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Published on: May 8, 2017
Neutrophil respiratory burst activity is not exaggerated in cystic fibrosis
Dean Kelk1, Jayden Logan2, Isabella Andersen1
1Children's Health and Environment Program, Child Health Research Centre, The University of Queensland, South Brisbane, Qld Australia.
Insights
Neutrophil reactive oxygen species (ROS) production is lower in stable cystic fibrosis (CF) patients, contrary to theories of exaggerated inflammation. This study found no increase in ROS during exacerbations, challenging existing hypotheses about CF lung disease progression.
Area of Science:
- Immunology
- Pulmonology
- Biochemistry
Background:
- Neutrophil-driven inflammation is central to progressive cystic fibrosis (CF) lung disease.
- Conflicting evidence exists regarding neutrophil respiratory burst function in CF, with older studies suggesting defects and newer studies indicating normal function.
Purpose of the Study:
- To investigate reactive oxygen species (ROS) production during respiratory burst activity in neutrophils from children and adults with CF.
- To determine if ROS production differs in clinically stable CF patients compared to controls and if it changes during acute pulmonary exacerbations.
Main Methods:
- Measured ROS amount and rate during PMA-stimulated respiratory burst in neutrophils from peripheral blood.
- Included children and adults with CF (stable, exacerbation admission, and discharge) and healthy/disease controls.
- Assessed associations between ROS production and high-sensitivity C-reactive protein.
Main Results:
- Clinically stable children with CF exhibited lower ROS production and rate compared to disease and healthy controls (p=0.008 and p=0.029, respectively).
- ROS production did not increase in CF patients upon hospital admission for exacerbations or decrease before discharge.
- No correlation was found between ROS production and systemic inflammation markers (high-sensitivity C-reactive protein).
Conclusions:
- The findings do not support the hypothesis that exaggerated respiratory burst activity contributes to the inflammation observed in CF lung disease.
- This suggests that other mechanisms may be responsible for the neutrophil-dominated inflammation in CF.
Background:
Exaggerated neutrophil-dominated inflammation underlies progressive cystic fibrosis (CF) lung disease. Older studies reported a defective respiratory burst in CF, but more recent studies suggest neutrophil function is normal.
Methods:
We measured the amount and rate of reactive oxygen species (ROS) during PMA-stimulated respiratory burst activity in children [70 CF, 13 disease controls, 19 health controls] and adults [31 CF, 14 health controls] in neutrophils harvested from peripheral blood. Blood was collected from participants with CF when clinically stable (60 children, 9 adults) and on hospital admission (38 children, 24 adults) and discharge (18 children, 21 adults) for acute pulmonary exacerbations.
Results:
When clinically stable, children with CF had lower ROS production [median 318,633, 25% 136,810 - 75% 569,523 RLU] than disease controls [median 599,459, 25% 425,566 - 75% 730,527 RLU] and healthy controls [median 534,073, 25% 334,057 - 75% 738,593 RLU] (p = 0.008). The rate of ROS production was also lower (p = 0.029). In neither children nor adults with CF did ROS production increase on hospital admission for acute pulmonary exacerbation, nor fall prior to discharge. There were no associations between ROS production and high-sensitivity C-reactive protein (indicating systemic inflammation) in either children or adults with CF.
Conclusions:
Our data do not support a role for exaggerated respiratory burst activity contributing to the exaggerated neutrophil-dominated inflammation seen with CF lung disease.
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