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Objective: This study analysed whether the persistence of both reversible airway obstruction (RAO) and elevated BE counts was associated to reduced asthma control and accelerated lung function decline in treated severe asthmatics., Methods: About 202 severe asthmatics were studied after 12-120 months of step-5 treatment associated to anti-IgE therapy. Following treatments, reversibility tests, after inhaling 400 mcg of Salbutamol, were performed. FEV 1  > 12% or ≤12% changes differentiated RAO+ from RAO- subjects. Blood eosinophil (BE) counts after treatment were considered., Results: Pre-/post-treatment bronchodilator FEV 1 % and ACT were lower (61% [50-71], 74.4% [62.5-83.7] and 20[18-22]), whereas BE were higher (380 cells/µl [170-590]) in RAO+ compared to RAO- subjects (77% [64-88], p = 0.0001, 81.8% [66.1-94.3], p = 0.0001, 21[18-23], p = 0.045 and 230 cells/µl [80-360], p = 0.003). A negative relationship between SABA-induced FEV 1 % changes and pre-bronchodilator FEV 1 % (β = -0.551%; p = 0.0001) and ACT (β = -0.059; p = 0.038) was found. Conversely, post-treatment BE levels were positively related (β = 145.565 cells/µl; p = 0.003) to FEV 1  > 12% increases. A rising trend of pre-/post-bronchodilator FEV 1 % in time was observed in RAO- subjects with BE < 300 cells/µl. Conversely, we highlighted significant declining tendencies of pre/post-bronchodilator FEV 1 % in RAO+ patients with BE > 300 cells/µl reaching lower values after more than 36 months of step-5 treatment (59.6% [39.9-72.1] vs 74[66.5-89.2] of RAO+ individuals with BE < 300 cells/µl [p = 0.026] and 81.6% [66.1-91.8] of RAO-subjects with BE > 300 cells/µl [p = 0.009])., Conclusion: Persistent SABA-induced FEV 1  > 12%, especially when associated to BE > 300 cells/ml, may be a marker of accelerated lung function decline in severe asthmatics despite maximal step-5 treatment. The highest bronchodilation associated to the lowest BE levels should be the main goal of asthma treatment to prevent such decline., (© 2021 John Wiley & Sons Ltd.)

Background: Mepolizumab (MEP) has been recently introduced to treat severe eosinophilic asthma. Trials have demonstrated a significant effectiveness in this asthma phenotype. We evaluated MEP efficacy on lung function, symptoms, asthma exacerbations, biologic markers, steroid dependence and controller treatment level in real-life., Methods: We retrospectively analyzed 134 severe asthmatics (61 males; mean age 58.3 ± 11; mean FEV 1 %:72 ± 21), treated with MEP for at least 6 months (mean duration:10.9 ± 3.7 months)., Results: FEV 1 % improved significantly after MEP. Mean FEF 25-75 also increased from 37.4 ± 25.4% to 47.2 ± 27.2% (p < 0.0001). Mean baseline blood eosinophil level was 712 ± 731/μL (8.4 ± 5.2%) decreasing to 151 ± 384/μL (1.6 ± 1.6%) (p < 0.0001), FENO levels decreased likewise. MEP treatment also led to a significant ACT improvement (mean pre:14.2 ± 4.4; mean post:20.5 ± 28) and exacerbations significantly fell from 3.8 ± 1.9 to 0.8 ± 1.1 (p < 0.0001). 74% of patients were steroid-dependent before MEP. 45.4% and 46.4% of them showed a suspension and dose reduction respectively (p < 0.0001). A significant number reduced also ICS doses. Only 67% of subjects used SABA as needed before MEP, falling to 20% after MEP. About 40% of patients highlighted a maintenance therapy step-down. Subjects showing an omalizumab treatment failure before MEP had a similar positive response when compared with omalizumab untreated patients., Conclusion: In real-life, MEP improved significantly all outcomes even small airway obstruction, suggesting its possible role also in distal lung region treatment. Furthermore, it demonstrated its high effectiveness in OC/ICS-sparing, in reducing SABA as needed and in stepping-down maintenance therapy. MEP is a valid alternative for patients with previous omalizumab treatment failure., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In the early stages of bronchial asthma, it is frequent to find subjects with a positive history and an FEV1 or FEV1/FVC > 80% of the predicted value. This study investigated if the test of reversibility showed a reversible airway obstruction (RAO) in 291 subjects with the above clinical and functional features. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and expiratory flows (PEF, MEF50, FEF(25-75)) were registered before and 20 minutes after salbutamol administration (200 mcg by MDI). Of 291 subjects, FEV1 increased in 73 (25%) after bronchodilator > or = 12% compared to baseline; the number of subjects with a > or = 35% increase in MEF50 or FEF(25-75) were similar in terms of percentage (respectively, 29.2% and 29%), whereas those with increases in FVC (> or = 12%) and in PEF (> or = 15%) were significantly lower (respectively, 2.7% and 12.3%). The percentage of subjects with RAO (FEV1 increase after bronchodilator > or = 12%) was lower (12%) in the subgroup (108 subjects), with an MEF50 > or = 70% of the value predicted at the baseline assessment, and higher (36%) in the subjects of the subgroup (183 subjects) with an MEF50 < 70%. In conclusion, it is advisable to carry out reversibility tests in all subjects with symptoms indicative of asthma even if their functional tests are "normal" because in a considerable number of cases the RAO was found to confirm the suspected diagnosis and provided a more reliable classification of the disease.