Fixed airflow obstruction relates to eosinophil activation in asthmatics

Abstract

Background: Some asthmatics develop irreversible chronic airflow obstruction, for example, fixed airflow obstruction (fixed-AO). This is probably a consequence of airway remodelling, but neither its relation to inflammation nor which asthma biomarkers can be clinically useful are elucidated. We hypothesized that the presence of type 2 inflammation relates to fixed-AO. Objectives:To evaluate the presence of four markers for type 2 inflammation in fixed airflow obstruction among asthmatics.Methods: This was a cross-sectional study of 403 participants with asthma, aged 17-75 years, from three Swedish centres. Fixed airflow obstruction was defined as forced expiratory volume during the first second (FEV 1 ) over forced vital capacity (FVC) being below the lower limit of normal (LLN). The following type 2 inflammation markers were assessed: exhaled nitric oxide (FeNO), serum periostin, serum eosinophil cationic protein (S-ECP), and urinary eosinophil-derived neurotoxin (U-EDN).Results: Elevated U-EDN (values in the highest tertile, ≥65.95 mg/mol creatinine) was more common in subjects with fixed-AO vs. subjects without fixed-AO: 55% vs. 29%, P < 0.001. Elevated U-EDN related to increased likelihood of having fixed-AO in both all subjects and never-smoking subjects, with adjusted (adjusted for sex, age group, use of inhaled corticosteroids last week, atopy, early-onset asthma, smoking history, and packyears) odds ratios (aOR) of 2.38 (1.28-4.41) and 2.51 (1.04-6.07), respectively. In a separate analysis, having both elevated S-ECP (>20 μg/L) and U-EDN was related to having the highest likelihood of fixed-AO (aOR (95% CI) 6.06(2.32-15.75)). Elevated serum periostin or FeNO did not relate to fixed-AO. Conclusions and clinical relevance:These findings support that type 2 inflammation, and in particular eosinophil inflammation, is found in asthma with fixed-AO.This could indicate a benefit from eosinophil-directed therapies. Further longitudinal studies are warranted to investigate causality and relation to lung function decline.

Relationship between airway inflammation and airflow limitation in elderly asthmatics

“…Our study demonstrated that increased sputum EDN levels but not sputum NE levels were associated with decreased %FEV 1 and %FVC in EA, which was not observed in the younger asthmatic patients. Our findings coincided with those of several studies, showing an association between increased urinary EDN and decreased FEV 1 in children [23,24] or decreased FEV 1 /FVC in adults [25]. In particular, the significant correlation between increased urinary EDN and decreased FEV 1 /FVC was observed in asthmatics ≥54 years old [25].…”

“…Our findings coincided with those of several studies, showing an association between increased urinary EDN and decreased FEV 1 in children [23,24] or decreased FEV 1 /FVC in adults [25]. In particular, the significant correlation between increased urinary EDN and decreased FEV 1 /FVC was observed in asthmatics ≥54 years old [25]. Additionally, 2 studies demonstrated that type-2 inflammation is amplified in EA [26,27].…”

Welcome to 2020

“…Fixed airflow limitation was associated with lower lumen area, thickened walls in distal airways, higher blood neutrophilia, plus blood and bronchoalveolar eosinophilia and high circulating periostin and ADAM33. So fixed airway obstruction is associated with Th2 markers as demonstrated in earlier studies …”

Adjuvant treatment with Xiaoqinglong formula for bronchial asthma

“…[1] This disease is mostly caused by extensive and changeable airflow obstruction. [2] It is a clinically refractory disease characterized by severe asthma, inability to lie down, shortness of breath in the nose and chest tightness. At present, there are about 300 million asthmatic patients in the world, and about 30 million of asthmatic patients in China.…”