BackgroundThe utility of the forced oscillations technique (FOT) in cystic fibrosis (CF) remains uncertain. The aim of this study was to explore the ability of lower‐frequency FOT indices, alone and after adjustment for the lung volume, to assess the extent of ventilation inhomogeneity in CF patients with varying disease severity.MethodsForty‐five children, adolescents, and adults with CF (age 6.9–27 years) underwent spirometry, FOT, and nitrogen multiple‐breath washout (N2‐MBW) measurements. The respiratory resistance and reactance at 5 Hz (Rrs5 and Xrs5, respectively) were recorded, and a novel FOT index, the specific respiratory conductance (sGrs), was computed as the reciprocal of Rrs5 divided by the functional residual capacity.ResultsThe sGrs correlated well with the lung clearance index (LCI) (Spearman's r: –.797), whereas the correlation of Rrs5 and Xrs5 with the LCI, albeit significant, was weaker (r: .643 and –.631, respectively). The sGrs emerged as the most robust predictor of LCI regardless of the severity of lung disease, as reflected by patients' age and lung function measurements. Most importantly, the relationship between sGrs and LCI remained unaffected by lung hyperinflation, as opposed to that of the LCI with the spirometric and standard FOT indices.ConclusionsIn CF patients, the FOT indices at 5 Hz and the novel, volume‐adjusted parameter sGrs, reflect the extent of lung involvement and the underlying ventilation inhomogeneity in a way comparable to N2‐MBW. Future research should explore the role of lower‐frequency FOT in assessing the severity and monitoring the progression of CF lung disease.