Multiple-Breath Washout as a Marker of Lung Disease in Preschoolers with Cystic Fibrosis.

BackgroundThe lung clearance index (LCI) measured by the multiple breath washout (MBW) test is sensitive to early lung disease in children with cystic fibrosis (CF). While LCI worsens during the preschool years in CF, there is limited evidence to clarify whether this continues during the early school age years, and whether the trajectory of disease progression as measured by LCI is modifiable.MethodsA cohort of children (healthy (HC) and CF) previously studied for 12 months as preschoolers were followed during school age (5–10 years). LCI was measured every 3 months for a period of 24 months using the Exhalyzer® D MBW nitrogen washout device. Linear mixed effects regression was used to model changes in LCI over time.ResultsA total of 582 MBW measurements in 48 healthy subjects and 845 measurements in 64 CF subjects were available. The majority of children with CF had elevated LCI at the first preschool and first school age visits (57.8% (37/64)), whereas all but six had normal forced expiratory volume in 1 s (FEV1) values at the first school age visit. During school age years, the course of disease was stable (−0.02 units·year−1 (95% CI −0.14; 0.10). LCI measured during preschool years, as well as the rate of LCI change during this time period, were important determinants of LCI and FEV1, at school age.ConclusionPreschool LCI was a major determinant of school age LCI; these findings further support that the preschool years are critical for early intervention strategies.

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Exercise testing and multiple breath washout as markers of lung disease among patients with cystic fibrosis

10.1183/13993003.congress-2015.pa2048 ◽

2015 ◽

Author(s):

Elpis Hatziagorou ◽

Asterios Kampouras ◽

Vasiliki Avramidou ◽

Kalliopi Kontouli ◽

Fotios Kirvassilis ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Exercise Testing ◽

Multiple Breath Washout

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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

ERJ Open Research ◽

10.1183/23120541.00094-2017 ◽

2018 ◽

Vol 4 (1) ◽

pp. 00094-2017 ◽

Cited By ~ 3

Author(s):

Rachel E. Foong ◽

Alana J. Harper ◽

Billy Skoric ◽

Louise King ◽

Lidija Turkovic ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Fluid Collection ◽

Lavage Fluid ◽

Sufficient Information ◽

Healthy Children ◽

Success Rates ◽

Lung Clearance ◽

Lung Clearance Index ◽

Multiple Breath Washout

The lung clearance index (LCI) from the multiple-breath washout (MBW) test is a promising surveillance tool for pre-school children with cystic fibrosis (CF). Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged <7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials. This study aimed to determine if relationships between LCI and clinical outcomes of CF lung disease differ when only two acceptable MBW trials are assessed.Healthy children and children with CF aged 3–6 years were recruited for MBW testing. Children with CF also underwent bronchoalveolar lavage fluid collection and a chest computed tomography scan.MBW feasibility increased from 46% to 75% when tests with two trials were deemed acceptable compared with tests where three acceptable trials were required. Relationships between MBW outcomes and markers of pulmonary inflammation, infection and structural lung disease were not different between tests with three acceptable trials compared with tests with two acceptable trials.This study indicates that pre-school MBW data from two acceptable trials may provide sufficient information on ventilation distribution if three acceptable trials are not possible.

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Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests

Thorax ◽

10.1136/thx.2006.068262 ◽

2007 ◽

Vol 62 (4) ◽

pp. 341-347 ◽

Cited By ~ 135

Author(s):

S. Lum ◽

P. Gustafsson ◽

H. Ljungberg ◽

G. Hulskamp ◽

A. Bush ◽

...

Keyword(s):

Cystic Fibrosis ◽

Early Detection ◽

Lung Disease ◽

Cystic Fibrosis Lung ◽

Cystic Fibrosis Lung Disease ◽

Multiple Breath Washout

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Slow and fast lung compartments in cystic fibrosis measured by nitrogen multiple-breath washout

Journal of Applied Physiology ◽

10.1152/japplphysiol.01274.2013 ◽

2014 ◽

Vol 117 (7) ◽

pp. 720-729 ◽

Cited By ~ 13

Author(s):

