Inert gas washout in preschool children

doi:10.1016/j.prrv.2005.09.009

Paediatric Respiratory Reviews

Volume 6, Issue 4, December 2005, Pages 239-245

https://doi.org/10.1016/j.prrv.2005.09.009 Get rights and content

Summary

The multiple-breath inert gas washout (MBW) method is used to measure the efficiency of ventilation distribution in the lungs and to measure the functional residual capacity (FRC). It involves recordings of the concentration of an inert marker gas and respiratory flow at the airway opening when a subject breathes through a sealed facemask or a mouthpiece. The MBW method is particularly useful for lung function testing in preschool children (2–6 years) because it requires only passive cooperation and tidal breathing. The lung clearance index (LCI) is the cumulative expired volume required to clear an inert gas from the lungs, divided by the FRC. The LCI has been shown to be more sensitive than spirometry or airway resistance measurements in detecting lung function abnormalities in young children with cystic fibrosis (CF). The MBW method may be useful also for screening for several other disorders that affect the peripheral airways in children.

Section snippets

INTRODUCTION

Over the last 10 years studies have shown that it is possible to measure lung function in many preschool children (3–6 years) using incentive spirometry,¹ by measurements of airway resistance with the forced oscillation² or the interrupter technique,³ or as specific resistance during tidal breathing in a body-box.⁴ Spirometry may be more informative but requires active co-operation in contrast to the resistance measurements that require tidal breathing only. On theoretical grounds it can be

MULTIPLE-BREATH WASHOUT AND OTHER GAS-MIXING TESTS

The effectiveness of ventilation distribution and gas mixing cannot be measured using oxygen (O₂) or carbon dioxide (CO₂) because these gases participate in the gas exchange across the alveolo–capillary membrane. Several inert gases, e.g., nitrogen (N₂), argon (Ar), helium (He) and sulphur hexafluoride (SF₆), are suitable for this purpose, however, because they have a relatively low solubility in blood and other tissues and can be easily be measured with fast responding analysers (Table 1).

This

EQUIPMENT AND PROCEDURES

Hardware for breath-by-breath MBW systems includes a gas analyser and a flow meter, measuring the inert gas concentration and the inspiratory and expiratory flows close to the mouth. In addition a device for delivering gas mixtures, a suitable inert marker gas mixture and a computer with a data acquisition board are needed. Fig. 1 shows a 3-year-old child performing a MBW while watching a video film. She wears a facemask sealed with therapeutic putty and connected to a pneumotachometer. The gas

REFERENCE VALUES

Only a few MBW studies including healthy subjects between aged 2–6 years have been published. Interestingly, reference values for LCI are similar across the age range from infancy to adolescence with a narrow distribution. This makes the MBW test even more clinically useful and this feature is particularly helpful when doing longitudinal follow-up of patients. LCI values obtained in healthy preschool children have been published by Aurora et al. using a SF₆ MBW method.⁹ These reference values

CLINICAL INTERPRETATION

An abnormally elevated LCI indicates uneven ventilation distribution, which can be the result of generalised peripheral airway obstruction or more focal airway disease associated with reduced regional ventilation. Studies in children with CF show that abnormal ventilation distribution is seen in the majority of patients with normal spirometry findings.9, 22, 23 In preschool children with CF, the MBW is a more sensitive method than both airway resistance measurements and spirometry in detecting

AVAILABILITY

Unfortunately, no MBW systems adapted for preschool children are today commercially available except for the ultrasound method. A task force group within the ATS (American Thoracic Society) and ERS (European Respiratory Society) will present standards for lung function testing methods and procedures in preschool children in a near future. Hopefully that will encourage manufacturers to start producing MBW systems of good quality at affordable prices.

CONCLUSIONS

Multiple-breath inert gas washout tests can be performed successfully in almost all children aged 3–6 years because they involve only normal tidal breathing. There is evidence that this test is more sensitive to airway involvement than spirometry or airway resistance measurements in preschool children with CF, suggesting that it may have a clinical role. It can be presumed that the MBW test is a more sensitive test also in other airway disorders that involve the peripheral airways in young

REFERENCES (24)

