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The cumulative effect of inflammation and infection on structural lung disease in early CF
Senin, 06 Mei 2019 17:15:59

Tim RosenowL. Clara MokLidija TurkovicLuke J. BerryPeter D. SlySarath RanganathanHarm A.W.M. TiddensStephen M. Stick

European Respiratory Journal 2019; DOI: 10.1183/13993003.01771-2018

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 below six with annual CT and bronchoalveolar lavage (BAL) were included. Structural lung disease on computed tomography (%Disease) was determined using the PRAGMA-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 Two hundred and sixty-five 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 [0.09, 0.54]; p=0.007) but not infection (0.23 [−0.01, 0.47]; p=0.060) detections. Reference equations are presented.

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.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Ms Mok has nothing to disclose.

Conflict of interest: Dr. Turkovic has nothing to disclose.

Conflict of interest: Dr. Berry has nothing to disclose.

Conflict of interest: Dr. Sly has nothing to disclose.

Conflict of interest: Dr. Ranganathan has nothing to disclose.

Conflict of interest: Dr. Tiddens reports other from Roche, other from Novartis, grants from CFF, grants from Vertex, grants from Gilead, grants from Chiesi, outside the submitted work; In addition, Dr. Tiddens has a patent Vectura licensed, and a patent PRAGMA-CF scoring system issued and I am heading the Erasmus MC-Sophia Children's Hospital core laboratory LungAnalysis.

Conflict of interest: Dr. Stick reports grants from NHMRC, during the conduct of the study.

Conflict of interest: Dr. Rosenow reports grants from National Health and Medical Research Council, during the conduct of the study; In addition, Dr. Rosenow has a patent PCT/AU2016/000079 pending.