Ex vivo innate responses to particulate matter from livestock farms in asthma patients and healthy individuals

Linsey E S De Groot,Marianne A Van De Pol,Flemming R Cassee,Dingyu Liu,Elena Pinelli,Miriam E Gerlofs-Nijland,Wim Kulik,Barbara S Dierdorp,Niki Fens,Peter J Sterk,René Lutter

doi:10.1186/s12940-020-00632-8

Abstract

BackgroundAsthma patients suffer from periodic acute worsening of symptoms (i.e. loss of asthma control or exacerbations), triggered by a variety of exogenous stimuli. With the growing awareness that air pollutants impact respiratory diseases, we investigated whether particulate matter (PM) derived from various livestock farms (BioPM) differentially affected innate and oxidative stress responses in asthma and health.MethodsPeripheral blood mononuclear cells (PBMCs), collected from patients sequentially before and during loss of asthma control and from healthy individuals, were exposed to BioPM collected from chicken, goat and pig farms (1 and 5 μg/ml), with or without pre-treatment with antioxidants. Cytokine release and oxidative stress were assessed.ResultsPBMCs produced IFNγ, IL-1β, IL-10 and TNFα upon stimulation with BioPM, with that from pig farms inducing the highest cytokine levels. Overall, cytokine production was irrespective of the presence or state of disease. However, PBMCs from stable asthma patients upon exposure to the three BioPM showed more extreme TNFα responses than those from healthy subjects. Furthermore, PBMCs obtained during loss of asthma control that were exposed to BioPM from pig farms showed enhanced IFNγ release as well as decreased oxidative stress levels upon pre-treatment with N-acetylcysteine (NAC) compared to stable disease. NAC, but not superoxide dismutase and catalase, also counteracted BioPM-induced cytokine release, indicating the importance of intracellular reactive oxygen species in the production of cytokines.ConclusionsBioPM triggered enhanced pro-inflammatory responses by PBMCs from both healthy subjects and asthma patients, with those from patients during loss of asthma control showing increased susceptibility to BioPM from pig farms in particular.

Highlights

Asthma is a chronic inflammatory lung disease associated with reversible airway obstruction and increased responsiveness of the airways to a variety of stimuli
The average time until loss of asthma control was 31.5 ± 4.8 days and this was associated with a significant increase in Asthma Control Questionnaire and Wisconsin Upper Respiratory Symptom Survey scores and a significant decrease in forced expiratory volume in 1 second (FEV1) % predicted compared to baseline
Peripheral blood mononuclear cell (PBMC) obtained during loss of asthma control demonstrated an enhanced IFNγ response upon exposure to BioPM from the pig farm, which was paralleled by oxidative stress

Summary

Introduction

Asthma is a chronic inflammatory lung disease associated with reversible airway obstruction and increased responsiveness of the airways to a variety of stimuli ( known as bronchial hyperresponsiveness). It is a heterogeneous disease with e.g. differences in treatment, severity and time of onset. Traffic-related PM drives the transcription of inflammatory mediators relevant to asthma and is a potent inducer of oxidative stress [6], as many of its components may act as a source of free radicals This is unlikely to be the case for PM collected from specific livestock farms (BioPM). With the growing awareness that air pollutants impact respiratory diseases, we investigated whether particulate matter (PM) derived from various livestock farms (BioPM) differentially affected innate and oxidative stress responses in asthma and health

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Discussion

Conclusion