R. Kraemer et al.
Intrapulmonary gas distribution in healthy children
Respir Physiol
(1986)
M.A. Wall et al.
Relationship between maldistribution of ventilation and airways obstruction in children with asthma
Respir Physiol
(1987)
P. Aurora et al.
Quality control for spirometry in preschool children with and without lung disease
Am J Respir Crit Care Med
(2004)
B. Klug et al.
Measurement of lung function in awake 2–4-year-old asthmatic children during methacholine challenge and acute asthma: a comparison of the impulse oscillation technique, the interrupter technique and transcutaneous measurement of oxygen versus whole-body plethysmography
Pediatr Pulmonol
(1996)
P.D. Bridge et al.
The measurement of airway resistance using the interrupter technique (Rint) in pre-school children in the ambulatory setting
Eur Respir J
(1999)
B. Klug et al.
Measurement of the specific airway resistance by plethysmography in young children accompanied by an adult
Eur Respir J
(1997)
P.T. Macklem et al.
Resistance of central and peripheral airways measured by a retrograde catheter
J Appl Physiol
(1967)
P.T. Macklem
The physiology of the small airways
Am J Respir Crit Care Med
(1998)
H.K. Ljungberg et al.
Peripheral airway function in childhood asthma, assessed by single-breath He and SF₆ washout
Pediatr Pulmonol
(2003)
S. Verbanck et al.
Conductive and acinar lung-zone contributions to ventilation inhomogeneity in COPD
Am J Respir Crit Care Med
(1998)

P. Aurora et al.

Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis

Am J Respir Crit Care Med

(2005)

M.A. Wall

Moment analysis of multibreath nitrogen washout in young children

J Appl Physiol

(1985)

Cited by (53)

