Sophie Yammine

False normal Lung Clearance Index in infants with cystic fibrosis due to software algorithms

Lung clearance index (LCI), a marker of ventilation inhomogeneity, is elevated early in children with cystic fibrosis (CF). However, in infants with CF, LCI values are found to be normal, although structural lung abnormalities are often detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package.

Changes in breathing pattern upon 100% oxygen in children at early school age

Nitrogen multiple-breath washout (N2MBW) is an increasingly used tidal breathing test in young children to assess ventilation inhomogeneity. However, the test requires 100% oxygen to perform. We aimed to examine the potential influence of pure oxygen on breathing pattern in school-aged children. We performed tidal breathing measurements under room air followed by N2MBW in 16 former preterm children and 24 healthy controls. We compared tidal volume (VT), coefficient of variation of VT (CVVT), respiratory rate (RR), and minute ventilation (VE) between tidal breathing and N2MBW, and between the start and end of tidal breathing. Mean (range) age was 6.8 (5.9, 9.0) years. VT, RR and VE showed no significant change upon oxygen-exposure, while CVVT significantly decreased by 5% (95% CI: 1.2, 9.0; p=0.012). However CVVT was also the only parameter which significantly decreased during tidal breathing. Overall, pure oxygen has no systematic effect on breathing pattern in young school-aged children. N2MBW can reliably be used as tracer gas in this age group.

Leaks during multiple-breath washout: characterisation and influence on outcomes

Nitrogen multiple-breath washout (N2MBW) is increasingly used in patients with cystic fibrosis. The current European Respiratory Society/American Thoracic Society consensus statement for MBW recommends the rejection of measurements with leaks. However, it is unclear whether this is necessary for all types of leaks. Here, our aim was to 1) model and 2) apply air leaks, and 3) to assess their influence on the primary MBW outcomes of lung clearance index and functional residual capacity. We investigated the influence of air leaks at various locations (pre-, intra- and post-capillary), sizes, durations and stages of the washout. Modelled leaks were applied to existing N2MBW data from 10 children by modifying breath tables. In addition, leaks were applied to the equipment during N2MBW measurements performed by one healthy adolescent. All modelled and applied leaks resulted in statistically significant but heterogeneous effects on lung clearance index and functional residual capacity. In all types of continuous inspiratory leaks exceeding a certain size, the end of the washout was not reached. For practical application, we illustrated six different “red flags”, i.e. signs that enable easy identification of leaks during measurements. Air leaks during measurement significantly influence N2MBW outcomes. The influence of leaks on MBW outcomes is dependent on the location, relation to breath cycle, duration, stage of washout and size of the leak. We identified a range of signs to help distinguish leaks from physiological noise. The influence of leaks on nitrogen MBW outcomes is complex, dynamic and dependent on the size, duration, location and position of leaks during the washout and breathing cycle http://ow.ly/PbHV30hB91H

Lung clearance index and moment ratios at different cut-off values in infant multiple-breath washout measurements

Multiple‐breath washout (MBW) is increasingly used for infant lung function testing. Current guidelines recommend calculating lung clearance index (LCI) and functional residual capacity (FRC) at 2.5% of normalized tracer gas concentration, without clear recommendation for moment ratios (MR). Whether the 2.5% cut‐off has the highest discriminative power to detect ventilation inhomogeneity in infants with lung diseases is unknown.

Respiratory rate in infants with cystic fibrosis throughout the first year of life and association with lung clearance index measured shortly after birth