P. M. Gustafsson ◽

P. D. Robinson ◽

M. Gilljam ◽

A. Lindblad ◽

B. K. Houltz

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Disease Severity ◽

Phase Iii ◽

Healthy Controls ◽

Lung Compartment ◽

Wide Range ◽

Multiple Breath Washout ◽

Lung Disease Severity ◽

And Function

Imaging studies describe significant ventilation defects across a wide range of cystic fibrosis (CF) related lung disease severity. These are unfortunately poorly reflected by phase III slope analysis–derived Scond and Sacin from multiple-breath washout (MBW). Methodology extending previous two-lung compartment model-based analysis is presented describing size and function of fast- and slow-ventilating lung compartments from nitrogen (N2) MBW and correlation to obstructive lung disease severity. In 37 CF subjects (forced expiratory volume in 1 s [FEV1] mean [SD] 84.8 [19.9] % predicted; abnormal lung clearance index [LCI] in 36/37, range 7.28–18.9) and 74 matched healthy controls, volume and specific ventilation of both fast and slowly ventilated lung compartments were derived from N2-based MBW with commercial equipment. In healthy controls lung emptying was characterized by a large compartment constituting 75.6 (8.4)% of functional residual capacity (FRC) with a specific ventilation (regional alveolar tidal volume/regional lung volume) of 13.9 (3.7)% and a small compartment with high specific ventilation (48.4 [15.7]%). In CF the slowly ventilated lung compartment constituted 51.9(9.1)% of FRC, with low specific ventilation of 5.3 (2.4)%. Specific ventilation of the slowly ventilated lung compartment showed stronger correlation with LCI (r2 = 0.70, P < 0.001) vs. Sacin (r2 = 0.44, P < 0.001) or Scond (no significant correlation). Overventilation of the fast lung compartment was no longer seen in severe CF lung disease. Magnitude and function of under- and overventilated lung volumes can be derived from routine N2 MBW in CF. Reported values agree with previous modelling-derived estimates of impaired ventilation and offer improved correlation to disease severity, compared with SnIII analysis.

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Quantification of Phenotypic Variability of Lung Disease in Children with Cystic Fibrosis

Genes ◽

10.3390/genes12060803 ◽

2021 ◽

Vol 12 (6) ◽

pp. 803

Author(s):

Mirjam Stahl ◽

Eva Steinke ◽

Marcus A. Mall

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Clinical Symptoms ◽

Phenotypic Variability ◽

Lung Structure ◽

Multiple Breath Washout ◽

Cftr Mutations ◽

Magnetic Resonance Imaging Mri ◽

And Function ◽

The Impact

Cystic fibrosis (CF) lung disease has the greatest impact on the morbidity and mortality of patients suffering from this autosomal-recessive multiorgan disorder. Although CF is a monogenic disorder, considerable phenotypic variability of lung disease is observed in patients with CF, even in those carrying the same mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or CFTR mutations with comparable functional consequences. In most patients with CF, lung disease progresses from childhood to adulthood, but is already present in infants soon after birth. In addition to the CFTR genotype, the variability of early CF lung disease can be influenced by several factors, including modifier genes, age at diagnosis (following newborn screening vs. clinical symptoms) and environmental factors. The early onset of CF lung disease requires sensitive, noninvasive measures to detect and monitor changes in lung structure and function. In this context, we review recent progress with using multiple-breath washout (MBW) and lung magnetic resonance imaging (MRI) to detect and quantify CF lung disease from infancy to adulthood. Further, we discuss emerging data on the impact of variability of lung disease severity in the first years of life on long-term outcomes and the potential use of this information to improve personalized medicine for patients with CF.

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How to Monitor Early Cystic Fibrosis Lung Disease. By Multiple-Breath Washout, Chest Computed Tomography, or Both?

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.201509-1862ed ◽

2016 ◽

Vol 193 (1) ◽

pp. 7-8 ◽

Cited By ~ 2

Author(s):

Florian Singer ◽

Carmen Casaulta ◽

Philipp Latzin

Keyword(s):

Computed Tomography ◽

Cystic Fibrosis ◽

Lung Disease ◽

Cystic Fibrosis Lung ◽

Chest Computed Tomography ◽

Cystic Fibrosis Lung Disease ◽

Multiple Breath Washout

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132 Multiple breath washout and forced oscillation technique to assess lung disease in cystic fibrosis

Journal of Cystic Fibrosis ◽

10.1016/s1569-1993(16)30370-8 ◽

2016 ◽

Vol 15 ◽

pp. S84 ◽

Cited By ~ 1

Author(s):

E. Hatziagorou ◽

D. Pappa ◽

D. Terzi ◽

V. Avramidou ◽

F. Kirvassilis ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Forced Oscillation ◽

Forced Oscillation Technique ◽

Multiple Breath Washout

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The quantitative link of lung clearance index to bronchial segments affected by bronchiectasis

Thorax ◽

10.1136/thoraxjnl-2017-210496 ◽

2017 ◽

Vol 73 (1) ◽

pp. 82-84 ◽

Cited By ~ 10

Author(s):

Sylvia Verbanck ◽

Gregory G King ◽

Wenxiao Zhou ◽

Anne Miller ◽

Cindy Thamrin ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Disease Severity ◽

Adult Patients ◽

Lung Clearance ◽

Lung Clearance Index ◽

Ventilation Heterogeneity ◽

Multiple Breath Washout ◽

Lung Disease Severity

In adult patients with cystic fibrosis (CF), the lung clearance index (LCI) derived from the multiple breath washout relates to both acinar and conductive ventilation heterogeneity. The latter component predicts an association between LCI and the number of bronchial segments affected by bronchiectasis. Here, we experimentally demonstrated this association in patients with CF, and also examined an ancillary group of patients with non-CF bronchiectasis. We conclude that lung disease severity in terms of number of bronchial segments results in an associated LCI increase, likely constituting a portion of LCI that cannot be reversed by treatment in patients with CF lung disease.

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