title: Hypoxia and sterile inflammation in cystic fibrosis airways: mechanisms and potential therapies.
abstract: 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.
authors.affiliation: School of Paediatrics and Child Health, The University of Western Australia, Nedlands, Australia.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Montgomery
authors.affiliation: Dept of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.|Division of Pediatric Pulmonology and Allergy, Cystic Fibrosis Center, Dept of Pediatrics, University of Heidelberg, Heidelberg, Germany.|These authors contributed equally.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
authors.affiliation: School of Paediatrics and Child Health, The University of Western Australia, Nedlands, Australia Anthony.Kicic@telethonkids.org.au.|Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, Australia.|Dept of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Australia.|Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Australia.|These authors contributed equally.
authors.forename: Anthony
authors.initials: A
authors.lastname: Kicic
authors.affiliation: School of Paediatrics and Child Health, The University of Western Australia, Nedlands, Australia.|Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, Australia.|Dept of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Australia.|Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Australia.|These authors contributed equally.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Stick
mesh_terms: D000818:Animals; D001987:Bronchiectasis / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000150:complications*; D004195:Disease Models, Animal; D004848:Epithelium / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000473:pathology*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017472:Receptors, Interleukin-1