Multiple Breath Inert Gas Washout Research Articles

Shedding light into the black box of infant multiple-breath washout.

Multiple-breath inert gas washout (MBW) is a sensitive technique to assess lung volumes and ventilation inhomogeneity in infancy. Poor agreement amongst commercially available setups and a lack of transparency in the underlying algorithms for the computation of infant MBW outcomes currently limit the widespread application of MBW as a surveillance tool in early lung disease. We determined all computational steps in signal processing and the calculation of MBW outcomes in the current infant WBreath/Exhalyzer D setup (Exhalyzer D device, Eco Medics AG; WBreath software version 3.28.0, ndd Medizintechnik AG; Switzerland). We developed a revised WBreath version based on current consensus guidelines and compared outcomes between the current (3.28.0) and revised (3.52.3) WBreath version. We analyzed 60 visits from 40 infants with cystic fibrosis (CF) and 20 healthy controls at 6 weeks and 1 year of age. Investigation into the algorithms in WBreath 3.28.0 revealed discrepancies from current consensus guidelines, which resulted in a potential overestimation of functional residual capacity (FRC) and underestimation of lung clearance index (LCI). We developed a revised WBreath version (3.52.3), which overall resulted in 6.7% lower FRC (mean (SD) -1.78 (0.99) mL/kg) and 14.1% higher LCI (1.11 (0.57) TO) than WBreath version 3.28.0. Comprehensive investigation into the signal processing and algorithms used for analysis of MBW measurements improves the transparency and robustness of infant MBW data. The revised software version calculates outcomes according to consensus guidelines. Future work is needed to validate and compare outcomes between infant MBW setups.

A novel method for infant multiple breath washout: First report in clinical practice.

Lung clearance index (LCI), measured using multiple breath inert gas washout (MBW) is a potentially useful test in infants with respiratory disease, particularly cystic fibrosis (CF). Clinical use is limited however by the need for specialist staff and equipment. We have previously described a novel method for infant MBW suitable for use outside of specialist laboratories. This study describes its performance in vivo in infants with CF and healthy controls, including a limited comparison with the respiratory mass spectrometer. Children aged less than 2 years with CF and controls underwent MBW testing on a single occasion. The practical applicability of the system was determined by the number of successful duplicate tests and within-subject repeatability. Twenty-five children (seven with CF, 18 healthy controls, all sedated with chloral hydrate) attempted MBW. Twenty patients (seven with CF) successfully underwent duplicate testing (80% success rate). Mean within-subject coefficient of variation for functional residual capacity (FRC) was 7.2% and for LCI 5.9%. Comparison of LCI with the mass spectrometer was limited but gave very similar values for LCI and FRC in those patients who underwent technically adequate tests with both methods. We have described a new MBW method that is feasible and reproducible in sedated infants. Results fall within the expected range, and well within accuracy limits set by international guidelines. This could provide a more accessible alternative to previously described systems for infant MBW, and overcomes many of the technical challenges inherent in conventional MBW.

One-year evolution and variability in multiple-breath washout indices in children and young adults with primary ciliary dyskinesia

ABSTRACTBackground and objective: Cross-sectional and longer-term studies have demonstrated abnormal yet stable multiple-breath inert gas washout (MBW) indices in patients with primary ciliary dyskinesia (PCD). This study aimed to assess the intermediate term evolution and the between-occasion variability of MBW indices in PCD over 1 year.Methods: Children and young adults with a confirmed diagnosis of PCD were included in this single-centre, prospective, observational, longitudinal study. Over 1 year, nitrogen (N2) MBW and spirometry were performed at three occasions during ordinary scheduled outpatient visits. Trends and variability in lung clearance index (LCI), moment ratios, normalized N2 concentration at six lung volume turnovers, and regional ventilation inhomogeneity indices of the conducting and intra-acinar airways (Scond*VT and Sacin*VT) were analysed using linear mixed models.Results: Forty-two patients, aged 6–29 years (median: 15.4), performed 116 N2 MBW test occasions and 96.6% were technically acceptable. A minimal, although significant, increase in LCI over 1 year (mean: 0.51 units, 95% CI: 0.12–0.91, p = 0.01) was found; while, all other N2 MBW indices and FEV1 remained unchanged. A moderate correlation was observed between LCI and FEV1 (r = −0.47, p = 0.0001). The limits of agreement between tests 1 year apart were for LCI: −1.96 to 2.98; Scond*VT: ± 0.039; Sacin*VT: −0.108 to 0.128.Conclusions: Children and young adults with PCD managed at a specialist centre showed slightly, but significant, increasing LCI and otherwise unchanged ventilation inhomogeneity indices and dynamic volumes over the intermediate term of 1 year. Estimates of the variability of N2 MBW indices may inform sample size calculations of future randomized controlled trials.

