Homeokinesis and short-term variability of human airway caliber

We hypothesized that short-term variation in airway caliber could be quanti fied by frequency distributions of respiratory impedance (Zrs) measured at high frequency. We measured Zrs at 6 Hz by forced oscillations during quiet breathing for 15 min in 10 seated asthmatic patients and 6 normal subjects in upright and supine positions before and after methacholine (MCh). We pl otted frequency distributions of Zrs and calculated means, skewness, kurtos is, and significance of differences between normal and log-normal frequency distributions. The data were close to, but usually significantly different from, a log-normal frequency distribution. Mean lnZrs in upright and supin e positions was significantly less in normal subjects than in asthmatic pat ients, but not after MCh and MCh in the supine position. The lnZrs SD (a me asure of variation), in the upright position and after MCh was significantl y less in normal subjects than in asthmatic patients, but not in normal sub jects in the supine position and after MCh in the supine position. We concl ude that 1) the configuration of the normal tracheobronchial tree is contin uously changing and that this change is exaggerated in asthma, 2) in normal lungs, control of airway caliber is homeokinetic, maintaining variation wi thin acceptable limits, 3) normal airway smooth muscle (ASM) when activated and unloaded closely mimics asthmatic ASM, 4) in asthma, generalized airwa y narrowing results primarily from ASM activation, whereas ASM unloading by increasing shortening velocity allows faster caliber fluctuations, 5) acti vation moves ASM farther from thermodynamic equilibrium, and 6) asthma may be a low-entropy disease exhibiting not only generalized airway narrowing b ut also an increased appearance of statistically unlikely airway configurat ions.