BACKGROUND Lung impairment in cystic fibrosis (CF) starts in infancy. However, tools to monitor early lung disease are limited. Respiratory rate (RR) as a key vital sign is easy to assess during sleep and is elevated during acute respiratory disease. Thus, elevated RR could indicate early lung impairment and potentially serve as a diagnostic tool in disease monitoring. METHODS In a prospective cohort of infants with CF diagnosed by newborn screening and healthy controls RR was measured and respiratory symptoms reported weekly throughout infancy. Infants performed a lung function measurement within the first weeks of life. RESULTS The analyses included 5656 measurements from 153 infants (43 with CF). RR declined from 43.2 (40.5)/min at 6 weeks of age to 28.3 (24.6)/min at 50 weeks in infants with CF (healthy controls). Infants with CF had consistently higher RR than controls (mean difference: 4.15/min; (95% CI 2.86-5.44); p < .001). In both study groups, RR was increased throughout the study period in infants with higher lung clearance indices (LCI) and during episodes of respiratory infections. CONCLUSIONS Infants with CF have a higher RR compared to healthy controls during the first year of life. The association with early LCI measurements, the current gold standard to assess physiology of peripheral airways persisted throughout the study period. This may indicate tracking of lung function by RR. It might thus be an early subtle sign of functional respiratory deficit. Further studies will show if RR can be used as a sensitive and promising marker to monitor early CF lung disease.

Ventilation and perfusion assessed by functional MRI in children with CF: reproducibility in comparison to lung function

BACKGROUND Chronic lung diseases such as cystic fibrosis (CF) can be monitored by imaging and lung function modalities. Magnetic resonance imaging (MRI) techniques such as matrix pencil (MP) decomposition allows for evaluation of regional impairment of fractional ventilation (RFV) and relative perfusion (RQ). However, reproducibility of MP MRI outcomes in children with CF is unknown. We examined short-term variability of ventilation and perfusion impairment from MP MRI and compared this to lung function outcomes. METHOD Twenty-threeCF and 12 healthy school-aged children underwent MRI and lung function tests on the same day on two occasions 24 h apart. Global ventilation inhomogeneity was assessed by the lung clearance index (LCI) from nitrogen-multiple breath washout (N2-MBW) technique. Intra-class-coefficient (ICC), percentage change, and Bland-Altman limits of agreement were evaluated to assess reproducibility. RESULTS Sixty-nine measurements from MP MRI and N2-MBW were performed. The ICC between two visits for RFV, RQ and LCI ranged between 0.60 and 0.90 in individuals with CF and healthy controls. In individuals with CF, percentage of change between the visits was 0.02% for RFV, -1.11% for RQ and 2.91% for LCI and limits of agreement between visits were - 4.3% and 3.9% for RFV, -4.4% and 3.7% for RQ, and -2.6 and 3.0 for LCI. CONCLUSIONS Functional imaging is reproducible and short-term changes in RFV and RQ greater than ±4.4% can be considered clinical meaningful. Very good short-term reproducibility, and easy application without the need for breathing maneuvers or contrast agent, makes MP MRI a promising surveillance method for CF.

Comparison of different analysis algorithms to calculate multiple-breath washout outcomes

Lung clearance index (LCI) is the main outcome of the multiple-breath washout (MBW) test. Current recommendations for LCI acquisition are based on low-grade evidence. The aim of this study was to challenge those recommendations using alternative methods for LCI analysis. Nitrogen MBW measurements from school-aged children, 20 healthy controls, 20 with cystic fibrosis (CF) and 17 with primary ciliary dyskinesia (PCD), were analysed using 1) current algorithms (standard), 2) three alternative algorithms to detect with higher precision the end of MBW testing and 3) two alternative algorithms to determine exhaled tracer gas concentrations. LCI values, intra-test repeatability, and ability to discriminate between health and lung disease were compared between these methods. The analysis methods strongly influenced LCI (mean±sd overall differences (%) between standard and alternative analysis methods: −4.9±5.7%; range: −66–19%), but did not improve intra-test variability. Discrimination between health and disease was comparable as areas under the receiver operator curves were not greater than that from standard analysis. This study supports current recommendations for LCI calculation in children. Alternative methods influence LCI estimates and hamper comparability between MBW setups. Alternative algorithms, whenever used, should be carefully reported. Lung clearance index values are strongly affected by the algorithms used for the analysis http://ow.ly/h2Rs30ktPiN