Introdução: Ainda que resultados de ensaios clínicos preconizem que o controle da asma possa ser obtido, as evidências epidemiológicas sugerem que há uma significante lacuna entre as metas terapêuticas e o grau corrente de controle da doença obtido na população geral. Assim, o desafio que se estabelece é desenvolver estratégias que permitam atingir e manter o controle da asma. Objetivo: avaliar o efeito de um programa educativo ambulatorial individualizado em pacientes com asma não controlada. Métodos: Estudo prospectivo envolvendo pacientes com idade igual ou maior que 14 anos, com asma não controlada, recrutados a partir do ambulatório de um hospital universitário. O estudo foi conduzido antes e depois de uma intervenção educacional para asma. Após uma visita ambulatorial de rotina, os participantes respondiam a questionário estruturado para avaliar o grau de controle da asma, os escores de qualidade de vida (questionário de Juniper) e a técnica inalatória. Os participantes também foram submetidos a testes de função pulmonar. Após, eles participaram de um programa educativo em asma que consistia de uma sessão inicial individualizada de 45 minutos e de entrevistas telefônicas de 30 minutos em 2, 4 e 8 semanas. Todos os participantes foram reavaliados após 3 meses. Resultados: 63 pacientes completaram o estudo. Na segunda avaliação, foi observada significante melhora no grau de controle da asma (p<0, 001): 28 pacientes (44,4%) passaram para asma parcialmente controlada e 6 (9,5%) para asma controlada. Também, o volume expiratório forçado no primeiro (VEF1) melhorou de 63,0±20,0% para 68,5±21.2% do previsto (p=0, 002) e os escores de qualidade de vida melhoraram em todos os domínios (p<0,05). A proporção de pacientes com técnica inalatória adequada melhorou significativamente de 15,4% para 46,2% (p=0, 021) para aqueles em uso do aerossol dosimetrado e de 21,3% para 76.6% (p<0, 001) para aqueles em uso de dispositivo em pó. A análise de regressão logística identificou a técnica inalatória incorreta na primeira avaliação independentemente associada com a resposta favorável à intervenção educativa. Conclusão: Este programa educativo para pacientes asmáticos ambulatoriais resultou em melhora do grau de controle da doença. Também houve significante melhora no VEF1 e nos escores de qualidade de vida. A técnica inalatória incorreta na avaliação inicial foi preditora de resposta favorável à intervenção educativa. / Introduction: Although the results of clinical trials advocate that asthma control can be reached in most patients, the epidemiologic evidence suggests that there is a significant gap between the treatment goals and the current level of asthma control achieved for the general population. Therefore, the challenge that remains is to find management strategies to ensure that this control is achieved and maintained. Objective: To evaluate the effect of an individualized education program on the level of asthma control. Methods: A prospective study involving patients aged 14 years or older, with uncontrolled asthma, recruited from the asthma outpatient clinic of an university hospital. The study was conducted in two phases (before and after the educational intervention). After a routine medical visit, the participants completed a structured questionnaire in order to assess the level of asthma control, the quality of life (Juniper questionnaire) and inhalation techniques. The participants also underwent pulmonary function testing. Subsequently, they participated in an asthma educational program, which consisted of one individualized 45 min session and of a 30 min phone interview at 2, 4 and 8 weeks. The participants were reevaluated after three months. Results: 63 patients completed the study. Between the first and second evaluations, there was a significant improvement in the level of asthma control (p<0.001): 28 (44.4%) changed to partly controlled disease and 6 (9.5%) to controlled disease. Also, the forced expiratory volume in the first second (FEV1) improved from 63.0±20.0% to 68.5±21.2% of predicted (p=0.002) and the quality of life scores improved significantly in all domains (p<0.05). The proportion of patients with adequate inhalation technique improved significantly from 15.4% to 46.2% (p=0.021) for those in use of metered-dose inhaler (MDI) and from 21.3% to 76.6% (p<0.001) for those in use of dry powder inhaler. Logistic regression analysis identified incorrect inhaler technique in the first evaluation independently associated with significant response to the educative intervention. Conclusions: This educational program for patients attending an asthma outpatient clinic resulted in an improvement on the level of asthma control. Also, there was significant improvement in FEV1 and in quality of life scores. Incorrect inhaler technique in the first evaluation was predictive of significant response to educational intervention.

