Exhaled breath condensate (EBC) is a non-invasive method of investigating airway inflammation associated with nitric oxide (NO) and the metabolites nitrite/nitrates (NOx) in diseases such as chronic obstructive pulmonary disease (COPD), but some of the variables affecting the results are unknown. It was hypothesised that 1) EBC would be influenced by lung volumes and the type of EBC collection device; 2) fractional exhaled NO (FENO) and EBC NOx in COPD patients would be altered by smoking and glucocorticosteroids (GCS); 3) cigarette smoke could contribute to the EBC NOx concentration while it may also decrease FENO indirectly by converting airway NO to NOx. It was found that EBC volume was significantly correlated with both tidal volume and minute volume. Comparing four EBC collection devices demonstrated greater efficiency with the ECoScreen?? than siliconised glass tubes or RTube?? but it gave factitiously high NOx levels. Total EBC protein levels over a 10-minute collection were significantly higher using the ECoScreen?? than either glass or RTube?? devices. A cross-sectional study of 96 COPD patients and 80 age-matched control subjects demonstrated that FENO levels in COPD patients were significantly higher than normal subjects when comparing either the combined groups or appropriate two subgroups: ex-smokers and smokers. GCS treatment demonstrated no significant effect on either FENO levels or EBC NOx, but EBC NOx was elevated in smokers. In vitro, cigarette smoke extract (CSE) induced significantly higher NOx and asymmetric dimethylarginine (ADMA) levels in A549 cells when compared with control media. The anti-oxidant, NAC pre-treatment partially reversed the elevated NOx levels but not the ADMA levels. This thesis is the first to report FENO and EBC NOx in COPD patients in an appropriate sample size to be able to evaluate each subgroup, and the increased EBC NOx levels found in smokers in vivo was consistent with the elevated NOx level in response to CSE observed in vitro. These data indicate that smoking-related airway inflammation and activation of the NO pathway are complex with both an increase in ADMA, NO, NOx and may be regulated by oxidative stress rather than the nitric oxide synthase (NOS) pathway.

<p>Two thirds of patients with diabetes avoid regularly monitoring their blood glucose levels because of the painful and invasive nature of current blood glucose detection. As an alternative to blood sample collection, exhaled breath condensate (EBC) has emerged as a promising non-invasive sample from which to monitor glucose levels. However, the inconsistency in the methods used to collect EBC significantly impacts the reliability of reported analyte concentrations in EBC. Furthermore, this dilute sample matrix requires a highly sensitive glucose biosensor to enable robust and accurate glucose detection at the point-of-care. Together, a reliable collection method and sensitive detection system can enable accurate modeling of glucose transport from blood to breath that is reflective of airway glucose homeostasis.</p> <p> I address this research gap by simultaneously designing a standardized EBC collection method that allows for separation of dead space and alveolar air and developing a competitive fluorescent biosensor that can resolve micromolar glucose concentrations changes. First, I develop a low-cost, automated condenser that selectively collects exhaled breath that has been exchanged with lung fluid based on the detection of higher breath temperatures that are characteristic of the lower respiratory regions. Using this device, I investigate the relationship between blood and EBC glucose in diabetic and normoglycemic human subjects. Next, I engineer the exquisitely sensitive <i>E. coli</i> glucose binding protein (GBP) with a chemo-enzymatic tag to selectively conjugate it to highly photostable quantum dots (QDs). Finally, I take advantage of the competitive binding of glucose (K_D=0.35 µM) and galactose (K_D=1.4 µM) to GBP to develop a fluorescent glucose biosensor using the GBP-QD conjugate.</p>

The aim of this study was to evaluate the relationship of oxidative stress (OS) marker s in exhaled breath condensate (EBC) in adult patients with cystic fibrosis (CF) to the severity of lung disease, nutritional status and systemic antioxidants and inflammatory markers, as well as to short - and medium - term development of pulmonary function and nutritional status, and finally to assess the response to treatment with inhaled corticosteroids (ICS). Methods: CF patients were examined in a stable phase of the disease during routine outpatient controls. EBC was collected using E C oScreen device (J aeger) in CF patients and in control group members. Nitrites and nitrates and 8 - isoprostane were examined using liquid chromatography and competitive enzyme immunoanalysis, respectively, in EBC as OS markers. Demographic data including the dominant pathogen of airway colonization and ICS treatment were recorded in CF patients. Lung function tests, chest X-ray s, nutritional statuses and systemic antioxidants and inflammatory markers were also examined using standard methods. The values of OS markers in EBC in patients with CF were compared with the control group and correlated to clinical parameters. Lung function tests and nutritional status es in CF patients were examined in one, three and five years intervals...

