Ventilation heterogeneity in the acinar and conductive zones of the normal ageing lung

Verbanck, Sylvia; Thompson, Bruce; Schuermans, Daniël; Kalsi, Harpal; Biddiscombe, Martyn; Stuart-Andrews, Chris; Hanon, Shane; Muylem, Alain Van; Paiva, Manuel; Vincken, Walter; Usmani, Omar

doi:10.1136/thoraxjnl-2011-201484

Cited by 110 publications

(152 citation statements)

References 31 publications

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“…All N 2 MBW indices corresponded well to preliminary reference values obtained with the same equipment and protocol in adults [24]. A small, linear age-dependent increase in N 2 MBW parameters (LCI, Scond and Sacin) was described before with the strongest association between age and LCI [25]. We confirmed a comparable rise in LCI (about 0.3 per 10 years).…”

Section: Washout Indices In Healthy Subjectssupporting

confidence: 72%

“…We confirmed a comparable rise in LCI (about 0.3 per 10 years). The possibly low sensitivity of our study to detect the age dependency of Scond and Sacin may be attributed to the smaller sample size (n540 versus n5120 [25]) with few individuals aged .55 years. Since only a marginal association between AUC (DTG-SBW) and age was detectable, we suggest the association between age and DTG-SBW indices be verified in a larger series.…”

Section: Washout Indices In Healthy Subjectsmentioning

confidence: 81%

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Double tracer gas single-breath washout: reproducibility in healthy subjects and COPD

et al. 2014

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The applicability and interpretation of inert tracer gas washout tests is hampered by the lack of feasible protocols and reproducibility data. We assessed feasibility, variability and reproducibility of a new easy to perform double tracer gas (DTG) single-breath washout (SBW) test and compared this with conventional nitrogen washouts.In 40 healthy nonsmokers and 20 patients with stable chronic obstructive pulmonary disease (COPD), we performed three N 2 vital capacity SBWs, three N 2 multiple-breath washouts and three tidal DTG-SBW tests. Follow-up was after 1 week, 1 month and 6 months. Main outcomes were the lung clearance index (LCI) (N 2 multiple-breath washout), slope of phase III (dN 2 ) (N 2 vital capacity SBW) and slope of phase III (SIIIDTG) (DTG-SBW).In healthy subjects, mean¡SD LCI at baseline was 6.94¡0.61, dN 2 0.99¡0.42% N 2 per litre and SIIIDTG -0.206¡0.108 g?mol -1 ?L -1 . In COPD, LCI and dN 2 were significantly higher (LCI 12.23¡2.67, dN 2 7.43¡5.38% N 2 per litre; p,0.001) and SIIIDTG significantly steeper (-0.653¡0.428 g?mol -1 ?L -1 , p,0.001). Reproducibility was high for main outcome parameters: the intraclass correlation coefficient over 6 months was 0.77 (0.86 in COPD) for LCI, 0.82 (0.89) for dN 2 and 0.83 (0.93) for SIIIDTG.The tidal DTG-SBW is a reproducible test in healthy and COPD subjects that seems attractive for use in routine clinical settings. @ERSpublications DTG-SBW may play a role in detection and monitoring of small airway diseases or as an outcome in drug trials

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Section: Washout Indices In Healthy Subjectssupporting

confidence: 72%

Section: Washout Indices In Healthy Subjectsmentioning

confidence: 81%

Double tracer gas single-breath washout: reproducibility in healthy subjects and COPD

et al. 2014

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“…Limited reference data are available and are device and gas specific (29,30). LCI declines through infancy and early childhood, remains constant in early childhood to adulthood, and slowly increases in the elderly (29,31). Age is an important predictor of other MBW indices (e.g., concentration-normalized phase III slope analysis indices, S cond and S acin ).…”