Introdução: Ainda que resultados de ensaios clínicos preconizem que o controle da asma possa ser obtido, as evidências epidemiológicas sugerem que há uma significante lacuna entre as metas terapêuticas e o grau corrente de controle da doença obtido na população geral. Assim, o desafio que se estabelece é desenvolver estratégias que permitam atingir e manter o controle da asma. Objetivo: avaliar o efeito de um programa educativo ambulatorial individualizado em pacientes com asma não controlada. Métodos: Estudo prospectivo envolvendo pacientes com idade igual ou maior que 14 anos, com asma não controlada, recrutados a partir do ambulatório de um hospital universitário. O estudo foi conduzido antes e depois de uma intervenção educacional para asma. Após uma visita ambulatorial de rotina, os participantes respondiam a questionário estruturado para avaliar o grau de controle da asma, os escores de qualidade de vida (questionário de Juniper) e a técnica inalatória. Os participantes também foram submetidos a testes de função pulmonar. Após, eles participaram de um programa educativo em asma que consistia de uma sessão inicial individualizada de 45 minutos e de entrevistas telefônicas de 30 minutos em 2, 4 e 8 semanas. Todos os participantes foram reavaliados após 3 meses. Resultados: 63 pacientes completaram o estudo. Na segunda avaliação, foi observada significante melhora no grau de controle da asma (p<0, 001): 28 pacientes (44,4%) passaram para asma parcialmente controlada e 6 (9,5%) para asma controlada. Também, o volume expiratório forçado no primeiro (VEF1) melhorou de 63,0±20,0% para 68,5±21.2% do previsto (p=0, 002) e os escores de qualidade de vida melhoraram em todos os domínios (p<0,05). A proporção de pacientes com técnica inalatória adequada melhorou significativamente de 15,4% para 46,2% (p=0, 021) para aqueles em uso do aerossol dosimetrado e de 21,3% para 76.6% (p<0, 001) para aqueles em uso de dispositivo em pó. A análise de regressão logística identificou a técnica inalatória incorreta na primeira avaliação independentemente associada com a resposta favorável à intervenção educativa. Conclusão: Este programa educativo para pacientes asmáticos ambulatoriais resultou em melhora do grau de controle da doença. Também houve significante melhora no VEF1 e nos escores de qualidade de vida. A técnica inalatória incorreta na avaliação inicial foi preditora de resposta favorável à intervenção educativa. / Introduction: Although the results of clinical trials advocate that asthma control can be reached in most patients, the epidemiologic evidence suggests that there is a significant gap between the treatment goals and the current level of asthma control achieved for the general population. Therefore, the challenge that remains is to find management strategies to ensure that this control is achieved and maintained. Objective: To evaluate the effect of an individualized education program on the level of asthma control. Methods: A prospective study involving patients aged 14 years or older, with uncontrolled asthma, recruited from the asthma outpatient clinic of an university hospital. The study was conducted in two phases (before and after the educational intervention). After a routine medical visit, the participants completed a structured questionnaire in order to assess the level of asthma control, the quality of life (Juniper questionnaire) and inhalation techniques. The participants also underwent pulmonary function testing. Subsequently, they participated in an asthma educational program, which consisted of one individualized 45 min session and of a 30 min phone interview at 2, 4 and 8 weeks. The participants were reevaluated after three months. Results: 63 patients completed the study. Between the first and second evaluations, there was a significant improvement in the level of asthma control (p<0.001): 28 (44.4%) changed to partly controlled disease and 6 (9.5%) to controlled disease. Also, the forced expiratory volume in the first second (FEV1) improved from 63.0±20.0% to 68.5±21.2% of predicted (p=0.002) and the quality of life scores improved significantly in all domains (p<0.05). The proportion of patients with adequate inhalation technique improved significantly from 15.4% to 46.2% (p=0.021) for those in use of metered-dose inhaler (MDI) and from 21.3% to 76.6% (p<0.001) for those in use of dry powder inhaler. Logistic regression analysis identified incorrect inhaler technique in the first evaluation independently associated with significant response to the educative intervention. Conclusions: This educational program for patients attending an asthma outpatient clinic resulted in an improvement on the level of asthma control. Also, there was significant improvement in FEV1 and in quality of life scores. Incorrect inhaler technique in the first evaluation was predictive of significant response to educational intervention.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2016-12-16T10:18:59Z No. of bitstreams: 2 Dissertação - Fernanda Cruvinel de Abreu - 2016.pdf: 9557097 bytes, checksum: 68075f9112c44b45bbb05a915e471610 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2016-12-16T16:48:58Z (GMT) No. of bitstreams: 2 Dissertação - Fernanda Cruvinel de Abreu - 2016.pdf: 9557097 bytes, checksum: 68075f9112c44b45bbb05a915e471610 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-12-16T16:48:59Z (GMT). No. of bitstreams: 2 Dissertação - Fernanda Cruvinel de Abreu - 2016.pdf: 9557097 bytes, checksum: 68075f9112c44b45bbb05a915e471610 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-11-16 / The main goal of asthma treatment is to achieve and maintain clinical control of the disease. The exhaled fraction nitric oxide (FeNO) level is considered a biomarker of airways inflammation and its important to conduct researches involving this measured and its relationship in evaluation of asthma control.Objective: To determine whether the FeNO level can be used to discriminate between patients with controlled, partially controlled and uncontrolled asthma. Materials and methods: The FeNO level and asthma control were evaluated in a retrospective and analytic cross– sectional study through data collected from asthmatic patients who were assessed by clinical history, asthma control, physical examination, spirometry, and FeNO level. Asthma