PMID- 37215020
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230810
DP  - 2023 May 10
TI  - The Impact of CFTR Modulator Triple Therapy on Type 2 Inflammatory Response in 
      Patients with Cystic Fibrosis.
LID - rs.3.rs-2846739 [pii]
LID - 10.21203/rs.3.rs-2846739/v1 [doi]
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 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 shows reduction in IgE but no change in AEC 
      after ETI therapy initiation. We think that the lack of influence on AEC argues 
      against an impact on previously established T2 inflammation and that the 
      reduction in IgE is likely related to antigen load reduction post ETI. 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.
FAU - Mehta, Ajay
AU  - Mehta A
AD  - University of Virginia School of Medicine.
FAU - Lee, Irene
AU  - Lee I
AD  - Baylor College of Medicine.
FAU - Li, Galvin
AU  - Li G
AD  - University of Virginia School of Medicine.
FAU - Jones, Marieke
AU  - Jones M
AD  - University of Virginia Department of Public Health Sciences.
FAU - Hanson, Lydia
AU  - Hanson L
AD  - University of Virginia School of Medicine.
FAU - Lonabaugh, Kevin
AU  - Lonabaugh K
AD  - University of Virginia School of Medicine.
FAU - List, Rhonda
AU  - List R
AD  - University of Virginia School of Medicine.
FAU - Borish, Larry
AU  - Borish L
AD  - University of Virginia School of Medicine.
FAU - Albon, Dana
AU  - Albon D
AUID- ORCID: 0000-0001-9055-3247
AD  - University of Virginia.
LA  - eng
GR  - R21 AI151496/AI/NIAID NIH HHS/United States
GR  - R56 AI158519/AI/NIAID NIH HHS/United States
GR  - U01 AI123337/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20230510
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
UIN - Allergy Asthma Clin Immunol. 2023 Jul 31;19(1):66. PMID: 37525180
PMC - PMC10197784
COIS- Competing interests: None of the authors have any competing interests to declare
EDAT- 2023/05/22 19:11
MHDA- 2023/05/22 19:12
PMCR- 2023/05/19
CRDT- 2023/05/22 12:19
PHST- 2023/05/22 19:12 [medline]
PHST- 2023/05/22 19:11 [pubmed]
PHST- 2023/05/22 12:19 [entrez]
PHST- 2023/05/19 00:00 [pmc-release]
AID - rs.3.rs-2846739 [pii]
AID - 10.21203/rs.3.rs-2846739/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2023 May 10:rs.3.rs-2846739. doi: 10.21203/rs.3.rs-2846739/v1.