Abstract
Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) patients both have chronic lung infection and neutrophilic inflammation, but there is a milder clinical phenotype in PCD. To understand the detailed inflammatory mechanisms in these two conditions in order to identify potential therapeutic targets and useful biomarkers of disease severity, spontaneously expectorated sputum was collected from CF and PCD patients with similar spirometry. Sputum was homogenized in phosphate-buffered saline, centrifuged, and the supernatants analyzed. Surprisingly, the level of neutrophil-stimulating activity was similar in CF and PCD patients, with a trend for lower amounts of CXC chemokines in CF patients. In an exploratory, hypothesis generating study, we found that levels of neutrophil elastase, cathepsin G, and elastin degradation products were significantly elevated in CF patients in exacerbation compared to stable PCD patients, despite similar spirometry in both groups. Neutrophil chemoattractants are similar or even reduced in CF compared with PCD, suggesting that they may not be useful therapeutic targets or biomarkers in CF. However, matrix-degrading enzymes were markedly higher in CF. Further research is needed to explore the reasons for the differences between PCD and CF, but if these findings are confirmed, we speculate that inhibition of neutrophil-derived proteolytic enzymes in CF patients may be a more useful therapeutic target than inhibiting neutrophil chemoattraction.
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