Objetivo: Estimar el nivel de control de asma en niños y adolescentes atendidos en los establecimientos de Essalud de la ciudad de Chiclayo, durante el período julio-diciembre 2013. Materiales y métodos: Estudio censal de tipo transversal descriptivo. Se incluyeron menores de edad de 5 a 18 años con diagnóstico de asma. Se identificaron a los pacientes en la base de datos de la red de salud Lambayeque y se les realizó una visita domiciliaria donde se les invitó al estudio y aplicó el instrumento de evaluación (Asthma Control Test - ACT). Resultados: Se identificó un total de 203 pacientes, llegándose a contactar y reclutar a 107 individuos. Se incluyeron 89 (83.2%) niños y 18 (16.8%) adolescentes con una mediana de edad de 7 años y 15 años respectivamente. Según el puntaje del ACT: 52 (48.6%) estaban mal controlados; 46 (42.9%), parcialmente controlados; y 9 (8.4%), bien controlados. En el caso de los niños, la frecuencia de “no control” fue de 48,31%, “parcialmente controlado” 43,82% y “controlado” 7,87%; y en los adolescentes fue de 50,00%, 38,59% y 11,11% respectivamente. Se evidenció una relación significativa entre el nivel de control y el nivel educativo del cuidador en niños (p=0,006) y adolescentes (p=0,005). Conclusiones: Se evidenció una frecuencia elevada de control inadecuado de asma, lo cual contrasta con otras realidades similares en donde más del 50% se hallan controlados. Se sugiere realizar iniciativas enfocadas alcanzar los niveles de control de realidades regionales similares.

INTRODUÇÃO: Há evidências consistentes a partir de estudos epidemiológicos de que os profissionais de limpeza têm um risco elevado de desenvolver asma. Os determinantes deste risco não são totalmente conhecidos. Esses trabalhadores estão expostos a agentes ocupacionais de baixo e alto peso molecular, tanto a agentes sensibilizantes, como a irritantes. É importante produzir evidências de que este risco está relacionado ao trabalho e não às condições sociais ou outros fatores concorrentes, conhecer a anormalidade patológica subjacente, e investigar os possíveis agentes. O acúmulo deste conhecimento permitirá a proposição de medidas para substituição ou controle do uso dos agentes envolvidos e prevenção da ocorrência de novos casos desnecessariamente. Além disso, o uso de novas técnicas não invasivas, como a citologia do escarro e A FeNO, poderá facilitar o diagnóstico precoce dos casos. Desta maneira, este estudo pretende avaliar se o ambiente de trabalho induz inflamação pulmonar em trabalhadores assintomáticos, antes da alteração das provas funcionais e a eficácia do escarro induzido e da FeNO NO como marcadores de inflamação pulmonar precoce entre trabalhadores de limpeza profissional não doméstica. MÉTODO: Os trabalhadores foram avaliados através da comparação da citologia do escarro, valores da FeNO, espirometria e PFE, realizados durante o período de trabalho e após as férias. A amostra foi caracterizada através do questionário de triagem do estudo de saúde respiratória da Comunidade Européia, questionário de sintomas respiratórios e a pontuação no ISAAC. RESULTADOS: Em nosso estudo, encontramos um aumento significativo dos valores do VEF1 após o período de férias, (pré 2,76 ± 0,57 e pós 2,94 ± 0,61; p < 0,05) apesar de estar dentro da normalidade, em ambos os períodos. A média das medidas do PFE também mostrou-se maior durante o período de férias em comparação ao período de trabalho, embora não estatisticamente significante (pré 366,6 ± 54,1 e pós 386,4 ± 62,9 e p > 0,05). Encontramos uma redução dos valores da medida da FeNO após as férias (pré 16,3 ± 9,7 e pós 13,8 ± 7,8 p < 0,05) e redução de eosinófilos (pré 0,019 ± 0,05 e pós 0,003 ± 0,01 p < 0,05), linfócitos (pré 0,16 ± 0,35 e pós 0,01 ± 0,09 p < 0,05) e macrófagos (pré 0,421 ± 0,47 e pós 0,235 ± 0,30 p < 0,05) na citologia do escarro induzido, realizada após o período de férias. CONCLUSÃO: Demonstramos que o ambiente ocupacional ao qual são expostos os trabalhadores de limpeza profissional não doméstica provoca inflamação nas vias aéreas de trabalhadores assintomáticos. Esta inflamação pode ser aferida por métodos não invasivos como escarro induzido e FeNo, antes do aparecimento de alterações nas provas funcionais, embora estes métodos ainda necessitem de padronização. São necessários novos estudos para quantificar a exposição ao cloro e sua relação com inflamação, assim como para padronizar o uso do escarro induzido e da FeNO no diagnóstico de doenças ocupacionais entre trabalhadores de limpeza, além de medidas preventivas e educativas nesta população / There is consistent evidence from epidemiological studies