PMID- 37525180
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240216
IS  - 1710-1484 (Print)
IS  - 1710-1492 (Electronic)
IS  - 1710-1484 (Linking)
VI  - 19
IP  - 1
DP  - 2023 Jul 31
TI  - The impact of CFTR modulator triple therapy on type 2 inflammatory response in 
      patients with cystic fibrosis.
PG  - 66
LID - 10.1186/s13223-023-00822-2 [doi]
LID - 66
AB  - BACKGROUND: Treatment of cystic fibrosis (CF) has been revolutionized by the use 
      of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators 
      such as elexacaftor/tezacaftor/ivacaftor (ETI) triple therapy. Prior studies 
      support a role for type 2 (T2) inflammation in many people with CF (PwCF) and 
      CF-asthma overlap syndrome (CFAOS) is considered a separate clinical entity. It 
      is unknown whether initiation of ETI therapy impacts T2 inflammation in PwCF. We 
      hypothesized that ETI initiation decreases T2 inflammation in PwCF. METHODS: A 
      single center retrospective chart review was conducted for adult PwCF. As markers 
      of T2 inflammation, absolute eosinophil count (AEC) and total immunoglobulin E 
      (IgE) data were collected longitudinally 12 months prior to ETI therapy 
      initiation and 12 months following therapy initiation. Multivariable analyses 
      adjusted for the age, gender, CFTR mutation, disease severity, inhaled steroid 
      use, and microbiological colonization. RESULTS: There was a statistically 
      significant reduction (20.10%, p < 0.001) in 12-month mean total IgE following 
      ETI initiation; this change remained statistically significant in the 
      multivariate model. The longitudinal analysis demonstrated no change in AEC 
      following therapy initiation. CONCLUSION: This study demonstrates that there is a 
      statistically significant percent reduction in mean total IgE but no change in 
      AEC following ETI initiation. ETI may lead to decreased antigen and superantigen 
      load in the airway as a result of improved mucociliary clearance and these 
      changes may drive the decline in total IgE, without influencing the epigenetic 
      drivers of eosinophilic inflammation. Further studies are warranted to determine 
      the underlying mechanism of ETI impact on T2 inflammation and possible role for 
      asthma immunomodulator therapy post ETI initiation in CFAOS.
CI  - (c) 2023. The Author(s).
FAU - Mehta, A M
AU  - Mehta AM
AD  - University of Virginia School of Medicine, Charlottesville, VA, USA.
FAU - Lee, I
AU  - Lee I
AD  - Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
FAU - Li, G
AU  - Li G
AD  - Department of Statistics, University of Virginia, Charlottesville, VA, USA.
FAU - Jones, M K
AU  - Jones MK
AD  - Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
FAU - Hanson, L
AU  - Hanson L
AD  - University of Virginia School of Medicine, Charlottesville, VA, USA.
FAU - Lonabaugh, K
AU  - Lonabaugh K
AD  - Department of Medicine, University of Virginia, Charlottesville, VA, USA.
FAU - List, R
AU  - List R
AD  - Department of Medicine, University of Virginia, Charlottesville, VA, USA.
FAU - Borish, L
AU  - Borish L
AD  - Department of Medicine, University of Virginia, Charlottesville, VA, USA.
AD  - Department of Microbiology, University of Virginia, Charlottesville, USA.
FAU - Albon, D P
AU  - Albon DP
AUID- ORCID: 0000-0001-9055-3247
AD  - Department of Medicine, University of Virginia, Charlottesville, VA, USA. 
      da9zj@uvahealth.org.
AD  - Departments of Medicine, University of Virginia School of Medicine, 800546, 
      Charlottesville, VA, 22908, USA. da9zj@uvahealth.org.
LA  - eng
GR  - R56 AI158519/AI/NIAID NIH HHS/United States
GR  - R21 AI151496/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20230731
PL  - England
TA  - Allergy Asthma Clin Immunol
JT  - Allergy, asthma, and clinical immunology : official journal of the Canadian 
      Society of Allergy and Clinical Immunology
JID - 101244313
UOF - Res Sq. 2023 May 10;:. PMID: 37215020
PMC - PMC10391773
COIS- None of the authors have any competing interests to declare.
EDAT- 2023/08/01 01:07
MHDA- 2023/08/01 01:08
PMCR- 2023/07/31
CRDT- 2023/07/31 23:41
PHST- 2023/04/25 00:00 [received]
PHST- 2023/07/10 00:00 [accepted]
PHST- 2023/08/01 01:08 [medline]
PHST- 2023/08/01 01:07 [pubmed]
PHST- 2023/07/31 23:41 [entrez]
PHST- 2023/07/31 00:00 [pmc-release]
AID - 10.1186/s13223-023-00822-2 [pii]
AID - 822 [pii]
AID - 10.1186/s13223-023-00822-2 [doi]
PST - epublish
SO  - Allergy Asthma Clin Immunol. 2023 Jul 31;19(1):66. doi: 
      10.1186/s13223-023-00822-2.