This thesis is based around examination of three mainstream inhaled drugs Formoterol, Budesonide and Beclomethasone for treatment of asthma and COPD. The areas investigated are these which have been raised in reports and studies, where there are concern, for drug use and assessment of their use. In reporting this work the literature study sets out a brief summary of the background and anatomy and physiology of the respiratory system and then discuses the mechanism of drug deposition in the lung, as well as the methods of studying deposition and pulmonary delivery devices. This section includes the basis of asthma and COPD and its treatment. In addition, a short section is presented on the role of the pharmacist in improving asthma and COPD patient¿s care. Therefore the thesis is divided into 3 parts based around formoterol, budesonide and beclomethasone. In the first case the research determines the in-vitro performance of formoterol and budesonide in combination therapy. In the initial stage a new rapid, robust and sensitive HPLC method was developed and validated for the simultaneous assay of formoterol and the two epimers of budesonide which are pharmacologically active. In the second section, the purpose was to evaluate the aerodynamic characteristics for a combination of formoterol and the two epimers of budesonide at inhalation flow rates of 28.3 and 60 L/min. The aerodynamic characteristics of the emitted dose were measured by an Anderson cascade impactor (ACI) and the next generation cascade impactor (NGI). In all aerodynamic characterisations, the differences between flow rates 28.3 and 60 were statistically significant in formoterol, budesonide R and budesonide S, while the differences between ACI and NGI at 60 were not statistically significant. Spacers are commonly used especially for paediatric and elderly patients. However, there is considerable discussion about their use and operation. In addition, the introduction of the HFAs propellants has led to many changes in the drug formulation characteristics. The purpose of the last section is to examine t h e performance of different types of spacers with different beclomethasone pMDIs. Also, it was to examine the hypothesis of whether the result of a specific spacer with a given drug/ brand name can be extrapolated to other pMDIs or brand names for the same drug. The results show that there are different effects on aerodynamic characterisation and there are significant differences in the amount of drug available for inhalation when different spacers are used as inhalation aids. Thus, the study shows that the result from experiments with a combination of a spacer and a device cannot be extrapolated to other combination.

No description available.

Anlässlich eines richterlichen Gutachtenauftrages zur Frage, ob das Tragen von Mund-Nase-Schutzmasken zu einer Verfälschung des Atemalkoholmesswertes zuungunsten des Angeklagten führen kann, erfolgte unter Pandemiebedingungen eine experimentelle Testreihe an 6 gesunden Proband*innen (4 Männer, 2 Frauen), die risikoarmen Freizeitalkoholkonsum betrieben. Pro Untersuchungstag wurde jeweils ein Maskentyp (Op.-Maske, Textilmaske, FFP2-Maske) untersucht. Nach Aufnahme einer individuell berechneten Menge Alkohol und einer 30-minütigen Resorptionsphase erfolgten in halbstündigen Abständen 6 aufeinanderfolgende Atemalkoholmessungen, wobei zwischen den Messungen jeweils im Wechsel eine der Masken oder keine Maske getragen wurde. Anschließend wurden Wertepaare für Zeiträume mit und ohne Maske gebildet und die stündlichen Atemalkoholabbauraten berechnet. Im Ergebnis unterschieden sich die Atemalkoholabbauraten mit und ohne Masken nicht voneinander. Fehlermeldungen durch das Atemalkoholmessgerät, die auf das vorherige Tragen einer Maske zurückzuführen sind, traten nicht auf.

Breathing is not a common subject in feminist studies. Breathing Matters introduces this phenomenon as a forceful potentiality for feminist intersectional theories, politics, and social and environmental justice. By analyzing the material and discursive as well as the natural and cultural enactments of breath in black lung disease, phone sex work, and anxieties and panic attacks, Breathing Matters proposes a nonuniversalizing and politicized understanding of embodiment. In this approach, human bodies are onceptualized as agential actors of intersectional politics. Magdalena Górska argues that struggles for breath and for breathable lives are matters of differential forms of political practices in which vulnerable and quotidian corpomaterial and corpo-affective actions are constitutive of politics. Set in the context of feminist poststructuralist and new materialist and postconstructionist debates, Breathing Matters offers a discussion of human embodiment and agency reconfigured in a posthumanist manner. Its interdisciplinary analytical practice demonstrates that breathing is a phenomenon that is important to study from scientific, medical, political, environmental and social perspectives. / Andning är inte ett vanligt förekommande ämne inom feministiska studier. Breathing Matters introducerar detta fenomen som har en potential för feministiska intersektionella teorier, politik, social rättvisa och klimaträttvisa. Genom analyser av materiella, diskursiva, naturliga och kulturella dimensioner av andningens formationer, i sjukdomen pneumokonios, telefonsexarbete samt ångest och panikattacker, föreslår Breathing Matters en icke-universialiserande och politiserad förståelse av förkroppsligande. Genom denna ansats konceptualiseras mänskliga kroppar som agentiella aktörer i en intersektionell politik. Magdalena Górska argumenterar att kampen för att andas och för andningsbara liv är ett angeläget ämne för differentiella former av politisk praktik. Denna sårbara och vardagliga praktik som både består av kroppsmateriella och kroppsaffektiva handlingar konstituerar politik. Placerad i en kontext av feminist poststrukturalistisk, nymaterialistisk och postkonstruktivistisk debatt erbjuder Breathing Matters en diskussion kring mänskligt förkroppsligande och agentskap som är omkonfigurerad på ett posthumanistiskt sätt. Den tvärvetenskapliga analytiska praktiken visar att andning är ett fenomen som är viktigt att studera från vetenskapliga, medicinska, politiska, miljömässiga och sociala perspektiv.

