Internal factors included age, sex, and race/ethnicity. External factors included socioeconomic status, environment, health perception, lack of motivation, parental education, disease/medication beliefs, family dynamics and planning, responsibility, severity, and exacerbations. Interventional factors included caregiver-family communication, asthma knowledge, specialty care, white coat adherence, number of prescriptions, asthma action plans, medication regimens, and technology. Conclusion: It is recommended that healthcare providers use a four-step process during inpatient and outpatient asthma visits. The steps include assess and educate, collaborate, problem-solve, and follow-up. Collectively, this method can help healthcare providers overcome many of the barriers that were identified.

Asthma is the most common chronic disease of childhood. Children diagnosed with asthma are twice as likely to have a comorbid anxiety disorder as their non-asthmatic peers. The presence of both asthma and anxiety in the pediatric patient creates an environment of poor asthma control, and places them at risk for a variety of negative health events. Little is known about comorbid anxiety’s role in asthma health maintenance. Research has identified the link between these two conditions but causation is difficult to conclude. The aim of this thesis is to assess the current state of the science regarding pediatric asthma and anxiety. This integrated review of the literature will identify the factors contributing to the vicious cycle of pediatric anxiety and asthma. Recommendations for practice and future research will be made.

Asthma is a common chronic respiratory disease where patients suffer from restricted airways and airway inflammation (mainly eosinophilic type 2 (T2) inflammation). Inhaled (ICS)/oral corticosteroids (OCS) and, more recently T2-targeting biologics, are prescribed as mainstay therapies for asthma. Despite these therapies, a subset of asthma patients continues to have symptoms and airway inflammation, suggesting an underlying additional asthma pathology. We have observed multiple airway autoantibodies in 55% of moderate-to-severe asthma patients associated with inadequate response to corticosteroids and anti-T2 biologics. Increased airway degranulation (eosinophilic and/or infective) together with lymphopenia (low lymphocyte counts) underlie these self-reactive/autoimmune-like events. In healthy individuals, regulatory lymphocytes limit the development and activity of self-reactive cells, including those capable of producing autoantibodies. Lymphopenia can lead to skewed non-regulatory to regulatory lymphocyte subsets that support a microenvironment with reduced ability to limit self-reactivity. In this study, wanted to measure B cell subsets by flow cytometry and non-regulatory to regulatory B cell ratios in asthma patients and healthy controls. To understand B cell compartmentalization, we analyzed peripheral and sputum B cells. We identified decreased regulatory B cells (Bregs), in particular CD5+ Bregs, and skewed non-regulatory to regulatory B cell ratios in both circulation and airways of asthma patients. Compared to healthy controls, only patients requiring daily OCS had significantly lower CD5+ Bregs, suggesting a reduced regulatory component in more severe patients. Further, CD5+ Bregs, capable of producing immunomodulatory interleukin-10, were significantly lower in patients with a history of multiple lymphopenic events (70% requiring daily OCS). Together, this supports the need to investigate lymphopenia-induced dysregulation of Bregs, increase in autoreactive B cells and airway autoreactivities, and subsequent progression into a more-severe therapy refractory autoimmune pathology. This opens a new avenue for asthma treatment, particularly for the severe population with airway autoimmune responses often not targeted/controlled by current anti-inflammatory therapies. / Thesis / Master of Science (MSc) / Asthma is a common respiratory disease where patients have difficulty breathing and airway inflammation. Corticosteroids and/or targeting biologic therapies are prescribed to reduce inflammation. Despite these treatments, some patients still have inflammation. In patients that don’t respond well to treatment, we have found evidence of self-attacking antibodies that can further lead to disease severity. These antibodies are produced by self-attacking B cells normally suppressed by regulatory B cells (Bregs). We wanted to measure if asthma patients have reduced ability to limit self-attacking B cells because of reduced Bregs. We found that asthma patients have lower Bregs and an imbalance of non-regulatory to regulatory B cells in the blood and airways. Together, we show B cell subsets that suggest a self-attacking asthma component, not targeted by current asthma treatments. Understanding the involvement of Bregs in asthma opens a new therapeutic option in those that don’t respond well to current treatment.

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