Long-term lung function in children following lobectomy for congenital lung malformation

Background/purposeTo date, the optimal management of asymptomatic congenital lung malformations (CLMs) is still debated. There is still scant and controversial information regarding the long-term assessment of pulmonary function (PF) after lobectomy in children. The aim of this study is to evaluate PF in children who underwent lobectomy for CLM in infancy, hypothesizing that patients operated during the first year of life retain a normal lung function. MethodsChildren operated between 2005 and 2016 at our institution underwent PF evaluation through spirometry/whole-body plethysmography, forced oscillation technique, and multiple-breath inert gas wash-out. ResultsOut of 85 patients who underwent lobectomy at a median age of 5months, 50 met the inclusion criteria, and 28 patients were tested. More than 80% of patients had normal FEV1 and FVC. The mean FEV1, FVC, FEF25–75% values were higher in the patients operated before reaching one year of age. ConclusionsThe long-term outcome after lobectomy was excellent for most patients, as they retained a normal long-term PF. Therefore, for asymptomatic patients, a surgical approach before one year of age to avoid complications such as malignancy and to ensure an optimal PF catch-up could be beneficial. Level of evidenceIII – Treatment Studies.

The effect of inert gas choice on multiple breath washout in healthy infants: differences in lung function outcomes and breathing pattern.

The detrimental effects on breathing pattern during multiple breath inert gas washout (MBW) have been described with different inhaled gases [100% oxygen (O2) and sulfur hexafluoride (SF6)] but detailed comparisons are lacking. N2- and SF6-based tests were performed during spontaneous quiet sleep in 10 healthy infants aged 0.7-1.3 yr using identical hardware. Differences in breathing pattern pre and post 100% O2 and 4% SF6 exposure were investigated, and the results obtained were compared [functional residual capacity (FRC) and lung clearance index (LCI)]. During 100% O2 exposure. mean inspiratory flow ("respiratory drive") decreased transiently by mean (SD) 28 (9)% ( P < 0.001), and end-tidal CO2 (carbon dioxide) increased by mean (SD) 0.3 (0.4)% units ( P < 0.05) vs. air breathing prephase. During subsequent N2 washin (i.e., recovery phase), the pattern of change reversed. No significant effect on breathing pattern was observed during SF6 testing. In vitro testing confirmed that technical artifacts did not explain these changes. Mean (SD) FRC and LCI in vivo were significantly higher with N2 vs. SF6 washout: 216 (33) vs. 186 (22) ml ( P < 0.001) and 8.25 (0.85) vs. 7.55 (0.57) turnovers ( P = 0.021). Based on these results, SF6 based MBW is the preferred methodology for tests in this age range. NEW & NOTEWORTHY Inert gas choice for multiple breath inert gas washout (MBW) in infants has important consequences on both breathing pattern during test performance and the functional residual capacity and lung clearance index values obtained. Data suggest the detrimental effect of breathing pattern of 100% O2 and movement of O2 across the alveolar capillary membrane, with direct effects on MBW outcomes. SF6 MBW during infancy avoids this and can be further optimized by addressing the sources of technical artifact identified in this work.

Inert gas washout: background and application in various lung diseases.

