Abnormal Lung Clearance Index Research Articles

Lung structural and functional impairments in young children with cystic fibrosis diagnosed following newborn screening – A nationwide observational study

BackgroundNon-invasive and sensitive clinical endpoints are needed to monitor onset and progression of early lung disease in children with cystic fibrosis (CF). We compared lung clearance index (LCI), FEV1, functional and structural lung magnetic resonance imaging (MRI) outcomes in Swiss children with CF diagnosed following newborn screening. MethodsLung function (LCI, FEV1) and unsedated functional and structural lung MRI was performed in 79 clinically stable children with CF (3 – 8 years) and 75 age-matched healthy controls. Clinical information was collected throughout childhood. ResultsLCI, ventilation and perfusion defects, and structural MRI scores were significantly higher in children with CF compared with controls, but FEV1 was not different between groups. Lung MRI outcomes correlated significantly with LCI (morphology score (r = 0.56, p < 0.001); ventilation defects (r = 0.43, p = 0.001); perfusion defects (r = 0.64, p < 0.001), but not with FEV1. Lung MRI outcomes were more sensitive to detect impairments in children with CF (abnormal ventilation and perfusion outcomes in 47 %, morphology score in 30 %) compared with lung function (abnormal LCI in 21 % and FEV1 in 4.8 %). Pulmonary exacerbations, respiratory hospitalizations, and increase in patient-reported cough was associated with higher LCI and higher structural and functional MRI outcomes. ConclusionsThe LCI and lung MRI outcomes non-invasively detect even mild early lung disease in young children with CF diagnosed following newborn screening. Pulmonary exacerbations and early respiratory symptoms were risk factors for structural and functional impairment in childhood.

A Pilot Study of Lung Clearance Index as a Useful Outcome Marker in the Follow-Up of Pediatric Patients with Non-Cystic Fibrosis Bronchiectasis?

The forced expiratory volume in one second (FEV1) is regularly used for the follow-up of patients with non-cystic fibrosis bronchiectasis (nCF-BE). The lung clearance index (LCI), measured by the multiple breath washout test, has been recently proposed as a lung function measure and a potential tool more sensitive than the FEV1 measured by spirometry in assessing airway changes seen on imaging. While several data have been endorsed as a useful endpoint in clinical trials of patients with early or mild CF lung disease and as the main outcome measure in clinical trials with CFTR modulators in children and adolescents with CF, few data are available in the context of non-CF bronchiectasis. The aim of this pilot study was to compare the LCI with the FEV1 as well as the forced vital capacity (FVC), the forced expiratory flow at 25-75% of the FVC (FEF 25-75%), and chest imaging based on the modified Reiff score in patients with primary ciliary dyskinesia (PCD) and non-CF, non-PCD bronchiectasis (PCD-BE and nCFnPCD-BE). Additionally, we compared each test's duration and the preferred technique. Twenty children were included; nine had PCD-BE and eleven had nCFnPCD-BE. The median age was twelve years (ages ranging between five and eighteen years). The median LCI was seven while the median z-scores of the FEV1, FVC, and FEF 25-75% were -0.6, 0, and -0.9, respectively. No significant associations or correlations were observed between LCI, spirometric parameters, or the modified Reiff score. However, nearly half of the population (n = 9) had an abnormal LCI, while only 10% had an abnormal FEV1. A total of 75% of children preferred MBW, despite it lasting five times longer than spirometry. In this paper, the authors suggest that LCI might be useful in a cohort of pediatric patients with PCD-BE and nCFnPCD-BE for detecting early lung function changes during their follow-up. Additionally, MBW seems to be preferred by patients. These data may encourage further studies on this topic.

Time Free From Hospitalization in Children and Adolescents With Cystic Fibrosis: Findings From FEV1, Lung Clearance Index and Peak Work Rate.

