Airway mechanics of mice and men

Detta är en avhandling från Clinical Physiology and Nuclear Medicine Unit, Department of Clinical Sciences, Malmö, Lund University

Sammanfattning: In this thesis we explore and further develop several techniques used in the animal laboratory as well as in the clinical setting. In particular, we expand the understanding and usefulness of plethysmographic techniques in small rodents. Study I shows that the pressure signal from an un-restrained plethysmograph (UP) depends largely on heating and humidification of the inhaled air. This brings into question the utility of a popular application of UP known as enhanced pause (Penh) as a measure of lung mechanical function. We also developed a mathematical model of UP, that links plethysmograph pressure to respiratory resistance, showing that unless lung volume is either measure or controlled, UP cannot be used to infer changes in airway resistance. In Study II a novel plethysmographic technique was developed to measure lung volume in paralyzed mice. The approach was to gently squeeze the chest of the mouse while recording pressure changes in the plethysmograph and the lungs. A thermal artifact inside the plethysmograph was discovered and we developed a numerical method to correct for it. The values for lung volumes obtained in non-paralyzed mice were similar to those obtained with our new technique. This technique was then used in Study III together with measurements of lung impedance and micro-CT to phenotype a transgenic mouse over-expressing TNF-alpha in alveolar type II cells. The lungs of this mouse showed features commonly seen in COPD, including increased lung volume and loss of alveolar septa. However, the lung also showed features of fibrosis with changes in intrinsic tissue properties. We conclude that over-expression of TNF-alpha leads to a phenotype that shares features of several diseases. Finally, in Study IV, the forced oscillation technique previously used in animals was adapted for use in humans. We made the novel finding that smokers have significantly increased expiratory airway resistance. The forced oscillation technique may provide the only way to measure this resistive abnormality as conventional forced expiratory maneuvers did not reveal any changes.

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