Multiple breath inert gas washout (MBW) is a lung function technique to measure ventilation inhomogeneity. The technique was developed more than 60 years ago, but not much used for many decades. Technical improvements, easy protocols and higher sensitivity compared with standard lung function tests in some disease groups have led to a recent renaissance of MBW. The lung clearance index (LCI) is a common measure derived from MBW tests, and offers information on lung pathology complementary to that from conventional lung function tests such as spirometry. The LCI measures the overall degree of pulmonary ventilation inhomogeneity. There are other MBW-derived parameters, which describe more regional airway ventilation and enable specific information on conductive or acinar ventilation inhomogeneity. How this specific ventilation distribution is exactly related to different disease processes has not entirely been examined yet. MBW measurements are performed during tidal breathing, making this technique attractive for children, even young children and infants. These benefits and the additional physiological information on ventilation inhomogeneity early in the course of lung diseases have led to increasing research activities and clinical application of MBW, especially in paediatric lung diseases such as cystic fibrosis (CF). In these patients, LCI detects early airway damage and enables monitoring of disease progression and treatment response. Guidelines for the standardisation of the MBW technique were recently published. These guidelines will, hopefully, increase comparability of LCI data obtained in different centres or intervention trials in children and adults. In this non-systematic review article, we provide an overview of recent developments in MBW, with a special focus on children. We first explain the physiological and technical background to this technique with a short explanation of several methodological aspects that are important for understanding the principle behind the technique and enable high quality measurements. We then provide examples of MBW application in different lung diseases of children and adults, with regards to both clinical application and research activities. Lastly, we report on ongoing clinical trials using MBW as outcome and give an outlook on possible future developments.

Novel methodology to perform sulfur hexafluoride (SF6)-based multiple-breath wash-in and washout in infants using current commercially available equipment.

Multiple-breath inert gas washout (MBW) is ideally suited for early detection and monitoring of serious lung disease, such as cystic fibrosis, in infants and young children. Validated commercial options for the MBW technique are limited, and suitability of nitrogen (N2)-based MBW is of concern given the detrimental effect of exposure to pure O2 on infant breathing pattern. We propose novel methodology using commercially available N2 MBW equipment to facilitate 4% sulfur hexafluoride (SF6) multiple-breath inert gas wash-in and washout suitable for the infant age range. CO2, O2, and sidestream molar mass sensor signals were used to accurately calculate SF6 concentrations. An improved dynamic method for synchronization of gas and respiratory flow was developed to take into account variations in sidestream sample flow during MBW measurement. In vitro validation of triplicate functional residual capacity (FRC) assessments was undertaken under dry ambient conditions using lung models ranging from 90 to 267 ml, with tidal volumes of 28-79 ml, and respiratory rates 20-60 per minute. The relative mean (SD, 95% confidence interval) error of triplicate FRC determinations by washout was -0.26 (1.84, -3.86 to +3.35)% and by wash-in was 0.57 (2.66, -4.66 to +5.79)%. The standard deviations [mean (SD)] of percentage error among FRC triplicates were 1.40 (1.14) and 1.38 (1.32) for washout and wash-in, respectively. The novel methodology presented achieved FRC accuracy as outlined by current MBW consensus recommendations (95% of measurements within 5% accuracy). Further clinical evaluation is required, but this new technique, using existing commercially available equipment, has exciting potential for research and clinical use.

Changes in multiple breath washout measures after raised volume rapid thoracoabdominal compression maneuvers in infants

Multiple breath inert gas washout (MBW) measurements in infants are performed supine and often obtained under sedation and thus are combined with other lung function tests such as raised volume rapid thoracoabdominal compression (RVRTC). In this study, we sought to determine the effects of RVRTC maneuvers on MBW measures. Compared with tests performed prior to RVRTC, MBW measured after RVRTC was associated with a small reduction in functional residual capacity and a more pronounced decrease in cumulative expired volume in both healthy children and children with obstructive lung disease (cystic fibrosis or recurrent wheeze) indicating a more efficient washout after the raised volume maneuvers. Lung Clearance Index (LCI) decreased significantly in infants with respiratory disease (change in LCI of -0.24 units post RVRTC; standard error (SE) ± 0.07 units; P = 0.0004), but not in healthy infants (change in LCI of -0.08 units; SE ± 0.11 units; P = 0.44). As the RVRTC maneuver affects MBW measurements in infants, the timing of testing procedures needs to be standardized in longitudinal studies.