High inspired oxygen fraction impairs lung volume and ventilation heterogeneity in healthy children: a double-blind randomised controlled trial
2019, British Journal of Anaesthesia
Citation Excerpt :
FRC was calculated by dividing the net amount of nitrogen exhaled during the washout by the difference in end-tidal gas concentrations from the beginning to the end of washout.14 To characterise the ventilation heterogeneities, LCI was obtained by counting the number of FRC turnovers required to reduce the end-tidal concentration of nitrogen to 1/20th (LCI5) and 1/40th (LCI2.5) of the starting concentrations.14 During each assessment, FRC and LCI measurements were performed in reproducible duplicates, and the average values were used for further analysis.
Although a high inspired oxygen fraction (FiO₂) is commonly used in paediatric anaesthesia, the impact on postoperative lung function is unclear. We compared lung volume, ventilation heterogeneity, and respiratory mechanics in anaesthetised children randomised to receive low or high FiO₂ intraoperatively.
In a double-blind randomised controlled trial, children scheduled for elective surgery were randomly assigned FiO₂ 100% (n=29) or FiO₂ 80% (n=29) during anaesthesia induction and emergence. During maintenance of anaesthesia, participants assigned FiO₂=100% at induction/emergence received FiO₂=80% (FiO₂>0.8 group); those randomised to FiO₂=80% at induction/emergence received FiO₂=35% intraoperatively (FiO₂ [0.8→0.35 group]). During spontaneous breathing, we measured the (i) functional residual capacity (FRC) and lung clearance index (ventilation inhomogeneity) by multiple-breath nitrogen washout; and (ii) airway resistance and respiratory tissue elastance by forced oscillations, before operation, after discharge from the recovery room, and 24 h after operation. Mean (95% confidence intervals) are reported.
Fifty eight children (12.9 [12.3–13.5] yr) were randomised; 22/29 (high group) and 21/29 (low group) children completed serial multiple-breath nitrogen washout measurements. FRC decreased in the FiO₂>0.8 group after discharge from recovery (–12.0 [–18.5 to –5.5]%; P=0.01), but normalised 24 h later. Ventilation inhomogeneity increased in both groups after discharge from recovery, but persisted in the FiO₂>0.8 group 24 h after surgery (6.1 [2.5–9.8%]%; P=0.02). Airway resistance and respiratory elastance did not differ between the groups at any time point.
FiO₂>0.8 decreases lung volume in the immediate postoperative period, accompanied by persistent ventilation inhomogeneity. These data suggest that FiO₂>0.8 should be avoided in anaesthetised children with normal lungs.
NCT02384616.
Early lung disease in infants with cystic fibrosis. Diagnostic tools and possible therapeutic pathways
2016, Revue des Maladies Respiratoires
Longtemps considérée comme cliniquement normale à la naissance, les données actuelles montrent que l’atteinte respiratoire fonctionnelle et structurale s’installe précocement chez les nourrissons atteints de mucoviscidose. Les modèles animaux développés dans les années 2000 ont montré l’étroitesse des voies aériennes dès la naissance, associée à des phénomènes inflammatoires et infectieux. Les données issues des cohortes de nourrissons dépistés pour la mucoviscidose montrent que 25 % d’entre eux, bien qu’asymptomatiques et suivis dans des centres spécialisés, ont des anomalies fonctionnelles respiratoires dès 3 mois de vie. Sur le plan structural, des dilatations des bronches sont retrouvées au même âge chez 28 % des enfants, un trappage aérique chez 68 %. La présence d’élastase des polynucléaires neutrophiles à 3 mois dans le lavage broncho-alvéolaire triple le risque de survenue de dilatations des bronches à 3 ans. Les outils actuellement disponibles (exploration fonctionnelle du nourrisson par technique de la jaquette, mesure de l’inhomogénéité de ventilation par rinçage à l’azote, imagerie par scanner thoracique en volume contrôlé, imagerie par résonance magnétique fonctionnelle) devraient faciliter, dans un avenir proche, la mise en place d’essais cliniques interventionnels précoces. La place de ces outils en pratique clinique quotidienne et la capacité des interventions précoces à modifier l’histoire de la maladie restent à préciser.
The lungs of infants with cystic fibrosis (CF) have been considered to be normal at birth. However, recent data indicates that this is unlikely to be true in most cases. Animal CF-models developed in the early 2000s have shown that constitutional airway narrowing may be present at birth, and is associated with both functional and structural abnormalities. Longitudinal birth cohort studies have shown that 25 % of CF infants followed in specialized centers, while being asymptomatic, showed decreased lung function at 3 months of age. Air trapping was present in 68 % and bronchiectasis in 28 % of patients at the same age. The presence of neutrophil elastase in the bronchoalveolar lavage at 3 months of age tripled the risk of bronchiectasis at the age of 3 years. Currently available tools such as infant pulmonary function tests (both the jacket and multiple breath washout) as well as high-resolution volume controlled chest-computed tomography or functional magnetic resonance imaging will facilitate early intervention trials in the very near future. The role of such tools for the routine follow-up of patients, and the ability of early therapeutic interventions to alter the natural history of CF-lung disease should soon be established.
Alternative outcomes for the multiple breath washout in children with CF
2015, Journal of Cystic Fibrosis
The lung clearance index (LCI) measured by multiple-breath washout (MBW) has been proposed as an outcome for clinical trials; however, MBW is time consuming and LCI can be affected by breathing pattern. We aimed to evaluate moment ratios and abbreviated LCI in school-aged children with mild-to-moderate CF lung disease.
Using existing data from three studies we assessed the sensitivity of moment ratios and abbreviated LCIs to (i) detect mild-to-moderate CF lung disease and (ii) detect treatment effects after 4 weeks of hypertonic saline or dornase alfa inhalation. MBW was measured by respiratory mass spectrometry using 4% ""sulphur hexafluoride as a tracer gas.
Compared to the traditional LCI, moment ratios and abbreviated LCIs were similarly sensitive to detect CF lung disease. Moment ratios consistently demonstrated treatment effects, whereas abbreviated LCIs were less sensitive.
Both moment ratios and abbreviated LCI are suitable to differentiate health from disease. Sensitivity is decreased for abbreviated LCIs in interventional studies in mild CF lung disease.
Frequency dependence of capnography in anesthetized rabbits
2014, Respiratory Physiology and Neurobiology
Citation Excerpt :
The multiple-breath washout of inert gases or of nitrogen by oxygen identifies the contribution of inhomogeneous ventilation to the obstructive lung disease (Gustafsson, 2005). The lung clearance index has thus been shown to be an early detector of lung function abnormalities in cystic fibrosis (Gustafsson, 2005; Robinson et al., 2010). With either method however, an airtight mask-to-face seal is mandatory for valid interpretation, and sedation may be required beyond a few months of age.
Aspirative capnography may be of help to diagnose early childhood asthma, but clinical usefulness in young children is limited by the relatively high respiratory rate. This study aimed to characterize the $F_{{CO}_{2}}$ time course during airway constriction in 8 anesthetized rabbits, artificially ventilated at 30, 60 and 80 breaths/min. Methacholine was inhaled to double the respiratory resistance measured at 8 Hz by the forced oscillation technique. The capnogram shape changed in response to both methacholine and ventilatory frequency. Slope of phase II, the peak of first-order time derivative and trough of the second-order time derivative of the $F_{{CO}_{2}}$ signal, were significantly attenuated after methacholine compared with baseline at all breathing rates (p < 0.02). Moreover, significant correlations between respiratory reactance and resistance were observed with the phase III slope and the angle described by phase II and phase III (p < 0.01). It is concluded that capnography may be useful to identify acute airway changes related to bronchoconstriction, even at high breathing frequencies.
Lung function measurement with multiple-breath-helium washout system
2013, Medical Engineering and Physics
Citation Excerpt :
The lung clearance index (LCI) has been commonly used as a measure of lung health and is defined as the total expired volume during washout divided by the FRC, for a fall in tracer gas concentration to 2.5% of the initial value [35–37]. It has been shown that the LCI is more sensitive than the spirometry in cystic fibrosis (CF) adults, and its mean value has been measured 13.1 ± 3.8 in CF patients and a much lower mean value of 6.7 ± 0.4 in normal subjects [26,34–39,43–45]. Other studies have also shown the increasing LCI with the age [34] and a higher range of LCI in emphysematous patients [40].
Multiple-breath-washout (MBW) measurements are regarded as a sensitive technique which can reflect the ventilation inhomogeneity of respiratory airways. Typically nitrogen is used as the tracer gas and is washed out by pure oxygen in multiple-breath-nitrogen washout (MBNW) tests. In this study, instead of using nitrogen, ⁴He is used as the tracer gas with smaller gas density which may be able to reach deeper into our lungs in a given time and the helium washout results may be more sensitive to the ventilation inhomogeneity in small airways. A multiple-breath-helium-washout (MBHW) system developed for the lung function study is also presented. Quartz tuning forks with a resonance frequency of 32,768 Hz have been used for detecting the change of the respiratory gas density. The resonance frequency of the quartz tuning fork decreases linearly with increasing density of the surrounding gas. Knowing the CO₂ concentration from the infrared carbon dioxide detector, the helium concentration can be determined. Results from 14 volunteers (3 mild asthmatics, 4 tobacco smokers, 1 with asthma history, 1 with COPD history, 5 normal) have shown that mild asthmatics have higher ventilation inhomogeneity in either conducting or acinar airways (or both). A feature has been found in washout curve of single breaths from 4 tobacco smokers with different length of smoking history which may indicate the early stage of respiratory ventilation inhomogeneity in acinar airways.
Sensitivity of multiple breath washout to detect mild-to-moderate asthma in adolescence
2019, Journal of Allergy and Clinical Immunology: In Practice

