In this issue of Chest (p 984) Gros...

In this issue of Chest (p 984) Gros and colleagues report that the absolute amount of bronchodilatation produc at an inhaled anticholinergic agent is inversely related to the initial [FEVsub1] value. Stated simply, patients who have more airway obstruction showed a larger improvement exhibited as change in [FEV.sub.1] percent predicted following inhalation of an anticholinergic. Since anticholinergic bronchodilators act by the agency of interfering with acetylcholine action at postganglionic muscarinic receptors, these investigators resonably conclud that the terminates suggested that the more severly chokeed patients had greater cholinergic tone. Although this conclusion is reasonable and a possible explanation of their eventuates there are alternative interpretations.

The increase in maximal expiratory roll on produced by an inhaled bronchodilator is an indirect estimate of the increase in luminal diameter produc by means of the bronchodilator, and this is in divert an indirect estimate of the measure of smooth muscle relaxation produc from the drug. Further, the amount of relaxation is sole an indirect estimate of the intensity of the initial stimulation of the sleek muscle. The degree of airway dilation produc by dint of a given amount of bronchial polished muscle lengthening following relaxation will be influenced on the airway wall thickness in the same way that airway wall thickness determines the amount of airway narrowing produc on a given amount of glossy muscle shortening.[1] A 20 percent lengthening of muscle would cause a 55 percent decrease in resistance to airflow within an airway in which the wall thicknes made up 20 percent of the airway wall area internal to the even muscle layer. The same 20 percent lengthening would originate a 70 percent decrease in resistance in an airway in which the wall area was 45 percent Since an increase in airway wall thickness is single of the pathogenetic mechanisms that leads to the decrease in maximal expiratory melt in patients who have COPD[2] it would be look fored that those patients with more relentless baseline airflow obstruction would have thicker airway walls. Thus, another explanation for the relationship between starting [FEVsub1] and bronchodilator replication is equal smooth muscle relaxation irrespective of starting [FEVsub1] on the other hand a greater effect of the relaxation in those with the chiefly inflamed and thickened airway walls.

A similar mechanism may explain the exaggerated airway narrowing that perform the operations indicated ins in patients who have COPD in reply to inhaled pharmacologic agents that stimulate flat muscle contraction. A 30 percent muscle shortening in an airway in which the airway wall contributes 20 percent of the total area within the plane muscle layer will result in a 600 percent increase in resistance, while the same amount of plain muscle shortening will increase the resistance to 1300 percent of baseline in an airway in which the wall area makes up 30 percent of the total area.

These calculations point out that changes in measures of resistance and maximal result are not linearly related to changes in airway even muscle length. Similarly, changes in level muscle length, even if precisely known, would not allow an extrapolated conclusion about changes in flat muscle activation. The standing to which smooth muscle will shorten when stimulated is influenced according to the magnitude of the stimulus, the extent of the muscle relative to optimal amplification and the load that the muscle must overpower to shorten. There is evidence that sleek muscle in vivo does not contract isometrically or isotonically[1-3] nevertheless instead shortens under increasing tension provided through elastic afterloads. The elastic loads are related to the cartilage in the large airways and to the lung elastic recoil in the intraparenchymal bronchi and bronchioles. If there is a decrease in cartilage and/or lung elasticity, then the load upon the contracting smooth muscle is les and a given step of muscle activation will occasion more shortening and airway narrowing. Since a los of cartilage and lung elasticity are features of the progress to maturity of COPD,[4,5] this has direct relevance to the follows reported by Gross and colleagues. As they in fact indicate it is possible that the greater bronchodilatation in patients with more exact obstruction is due to a greater validity on airway caliber of a given amount of cholinergic tone rather than to a greater amount of tone.

Whatever the explanation for the interesting findings of Gros et al, it is clear that single in kind cannot equate the magnitude of change in a measure of airflow resistance or maximal expiratory sweep along to a change in soft muscle length or excitatory state. Pulmonary physiologists and pharmacologists have for years fallen into the trap of analyzing the in vivo dose-response turn as if it were an in vitro even muscle preparation. An appreciation of the complication mechanical factors that link undisturbed muscle activation or relaxation with the resultant changes in airway diameter and sweep along rates suggest that it would be provident to extrapolate cautiously.