Study and development of a holdingchamber for inhalation

Tese de Doutoramento em Engenharia MecânicaAsthma is a respiratory disease that causes chronic airway inflammation. Affecting more than 300 million individuals worldwide, it is a growing public health hazard. Inhalation therapy is the preferred strategy for medication delivery. This therapy is executed through specific delivery devices, whereas the pressurized Metered-Dose Inhaler (pMDI) is one of the most preferred. However, the pMDI efficiency is highly dependent on a correctly executed inhalation procedure. For children under 5 years old (or elderly individuals), it is advisable to use the pMDI coupled with an add-on device (i.e. spacer). Within the spacers, the Valved Holding Chamber (VHC) is the mostly used, due to its good capacity to reduce the pMDI spray coarse fraction and the oral-pharyngeal deposition ( 80%). Additionally, the VHC’s one-way valve allows the patient to maintain his tidal breathing during treatment. The VHC typically delivers a Fine Particle Mass (FPM) that is 20% of the labelled dose. Several design characteristics dictate the VHC performance, such as, the dimensions and the materials. The study herein focus on the assessment of eight commercial VHCs, through experimental and numerical methods. An experimental setup was developed, allowing the evaluation of the devices at constant flow rate (30 L/min and 60 L/min) and at variable flow (sine breath pattern). The waveform was obtained through a breathing simulator specially developed for this purpose, based in a cam-follower mechanism. The salbutamol sulphate (i.e. Ventolin) was collected using a cascade impactor (i.e. MSLI), and assessed by UV-Vis spectrophotometry analysis. Several metrics, regarding VHC performance, were calculated. Results have shown that the VHC capacity reduce the oral-pharyngeal deposition (64% - 94%), which is deeply related with the VHC valve design. It was observed that the VHC reduces the plume coarse fraction ( 70%), keeping the FPM bioequivalent to the pMDI solo. A correlation between the fine particle fraction and the volume of air passing through the VHC was proposed. Patient relevant metrics were suggested to classify the VHC devices upon quantitative and qualitative characteristics. A Computational Fluid Dynamics (CFD) model was developed where the air flow (i.e. 60 L/min)) was calculated along with the pMDI spray modelling as a discrete phase. The spray particle-wall interaction was modelled using different approaches and compared against literature and experimental data. This study, shed some light upon the spray evaporation process inside the VHC, showing that the efficiency of evaporation process is related with the VHC volume. A new VHC design, based in CFD dimensional optimisation of the VHC body is proposed, which shows an improvement of the FPM delivered.A asma é uma doença respiratória que causa a inflamação crónica das vias aéreas. Mundialmente, afeta mais de 300 milhões de indivíduos e é um problema crescente de saúde publica. A terapia de inalação é a estratégia preferida para administrar a medicação de controlo ou de alívio. Esta terapia é executada através de dispositivos específicos, entre os quais o Inalador Pressurizado com Válvula Doseadora (IPVD) é o mais usual. Contudo, a eficiência do IPVD é dependente de uma técnica de inalação correta. Para crianças com menos de 5 anos (ou idosos), é recomendável o uso do IPVD acoplado a um espaçador. Entre os espaçadores, a Câmara Expansora (CE) é a mais utilizada, devido à sua boa capacidade de redução das partículas grandes do aerossol do IPVD, e da redução da deposição orofaringeal ( 80%). Adicionalmente, a válvula de sentido único da CE, permite que o paciente mantenha a sua respiração normal durante o tratamento. A CE emite, tipicamente, uma massa de partículas finas (MPF) que é 20% da dose calibrada do IPVD. Este estudo foca-se na avaliação de oito CEs, através de uma metodologia experimental e numérica. Uma instalação experimental foi projetada para a avaliação dos dispositivos a fluxo constante (30 L/min e 60 L/min) e variável (um padrão respiratório sinusoidal). A onda foi obtida através de um simulador respiratório especialmente desenvolvido para este propósito, o qual foi baseado num mecanismo cam-seguidor. O sulfato de salbutamol (Ventilan HFA) foi recolhido utilizando um impactor em cascata em vários estágios (Aparelho C da Farmacopeia Portuguesa), e quantificado por espetrofotometria UV-Visivel. Foram calculadas várias métricas sobre o desempenho das CEs. Os resultados demonstram a capacidade da CE para reduzir a deposição orofaringeal (64% - 94%), a qual está intrinsecamente relacionada com o design da válvula do dispositivo. Foi observado que a CE reduz a fração de partículas grandes na pluma ( 70%), mantendo a MPF bioequivalente à emitida pelo IPVD. Foi proposta uma correlação entre a fração de partículas finas e o volume de ar que atravessa a CE. Foram também sugeridas métricas com relevância para o paciente, que classificam as CEs de forma quantitativa e qualitativa. Foi desenvolvido um modelo de Dinâmica Computacional de Fluidos (DCF), onde o fluxo de ar (a 60 L/min) foi calculado juntamente com o aerossol do IPVD, tendo sido este modelado como uma fase discreta. A interação entre partícula e parede foi modelada utilizando diferentes aproximações matemáticas, sendo posteriormente comparadas com a literatura e dados experimentais. Este estudo contribui com um melhor conhecimento do processo de evaporação das gotas do aerossol dentro da CE, onde se verificou que este processo está relacionado com o volume da CE. Foi proposto em novo design para CE, baseado numa otimização das dimensões do corpo da CE, que demonstra melhoria da MPF emitida

