title: Recovery from pneumonia requires efferocytosis which is impaired in smokers and those with low body mass index and enhanced by statins.
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.
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, UK Department of Respiratory Research, Aintree University Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Wootton
authors.affiliation: CHICAS, Lancaster University Medical School, Lancaster University, Lancaster, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Diggle
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Court
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Odiri
authors.initials: O
authors.lastname: Eneje
authors.affiliation: Department of Respiratory Research, Aintree University Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Lynne
authors.initials: L
authors.lastname: Keogan
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Macfarlane
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wilks
authors.affiliation: Department of Respiratory Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Manchester Academic Health Science Centre and Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodhead
authors.affiliation: CHICAS, Lancaster University Medical School, Lancaster University, Lancaster, UK.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D015992:Body Mass Index; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D017714:Community-Acquired Infections / Q000628:therapy*; D015897:Comorbidity; D004739:England; D005434:Flow Cytometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016676:Macrophages, Alveolar / Q000502:physiology; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D011014:Pneumonia / Q000628:therapy*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Macrophage Biology; Neutrophil Biology; Pneumonia; Tobacco and the lung