Lung Clearance Index Values Research Articles

How Does the Corrected Exhalyzer Software Change the Predictive Value of LCI in Pulmonary Exacerbations in Children with Cystic Fibrosis?

Aim: Recently, the most commonly used for multiple breath washout device, the Exhalyzer D, has been shown to overestimate lung clearance index (LCI) results due to a software error. Our study aimed to compare the predictive values of LCI in the CF pulmonary exacerbations (PE) calculated with the updated (3.3.1) and the previous (3.2.1) version of the Spiroware software. Materials and Methods: The measurements were performed during 259 visits in CF pediatric patients. We used 39ΔPE pairs (PE preceded by stable visit) and 138ΔS pairs (stable visit preceded by stable visit) to compare the LCI changes during PE. The areas under the receiver operating curves (AUCROC) and odds ratios were calculated based on the differences between ΔPEs and ΔSs. The exacerbation risk was estimated using a logistic regression model with generalized estimating equations (GEE). Results: There were statistically significant differences in LCI 2.5% median values measured using the two versions of the software in the stable condition but not during PE. The AUCROC for changes between the two consecutive visits for LCI did not change significantly using the updated Spiroware software. Conclusions: Despite the lower median values, using the recalculated LCI values does not influence the diagnostic accuracy of this parameter in CF PE.

Lung clearance index in children with cystic fibrosis previously diagnosed with CRMS/CFSPID: A monocentric prospective experience.

No data are available on the values and role of lung clearance index (LCI) in cystic fibrosis (CF) Screen Positive Inconclusive Diagnosis (CFSPID) progressed to CF diagnosis (CFSPID > CF). This study aimed to assess the value of the LCI in correctly predicting the progression of CFSPID to CF. This is a prospective study carried out at the CF Regional Center of Florence, Italy fromSeptember 1, 2019. We compared LCI values in children with CF diagnosed for positive newborn screening (NBS), CFSPID or CFSPID > CF for pathological sweat chloride (SC). The Exhalyzer-D (EcoMedics AG, Duernten, Switzerland, software version 3.3.1) was used to conduct the LCI tests, every 6 months on stable children. Forty-two cooperating children were enrolled (mean age at LCI tests: 5.4 years, range: 2.7-8.7): 26 (62%) had CF, 8 (19%) were CFSPID > CF for positive SC, while 8 (19%) kept the CFSPID label at last LCI test. The mean LCI value for patients with CF (7.39; 5.98-10.24) was statistically higher compared to both the mean LCI in the CFSPID > CF (6.62; 5.69-7.58) and in CFSPID (6.56; 5.64-7.21). Most of asymptomatic CFSPID or progressed to CF have normal LCI. Further data on the longitudinal course of LCI during follow up of CFSPID and on larger cohorts is needed.

Effect of Dornase Alfa on the Lung Clearance Index in Children with Cystic Fibrosis: A Lesson from a Case Series.

Dornase alfa (DNase) is the only mucus-degrading agent that has proven efficacy in cystic fibrosis (CF). Few studies have evaluated the effects of DNase on the lung clearance index (LCI). We report the experience of two CF centers in which LCI monitoring was used to evaluate the efficacy of DNase therapy. This is a prospective and observational study, evaluating the effects of DNase therapy on LCI values in three CF children followed at CF centers in Florence and Catania, Italy. In both centers, LCI was performed routinely, every 3-6 months, based on the clinical picture and severity of the lung disease. In this study, we evaluated the LCI before and after long-term DNase therapy. DNase improved LCI values in the absence of respiratory exacerbations: in case n. 1 LCI decreased by 39% in 16 months (from 11.1 to 6.8); in case n. 2 by 20% in 12 months (from 9.3 to 7.4); in case n. 3 by 24% in 16 months (from 9.3 to 7.0). This case series confirms the efficacy of DNase therapy in CF children, as demonstrated by the LCI reduction in treated patients. Furthermore, our results suggest that LCI is a sensitive marker of disease and can be used for the evaluation of response to treatment.