View all citing articles on Scopus

View full text

MINI-SYMPOSIUM: LUNG FUNCTION IN PRESCHOOL CHILDRENInert gas washout in preschool children

Summary

Section snippets

INTRODUCTION

MULTIPLE-BREATH WASHOUT AND OTHER GAS-MIXING TESTS

EQUIPMENT AND PROCEDURES

REFERENCE VALUES

CLINICAL INTERPRETATION

AVAILABILITY

CONCLUSIONS

Respir Physiol

Respir Physiol

Quality control for spirometry in preschool children with and without lung disease

Am J Respir Crit Care Med

Measurement of lung function in awake 2–4-year-old asthmatic children during methacholine challenge and acute asthma: a comparison of the impulse oscillation technique, the interrupter technique and transcutaneous measurement of oxygen versus whole-body plethysmography

Pediatr Pulmonol

The measurement of airway resistance using the interrupter technique (Rint) in pre-school children in the ambulatory setting

Eur Respir J

Measurement of the specific airway resistance by plethysmography in young children accompanied by an adult

Eur Respir J

Resistance of central and peripheral airways measured by a retrograde catheter

J Appl Physiol

The physiology of the small airways

Am J Respir Crit Care Med

Peripheral airway function in childhood asthma, assessed by single-breath He and SF6 washout

Pediatr Pulmonol

Conductive and acinar lung-zone contributions to ventilation inhomogeneity in COPD

Am J Respir Crit Care Med

Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis

Am J Respir Crit Care Med

Moment analysis of multibreath nitrogen washout in young children

J Appl Physiol

MINI-SYMPOSIUM: LUNG FUNCTION IN PRESCHOOL CHILDREN
Inert gas washout in preschool children

Peripheral airway function in childhood asthma, assessed by single-breath He and SF₆ washout