Effects of increasing doses of beta-agonists on airway and parenchymal hysteresis

We examined the effects of a deep inhalation on airway caliber before and after increasing doses of a beta-agonist in eight subjects, including one former and two current but mild asthmatics. With bronchodilation the increase in maximal flow on the partial flow-volume curve (P), initiated from functional residual capacity, exceeded that seen on the maximal curve (M), initiated from total lung capacity, such that isovolumic maximal flows diminished after a deep inhalation; i.e., M/P ratios fell with bronchodilation, as we and others have found. Five of eight reversed this downward trend in M/P ratios at higher cumulative doses. Quasistatic pressure-volume curves (QSPV) were simultaneously performed on two of these five and demonstrated a decrease in pressure-volume hysteresis (PVH) at the higher doses associated with a rising M/P ratio. Three of eight had continuing low and diminishing M/P ratio up to the highest dose given. QSPV were performed in two of these three and indicated no change in PVH at any of the doses. One of these two had a repeat study using a subcutaneous beta-agonist after the inhaled drug was given, and the M/P ratio rose as QSPV PVH fell. These data support the relative hysteresis analysis of airway and parenchyma as an explanation for volume history effects on airway caliber.