that the cleaning professionals have a high risk of developing asthma. The determinants of this risk are not fully known. These workers are exposed to occupational agents of low and high molecular weight, both the sensitizing agents, such as irritant. It is important to produce evidence that this risk is related to work and not social conditions or other competitive factors, know the underlying pathological abnormality, and investigate possible agents. The accumulation of this knowledge will allow proposing measures to replace or control the use of the agents involved and preventing the occurrence of new cases unnecessarily. In addition, the use of new non-invasive techniques, such as sputum cytology and the FeNO may facilitate early diagnosis of cases. Thus, this study aims to assess if the work environment induces lung inflammation in asymptomatic workers, before the change of functional tests and the effectiveness of induced sputum and exhaled NO as early lung inflammation markers between professional cleaning workers. METHOD: Workers were evaluated by comparing the sputum cytology, FeNO values, spirometry and PEF, made during the work period and after the holidays. The sample was characterized by screening questionnaire of respiratory health study of the European Community, questionnaire of respiratory symptoms and a score in ISAAC. RESULTS: In our study, we found a significant increase in FEV1 values after the vacational period, (pre 2.76 ± 0.57 and 2.94 ± 0.61; post; p < 0.05) despite of being within the normal range in both periods. The average peak flow measurements also was higher during the vacational period compared to the period of work, although not statistically significant (366.6 ± 54.1 pre and post 386.4 ± 62.9; p > 0.05). We found a reduction of the exhaled measured values of NO after the holidays (pre and post 16.3 ± 9.7, 13.8 ± 7.8; p < 0.05), reduction of eosinophils (pre and post 0.05 ± 0.019, 0.003 ± 0.01; p < 0.05), lymphocytes (pre and post 0.16 ± 0.35, 0.01 ± 0.09; p < 0.05) and macrophages (pre and post 0.421 ± 0.47 0.235 ± 0 30 p < 0.05) in induced sputum cytology, performed after the holiday period. CONCLUSION: We demonstrate that the occupational environment to which professional cleaning non-domestic workers are exposed causes inflammation in the airways of asymptomatic workers. This inflammation can be measured by non-invasive methods such as induced sputum and FeNo, before the onset of changes in functional tests, although these methods still require standardization. Further studies are needed to quantify the exposure to chlorine and its relation to inflammation, as well as to standardize the use of induced sputum and exhaled nitric oxide in the diagnosis of occupational diseases among cleaning workers, and preventive and educational measures in this population

INTRODUÇÃO: Há evidências consistentes a partir de estudos epidemiológicos de que os profissionais de limpeza têm um risco elevado de desenvolver asma. Os determinantes deste risco não são totalmente conhecidos. Esses trabalhadores estão expostos a agentes ocupacionais de baixo e alto peso molecular, tanto a agentes sensibilizantes, como a irritantes. É importante produzir evidências de que este risco está relacionado ao trabalho e não às condições sociais ou outros fatores concorrentes, conhecer a anormalidade patológica subjacente, e investigar os possíveis agentes. O acúmulo deste conhecimento permitirá a proposição de medidas para substituição ou controle do uso dos agentes envolvidos e prevenção da ocorrência de novos casos desnecessariamente. Além disso, o uso de novas técnicas não invasivas, como a citologia do escarro e A FeNO, poderá facilitar o diagnóstico precoce dos casos. Desta maneira, este estudo pretende avaliar se o ambiente de trabalho induz inflamação pulmonar em trabalhadores assintomáticos, antes da alteração das provas funcionais e a eficácia do escarro induzido e da FeNO NO como marcadores de inflamação pulmonar precoce entre trabalhadores de limpeza profissional não doméstica. MÉTODO: Os trabalhadores foram avaliados através da comparação da citologia do escarro, valores da FeNO, espirometria e PFE, realizados durante o período de trabalho e após as férias. A amostra foi caracterizada através do questionário de triagem do estudo de saúde respiratória da Comunidade Européia, questionário de sintomas respiratórios e a pontuação no ISAAC. RESULTADOS: Em nosso estudo, encontramos um aumento significativo dos valores do VEF1 após o período de férias, (pré 2,76 ± 0,57 e pós 2,94 ± 0,61; p < 0,05) apesar de estar dentro da normalidade, em ambos os períodos. A