The cumulative effect of inflammation and infection on structural lung disease in early cystic fibrosis

Tim Rosenow, L. Clara Mok, Lidija Turkovic, Luke J. Berry, Peter D. Sly, Sarath Ranganathan, Harm A.W.M. Tiddens, Stephen M. Stick

Research output: Contribution to journalArticle

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Abstract

Introduction: Pulmonary inflammation and infection are important clinical and prognostic markers of lung disease in cystic fibrosis (CF). However, whether in young children they are transient findings or have cumulative, long-term impacts on respiratory health is largely unknown. We aimed to determine whether their repeated detection has a deleterious effect on structural lung disease. Methods: All patients aged <6 years with annual computed tomography (CT) and bronchoalveolar lavage (BAL) were included. Structural lung disease on CT (%Disease) was determined using the PRAGMA-CF (Perth–Rotterdam Annotated Grid Morphometric Analysis for CF) method. The number of times free neutrophil elastase (NE) and infection were detected in BAL were counted, to determine cumulative BAL history. Linear mixed model analysis, accounting for repeat visits and adjusted for age, was used to determine associations. Results: 265 children (683 scans) were included for analysis, with BAL history comprising 1161 visits. %Disease was significantly associated with the number of prior NE (0.31, 95% CI 0.09–0.54; p=0.007) but not infection (0.23, 95% CI −0.01–0.47; p=0.060) detections. Reference equations were determined. Conclusions: Pulmonary inflammation in surveillance BAL has a cumulative effect on structural lung disease extent, more so than infection. This provides a strong rationale for therapies aimed at reducing inflammation in young children.

Original languageEnglish
Article number1801771
JournalEuropean Respiratory Journal
Volume54
Issue number1
DOIs
Publication statusPublished - 11 Jul 2019

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Bronchoalveolar Lavage
Cystic Fibrosis
Lung Diseases
Inflammation
Infection
Leukocyte Elastase
Pneumonia
History
Tomography
Linear Models
Biomarkers
Health

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Rosenow, Tim ; Clara Mok, L. ; Turkovic, Lidija ; Berry, Luke J. ; Sly, Peter D. ; Ranganathan, Sarath ; Tiddens, Harm A.W.M. ; Stick, Stephen M. / The cumulative effect of inflammation and infection on structural lung disease in early cystic fibrosis. In: European Respiratory Journal. 2019 ; Vol. 54, No. 1.
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abstract = "Introduction: Pulmonary inflammation and infection are important clinical and prognostic markers of lung disease in cystic fibrosis (CF). However, whether in young children they are transient findings or have cumulative, long-term impacts on respiratory health is largely unknown. We aimed to determine whether their repeated detection has a deleterious effect on structural lung disease. Methods: All patients aged <6 years with annual computed tomography (CT) and bronchoalveolar lavage (BAL) were included. Structural lung disease on CT ({\%}Disease) was determined using the PRAGMA-CF (Perth–Rotterdam Annotated Grid Morphometric Analysis for CF) method. The number of times free neutrophil elastase (NE) and infection were detected in BAL were counted, to determine cumulative BAL history. Linear mixed model analysis, accounting for repeat visits and adjusted for age, was used to determine associations. Results: 265 children (683 scans) were included for analysis, with BAL history comprising 1161 visits. {\%}Disease was significantly associated with the number of prior NE (0.31, 95{\%} CI 0.09–0.54; p=0.007) but not infection (0.23, 95{\%} CI −0.01–0.47; p=0.060) detections. Reference equations were determined. Conclusions: Pulmonary inflammation in surveillance BAL has a cumulative effect on structural lung disease extent, more so than infection. This provides a strong rationale for therapies aimed at reducing inflammation in young children.",
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The cumulative effect of inflammation and infection on structural lung disease in early cystic fibrosis. / Rosenow, Tim; Clara Mok, L.; Turkovic, Lidija; Berry, Luke J.; Sly, Peter D.; Ranganathan, Sarath; Tiddens, Harm A.W.M.; Stick, Stephen M.

In: European Respiratory Journal, Vol. 54, No. 1, 1801771, 11.07.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The cumulative effect of inflammation and infection on structural lung disease in early cystic fibrosis

AU - Rosenow, Tim

AU - Clara Mok, L.

AU - Turkovic, Lidija

AU - Berry, Luke J.

AU - Sly, Peter D.

AU - Ranganathan, Sarath

AU - Tiddens, Harm A.W.M.

AU - Stick, Stephen M.

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N2 - Introduction: Pulmonary inflammation and infection are important clinical and prognostic markers of lung disease in cystic fibrosis (CF). However, whether in young children they are transient findings or have cumulative, long-term impacts on respiratory health is largely unknown. We aimed to determine whether their repeated detection has a deleterious effect on structural lung disease. Methods: All patients aged <6 years with annual computed tomography (CT) and bronchoalveolar lavage (BAL) were included. Structural lung disease on CT (%Disease) was determined using the PRAGMA-CF (Perth–Rotterdam Annotated Grid Morphometric Analysis for CF) method. The number of times free neutrophil elastase (NE) and infection were detected in BAL were counted, to determine cumulative BAL history. Linear mixed model analysis, accounting for repeat visits and adjusted for age, was used to determine associations. Results: 265 children (683 scans) were included for analysis, with BAL history comprising 1161 visits. %Disease was significantly associated with the number of prior NE (0.31, 95% CI 0.09–0.54; p=0.007) but not infection (0.23, 95% CI −0.01–0.47; p=0.060) detections. Reference equations were determined. Conclusions: Pulmonary inflammation in surveillance BAL has a cumulative effect on structural lung disease extent, more so than infection. This provides a strong rationale for therapies aimed at reducing inflammation in young children.

AB - Introduction: Pulmonary inflammation and infection are important clinical and prognostic markers of lung disease in cystic fibrosis (CF). However, whether in young children they are transient findings or have cumulative, long-term impacts on respiratory health is largely unknown. We aimed to determine whether their repeated detection has a deleterious effect on structural lung disease. Methods: All patients aged <6 years with annual computed tomography (CT) and bronchoalveolar lavage (BAL) were included. Structural lung disease on CT (%Disease) was determined using the PRAGMA-CF (Perth–Rotterdam Annotated Grid Morphometric Analysis for CF) method. The number of times free neutrophil elastase (NE) and infection were detected in BAL were counted, to determine cumulative BAL history. Linear mixed model analysis, accounting for repeat visits and adjusted for age, was used to determine associations. Results: 265 children (683 scans) were included for analysis, with BAL history comprising 1161 visits. %Disease was significantly associated with the number of prior NE (0.31, 95% CI 0.09–0.54; p=0.007) but not infection (0.23, 95% CI −0.01–0.47; p=0.060) detections. Reference equations were determined. Conclusions: Pulmonary inflammation in surveillance BAL has a cumulative effect on structural lung disease extent, more so than infection. This provides a strong rationale for therapies aimed at reducing inflammation in young children.

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