A potencialidade do eletrodo de cobre em meio alcalino foi demonstrada para o determinação de etanol a +0,6 V vs Ag/AgCl. A participação de espécies solúveis de Cu(III) no processo eletrocatalítico envolvendo a oxidação do etanol foi demonstrada por experimentos utilizando eletrodo disco-anel. A influência do potencial de pré-tratamento no sinal anódico foi investigada e correlacionada com a morfologia dos filmes formados na superfície do eletrodo por EDS (Energy Dispersive X-Ray Spectroscopy), indicando que as espécies de Cu(III) são originadas a partir da oxidação da camada de CuO. As medidas de etanol foram realizadas por amperometria em 0,6 V (vs Ag/AgCl). A repetibilidade das medidas utilizando padrão aquoso de etanol 0,05 % (v/v) foi de 3 % (v/v) e os limites de detecção e quantificação foram de 0,005 % (v/v) e 0,01 % (v/v), respectivamente. Nas condições experimentais otimizadas, o sensor amperométrico foi utilizado para o monitoramento da concentração de etanol no ar exalado (BrAC), que foi convenientemente coletado em um balão de borracha (V = 3 L) e introduzido em uma solução de NaOH 1 mol L-1 (V = 10 mL). O sensor apresentou uma faixa linear para concentrações de etanol em ar exalado na faixa de 0,26 – 130 mg L-1, operando de acordo com os parâmetros analíticos especificados na Legislação Brasileira para a quantificação de etanol no ar exalado em condutores de veículos automotores. A constante de eliminação de etanol do corpo humano também foi investigada e os resultados concordaram com os valores da literatura. Empregando-se eletrodos de Cu e Au foram também desenvolvidas outras metodologias para a quantificação de dipirona, glicose e ácido ascórbico e sistemas em fluxo. Estudos sobre o desenvolvimento e propriedades de um sistema gerador-coletor foram realizados e o dispositivo foi utilizado em titulações de substâncias redutoras com iodo gerado eletroquimicamente. / A copper disc working electrode in alkaline solutions was demonstrated to act as a suitable amperometric sensor for ethanol determination at +0.6 V vs Ag/AgCl. The participation of free-soluble Cu(III) species in the electrocatalytic process involving the anodic oxidation of ethanol has been demonstrated by rotating ring-disc electrode voltammetry. The influence of the pretreatment potential on the anodic signal was investigated and a correlation with the morphology of the electrode surface characterized by Energy Dispersive X-Ray Spectroscopy (EDS) indicated that the Cu(III) species is originated from the oxidation of a CuO layer. Ethanol measurements were performed in the amperometric mode at 0.6 V (vs Ag/AgCl). The repeatability of the measurements for a 0.05 % aqueous ethanol solution was estimated as 3 %, and the detection and quantification limits were determined as 0.005 % and 0.01 %, respectively. At the optimum experimental conditions, the amperometric sensor was used to monitor the concentration of ethanol in breath (BrAC), which was conveniently collected in a rubber air balloon (volume = 3 L) and introduced in a 1 mol L-1 NaOH working solution (volume = 10 mL). The sensor can measure a person\'s breath ethanol over the concentration range 0.26 - 130 mg L-1 by operating it according to an established protocol, of which the analytical parameters are specified by the Brazilian Legislation for BrAC measurements in drivers. The rate of ethanol degradation in the body was followed, and the results agree with predictions in the literature. Methodologies for the determination of dipyrone, glucose and ascorbic acid were also developed by using Cu and Au electrodes. Features of a dual-band electrochemical cell were investigated towards the development of a generator-collector system, which was employed in titrations with electrogenerated iodine.