The Relation between Vitamin D Level and Lung Clearance Index in Cystic Fibrosis-A Pilot Study.

Background: Life expectancy has increased in cystic fibrosis (CF) patients; however, the rate of mortality is still high, and in a majority of cases, the cause of death is due to respiratory deterioration. Vitamin D plays an important role in immunity and infection prophylaxis, as its deficiency is associated with frequent infections. In CF patients, a deficit of liposoluble vitamins is common, despite daily supplementation. The aim of this study is to evaluate the relation between vitamin D status and lung function expressed by lung clearance index (LCI) in patients with CF. We also assessed the relation of factors such as nutritional status, genotype, and associated comorbidities such as Pseudomonas infection, cystic fibrosis-related diabetes (CFRD), and cystic fibrosis liver disease (CFLD) with vitamin D and LCI. Methods: A cross-sectional study was conducted at the National Cystic Fibrosis Center by analyzing patients with CF who presented in our center between November 2017 and November 2019. We enrolled in the study patients diagnosed with CF, who were followed up in our CF center and who were able to perform lung function tests. Patients in exacerbation were excluded. Results: A strong negative correlation was found between vitamin D and LCI (r = −0.69, p = 0.000). A lower vitamin D storage was found in patients with CFLD and CFRD. Higher LCI values were found among patients with chronic Pseudomonas infection, with BMI under the 25th percentile, or with associated CFLD. Conclusion: In CF patients, vitamin D plays an important role, and its deficit correlates with an impaired LCI. Vitamin D deficit is a risk factor in patients with associated comorbidities such as CFLD and CFRD. Chronic infection with Pseudomonas, the presence of impaired nutritional status, and CFLD are associated with a prolonged LCI.

Association of lung clearance index with survival in individuals with cystic fibrosis

The lung clearance index (LCI) assesses global ventilation inhomogeneity and is a sensitive biomarker of airway function in cystic fibrosis (CF) lung disease. We examined the association of LCI with the risk of death or lung transplantation (LTx) in individuals with CF. We performed a retrospective analysis in a cohort of individuals with CF aged ≥5 years with LCI and forced expired volume in 1 s (FEV1) measurements performed between 1980 and 2006. The outcome was time until death or LTx. We used the earliest available LCI and FEV1 values in a Cox proportional hazards regression adjusted for demographic and clinical variables. For sensitivity analyses, we used the mean of the first three LCI and FEV1 measurements, stratified the cohort based on age, and investigated individuals with normal FEV1. In total, 237 individuals with CF with a mean (range) age of 13.9 (5.6-41.0) years were included. The time-to-event analysis accrued 3813 person-years and 94 (40%) individuals died or received LTx. Crude hazard ratios were 1.04 (95% CI 1.01-1.06) per 1.0 z-score increase in LCI and 1.25 (95% CI 1.11-1.41) per 1.0 z-score decrease in FEV1. After adjusting LCI and FEV1 mutually in addition to sex, age, body mass index and number of hospitalisations, hazard ratios were 1.04 (95% CI 1.01-1.07) for LCI and 1.12 (95% CI 0.95-1.33) for FEV1. Sensitivity analyses yielded similar results and using the mean LCI strengthened the associations. Increased ventilation inhomogeneity is associated with greater risk of death or LTx. Our data support LCI as novel surrogate of survival in individuals with CF.

WS06.1 Clinical value of Lung Clearance Index among patients with cystic fibrosis

WS06.1 Clinical value of Lung Clearance Index among patients with cystic fibrosis

Changes in mucociliary clearance over time in children with cystic fibrosis.

