The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index; none of the 6 sources its claims cite is checked for support yet.
Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis
Open accessAbstract
BACKGROUND: A sensitive and valid non-invasive marker of early cystic fibrosis (CF) lung disease is sought. The lung clearance index (LCI) from multiple-breath washout (MBW) is known to detect abnormal lung function more readily than spirometry in children and teenagers with CF, but its relationship to structural lung abnormalities is unknown. A study was undertaken to determine the agreements between LCI and spirometry, respectively, with structural lung disease as measured by high-resolution computed tomography (HRCT) in children and teenagers with CF. METHODS: A retrospective study was performed in 44 consecutive patients with CF aged 5-19 years (mean 12 years). At an annual check-up inspiratory and expiratory HRCT scans, LCI and spirometric parameters (forced expiratory volume in 1 s (FEV1) and maximal expiratory flow when 75% of forced vital capacity was expired (FEF75)) were recorded. Abnormal structure was defined as a composite HRCT score of >5%, the presence of bronchiectasis or air trapping >30%. Abnormal lung function was defined as LCI above the predicted mean +1.96 residual standard deviations (RSD), or FEV1 or FEF75 below the predicted mean -1.96 RSD. Sensitivity/specificity assessments and correlation analyses were done. RESULTS: The sensitivity to detect abnormal lung structure was 85-94% for LCI, 19-26% for FEV1 and 62-75% for FEF75. Specificity was 43-65% for LCI, 89-100% for FEV1 and 75-88% for FEF75. LCI correlated better with HRCT scores (Rs +0.85) than FEV1 (-0.62) or FEF75 (-0.66). CONCLUSIONS: LCI is a more sensitive indicator than FEV1 or FEF75 for detecting structural lung disease in CF, and a normal LCI almost excludes HRCT abnormalities. The finding of an abnormal LCI in some patients with normal HRCT scans suggests that LCI may be even more sensitive than HRCT scanning for detecting lung involvement in CF.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In 44 children and teenagers with cystic fibrosis, the lung clearance index (LCI) from multiple-breath washout was more sensitive than FEV₁ or FEF₇₅ for detecting HRCT-defined structural lung disease, and a normal LCI almost excluded HRCT abnormalities. LCI also correlated more strongly with HRCT scores than spirometry, although its specificity was lower.
Key findings
- Sensitivity for detecting abnormal lung structure was 85–94% for LCI, 19–26% for FEV₁, and 62–75% for FEF₇₅; specificity was 43–65% for LCI, 89–100% for FEV₁, and 75–88% for FEF₇₅.
- LCI correlated better with the HRCT composite score (Rₛ +0.85) than FEV₁ (−0.62) or FEF₇₅ (−0.66).
- Of 27 patients with an abnormal composite HRCT score (>5%), 25 had elevated LCI, 17 had abnormal FEF₇₅, and 7 had reduced FEV₁; of 17 patients with normal HRCT scores (<5%), 6 had elevated LCI, 2 had abnormal FEF₇₅, and all had normal FEV₁.
- Bronchiectasis was diagnosed in 26 patients (59%), abnormal composite HRCT score in 27 (61%), and pathological gas trapping in 16 (36%).
Methods
- Retrospective study over 30 months in 44 consecutive patients with CF aged 5–19 years (mean and median age 12.2 years) at the Göteborg CF centre; annual review included inspiratory and expiratory HRCT, tidal-breathing multiple-breath SF₆ washout for LCI, and spirometry (FEV₁, FEF₇₅).
- Abnormal structure was defined as composite HRCT score >5%, presence of bronchiectasis, or air trapping >30%; abnormal lung function was defined as LCI above +1.96 z-scores or FEV₁/FEF₇₅ below −1.96 z-scores.
- Sensitivity/specificity and Spearman rank correlations were calculated for LCI, FEV₁, and FEF₇₅ against HRCT-defined structural abnormalities.
Limitations
- Stated: the study was cross-sectional, so it cannot show whether LCI rises with advancing structural lung changes over time; longitudinal studies are needed. The HRCT protocol used 15 mm gaps between inspiratory images and only three expiratory images, which may underestimate structural abnormalities and air trapping. The sample included only children/teenagers older than 5 years who could perform spirometry, with a slight male over-representation (61% vs 52% in the entire CF population), and tests were not always performed on the same day (same day in 26/44 patients, 59%; all but one within one day).