média das medidas do PFE também mostrou-se maior durante o período de férias em comparação ao período de trabalho, embora não estatisticamente significante (pré 366,6 ± 54,1 e pós 386,4 ± 62,9 e p > 0,05). Encontramos uma redução dos valores da medida da FeNO após as férias (pré 16,3 ± 9,7 e pós 13,8 ± 7,8 p < 0,05) e redução de eosinófilos (pré 0,019 ± 0,05 e pós 0,003 ± 0,01 p < 0,05), linfócitos (pré 0,16 ± 0,35 e pós 0,01 ± 0,09 p < 0,05) e macrófagos (pré 0,421 ± 0,47 e pós 0,235 ± 0,30 p < 0,05) na citologia do escarro induzido, realizada após o período de férias. CONCLUSÃO: Demonstramos que o ambiente ocupacional ao qual são expostos os trabalhadores de limpeza profissional não doméstica provoca inflamação nas vias aéreas de trabalhadores assintomáticos. Esta inflamação pode ser aferida por métodos não invasivos como escarro induzido e FeNo, antes do aparecimento de alterações nas provas funcionais, embora estes métodos ainda necessitem de padronização. São necessários novos estudos para quantificar a exposição ao cloro e sua relação com inflamação, assim como para padronizar o uso do escarro induzido e da FeNO no diagnóstico de doenças ocupacionais entre trabalhadores de limpeza, além de medidas preventivas e educativas nesta população / There is consistent evidence from epidemiological studies that the cleaning professionals have a high risk of developing asthma. The determinants of this risk are not fully known. These workers are exposed to occupational agents of low and high molecular weight, both the sensitizing agents, such as irritant. It is important to produce evidence that this risk is related to work and not social conditions or other competitive factors, know the underlying pathological abnormality, and investigate possible agents. The accumulation of this knowledge will allow proposing measures to replace or control the use of the agents involved and preventing the occurrence of new cases unnecessarily. In addition, the use of new non-invasive techniques, such as sputum cytology and the FeNO may facilitate early diagnosis of cases. Thus, this study aims to assess if the work environment induces lung inflammation in asymptomatic workers, before the change of functional tests and the effectiveness of induced sputum and exhaled NO as early lung inflammation markers between professional cleaning workers. METHOD: Workers were evaluated by comparing the sputum cytology, FeNO values, spirometry and PEF, made during the work period and after the holidays. The sample was characterized by screening questionnaire of respiratory health study of the European Community, questionnaire of respiratory symptoms and a score in ISAAC. RESULTS: In our study, we found a significant increase in FEV1 values after the vacational period, (pre 2.76 ± 0.57 and 2.94 ± 0.61; post; p < 0.05) despite of being within the normal range in both periods. The average peak flow measurements also was higher during the vacational period compared to the period of work, although not statistically significant (366.6 ± 54.1 pre and post 386.4 ± 62.9; p > 0.05). We found a reduction of the exhaled measured values of NO after the holidays (pre and post 16.3 ± 9.7, 13.8 ± 7.8; p < 0.05), reduction of eosinophils (pre and post 0.05 ± 0.019, 0.003 ± 0.01; p < 0.05), lymphocytes (pre and post 0.16 ± 0.35, 0.01 ± 0.09; p < 0.05) and macrophages (pre and post 0.421 ± 0.47 0.235 ± 0 30 p < 0.05) in induced sputum cytology, performed after the holiday period. CONCLUSION: We demonstrate that the occupational environment to which professional cleaning non-domestic workers are exposed causes inflammation in the airways of asymptomatic workers. This inflammation can be measured by non-invasive methods such as induced sputum and FeNo, before the onset of changes in functional tests, although these methods still require standardization. Further studies are needed to quantify the exposure to chlorine and its relation to inflammation, as well as to standardize the use of induced sputum and exhaled nitric oxide in the diagnosis of occupational diseases among cleaning workers, and preventive and educational measures in this population