Characterization of acinar airspace involvement in asthmatic patients by using inert gas washout and hyperpolarized 3helium magnetic resonance

The multiple-breath inert gas washout parameter acinar ventilation heterogeneity (Sacin) is thought to be a marker of acinar airway involvement but has not been validated by using quantitative imaging techniques in asthmatic patients. We aimed to use hyperpolarized (3)He diffusion magnetic resonance at multiple diffusion timescales and quantitative computed tomographic (CT) densitometry to determine the nature of acinar airway involvement in asthmatic patients. Thirty-seven patients with asthma and 17 age-matched healthy control subjects underwent spirometry, body plethysmography, multiple-breath inert gas washout (with the tracer gas sulfur hexafluoride), and hyperpolarized (3)He diffusion magnetic resonance. Asubset of asthmatic patients (n= 27) underwent quantitative CT densitometry. Ninety-four percent (16/17) of patients with an increased Sacin had Global Initiative for Asthma treatment step 4 to 5 asthma, and 13 of 17 had refractory disease. The apparent diffusion coefficient (ADC) of (3)He at 1 second was significantly higher in patients with Sacin-high asthma compared with that in healthy control subjects (0.024 vs 0.017, P< .05). Sacin correlated strongly with ADCs at 1 second (R= 0.65, P< .001) but weakly with ADCs at 13 ms (R= 0.38, P< .05). ADCs at both 13 ms and 1 second correlated strongly with the mean lung density expiratory/inspiratory ratio, a CT marker of expiratory air trapping (R= 0.77, P< .0001 for ADCs at 13 ms; R=0.72,P<.001 for ADCs at 1 second). Sacin is associated with alterations in long-range diffusion within the acinar airways and gas trapping. The precise anatomic nature and mechanistic role in patients with severe asthma requires further evaluation.

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.

Effect of equipment dead space on multiple breath washout measures.

Multiple breath inert gas washout (MBW) systems are designed to minimize equipment dead space volume (Vd). Animal and infant studies have demonstrated the impact of increased Vd on MBW measurements. In this study, we investigate the effect of Vd of a nitrogen (N2 ) MBW system on MBW measurements in preschool children. N2 MBW measurements were performed in healthy adults under standard conditions; Vd was added to match the relationship between Vd and lung volumes observed in preschool children. Subsequently, subjects were measured on a sulfur hexafluoride (SF6 ) MBW system under standard conditions and with Vd added to match that of the N2 MBW system. Healthy preschool children and children with cystic fibrosis were tested on both the N2 MBW and SF6 MBW in random order on the same day. A correction equation was derived based on the adult experiments and tested on the preschool data. Increasing the Vd of the N2 MBW system resulted in a higher lung clearance index (LCI). A strong non-linear relationship between N2 LCI and the Vd/tidal volume was observed. When the Vd was equivalent between systems, LCI measured by the SF6 MBW system was similar to that measured by the N2 MBW. LCI was higher on the N2 MBW than the SF6 MBW in preschool children. Correcting for the equipment Vd of the N2 MBW resulted in better agreement. Equipment Vd affects LCI measurements especially in young children where Vd is large relative to lung volumes.

P100 The Feasibility Of Using Commercial Multiple Breath Nitrogen Washout Devices In School-aged Children

