The lung clearance index in young infants: impact of tidal volume and dead space

Abstract

Lung clearance index (LCI), measured by multiple breath washout (MBW), is one of the most frequently used measures of ventilation inhomogeneity. This study was designed to investigate the effect of lung volumes on LCI in young infants. The dependence of LCI on dead space volume (VD), tidal volume (VT) and functional residual capacity (FRC) was investigated by mathematical modeling and by MBW measurements using sulfur hexafluoride (SF6) as a tracer gas. MBW was performed in 150 infants, of median postmenstrual age 46.7 weeks, followed up after neonatal intensive care. Wheezing was assessed in 90 of these infants by computerized respiratory sound analysis during quiet sleep. The strongest correlation was observed between LCI and the volume ratios VT/FRC (Spearman rank order correlation coefficient Rs = 0.688, p < 0.001), VD/VT (Rs = 0.733, p < 0.001) and VD/FRC (Rs = 0.854, p < 0.001). LCI calculated from VD, VT, and FRC was linearly related to measured LCI with a coefficient of determination of 75%. There were no significant differences between wheezers and non-wheezers in postmenstrual age and body weight, but FRC was significantly increased (p < 0.001) and median (interquartile range) LCI significantly decreased (5.83 (5.45-6.51) versus (6.54 (6.03-7.22), p < 0.001) in wheezing compared to non-wheezing infants. Model calculations also showed that LCI was significantly reduced in wheezing infants (5.09 (4.79-5.62) versus 5.43 (5.08-5.82), p < 0.018), indicating that the reduction can be explained by differences in the lung volumes, not by improved ventilation homogeneity. In conclusion, the strong dependence of LCI on lung volumes in young infants can lead to misinterpretations regarding the homogeneity of alveolar ventilation.

Current methodological and technical limitations of time and volumetric capnography in newborns

“…These differences may alter CO 2 measurements as well as the interpretation of time-based and volumetric capnograms and derived parameters [30, 31]. Furthermore, the impact of the patient interface on CO 2 measurements in breathed air and on the homogeneity of the alveolar ventilation [32] is much higher in neonates than in adults, as neonates have a much higher ratio of V Dapp to tidal volume [12, 33]. Thus, difficulties in capnographic measurements are greater in smaller infants.…”

Infant multiple breath washout using a new commercially available device: Ready to replace the previous setup?

“…Depending on the infants’ age and technique applied, testing can be done either during natural sleep, or under sedation. Technical dead space of the equipment remains proportionally large compared to the lung volume, despite substantial efforts to reduce it . Recording physiological signals can be technically challenging at this age.…”

“…Technical dead space of the equipment remains proportionally large compared to the lung volume, despite substantial efforts to reduce it. 15,16 Recording physiological signals can be technically challenging at this age. Infants aged 4-6 weeks breathe at fast rates and low flows varying over time.…”

Relationship between computerized wheeze detection and lung function parameters in young infants

“…The significant reduction of the LCI, a frequently used index of alveolar ventilation homogeneity, corresponded to the alterations in FRC SF6 , as wheezing was unlikely to improve the homogeneity of alveolar ventilation. The reduced LCI in expiratory wheezers may have been caused by increases in functional residual capacity: As V T did not differ between wheezers and non‐wheezers, according to the definition of the LCI, an increased functional residual capacity would result in a decrease in the LCI . Moreover, the similar paO 2 and pCO 2 in wheezers and non‐wheezers suggests that the increase of FRC SF6 in wheezing infants may be an effective adaptive mechanism to maintain gas exchange.…”