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Background Tezepelumab inhibits TSLP thus acting on downstream IL 4,5 and 13, in turn reducing respective levels of IgE, eosinophils and FeNO (Niox Vero). There is a high degree of expression of IL13 but not IL5 in human small airways smooth muscle. Here we assessed the effects of tezepelumab on spirometry outcomes of large (FEV1) and small (FEF25–75) airways in relation to type 2 biomarkers in patients with uncontrolled severe asthma.Methods We reviewed our severe asthma MDT identifying 38 patients who were commenced on tezepelumab. Their data were reviewed prior to commencing tezepelumab and at subsequent clinic review.Results Mean baseline values (SEM) were: age 52.1 years (2.5); BMI 29.6 kg/m2 (0.9); duration on tezepelumab 7.8 months (0.4); eosinophils 745cells/uL (81); FeNO 56.9ppb (7.4); total IgE 641.6 kU/L (167.9); FEV1% predicted 74.3% (3.4); FEF25–75 % predicted 54.2% (5.9); ACQ 2.7 (0.3); AER 3.9 (0.5).The mean changes (95% CI) in response to tezepelumab were as follows: total IgE 207.3 kU/L (49.9, 364.7) p<0.05, eosinophils 592cells/uL (427, 757) p<0.001, FeNO 29.3ppb (16.9, 41.7) p<0.001, FEV1% predicted 9.6% (3.2, 15.9) p<0.01, FEF25–75 % predicted 15.7 (5.7, 25.7) p<0.01, ACQ 1.0 (0.4, 1.6) p<0.01, AER 2.9 (2.0, 3.7) p<0.001.A better correlation was found between change in FeNO and change in% predicted FEF25–75 (r=-0.65, p<0.001) (figure 1), than change in% predicted FEV1 (r=-0.41, p<0,05). However the change in eosinophils in response to tezepelumab did not significantly correlate with change in either% predicted FEF25–75 or FEV1.Abstract P204 Figure 1Scatter plot of the change in FEF25–75% against change in FeNO showing linear regression line and 95%CIConclusions The response to tezepleumab was relatively greater in small than large airways. Moreover, suppression of FeNO but not eosinophils with tezepelumab was associated with improvements in FEF25–75, in keeping with expression of IL13 but not IL5 in small airways smooth muscle.