Computed cardiopulmonography and the idealized lung clearance index, iLCI2.5, in early-stage cystic fibrosis

Abstract

This study explored the use of computed cardiopulmonography (CCP) to assess lung function in early-stage cystic fibrosis (CF). CCP has two components. The first is a particularly accurate technique for measuring gas exchange. The second is a computational cardiopulmonary model where patient-specific parameters can be estimated from the measurements of gas exchange. Twenty-five participants (14 healthy controls, 11 early-stage CF) were studied with CCP. They were also studied with a standard clinical protocol to measure the lung clearance index (LCI_2.5). Ventilation inhomogeneity, as quantified through CCP parameter σlnCl, was significantly greater (P < 0.005) in CF than in controls, and anatomical deadspace relative to predicted functional residual capacity (DS/FRCpred) was significantly more variable (P < 0.002). Participant-specific parameters were used with the CCP model to calculate idealized values for LCI_2.5 (iLCI_2.5) where extrapulmonary influences on the LCI_2.5, such as breathing pattern, had all been standardized. Both LCI_2.5 and iLCI_2.5 distinguished clearly between CF and control participants. LCI_2.5 values were mostly higher than iLCI_2.5 values in a manner dependent on the participant's respiratory rate (r = 0.46, P < 0.05). The within-participant reproducibility for iLCI_2.5 appeared better than for LCI_2.5, but this did not reach statistical significance (F ratio = 2.2, P = 0.056). Both a sensitivity analysis on iLCI_2.5 and a regression analysis on LCI_2.5 revealed that these depended primarily on an interactive term between CCP parameters of the form σlnCL*(DS/FRC). In conclusion, the LCI_2.5 (or iLCI_2.5) probably reflects an amalgam of different underlying lung changes in early-stage CF that would require a multiparameter approach, such as potentially CCP, to resolve.NEW & NOTEWORTHY Computed cardiopulmonography is a new technique comprising a highly accurate sensor for measuring respiratory gas exchange coupled with a cardiopulmonary model that is used to identify a set of patient-specific characteristics of the lung. Here, we show that this technique can improve on a standard clinical approach for lung function testing in cystic fibrosis. Most particularly, an approach incorporating multiple model parameters can potentially separate different aspects of pathological change in this disease.

Keywords: laser absorption spectroscopy; log-normal lung; lung function testing; multibreath washout; nitrogen washout.