Exercise has become a vital component of the therapy regimen prescribed to cystic fibrosis (CF) patients due to its systemic benefits, such as increased sputum expectoration, attenuation of the expected 2-3% annual decline in pulmonary function, and extended life expectancy. However, exercise still is not viewed as being as beneficial as pharmacological treatments by many CF patients and can be intimidating. My aims in this study were two-fold; first, to determine the ideal exercise intensity for individuals with CF; and second, to determine if exercise at this ideal intensity could provide improvements in ion regulation in the lungs, which was measured using exhaled breath condensate (EBC) collection and nasal potential difference (NPD), that were comparable to one of their standard pharmacological therapies, albuterol. I hypothesized that with moderate intensity exercise, Na⁺ absorption would decrease from baseline due to Na⁺ channel inhibition, rather than increase or remain unchanged, as was expected with albuterol, and cause an even greater increase Cl- secretion compared to albuterol due to activation of both CF-dependent and independent Cl- efflux with exercise. CF (n=14) and healthy (n=16) subjects completed three visits, a baseline screening and two treatment visits. I collected EBC at baseline, 30- and 60-minutes post-albuterol administration on one visit, and at baseline and during three separate 15 min exercise bouts at low, moderate and high intensity on the other visit. Following the EBC collection, NPD was performed at 30- and 80-minutes post albuterol or following moderate and high intensity exercise. We also measured spirometry and diffusing capacity of the lungs for nitric oxide (DLNO) during each visit at the various time points. In CF subjects, moderate intensity exercise resulted in greater improvements in DLNO (39 ± 29vs.15 ± 22% change from baseline, exercise vs. albuterol respectively), similar levels of bronchodilation compared to 60-minutes post-albuterol administration, no change in Na⁺ absorption, and a four-fold increase in Cl- secretion. Our results suggest that moderate intensity exercise is the best dose for CF patients, and can provide comparable changes as its pharmacological counterpart albuterol, when compared over a short term duration.

Multiple biomarkers of oxidative stress have been measured and used in human medicine to diagnose and monitor airway disease. The purpose of the study was to determine if similar relationships existed between inflammatory and oxidative stress biomarkers in exhaled breath condensate (EBC), bronchoalveolar lavage fluid (BALF), red blood cells, white blood cells, and plasma; and cytokine expression in airway inflammatory cells and mucosal biopsies of RAO-affected horses and their controls. Sixteen horses in pairs were used: 8 non-RAO-affected (controls) and 8 RAO-affected horses. Samples from all horses were collected at remission (S1), during environmental challenge (S2) and at recovery (S3). RAO-affected horses had significant alterations in cellular glutathione peroxidase (cGPx) activity, ascorbic acid and pH in a number of biological samples. Concentrations of 8-isoprostanes, isofurans, amino acids and mRNA expression of interleukin 4 (IL4), gamma interferon (INFγ), inducible nitric oxide synthase (iNOS), extracellular glutathione peroxidase (GPx-3), and cytosolic superoxide dismutase (SOD-1) were not significantly different or were at the limits of detection. Conductivity was measured and assessed as a potential correctional factor for respiratory fluid dilution. The alterations in biomarker concentrations demonstrate that oxidative stress is an important component of airway inflammation in RAO-affected horses. Further research is warranted in the use of biomarkers and the effects of dietary interventions. / Master of Science