BackgroundAn exercise test combined with a multiple breath washout nitrogen test (MBWN2) may offer a comprehensive clinical evaluation of cystic fibrosis (CF) disease in children with normal spirometry. The purpose of the present study is to explore whether information derived from spirometry, MBWN2, and exercise tests can help the CF multidisciplinary team to characterize time free from hospitalization due to pulmonary exacerbation (PE) in a cohort of pediatric patients with CF.MethodsThis prospective observational study was carried out at the Lombardia Region Reference Center for Cystic Fibrosis in Milano, Italy. In 2015, we consecutively enrolled children and adolescents aged <18 years with spirometry, MBWN2, and Godfrey exercise test performed during an outpatient visit.ResultsOver a median follow-up time of 2.2 years (interquartile range [IQR], 2.01; 3.18), 28 patients aged between 13.0 and 17.4 years were included. When lung functions were outside the normal range, 50% of patients were hospitalized 4 months after the outpatient visit, and their response to exercise was abnormal (100%). Half of the individuals with normal forced expiratory volume in the first second (FEV1) and abnormal lung clearance index (LCI) experienced the first hospital admission 9 months after the clinic visit, and 84.2% presented an abnormal response to exercise. Conversely, 15.8% had abnormal exercise responses when lung functions were considered normal, with half of the adolescents hospitalized at 11 months.ConclusionMaintaining ventilation homogeneity, along with a normal ability to sustain intense work, may have a positive impact on the burden of CF disease, here conceived as time free from hospitalization due to PE.

Chest X-rays are less sensitive than multiple breath washout examinations when it comes to detecting early cystic fibrosis lung disease.

AimAnnual chest X‐ray is recommended as routine surveillance to track cystic fibrosis (CF) lung disease. The aim of this study was to investigate the clinical utility of chest X‐rays to track CF lung disease.MethodsChildren at Gothenburg's CF centre who underwent chest X‐rays, multiple breath washouts and chest computed tomography examinations between 1996 and 2016 were included in the study. Chest X‐rays were interpreted with Northern Score (NS). We compared NS to lung clearance index (LCI) and structural lung damage measured by computed tomography using a logistic regression model.ResultsA total of 75 children were included over a median period of 13 years (range: 3.0‐18.0 years). The proportion of children with abnormal NS was significantly lower than the proportion of abnormal LCI up to the age of 4 years (p < 0.05). A normal NS and a normal LCI at age 6 years were associated with a median (10‐90th percentile) total airway disease of 1.8% (0.4‐4.7%) and bronchiectasis of 0.2% (0.0‐1.5%).ConclusionChest X‐rays were less sensitive than multiple breath washout examinations to detect early CF lung disease. The combined results from both methods can be used as an indicator to perform chest computed tomography less frequently.

Lung Clearance Index to Detect Early Pulmonary Changes in Children with Sickle Cell Disease

<i>Objective:</i> Pulmonary complications including acute chest syndrome, are leading causes of sickle cell disease (SCD) related morbidity and mortality. Prior studies have shown that patients with pulmonary complications have evidence of pulmonary involvement reflected in lung functions trends as early as childhood. Spirometry is the current standard for measuring lung function. Growing evidence suggests that lung clearance index (LCI) which is a commonly reported parameter of multiple breath washout (MBW) tests, is more sensitive than spirometry measurements in the early identification of pulmonary changes in pediatric patients. The aim of our study was to determine if this relationship between LCI and spirometry existed within the pediatric sickle cell population. <i>Study Design: </i>This is a cross-sectional, retrospective study to compare LCI to spirometry measurements in children with SCD. Charts were reviewed of clinic encounters at Phoenix Children’s Hospital from March 1, 2013 – June 30, 2017. Spirometry and MBW measurements were collected from 23 patients between the ages of 5 years – 22 years. The MBW utilized sulfur hexafluoride (SF₆) as the tracer gas. Demographics and SCD variant (e.g. HbSS, HbSC, etc.) for each encounter were also collected. <i>Results: </i>Our results show that LCI correlates to FEV₁% predicted (Spearman’s coefficient -0.44, p = 0.003) and FEF_25-75% (Spearman’s coefficient -0.49, p <0.001) over time. Based on demographics, LCI is affected by weight (p = 0.046) but not age or height. When comparing LCI and FEV₁% predicted, abnormal LCI results were noted to occur even in the presence of normal FEV₁% predicted measurements. <i>Conclusions: </i>Our data support LCI correlating with spirometry measurements, but more studies are necessary to explore whether LCI can be used as a screening test to detect pulmonary changes in young children with SCD. Earlier monitoring of lung function will allow for preventative therapies and delayed progression of pulmonary dysfunction.

Impulse oscillometry indices to detect an abnormal lung clearance index in childhood cystic fibrosis.