(a) To quantify changes in mucociliary clearance (MCC) over time in children with cystic fibrosis (CF) and the relationship between MCC and rate of infection with Pseudomonas aeruginosa (PA); (b) to determine the impact of MCC on the evolution of CF lung disease; and (c) to explore the role of mucus composition as a determinant of MCC. Children with CF, who had previously undergone an MCC measurement (visit 1), underwent the following tests 3 to 10 years later: (a) second MCC measurement (visit 2); (b) multiple breath washout to assess ventilation inhomogeneity, expressed as lung clearance index (LCI); (c) high resolution computed tomography lung scan (HRCT); and (d) induced sputum test. Number of PA + cultures/year between visits was documented and mucus dry weight was quantified in the children and adult controls. Nineteen children completed both visits. Median time between visits was 4.6 years. Clearance declined 30% between visits. Lower MCC on visit 2 was associated with more PA+ cultures/year between visits. Lower MCC values on visit 1 were associated with higher LCI values and higher HRCT scores on visit 2. Mucus dry weight was significantly higher in children with CF compared with controls. Higher dry weights were associated with lower MCC. Mucociliary clearance declines significantly over time in children with CF. The decline is associated with PA infection rate and is affected by mucus composition. Children with early slowing of MCC appear to be at risk for developing ventilation inhomogeneity and parenchymal lung damage when they are older.

End-expiratory lung volume assessment using helium and carbon dioxide in an experimental model of pediatric capnoperitoneum.

Capnoperitoneum during laparoscopy leads to cranial shift of the diaphragm, loss in lung volume, and risk of impaired gas exchange. Infants are susceptible to these changes and bedside assessment of lung volume during laparoscopy might assist with optimizing the ventilation. Thus, the primary aim was to investigate the monitoring value of a continuous end-expiratory lung volume (EELV) assessment method based on CO2 dynamics ( ) in a pediatric capnoperitoneum model by evaluating the correlation and trending ability against helium washout (EELVHe ). Intra-abdominal pressure (IAP) was randomly varied between 0, 6, and 12mmHg with CO2 insufflation, while positive end-expiratory pressure (PEEP) levels of 3, 6, and 9cm H2 O were randomly applied in eight anesthetized and mechanically ventilated chinchilla rabbits. Concomitant and EELVHe and lung clearance index (LCI) were obtained under each experimental condition. Significant correlations were found between and EELVHe before capnoperitoneum (r=.85, P<.001), although increased IAP distorted this relationship. The negative influence of IAP was counteracted by the application of PEEP 9, which restored the correlation between and EELVHe and resulted in 100% concordance rate between the methods regarding changes in lung volume. EELVHe and LCI showed a curvilinear relationship, and an EELVHe of approximately 20mLkg-1 , determined with a receiver operating characteristic curve, was associated with near-normal LCI values. In this animal model of pediatric capnoperitoneum, reliable assessment of changes in EELV based on requires an open lung strategy, defined as EELV above approximately 20mLkg-1 .

Lung clearance index evaluation in detecting nocturnal hypoxemia in cystic fibrosis patients: Toward a new diagnostic tool

Nocturnal hypoxemia adversely affects outcomes in patients with cystic fibrosis (CF). Although an early detection of this abnormality may be desirable, still its predictability remains uncertain. The Lung Clearance Index (LCI) is a measure of lung ventilation distribution obtained from a multiple-breath washout technique (MBW), recently implemented in patients with CF. This study aimed to establish whether the LCI predicts nocturnal hypoxemia in patients with stable CF, with mild to moderate disease, and normal diurnal gas exchange. 31 stable patients (15 males, mean age 17.4±5.2 years) with mild to moderate CF, normoxic when awake, were enrolled. In all patients we performed nocturnal cardio-respiratory polygraphy, lung function measurement, and MBW test to derive LCI values. LCI was abnormal in most of the patients and inversely correlated with mean nocturnal SpO2 (r=-0.880 p<0.01). A receiver operating characteristic (ROC) analysis, performed to assess whether LCI predicted nocturnal hypoxemia, revealed a high predictive accuracy of LCI for nocturnal desaturation (AUC=0.96; Youden index=0.79). Forced expiratory volume in 1s (FEV1) was predictive only in patients with more severe airway obstruction, with a moderate degree of accuracy (AUC 0.71). The LCI showed a high effectiveness in predicting nocturnal hypoxemia in stable patients with CF, particularly when compared with a traditional parameter of lung function such as FEV1.