control was determined by the criteria of the Global Initiative for Asthma, and classified as controlled asthma, partially controlled asthma, and uncontrolled asthma. The FeNO values were classified as low (<25 ppb) or intermediate/high (≥25 ppb), based on the American Thoracic Society recommendations. Results: The symptoms of 81 asthmatic patients were classified as controlled (34 [42%] patients), partially controlled (27 [33,3%] patients), and uncontrolled (20 [24.7%] patients). The FeNO level discriminated between the uncontrolled and controlled groups (p = 0,01) and between the uncontrolled and partially controlled groups (p = 0,01), but not between the controlled and partially controlled groups (p = 0,98). An FeNO level >30 ppb was associated with uncontrolled asthma (p < 0,01) with an area under the receiver operating characteristic curve of 0,78 (95% confidence interval, 0,65-0,89). Conclusions: The FeNO level aided the identification of uncontrolled asthma. This measurement may can be helpful in determining asthma control. / O principal objetivo do tratamento da asma é alcançar e manter o controle clínico da doença. A medida da Fração Exalada do Óxido Nítrico (FeNO) é considerada um biomarcador da inflamação das vias aéreas sendo de extrema importância a realização de pesquisas envolvendo essa medida e a avaliação do nível de controle da asma. Objetivo: Verificar se a medida da FeNO discrimina pacientes com asma controlada, parcialmente controlada e não controlada. Materiais e métodos: Realizou-se um estudo restrospectivo, transversal analítico por meio da coleta de dados de pacientes asmáticos que foram avaliados em relação a sua história clínica, nível de controle da asma, exame físico, espirometria e FeNO. O nível de controle da asma foi determinado conforme critério da Global Initiative for Asthma (GINA), classificados como controlados, parcialmente controlados e não controlados. Os valores da FeNO foram classificados em baixo ou intermediário/alto (baixo <25 ppb e intermediário/elevado ≥ 25 ppb), de acordo com as recomendações da American Thoracic Society (ATS). Resultados: Foram incluídos 81 pacientes asmáticos classificados em controlados 34 (42%), parcialmente controlados 27 (33,3%) e não controlados 20 (24,7%). A medida da FeNO discriminou o grupo não controlado dos grupos controlado (p = 0,01) e parcialmente controlado (p = 0,01), mas não discriminou os grupos controlado e parcialmente controlado (p = 0,98). FENO >30 estava associado a asma não controlada (p <0,01) com área sob a curva ROC de 0,78 (Intervalo de Confiança 95%, 0.65- 0.89).Conclusão: A FeNO foi capaz de identificar asmáticos não controlados. Isso sugere que sua medida pode ser útil na determinação do controle da asma

Despite national guidelines, the management of difficult asthma remains suboptimal, and there may be opportunities for pharmacists to improve asthma outcomes. This six-month prospective, randomised, open study investigated the effects of pharmaceutical care across primary and secondary care on difficult asthma. Fifty-two patients attending a hospital difficult asthma clinic were randomised (1:1) to receive usual medical care (UC), or pharmacist interventions (PI) comprising asthma review, education, and medicines optimisation from a hospital advanced clinical pharmacist, plus follow-up targeted Medicines Use Review (t-MUR) from community pharmacists. Forty-seven patients completed the study. More interventions were performed in the PI group at baseline (total 79 vs. 34, p<0.001), but only six patients received a t-MUR. At six-months, PI were non-inferior to UC for all outcomes. The primary outcome measure was Juniper’s Asthma Control Questionnaire score and reduced (improved) from a median (IQ) score of 2.86 (2.25, 3.25) and 3.00 (1.96, 3.71) in the PI and UC groups respectively to 2.57 (1.75, 3.67) and 2.29 (1.50, 3.50). At baseline, 58.8%, 46.9% and 17.6% of patients had optimal inhaler technique using Accuhalers, Turbohalers or pMDIs; education improved technique but this was not maintained at six-months. Adherence rates <80% were observed in 57.5% of patients at baseline, and was improved in the PI group at six-months (10/20 PI vs. 3/21 UC had adherence rates of 80-120%, p=0.020). This study demonstrates that the management of difficult asthma by specialist pharmacists is as effective as usual medical care. Future research should investigate whether pharmacist-led follow-up produces further improvements. / The Pharmaceutical Trust for Educational and Charitable Objects (PTECO) (now known as Pharmacy Research UK).

Introduction Asthma is a common and heterogeneous disease in primary care. Asthma phenotypes are recognisable clusters of for example clinical characteristics. Current asthma symptoms and previous exacerbations are used to assess the level of asthma control. Asthma control is used clinically to plan follow-up strategies. Aim The aim of this study is to examine if an data-driven algorithm based on sex and age of onset can categorize an asthma population at a primary care center into three phenotypes with different risk of disease. To investigate if the results can be generalized by comparing to an epidemiological survey in Sweden. Secondary aims are to investigate if these phenotypes predict the level of follow-up and which factors influence asthma control. Methods In this cross-sectional study, 335 participants from one primary care site and 1442 participants from an epidemiological study were compared on sex, age, medical treatment, respiratory allergy, smoking, asthma symptoms and exacerbations. Logistic regression analyses focusing on factors affecting asthma control were performed in a consolidated dataset. Results An adult asthma population can easily be categorized according to the data-driven algorithm. However, these phenotypes do not predict follow-up strategies. Clinical follow-up based on level of asthma control, did not differ between the phenotypes. There were statistically significant differences between the phenotypes regarding respiratory allergy and smoking. In the logistic regression, smoking has the highest odds for poor asthma control. Conclusion The clinical use of the data-driven phenotypes were limited. Follow-up strategies are probably best based on traditional clinical outcomes like asthma control.

