Předkládaná Diplomová práce se zabývá analýzou a tvorbou modelů dýchacích cest předčasně narozených dětí. Nejprve je položen teoretický základ v oblasti vývoje dýchacího ústrojí a tvorby modelů dýchacích cest. Poté jsou představeny využité zobrazovací modality a popsány metody pro práci s obrazovými daty. Praktická část práce se zabývá vytvořením modelů dýchacích cest tří novorozenců. Všechny tyto modely jsou vytvořeny na základě klinických CT a MRI dat novorozenců narozených ve 30. týdnu gestačního věku. U těchto vytvořených modelů jsou dále analyzovány vybrané parametry související s anatomickou strukturou dýchacích cest. Na základě analýzy těchto parametrů byl následně navrhnut reprezentativní model, odpovídající dýchacím cestám novorozence daného gestačního věku.

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This research was aimed at the development and validation of new in vitro methods capable of predicting in vivo drug deposition from dry powder inhalers, DPIs, in lung-normal human adults. Three physical models of the mouth, throat and upper airways, MT-TB, were designed and validated using the anatomical literature. Small, medium and large versions were constructed to cover approximately 95% of the variation seen in normal adult humans of both genders. The models were housed in an artificial thorax and used for in vitro testing of drug deposition from Budelin Novolizer DPIs using a breath simulator to mimic inhalation profiles reported in clinical trials of deposition from the same inhaler. Testing in the model triplet produced results for in vitro total lung deposition (TLD) consistent with the complete range of drug deposition results reported in vivo. The effect of variables such as in vitro flow rate were also predictive of in vivo deposition. To further assess the method’s robustness, in vitro drug deposition from 5 marketed DPIs was assessed in the “medium” MT-TB model. With the exception of Relenza Diskhaler, mean values for %TLD+SD differed by only < 2% from their literature in vivo. The relationship between inhaler orientation and in vitro regional airway deposition was determined. Aerosol drug deposition was found to depend on the angle at which an inhaler is inserted into the mouth although the results for MT deposition were dependent on both the product and the formulation being delivered. In the clinic, inhalation profiles were collected from 20 healthy inhaler naïve volunteers (10M, 10F) before and after they received formal inhalation training in the use of a DPI. Statistically significant improvements in Peak Inhalation Flow Rate (PIFR) and Inhalation Volume (V) were observed following formalized training. The shapes of the average inhalation profiles recorded in the clinic were found to be comparable to the simulated profiles used in the in vitro deposition studies described above. In conclusion, novel in vitro test methods are described that accurately predict both the average and range of aerosol airway drug deposition seen from DPIs in the clinic.

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