Highlights
- •CF pulmonary exacerbations (PEx) were clustered into 3 distinct groups based on blood inflammation.
- •Neutrophil-predominant PEx events presented with shorter onset of symptoms and larger drop in lung function.
- •Pauci-inflammatory PEx events presented with longer onset of symptoms and a lower rate of lung function recovery after IV antibiotics.
Abstract
Background
Adults with cystic fibrosis (CF) develop exuberant inflammatory responses during pulmonary
exacerbations (PEx) but whether distinct systemic inflammatory profiles can be identified
and whether these associate with disparate treatment outcomes are unclear. We conducted
a pilot study to address this question and hypothesized that CF adults with a pauci-inflammatory
phenotype might derive less clinical benefit from intravenous (IV) antibiotic treatment
than patients with other systemic inflammatory phenotypes.
Methods
Six proteins reflective of systemic inflammation were examined in 37 PEx from 28 unique
CF subjects. We applied exploratory factor analysis and cluster analysis to identify
biological clusters. Levels of blood proteins at PEx and clinical outcomes following
IV antibiotic treatment were compared between clusters.
Results
Three clusters of PEx were identified. The pauci-inflammatory phenotype was characterized
by lower levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α,
calprotectin, and C-reactive protein (CRP) (p < 0.05). Higher levels of IL-6 and IL-1β were observed in the other 2 inflammatory
clusters, but one of them was associated with higher calprotectin levels (p = 0.001) (neutrophil-predominant phenotype); whereas the other was associated with
increased TNF-α and IL-10 levels (p < 0.001) (pro-inflammatory phenotype). A greater proportion of events from the neutrophil-predominant
phenotype presented with acute respiratory symptoms and a larger decrease in ppFEV1 from baseline to hospital admission than the other two inflammatory phenotypes (p = 0.03).
Conclusions
Three distinct inflammatory phenotypes were identified at PEx admission and each presented
with unique clinical characteristics.
Keywords
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Article info
Publication history
Published online: December 25, 2022
Accepted:
December 20,
2022
Received in revised form:
December 6,
2022
Received:
August 2,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