Les phénotypes de l’asthme sont affectés par l’exposition à de multiples facteurs durant la grossesse. Pour évaluer cette hypothèse, deux études ont été menées : l’une en France, l’autre au Liban. Dans l'étude française, l'objectif était de décrire les phénotypes respiratoires de sifflement chez l’enfant entre l’âge de deux mois et d’un an, et d'évaluer les facteurs de risque associés à ces phénotypes de sifflement dans une grande cohorte de naissance. Dans l'étude libanaise, les objectifs étaient d'évaluer les associations entre l'utilisation de médicaments, d'alcool, de cigarettes et/ou de narguileh, et l'exposition aux pesticides/détergents pendant la grossesse avec l'asthme infantile au Liban et de valider la version arabe du test de contrôle de l'asthme (ACT) chez ces enfants et d’identifier les facteurs de risque qui pourraient affecter le contrôle de l'asthme.Méthodes: Nous avons étudié 18 041 nourrissons de la cohorte de naissance ELFE (Étude Longitudinale Française depuis l'Enfance). Les parents ont signalé une respiration sifflante et des symptômes respiratoires à deux et 12 mois, et ont répondu à un questionnaire complet (exposition pendant la grossesse, allergie parentale). Le plan d'étude du projet libanais consistait en une étude cas-témoins, menée entre Décembre 2015 et Avril 2016, recrutant 1503 enfants, âgés de 3 à 17 ans. Le questionnaire administré évaluait les caractéristiques sociodémographiques (âge, sexe, niveau d'éducation des deux parents), les antécédents familiaux d'asthme et d'autres facteurs de risque connus de l'asthme (système de chauffage à domicile, antécédents d'otites récidivantes, humidité dans la maison, enfant allant à une garderie, fumer et boire de l'alcool pendant la grossesse, exposition aux pesticides et aux détergents).Résultats: Les enfants sans symptômes (témoins) représentaient 77,2%, 2,1% avaient une respiration sifflante à deux mois mais pas de respiration sifflante à un an (sifflement intermittent), 2,4% avaient une respiration sifflante persistante et 18,3% avaient une respiration sifflante à un an. En comparant les sifflements persistants aux contrôles, on a observé qu’avoir un frère ou une sœur (ORa = 2,19) ou deux frères et sœurs (ORa = 2,23) contre aucun, une toux nocturne (OR = 5,2), une détresse respiratoire (OR = 4,1) et un excès de sécrétions bronchiques (OR = 3,47 ) à deux mois, un reflux chez l'enfant à 2 mois (OR = 1,55), des antécédents d'asthme maternel (OR = 1,46) et le tabagisme maternel pendant la grossesse (OR = 1,57) étaient significativement associés à une respiration sifflante persistante. Ces mêmes facteurs, avec en sus une éruption cutanée chez l'enfant à 2 mois (OR = 1,13) et des antécédents paternels d'asthme (OR = 1,32) étaient significativement associés à une augmentation de la probabilité d'une respiration sifflante. Avoir un frère (ORa = 1,9) en comparaison à ne pas en avoir, une toux nocturne à 2 mois (OR = 1,76) et un excès de sécrétions bronchiques à 2 mois (OR = 1,65) étaient significativement associés à une respiration sifflante persistante par rapport à une respiration sifflante intermittente.... / Asthma in childhood seems affected by exposure to various factors in early life. To assess this hypothesis, we conducted 2 studies: one in France, and the other in Lebanon. In the French study, we aimed at describing wheezing phenotypes between the ages of two months and one year, and assess risk factors associated with these wheezing phenotypes in a large birth cohort. In the Lebanese study, the aims were to evaluate the associations between caregiver-reported use of medications, alcohol, cigarette and/or waterpipe (WP), and exposure to pesticides/detergents during pregnancy with childhood-onset asthma in Lebanon and to validate the Arabic version of the Asthma Control Test (ACT) among these children and identify risk factors that might affect asthma control.Methods: We studied 18,041 infants from the ELFE (French Longitudinal Study of Children) birth cohort. Parents reported wheezing and respiratory symptoms at two and 12 months, and answered a complete questionnaire (exposure during pregnancy, parental allergy).The study design of the Lebanese project consisted of a case-control study, conducted between December 2015 and April 2016, recruited 1503 children, aged between 3-16 years old. A questionnaire assessed the sociodemographic characteristics (age, gender, education level of both parents), the family history of asthma, and other known risk factors of asthma (heating system at home, child history of recurrent otitis, humidity in the house, child went to a daycare, smoking and drinking alcohol during pregnancy, exposure to pesticides and detergents).Results: Children with no symptoms (controls) accounted for 77.2%, 2.1% had had wheezing at two months but no wheezing at one year (intermittent wheezing), 2.4% had persistent wheezing, while 18.3% had incident wheezing at one year. Comparing persistent wheezing to controls showed that having one sibling (ORa=2.19) or 2 siblings (ORa=2.23) compared to none, nocturnal cough (OR=5.2), respiratory distress (OR=4.1) and excess bronchial secretions (OR=3.47) at two months, reflux in the child at 2 months (OR=1.55), maternal history of asthma (OR=1.46) and maternal smoking during pregnancy (OR=1.57) were significantly associated with persistent wheezing. These same factors, along with cutaneous rash in the child at 2 months (OR=1.13) and paternal history of asthma (OR=1.32) were significantly associated with increased odds of incident wheezing. Having one sibling (ORa=1.9) compared to none, nocturnal cough at 2 months (OR=1.76) and excess bronchial