Effects of methacholine on small airway function measured by forced oscillation technique and multiple breath nitrogen washout in normal subjects

Respir Physiol Neurobiol. 2005 Aug 25;148(1-2):165-77. doi: 10.1016/j.resp.2005.05.001.


The multiple breath nitrogen washout (MBNW) can be analysed to produce the parameters Scond and Sacin as measures of ventilation heterogeneity in conductive and acinar airways, respectively. The derivation of these parameters is based on a model of pulmonary ventilation and results of similar modelling suggest that respiratory system conductance (Grs) measured by forced oscillation technique (FOT) is also sensitive to heterogeneity and to airway closure. Therefore, Scond, the volume of gas trapping at FRC (VtrappedFRC) and Grs may be inter-related parameters. These relationships were examined in 12 normals under baseline and bronchoconstricted states. Specific Grs was measured at 5Hz (sGrs5=Grs5/FRC) and Scond, Sacin and VtrappedFRC by MBNW, before and after methacholine challenge. Scond was independently predicted by VtrappedFRC and FRC in a multivariate model (R2=0.68, p=0.002). Post methacholine challenge, Scond related only to VtrappedFRC (R2=0.79, p<0.0001). The absolute change in Scond induced by methacholine challenge were predicted by the changes in VtrappedFRC and sGrs5 in a multivariate model (R2=0.82, p=0.0002). Sacin was unrelated to VtrappedFRC and sGrs5 before and after methacholine challenge. In conclusion, Scond and sGrs5 are measurements that are sensitive to changes occurring to the function of peripheral conducting airways, in particular heterogeneity and airway closure, while Sacin and presumably heterogeneity in terminal airways, are independent of these. Scond is also related to lung size. We review the current state of knowledge of FOT and MBNW in obstructive lung diseases and discuss future research directions.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Airway Resistance / drug effects*
  • Bronchi / drug effects
  • Bronchoconstrictor Agents / pharmacology*
  • Female
  • Humans
  • Male
  • Methacholine Chloride / pharmacology*
  • Nitrogen
  • Plethysmography / methods
  • Pulmonary Ventilation / drug effects*
  • Respiratory Function Tests / methods*
  • Respiratory Mechanics / drug effects*
  • Spirometry / methods
  • Vital Capacity / drug effects


  • Bronchoconstrictor Agents
  • Methacholine Chloride
  • Nitrogen