Markers that can Reflect Asthmatic Activity before and after Reduction of Inhaled Corticosteroids: A Pilot Study

Abstract

Evaluation of airway inflammation is important in achieving adequate dosing of inhaled corticosteroids (ICS) for treating bronchial asthma. However, there is no evaluation tool that can be used in clinical settings. We examined biomarkers that can precisely reflect airway inflammation when ICS are decreased in stable asthmatic patients. This was a 12-week, single-arm, open-label clinical study performed at a single university hospital. Twenty-five patients (6 male and 19 female) with stable asthma were included in this study. We investigated whether the levels of nitrite and nitrate in exhaled breath condensate (EBC) increase after ICS reduction. We also investigated whether blood eosinophils, serum immunoglobulin E (IgE), high-sensitivity C reactive protein (hs-CRP), interleukin (IL)-13, IL-17, and periostin are different before and after ICS reduction. Peak expiratory flow (PEF), pulmonary function tests, asthma control test (ACT), and asthma quality of life questionnaire (AQLQ) were also examined. We considered an unscheduled hospital visit due to asthmatic symptoms and decline in average PEF over one week by more than 10% to indicate disease instability, and compared patients with stable and unstable disease for analysis. Unstable status was detected in 5 patients. Age, sex, asthma duration, ACT and AQLQ scores, and the level of serum IgE did not differ between stable and unstable groups. In the unstable group, the total concentration of nitrite and nitrate at the last visit was 9.84 (6.65–11.24) μM. Surprisingly, this was similar to the concentration at the first visit (5.58 (2.94–17.29) μM). Serum periostin before ICS reduction (141.9 [107.7–147.7] pg/mL) was higher in the unstable group than in the stable group (91.5 [78.75–103.5] pg/mL). The unstable group had a higher peripheral blood eosinophil count and wider diurnal variation of PEF at the first visit compared to the stable group. Higher eosinophils in peripheral blood and wider diurnal variation of PEF were predictive markers for unstable disease after ICS reduction. Serum periostin is another candidate for the predictive marker.

Relationships between adult asthma and oxidative stress markers and pH in exhaled breath condensate: a systematic review

“…In cross‐sectional studies, patients who were treated with ICS had significantly lower values of NO x and NT in the EBC compared to steroid‐naïve asthmatic individuals . These findings corroborate the expectation that corticosteroid treatment may suppress the inhibition of oxidative stress and the pro‐inflammatory response in the inflamed airways . Exhaled breath condensate H 2 O 2 levels derived from those with current symptoms of asthma are higher than those without symptoms.…”

“…Most studies that assessed the associations of the EBC oxidative stress markers in inflammatory airways of asthma diseases have relied on a cross‐sectional design. Additional longitudinal studies are needed in order to improve the utility of EBC collection and measurement of biomarkers to (i) predict responsiveness to specific pharmacological therapies such as corticosteroids in patients with asthma (ii) help determine the prognosis of disease, (iii) evaluate stability these markers over time, (iv) if the changes in these biomarkers are related to changes in asthma severity or (v) can predict remission of disease .…”

Recent developments regarding periostin in bronchial asthma

“…But if they show low serum periostin, administration of other agents should be considered because type 2 antagonists would be ineffective for them. 56 This result is compatible with the notion that serum periostin, as a biomarker, reflects hyporesponsiveness to ICS.…”

Biomarkers for severe allergic asthma in children: could they be useful to guide disease control and use of omalizumab?

“…Periostin, a protein of the extracellular matrix induced by IL-4 and IL-13 in the lung epithelial cells and in fibroblasts, plays a role in epithelial fibrosis and infiltration of the tissues by the eosinophils [78,79]. Serum periostin has been proposed as a biomarker of allergic asthma: high serum periostin levels are correlated with lung eosinophilia [80] and respiratory function [81] and are predictive of the response to ICSs [82,83], omalizumab [84], and lebrikizumab (anti-IL13 antibody). Furthermore, a faster decline in respiratory function has been seen observed when serum periostin levels are high [85].…”