Introdução: As doenças cardíacas ou do aparelho circulatório são as principais causas de morte na população brasileira, sendo responsável por um terço dos óbitos. Embora o tratamento conservador seja amplamente adotado, grande parte das doenças cardiovasculares necessita e tem como tratamento a cirurgia cardíaca, da qual as mais comuns são a cirurgia de revascularização do miocárdio (CRVM) e de troca valvar. Atualmente existem diversos estudos avaliando a função pulmonar ou a capacidade funcional para o acompanhamento do tratamento conservador ou em situação pré-operatória, porém estudos avaliando e correlacionando essas variáveis no pré-cirúrgico são escassos na literatura científica não sendo possível averiguar a existência da relação entre os níveis de nitrito e nitrato e o desempenho nos testes de capacidade funcional. Objetivo: Avaliar a correlação nitrito/nitrato (NOx) do condensado do exalado pulmonar (CEP) e a distância caminhada nos testes de caminhada de 6 minutos (TC6) e shuttle walk test (SWT), além de verificar se a utilização de medicações contendo betabloqueadores, nitrato ou enzima conversora de angiotensina (IECA) podem influenciar nas concentrações de nitrito/nitrato no CEP e nas distâncias caminhadas no TC6 e no SWT e comparar seu comportamento entre valvopatas e coronariopatas no pré operatório de cirurgia cardíaca. Metodologia: Foram selecionados 73 pacientes, dos quais 28 eram coronariopatas e 45 valvopatas, de ambos os sexos, com idade entre 20 e 80 anos, feita coleta do CEP para análise do NOx e submetidos ao TC6 e ao SWT para avaliação da distância caminhada. Resultados: Na análise das concentrações de NOx do CEP não foi encontrada diferença estatisticamente significativa entre as medicações utilizadas via oral contendo nitrato (dinitrato de isossorbida), IECA (captopril ou enalapril) e/ou betabloqueador ou entre os pacientes do grupo coronariopata e grupo valvopata (p>0,05). Houve diferença estatisticamente significativa no TC6 nos valores de frequência cardíaca (FC) inicial, final e repouso e no valor referente à dispnéia final, e no SWT nos valores de FC inicial, final e repouso, na pressão arterial sistólica (PAS) inicial e no valor referente à dispnéia final entre os grupos coronariopata e valvopata. No entanto, foram interrompidos 4 TC6 e 7 SWT do grupo coronariopata devido ao desencadeamento de dor precordial, fato não ocorrido no grupo valvopata, apresentando nível de significância. A FC inicial e de repouso no TC6 e a FC final no SWT dos pacientes que não ingeriram nenhum medicamento antes do teste é diferente em relação à dos pacientes que fizeram uso de quaisquer medicamentos descritos antes do teste sugerindo a ação de medicamentos que modulam a FC como os betabloqueadores. Foi constatado correlação positiva moderada entre o NOx do CEP e os valores de PAS inicial e final de coronariopatas e correlação negativa fraca a moderada entre o NOx do CEP e os valores de FC final e de dispnéia final nos valvopatas no TC6, além da correlação positiva moderada entre o NOx do CEP e os valores de PAS inicial de indivíduos coronariopatas e correlação negativa fraca a moderada entre o NOx do CEP e os valores de FC inicial nos valvopatas no SWT. Foi identificado correlação negativa moderada na distância caminhada no TC6 e no SWT apenas nos indivíduos coronariopatas. Conclusões: Não foram identificadas influências do uso de medicações betabloqueadoras, nitrato ou IECA sobre a dosagem de NOx ou a distância caminhada em nenhum dos testes e em nenhum dos grupos, no entanto coronariopatas com níveis mais elevados de NOx apresentaram uma distância deambulada menor. / Introduction: Heart disease or circulatory system diseases are the leading causes of death in our population, accounting for one third of deaths. Although conservative treatment is widely adopted, part of cardiovascular disease treatment demands heart surgery, of which the most common are coronary artery bypass grafting (CABG) and valve replacement. Currently there are many studies evaluating lung function or functional capacity for monitoring of conservative treatment or preoperative situation, but studies assessing and correlating these variables in pre surgical are rare in the literature is not possible to ascertain the existence of the relationship between levels of nitrite and nitrate (NOx) in exhaled breath condensate (EBC) and performance in functional ability tests. Methods: were selected 73 patients, 28 with coronary artery diseas and 45 with heart valve disease of both genders, aged 20 to 80 years old. The EBC was collected for analysis of NOx and performed the six minutes walking test (6MWT) and shuttle walk test (SWT) to evaluate the distance walked. Results: the analysis of the concentrations of NOx in EBC has no statistically significant difference found between the medications used, such as oral nitrate (isosorbide dinitrate), ace inhibitors (captopril or enalapril) and/or beta-blockers in both coronary artery disease and heart valve disease (p> 0.05). There was a statistically significant difference in 6MWT for HR initial, final and rest and final dyspnea, and in SWT for HR initial, final and rest, the initial SBP and the final dyspnea between the coronary artery disease e heart valve disease. However, were interrupted 4 6MWT and 7 SWT from coronary artery disease related to chest pain, this fact was not related in patients with valve disease, presenting a significance level. The initial and resting HR during the 6MWT and in SWT final HRr patients not ingesting any medication before the test is different from patients who used any medications before the test, suggesting the action of drugs that modulate the HR, such as beta blockers. Moderate positive correlation was found between the NOx in EBC and SBP initial and final in coronary disease and weak to moderate correlation between the NOx in EBC and final HR and final dyspnea in 6MWT from heart valve disease. Besides the positive moderate correlation between NOx in the EBC and the SBP initial in coronary disease during 6MWT and weak to moderate negative correlation between NOx in the EBC and the HR initial in valve disease during SWT. Moderate negative correlation was identified in the distance walked during the 6MWT and SWT only between individuals with coronary artery disease. Conclusions: the use of beta-blocker drugs, ace inhibitors or nitrate evidenciates no influence on the NOx or on the distance walked in any tests, and none of the groups, however, individuals with coronary artery disease showed higher NOx levels and performed lower distance walked.

Introdução: As doenças cardíacas ou do aparelho circulatório são as principais causas de morte na população brasileira, sendo responsável por um terço dos óbitos. Embora o tratamento conservador seja amplamente adotado, grande parte das doenças cardiovasculares necessita e tem como tratamento a cirurgia cardíaca, da qual as mais comuns são a cirurgia de revascularização do miocárdio (CRVM) e de troca valvar. Atualmente existem diversos estudos avaliando a função pulmonar ou a capacidade funcional para o acompanhamento do tratamento conservador ou em situação pré-operatória, porém estudos avaliando e correlacionando essas variáveis no pré-cirúrgico são escassos na literatura científica não sendo possível averiguar a existência da relação entre os níveis de nitrito e nitrato e o desempenho nos testes de capacidade funcional. Objetivo: Avaliar a correlação nitrito/nitrato (NOx) do condensado do exalado pulmonar (CEP) e a distância caminhada nos testes de caminhada de 6 minutos (TC6) e shuttle walk test (SWT), além de verificar se a utilização de medicações contendo betabloqueadores, nitrato ou enzima conversora de angiotensina (IECA) podem influenciar nas concentrações de nitrito/nitrato no CEP e nas distâncias caminhadas no TC6 e no SWT e comparar seu comportamento entre valvopatas e coronariopatas no pré operatório de cirurgia cardíaca. Metodologia: Foram selecionados 73 pacientes, dos quais 28 eram coronariopatas e 45 valvopatas, de ambos os sexos, com idade entre 20 e 80 anos, feita coleta do CEP para análise do NOx e submetidos ao TC6 e ao SWT para avaliação da distância caminhada. Resultados: Na análise das concentrações de NOx do CEP não foi encontrada diferença estatisticamente significativa entre as medicações utilizadas via oral contendo nitrato (dinitrato de isossorbida), IECA (captopril ou enalapril) e/ou betabloqueador ou entre os pacientes do grupo coronariopata e grupo valvopata (p>0,05). Houve diferença estatisticamente significativa no TC6 nos valores de frequência cardíaca (FC) inicial, final e repouso e no valor referente à dispnéia final, e no SWT nos valores de FC inicial, final e repouso, na pressão arterial sistólica (PAS) inicial e no valor referente à dispnéia final entre os grupos coronariopata e valvopata. No entanto, foram interrompidos 4 TC6 e 7 SWT do grupo coronariopata devido