Lung clearance index for early detection of pulmonary complications after allo-HSCT in children.

Pulmonary chronic graft-vs-host disease (cGvHD) after hematopoietic stem cell transplantation (HSCT) is characterized by impairment of the small airways. Assessment of lung clearance index (LCI) gained from multiple breath washout (MBW) is more sensitive than spirometry in detection of small airways disease. The aim of this study was to describe the development of LCI during the first year after pediatric HSCT and how LCI relates to other pulmonary function parameters and cGvHD. This prospective, longitudinal study included 28 pediatric HSCT-recipients. Spirometry, Sulfur hexafluoride MBW and diffusion capacity of the lungs were performed before and at 3, 6, 9, and 12 months after HSCT. Respiratory symptoms and signs of cGvHD were recorded at each visit. Before HSCT, 47.8% had abnormal LCI and 12.5% had abnormal forced expiratory volume in 1 second (FEV1 ). Patients with persisting respiratory symptoms 12 months post-HSCT had higher median LCI (factor 5.7, P = 0.0018) and lower FEV1 z-scores (-1.5, P = 0.033) post-HSCT compared to patients free of respiratory symptoms. Overall, post-HSCT LCI values were 3.49 times higher and FEV1 was 2.31 z-scores lower in eight patients with cGvHD in any organ system compared with patients without cGvHD (P = 0.0089 and P < 0.0001). LCI values during the first 3 months were not predictive of pulmonary cGvHD. LCI is a sensitive marker for cGvHD and high LCI values were associated with persisting respiratory symptoms after 1 year. Further evaluation of MBW in early detection of HSCT-related pulmonary complications require larger patient cohorts and closer follow-up during the first months after HSCT.

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.

Ventilation inhomogeneity in infants with recurrent wheezing

BackgroundThe care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease...

Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index

PurposePrimary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients.MethodsSpirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded.ResultsLung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3).ConclusionThis study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient’s age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments.

Lung Clearance Index (LCI) in Patients with Bronchiolitis Obliterans: A Preliminary Report and Comparison to Cystic Fibrosis Patients

Bronchiolitis obliterans (BO) is a chronic airway disease following an insult to the lower respiratory tract. Lung clearance index (LCI) measures ventilation inhomogeneity and has been studied in cystic fibrosis (CF). We aimed to evaluate LCI in BO and to compare it to LCI in CF patients. LCI was measured in BO patients, compared to CF patients, and correlated with spirometry and CT findings. Twenty BO patients and 26 CF patients (with similar mean age and BMI) underwent evaluation. FEV1% and FEF25-75% predicted were significantly lower in the BO group (60.5±17.8 vs. 72.7±20.7, p=0.041, and 42.8±22.8 vs. 66.4±37.4, p=0.017, respectively). In both groups, LCI was inversely correlated with FVC%, FEV1%, and FEF25-75% predicted. LCI % was slightly higher (190.4±63.5 vs. 164.9±39.4, p=0.1) and FRC gas% (measured by multiple breath washout) was significantly higher in the BO group (92.5±35.9 vs. 71.3±18, p=0.014). The strength of statistical association between the lower FEF25-75% values and the higher LCI values was stronger in BO patients. Similar to CF, LCI may provide estimation of ventilation inhomogeneity in BO. The results indicate greater small airway involvement and air trapping in BO. Further prospective longitudinal studies evaluating the correlation of LCI measurements with multiple clinical and physiological parameters should be performed to assess the clinical benefit of LCI measurement in BO.

Maximal mid-expiratory flow is a surrogate marker of lung clearance index for assessment of adults with bronchiectasis.

