Antimicrobial Peptides SLPI and Beta Defensin-1 in Sputum are Negatively Correlated with FEV1

Int J Chron Obstruct Pulmon Dis. 2021 May 28:16:1437-1447. doi: 10.2147/COPD.S301622. eCollection 2021.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) and asthma have heterogeneous inflammation with inhaled corticosteroids (ICS) as a mainstay of treatment. There is increased prevalence of non-typeable Haemophilus influenzae (NTHi) persistence in airways of patients with neutrophilic airway inflammation, potentially due to suppressed host defence after corticosteroid treatment. Antimicrobial peptides (AMPs) have antimicrobial activity against pathogens and immunomodulatory effects. We investigated whether AMPs associate with NTHi presence in COPD and asthma, and whether ICS alter this.

Methods: Secretory leukocyte protease inhibitor (SLPI), osteopontin, elafin and beta defensin-1 were measured in sputum supernatants from healthy donors (n=9), asthmatics (n=21) and patients with COPD (n=14). Elafin and beta defensin-1 were measured in a primary human bronchial epithelial cells (HBECs) from healthy and COPD donors infected with NTHi and pre-treated with fluticasone propionate (FP) and budesonide (BUD). Internalised NTHi was quantified by qPCR.

Results: Sputum SLPI was negatively correlated with FEV1 (p<0.001, r=-0.610), FEV1% predicted (p<0.001, r=-0.583) and FEV1/FVC (p=0.001, r=-0.528). Sputum beta defensin-1 was negatively associated with FEV1 (p<0.001***r=-0.594). SLPI and beta defensin-1 levels in sputum were higher in the healthy controls and COPD group compared to the asthma group (p=0.001 and p=0.014) and (p<0.001 and p=0.007, respectively). ICS use was associated with higher sputum osteopontin compared to those with no ICS use. NTHi infection of COPD HBECs produced higher levels of beta defensin-1 compared to healthy donors (mean (SD) release: 45.1pg/mL (7.3) vs 21.2pg/mL (7.3) respectively, p=0.014). Elafin release from HBECs from COPD donors did not change following NTHi infection; however, elafin from healthy donors was significantly reduced (%mean reduction: 23.7%, 95% confidence intervals (CI) of reduction: 5.3-38.4%, p<0.01).

Conclusion: Sputum SLPI and beta defensin-1 may be markers to identify those patients with declining lung function. ICS use was associated with higher sputum osteopontin compared to those with no ICS use.

Keywords: antimicrobial peptide; chronic obstructive pulmonary disease; non-typeable haemophilus influenzae.

MeSH terms

  • Humans
  • Pore Forming Cytotoxic Proteins
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Secretory Leukocyte Peptidase Inhibitor
  • Sputum
  • beta-Defensins*

Substances

  • Pore Forming Cytotoxic Proteins
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor
  • beta-Defensins

Grants and funding

MRC Proximity to Discovery Grant, National Institute of Health Research, Oxford Health Service Research Committee, Pfizer.The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. This report was independent research supported by the National Institute for Health Research (Dr Mona Bafadhel, PDF-2013-06-052). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.