- Evident: this was a single-centre retrospective study with a small sample, and HRCT was treated as the reference standard despite acknowledged limitations; LCI specificity was modest, with abnormal LCI in about one-third of patients with normal HRCT scores.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Specificity was 43-65% for LCI, 89-100% for FEV 1 and 75-88% for FEF 75 .”
- Also stated in: § RESULTS · plain
“The specificity in the detection of structural lung disease was, however, higher for FEV 1 (89-100%) and FEF 75 (75-88%) than for LCI (43-65%).”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The sensitivity to detect abnormal lung structure was 85-94% for LCI, 19-26% for FEV 1 and 62-75% for FEF 75 .”
- Also stated in: § RESULTS · plain
“The LCI had the best sensitivity (85-94%) for detecting structural lung abnormalities (bronchiectasis, composite HTCT score and air trapping) (table 2).”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LCI and FEF 75 showed closer agreement with findings of structural lung abnormalities than did FEV 1 (table 1).”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The sensitivity to detect abnormal lung structure was 85-94% for LCI, 19-26% for FEV 1 and 62-75% for FEF 75 .”
- Also stated in: § RESULTS · plain
“The sensitivity for FEV 1 ranged from 19% to 26% and for FEF 75 from 62% to 75%.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The sensitivity to detect abnormal lung structure was 85-94% for LCI, 19-26% for FEV 1 and 62-75% for FEF 75 .”
- Also stated in: § RESULTS · plain
“The sensitivity for FEV 1 ranged from 19% to 26% and for FEF 75 from 62% to 75%.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Specificity was 43-65% for LCI, 89-100% for FEV 1 and 75-88% for FEF 75 .”
- Also stated in: § RESULTS · plain
“The specificity in the detection of structural lung disease was, however, higher for FEV 1 (89-100%) and FEF 75 (75-88%) than for LCI (43-65%).”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Specificity was 43-65% for LCI, 89-100% for FEV 1 and 75-88% for FEF 75 .”
- Also stated in: § RESULTS · plain
“The specificity in the detection of structural lung disease was, however, higher for FEV 1 (89-100%) and FEF 75 (75-88%) than for LCI (43-65%).”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the other hand, many patients in the present study who had normal FEV 1 or FEF 75 results showed evidence of quite advanced structural lung damage.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LCI is a more sensitive indicator than FEV 1 or FEF 75 for detecting structural lung disease in CF, and a normal LCI almost excludes HRCT abnormalities.”
- Also stated in: § DISCUSSION · hedged
“Of 27 patients with abnormal HRCT scores, 25 had elevated LCI and 22/26 patients with evidence of bronchiectasis had abnormal LCI, which suggests that a normal LCI in a subject with CF almost excludes structural lung damage.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § DISCUSSION · hedged
In the paper
“It is known that air trapping can be seen in normal individuals, 48”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > Measurement of lung structure
What the sources say
- Not matchedcites [48]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Not matched
- It may state two separate claims as one. 14
- Probably not a substantial claim. 6
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Seventeen patients had normal HRCT scores ((5%); 6 of these had elevated LCI, 2 had abnormal FEF 75 and all had FEV 1 within normal limits.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 27 patients with an HRCT score .5%, 25 had an abnormally elevated LCI, 17 had abnormal FEF 75 results and 7 had reduced FEV 1 .”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LCI correlated better with HRCT scores (Rs +0.85) than FEV 1 (20.62) or FEF 75 (20.66).”