The objective of our cross-sectional study was to assess the relationships between indices of multiple breath washout (MBW) and impulse oscillometry system (IOS) in cystic fibrosis in forty consecutive children (median age 8.1 years) in stable conditions and to evaluate whether cut-off values of IOS indices may help to avoid MBW, which is time-consuming. IOS measurements took a median duration of 3 min, while MBW measurements took a median duration of 49 min. Lung Clearance Index (LCI2.5% ) depicted significant linear correlations with z-scores of R5Hz, R5-20Hz, X5Hz, AX, and Fres (r2 = 0.27 to 0.51). Receiver-operator characteristic curves were constructed and showed that the best compromise was obtained with the z-score of Fres, with a cut-off value of -1.37 that had a sensitivity of 0.966, a specificity of 0.636, and a negative predictive value of 0.875. This z-score is useful for excluding increased LCI2.5% when below -1.37 using the reference set of Gochicoa et al. In conclusion, IOS measurement is easily and rapidly obtained in children and may be clinically useful for excluding increased LCI2.5% , thus allowing the time-consuming MBW test to be avoided.

Abnormal Lung Clearance Index in Cystic Fibrosis Children with Normal FEV1 and Single-Breath Nitrogen Washout Test.

Single- and multiple-breath washout tests (SBW and MBW) measure ventilation inhomogeneity, but the relationship between them is unclear. Forty-three subjects with cystic fibrosis (CF) and healthy controls (HC) 8-21years of age were recruited (CF = 30 and HC = 13) and performed nitrogen MBW, vital capacity SBW, spirometry, and plethysmography. Mean phase III slope from SBW (SIII) and lung clearance index (LCI) were significantly different between CF and HC (p = 0.017 and p < 0.0001, respectively). Based on Pearson correlation, SIII and LCI showed strong correlation (ρ = 0.81, p < 0.0001). Both SIII and LCI significantly correlated with spirometry (all p < 0.05). Among CF subjects with normal FEV1 (≥ 80%; n = 17), 76% (n = 13) had normal SIII but abnormal LCI. We conclude that LCI can be abnormal despite normal SIII and FEV1 in CF children. Although LCI and SIII showed strong correlation, our results suggest that LCI is a better test to detect ventilation inhomogeneity in CF children with normal FEV1.

Multiple breath washout: A noninvasive tool for identifying lung disease in symptomatic military deployers

RationaleMilitary deployments to austere environments since November 9, 2001 may put “deployers” at risk for respiratory disease. Sensitive, noninvasive tools for detecting large and small airways injury are needed to identify early disease and help inform management for this at-risk population. ObjectivesWe examined multiple breath washout (MBW) as a tool for identifying deployment-related airways disease and assessed host and exposure risk factors compared to healthy controls. MethodsBetween March 2015 and March 2020, 103 healthy controls and 71 symptomatic deployers with asthma and/or distal lung disease completed a questionnaire, spirometry and MBW testing. SAS v. 9.4 was used to compare MBW parameters between deployers and controls via univariate analyses and adjusted for demographic factors using multiple linear regression. Measurements and main resultsDeployers were significantly more likely than controls to have an abnormal lung clearance index (LCI) score indicating global ventilation inhomogeneity. Adjusting for sex, smoking status, smoking pack-years and body mass index, LCI scores were significantly more abnormal among those with deployment-related asthma and distal lung disease compared to controls. The unadjusted variable Sacin (a marker of ventilation inhomogeneity in the acinar airways) was higher and thus more abnormal in those with both proximal and distal airways disease. Deployers who reported more frequent exposure to explosive blasts had significantly higher LCI scores. ConclusionsThis study demonstrates the utility of MBW in evaluating exposure-related airways disease in symptomatic military personnel following deployment to austere environments, and is the first to link exposure to explosive blasts to measurable small airways injury.

Lung clearance index and steroid response in pediatric severe asthma.

Lung clearance index (LCI) is a measure of airway disease that has been shown to be abnormal in asthma. We hypothesized that LCI would be higher (worse) in children with severe therapy-resistant asthma (STRA) compared with difficult asthma (DA) and healthy controls and that LCI would fall in response to parenteral steroids in STRA. Sixty-four children with asthma who were prescribed high-dose asthma therapy (GINA steps 4 or 5) performed LCI and spirometry. Forty-three had STRA and 21 DA. Thirty-nine of forty-three STRA patients attended for a clinically indicated bronchoscopy during which an intramuscular injection of triamcinolone was given. LCI, spirometry, and fractional exhaled nitric oxide (FeNO) were performed on the day of the bronchoscopy and repeated 4 weeks later. LCI was more abnormal in STRA (median: 7.40, range: 5.58-12.34) than in DA (6.55, 5.77-7.75), P = .0006, and healthy controls (6.53, 5.57-7.35), P = .005. In contrast to the first second forced expired volume (FEV1 ), LCI improved following systemic steroids; of 20 STRA patients with an abnormal LCI at baseline, 13 improved following triamcinolone. LCI and FeNO responses were concordant. There is a subgroup of children with STRA in whom LCI is elevated who improve following parenteral steroids. LCI may be a valuable additional domain in assessing steroid response in pediatric asthma.