Background Multiple breath inert-gas washout (MBW) using sulphur hexafluoride (SF 6 ) measured by mass spectrometry (MS), is sensitive to early lung disease in children with Cystic Fibrosis (CF) 1 but is not widely available. To increase the accessibility of MBW, commercial devices have been adapted using nitrogenwashout (N 2 -MBW). Our aim was to assess the feasibility of two commercial N 2 -MBW devices as supplied by the manufacturers compared to a custom-built MS system in school-aged children. Methods Patients with CF and controls performed MBW on three devices; the Exhalyzer ® D (ECO MEDICS AG); the EasyOne Pro ® LAB (ndd Medizintechnik AG) and the MS system (AMIS 2000, Innovision ApS) on the same test occasion (order randomised). Attempts were made to obtain 3 technically acceptable runs/device (maximum 8 attempts on each). During testing children watched a DVD and were encouraged to breathe normally. Data were analysed using the ‘clinical application’ setting for both commercial devices, and customised software for the MS. Quality control was in accordance with the ATS/ERS consensus statement 1 and manufacturers’ guidelines. Results 14 control (mean[range]age: 15.0[12.5–16.7]yrs) and 18 children with CF (13.5[7.8–17.4]yrs) were assessed. The median (range) number of runs attempted were: MS 3(3–8), Exhalyzer ® D 4(3–6), EasyOne Pro ® LAB 4(3–8). Average calibration time was shorter for EasyOne Pro ® LAB (5 min) than either MS (11 mins) or Exhalyzer ® D (12 min). Total test duration was similar between devices and dependent on disease severity. 3 acceptable MBW runs were achieved in all children using the MS, 75% with the EasyOne Pro ® LAB, and 47% on the Exhalyzer ® D system (see Table). Reasons for failure with Exhalyzer ® D were usually due to technical/equipment problems, whereas for the EasyOne Pro ® LAB these were generally associated with marked changes of breathing pattern at commencement of washout, leading to exclusion of one or more runs. Discussion Despite use in an experienced MBW centre, our initial attempts to implement commercial MBW devices according to manufacturers’ guidelines resulted in a relatively low success rate in schoolchildren when compared to MS. Subsequent feedback to manufacturers has led to further adaptations which should improve feasibility in future, although this has yet to be assessed in very young children. Reference Robinson et al . Eur Resp J 2013

Clinical significance of small airway obstruction markers in patients with asthma

The role of small airway obstruction in the clinical expression of asthma is incompletely understood. We tested the hypotheses that markers of small airway obstruction are associated with (i) increased asthma severity, (ii) impaired asthma control and quality of life and (iii) frequent exacerbations. Seventy-four adults with asthma and 18 healthy control subjects underwent impulse oscillometry (IOS), multiple breath inert gas washout (MBW), body plethysmography, single-breath determination of carbon monoxide uptake and spirometry. Patients completed the six-point Asthma Control Questionnaire (ACQ-6) and standardized Asthma Quality of Life Questionnaire [AQLQ(S)]. Asthma severity was classified according to the Global Initiative for Asthma (GINA) treatment steps. The putative small airway obstruction markers Sacin , resistance at 5 Hz minus resistance at 20 Hz (R5-R20) and reactance area (AX) were not independently associated with asthma severity, control, quality of life or exacerbations. In contrast, markers of total (R5) and mean airway resistance of large and small airways (R20) were significantly higher in the severe asthma group compared with the mild-moderate group (0.47 vs. 0.37, P < 0.05 for R5; 0.39 vs. 0.31, P < 0.01 for R20). The strongest independent contributors to ACQ-6 score were R20 and forced expiratory volume in one second (% pred.), and the strongest independent contributors to AQLQ(S) score were R20 and forced vital capacity (% pred.). A history of one or more exacerbations within the previous year was independently associated with R20. Previously reported markers of small airway obstruction do not appear to be independently associated with asthma disease expression. In contrast, the IOS parameter R20, a marker of mean airway resistance of both large and small airways, appears to have independent clinical significance. These observations require confirmation in prospective longitudinal studies.

