Local Lung Function And Airway Size Response During Methacholine Challenge And Salbutamol Treatment Measured Using High-Resolution Dynamic CT And Functional Lung Imaging

RATIONALE : The capacity to quantify both the symptoms of asthma and the effect of new and current treatments is necessary to relieve societal burden and improve quality of life for sufferers. Asthma typically presents as airway constriction, causing increase in airway resistance resulting in reduced peak flows. The regional distribution of these effects is not well understood. Current computed tomography based methods are capable of measuring regional ventilation and specific volumes, but not dynamic flow. In order to fully investigate the functional effects of asthma, measurement of airway flow throughout the breath and across the airway tree is required. In this study we use dynamic CT to measure airway flows and airway diameters during a methacholine challenge and salbutamol treatment in mice. METHODS : Dynamic X-ray computed tomographic (CT) imaging (Dubsky et al. 2012 J. Roy. Soc. Interface) was used to provide 4D flow and structure of house dust mite sensitised BALB/c mice. Subjects were consecutively treated with interventions of low dose methacholine, high dose methacholine and salbutamol treatment. Imaging was performed after each intervention. Our novel and unique image analysis methods were used to measure regional peak flows throughout the airway tree, and airway size measurement for hundreds of airways within the mouse. RESULTS : Results showed significant regional variations in response for all interventions. Regions at the base of the lung showed larger response to methacholine challenge. Furthermore, large compensation effects were seen throughout the lung. Changes in airway size were also seen to be regional. Paradoxical effects were also shown, in that some airways increased in size due when subjected to low doses of methacholine, an airway constrictor. It is speculated that these effects may also be the result of regional compensation. The large amount of data available through our method allows correlation between airway response and regional peak flows, providing a tool to elucidate the effects of asthma attack regionally across the whole organ – a vast improvement over global methods such as spirometry, or morphological methods such as static CT. CONCLUSIONS : Regional peak flow and airway calibre was measured across the lung during methacholine challenge and salbutamol treatment in mice using dynamic CT and novel image analysis methods. Significant and complicated regional effects were shown, and complex interactions between airway size response and peak flow was shown, demonstrating that regional dynamic functional measurements across the entire lung function are essential for understanding lung function during asthma.