Effect of microwave heating with different exposure times on physical and chemical parameters of olive oil

This study reflects the effect of different microwave heating times (1, 3, 5, 10 and 15 min) on physical and chemical characteristics of three Portuguese olive oils from three protected designation of origin (PDO), "Azeite de Tras-os-Montes PDO", "Azeites da Beira Interior PDO", and "Azeite de Moura PDO". The parameters evaluated were free acidity, peroxide value, specific extinction coefficients (K-232 and K-270), color and chlorophylls and carotenoids content. A differential pulse voltammeter was also used to monitor the changes in a-tocopherol content. The results showed that microwave heating produce losses in the quality of the different analysed olive oils. The heating time did not promote the occurrence of hydrolysis in the samples since no changes in free acidity values were found. All other parameters were affected by exposure time in a similar way: in the firsts 3 min no marked changes were observed, after that the quality of the oil decrease significantly. The microwave heating time also affects the total chlorophylls, carotenoids and alpha-tocopherol contents which clearly decreased as long as the exposure time increases. After 15 min of heating the electrochemical signal, due to the alpha-tocopherol, disappear completely in the voltamogram

A CFD study of a pMDI plume spray

Uncorrected proofAsthma is an inflammatory chronic disease characterized by airway obstructions disorders. The treatment is usually done by inhalation therapy, in which pressurized metered-dose inhalers (pMDIs) are preferred devices. The objective of this paper is to characterize and simulate a pMDI spray plume by introducing realistic factors through a computational fluid dynamics (CFD) study. Numerical simulations were performed with Fluent® software, by using a three-dimensional “testbox” for room environment representation. A salbutamol/HFA-134a formulation was used for characterization, whose properties taken as input for the CFD simulations. Spray droplets were considered to be composed by ethanol, salbutamol and HFA-134a. Propellant evaporation was taken into consideration, as well as, drag coefficient correction. Results showed an air temperature drop of 3.3 °C near the nozzle. Also, an increase in air velocity of 3.27 m/s was noticed. The CFD results seem to be in good agreement with Dunbar (1997) data on particle average velocity along the axial distance from the nozzle.National Funds-Portuguese Foundation for Science and Technology, under Strategic Project PEst-C/EME/UI4077/2011 and PEst-OE/EME/299UI0252/201

Left atrial volume quantification using cardiac MRI in atrial fibrillation: comparison of the Simpson’s method with biplane area-length, ellipse, and three-dimensional methods

PURPOSELeft atrial volume is an important predictor of future arrhythmias, and it can be assessed by several different methods. Simpson’s method is well accepted as a reference standard, although no standardization exists for cardiac magnetic resonance (CMR). We aimed to compare the estimations of left atrial volumes obtained by the Simpson’s method with three other methods. MATERIALS AND METHODSEighty-one consecutive patients referred for CMR imaging between February 2007 and May 2010 were included in the study (47 males; mean age, 59.4±11.5 years; body mass index, 26.3±3.7 kg/m2). Left atrial volume measurements were performed using the Simpson’s, biplane area-length, ellipse, and three-dimensional methods. Results were correlated using a Bland-Altman plot and linear regression models and compared by two-tailed paired-sample t tests. Reader variability was also calculated. RESULTSLeft atrial volume measurements using the biplane area-length technique showed the best correlation with Simpson’s method (r=0.92; P 0.99). CONCLUSIONThe biplane area-length method can be used for left atrial volume measurement when the Simpson’s method cannot be performed. If these two methods are not feasible, then all methods are highly reproducible and can be used, but should not be used interchangeably for follow-up studies