Persistence of both reversible airway obstruction and higher blood eosinophils may predict lung function decline in severe asthma

Abstract

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.

Pathophysiology of Bronchiectasis

“…73 There are therefore significant challenges in implementing anti-inflammatory treatment in bronchiectasis, as it is not immediately obvious how to identify patients with eosinophilic disease in clinical practice. Blood eosinophils counts are validated in COPD and asthma, [162][163][164][165] but more work is needed to validate them in bronchiectasis. Sputum counts are not practical to implement in widespread clinical care.…”

Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study

“…In addition, other lung function parameters may act as phenotypic or prognostic markers. Persistent reversible airway obstruction, when also associated with elevated blood eosinophil counts, can be a marker of accelerated lung function decline [ 13 ]. Furthermore, impaired forced expiratory flow between 25 and 75% of vital capacity (FEF 25–75 ) has been associated with small-airway disease, bronchial hyperresponsiveness, and airway inflammation, and is a potential early marker of airway obstruction [ 14 ].…”