secretions at 2 months (OR=1.65) were significantly associated with persistent compared to intermittent wheezing.In the Lebanese study, the multivariate analysis showed that children living in North and South Lebanon and the children living in areas where pesticides are frequently used had an increased risk of asthma (ORa=1.625; ORa=13.65; ORa=3.307) respectively. Smoking WP during pregnancy and cigarette during lactation would increase the risk of asthma in children (ORa=6.11; ORa=3.44 respectively). A high Cronbach’s alpha was found for the full scale (0.959). As for the asthma control scale (ACT), the correlation factors between each item of the ACT scale and the whole scale ranged between 0.710 and 0.775 (p<0.001 for all items). Mother’s low educational level as well as the history of asthma in the mother and the father would significantly increase the risk of uncontrolled asthma (Beta= 1.862; Beta= 3.534; and Beta= 1.885 respectively). Cigarette smoking during breastfeeding and waterpipe smoking by the mother during pregnancy were both significantly associated with uncontrolled asthma (Beta= 2.105; Beta=2.325 respectively). Mother’s high educational level was significantly associated with more asthma control (Beta= -0.715).

INTRODUÇÃO: A asma grave acomete menos de 10% dos asmáticos, mas tem um impacto desproporcional sobre a utilização de recursos de saúde, contribuindo para, pelo menos, metade dos custos diretos e indiretos da doença. A proporção de indivíduos obesos ou com sobrepeso é elevada em pacientes com asma grave. Na verdade, a obesidade é um fator de risco para a asma, está associada com a gravidade da doença, com pior resposta a corticosteroides e pior controle clínico. Estudos sobre os efeitos da perda de peso em pacientes com asma ainda são escassos. OBJETIVOS: Avaliar o impacto da perda de peso com medidas clínicas em pacientes com asma grave e obesidade. MÉTODOS: Este é um estudo prospectivo randomizado aberto com dois grupos paralelos. Os participantes eram obesos e com asma grave e que, depois de um período de run-in de três meses, não estavam controlados de acordo com critérios da GINA. Os pacientes elegíveis foram randomizados em uma proporção de 2:1 (perda de peso: controle). Todos os participantes passaram por consultas bimensais no ambulatório de asma e foram acompanhados por seis meses. O desfecho primário foi o nível de controle da asma seis meses após o início do programa de redução de peso medido pelo Questionário de Controle da Asma (ACQ). Os desfechos secundários incluíram o Teste de Controle da Asma (ACT), resultados de função pulmonar, o Questionário Respiratório de St. George (SGRQ), a mudança na reatividade brônquica à metacolina, o uso diário de medicação de alívio para asma, percentagem de dias livres de sintomas, número de visitas ao pronto-socorro e exacerbações, marcadores de inflamação das vias aéreas medidos pelo escarro induzido e pelo óxido nítrico exalado (FeNO). IgE, proteína C reactiva, eotaxina, leptina e Transforming Growth Factor beta 1 (TGF 1) também foram medidos. RESULTADOS: Trinta e três foram randomizados. O grupo era composto predominantemente de mulheres com obstrução moderada, aprisionamento de ar, aumento da resistência das vias aéreas e marcada eosinofilia no escarro. O aumento dos níveis séricos de IgE foram consistentes com uma predominância de asma atópica. Dos 22 pacientes randomizados para submeterem-se a tratamento para a obesidade, 12 atingiram a meta de perda de peso de, pelo menos, 10% do peso corporal. A redução de peso no grupo de tratamento foi associada com melhor controle da asma medido pelo ACQ, ACT e SGRQ. Houve aumento de dias sem sintomas, menor uso de medicação de resgate e menos visitas ao serviço de emergência durante o período de estudo. Não houve diferença no número de exacerbações. A capacidade vital forçada (CVF) aumentou significativamente no grupo de tratamento e permaneceu inalterada no grupo de controle. As outras medidas da função pulmonar não mostraram diferenças entre os grupos. A hiperreatividade das vias aéreas, níveis de óxido nítrico exalado e celularidade do escarro induzido não se alterou ao longo do estudo. Os níveis de leptina diminuíram em ambos os grupos. Os níveis séricos de IgE, proteína C-reactiva, eotaxina, e TGF-1 não se alteraram. CONCLUSÃO: Nosso estudo adiciona informações à controvérsia sobre o impacto da obesidade e seu tratamento no controle da asma. Nossos resultados sugerem que a redução de peso em pacientes obesos com asma grave melhore os resultados de asma por mecanismos não relacionados com a inflamação das vias aéreas e que o controle da asma pobre em pessoas obesas é, pelo menos em parte, o resultado de fatores relacionados com a obesidade. A abordagem terapêutica para pacientes obesos com dificuldade de tratar a asma deve ser destinada à redução de peso, bem como à intensificação do tratamento anti-inflamatório / INTRODUTION: Severe asthma affects less than 10% of asthmatics, but has a disproportionate impact on the use of health resources, contributing to at least half of the direct and indirect costs of the disease. The proportion of obese or overweight individuals is elevated in patients with severe asthma. In fact, obesity is a risk factor for asthma, is associated with the severity of the disease, a poor response to corticosteroids and worse clinical control. Studies on the effects of weight loss in patients with asthma are still scarce. OBJECTIVES: Assess the impact of weight loss with a medical weight loss program in patients with severe asthma associated with obesity. METHODS: This is a prospective open study with two randomized parallel