The FEF25-75/FVC ratio is associated with methacholine airway responsiveness. The normative aging study

Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1574-9. doi: 10.1164/ajrccm.159.5.9803063.


Airway responsiveness is known to be partly explained by geometric and anatomic factors. This cross-sectional investigation was undertaken to determine whether FEF25-75/FVC as a surrogate measure of airway size relative to lung size is associated with airway responsiveness to methacholine. Posteroanterior chest radiographs and spirometry were performed on a group of 929 middle aged and older men from an ongoing longitudinal study, the Normative Aging Study, who returned for their regularly scheduled examination between 1984 and 1989. Subjects had a mean age of 60.5 +/- 7.7 yr. FEV1, FEF25-75, and FVC were taken from spirometric results and FEF25-75/FVC ratios were obtained. Main bronchus (MB) and tracheal (TR) diameters and lung area (LA) were obtained from chest radiographs, and ratios of MB/LA and TR/LA were calculated for each subject and compared with FEF25-75/ FVC as measures of airway size relative to lung size. In a multiple linear regression model adjusting for age, height, initial FEV1, smoking, eosinophil count, and IgE level, FEF25-75/FVC was significantly related to the degree of methacholine airway responsiveness as measured by Log10 dose response slope (beta = -0.37, p < 0.001). Controlling for the same variables, both MB/LA (beta = -149.07, p < 0.001) and TR/LA (beta = -125.87, p < 0.001) were significant predictors of the degree of bronchial responsiveness in separate regression models; however, their effects were greatly attenuated when FEF25-75/ FVC was present in the same model. Similar results were obtained after excluding subjects with FEV1/ FVC </= 0.70 and subjects who had any smoking history. We conclude that FEF25-75/FVC as a surrogate measure of airway size relative to lung size is significantly associated with airway responsiveness.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / physiology
  • Bronchi / drug effects*
  • Bronchoconstrictor Agents / pharmacology*
  • Bronchography
  • Humans
  • Lung / diagnostic imaging
  • Male
  • Maximal Midexpiratory Flow Rate* / physiology
  • Methacholine Chloride / pharmacology*
  • Middle Aged
  • Radiography, Thoracic
  • Reference Values
  • Trachea / diagnostic imaging
  • Vital Capacity* / physiology


  • Bronchoconstrictor Agents
  • Methacholine Chloride