S120 Post-hoc analysis of transcriptomic and clinical predictors of remission in the ATLANTIS cohort

Background

Asthma remission is an emerging paradigm of disease management, recently recognised as a management objective by several international guidelines. However, the baseline predictors (clinical and biological) of remission need to be further clarified, alongside the development of disease activity tools as putative treatment targets and understanding biological predictors.

Methods

We conducted a retrospective, exploratory analysis of the Assessment of Small Airways Involvement in Asthma (ATLANTIS) study. Remission was, ‘Asthma Control Questionnaire-6 (ACQ-6) < 1.5, no maintenance OCS, no exacerbations and a pre-bronchodilator FEV₁% predicted absolute decline < 10%’ over 12 months of follow up. A multivariable logistic regression assessed potential predictors of remission. The Small Airways Dysfunction Tool (SADT) questionnaire measured Small Airways Disease (SAD), with high scores representing less severe SAD. Factor analysis of the SADT, FeNO, BEC, ACQ-6 and pre-bronchodilator FEV₁ generated a Low Disease Activity (LDA) tool, with the lower quartile of scores being LDA. A subset (295/684) with nasal RNAseq transcriptomics data underwent differential gene expression, extracting differentially expressed pathways underlying remission.

Results

Overall, 309/684 (45.2%) were in remission. Significantly fewer severe (GINA 4–5) asthmatics were in remission compared to non-remission (31.7% vs. 58.8%, p < 0.001). Significantly more patients with high T2 biomarkers were in non-remission (12.1% vs. 6.92%, p = 0.01). Lower FeNO (OR: 2.06, 95%CI: 1.05 - 2.53), male sex (OR: 2.06, 95%CI: 1.40–3.20), better lung function (OR: 1.02, 95%CI: 1.01–1.04) and higher SADT (OR: 1.28, 95%CI: 1.05 -1.55) were predictors of remission. Risk factors for non-remission were higher prior exacerbation history (OR: 0.405, 95%CI: 0.226–0.726), severe asthma (OR: 0.570, 95%CI: 0.333–0.975) and higher BMI (OR: 0.960, 95%CI: 0.926–1.00). A novel LDA tool related baseline LDA to better QOL, increased likelihood of remission, and fewer exacerbations. Finally, using nasal transcriptomics, we identified that upregulated ‘Interleukin-4 and Interleukin-13 signalling’ was the only differentially expressed pathway which passed FDR in remission patients.

Interpretation

We have performed a comprehensive analysis, assessing both clinical and transcriptional predictors of remission. We show that greater SAD is associated with a lower likelihood of remission and developed an LDA tool as a potential target for remission guided therapies.