ao desencadeamento de dor precordial, fato não ocorrido no grupo valvopata, apresentando nível de significância. A FC inicial e de repouso no TC6 e a FC final no SWT dos pacientes que não ingeriram nenhum medicamento antes do teste é diferente em relação à dos pacientes que fizeram uso de quaisquer medicamentos descritos antes do teste sugerindo a ação de medicamentos que modulam a FC como os betabloqueadores. Foi constatado correlação positiva moderada entre o NOx do CEP e os valores de PAS inicial e final de coronariopatas e correlação negativa fraca a moderada entre o NOx do CEP e os valores de FC final e de dispnéia final nos valvopatas no TC6, além da correlação positiva moderada entre o NOx do CEP e os valores de PAS inicial de indivíduos coronariopatas e correlação negativa fraca a moderada entre o NOx do CEP e os valores de FC inicial nos valvopatas no SWT. Foi identificado correlação negativa moderada na distância caminhada no TC6 e no SWT apenas nos indivíduos coronariopatas. Conclusões: Não foram identificadas influências do uso de medicações betabloqueadoras, nitrato ou IECA sobre a dosagem de NOx ou a distância caminhada em nenhum dos testes e em nenhum dos grupos, no entanto coronariopatas com níveis mais elevados de NOx apresentaram uma distância deambulada menor. / Introduction: Heart disease or circulatory system diseases are the leading causes of death in our population, accounting for one third of deaths. Although conservative treatment is widely adopted, part of cardiovascular disease treatment demands heart surgery, of which the most common are coronary artery bypass grafting (CABG) and valve replacement. Currently there are many studies evaluating lung function or functional capacity for monitoring of conservative treatment or preoperative situation, but studies assessing and correlating these variables in pre surgical are rare in the literature is not possible to ascertain the existence of the relationship between levels of nitrite and nitrate (NOx) in exhaled breath condensate (EBC) and performance in functional ability tests. Methods: were selected 73 patients, 28 with coronary artery diseas and 45 with heart valve disease of both genders, aged 20 to 80 years old. The EBC was collected for analysis of NOx and performed the six minutes walking test (6MWT) and shuttle walk test (SWT) to evaluate the distance walked. Results: the analysis of the concentrations of NOx in EBC has no statistically significant difference found between the medications used, such as oral nitrate (isosorbide dinitrate), ace inhibitors (captopril or enalapril) and/or beta-blockers in both coronary artery disease and heart valve disease (p> 0.05). There was a statistically significant difference in 6MWT for HR initial, final and rest and final dyspnea, and in SWT for HR initial, final and rest, the initial SBP and the final dyspnea between the coronary artery disease e heart valve disease. However, were interrupted 4 6MWT and 7 SWT from coronary artery disease related to chest pain, this fact was not related in patients with valve disease, presenting a significance level. The initial and resting HR during the 6MWT and in SWT final HRr patients not ingesting any medication before the test is different from patients who used any medications before the test, suggesting the action of drugs that modulate the HR, such as beta blockers. Moderate positive correlation was found between the NOx in EBC and SBP initial and final in coronary disease and weak to moderate correlation between the NOx in EBC and final HR and final dyspnea in 6MWT from heart valve disease. Besides the positive moderate correlation between NOx in the EBC and the SBP initial in coronary disease during 6MWT and weak to moderate negative correlation between NOx in the EBC and the HR initial in valve disease during SWT. Moderate negative correlation was identified in the distance walked during the 6MWT and SWT only between individuals with coronary artery disease. Conclusions: the use of beta-blocker drugs, ace inhibitors or nitrate evidenciates no influence on the NOx or on the distance walked in any tests, and none of the groups, however, individuals with coronary artery disease showed higher NOx levels and performed lower distance walked.

