Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies
MetadataShow full item record
Copyright Â© ERS 2017. Cystic fibrosis is one of the most common autosomal recessive genetic diseases in Caucasian populations. Diagnosis via newborn screening and targeted nutritional and antibiotic therapy have improved outcomes, however respiratory failure remains the key cause of morbidity and mortality. Progressive respiratory disease in cystic fibrosis is characterised by chronic neutrophilic airway inflammation associated with structural airway damage leading to bronchiectasis and decreased lung function. Mucus obstruction is a characteristic early abnormality in the cystic fibrosis airway, associated with neutrophilic inflammation often in the absence of detectable infection. Recent studies have suggested a link between hypoxic cell death and sterile neutrophilic inflammation in cystic fibrosis and other diseases via the IL-1 signalling pathway. In this review, we consider recent evidence regarding the cellular responses to respiratory hypoxia as a potential driver of sterile neutrophilic inflammation in the lung, current knowledge on hypoxia as a pathogenic mechanism in cystic fibrosis and the potential for current and future therapies to alleviate hypoxia-driven sterile inflammation.
Showing items related by title, author, creator and subject.
Pittman, J.; Wylie, K.; Akers, K.; Storch, G.; Hatch, J.; Quante, J.; Frayman, K.; Clarke, N.; Davis, M.; Stick, S.; Hall, Graham; Montgomery, G.; Ranganathan, S.; Davis, S.; Ferkol, T.; AREST CF (2017)RATIONALE: The underlying defect in the cystic fibrosis (CF) airway leads to defective mucociliary clearance and impaired bacterial killing, resulting in endobronchial infection and inflammation that contributes to ...
Elastase exocytosis by airway neutrophils is associated with early lung damage in children with cystic fibrosisMargaroli, C.; Garratt, L.W.; Horati, H.; Dittrich, A.S.; Rosenow, T.; Montgomery, S.T.; Frey, D.L.; Brown, M.R.; Schultz, C.; Guglani, L.; Kicic, Anthony ; Peng, L.; Scholte, B.J.; Mall, M.A.; Janssens, H.M.; Stick, S.M.; Tirouvanziam, R. (2019)Copyright © 2019 by the American Thoracic Society. Rationale: Neutrophils are recruited to the airways of individuals with cystic fibrosis (CF). In adolescents and adults with CF, airway neutrophils actively exocytose the ...
Multiple-breath washout outcomes are sensitive to inflammation and infection in children with cystic fibrosisRamsey, K.; Foong, R.; Grdosic, J.; Harper, A.; Skoric, B.; Clem, C.; Davis, M.; Turkovic, L.; Stick, S.; Davis, S.; Ranganathan, S.; Hall, Graham (2017)© 2017 by the American Thoracic Society. Rationale: The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. The lung clearance index is increased in the presence ...