Nicola J Ronan1, Gisli G Einarsson2, Maria Twomey3, Denver Mooney2, David Mullane4, Muireann NiChroinin4, Grace O'Callaghan1, Fergus Shanahan5, Desmond M Murphy1, Owen J O'Connor3, Cathy A Shortt4, Michael M Tunney2, Joseph A Eustace6, Michael M Maher3, J Stuart Elborn7, Barry J Plant8. 1. Cork Cystic Fibrosis Centre, Cork University Hospital, University College Cork, Cork, Ireland; HRB Clinical Research Facility, Cork University Hospital, University College Cork, Cork, Ireland. 2. CF & Airways Microbiology Research Group, Queen's University Belfast, Belfast, Northern Ireland. 3. Department of Radiology, Cork University Hospital, University College Cork, Cork, Ireland. 4. Cork Cystic Fibrosis Centre, Cork University Hospital, University College Cork, Cork, Ireland. 5. Department of Medicine, London, England. 6. HRB Clinical Research Facility, Cork University Hospital, University College Cork, Cork, Ireland. 7. CF & Airways Microbiology Research Group, Queen's University Belfast, Belfast, Northern Ireland; Imperial College and Royal Brompton Hospital, London, England. 8. Cork Cystic Fibrosis Centre, Cork University Hospital, University College Cork, Cork, Ireland; HRB Clinical Research Facility, Cork University Hospital, University College Cork, Cork, Ireland. Electronic address: b.plant@ucc.ie.
Abstract
BACKGROUND: Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact of cystic fibrosis transmembrane conductance regulator modulation on multiple modalities of patient assessment. METHODS: Thirty-three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra-low-dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed. RESULTS: Significant improvements in FEV1, BMI, and sweat chloride levels were observed post-ivacaftor treatment. Improvement in ultra-low-dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)-1β, IL-6, and IL-8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03). CONCLUSIONS: Early and sustained improvements on ultra-low-dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota.
BACKGROUND:Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact of cystic fibrosis transmembrane conductance regulator modulation on multiple modalities of patient assessment. METHODS: Thirty-three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra-low-dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed. RESULTS: Significant improvements in FEV1, BMI, and sweat chloride levels were observed post-ivacaftor treatment. Improvement in ultra-low-dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)-1β, IL-6, and IL-8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03). CONCLUSIONS: Early and sustained improvements on ultra-low-dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota.
Authors: Stella Joyce; Brian W Carey; Niamh Moore; David Mullane; Michael Moore; Mark F McEntee; Barry J Plant; Michael M Maher; Owen J O'Connor Journal: Pediatr Radiol Date: 2021-03-20
Authors: Lo M Sosinski; Christian Martin H; Kerri A Neugebauer; Lydia-Ann J Ghuneim; Douglas V Guzior; Alicia Castillo-Bahena; Jenna Mielke; Ryan Thomas; Marc McClelland; Doug Conrad; Robert A Quinn Journal: J Cyst Fibros Date: 2021-11-22 Impact factor: 5.527
Authors: John Paul Clancy; Calvin U Cotton; Scott H Donaldson; George M Solomon; Donald R VanDevanter; Michael P Boyle; Martina Gentzsch; Jerry A Nick; Beate Illek; John C Wallenburg; Eric J Sorscher; Margarida D Amaral; Jeffrey M Beekman; Anjaparavanda P Naren; Robert J Bridges; Philip J Thomas; Garry Cutting; Steven Rowe; Anthony G Durmowicz; Martin Mense; Kris D Boeck; William Skach; Christopher Penland; Elizabeth Joseloff; Hermann Bihler; John Mahoney; Drucy Borowitz; Katherine L Tuggle Journal: J Cyst Fibros Date: 2018-06-20 Impact factor: 5.482
Authors: Scott C Bell; Marcus A Mall; Hector Gutierrez; Milan Macek; Susan Madge; Jane C Davies; Pierre-Régis Burgel; Elizabeth Tullis; Claudio Castaños; Carlo Castellani; Catherine A Byrnes; Fiona Cathcart; Sanjay H Chotirmall; Rebecca Cosgriff; Irmgard Eichler; Isabelle Fajac; Christopher H Goss; Pavel Drevinek; Philip M Farrell; Anna M Gravelle; Trudy Havermans; Nicole Mayer-Hamblett; Nataliya Kashirskaya; Eitan Kerem; Joseph L Mathew; Edward F McKone; Lutz Naehrlich; Samya Z Nasr; Gabriela R Oates; Ciaran O'Neill; Ulrike Pypops; Karen S Raraigh; Steven M Rowe; Kevin W Southern; Sheila Sivam; Anne L Stephenson; Marco Zampoli; Felix Ratjen Journal: Lancet Respir Med Date: 2019-09-27 Impact factor: 30.700
Authors: Matthew M Willmering; David J Roach; Elizabeth L Kramer; Laura L Walkup; Zackary I Cleveland; Jason C Woods Journal: J Cyst Fibros Date: 2020-12-04 Impact factor: 5.482