{
  "abstract": "Objectives To evaluate changes in systemic inflammation in people with (pw) CF chronically infected with Pseudomonas aeruginosa (Pa) after ≥6 months of the CFTR modulator, Elexacaftor/Tezacaftor/Ivacaftor (ETI).Methods Retrospective review of pwCF at Royal Brompton Hospital with Leeds-defined chronic Pa infection ≥1 of the 2 years pre-ETI. Serum inflammatory markers (immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), C-reactive protein (CRP), white cell (WCC), neutrophil, lymphocyte, and eosinophil counts) taken at annual assessment were assessed at baseline (closest prior to starting ETI) and paired to values after ETI start (6–24 m). Subanalysis by sex, genotype (homozygous F508del vs. others), persistence of airway sample Pa positivity, and percent predicted forced expiratory value in one second (ppFEV 1) analysis performed using either paired t-test or Mann-Whitney test.Results In 168 patients included, there was reduction in absolute IgG/A/M, CRP, WCC and neutrophil count after ETI initiation. Analysis as a proportion of baseline showed reduction in IgG/A/M, WCC and neutrophils with no difference for CRP, lymphocytes and eosinophils ( table 1). Subanalysis showed no difference in observed change by genotype or sex.120 patients had complete paired data for annual Pa culture frequency and inflammatory markers 1 year before and 2 years after starting ETI. At their year 2 annual assessment, 23% of patients were no longer growing Pa in the sample provided; a subanalysis showed no difference in observed inflammatory marker change based on this Pa status.ppFEV1 showed a median(IQR) increase of 9.62(1.71,23.88)% (p<0.001) post-ETI. Patients with ppFEV1 increase >10%, compared to those without increase, showed greater neutrophil reduction (-2.9 vs -0.7 x 109/L, p=0.04), with no difference noted for other inflammatory markers.Abstract S69 Table 1 Inflammatory Marker Absolute reduction P value Percentage reduction P value IgG (6.4–16.0 g/L) - 2.1 g/L <0.001 16.4 % <0.001 IgA (0.7–3.2 g/L) -0.3 g/L <0.001 15.3 % <0.001 IgM (0.5–2.8 g/L) - 0.1 g/L <0.001 9.0 % <0.001 CRP (0–5 mg/L) - 2.0 mg/L <0.01 50.0% ns WCC (5.1 – 11.4 x109/L) - 1.7 x109/L <0.001 20.5 % <0.001 Neutrophils (2.6–7.9 x109/L) -1.5 x109/L <0.001 26.3 % <0.01 Lymphocytes (1.3–3.7 x109/L) -0.1 x109/L ns 4.8% ns Eosinophils (0.1–0.5 x109/L) 00 x109/L ns 0.0% <0.01 Conclusion In those with chronic Pa infection, taking ETI for at least 6 months was associated with a reduction from baseline in systemic inflammation. When we sub-analysed by sex, genotype, and clearance of Pa in the sample provided, we did not see inflammatory marker differences. Those with a >10% improvement in ppFEV 1 experienced greater reduction in neutrophil count, suggesting an association between change in systemic inflammation and airway health on ETI. Post-ETI inflammatory change and its impact warrants further exploration.",
  "authors": [
    {
      "affiliations": [
        "Department of PRM, Royal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Y Rajeev"
    },
    {
      "affiliations": [
        "Cystic Fibrosis Centre Innsbruck, Medical University of Innsbruck, Department of Child and Adolescent Health, Innsbruck, Austria"
      ],
      "name": "T Fuchs"
    },
    {
      "affiliations": [
        "Department of PRM, Royal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK",
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "JA King"
    },
    {
      "affiliations": [
        "Department of PRM, Royal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK",
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "JC Davies"
    }
  ],
  "title": "S69 Reduction in serum markers of inflammation in people with cystic fibrosis who are chronically infected with pseudomonas aeruginosa is seen after treatment with Elexacaftor/Tezacaftor/Ivacaftor",
  "uid": "b4bb44cf-34f9-58c5-bca8-434ab2a003dd"
}