Ventilation heterogeneity and oscillometry predict asthma control improvement following step-up inhaled therapy in uncontrolled asthma.

Abnormal peripheral airway function is an important feature of asthma and relates to asthma symptoms and poor asthma control. We aimed to determine whether peripheral airway function, as measured by forced oscillatory impedance and multiple-breath nitrogen washout (MBNW), relates to symptom improvement in asthmatic participants with uncontrolled asthma, after stepping up to high-dose ICS/LABA treatment. A total of 19 subjects (14 females, mean age: 29.9 ± 13.6 years) with uncontrolled asthma, as defined by an ACQ5 > 1.5, taking 500 μg/day fluticasone equivalent or less, underwent spirometry, plethysmography, fractional exhaled FeNO, forced oscillatory resistance (Rrs5Hz ) and reactance (Xrs5Hz ), and indices of MBNW ventilation heterogeneity (lung clearance index (LCI), diffusion-convection-dependent (Sacin) and convection-dependent (Scond)). Measurements were made before and after 8 weeks of treatment with fluticasone/formoterol combination inhaler 250/10 μg, 2 puffs twice daily. Treatment improved ACQ5 (P = 0.0002), FEV1 (P = 0.02), FVC (P = 0.04), FeNO (P = 0.0008), Xrs5Hz (P = 0.01), LCI (P = 0.0002), Sacin (P = 0.006) and Scond (P = 0.01). At baseline, ACQ5 correlated with Xrs5Hz (rs = 0.52, P = 0.03) and Rrs5Hz (rs = 0.55, P = 0.02). The improvement in ACQ5 was predicted by more abnormal baseline LCI (P = 0.03), Scond (P = 0.02) and Rrs5Hz (P = 0.006). Baseline Scond was the best predictor of a clinically meaningful improvement in asthma control (ΔACQ > 0.5, ROC-AUC = 0.91, P = 0.007). Step-up to high-dose combination treatment in uncontrolled asthma is associated with improved peripheral airway function as measured by Xrs5Hz and MBNW. Baseline MBNW and FOT parameters correlated with the improvement in symptoms and may predict a positive response to up-titration in uncontrolled asthmatic patients.

Abnormal Lung Clearance Index in Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) Children with Otherwise Normal FEV1.

In preschool children with cystic fibrosis (CF), lung clearance index (LCI) is a sensitive test to detect early lung disease. Some children with CF screen positive, inconclusive diagnosis (CFSPID) may in time develop clinical features of CF. LCI has not been studied in CFSPID children. LCI and spirometry were performed in preschool age children with CF, CFSPID, and non-CF healthy controls (HCs) during two visits. Fifty-four preschool age children (HC n = 18, CFSPID n = 17, and CF n = 19) were tested. Mean LCI from the CFSPID group was not statistically different from HC (p = 0.49), but significantly different when compared to CF (p = 0.04). LCI was abnormal in 2 CFSPID children who carried potentially deleterious CFTR variants. Mean forced expiratory volume in 1s (FEV1) was not statistically different between CFSPID and CF (p = 0.26). LCI can potentially detect early lung disease in CFSPID individuals as part of assessing their risk for reclassification to CF diagnosis.

Lung clearance index: assessment and utility in children with asthma.

There is increasing evidence that ventilation heterogeneity and small airway disease are significant factors in asthma, with evidence suggesting that the small airways are involved from an early stage in childhood asthma. Spirometry is commonly used to monitor lung function in asthmatics; however, it is not sensitive to small airway disease. There has been renewed interest in multibreath washout (MBW) tests, with recognition of the lung clearance index (LCI) as a global index of abnormality in gas mixing of the lungs that therefore also reflects small airway disease. This review summarises the technical and practical aspects of the MBW/LCI in children, and the differences between commercially available equipment. Children with severe asthma are more likely to have an abnormal LCI, whereas most children with mild-to-moderate asthma have an LCI within the normal range, but slightly higher than age-matched healthy controls. Monitoring children with asthma with MBW alongside standard spirometry may provide useful additional information.