- Also stated in: § RESULTS · boosted
“The LCI had a markedly stronger correlation with all six structural abnormality scores (R s 0.65 to 0.85) than did the FEV 1 (R s 20.35 to 20.62) or FEF 75 (R s 20.44 to 20.66) (table 3).”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § RESULTS · boosted
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The study involved only children and teenagers who could perform spirometric tests and who were aged .5 years because the routine schedule includes HRCT scans only above that age.The relationships between LCI and HRCT abnormalities in younger and older patients therefore remain to be determined.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As expected, the FEV 1 had a low sensitivity, making it of little value in early disease detection in CF.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“There was a slight over-representation of males (61%) in the study population compared with 52% in the entire CF population.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Another explanation for the somewhat low specificity of the LCI could be that our HRCT protocol might have missed some structural aberrations.Only three expiratory images were obtained, which may limit the ability to detect the full extent of air trapping.In addition, for the inspiratory CT scans there are relatively large gaps of 15 mm between the CT images, which potentially result in underestim”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
What the sources say
- Not matchedcites [36]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The MBW parameters were determined without having information on the CT scan.Furthermore, patient identity, demographic information or lung function findings were not available to the observer scoring the images.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All scans were blinded to date and patient identification and were scored in random order by an experienced observer 21 24 25 using an adapted scoring system developed by Brody et al. 22 47”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > Measurement of lung structure
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“The LCI is a measure of overall ventilation inhomogeneity in the lungs, which occurs at branch points in large or small airways including very small airways close to or within the gas exchange zone.53”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
What the sources say
- Not matchedcites [53]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All investigations were carried out in clinically stable patients during their annual review at the CF centre.They were undertaken on the same day in 26 of the patients (59%), and in all remaining patients but one there was only one day between any of the tests.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The patient group included a sample of approximately one-third of all patients with CF attending the CF Center in Go ¨teborg.This sample constituted all consecutive patients over a 30-month period aged ,20 years who were investigated with spirometry and MBW as part of their annual review and, in addition, HRCT which is done routinely every third year in patients older than 5 years.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Geometric alterations in very small airways due to airway wall thickening or mucus accumulation can result in uneven ventilation distribution, but such alterations may not be detected by HRCT scanning.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The better specificity of FEV 1 compared with the LCI means that, when FEV 1 starts to decline, major bronchiectasis or other structural damage is likely to be present.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The specificity of LCI was modest, however, because LCI was abnormal in onethird of the patients with normal HRCT scores, half of those without evidence of bronchiectasis, and in more than half of those without diagnosed air trapping.”
§ Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
The relationship of LCI to structural lung abnormalities in CF has not been reported previously.
“The relationship of LCI to structural lung abnormalities in CF has, however, not been reported previously.”
“The lung clearance index (LCI) from multiple-breath washout (MBW) is known to detect abnormal lung function more readily than spirometry in children and teenagers with CF, but its relationship to structural lung abnormalities is unknown.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Reported LCI correlation range omits the lowest value
MinorThe stated range starts at 0.65, but table 3 reports an LCI correlation of 0.64 for bronchiectasis.
“The LCI had a markedly stronger correlation with all six structural abnormality scores (R s 0.65 to 0.85)”
“| LCI | 0.85*** | 0.64*** | 0.73*** | 0.76*** | 0.79*** | 0.65*** |”
Citations
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Multiple-Breath Washout as a Marker of Lung Disease in Preschool Children with Cystic Fibrosis
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Self-citation
Metadata
- Authors
- Gustafsson, P. M., De Jong, P. A., Tiddens, H. A. W. M., & Lindblad, A.
- Affiliations
- Drottning Silvias barn- och ungdomssjukhus (SE)
- Erasmus MC - Sophia Children’s Hospital (NL)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Gustafsson, P M
- Venue
- Thorax
- Publisher
- BMJ
- Published
- 2007-09-17
- Volume
- 63
- Issue
- 2
- Pages
- 129-134
- ISSN
- 0040-6376 (ISSN-L)
- OpenAlex
- W2052470792
- Cited by
- 364
- References
- 55
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 14 · 2023: 22 · 2022: 19 · 2021: 30 · 2020: 25 · 2019: 23 · 2018: 13 · 2017: 22 · 2016: 22 · 2015: 30 · 2014: 18 · 2013: 21 · 2012: 21
- FWCI
- 11.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Thorax (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- British Columbia Lung Association
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Keywords
- cystic fibrosis, lung clearance index, multiple breath washout, spirometry, structural lung disease, high-resolution computed tomography, bronchiectasis, air trapping, FEV1, FEF75, children and adolescents
- MeSH terms
- Adolescent, Adult, Breath Tests, Bronchiectasis, Child, Child, Preschool, Cross-Sectional Studies, Cystic Fibrosis, Female, Forced Expiratory Volume, Humans, Lung, Male, Respiratory Function Tests, Retrospective Studies, Sensitivity and Specificity, Spirometry, Tomography, X-Ray Computed, Ultrasonography
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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