Angesichts der nach wie vor hohen Mortalität und Morbidität des Bronchialkarzinoms ist die Entwicklung geeigneter Methoden zur früheren Diagnostik eine wichtige Notwendigkeit, um die geringe durchschnittliche 5-Jahres-Überlebensrate von 15% – 18% zu steigern. Unter diesem Gesichtspunkt wurde in der vorliegenden Arbeit das Atemkondensat von Patienten mit Bronchialkarzinom als nicht-invasiv und kostengünstig zu gewinnendes Medium auf das Vorliegen eines potentiellen Screeningmarkers – dem methylierten Tumorsuppressor-Gen p16 – untersucht. Dazu wurde ein Versuchsablauf entwickelt, bei dem trotz des geringen DNA-Gehaltes im Atemkondensat p16-Methylierungen nachgewiesen werden konnten. Die letztendlich etablierte Methode war eine methylierungsspezifische nested-PCR mit anschließendem Restriktionsverdau durch das Restriktionsenzym BstUI. Des Weiteren erfolgte die Untersuchung von in Paraffin eingebetteten Tumorpräparaten der Patienten. In der anschließenden statistischen Auswertung wurde der Einfluss von verschiedenen Faktoren wie COPD-Grad, Tumorlage, Tumorart, Nikotinabusus und stattgehabte Chemo- oder Strahlentherapie auf den Methylierungsstatus des p16-Gens analysiert.

Lúpus eritematoso sistêmico juvenil é uma doença inflamatória autoimune multifatorial com elevação de citocinas inflamatórias e com gravidade variável. Estudos observaram associação entre exposição a poluição do ar e aumento do número de internações hospitalares devido à exacerbação das doenças reumáticas pediátricas e aumento no risco de crianças portadoras de lúpus eritematoso sistêmico juvenil apresentarem atividade de doença moderada /grave após exposição a material particulado e dióxido de nitrogênio. Exposição à poluição do ar pode acarretar agravo agudo em doenças reumatológicas pediátricas, incluindo lúpus eritematoso sistêmico juvenil. Objetivos: Avaliar o efeito da exposição real a poluentes atmosféricos sobre biomarcadores inflamatórios em condensado do ar exalado e sobre a fração de monóxido de nitrogênio em ar exalado em pacientes com lúpus eritematoso sistêmico juvenil. Avaliar ainda, a correlação entre os biomarcadores inflamatórios no ar exalado e atividade da doença. Métodos: Estudo longitudinal de painel de medidas repetidas realizado em 108 visitas consecutivas de pacientes com diagnóstico de lúpus eritematoso sistêmico juvenil sem doenças respiratórias. Por 4 semanas consecutivas, medidas diárias individuais de dióxido de nitrogênio, material particulado fino, temperatura ambiental e humidade relativa do ar foram obtidos. Este ciclo foi repetido a cada 2,5 meses ao longo de um ano, além disso, citocinas do condensado do ar exalado (interleucinas 6, 8, 17 e fator de necrose tumoral-alfa), fração exalada de monóxido de nitrogênio e parâmetros de atividade de doença foram coletados semanalmente. Modelos específicos de equação estimada generalizada foram usadas para avaliar o impacto destes poluentes no risco de Systemic Lupus Erythematosus Disease Activity Index 2000 >= 8, citocinas no condensado do ar exalado e fração exalada de monóxido de nitrogênio, considerando o efeito fixo para medidas repetidas. Os modelos foram ajustados para provas de fase aguda, índice de massa corpórea, infecções, medicações e variáveis meteorológicas. Resultados: Efeito positivo nas medidas de desfechos foi observado para um aumento do intervalo interquartil do material particulado fino (18.12 ?g/m3). Um aumento do intervalo interquartil na média móvel de 7 dias no material particulado fino (lag0 to lag6) foi associado a um aumento de 0.1pg/ml (95%IC:0.01;0.19) e 0.9pg/ml (95%IC:0.05;0,12) nos níveis de interleucina 17 e fator de necrose tumoral-? do condensado do ar exalado, respectivamente. Também foi observado um aumento no risco de Systemic Lupus Erythematosus Disease Activity Index 2000 >= 8 de 1.47(95%CI:1.10;1.84) associado ao aumento da média móvel de material particulado fino. Em adição, um efeito a curto prazo na fração exalada de monóxido de nitrogênio foi evidenciado, medida móvel de 3 dias do material particulado fino foi associada com um aumento