Lung clearance index in detection of post-transplant bronchiolitis obliterans syndrome.

BackgroundLong-term outcomes after lung transplantation are often limited by the development of obliterative bronchiolitis (OB), which is clinically defined using spirometry as bronchiolitis obliterans syndrome (BOS). Lung clearance index (LCI), derived from multiple breath washout (MBW) testing, is a global measure of ventilation heterogeneity that has previously been shown to be a more sensitive measure of obstructive small airway diseases than spirometry. We aimed to assess the feasibility of LCI in adult lung transplant patients and to compare LCI to BOS grade.Methods51 stable adult double-lung transplant recipients performed sulfur hexafluoride MBW in triplicate on a single occasion, using a closed-circuit Innocor device. BOS grades were derived from serial spirometry according to International Society for Heart and Lung Transplantation criteria and, where available, high-resolution computed tomography (HRCT) evidence of OB was recorded.ResultsLCI was successfully performed in 98% of patients. The within-visit coefficient of variation for repeat LCI measurements was 3.1%. Mean LCI increased significantly with BOS grades: no BOS (n=15), LCI 7.6; BOS-0p (n=16), LCI 8.3; BOS-1 (n=11), LCI 9.3; BOS-2–3 (n=9), LCI 13.2 (p<0.001). 27 patients had HRCT within 12 months. LCI in those with HRCT evidence of OB was higher than those without OB (11.1 versus 8.2, p=0.006). 47% patients displayed abnormal LCI (>7) despite a normal forced expiratory volume in 1 s (FEV1) (>80% of baseline).ConclusionsLCI measurement in lung transplant recipients is feasible and reproducible. LCI increased with increasing BOS grade. A significant proportion of this cohort had abnormal LCI with preserved FEV1, suggesting early subclinical small airway dysfunction, and supporting a role for MBW in the early identification of BOS.

Relationship between respiratory function and need for NIV in childhood SMA.

BackgroundSpinal muscular atrophy (SMA) causes progressive respiratory muscle weakness but respiratory function (RF) in those using noninvasive ventilation (NIV) is not well described.ObjectiveTo describe RF in childhood SMA and assess differences between those using and not using NIV.MethodsA cross‐sectional study of childhood SMA assessed polysomnography (PSG), spirometry, forced oscillation technique (FOT), lung clearance index (LCI), sniff nasal inspiratory pressures, peak cough flow, maximal inspiratory and expiratory pressure, and NIV use and indication.ResultsTwenty‐five children (median age [interquartile range], 8.96 [5.63] years; 10 F) with SMA 1 (n = 3), 2 (n = 15), and 3 (n = 7) were recruited. Spirometry and FOT testing was feasible in children as young as 3 years. Ten (40%) required NIV, 5 for sleep‐disordered breathing (SDB), and 5 initiated during lower respiratory tract infection (LRTI). Children requiring NIV were older (median, 10.52 vs 5.67 years; P < .02) with more abnormal forced vital capacity (FVC) z‐score (−5.70 vs −1.39, P < .02), Rsr8 z‐score (1.97 vs 0.50, P = .04), and LCI (8.84 vs 7.34, P = .01). Two had normal RF and SDB. For FVC z‐score less than −2.5 and LCI greater than 7.5, the odds ratio for NIV was 10.70 (95% confidence interval [CI], 1.39‐82.03) and 2 (95% CI, 0.40‐10.31), respectively. All children with LCI greater than 8 used NIV. FVC z‐score and LCI are associated with maximum transcutaneous carbon dioxide on PSG (r = 0.43, P < .001).ConclusionNIV is common in SMA. Normal RF does not exclude SDB. Children with more abnormal FVC and LCI should be considered at risk of starting NIV during/following an LRTI.

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.

Abnormal preschool Lung Clearance Index (LCI) reflects clinical status and predicts lower spirometry later in childhood in cystic fibrosis

BackgroundClinical and prognostic value of preschool Multiple Breath Washout (MBW) remains unclear. MethodsInitial MBW results (Exhalyzer® D, EcoMedics AG) in preschool Cystic Fibrosis (CF) subjects (age 2–6 years) at a time of clinical stability were compared to (1) concurrent clinical status measures and (2) later spirometry outcomes. Abnormal Lung Clearance Index (LCI) was defined using published reference data (ULN for LCI 8.0). ResultsLCI was abnormal in 56% (28/50), with mean (SD) LCI 8.61(1.85) at age 4.71(1.3) years. Abnormal LCI was associated with higher dornase alfa use, previous positive bacterial cultures and pF508.del homozygous genotype. Later spirometry (n = 44; mean (SD) 2.3(0.5) years after MBW) demonstrated that abnormal initial preschool LCI was a strong predictor of lower later spirometry outcomes. ConclusionAbnormal preschool LCI was associated with concurrent measures of clinical status and later spirometry deficits, suggesting early prognostic utility of MBW testing in this age range.

