The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials

Foong, Rachel E.; Harper, Alana; King, Louise; Turkovic, Lidija; Davis, Michael F.; Clem, Charles; Rosenow, Tim; Davis, Stephanie D.; Ranganathan, Sarath; Hall, Graham L.; Ramsey, Kathryn

doi:10.1183/23120541.00094-2017

Cited by 8 publications

(6 citation statements)

References 18 publications

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“…Intra-test repeatability is not affected while total test time is reduced significantly. These findings could be replicated in pre-school children suffering from cystic fibrosis using an N 2 -based setup 51 with all three studies opposing current general recommendations 35 . Although we were able to acquire at least two successful runs in at least 90% of asthmatic patients and all non-asthmatic controls, using an earlier stopping point may eventually contribute to even higher success rates.…”

Section: Discussionmentioning

confidence: 75%

Feasibility and clinical applications of multiple breath wash-out (MBW) testing using sulphur hexafluoride in adults with bronchial asthma

Lenz

Schäfer

Gawlitza

et al. 2020

Sci Rep

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Ventilation heterogeneity is frequent in bronchial asthma and can be assessed using multiple breath wash-out testing (MBW). Most data is available in paediatric patients and using nitrogen as a tracer gas. We aimed to evaluate sulphur hexafluoride (SF 6) MBW in adult asthmatics. Spirometry, wholebody plethysmography, impulse oscillometry and SF 6-MBW were prospectively performed. MBW parameters reflecting global (lung clearance index, LCI), acinar (S acin) and conductive (S cond) ventilation heterogeneity were derived from three consecutive wash-outs. LCI was calculated for the traditional 2.5% and an earlier 5% stopping point that has the potential to reduce wash-out times. 91 asthmatics (66%) and 47 non-asthmatic controls (34%) were included in final analysis. LCI 2.5 and Lci 5 were higher in asthmatics (p < 0.001). Likewise, S acin and S cond were elevated (p < 0.001 and p < 0.01). Coefficient of variation was 3.4% for LCI 2.5 and 3.5% for LCI 5 in asthmatics. Forty-one asthmatic patients had normal spirometry. ROC analysis revealed an AUC of 0.906 for the differentiation from non-asthmatic controls exceeding diagnostic performance of individual and conventional parameters (AUC = 0.819, p < 0.05). Sf 6-MBW is feasible and reproducible in adult asthmatics. Ventilation heterogeneity is increased as compared to non-asthmatic controls persisting in asthmatic patients with normal spirometry. Diagnostic performance is not affected using an earlier LCI stopping point while reducing wash-out duration considerably. Disease control is the primary goal of asthma therapy being linked to absence of symptoms and exacerbations 1. Regrettably, up to half of the patients are poorly controlled 2,3. Despite therapeutic advances, numbers remained fairly unaltered during the last decade. The clinical and pathophysiological explanations associated with poor disease control are heterogenous. In general, more severe disease is related to more frequent exacerbations, health care contacts 3 and symptoms 4. Lung function is also impaired in severe disease indicated by a lower forced expiratory volume in one second (FEV 1) and lower forced vital capacity (FVC) 3. Both parameters represent rather central sites of obstruction. However, involvement of peripheral airways is common in the majority of asthmatic patients 5. This holds true across the whole spectrum of severity 6 and may be a consequence of several influencing factors. These include inflammation, wall thickening, smooth muscle hypertrophy, and mucus 7-10. However, changes in the lung periphery are still often missed by commonly used techniques such as spirometry. Impulse oscillometry (IOS) is an inexpensive non-invasive technique to measure airway resistance. It was shown to identify small airway obstruction 11 , the related characteristics of disease control 12,13 and response to

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Section: Discussionmentioning

confidence: 75%

Feasibility and clinical applications of multiple breath wash-out (MBW) testing using sulphur hexafluoride in adults with bronchial asthma

Lenz

Schäfer

Gawlitza

et al. 2020

Sci Rep

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“…Flow and molar mass (MM) signals were measured by an ultrasonic flowmeter (Exhalyzer D, Eco Medics AG; WBreath 3.28.0, ndd Medizintechnik AG) with 4% sulfur hexafluoride (SF 6 ) as the heavy tracer gas. Each visit had at least two acceptable MBW trials with FRC values within 10% of the mean 19 …”

Section: Methodsmentioning

confidence: 99%

Shedding light into the black box of infant multiple‐breath washout

Oestreich

Wyler

Latzin

et al. 2021

Pediatric Pulmonology

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Background: 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. Methods: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.Results: 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. Conclusion: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.

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“…The blinded data were subject to quality control by a physician trained and experienced in N 2 ‐MBW testing (ECFS‐CTN certification). At least two acceptable trials were required in each measurement session 19 and the coefficient of variation of the respective parameters had to be less than 10%. The parameters of interest derived from the N 2 ‐MBW included FRC, LCI 2.5 , Scond*Vt, and Sacin*Vt. LCI 2.5 was calculated as the number of lung volume turnovers corresponding to FRC to reach 2.5% (1/40th) of the starting nitrogen concentration 17,20 .…”

Section: Methodsmentioning

confidence: 99%

Reflex zone stimulation reduces ventilation inhomogeneity in cystic fibrosis: A randomised controlled cross‐over study

Plešková

Koucký

Medunová

et al. 2021

Pediatric Pulmonology

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Background: The reflex zone stimulation technique (RST) activates complex motor responses and has a positive impact on the locomotor system. This technique may also indirectly affect breathing; however, the use of this technique as adjunct of the treatment of cystic fibrosis (CF) has not yet been characterised.Methods: We performed a randomised controlled single-centre interventional trial to evaluate the short-term effects of RST on lung function in 21 paediatric CF patients with normal baseline spirometry. The effect of 30 min of RST was compared to that of sham therapy in a crossover design. The interventions were performed in random order and planned 6 months apart. The primary outcome was a change in global ventilation inhomogeneity after intervention, assessed by lung clearance index (LCI 2.5 ) derived from a nitrogen multiple breath washout test. Secondary outcomes included changes in regional ventilation inhomogeneity (indices of acinar [Sacin*Vt] and conductive airway [Scond*Vt] inhomogeneity) and spirometry parameters (inspiratory capacity, forced vital capacity, and forced expiratory volume in 1 s). Trunk deformity was assessed by physiotherapists at study entry.Results: After the RST intervention, the LCI 2.5 (p = .004) and Scond*Vt (p = .009) decreased significantly, while inspiratory capacity increased (p = .012). In the shamtherapy group, none of the parameters changed significantly. Trunk deformity was seen in 76.5% of all patients, and 92.9% of those with trunk deformity showed a decrease in LCI 2.5 after RST. Conclusion:RST has multiple positive short-term effects on lung function, especially in CF patients with trunk deformities.

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The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials

Cited by 8 publications

References 18 publications

Feasibility and clinical applications of multiple breath wash-out (MBW) testing using sulphur hexafluoride in adults with bronchial asthma

Feasibility and clinical applications of multiple breath wash-out (MBW) testing using sulphur hexafluoride in adults with bronchial asthma

Shedding light into the black box of infant multiple‐breath washout

Reflex zone stimulation reduces ventilation inhomogeneity in cystic fibrosis: A randomised controlled cross‐over study

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