de 0.75ppb (95%IC:0.38;1.29) na fração exalada de monóxido de nitrogênio. Conclusão: Exposição a partículas finas inaláveis pode aumentar a inflamação das vias aéreas e posterior inflamação sistêmica nos pacientes com lúpus eritematoso sistêmico juvenil / Systemic lupus erythematosus is an inflammatory multisystem, autoimmune disease with elevated inflammatory interleukins levels. Exposure to air pollution may trigger pulmonary inflammation/systemic inflammation. Objective: The objective of this study was to investigate the association between daily individual exposure to air pollutants and airway inflammation and disease activity in childhood-onset systemic lupus erythematosus patients. A longitudinal panel study was carried out in 108 consecutive appointments with childhood-onset systemic lupus erythematosus patients without respiratory diseases. Methods: Over four consecutive weeks, daily individual measures of nitrogen dioxide, fine particulate matter, ambient temperature, and humidity were obtained. This cycle was repeated every 2.5 months along 1 year, and cytokines of exhaled breath condensate (interleukins 6, 8, 17 and tumoral necrose factor-alpha), fractional exhaled nitrogen monoxide, and disease activity parameters were collected weekly. Specific generalized estimation equation models were used to assess the impact of these pollutants on the risk of Systemic Lupus Erythematous Disease Activity Index 2000 >= 8, exhaled breath condensate cytokines, and fractional exhaled nitrogen monoxide, considering the fixed effects for repetitive measurements. The models were adjusted for inflammatory indicators, body mass index, infections, medication, and weather variables. Results: An interquartile range increase in fine particulate matter 4-day moving average (18.12ug/m3) was associated with an increase of 0.05 pg/ml (95% CI 0.01; 0.09, p = 0.03) and 0.04 pg/ml (95% CI 0.02; 0.06, p = 0.01) in interleukin 17 and tumoral necrosis factor-alpha exhaled breath condensate levels, respectively. Additionally, a short-term effect on fractional exhaled nitrogen monoxide was observed: the fine particulate matter 3-day moving average was associated with a 0.75 ppb increase (95% CI 0.38; 1.29, p = 0.03) in fractional exhaled nitrogen monoxide. Also, an increase of 1.47 (95% CI 1.10; 1.84) in the risk of Systemic Lupus Erythematous Disease Activity Index 2000 >= 8 was associated with fine particulate matter 7-day moving average. Conclusion: Exposure to inhalable fine particles increases airway inflammation/pulmonary and then systemic inflammation in childhood-onset systemic lupus erythematosus patients

Lúpus eritematoso sistêmico juvenil é uma doença inflamatória autoimune multifatorial com elevação de citocinas inflamatórias e com gravidade variável. Estudos observaram associação entre exposição a poluição do ar e aumento do número de internações hospitalares devido à exacerbação das doenças reumáticas pediátricas e aumento no risco de crianças portadoras de lúpus eritematoso sistêmico juvenil apresentarem atividade de doença moderada /grave após exposição a material particulado e dióxido de nitrogênio. Exposição à poluição do ar pode acarretar agravo agudo em doenças reumatológicas pediátricas, incluindo lúpus eritematoso sistêmico juvenil. Objetivos: Avaliar o efeito da exposição real a poluentes atmosféricos sobre biomarcadores inflamatórios em condensado do ar exalado e sobre a fração de monóxido de nitrogênio em ar exalado em pacientes com lúpus eritematoso sistêmico juvenil. Avaliar ainda, a correlação entre os biomarcadores inflamatórios no ar exalado e atividade da doença. Métodos: Estudo longitudinal de painel de medidas repetidas realizado em 108 visitas consecutivas de pacientes com diagnóstico de lúpus eritematoso sistêmico juvenil sem doenças respiratórias. Por 4 semanas consecutivas, medidas diárias individuais de dióxido de nitrogênio, material particulado fino, temperatura ambiental e humidade relativa do ar foram obtidos. Este ciclo foi repetido a cada 2,5 meses ao longo de um ano, além disso, citocinas do