Little is known about the comparative diagnostic value of lung clearance index (LCI) and maximal mid-expiratory flow (MMEF) in bronchiectasis. We compared the diagnostic performance, correlation and concordance with clinical variables, and changes of LCI and MMEF% predicted during bronchiectasis exacerbations (BEs). Patients with stable bronchiectasis underwent history inquiry, chest high-resolution computed tomography (HRCT), multiple-breath nitrogen wash-out test, spirometry and sputum culture. Patients who experienced BEs underwent these measurements during onset of BEs and 1 week following antibiotics therapy. Sensitivity analyses were performed in mild, moderate and severe bronchiectasis. We recruited 110 bronchiectasis patients between March 2014 and September 2015. LCI demonstrated similar diagnostic value with MMEF% predicted in discriminating moderate-to-severe from mild bronchiectasis. LCI negatively correlated with MMEF% predicted. Both parameters had similar concordance in reflecting clinical characteristics of bronchiectasis and correlated significantly with forced expiratory flow in one second, age, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, ventilation heterogeneity and bilateral bronchiectasis. In exacerbation cohort (n = 22), changes in LCI and MMEF% predicted were equally minimal during BEs and following antibiotics therapy. In sensitivity analyses, both parameters had similar diagnostic value and correlation with clinical variables. MMEF% predicted is a surrogate of LCI for assessing bronchiectasis severity.

New time-saving predictor algorithm for multiple breath washout in adolescents.

Multiple breath washout (MBW) is an informative but time-consuming test. This study evaluates the uncertainty of a time-saving predictor algorithm in adolescents. Adolescents were recruited from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC2000) birth cohort. MBW trials were performed at 13 y of age with Innocor model Inn00400 using sulfur hexafluoride (SF6) as tracer gas. Measurements were analyzed using a mixed model focusing on two prediction points doubling (t5%) and quadrupling (t10%) the standard end point (t2.5%). One hundred and seventy-two MBW trials conducted in 78 adolescents with and without asthma from COPSAC2000 were included. At t10%, the washout time (WoT) was reduced by 41%, and an uncertainty of 0.159 lung clearance index (LCI) units was introduced (±2 SD), ±1.27). At t5%, the WoT was reduced by 25%, with an uncertainty of 0.083 LCI units (±0.558). The optimal prediction point, which led to most saved time and least uncertainty was t5%. The predictor algorithm is capable of shortening the MBW test time but introduces an increasing uncertainty with earlier prediction points. This first-of-a-kind prediction algorithm holds promise in shortening the MBW test in children but should be used with caution in subjects with normal LCI values.

Ventilation Heterogeneity and Airway Hyperreactivity in Children with Well Controlled Asthma

Rationale: In asthma, airway inflammation, obstruction and reactivity may lead to ventilation heterogeneity; our understanding of this process is limited in asthmatic children. Objectives and Methods: The study’s objective was to measure ventilation heterogeneity, by the lung clearance index (LCI), in children with well controlled asthma and assess the association of LCI with airway reactivity through methacholine challenge tests. LCI and spirometry were measured in 24 children with asthma and 21 healthy controls between 4 and 10 years of age. Sixteen children with asthma and 11 healthy controls also performed methacholine challenge tests. Results: LCI was higher in children with asthma compared to healthy controls (7.58 vs 6.79, p=0.004); no differences in FEV1 or FEF25-75 were noted between groups. Ages were similar (p=0.54); however, the slope of LCI versus age differed between groups (p=0.001). The LCI slope increased with age in asthmatics. Further, higher LCI values were associated with decreasing PC20 (provocative concentration of methacholine to decrease baseline FEV1 by 20%) values in children with asthma (p=0.02), but not healthy controls (p=0.16). Conclusions: Ventilation heterogeneity is present from preschool age in children with well controlled asthma. The relationship between ventilation heterogeneity and airway reactivity suggests that normalizing ventilation heterogeneity may be an important therapeutic target for treating children with asthma.

