Unexpected results in infant multiple breath washout: Is the truth hidden in the washin?

Abstract

Unexpected Results in Infant Multiple Breath Washout: Is the Truth Hidden in the Washin?Recently, a refined software algorithm for infant multiple breath washout (MBW) analysis was proposed aiming to improve the accuracy of tracer gas evaluation. 1 The use of this algorithm revealed high lung clearance index (LCI) values in infants with cystic fibrosis (CF) which were previously found to be normal. Foong et al. used this algorithm to retrospectively analyze infant MBW data from healthy, CF, and preterm infants 2 and report an increase in LCI in CF and preterm groups. However, in the majority of healthy subjects they also found higher LCI values compared with those reported previously for healthy infants, measured either by massspectrometer 3 or by ultrasonic flowmeter systems. 1 Those high LCI values of up to 12 lung turnovers in healthy subjects are clearly counterintuitive.Besides algorithm-related errors, 4 other factors can affect MBW indices, for example, insufficient foreign tracer gas washin. In MBW tests using foreign tracer gases (in this case, SF 6 ) the tracer gas needs to equilibrate between inspired and expired tracer gas fractions before starting the washout. In the present setup for infant MBW, the operator manually stops the washin and starts the washout, but there is no clear online display of a complete washin. 1 Thus, it is easily possible to terminate the washin earlier than required. We hypothesized that a noncomplete tracer gas washin phase could lead to false washout outcomes.To examine this, we simulated different degrees of incomplete washin using a 4% SF 6 MBW measurement from a healthy infant. We truncated the washin stepwise and conventionally analyzed the washout (see online supplement, OLS). Washin incompleteness resulted in increased LCI, functional residual capacity (FRC) and cumulative expired volume (CEV), using the proposed (manual modus) as well as the old algorithm (automatic modus). 1 Using the manual modus, the increase was even more pronounced. Interestingly, the more incomplete the washin, the later the "target" washout breath (at 1/40th of the initial SF 6 concentration) where LCI is calculated (linear regression analysis, R 2 0.79, P < 0.001) and the higher the washout outcomes. We were able to reproduce the same results in vitro using a Plexiglas infant lung model (see OLS).Based on the physiology of the MBW test, during an incomplete washin the tracer gas fraction within the lungs is lower and predominantly distributed in fast ventilated lung compartments. Depending on the algorithms for determining the "target" washout breath, using a relative (1/40th) or absolute tracer gas concentration step, incomplete washin will result in shorter or longer washout times, respectively. In systems that measure molar mass (MM) and calculate those steps based on MM differences, washin incompleteness leads to overestimations in LCI, FRC, CEV ( Fig. 1). An incomplete washin leads to lower end-expiratory MM at the end of the washin (EEMM WI ) compared with the complete washin. This rela...

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

“…The inability to retrieve absolute SF 6 concentrations remains one of the major drawbacks of the old setup. As the MM‐step determines the relevant SF 6 concentration per breath, any manipulation in the washout curve (eg, cutting the end of the washout) will affect MBW indices.…”

“…Prior to analysis, flow, volume, MM, and environmental corrections were applied as previously described . End‐tidal SF 6 concentration (Cet,SF 6 ) per breath was estimated indirectly from the MMms signal between 65 and 95% of expired volume based on fixed MM differences between washin and washout [end‐inspiratory (EIMM)‐step] . Due to the lack of signals for other gas components (O 2 , CO 2 , N 2 ) the software provided only normalized end‐tidal SF 6 values per breath for the whole washout curve.…”

“…Recent reports have raised concern about the accuracy and the transparency of MMms signal processing . For example, minor changes in software or environmental parameters, and insufficient inert gas washin can alter significantly MBW outcomes . These shortcomings may impact upon ongoing trials involving infant MBW and current normative data …”

“…7 For example, minor changes in software or environmental parameters, and insufficient inert gas washin can alter significantly MBW outcomes. [8][9][10] These shortcomings may impact upon ongoing trials involving infant MBW 11,12 and current normative data. 1,13 Lung function testing is promising but yet challenging in infants due to technical and physiological reasons.…”

Pediatric Pulmonology year in review 2017: Part 3

“…The use of the multiple breath washout test (MBW) technique to measure the lung clearance index (LCI) has been increasingly used to assess ventilation inhomogeneity, but measurement of LCI in infants is challenging. Kentgens et al demonstrated the importance of determining an appropriate washin time of a foreign tracer gas (eg, SF6) using a commercially available MBW device . The current system requires the operator to manually stop the washin before beginning the washout.…”