Lung clearance index is elevated in young children with symptom-controlled asthma.

BackgroundPulmonary function testing has been recommended as an adjunct to symptom monitoring for assessment of asthma control. Lung clearance index (LCI) measures ventilation inhomogeneity and is thought to represent changes in the small airways. It has been proposed as a useful early marker of airway disease in asthmatic subjects, and determining it is feasible in preschool children. This study aims to assess whether LCI remains elevated in symptomatically controlled asthmatic children with a history of severe asthma, compared with healthy controls. A secondary aim was to determine whether the results were consistent across the preschool and school‐aged populations.MethodsUsing a case‐control design, we compared 33 children with currently well‐controlled symptoms who had a history of severe asthma, to 45 healthy controls (age 3‐15 years) matched by age, height, and sex. We performed multiple breath washout tests using sulfur hexafluoride as a tracer gas, to determine their LCI and Scond values.ResultsIn the overall study, LCI z‐score values were on average 0.86 units (95% confidence interval: 0.24‐1.47, P = 0.01, t‐test) higher in children with a history of severe asthma with current well‐controlled symptoms compared with healthy controls. In addition, within the subgroup of preschool children (age ≤ 6), the asthmatic had significantly higher LCI z‐score values than their healthy controls peers (mean (SD), 0.57 (2.18) vs −1.10 (1.00), P = 0.03, t‐test). Twenty‐seven percent (27%; 9/33) of subjects had an LCI value greater than the upper limit of our healthy controls despite being symptom controlled. Amongst preschool children, 5 (42%; 5/12) of the asthmatic children had abnormal LCI at the individual level.ConclusionsLCI is elevated in children with asthma, which may be driven by differences in the preschool population. LCI may be useful in defining preschool asthma endotypes with persistent ventilation inhomogeneity despite symptomatic control.

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...

Pulmonary function deficits in newborn screened infants with cystic fibrosis managed with standard UK care are mild and transient.

With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants.Forced expiratory volume in 0.5 s (FEV0.5), lung clearance index (LCI) and plethysmographic functional residual capacity were measured at ∼3 months, 1 year and 2 years in 62 infants with CF and 34 controls.By 2 years there was no significant difference in FEV0.5 z-score between CF and controls, whereas mean LCI z-score was 0.81 (95% CI 0.45-1.17) higher in CF. However, there was no significant association between LCI z-score at 2 years with either 3-month or 1-year results. Despite minimal average group changes in any ILF outcome during the second year of life, marked within-subject changes occurred. No child had abnormal LCI or FEV0.5 on all test occasions, precluding the ability to identify "high-risk" infants in early life.In conclusion, changes in lung function are mild and transient during the first 2 years of life in newborn screened infants with CF when managed according to a standardised UK treatment protocol. Their potential role in tracking disease to later childhood will be ascertained by ongoing follow-up.

Agreement between multiple-breath nitrogen washout systems in children and adults

BackgroundComparability of multiple breath washout (MBW) systems has been little explored. We assessed agreement in lung clearance index (LCI) from two similar, commercial nitrogen MBW setups in patients with Cystic Fibrosis (CF) and controls. MethodsThe EasyOne Pro (NDD) and Exhalyzer D (EM) were randomly applied in 85 adults (34 with CF) and 97 children (47 with CF and normal forced expiratory volume in one second). We assessed differences between setups in LCI, lung volumes and breathing pattern and diagnostic performance for detecting abnormal lung function. ResultsCompared to NDD, EM measured higher LCI, functional residual capacity and cumulative expired volume while respiratory rate was lower. Mean difference (limits of agreement) in LCI was 1.30 (−2.34 to 4.94). In CF, prevalence of abnormal LCI was greater in children and similar in adults using EM compared to NDD. ConclusionsAgreement of MBW outcomes between setups is poor and explained by nitrogen measurement techniques and breathing pattern.