Between-visit variability of small airway obstruction markers in patients with asthma

To the Editor: Clinical trials in patients with airway diseases often use forced expiratory volume in 1 s (FEV1) as the sole physiological outcome measure. However, FEV1 is thought to be insensitive to obstruction of the smaller airways, which may be particularly relevant in asthma [1]. Putative markers of small airway obstruction include measures of airway resistance using impulse oscillometry (IOS) [2] and indices of ventilation heterogeneity derived from multiple-breath inert gas washout (MBW) [3]. We recently showed that increased airway resistance at 5 Hz ( R 5) and 20 Hz ( R 20) is associated with worse asthma control and more frequent exacerbations [4], and Farah et al. [5] demonstrated that MBW parameters may be responsive to asthma therapy. In order to conduct clinical trials using these alternative outcome measures, it is necessary to be assured of their repeatability and stability over time. Moreover, an estimate of between-visit variability in the stable state is required so that sample size calculations can be performed. We therefore aimed to determine the between-visit variability of a range of IOS and MBW indices in a group of patients with asthma in the stable state. We investigated between-visit variability over two time intervals, namely 2 weeks and 3 months, in order to encompass the typical lengths of treatment period that are used in clinical trials. We recruited 18 adults (age >18 years) with moderate-to-severe asthma (Global Initiative for Asthma treatment steps 3–5 [6]), diagnosed by a specialist asthma physician in a secondary care setting, according to British Thoracic Society guidelines [ …

Validation of multiple‐breath washout equipment for infants and young children

The new ATS/ERS consensus report recommends in vitro validation of multiple-breath inert gas washout (MBW) equipment based on a lung model with simulated physiologic conditions. We aimed to assess accuracy of two MBW setups for infants and young children using this model, and to compare functional residual capacity (FRC) from helium MBW (FRC(MBW)) with FRC from plethysmography (FRC(pleth)) in vivo. The MBW setups were based on ultrasonic flow meter technology. Sulfur hexafluoride and helium were used as tracer gases. We measured FRC in vitro for specific model settings with and without carbon dioxide and calculated differences of measured to generated FRC. For in vivo evaluation, difference between FRC(MBW) and FRC(pleth) was calculated in 20 healthy children, median age 6.1 years. Coefficient of variation (CV) was calculated per FRC. In the infant model (51 runs, FRC 80-300 ml), mean (SD) relative difference between generated and measured FRCs was 0.7 (4.7) %, median CV was 4.4% for measured FRCs. In the young child model, one setting (8 runs, FRC 400 ml) showed a relative difference of up to 13%. For the remaining FRCs (42 runs, FRC 600-1,400 ml), mean (SD) relative difference was -2.0 (3.4) %; median CV was 1.4% for measured FRCs. In vivo FRC(pleth) exceeded FRC(MBW) values by 37% on average. Both setups measure lung volumes in the intended age group reliably and reproducibly. Characteristics of different techniques should be considered when measuring lung volumes in vivo.

Validation of a Photoacoustic Gas Analyser for the Measurement of Functional Residual Capacity Using Multiple-Breath Inert Gas Washout

Background: The respiratory mass spectrometer is the current gold-standard technique for performing multiple-breath inert gas washout (MBW), but is expensive and lacks portability. A number of alternative techniques have recently been described. Objectives: We aimed to validate, using an in vitro lung model, an open-circuit MBW system that utilises a portable photoacoustic gas analyser, with sulphur hexafluoride (SF₆) as the inert tracer gas. Methods: An acrylic glass lung model was utilised to assess the accuracy of functional residual capacity (FRC) measurements derived from MBW. Measurements were performed in triplicate at 20 combinations of simulated FRC, tidal volume and respiratory rate. FRC measured using MBW (FRC_mbw) was compared to FRC calculated from the known dimensions of the model (FRC_calc). MBW was also performed in 10 healthy subjects and 14 patients with asthma. Results: The MBW system measured FRC with high precision. The mean bias of FRC_mbw with respect to FRC_calc was -0.4% (95% limits of agreement of -4.6 and 3.9%). The mean coefficient of variation of triplicate FRC measurements was 4.0% in vivo and 1.0% in vitro. MBW slightly underestimated low lung volumes and overestimated high lung volumes, but this did not cause a significant error in lung clearance index except at lung volumes below 1,500 ml. Conclusions: The open-circuit MBW system utilising SF₆ as the inert tracer gas and a photoacoustic gas analyser is both accurate and repeatable within the adult range of lung volumes. Further modifications would be required before its use in young children or infants.

