Normal Range of Methacholine Responsiveness in Relation to Prechallenge Pulmonary Function: Conclusion

A number of mechanisms have been proposed as the basis for the relationship between nonspecific airway responsiveness and prechallenge pulmonary function.’ Because resistance to flow through a tube is inversely proportional to the radius to the fourth power, a given degree of bronchoconstrictor-induced circumferential airway narrowing can be expected to cause a proportionally larger increase in airway resistance in a narrow airway than in a wider airway. Intersubject differences in the distribution of resistance along the bronchial tree may influence both the pattern of aerosol deposition and the relative impact on total airway resistance of bronchoconstriction at particular sites such as the peripheral airways. Airway hyperresponsiveness may result in heightened bronchomotor tone prior to challenge and thereby be correlated with reduced prechallenge pulmonary function. The convention of expressing responsiveness in terms of percentage of change in FEV, (eg, PD20FEV,) imposes a mathematical relationship between FEVj and such measures of responsiveness. In subjects with lung disease, additional mechanisms may contribute to the direct relationship between prechallenge FEV, and PD20FEV,.

Inflamed, edematous bronchial mucosa can be expected to occupy a greater proportion of airway lumen than normal mucosa for a given degree of bronchial smooth muscle narrowing, decreasing both FEV, and PD20FEV,. Inflammation and emphysema may also decrease the mechanical load against which bronchial smooth muscle must contract, leading to greater responsiveness in persons with low prechallenge pulmonary function. buy tavist online

An alternative, or additional, hypothetical explanation for the cross-sectional relationship between FEV, and PD20FEV, is that airway hyperresponsiveness precedes and is a risk factor for impaired growth or accelerated decline of pulmonary function. This theory, often considered a central part of the “Dutch hypothesis” first proposed by Van der Lende and coworkers, is the subject of ongoing investigation in prospective longitudinal studies.
Although the relationship of prechallenge pulmonary function to nonspecific airway responsiveness is consistent in a number of population studies, prechallenge FEVl appears to explain only a small proportion of the variance in PD20FEVj seen in the population. This is not surprising inasmuch as the control of bronchomotor tone involves a complex, integrated physiologic system, and prechallenge pulmonary function is undoubtedly only one of many factors that influence this system.

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