Section: Normal Value Reference Datamentioning

confidence: 99%

Multiple-Breath Washout as a Lung Function Test in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report

et al. 2015

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The lung clearance index (LCI) is a lung function parameter derived from the multiple-breath washout (MBW) test. Although first developed 60 years ago, the technique was not widely used for many years. Recent technological advances in equipment design have produced gains in popularity for this test among cystic fibrosis (CF) researchers and clinicians, particularly for testing preschool-aged children. LCI has been shown to be feasible and sensitive to early CF lung disease in patients of all ages from infancy to adulthood. A workshop was convened in January 2014 by the North American Cystic Fibrosis Foundation to determine the readiness of the LCI for use in multicenter clinical trials as well as clinical care. The workshop concluded that the MBW text is a valuable potential outcome measure for CF clinical trials in preschool-aged patients and in older patients with FEV 1 in the normal range. However, gaps in knowledge about the choice of device, gas, and standardization across systems are key issues precluding its use as a clinical trial end point in infants. Based on the current evidence, there are insufficient data to support the use of LCI or MBW parameters in the routine clinical management of patients with CF.

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“…Recently, age dependency of LCI during adulthood (between 25 and 65 years of age) has been reported, showing that gas mixing becomes more heterogeneous with age [33]. This suggests that gas mixing is more heterogeneous both in the very young and in elderly adults, although formal longitudinal studies across wide age ranges are required to confirm this.…”

Section: Paediatric Lung Functionmentioning

confidence: 89%

Age and height dependence of lung clearance index and functional residual capacity

Lum¹,

et al. 2012

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The lung clearance index (LCI) is more sensitive than spirometry in detecting abnormal lung function in children with cystic fibrosis. LCI is thought to be independent of age, but recent evidence suggests that the upper limit of normal is higher in infants and preschool children than in older subjects. This study examines whether LCI remains independent of body size throughout childhood.Multiple-breath washout data from healthy children and adolescents were collated from three centres using the mass spectrometer system and the inert gas sulfur hexafluoride. Reference equations for LCI and functional residual capacity (FRC) were constructed using the LMS (lambda-mu-sigma) method.Data were available from 497 subjects (2 weeks to 19 years of age) tested on 659 occasions. LCI was dependent on body size, decreasing in a nonlinear pattern as height increased. Changes were particularly marked in the first 5 years of life. Height, age and sex were all independent predictors of FRC. Minimal between-centre differences allowed unified reference equations to be developed.LCI is not independent of body size. Although a constant upper normal limit would suffice for cross-sectional clinical assessments from 6 years of age, appropriate reference equations are essential for accurate interpretation of results during early childhood. KEYWORDS: Children, functional residual capacity, lung clearance index, reference values, ventilation inhomogeneity M easuring the efficiency of ventilation distribution within the lung offers the exciting potential to detect early disease processes missed by conventional flow-based lung function techniques such as spirometry. Multiple-breath inert-gas washout (MBW) is a noninvasive tidal breathing test, feasible across all ages, which offers improved sensitivity, compared with spirometry, to detect early cystic fibrosis lung disease throughout childhood [1][2][3].It is generally thought that LCI is independent of body size. However, cross-sectional studies in infants have suggested that the upper limit of normal (ULN) for global measures of ventilation distribution inhomogeneity, such as lung clearance index (LCI), may be higher compared with older subjects [3,4]. Such differences, which could arise from developmental changes or differences in measurement conditions, may preclude identification of early lung disease in both cross-sectional and longitudinal studies. Furthermore, appropriate normative data for functional residual capacity (FRC) derived from MBW (FRCMBW) spanning the paediatric age range are lacking. The aim of this study was to investigate the relationship between body size and LCI from infancy to young adulthood, and establish reference equations for both LCI and FRCMBW across this age range. METHODSMBW was performed in healthy children at three specialised paediatric centres in the UK, Sweden and Canada as described previously [3,[5][6][7][8][9][10]. Briefly, during wash-in, a dry air mixture containing Gustafsson) and protocols in all centres [11]. Please see the online su...

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Ventilation heterogeneity in the acinar and conductive zones of the normal ageing lung

Cited by 110 publications

References 31 publications

Double tracer gas single-breath washout: reproducibility in healthy subjects and COPD

Double tracer gas single-breath washout: reproducibility in healthy subjects and COPD

Multiple-Breath Washout as a Lung Function Test in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report

Age and height dependence of lung clearance index and functional residual capacity

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