Recovery from pneumonia requires efferocytosis which is impaired in smokers and those with low body mass index and enhanced by statins

Daniel G. Wootton, Peter J. Diggle, Joanne Court, Odiri Eneje, Lynne Keogan, Laura Macfarlane, Sarah Wilks, Mark Woodhead, Stephen B. Gordon

Research output: Contribution to journalArticle

Abstract

Background Efferocytosis (the phagocytosis of apoptotic self cells) is a key mechanism in the resolution of inflammatory processes such as community-acquired pneumonia (CAP). Efferocytosis therefore represents a modifiable target for therapy aimed at enhancing intrinsic recovery mechanisms. It is currently not known which patients recovering from CAP would mostly benefit from a strategy aimed at enhancing efferocytosis. Methods We recruited a cohort of patients with CAP admitted to a hospital in Liverpool. One month into recovery, subjects were invited for research bronchoscopy and bronchoalveolar lavage. An ex vivo efferocytosis assay was performed by challenging alveolar macrophages with autologous, apoptotic neutrophils. The percentage of alveolar macrophages that had undergone efferocytosis was determined by flow cytometry. We conducted a multivariable regression using a linear mixed effects model to determine which clinical parameters were most closely associated with efferocytosis. Results We observed high rates of comorbidity among this CAP cohort. Efferocytosis was measured in 22 subjects. We assessed multiple combinations of clinical parameters for association with efferocytosis and found the best-fitting model included an interaction between smoking status and prior statin use-smoking being associated with decreased efferocytosis and statin use with increased efferocytosis. These effects were modified by an association between efferocytosis and body mass index (BMI), such that as BMI increased so did efferocytosis. Conclusions This is the first study to measure efferocytosis in patients recovering from CAP. The results suggest that smokers with low BMI have impaired efferocytosis and may benefit from a statin to boost recovery.

Original languageEnglish (US)
JournalThorax
DOIs
StateAccepted/In press - Jul 28 2016
Externally publishedYes

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pneumonia
Body Mass Index
Alveolar Macrophages
Smoking
Bronchoscopy
Bronchoalveolar Lavage
Phagocytosis
Comorbidity
Flow Cytometry
Neutrophils
Research

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Wootton, D. G., Diggle, P. J., Court, J., Eneje, O., Keogan, L., Macfarlane, L., ... Gordon, S. B. (Accepted/In press). Recovery from pneumonia requires efferocytosis which is impaired in smokers and those with low body mass index and enhanced by statins. Thorax. https://doi.org/10.1136/thoraxjnl-2016-208505

Recovery from pneumonia requires efferocytosis which is impaired in smokers and those with low body mass index and enhanced by statins. / Wootton, Daniel G.; Diggle, Peter J.; Court, Joanne; Eneje, Odiri; Keogan, Lynne; Macfarlane, Laura; Wilks, Sarah; Woodhead, Mark; Gordon, Stephen B.

In: Thorax, 28.07.2016.

Research output: Contribution to journalArticle

Wootton, Daniel G. ; Diggle, Peter J. ; Court, Joanne ; Eneje, Odiri ; Keogan, Lynne ; Macfarlane, Laura ; Wilks, Sarah ; Woodhead, Mark ; Gordon, Stephen B. / Recovery from pneumonia requires efferocytosis which is impaired in smokers and those with low body mass index and enhanced by statins. In: Thorax. 2016.
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