Elsevier

Respiratory Medicine

Volume 162, February 2020, 105875
Respiratory Medicine

Elevated eosinophils, IL5 and IL8 in induced sputum in asthma patients with accelerated FEV1 decline

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Highlights

  • Significant part of patients with mild asthma present with accelerated FEV1 decline.

  • Accelerated FEV1 decline was associated with eosinophils in induced sputum.

  • Patients with accelerated FEV1 decline had increased IL5 and IL8 in induced sputum.

  • Eosinophils, IL5, IL8 have potential to directly influence airway remodelling.

  • Eosinophils, IL5, IL8 potential biomarkers and therapeutic targets of remodelling.

Abstract

Background

Some patients with asthma present with accelerated lung function decline. This phenomenon is mostly associated with severe exacerbations and with poor asthma control.

Objective

Our aim was to detect the extent of FEV1 decline in patients with mild asthma and to discriminate clinical, functional and inflammatory factors associated with accelerated FEV1 decline.

Methods

We recruited 50 patients with mild asthma for pulmonary function testing and induced sputum sampling 12–15 years after the initial diagnosis. In 33 patients, from whom sputum of a good quality was obtained, inflammatory cells were counted and concentrations of cytokines IL-2, IL-4, IL-5, IL-8, IL-10, IFN-γ, angiogenin and VEGF in the sputum were measured by cytometric bead array.

Results

Eighteen of 33 patients presented with accelerated FEV1 decline of more than 30 ml/year, with a mean (SEM) of 43.2 (3.9) ml/year, compared to 15 control patients with a FEV1 decline of 14.4 (2.1) ml/year. In the accelerated FEV1 decline group, we found elevated sputum levels of IL5 with a median (IQR) of 1.8 (0.4–3.2) pg/ml vs. 0.2 (0.1–1.2) pg/ml, p = 0.04; IL8 with a mean (SEM) of 1503 (194) pg/ml vs. 938 (177) pg/ml, p = 0.04; and eosinophils with a median (IQR) of 223 (41–1020) cells/μl vs. 39 (1–190) cells/μl, p = 0.03. No significant differences in other measured parameters were detected between the two groups.

Conclusion

Elevated sputum eosinophils, IL5 and IL8, which have a potential to stimulate airway remodelling, might be a useful non-invasive biomarkers and therapeutic targets of accelerated FEV1 decline in asthma patients.

Keywords

Asthma
Lung function decline
Eosinophils
IL5
IL8

Abbreviations

FEV1
forced expiratory volume in first second
FVC
forced vital capacity
TI
Tiffeneau index
FeNO
exhaled nitric oxide
PD20
provocative dose causing 20% drop
post BD
post bronchodilation
IL
interleukin
IL5-R
interleukin 5 receptor
VEGF
vascular endothelial growth factor
IFNγ
interferon gamma
TGFβ
transforming growth factor beta
BAL
broncho-alveolar lavage
ASM
airway smooth muscle
TNNC
total number of non-squamous cells
ICS
inhaled corticosteroids
LABA
long acting beta agonists
SABA
short acting beta agonist
ACT
asthma control test
BMI
body mass index
SEM
standard error of the mean
IQR
interquartile range
p
probability

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Elevated IL5 and IL8 and eosinophils in induced sputum in asthma patients with accelerated FEV1 decline.