Lung clearance index in adults with non-cystic fibrosis bronchiectasis.

BackgroundLung clearance index (LCI) is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout (MBW) technique. We aimed to determine the clinical utility of LCI in non-CF bronchiectasis, and to assess two novel MBW parameters that distinguish between increases in LCI due to specific ventilation inequality (LCIvent) and increased respiratory dead space (LCIds).MethodsForty-three patients with non-CF bronchiectasis and 18 healthy control subjects underwent MBW using the sulphur hexafluoride wash-in technique, and data from 40 adults with CF were re-analysed. LCIvent and LCIds were calculated using a theoretical two-compartment lung model, and represent the proportional increase in LCI above its ideal value due to specific ventilation inequality and increased respiratory dead space, respectively.ResultsLCI was significantly raised in patients with non-CF bronchiectasis compared to healthy controls (9.99 versus 7.28, p < 0.01), and discriminated well between these two groups (area under receiver operating curve = 0.90, versus 0.83 for forced expiratory volume in one second [% predicted]). LCI, LCIvent and LCIds were repeatable (intraclass correlation coefficient > 0.75), and correlated significantly with measures of spirometric airflow obstruction.ConclusionLCI is repeatable, discriminatory, and is associated with spirometric airflow obstruction in patients with non-CF bronchiectasis. LCIvent and LCIds are a practical and repeatable alternative to phase III slope analysis and may allow a further level of mechanistic information to be extracted from the MBW test in patients with severe ventilation heterogeneity.

S45 Specific ventilation inequality and dead space components of lung clearance index in patients with asthma and cystic fibrosis

BackgroundLung clearance index (LCI) is a widely reported marker of gas mixing inefficiency within the airways that is derived using the multiple breath inert gas washout (MBW) technique. We developed...

Aerobic Fitness in Children and Young Adults with Primary Ciliary Dyskinesia

BackgroundAlthough aerobic fitness is regarded as an overall prognostic measure of morbidity and mortality, its evaluation in the chronic progressive sinopulmonary disease primary ciliary dyskinesia (PCD) has been infrequently and inconsistently reported. Here we assessed peak oxygen uptake (VO2peak) in a large well-characterized cohort of PCD patients, and explored whether VO2peak was associated with parameters of pulmonary function, self-reported physical limitations, and physical activity level.MethodsVO2peak, spirometry, diffusing capacity, whole-body plethysmography, and nitrogen multiple breath inert gas washout (N2 MBW) were assessed in a cross-sectional, single-occasion study of clinically stable children and young adults with PCD. We used a questionnaire including self-reported physical limitations in everyday life or in vigorous activities, and estimation of weekly hours of strenuous physical activity. VO2peak in PCD patients was compared with that in matched, healthy control subjects and a national reference.ResultsForty-four PCD patients aged 6–29 years exhibited reduced VO2peak compared to healthy controls (P<0.001) and the national reference. VO2peak was abnormal (z-score <–1.96) in 34% of PCD patients. Spirometric values, RV/TLC, and indices of N2 MBW were significantly abnormal, but VO2peak only correlated with FEV1 and DLCO/VA. VO2peak correlated with complaints of moderate or significant limitations in vigorous activities (P = 0.0001), exhibited by 39% of PCD patients.ConclusionOne-third of PCD patients exhibited substantially lower aerobic fitness than healthy subjects. Aerobic fitness correlated with FEV1, DLCO/VA and self-reported complaints of limitations in vigorous physical activity. These findings are most likely explained by PCD pulmonary disease and its impact on pulmonary function and physical ability. Considering fitness as an important outcome and including regular strenuous physical activity in PCD treatment would probably altogether increase pulmonary clearance, lung function, aerobic fitness, and quality of life, and prevent lifestyle-related diseases.

S9 Cluster Analysis Reveals a Distinct Small Airway-Predominant Phenotype of Asthma

Introduction and objectivesAsthma is an inflammatory disease that is treated with inhaled corticosteroids, but some patients manifest persistent symptoms despite this. Small airway dysfunction may account for treatment resistance in...