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Introduction COPD patients with type 2(T2) inflammation respond better to inhaled corticosteroids (ICS). However, it is unclear whether there is a difference in assessing treatment response using fractional exhaled nitric oxide (FeNO) or blood eosinophil count (BEC), particularly in the context of variable ICS adherence.Aim To evaluate the impact of ICS adherence on exacerbations among patients with COPD, stratified by T2 inflammation using BEC and FeNO.Method A six-month, single centre prospective cohort study (23/YH/0041) was conducted at Glenfield Hospital, Leicester, UK, targeting COPD patients receiving triple inhaled therapy with ≥2 exacerbations in the preceding year. Inhaler use was digitally monitored to objectively measure adherence. Participants were stratified by T2 inflammatory status using BEC (T2High: BEC ≥0.3×10 9/L) or non-T2High, FeNOHigh (≥20 ppb) or FeNOLow, and adherence level (AdhHigh ≥75% or AdhLow <75%). Primary outcomes included exacerbation frequency, time to first exacerbation (TTFE) and health-related quality of life via St. George’s Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT).Results 104 patients (mean age 67±9 yrs and FEV1=1.1±0.5L) were included. The T2High-AdhHigh group (n=18) had significantly longer TTFE (HR=0.36,95%CI:0.14–0.95, p=0.046) and lower risk of hospitalisation (OR=0.14,95%CI: 0.03–0.72, p=0.02) than T2High-AdhLow group (n=23). Similarly, FeNOHigh-AdhHigh group(n=17) showed longer TTFE (HR=0.48,95%CI:0.22–1.01, p=0.051) and lower risk of hospitalisation (OR=0.06,95%CI: 0.01–0.68, p=0.02) than FeNOHigh-AdhLow group(n=19). Regardless of adherence, no difference in the hospitalisation risk was observed in FeNOLow (n=62) or non-T2High(n=63) groups. High adherence in non-T2High participants led to a trend towards shorter TTFE (HR=1.76, p=0.05).In the T2High group, low adherence was associated with worsening mean (SD) SGRQ scores from 62.9 (16.3) at baseline to 67.2 (13.9) at the final visit (p=0.03), and CAT scores, 24.5(7.9) to 26.8(6.4), p=0.009, exceeding the minimum clinically important difference. In contrast, high-adherence T2High and FeNOHigh groups maintained stable health status. Among non-T2High and FeNOLow participants, high adherence was paradoxically associated with increasing SGRQ and CAT scores.FeNO and BEC demonstrated poor concordance (Cohen’s κ = -0.06), suggesting they identify distinct groups of T2 inflammation.Abstract S172 Figure 1Conclusion Objective ICS adherence influenced clinical outcomes differently by T2 phenotypes. FeNO was as predictive as BEC and may serve as a bedside tool.