Both nasal vs. oral breathing and mouthpiece vs. facemask affect LCI measurements in adults. This effect was minimal in preschool children, where switching between interfaces is most likely to occur.
The lung clearance index (LCI), measured by multiple breath washout (MBW), reflects global ventilation inhomogeneity and is a sensitive marker of early obstructive airway disease. For the MBW test to accurately reflect a subject’s gas mixing within the lungs, the breathing pattern should represent physiologically appropriate tidal volumes (V T ) and respiratory rate (RR). We aimed to assess whether changes in V T impact MBW outcome measures with a series of prospective and retrospective studies. MBW testing was performed using the Exhalyzer ® D (EcoMedics AG, Switzerland). Healthy adult subjects performed MBW with uninstructed tidal breathing and a series of instructed tidal breathing tests, designed to isolate specific features of the breathing pattern. In addition, we retrospectively analyzed MBW data from two pediatric multi-centre interventional studies of cystic fibrosis (CF) subjects to determine the range of V T observed during uninstructed breathing, and whether breathing outside this range impacted results. The LCI was lower, but not significantly different between deep breathing at 20 ml/kg body weight and uninstructed tidal breathing; whereas LCI was significantly higher during shallow breathing compared with normal tidal breathing. For the majority of subjects with CF (80%), V T ranged from 9-15mL/kg. Within the observed V T range, LCI was similar in trials with mean V T / kg below this range compared to trials with V T /kg within the range. If subjects breathe naturally and are not instructed to use specific targets, the range of V T is within physiologically appropriate limits and normal variations observed do not impact MBW outcomes.
Breathing 100% oxygen has been reported to decrease tidal volume (VT) in infants [1] and recent evidence published in the European Respiratory Journal suggest that transient less pronounced effects are also seen in preschool children [2]. It is unclear whether there is an age dependency beyond infancy in the response to 100% oxygen or whether it is limited to young children. Here we investigate the effects of 100% oxygen on breathing pattern across a spectrum of ages to identify the change in VT that occurs when subjects breathe 100% oxygen during a multiple breath nitrogen washout (MBNW) test.MBNW testing was performed [3] with the Exhalyzer® D using Spiroware 3.1 software (EcoMedics AG, Dürnten, Switzerland). Preschool children were tested using a mask whereas older children and adults used a mouth piece. All trials were re-run through Spiroware 3.2.0 to obtain breath-by-breath output of VT, respiratory rate (RR) and minute ventilation (V′E) for all pre-washout and washout breaths. The average VT , RR and V′E of the last 5 breaths of the pre-phase was compared to each washout breath to calculate a relative change in each parameter. We also compared the final 5 breaths of the pre-phase to the average all of breaths collected during the washout phase. A non-linear regression analysis was used to model the breath-by-breath changes. In total data collected from 112 preschool children (50 healthy and 62 with cystic fibrosis (CF)) [4], 18 school age children (all with CF) [5] and 10 adults (all healthy) were include in the analysis. Combined, the subjects ranged from 2.5 years to 29 years of age (median 4.8 years, interquartile range (3.7-17.5)) and 63% of participants were male.Exposure to 100% oxygen resulted in an initial decrease in VT, RR and V′E in all three age groups (figure 1), followed by a return to pre-phase levels. This effect was observed in both healthy subjects and those with CF. The average VT of the entire washout was not significantly different when compared to the pre-phase in all groups (0.8% decrease in healthy preschool children, 3.2% and 3.9% decrease in preschool and school age children with CF, respectively, and a 1.6% decrease in healthy adults).Our findings are thus consistent with two recent studies that compared the average pre-phase VT to the average VT during the washout phase in preschool [2] and school age children [6]. FOONG et al.[2] observed a 13 mL (4.8%) decrease in VT whereas JOST et al.[6] observed a 9.7 mL (3.5%) decrease in VT. In infants, breath-by-breath analysis demonstrated temporary hypoventilation driven by a decrease in VT after 2-4 breaths, which remained low for 10-25 breaths before returning to baseline [1]. Therefore, changes in tidal breathing in response to exposure to 100% oxygen observed in infants are not unique to this age group. Rather, they are a phenomena exhibited by subjects of all ages with the magnitude of the effect being small after early infancy. This is important for longitudinal studies with MBNW measurements, as breathing 100% oxygen is unlikely...
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