groups. The participants were obese and with severe asthma and, after a three month run-in period, were not controlled according to GINA criteria. Eligible patients were randomized in a 2:1 ratio (weight loss:control). All participants attended bimonthly consultations in the asthma clinic and were followed for six months. The primary outcome measure was the level of asthma control 6 months after initiation of the weight reduction program quantified by using the Asthma Control Questionnaire (ACQ). Secondary clinical outcomes included the Asthma Control Test (ACT), lung function results, score on the St. Georges Respiratory Questionnaire (SGRQ), change in metacholine reactivity, daily use of asthma reliever medication, percentage of asthma symptom free days, number of visits to emergency room and exacerbations, markers of airway cellular inflammation measured in induced sputum and with exhaled nitric oxide (FeNO). IgE, C reactive protein, leptin, eotaxin and Transforming Growth Factor beta 1 (TGF1) levels in serum were also measured. RESULTS: Thirty-three patients were randomized. The group consisted predominantly of women with moderate airflow obstruction, air trapping, increased airway resistance and marked eosinophilia in the sputum. The increased serum levels of IgE were consistent with a predominance of atopic asthma. Of the 22 patients randomized to undergo treatment for obesity, 12 achieved the weight loss goal of at least 10% of body weight. The reduction in weight in the treatment group was associated with improvement in the control as measured by ACQ, ACT and SGRQ. There was increase of symptom-free days, less use of rescue medication and fewer visits to the emergency room during the study period. There were no differences in the number of exacerbations. The forced vital capacity (FVC) increased significantly in the treatment group and remained unchanged in the control group. The other measures of the pulmonary function showed no differences between groups. The airway hyperresponsiveness, exhaled nitric oxide levels and induced sputum cellularity did not change throughout the study. Leptin levels decreased in both groups. Serum levels of IgE, C-reactive protein, eotaxin, and TGF-1 did not change. CONCLUSION: Our study adds information to the controversy about the impact of obesity and its treatment on asthma control. Our results suggest that weight reduction in obese patients with severe asthma improves asthma outcomes by mechanisms not related to airway inflammation and that poor asthma control in people who are obese is at least in part the result of obesity-related factors. The therapeutic approach for obese patients with difficult-to-treat asthma should therefore be aimed at weight reduction as well as on intensifying antiinflammatory treatment

BACKGROUND: Asthma is a chronic inflammatory disease of the airways that disproportionately affects low-income and minority children in the United States. Some studies have found a clear link between poor housing quality and exposure to allergen triggers associated with increased risk of asthma. Other studies have evaluated the relationship between stressful circumstances due to chronic illness, premature birth or violence on asthma outcomes. Psychological stress is thought to weaken the immune and neuroendocrine response making the body more vulnerable to environmental allergens. Studies have been done to assess the impact of psychological stress due to violence or the care of long term-critically ill children on increased asthma morbidity. However, asthma morbidity is not equal in all low-income and minority communities. It is possible that a form of stress - housing stress - which results from living in substandard housing conditions, may in fact provide more insight into the pathways linking indoor home exposures and stress in a way that leads to greater asthma susceptibility. Few studies have been done to assess the impact of stress due to substandard housing conditions. OBJECTIVE: To determine the impact of severe housing stress due to dilapidation, mold and a lack of housing control on child asthma control and on caregiver asthma-related quality of life. METHODS: A total of 143 children with asthma living in Boston, Massachusetts and between the ages of 4 and 18 were enrolled in the Boston Allergen Sampling Study between 2008 and 2011. Home visits were conducted to measure the levels of common allergens in the home and assess child asthma control, housing stress, perceived stress, and caregiver asthma-related quality of life. Housing stress was assessed based on resident perceptions of dilapidation, mold, and a lack of housing control; perceived stress for the caregiver was assessed using the Perceived-Stress Scale (PSS); child asthma control was assessed using Asthma Control Test (ACT) scores; and caregiver asthma-related quality of life was assessed using the Pediatric Asthma Caregiver Quality of Life (PACQOL) questionnaires. RESULTS: In a multivariate logistic regression severe housing stress was associated with 7.5 times increased odds of poor asthma control (OR = 7.51, 95%CI 2.7 to 20.79, p<0.0001) for the child and 3.0 times increased odds of poor caregiver asthma-related quality of life (OR = 3.02, 95%CI 1.37 to 6.63, p<0.006). This association was significant after adjusting for potential confounders. CONCLUSIONS: Independent of allergen exposure, the association between severe housing stress and asthma health outcomes for both the child and caregiver indicate that there is an emotional stress-based pathway directly tied to poor housing quality that poses increased risk for worse asthma health outcomes.