Asthma is the most common chronic disease among children worldwide. The prescribing patterns of the medication used to treat asthma in South Africa, as well as the prevalence of paediatric asthma are of interest and need to be investigated. A drug utilisation review was performed to determine the prevalence of asthma, and in particular paediatric asthma in a section of the private health care sector of South Africa. The prescribing patterns of asthma medication were investigated according to different demographic factors, such as gender, geographical area and prescriber type. Data from a medical claims database were extracted and processed to reveal the different prescribing patterns from 1 January 2005 to 31 December 2008. Medication from the MIMS® pharmacological groups 10.2 and 10.4 were used as a basis for asthma medication. Patients had to use at least one medicine item from one of these groups to be included in the study. The prevalence of asthma in the general population showed an increase from 2005 to 2008. The prevalence of asthma as a part of the total database according to the number of patients increased from 23.01% in 2005 (n=347342) to 24.72% in 2008 (n=240854), although the number of patients on the total database decreased from 2005 to 2008. When investigating the number of prescriptions that were dispensed during 2008, asthma prescriptions comprised 7.16% (n=484983) of all prescriptions and the number of asthma medicine items that were dispensed made up 3.72% (n=611139) of the total number of medicine items dispensed in 2008. Paediatric asthma was divided into two age groups for the purpose of this study namely, 0 - 4 years of age and older than 4 years, but younger or equal to 11 years of age ( >4 - 11 years), according to a previous study done by the National Heart Lung and Blood Institute (NHLBI). The results from the data confirmed that the prevalence of asthma was higher in the younger age group. The number of patients using asthma medication in the 0 - 4 years age group comprised 44.40% (n=11306) of the total number of patients in this age group on the database in 2008, compared to 32.84% (n=28347) in the >4 - 11 years age group. Asthma was more common among male patients, whether they were included in the paediatric groups or not. The geographical distribution of paediatric asthma seemed to be connected to the provinces without coastlines and different mining facilities. The combination of asthma medication with antibiotics and systemic corticosteroids were investigated and it was concluded that antibiotics that were used for respiratory tract infections were prescribed the most frequently to asthma patients. The refill–adherence rates of patients with asthma were not satisfactory when considering that asthma is a chronic disease. The average adherence rate for all the asthma products that were brought into account when calculating the refill–adherence rate was 60.95%. A rate above 90% indicates optimal patient adherence. In conclusion this study determined that asthma has a significant prevalence among children in South Africa. The prescribing patterns for the different medication used in the treatment of asthma were investigated and recommendations for further research in this field of study were made. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

Asthma is the most common chronic disease among children worldwide. The prescribing patterns of the medication used to treat asthma in South Africa, as well as the prevalence of paediatric asthma are of interest and need to be investigated. A drug utilisation review was performed to determine the prevalence of asthma, and in particular paediatric asthma in a section of the private health care sector of South Africa. The prescribing patterns of asthma medication were investigated according to different demographic factors, such as gender, geographical area and prescriber type. Data from a medical claims database were extracted and processed to reveal the different prescribing patterns from 1 January 2005 to 31 December 2008. Medication from the MIMS® pharmacological groups 10.2 and 10.4 were used as a basis for asthma medication. Patients had to use at least one medicine item from one of these groups to be included in the study. The prevalence of asthma in the general population showed an increase from 2005 to 2008. The prevalence of asthma as a part of the total database according to the number of patients increased from 23.01% in 2005 (n=347342) to 24.72% in 2008 (n=240854), although the number of patients on the total database decreased from 2005 to 2008. When investigating the number of prescriptions that were dispensed during 2008, asthma prescriptions comprised 7.16% (n=484983) of all prescriptions and the number of asthma medicine items that were dispensed made up 3.72% (n=611139) of the total number of medicine items dispensed in 2008. Paediatric asthma was divided into two age groups for the purpose of this study namely, 0 - 4 years of age and older than 4 years, but younger or equal to 11 years of age ( >4 - 11 years), according to a previous study