Neutrophils in asthma: the good, the bad and the bacteria

Helena Crisford; Elizabeth Sapey; Geraint B Rogers; Steven Taylor; Prasad Nagakumar; Ravi Lokwani; Jodie L Simpson

doi:10.1136/thoraxjnl-2020-215986

Neutrophils in asthma: the good, the bad and the bacteria

Thorax. 2021 Feb 25;76(8):835-844. doi: 10.1136/thoraxjnl-2020-215986. Online ahead of print.

Authors

Helena Crisford¹, Elizabeth Sapey^{1

2}, Geraint B Rogers^{3

4}, Steven Taylor^{3

4}, Prasad Nagakumar^{1

5}, Ravi Lokwani⁶, Jodie L Simpson⁷

Affiliations

¹ Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
² University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
³ SAHMRI Microbiome Research Laboratory, Flinders University College of Medicine and Public Health, Adelaide, South Australia, Australia.
⁴ Microbiome and Host Health, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
⁵ Respiratory Medicine, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
⁶ Faculty of Health and Medicine, Priority Research Centre for Healthy Lungs, The University of Newcastle, Callaghan, New South Wales, Australia.
⁷ Faculty of Health and Medicine, Priority Research Centre for Healthy Lungs, The University of Newcastle, Callaghan, New South Wales, Australia jodie.simpson@newcastle.edu.au.

Abstract

Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not respond well to classical therapies. Currently, there are no specific therapeutic options for these patients, such as neutrophil-targeting biologics.Neutrophils comprise 70% of the total circulatory white cells and play a critical defence role during inflammatory and infective challenges. This makes them a problematic target for therapeutics. Furthermore, neutrophil functions change with age, with reduced microbial killing, increased reactive oxygen species release and reduced production of extracellular traps with advancing age. Therefore, different therapeutic strategies may be required for different age groups of patients.The pathogenesis of neutrophil-dominated airway inflammation in adults with asthma may reflect a counterproductive response to the defective neutrophil microbial killing seen with age, resulting in bystander damage to host airway cells and subsequent mucus hypersecretion and airway remodelling. However, in children with asthma, neutrophils are less associated with adverse features of disease, and it is possible that in children, neutrophils are less pathogenic.In this review, we explore the mechanisms of neutrophil recruitment, changes in cellular function across the life course and the implications this may have for asthma management now and in the future. We also describe the prevalence of neutrophilic asthma globally, with a focus on First Nations people of Australia, New Zealand and North America.

Keywords: asthma; asthma mechanisms; bacterial infection; neutrophil biology; paediatric asthma.

Publication types

Review

Abstract

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