INTRODUÇÃO: A asma grave acomete menos de 10% dos asmáticos, mas tem um impacto desproporcional sobre a utilização de recursos de saúde, contribuindo para, pelo menos, metade dos custos diretos e indiretos da doença. A proporção de indivíduos obesos ou com sobrepeso é elevada em pacientes com asma grave. Na verdade, a obesidade é um fator de risco para a asma, está associada com a gravidade da doença, com pior resposta a corticosteroides e pior controle clínico. Estudos sobre os efeitos da perda de peso em pacientes com asma ainda são escassos. OBJETIVOS: Avaliar o impacto da perda de peso com medidas clínicas em pacientes com asma grave e obesidade. MÉTODOS: Este é um estudo prospectivo randomizado aberto com dois grupos paralelos. Os participantes eram obesos e com asma grave e que, depois de um período de run-in de três meses, não estavam controlados de acordo com critérios da GINA. Os pacientes elegíveis foram randomizados em uma proporção de 2:1 (perda de peso: controle). Todos os participantes passaram por consultas bimensais no ambulatório de asma e foram acompanhados por seis meses. O desfecho primário foi o nível de controle da asma seis meses após o início do programa de redução de peso medido pelo Questionário de Controle da Asma (ACQ). Os desfechos secundários incluíram o Teste de Controle da Asma (ACT), resultados de função pulmonar, o Questionário Respiratório de St. George (SGRQ), a mudança na reatividade brônquica à metacolina, o uso diário de medicação de alívio para asma, percentagem de dias livres de sintomas, número de visitas ao pronto-socorro e exacerbações, marcadores de inflamação das vias aéreas medidos pelo escarro induzido e pelo óxido nítrico exalado (FeNO). IgE, proteína C reactiva, eotaxina, leptina e Transforming Growth Factor beta 1 (TGF 1) também foram medidos. RESULTADOS: Trinta e três foram randomizados. O grupo era composto predominantemente de mulheres com obstrução moderada, aprisionamento de ar, aumento da resistência das vias aéreas e marcada eosinofilia no escarro. O aumento dos níveis séricos de IgE foram consistentes com uma predominância de asma atópica. Dos 22 pacientes randomizados para submeterem-se a tratamento para a obesidade, 12 atingiram a meta de perda de peso de, pelo menos, 10% do peso corporal. A redução de peso no grupo de tratamento foi associada com melhor controle da asma medido pelo ACQ, ACT e SGRQ. Houve aumento de dias sem sintomas, menor uso de medicação de resgate e menos visitas ao serviço de emergência durante o período de estudo. Não houve diferença no número de exacerbações. A capacidade vital forçada (CVF) aumentou significativamente no grupo de tratamento e permaneceu inalterada no grupo de controle. As outras medidas da função pulmonar não mostraram diferenças entre os grupos. A hiperreatividade das vias aéreas, níveis de óxido nítrico exalado e celularidade do escarro induzido não se alterou ao longo do estudo. Os níveis de leptina diminuíram em ambos os grupos. Os níveis séricos de IgE, proteína C-reactiva, eotaxina, e TGF-1 não se alteraram. CONCLUSÃO: Nosso estudo adiciona informações à controvérsia sobre o impacto da obesidade e seu tratamento no controle da asma. Nossos resultados sugerem que a redução de peso em pacientes obesos com asma grave melhore os resultados de asma por mecanismos não relacionados com a inflamação das vias aéreas e que o controle da asma pobre em pessoas obesas é, pelo menos em parte, o resultado de fatores relacionados com a obesidade. A abordagem terapêutica para pacientes obesos com dificuldade de tratar a asma deve ser destinada à redução de peso, bem como à intensificação do tratamento anti-inflamatório / INTRODUTION: Severe asthma affects less than 10% of asthmatics, but has a disproportionate impact on the use of health resources, contributing to at least half of the direct and indirect costs of the disease. The proportion of obese or overweight individuals is elevated in patients with severe asthma. In fact, obesity is a risk factor for asthma, is associated with the severity of the disease, a poor response to corticosteroids and worse clinical control. Studies on the effects of weight loss in patients with asthma are still scarce. OBJECTIVES: Assess the impact of weight loss with a medical weight loss program in patients with severe asthma associated with obesity. METHODS: This is a prospective open study with two randomized parallel groups. The participants were obese and with severe asthma and, after a three month run-in period, were not controlled according to GINA criteria. Eligible patients were randomized in a 2:1 ratio (weight loss:control). All participants attended bimonthly consultations in the asthma clinic and were followed for six months. The primary outcome measure was the level of asthma control 6 months after initiation of the weight reduction program quantified by using the Asthma Control Questionnaire (ACQ). Secondary clinical outcomes included the Asthma Control Test (ACT), lung function results, score on the St. Georges Respiratory Questionnaire (SGRQ), change in metacholine reactivity, daily use of asthma reliever medication, percentage of asthma symptom free days, number of visits to emergency room and exacerbations, markers of airway cellular inflammation measured in induced sputum and with exhaled nitric oxide (FeNO). IgE, C reactive protein, leptin, eotaxin and Transforming Growth Factor beta 1 (TGF1) levels in serum were also measured. RESULTS: Thirty-three patients were randomized. The group