done by the National Heart Lung and Blood Institute (NHLBI). The results from the data confirmed that the prevalence of asthma was higher in the younger age group. The number of patients using asthma medication in the 0 - 4 years age group comprised 44.40% (n=11306) of the total number of patients in this age group on the database in 2008, compared to 32.84% (n=28347) in the >4 - 11 years age group. Asthma was more common among male patients, whether they were included in the paediatric groups or not. The geographical distribution of paediatric asthma seemed to be connected to the provinces without coastlines and different mining facilities. The combination of asthma medication with antibiotics and systemic corticosteroids were investigated and it was concluded that antibiotics that were used for respiratory tract infections were prescribed the most frequently to asthma patients. The refill–adherence rates of patients with asthma were not satisfactory when considering that asthma is a chronic disease. The average adherence rate for all the asthma products that were brought into account when calculating the refill–adherence rate was 60.95%. A rate above 90% indicates optimal patient adherence. In conclusion this study determined that asthma has a significant prevalence among children in South Africa. The prescribing patterns for the different medication used in the treatment of asthma were investigated and recommendations for further research in this field of study were made. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A asma é um distúrbio crônico pulmonar caracterizado por inflamação, obstrução e remodelamento brônquico, levando a sintomas como sibilo, tosse e falta de ar. A terapia antiasmática consiste em corticosteroides inalados e agonistas &#946;2 de curta ou longa duração. O tratamento é limitado por efeitos colaterais e refratariedade de alguns pacientes, justificando a necessidade de novas terapias. Estudos demonstram que a 15-deoxy-delta- 12,14-prostaglandina J2 (15d-PGJ2), um ligante endógeno de receptores ativados por proliferadores de peroxissomos do tipo gama (PPAR-&#947;), é capaz de reduzir a expressão de citocinas pró-inflamatórias, o que pode resultar em benefícios no tratamento de doenças com esse perfil. O objetivo deste estudo foi avaliar o potencial anti-inflamatório e antiasmático da 15d-PGJ2 em modelos experimentais de asma. Camundongos A/J machos foram sensibilizados nos dias 0 e 7 através de injeção subcutânea (s.c.), contendo ovoalbumina (OVA) e Al(OH)3, e desafiados com 4 instilações intranasais (i.n.) de OVA em intervalos semanais. O tratamento com 15d-PGJ2 (30 e 100 &#61549;g/Kg, s.c.) foi realizado 30 min antes dos desafios a partir da terceira provocação antigênica. Em outro modelo, camundongos A/J foram desafiados intranasalmente com extrato de ácaro 3 vezes por semana durante 3 semanas. As administrações de 15d-PGJ2 (30, 70 e 100 g/Kg, s.c. e 0,65; 1,5 e 2,3 g/animal, i.n.) foram realizadas a partir da 3 semana, 30 min antes dos desafios. As análises ocorreram 24 h após o último desafio. Nossos resultados mostraram que, em camundongos previamente sensibilizados e desafiados com OVA, a administração de 15d-PGJ2 limitou significativamente o influxo peribrônquico de eosinófilos e neutrófilos, bem como a produção de muco por células caliciformes e fibrose sub-epitelial, além da hiperreatividade das vias aéreas e produção de IL-5. A redução do epitélio brônquico e das citocinas IL-13 e TNF-&#945; foram observadas somente na maior dose administrada. No modelo HDM a inflamação e o remodelamento foram atenuados em todas as doses administradas do composto, enquanto que a hiperresponssividade brônquica foi inibida apenas nas doses de 70 e 100 &#956;g/Kg (via sistêmica) e na dose intermediária dada topicamente (1,5 &#956;g/animal, i.n.). Os níveis de citocinas foram atenuados pelo tratamento subcutâneo, porém somente os níveis de IL-17, eotaxina-1 e TNF-&#945; foram inibidos com a dose intranasal de 0,65 g/animal. O aumento da expressão de NF-&#954;B, induzido por provocação com HDM também foi reduzido significativamente pela administração de 15d-PGJ2. Em conjunto, nossos dados indicam que o tratamento com 15d-PGJ2 inibe alterações cruciais associadas à patogênese da asma, em modelos experimentais distintos da doença, demonstrando possuir grande potencial para controlar e reverter inflamação, hiperreatividade e remodelamento pulmonar desencadeados por provocação alérgica. / Asthma is a chronic pulmonary disorder characterized by inflammation, obstruction and airway remodeling, leading to symptoms such as wheezing, coughing and