A Probative Approach for Noninvasive Evaluation of Airway Hyperresponsiveness and Remodeling in Adult Asthmatics

We propose a probative approach for noninvasive evaluation of airway hyperresponsiveness (AHR) and remodeling to investigate their outcome in adult asthmatics treated according to the Global Initiative for Asthma (GINA) guideline. Pulmonary function and AHR to methacholine were measured twice with an interval of 24.3 +/- 3.4 months in 18 adult asthmatics during the ongoing treatments. Mathematical formulas previously used in an animal model were applied in human asthmatics to eliminate the effect of airway wall thickening on respiratory resistance (Rrs), calculating indices for the proportional changes with time in airway wall thickness (PW(1)/PW(0)) and airway smooth muscle shortening (PMS(1)/PMS(0)), respectively. The minimum cumulative dose of methacholine (Dmin), an ordinary index of AHR measured with the oscillometry Asthograph, correlated with the asthma severity. The disease periods significantly correlated with the indices of airflow limitation. While there was no change in PW(1)/PW(0) (1.00 +/- 0.07) during the assessment periods, methacholine-induced airway smooth muscle shortening was attenuated by 46% (PMS(1)/PMS(0)=0.54 +/- 0.16). Less improvement in PMS(1)/PMS(0) was seen with a correlation to the disease periods, but PMS(1)/PMS(0) improved correlating to the relative length of the assessment period with ongoing treatments in the disease period. In conclusion, this probative approach may be useful to investigate the outcome of AHR and remodeling in human asthmatics, and shows that remodeling may get worse with time or may halt and AHR may improve with a stepwise, early intervention and prolonged treatment given according to the GINA guideline.