consisted predominantly of women with moderate airflow obstruction, air trapping, increased airway resistance and marked eosinophilia in the sputum. The increased serum levels of IgE were consistent with a predominance of atopic asthma. Of the 22 patients randomized to undergo treatment for obesity, 12 achieved the weight loss goal of at least 10% of body weight. The reduction in weight in the treatment group was associated with improvement in the control as measured by ACQ, ACT and SGRQ. There was increase of symptom-free days, less use of rescue medication and fewer visits to the emergency room during the study period. There were no differences in the number of exacerbations. The forced vital capacity (FVC) increased significantly in the treatment group and remained unchanged in the control group. The other measures of the pulmonary function showed no differences between groups. The airway hyperresponsiveness, exhaled nitric oxide levels and induced sputum cellularity did not change throughout the study. Leptin levels decreased in both groups. Serum levels of IgE, C-reactive protein, eotaxin, and TGF-1 did not change. CONCLUSION: Our study adds information to the controversy about the impact of obesity and its treatment on asthma control. Our results suggest that weight reduction in obese patients with severe asthma improves asthma outcomes by mechanisms not related to airway inflammation and that poor asthma control in people who are obese is at least in part the result of obesity-related factors. The therapeutic approach for obese patients with difficult-to-treat asthma should therefore be aimed at weight reduction as well as on intensifying antiinflammatory treatment

L’étude des marqueurs biologiques dans la broncho-pneumopathie chronique obstructive (BPCO) et l'asthme, deux maladies respiratoires chroniques affectant des millions de personnes dans le monde, pourrait améliorer leur diagnostic, leur traitement et leur prévention.Cette thèse comprend deux parties. La première visait à évaluer l'association entre un marqueur spécifique des poumons, la protéine surfactant D (SP-D) sérique, et la BPCO, et à trouver un seuil de SP-D capable de discriminer les patients BPCO des témoins. Elle a été réalisée dans le cadre d’une étude cas-témoin au Liban incluant des patients BPCO (n=90), des asthmatiques (n=124) et des témoins (n=180). La deuxième partie visait à évaluer les associations chez les adultes des marqueurs de l’inflammation systémique (protéine C-réactive ultra-sensible, hs-CRP (n=252), et des cytokines (n=283)) et des marqueurs de dommages dus au stress oxydant (8-isoprostanes 8-IsoPs (n=258) du condensat de l’air exhalé) avec les phénotypes de l’asthme.Elle a été réalisée dans le cadre de l'étude épidémiologique longitudinale Française des facteurs génétiques et environnementaux de l'asthme (EGEA).Les résultats ont montré que les niveaux de SP-D sériques étaient associés positivement avec la BPCO et des seuils des niveaux de SP-D chez ces patients ont été identifiés avec d'excellentes valeurs discriminantes. Dans EGEA, aucune association n'a été trouvée entre les niveaux de hs-CRP sériques et le contrôle de l’asthme. Des profils de cytokines sériques (identifiés par analyse en composante principale) avec des niveaux élevés d’interleukine(IL)-1Ra et d’IL-10 ont été associés avec moins de crises d'asthme et un risque plus faible d'un mauvais contrôle de l'asthme sept ans plus tard. Les résultats des analyses préliminaires sur les associations entre les niveaux de 8-IsoPs et les phénotypes de l'asthme sont également présentés.Globalement, ces résultats ont montré l'utilité d'étudier les marqueurs biologiques en lien avec la BPCO et l'asthme. / Studying the biological markers in chronic obstructive pulmonary disease (COPD) and asthma, two chronic respiratory diseases affecting millions of individuals around the world, could improve their diagnosis, their treatment and their prevention.This thesis includes two parts. The first aimed to assess the association between a lung-specific biomarker, serum Surfactant Protein D (SP-D), and COPD, and to find cut-off points able to discriminate COPD patients from controls using SP-D levels. It was performed in a case-control study in Lebanon including COPD (n=90) and asthma patients (n=124) and controls (n=180). The second part aimed to assess the cross-sectional and longitudinal associations in adults for systemic inflammatory biomarkers (high sensitivity C reactive protein hs-CRP (n=252) and cytokines (n=283) as well as biomarkers of damage due to oxidative stress (8-Isoprostanes 8-IsoPs (n=258) from the exhaled breath condensate) and asthma outcomes.It was performed in the French longitudinal epidemiological study on the genetics and environmental factors of asthma (EGEA).Results showed that serum SP-D levels were positively associated with COPD and thresholds for SP-D levels in these patients were identified with excellent discriminant values. In EGEA, no association was found between serum hs-CRP levels and asthma control. Serum cytokine profiles (identified by principal component analysis) with high levels of interleukin (IL)-1Ra and IL-10 were associated with less asthma attacks and lower risk of poor asthma control in adults seven years later. The results of the preliminary analyses on the associations between the levels of 8-IsoPs and asthma outcomes are also presented.Overall, these results have shown the usefulness of studying the biological markers related to COPD and asthma.