breathlessness. Asthma therapy is based on inhaled corticosteroids and short or long term-&#946;2 agonists. The treatment is limited by side effects and some refractory patients, justifying the study for new therapies. Studies have demonstrated that 15-deoxy-delta-12 ,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPAR-&#947;) can reduce pro-inflammatory cytokines expression, providing a protective effect in diseases with this profile. The aim of this study was to evaluate the anti-inflammatory and antiasthmatic properties of 15d-PGJ2 in murine models of experimental asthma. A/J mice rats were sensitized on days 0 and 7 by subcutaneous (s.c.) injection , containing ovalbumin (OVA) and Al(OH)3, and challenged with 4 intranasal OVA instillations at weekly intervals. 15d-PGJ2 treatment (30 and 100 &#956;g/Kg) was performed 30 min before the challenges from the third antigen challenge. In another model, A/J mice were intranasally (i.n.) challenged with mite extract 3 times per week for 3 weeks. The administration of 15d-PGJ2 (30, 70 and 100 &#956;g /Kg, s.c. and 0.65, 1.5 and 2.3 &#956;g / animal, i.n.) were performed from the 3rd week, 30 min before the challenges. The analyzes were 24 h after the last challenge. Our results showed that in previously OVA-sensitized and challenged mice, administration of 15d-PGJ2 limited significantly (p <0.05), eosinophilic and neutrophilic inflammation and mucus production by goblet cells and sub-epithelial fibrosis, as well as airways hyperreactivity and IL-5 production. The reduction of bronchial epithelium and IL-13 and TNF-&#945; were observed only at the highest dose administered. In HDM model, inflammatory and remodeling parameters were attenuated in all administered doses of compound, whereas bronchial hyperresponsiveness was inhibited only at doses of 70 and 100 &#956;g/kg (s.c.) and 1.5 &#956;g/animal (i.n.). Serum cytokine levels were attenuated by subcutaneous treatment, but only IL-17, Eotaxin-1 and TNF-&#945; was inhibited by intranasal dose of 0.65 &#956;g/ animal. The increased expression of NF-kB induced by HDM challenge was also significantly reduced by the administration of 15d-PGJ2. Together, our data indicate that treatment with 15d-PGJ2 inhibits critical changes associated with the pathogenesis of asthma in different experimental models of the disease, demonstrating great potential to control and reverse pulmonary inflammation, hyperresponsiveness and remodeling triggered by allergen challenge.

Es va determinar el risc d'asma i la seva associació amb les exposicions laborals, així com la càrrega d'asma relacionat amb el treball, entre professionals sanitaris. Després de validar un qüestionari nou, es va administrar una enquesta a 5600 metges, infermers, i tècnics en teràpia respiratòria i ocupacional a Texas (tasa de resposta-66%). S'evidencia un risc elevat d'asma desprès d'haver començat a treballar per tasques de neteja general, desinfecció d'instruments mèdics, l'ús de guants de làtex i l'administració de medicaments en aerosol. També s'evidencien associacions significatives entre símptomes de hiperreactivitat bronquial i l'ús de productes generals de neteja, l'administració de medicaments en aerosol, l'aplicació de productes adhesius/dissolvents, i en persones amb antecedents d'exposició a un vessament químic. El risc per làtex desaparegué desprès de l'any 2000. Les exposicions laborals contribueixen de manera important a l'asma en el personal sanitari, justificant tant la implementació de controls adequats com la recerca addicional. / The magnitude of asthma risk, its associations with occupational exposures, and the burden of work-related asthma was estimated in healthcare professionals. After validating a new asthma questionnaire, a cross-sectional survey was conducted among 5600 Texas physicians, nurses, respiratory therapists and occupational therapists (response rate, 66%). Elevated risks of asthma after entry into the profession were found for general cleaning tasks, medical instrument cleaning, use of powdered latex gloves, and administration of aerosolized medications. Significant associations were also found between bronchial hyperresponsiveness-related symptoms and use of general cleaning products, administration of aerosolized medications, use of adhesives or solvents as products in patient care, and with a history of acute exposure to a chemical spill. The risk associated with latex disappeared after the year 2000. Occupational exposures contribute importantly to asthma among healthcare professionals and are not trivial, meriting both further study and implementation of appropriate controls.

