Original Article|Articles in Press

Pulmonary exacerbation inflammatory phenotypes in adults with cystic fibrosis

Published:December 25, 2022DOI:


      • 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.



      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.


      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.


      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).


      Three distinct inflammatory phenotypes were identified at PEx admission and each presented with unique clinical characteristics.


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