Abstract Rationale Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of type-2 (T2) airway inflammation. In contrast to its well-established role in asthma, FeNO has been less thoroughly investigated in Chronic Obstructive Pulmonary Disease (COPD), partly because active smoking is thought to suppress FeNO levels. Methods In this retrospective real-life study, we analyzed FeNO measurements in stable, spirometry-confirmed (FEV1/FVC 70%) COPD outpatients with at least 10 pack-years smoking history at a Belgian tertiary care facility. Patients with concomitant asthma were excluded. In those COPD patients with at least one FeNO measurement during the study period, we collected baseline characteristics including sex, age, BMI, smoking status/history, FEV1 % predicted, GOLD grade, number of exacerbations in the year prior to FeNO measurement, and use of inhaled corticosteroids (ICS) at the time of FeNO assessment. We used two FeNO cut-offs (20 and 25 ppb, respectively) for comparison of T2-low and T2-high phenotypes. We repeated these analyses in former smokers only. Results Median FeNO for the entire cohort (338 patients) was 17 ppb 10-26. 124 patients (37%) and 91 patients (27%) presented FeNO values ≥20 ppb and ≥25 ppb, respectively. Male sex (p = 0.015) and older age (p = 0.004) were associated with FeNO ≥20 ppb. There was no difference in number of pack-years, BMI, FEV1% predicted, GOLD grade, number of exacerbations in the previous year and use of ICS at the time of FeNO assessment between FeNO ≥ and 20 ppb subgroups. FeNO values were significantly lower in active smokers (10 ppb 7-15) as compared to former smokers (19 ppb 13-27) (p = 0.0009). After exclusion of active smokers, male sex remained the only variable associated with type-2 inflammation (p = 0.02) and this association was maintained irrespective of the FeNO threshold applied (20 or 25 ppb). Conclusions In this COPD population, higher FeNO levels, - suggesting T2-high inflammation - were associated with male sex, older age and being a former smoker rather than a current smoker. In former smokers, the correlation between higher FeNO levels and age was no longer observed, while the association with male sex remained present. The observed sex-related differences may indicate that women with COPD could present lower FeNO levels simply because they are female despite having clinically relevant T2-inflammation at lower FeNO thresholds. Such sex-related variability in FeNO should be considered before translating FeNO thresholds into treatment eligibility criteria. This abstract is funded by: None
Michotte et al. (Fri,) studied this question.