La contaminació atmosfèrica és un problema de salut pública, causa més de 380 000 morts a la Unió Europea. La present tesis té per objectius avaluar l'exposició i efectes sobre el tracte respiratori de la contaminació provinent del tràfic. Les concentracions exteriors y personals de sulfurs i de carbó són bons indicadors de exposició personal en una ciutat mediterrània; per a PM2.5 hi ha altres fonts a considerar. La molèstia deguda a la contaminació no és un bon indicador d'exposició, però reflecteix la percepció del subjecte. La contaminació que prové del tràfic augmenta els símptomes d'asma y probablement també causa asma en adults. El PM2.5 provinent de la combustió augmenta la permeabilitat de la barrera epitelial pulmonar. El tràfic és una font important de contaminació. Es requereixen eines adequades per a mesurar la seva exposició. La contaminació del tràfic es un factor de risc important per a la salut respiratòria. / La contaminación atmosférica es un problema de salud pública, causa 380 000 muertes anuales en la Unión Europea. Esta tesis tiene como objetivo evaluar la exposición a la contaminación debida al tráfico y sus efectos en la salud respiratoria. Los niveles diarios de carbón y sulfuro medidos centralmente son buenos indicadores de exposición personal en una ciudad mediterránea, para PM2.5 fuentes de emisión alternas se tienen que considerar. La molestia debida a la contaminación no es un marcador de exposición, pero es importante porque refleja las percepciones individuales. La contaminación proveniente del tráfico aumento los síntomas del asma, y probablemente también causa asma en adultos. El PM2.5 proveniente de la combustión aumenta la permeabilidad de la barrera epitelial pulmonar. El tráfico es una fuente importante de la contaminación. Herramientas adecuadas para medir su exposición son requeridas. La contaminación del tráfico es un factor de riesgo importante para la salud respiratoria. / Air pollution is a major public health concern causing annually 380 000 deaths in the European Union. This thesis aims to study traffic-related air pollution exposure assessment and its association with respiratory effects. Daily levels of carbon and sulphur of outdoor central measurements are good surrogates for personal exposure in a Mediterranean setting; for PM2.5 other sources have to be taken into account. Annoyance due to air pollution is not a valid maker of air pollution exposure but is valuable in its own right as it integrates individual perceptions. Traffic-related air pollution increases asthma symptoms in adults and an association with new asthma onset is suggested. Furthermore, PM2.5 from combustion might lead to an increase in the lung's epithelial barrier permeability. Traffic-related air pollution is a major source of pollution. Adequate tools to assess its exposure are still needed. Traffic-related air pollution is an important risk factor for respiratory morbidity.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A asma é um distúrbio crônico pulmonar caracterizado por inflamação, obstrução e remodelamento brônquico, levando a sintomas como sibilo, tosse e falta de ar. A terapia antiasmática consiste em corticosteroides inalados e agonistas &#946;2 de curta ou longa duração. O tratamento é limitado por efeitos colaterais e refratariedade de alguns pacientes, justificando a necessidade de novas terapias. Estudos demonstram que a 15-deoxy-delta- 12,14-prostaglandina J2 (15d-PGJ2), um ligante endógeno de receptores ativados por proliferadores de peroxissomos do tipo gama (PPAR-&#947;), é capaz de reduzir a expressão de citocinas pró-inflamatórias, o que pode resultar em benefícios no tratamento de doenças com esse perfil. O objetivo deste estudo foi avaliar o potencial anti-inflamatório e antiasmático da 15d-PGJ2 em modelos experimentais de asma. Camundongos A/J machos foram sensibilizados nos dias 0 e 7 através de injeção subcutânea (s.c.), contendo ovoalbumina (OVA) e Al(OH)3, e desafiados com 4 instilações intranasais (i.n.) de OVA em intervalos semanais. O tratamento com 15d-PGJ2 (30 e 100 &#61549;g/Kg, s.c.) foi realizado 30 min antes dos desafios a partir da terceira provocação antigênica. Em outro modelo, camundongos A/J foram desafiados intranasalmente com extrato de ácaro 3 vezes por semana durante 3 semanas. As administrações de 15d-PGJ2 (30, 70 e 100 g/Kg, s.c. e 0,65; 1,5 e 2,3 g/animal, i.n.) foram realizadas a partir da 3 semana, 30 min antes dos desafios. As análises ocorreram 24 h após o último desafio. Nossos resultados mostraram que, em camundongos previamente sensibilizados e desafiados com OVA, a administração de 15d-PGJ2 limitou significativamente o influxo peribrônquico de eosinófilos e neutrófilos, bem como a produção de muco por células caliciformes e fibrose sub-epitelial, além da hiperreatividade das vias aéreas e produção de IL-5. A redução do epitélio brônquico e das citocinas IL-13 e TNF-&#945; foram observadas somente na maior dose administrada. No modelo HDM a inflamação e o remodelamento foram atenuados em todas as doses administradas do composto, enquanto que a hiperresponssividade brônquica foi inibida apenas nas doses de 