Avaliamos as mudanças no padrão respiratório, movimento toracoabdominal e ventilação em portadores de DPOC e indivíduos sadios. Estudou-se 45 indivíduos entre 45 e 75 anos conforme o VEF1. Utilizou-se sistemas de pletismografia respiratória por indutância, análise metabólica de gases em posição semi-sentada ao repouso e radiografia de tórax para a mobilidade diafragmática. Os grupos DPOC apresentaram redução do TI, TTOT, aumento do VC/TI, f, VE, das relações VEM/VC, VE/VO2, VE/VCO2 e diminuição da SpO2. Redução da mobilidade do diafragma e aumento da VEM/VC associaram-se à ineficiência da ventilação e a alterações no modelo ventilatório utilizado, sem alterações no movimento toracoabdominal. / We assessed changes in breathing patterns, thoracoabdominal movement and ventilation in COPD sufferers and healthy individuals. Forty-five individuals between 45 and 75 were grouped by FEV1. Inductive plethysmographic equipment, respiratory metabolism measuring (with subject at rest in semi-recumbent position), and radiographic measurement of diaphragm mobility were used. The COPD groups presented reduction in TI and TTOT and increased VT/TI, f, VE, and VD/VT, VE/VO2, VE/VCO2 and decreased SpO2. Reduction in diaphragm mobility and increase of VEM/VC were associated with ventilatory inefficiency and alterations in the ventilatory model used. No alterations in thoracoabdominal movement

Ein nicht-invasiver Atemtest zur Lungenkrebsdetektion setzt Kenntnis über lungenkrebsspezifische Substanzen voraus. Die Identifizierung von Lungenkrebsbiomarkern in der Atemluft war das Ziel dieser Arbeit. Leichtflüchtige organische Substanzen (VOC) wurden als Zielkomponenten ausgewählt. Für die VOC-Analytik wurde eine SPME-GC-MS-Methode entwickelt und sowohl auf Modellsysteme als auch auf Realproben angewendet. Drei Lungenadenokarzinomzelllinien wurden in-vitro untersucht. Die VOC-Analyse wurde mit drei verschiedenen Probenahmestrategien durchgeführt und es war ein deutlicher Hintergrundeinfluss der eingesetzten Einwegzellkulturflaschen auf das analysierte VOC-Profil feststellbar. Trotzdem konnten signifikante Unterschiede zwischen Tumorzellen und zellfreien Nährmedien beobachtet werden: 1-Propanol wurde von den Zellen produziert, während der Gehalt einiger Aldehyde sank. Die eingeschränkte Ähnlichkeit des gewählten Zellkulturmodells mit realen Atemluftproben bedingt eine geringe Eignung dieser Ergebnisse für die Biomarkerableitung. Ein Gasmodell auf Basis angefeuchteter, synthetischer Luft wurde als Grundlage für die qualitätsgesicherte, quantitative VOC-Analyse der realen Atemluftproben konzipiert. Diese Modellluft wurde mit 24 Zielsubstanzen (Alkane, Aromaten, sauerstoffhaltige Spezies) sowie 3 Matrix-VOC mit starker Dominanz in den Atemluftproben (Isopren, Aceton, 2-Propanol) angereichert. In Kooperation mit zwei Berliner Kliniken wurden 37 Atemluftproben von Lungenkrebspatienten und 23 Proben von Gesunden gesammelt. Die Anwendung von 1-Butanol als univariater Marker erlaubt eine Erkennung von Lungenkrebs mit einer Sensitivität von 92% und Spezifität von 78%. Durch lineare Diskriminanzanalyse konnte ein Set aus 4 VOC (1-Butanol, 2-Butanon, 2-Pentanon, n-Hexanal) ermittelt werden, welches ebenfalls eine Sensitivität von 92% und mit 87% eine höhere Spezifität aufwies. Gegebenenfalls handelt es sich bei diesen Substanzen jedoch nur um allgemeine Krankheitsmarker. / A non-invasive breath test for lung cancer detection would be favorable but knowledge on lung cancer specific substances is required. This work aims at the identification of potential lung cancer biomarkers in breath. Volatile organic compounds (VOC) were chosen as targets and a SPME-GC-MS method was developed to analyze the VOC profiles of model systems and real samples. Three lung adenocarcinoma cell lines were investigated in-vitro. The VOC analysis, carried out with 3 different sampling strategies, was influenced by the VOC background of the used disposable culture vessels. Changes in the VOC profiles of cell lines compared to cell-free culture media were obvious: 1-propanol was released by the tumor cells whereas the content of some aldehydes was diminished. The similarity of this model system with real breath samples of lung cancer patients was seen to be insignificant. Consequently, these cell cultures were not suitable for biomarker identification. A gaseous model consisting of humidified synthetic air was developed. It was fortified with 24 target VOC (alkanes, aromatics and oxygenated species) as well as 3 matrix compounds (isoprene, acetone and 2-propanol) dominating patients’ VOC profiles in breath. This model was used for the quality assured quantitative VOC analysis in real breath samples. In cooperation with two hospitals 37 single mixed expiratory breath samples from lung cancer patients and 23 from healthy controls were collected. Applying 1-butanol as an univariate biomarker patients and controls were discriminated with a sensitivity of 92% and a specificity of 78%. Linear discriminant analysis displayed a set of 4 VOC (1-butanol, 2-butanone, 2-pentanone, n-hexanal) with similar sensitivity but higher specificity of 87%. However, these potential biomarkers might rather be a consequence of illness in general.