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. Our aim was to challenge the validity of these software algorithms. We compared multiple breath washout (MBW) results of current software algorithms (automatic modus) to refined algorithms (manual modus) in 17 asymptomatic infants with CF, and 24 matched healthy term-born infants. The main difference between these two analysis methods lies in the calculation of the molar mass differences that the system uses to define the completion of the measurement. In infants with CF the refined manual modus revealed clearly elevated LCI above 9 in 8 out of 35 measurements (23%), all showing LCI values below 8.3 using the automatic modus (paired t-test comparing the means, P < 0.001). Healthy infants showed normal LCI values using both analysis methods (n = 47, paired t-test, P = 0.79). The most relevant reason for false normal LCI values in infants with CF using the automatic modus was the incorrect recognition of the end-of-test too early during the washout. We recommend the use of the manual modus for the analysis of MBW outcomes in infants in order to obtain more accurate results. This will allow appropriate use of infant lung function results for clinical and scientific purposes.

Using the same cut-off for sulfur hexafluoride and nitrogen multiple-breath washout may not be appropriate.

Recent evidence suggests that results from multiple-breath washout (MBW) using nitrogen (N 2 ) as washout gas are different to those obtained by using sulfur hexafluoride (SF 6 ). Explanations were mainly related to different MBW equipment and gas properties. We aim to mention a new aspect, namely using the same cut-off in both techniques to determine lung clearance index (usually 2.5% of initial tracer concentration) irrespective of additional contribution of tissue-nitrogen in N 2 -MBW. In a simple model calculation we subtracted 1% tissue-N 2 from the N 2 -MBW in real washout traces from two children, one with cystic fibrosis (CF) and one healthy. This "SF 6 -washout simulation" decreased LCI differently in the children. In the healthy subject 1/40 th (2.5%) was achieved two breaths earlier compared to the original signal and changed LCI from 6.7 to 5.9 (12%), while in CF 1/40 th was achieved 19 breaths earlier leading to a LCI decrease from 13.7 to 10.0 (27%). It would have been required to wash out SF6 until 1/66 th (1.5%) to be comparable to N 2 washout at 1/40th (2.5%), or to stop N2-MBW already at 3.5% of the starting concentration to make both techniques comparable. We show that a basic physiological-mathematical difference between both techniques additionally accounts for different sensitivities and poor agreement between SF 6 - and N 2 -MBW. The best way of adjusting for the contribution of tissue-N 2 needs to be examined in future studies. Thus, despite increasing use in different disease groups, the books on MBW technology are obviously not closed yet.

EPS04.2 Infant lung function: First report of a novel infant multiple breath washout apparatus

Objectives The value of lung clearance index (LCI) is well recognised in children and adults and has also been shown to be elevated in infants with CF. At present, there are considerable technical challenges in measuring LCI in infants. There is no simple method of assessing lung function in this population. The Innocor photoacoustic gas analyser measures very low concentrations of the inert tracer gas SF6. This has been developed into a novel mixed open–closed circuit system: expired gas is collected during washout to measure Functional Residual Capacity (FRC) and cumulative expired volume. This permits a low deadspace and ability to perform at rapid ventilation rates. Methods A prototype system was assessed using a lung model based on a mechanically driven 100 ml syringe and ventilation tank. The model delivered FRC's of 100–250 ml, with corresponding tidal volumes of 30–90 ml and respiratory rates of 20–40 min −1 . Improvements to hardware and washin protocol were made following initial testing. Results Following modification, overall mean error of FRC measurement was 0.04%. Actual mean FRC (ml) are shown in Table 1. Of 21 repeats, only 1 measurement was outside ±5% error range for FRC. Table 1Model FRC a (ml)Measured FRC (95% CI) (ml)Mean (SD) % error10299.2 (97.0–101.5)−1.76 (1.8)202203.3 (199.4–207.3)1.17 (2.34)252250.6 (247.4–253.8)−0.18 (1.63)aIncludes deadspace. Conclusion This system is capable of highly accurate measurement of FRC at volumes down to 100 ml in a realistic infant lung simulation. Accuracy is superior to previously described systems at higher FRC, and within the targets set by guidelines. In vivo testing is due to commence in 2015.