Altered Airway Mechanics in the Context of Obesity and Asthma.

The obesity epidemic is causing a rise in asthma incidence due to the appearance of an obesity-specific late-onset non-allergic (LONA) phenotype. We investigated why only a subset of obese participants develop LONA asthma by determining how obesity, both alone and in combination with LONA asthma, affects the volume dependence of respiratory system impedance. We also determined how obesity and asthma affect impedance during and following challenge with the PC20 dose of methacholine. We found during passive exhalation that all obese participants, in contrast to lean controls and lean asthmatics, experienced similarly profound elevations in lung elastance as they approached functional residual capacity. We also found, however, that the LONA asthmatics had a greater negative dependence of airway resistance on lung volume over the middle of the volume range compared to the other groups. Methacholine challenge with the PC20 dose led to comparable changes in respiratory system impedance in the 4 study groups, but the doses themselves were substantially lower in both obese and lean asthmatic participants compared to obese and lean controls. Also, the obese LONA asthmatics had higher breathing frequencies and lower tidal volumes post challenge compared to the other participants. Taken together, these results suggest that all obese individuals experience substantial lung collapse as they approach FRC, presumably due to the weight of the chest wall. It remains unclear why obese LONA asthmatics are hyperresponsive to methacholine while obese non-asthmatic individuals are not.