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. 2024 Dec;79(12):3528-3533.
doi: 10.1111/all.16198. Epub 2024 Jun 16.

Type 2 inflammation in cystic fibrosis is a predictor of mortality and targeted with CFTR modulator therapy

Daniel P Cook  1 , Ashley Y Wu  2 , Christopher M Thomas  1 , Robert G Hamilton  3 , Ray Stokes Peebles Jr  1   4   5 , Vern Eric Kerchberger  1   6
Affiliations

Type 2 inflammation in cystic fibrosis is a predictor of mortality and targeted with CFTR modulator therapy

Daniel P Cook et al. Allergy. 2024 Dec.
No abstract available

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript.

Figures

FIGURE 1
FIGURE 1
T2 inflammation exists as an endotype of CF and is associated with decreased pulmonary function, greater infections with hallmark CF pathogens, increased burden of CF complications and comorbid disease, and decreased survival. (A) A PheWAS Manhattan plot showing enrichment of PheCodes in T2 CF subjects compared to non‐T2 CF subjects. Phecodes (grouped by category) are on the x‐axis and the −log10 (p‐value) is on the y‐axis. The red line reflects the Bonferroni threshold (1.58 × 10−4). Top hits from Infectious Diseases, Hematopoietic, and Respiratory chapters are annotated. For each hit, an upward pointing triangle represents a positive association with T2 signature in CF (OR greater than 1), and a lighter shaded downward pointing triangle represents a negative association (OR <1). Each color corresponded to the annotated category on the x‐axis. (B) Histogram distribution of highest lifetime FEV1/FVC ratio values in non‐T2 CF subjects compared to T2 CF subjects (n = 376). Solid line represents mean and dashed line represents interquartile range. p‐values of comparisons of non‐T2 CF to T2 CF are listed on lower graph. (C) Kaplan–Meier estimate of survival probability comparing T2 CF subjects (dark blue) with non‐T2 CF (light blue) subjects. Among all adults surviving to age 18, overall survival was significantly lower based on T2 status, with 61% (95% CI: 53% to 71%) of T2 CF versus 77% (95% CI: 65% to 90%) of non‐T2 CF reaching age 50 years old (p = 0.013 by Log‐rank test). Number of surviving in the electronic health record (at risk) and dead (events) are shown in the decade lower table at each decade (20–60). FEV1, forced expiratory volume in the first second; FVC, forced vital capacity. (D, E) Waterfall plots of percent change in total serum IgE levels in CF subjects treated with CFTR modulator therapy. Serum IgE percent change following initiation of modulator therapy in individuals receiving (D) highly effective CFTR modulator therapy (ETI or Ivacaftor in patients with a gating mutation, n = 155) and (E) non highly effective CFTR modulator therapy (Lumacaftor/Ivacaftor or Tezacaftor/Ivacaftor, or Ivacaftor in patients without a gating mutation, n = 59). p‐values are displayed on corresponding graph.
See this image and copyright information in PMC

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