Airway Inflammation and Host Responses in the Era of CFTR Modulators
The arrival of cystic fibrosis transmembrane conductance regulator (CFTR) modulators as a new class of treatment for cystic fibrosis (CF) in 2012 represented a pivotal advance in disease management, as these small molecules directly target the upstream underlying protein defect. Further advancements...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/17/6379 |
| _version_ | 1797554769979506688 |
|---|---|
| author | Karen Keown Ryan Brown Declan F. Doherty Claire Houston Michael C. McKelvey Shannice Creane Dermot Linden Daniel F. McAuley Joseph C. Kidney Sinéad Weldon Damian G. Downey Clifford C. Taggart |
| author_facet | Karen Keown Ryan Brown Declan F. Doherty Claire Houston Michael C. McKelvey Shannice Creane Dermot Linden Daniel F. McAuley Joseph C. Kidney Sinéad Weldon Damian G. Downey Clifford C. Taggart |
| author_sort | Karen Keown |
| collection | DOAJ |
| description | The arrival of cystic fibrosis transmembrane conductance regulator (CFTR) modulators as a new class of treatment for cystic fibrosis (CF) in 2012 represented a pivotal advance in disease management, as these small molecules directly target the upstream underlying protein defect. Further advancements in the development and scope of these genotype-specific therapies have been transformative for an increasing number of people with CF (PWCF). Despite clear improvements in CFTR function and clinical endpoints such as lung function, body mass index (BMI), and frequency of pulmonary exacerbations, current evidence suggests that CFTR modulators do not prevent continued decline in lung function, halt disease progression, or ameliorate pathogenic organisms in those with established lung disease. Furthermore, it remains unknown whether their restorative effects extend to dysfunctional CFTR expressed in phagocytes and other immune cells, which could modulate airway inflammation. In this review, we explore the effects of CFTR modulators on airway inflammation, infection, and their influence on the impaired pulmonary host defences associated with CF lung disease. We also consider the role of inflammation-directed therapies in light of the widespread clinical use of CFTR modulators and identify key areas for future research. |
| first_indexed | 2024-03-10T16:36:46Z |
| format | Article |
| id | doaj.art-5c5eaed75926438bb997f9262882c9c9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:36:46Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5c5eaed75926438bb997f9262882c9c92023-11-20T12:21:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012117637910.3390/ijms21176379Airway Inflammation and Host Responses in the Era of CFTR ModulatorsKaren Keown0Ryan Brown1Declan F. Doherty2Claire Houston3Michael C. McKelvey4Shannice Creane5Dermot Linden6Daniel F. McAuley7Joseph C. Kidney8Sinéad Weldon9Damian G. Downey10Clifford C. Taggart11Airway Innate Immunity Research (AiiR) group, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKAirway Innate Immunity Research (AiiR) group, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKAirway Innate Immunity Research (AiiR) group, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKAirway Innate Immunity Research (AiiR) group, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKAirway Innate Immunity Research (AiiR) group, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKAirway Innate Immunity Research (AiiR) group, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKAirway Innate Immunity Research (AiiR) group, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKWellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKBelfast Health and Social Care Trust, Belfast BT13 1FD, Northern Ireland, UKAirway Innate Immunity Research (AiiR) group, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKWellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKAirway Innate Immunity Research (AiiR) group, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKThe arrival of cystic fibrosis transmembrane conductance regulator (CFTR) modulators as a new class of treatment for cystic fibrosis (CF) in 2012 represented a pivotal advance in disease management, as these small molecules directly target the upstream underlying protein defect. Further advancements in the development and scope of these genotype-specific therapies have been transformative for an increasing number of people with CF (PWCF). Despite clear improvements in CFTR function and clinical endpoints such as lung function, body mass index (BMI), and frequency of pulmonary exacerbations, current evidence suggests that CFTR modulators do not prevent continued decline in lung function, halt disease progression, or ameliorate pathogenic organisms in those with established lung disease. Furthermore, it remains unknown whether their restorative effects extend to dysfunctional CFTR expressed in phagocytes and other immune cells, which could modulate airway inflammation. In this review, we explore the effects of CFTR modulators on airway inflammation, infection, and their influence on the impaired pulmonary host defences associated with CF lung disease. We also consider the role of inflammation-directed therapies in light of the widespread clinical use of CFTR modulators and identify key areas for future research.https://www.mdpi.com/1422-0067/21/17/6379cystic fibrosisinflammationinfectionCFTR modulator |
| spellingShingle | Karen Keown Ryan Brown Declan F. Doherty Claire Houston Michael C. McKelvey Shannice Creane Dermot Linden Daniel F. McAuley Joseph C. Kidney Sinéad Weldon Damian G. Downey Clifford C. Taggart Airway Inflammation and Host Responses in the Era of CFTR Modulators International Journal of Molecular Sciences cystic fibrosis inflammation infection CFTR modulator |
| title | Airway Inflammation and Host Responses in the Era of CFTR Modulators |
| title_full | Airway Inflammation and Host Responses in the Era of CFTR Modulators |
| title_fullStr | Airway Inflammation and Host Responses in the Era of CFTR Modulators |
| title_full_unstemmed | Airway Inflammation and Host Responses in the Era of CFTR Modulators |
| title_short | Airway Inflammation and Host Responses in the Era of CFTR Modulators |
| title_sort | airway inflammation and host responses in the era of cftr modulators |
| topic | cystic fibrosis inflammation infection CFTR modulator |
| url | https://www.mdpi.com/1422-0067/21/17/6379 |
| work_keys_str_mv | AT karenkeown airwayinflammationandhostresponsesintheeraofcftrmodulators AT ryanbrown airwayinflammationandhostresponsesintheeraofcftrmodulators AT declanfdoherty airwayinflammationandhostresponsesintheeraofcftrmodulators AT clairehouston airwayinflammationandhostresponsesintheeraofcftrmodulators AT michaelcmckelvey airwayinflammationandhostresponsesintheeraofcftrmodulators AT shannicecreane airwayinflammationandhostresponsesintheeraofcftrmodulators AT dermotlinden airwayinflammationandhostresponsesintheeraofcftrmodulators AT danielfmcauley airwayinflammationandhostresponsesintheeraofcftrmodulators AT josephckidney airwayinflammationandhostresponsesintheeraofcftrmodulators AT sineadweldon airwayinflammationandhostresponsesintheeraofcftrmodulators AT damiangdowney airwayinflammationandhostresponsesintheeraofcftrmodulators AT cliffordctaggart airwayinflammationandhostresponsesintheeraofcftrmodulators |