70 e 100 &#956;g/Kg (via sistêmica) e na dose intermediária dada topicamente (1,5 &#956;g/animal, i.n.). Os níveis de citocinas foram atenuados pelo tratamento subcutâneo, porém somente os níveis de IL-17, eotaxina-1 e TNF-&#945; foram inibidos com a dose intranasal de 0,65 g/animal. O aumento da expressão de NF-&#954;B, induzido por provocação com HDM também foi reduzido significativamente pela administração de 15d-PGJ2. Em conjunto, nossos dados indicam que o tratamento com 15d-PGJ2 inibe alterações cruciais associadas à patogênese da asma, em modelos experimentais distintos da doença, demonstrando possuir grande potencial para controlar e reverter inflamação, hiperreatividade e remodelamento pulmonar desencadeados por provocação alérgica. / Asthma is a chronic pulmonary disorder characterized by inflammation, obstruction and airway remodeling, leading to symptoms such as wheezing, coughing and breathlessness. Asthma therapy is based on inhaled corticosteroids and short or long term-&#946;2 agonists. The treatment is limited by side effects and some refractory patients, justifying the study for new therapies. Studies have demonstrated that 15-deoxy-delta-12 ,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPAR-&#947;) can reduce pro-inflammatory cytokines expression, providing a protective effect in diseases with this profile. The aim of this study was to evaluate the anti-inflammatory and antiasthmatic properties of 15d-PGJ2 in murine models of experimental asthma. A/J mice rats were sensitized on days 0 and 7 by subcutaneous (s.c.) injection , containing ovalbumin (OVA) and Al(OH)3, and challenged with 4 intranasal OVA instillations at weekly intervals. 15d-PGJ2 treatment (30 and 100 &#956;g/Kg) was performed 30 min before the challenges from the third antigen challenge. In another model, A/J mice were intranasally (i.n.) challenged with mite extract 3 times per week for 3 weeks. The administration of 15d-PGJ2 (30, 70 and 100 &#956;g /Kg, s.c. and 0.65, 1.5 and 2.3 &#956;g / animal, i.n.) were performed from the 3rd week, 30 min before the challenges. The analyzes were 24 h after the last challenge. Our results showed that in previously OVA-sensitized and challenged mice, administration of 15d-PGJ2 limited significantly (p <0.05), eosinophilic and neutrophilic inflammation and mucus production by goblet cells and sub-epithelial fibrosis, as well as airways hyperreactivity and IL-5 production. The reduction of bronchial epithelium and IL-13 and TNF-&#945; were observed only at the highest dose administered. In HDM model, inflammatory and remodeling parameters were attenuated in all administered doses of compound, whereas bronchial hyperresponsiveness was inhibited only at doses of 70 and 100 &#956;g/kg (s.c.) and 1.5 &#956;g/animal (i.n.). Serum cytokine levels were attenuated by subcutaneous treatment, but only IL-17, Eotaxin-1 and TNF-&#945; was inhibited by intranasal dose of 0.65 &#956;g/ animal. The increased expression of NF-kB induced by HDM challenge was also significantly reduced by the administration of 15d-PGJ2. Together, our data indicate that treatment with 15d-PGJ2 inhibits critical changes associated with the pathogenesis of asthma in different experimental models of the disease, demonstrating great potential to control and reverse pulmonary inflammation, hyperresponsiveness and remodeling triggered by allergen challenge.

Determina el impacto del seguimiento farmacoterapéutico, sobre la técnica en el uso de los medicamentos de inhalación y en el conocimiento de la enfermedad, en los pacientes ambulatorios con asma bronquial. Realiza un estudio cuasi-experimental en pacientes ambulatorios con diagnóstico de asma bronquial, con medición de las variables respuesta antes y después, sin grupo control. Participan siete pacientes durante cinco meses que duro el periodo de intervención. A través de la intervención farmacéutica se hizo una evaluación de la técnica inhalatoria y del conocimiento que tiene el paciente asmático acerca de su enfermedad; asimismo, se registraron los PRM identificados, detallando sus causas y consecuencias, las intervenciones realizadas para resolverlos y los resultados de la intervención. Encuentra que los resultados de la evaluación de la técnica inhalatoria de los pacientes tiene una media de error de 63,35% antes de la intervención y de 28,57% después de la misma; el conocimiento en relación a su enfermedad tiene una media de respuestas acertadas de 29,29% antes de la intervención y de 65% después de la misma.Se registra un total de 5 PRM en tres pacientes de los siete que participaron en el estudio, la resolución se realiza con educación a los paciente en 80%(4 de 5) y derivación al médico en 20% (1 de 5), de esta forma se logra resolver el 60%(3 de 5) de los casos de manera positiva, el 20% (1 de 5) de los casos parcialmente y el 20%(1 de 5) restante no se resolvió. Concluye que el seguimiento farmacoterapéutico mejora el uso de los medicamentos de inhalación y el conocimiento de la enfermedad en los pacientes ambulatorios con asma bronquial, pero esto no se puede generalizar porque la muestra del presente estudio no es representativa. / Tesis