Highlights d Dysbiosis can lead to increased colon tumor susceptibility and CD8 + IFNg + T cells d Increased colon CD8 + IFNg + T cells are associated with more inflammation and tumors d Dysbiosis and increased tumorigenesis are associated with greater T cell exhaustion

Particle size of nebulized aerosols can be measured directly using laser diffraction or by evaluating aerodynamic properties by cascade impaction. As of today, there are no generally accepted standards for measuring particle size distribution from nebulizers. Laser diffraction has been questioned because of potential evaporative losses of the small particles at the edge of the plume, causing an apparent shift in the particle size distribution and thus a larger mass median diameter (MMD). When particle-sizing wet aerosols, cascade impaction may give rise to an apparent shift in the distribution, resulting in a smaller mass median aerodynamic diameter (MMAD) due to evaporative losses of aerosol droplets as they enter the impactor at ambient temperature. The modified low-flow Marple 296 Personal Cascade Impactor (MPCI) is currently being proposed as the European standard for wet aerosol analysis to minimize evaporative losses during sampling. The present study compared the particle size distribution of salbutamol and sodium cromoglycate aerosols nebulized by the Pari LC Star, using laser diffraction (Malvern Mastersizer X; MMX) and cascade impaction (Andersen Cascade Impactor [ACI] and the commercially available MPCI), which was either at ambient temperature or cooled to the nebulized aerosol temperature (10 degrees C). MMDs obtained with the MMX were virtually identical to the MMADs measured with both impactors when cooled with no significant differences in geometric standard deviation (sigma(g)). When the impactors were operated at ambient temperature, MMADs were smaller (18 to 30%) with a significantly larger sigma(g) (p < 0.05) compared to the MMX. These findings suggest that droplet distribution data for wet aerosol where evaporation process has not been minimized must be viewed with caution. There was no evidence suggesting a significant evaporative loss of small droplets from the edge of the plume during laser particle sizing. The MPCI does not minimize evaporative losses of aerosol particles during sampling.

The ability to predict drug deposition of inhaled drugs used in cystic fibrosis (CF) is important if there is a need to target specific doses of drug to the lungs of individual patients. The gold standard of measuring pulmonary deposition is the quantification of an aerosolized radiolabel either mixed with the drug solution or tagged directly to the compound of interest. Accuracy of the quantification could be assured if there is agreement between the amount of radioactivity before and after administration. Before administration, the radiolabel is concentrated in the well of the nebulizer, whereas after administration, it is distributed throughout the nebulizer, the expiratory filter and connectors, and the upper airway, stomach, trachea, and lung. Not only is the geometry of the distribution that is presented to the gamma camera different, but there are different attenuation factors for the various body tissues. The primary aim of this study was to evaluate the accuracy of the quantification of deposition. Secondary goals were to compare in vitro nebulizer performance with that measured in vivo during the deposition study. Eighty milligrams of tobramycin and technetium bound to human serum albumin was administered to 10 normal adults using a Pari LC Jet Plus (Pari Respiratory Equipment, Inc., Richmond, VA) breath-enhanced nebulizer. Techniques were developed that allowed for the accounting of 99 +/- 2% of the initial radioactivity. The fraction of the rate of lung deposition to total body deposition was the in vivo respirable fraction (0.62 +/- 0.07), which closely agreed with in vitro measurements of respirable fraction (0.62 +/- 0.04). Drug output measured from the change in weight and concentration in the nebulizer systematically overestimated drug output measured by the deposition study. The results indicate that 11.8 of the initial 80 mg would be deposited in the lungs. This technique could be adapted to accurately quantify the amount of deposition on any inhaled therapeutic agent, but caution must be used when extrapolating performance of a nebulizer on the bench to expected deposition in patients.

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