Limitations of regional ventilation inhomogeneity indices in children with cystic fibrosis

Background: S_cond is a multiple breath washout (MBW) index that measures convection-dependent ventilation inhomogeneity (CDI) arising within conductive airways, but the calculation method is unreliable in subjects with advanced cystic fibrosis (CF) lung disease. A new CDI index, S_cond *, has been proposed for use in adults with CF and moderate to severe ventilation inhomogeneity. We aimed to evaluate the most appropriate CDI index in children and adolescents with CF and various degrees of inhomogeneity, and from that the most appropriate diffusion-convection-interaction index (S_acin or S_acin *).

Methods: S_cond , S_acin and the alternative indices, S_cond *, and S_acin * were retrospectively calculated in subjects with CF aged 3 to 18 years and age-matched controls, who underwent sulfur hexafluoride MBW between 2003 and 2015. The upper limit of normal was based on 95th percentile of the control population.

Results: One hundred and twenty-seven subjects with CF (44% male; mean age ± SD: 7.5 years ± 4.9) and 94 controls (53% male; 7.9 years ± 5.1) were included in the final analysis. All measures of ventilation inhomogeneity were significantly higher in children with CF. As predicted, S_cond reached a maximum value at lung clearance index (LCI) values of approximately 9. In subjects with LCI ≥ 9 S_cond * showed good correlation with LCI, whilst S_cond had no relationship with LCI (Spearman rank correlation S_cond */LCI, 0.49; P < .01; S_cond /LCI, -0.068; P = .46). In subjects with mild disease (LCI < 9) S_cond was more frequently abnormal than S_cond * (37% vs 16%; P = .01).

Conclusions: S_cond and S_acin are sensitive indices of early regional inhomogeneity, but are of no value when LCI ≥ 9. In these subjects, S_cond * & S_acin * are potential alternatives.