condensado do ar exalado (interleucinas 6, 8, 17 e fator de necrose tumoral-alfa), fração exalada de monóxido de nitrogênio e parâmetros de atividade de doença foram coletados semanalmente. Modelos específicos de equação estimada generalizada foram usadas para avaliar o impacto destes poluentes no risco de Systemic Lupus Erythematosus Disease Activity Index 2000 >= 8, citocinas no condensado do ar exalado e fração exalada de monóxido de nitrogênio, considerando o efeito fixo para medidas repetidas. Os modelos foram ajustados para provas de fase aguda, índice de massa corpórea, infecções, medicações e variáveis meteorológicas. Resultados: Efeito positivo nas medidas de desfechos foi observado para um aumento do intervalo interquartil do material particulado fino (18.12 ?g/m3). Um aumento do intervalo interquartil na média móvel de 7 dias no material particulado fino (lag0 to lag6) foi associado a um aumento de 0.1pg/ml (95%IC:0.01;0.19) e 0.9pg/ml (95%IC:0.05;0,12) nos níveis de interleucina 17 e fator de necrose tumoral-? do condensado do ar exalado, respectivamente. Também foi observado um aumento no risco de Systemic Lupus Erythematosus Disease Activity Index 2000 >= 8 de 1.47(95%CI:1.10;1.84) associado ao aumento da média móvel de material particulado fino. Em adição, um efeito a curto prazo na fração exalada de monóxido de nitrogênio foi evidenciado, medida móvel de 3 dias do material particulado fino foi associada com um aumento de 0.75ppb (95%IC:0.38;1.29) na fração exalada de monóxido de nitrogênio. Conclusão: Exposição a partículas finas inaláveis pode aumentar a inflamação das vias aéreas e posterior inflamação sistêmica nos pacientes com lúpus eritematoso sistêmico juvenil / Systemic lupus erythematosus is an inflammatory multisystem, autoimmune disease with elevated inflammatory interleukins levels. Exposure to air pollution may trigger pulmonary inflammation/systemic inflammation. Objective: The objective of this study was to investigate the association between daily individual exposure to air pollutants and airway inflammation and disease activity in childhood-onset systemic lupus erythematosus patients. A longitudinal panel study was carried out in 108 consecutive appointments with childhood-onset systemic lupus erythematosus patients without respiratory diseases. Methods: Over four consecutive weeks, daily individual measures of nitrogen dioxide, fine particulate matter, ambient temperature, and humidity were obtained. This cycle was repeated every 2.5 months along 1 year, and cytokines of exhaled breath condensate (interleukins 6, 8, 17 and tumoral necrose factor-alpha), fractional exhaled nitrogen monoxide, and disease activity parameters were collected weekly. Specific generalized estimation equation models were used to assess the impact of these pollutants on the risk of Systemic Lupus Erythematous Disease Activity Index 2000 >= 8, exhaled breath condensate cytokines, and fractional exhaled nitrogen monoxide, considering the fixed effects for repetitive measurements. The models were adjusted for inflammatory indicators, body mass index, infections, medication, and weather variables. Results: An interquartile range increase in fine particulate matter 4-day moving average (18.12ug/m3) was associated with an increase of 0.05 pg/ml (95% CI 0.01; 0.09, p = 0.03) and 0.04 pg/ml (95% CI 0.02; 0.06, p = 0.01) in interleukin 17 and tumoral necrosis factor-alpha exhaled breath condensate levels, respectively. Additionally, a short-term effect on fractional exhaled nitrogen monoxide was observed: the fine particulate matter 3-day moving average was associated with a 0.75 ppb increase (95% CI 0.38; 1.29, p = 0.03) in fractional exhaled nitrogen monoxide. Also, an increase of 1.47 (95% CI 1.10; 1.84) in the risk of Systemic Lupus Erythematous Disease Activity Index 2000 >= 8 was associated with fine particulate matter 7-day moving average. Conclusion: Exposure to inhalable fine particles increases airway inflammation/pulmonary and then systemic inflammation in childhood-onset systemic lupus erythematosus patients