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

Hippocrates predicted many years ago that breath could tell something related with our health. On his treaties, he indicated that when the body starts moving after sleeping, and breathe with more frequency, something hot and acid is expelled with air. It is possible to predict a disease from breath, but it has not been until recent years that last developments in breath analysis has allowed to detect compounds precisely and to associate the presence of these compounds to certain diseases. The use of breath analysis in clinical diagnosis and exposure to contaminants presents great advantages as this is a non-invasive technique, compared with other techniques such as blood or urine analyses. Two new instrumental methodologies have been developed in the present thesis, which are based on adsorbent micro-traps, specifically designed for the analysis of volatile compounds in breath and environmental samples. These equipments are versatile and low cost, compared to other commercially available instrumentations. One of the methodologies developed has been designed for the analysis volatile compounds in breath samples, showing efficiency and resolutions unknown up to know. It has allowed detecting exposure to volatile contaminants in a range of concentrations that the current techniques cannot achieve. The second equipment has been developed for the analysis of the same contaminants in other biological matrixes, in this case blood. It has been used to assess the mechanism followed by the inhaled compounds when entering the human body. These new methodologies were evaluated in different exposure studies. 2,5-dimethylfurean was detected with a high sensitivity and allowed to determine the smoking habits of a wide group of individuals, also 48 hours after smoking. The levels of contamination due environmental tobacco smoke were also evaluated in different environments. The high sensitivity of the developed techniques allowed us to demonstrate the contamination of passive smokers by environmental tobacco smoke (ETS) after few hours of being in contact with. Breath levels of the smoking biomarker after few hours in contact with ETS where at the same level that those found in smokers who smoke few cigarettes per day / Que l’alè ens deia alguna cosa de la nostra salut ja ho va intuir Hipòcrates. Al Tractat Mèdic hi va escriure: “Així, doncs, quan el cos es posa en moviment després de dormir i respira amb més freqüència, quelcom calent i àcid és expulsat amb l’aire. D’això en venen malalties si hom no pren precaucions.” Sí, de l’olor de l’alè s’intuïen malalties però no ha estat fins als darrers anys, que els nous avanços en les tècniques d’anàlisi no han proporcionat els mecanismes adients per detectar els compostos de forma inequívoca i poder associar la seva presència a l’alè a determinades malalties. Tant des d’un punt de vista mèdic com d’exposició a contaminants, el principal avantatge de poder disposar d’una anàlisi d’alè consisteix en la metodologia diagnòstica, que no és invasiva i, per tant, no presenta els inconvenients associats a altres tècniques convencionals, com son l’anàlisi de sang i d’orina. En aquesta tesi s’han desenvolupat dos noves metodologies instrumentals, basades en micro-trampes d’adsorció, especialment dissenyades per a l’anàlisi de compostos volàtils en mostres gasoses, principalment mostres ambientals i mostres d’alè humà. Aquests nous equipaments es caracteritzen per la seva versatilitat i molt baix cost, si es comparen amb els equips comercials actuals. Un dels prototips s’ha dissenyat per a l’anàlisi de mostres d’alè, mostrant una eficàcia i resolució desconeguda fins ara, el que ha permès detectar l’exposició a contaminants volàtils a uns nivells que les tecnologies actuals no permeten assolir. El segon equipament ha estat desenvolupat per permetre analitzar els mateixos contaminants en matrius biològiques, en aquest cas sang, i poder determinar de quina manera i en quin percentatge els compostos que inhalem per exposició arriben a entrar en el cos humà. Aquestes noves metodologies s’han avaluat en diferents estudis d’exposició. S’ha pogut detectar un compost, el 2,5-dimetilfuran, amb una elevada sensibilitat per a la detecció de l’hàbit fumador de les persones, inclús després de més de 48 h d’haver fumat una cigarreta. També s’han estudiat els nivells de contaminació pel fum ambiental del tabac que tenen lloc en diferents ambients (locals de fumadors i no-fumadors). L’elevada sensibilitat de les tècniques desenvolupades ha permès demostrar “in-situ” per primera vegada que els fumadors passius només requereixen unes poques hores de contacte en un ambient contaminat pel fum del tabac per presentar nivells de contaminació a l’alè similars als dels fumadors de poques cigarretes al dia