Antimicrobial peptides, disease severity and exacerbations in bronchiectasis

Oriol Sibila (Lead / Corresponding author), Lídia Perea, Elisabet Cantó, Amelia Shoemark, Diane Cassidy, Alexandria Holly Smith, Guillermo Suarez-cuartin, Ana Rodrigo-troyano, Holly R. Keir, Martina Oriano, Samantha Ong, Silvia Vidal, Francesco Blasi, Stefano Aliberti, James D. Chalmers

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Abstract

Rationale: Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease.

Objectives: To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis.

Methods: A total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk.

Measurements and main results: AMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months.

Conclusions: Patients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis.
Original languageEnglish
Number of pages8
JournalThorax
Early online date5 Jul 2019
DOIs
Publication statusE-pub ahead of print - 5 Jul 2019

Fingerprint

Secretory Leukocyte Peptidase Inhibitor
Bronchiectasis
Disease Progression
Peptides
Sputum
Pseudomonas Infections
Pseudomonas aeruginosa
Phenotype
Lactoferrin
Forced Expiratory Volume
Muramidase
Serum
Lung Diseases
Chronic Disease
Enzyme-Linked Immunosorbent Assay
Lung

Keywords

  • Bronchiectasis
  • pseudomonas aeruginosa
  • LL-37
  • SLPI
  • elastase activity

Cite this

Sibila, Oriol ; Perea, Lídia ; Cantó, Elisabet ; Shoemark, Amelia ; Cassidy, Diane ; Smith, Alexandria Holly ; Suarez-cuartin, Guillermo ; Rodrigo-troyano, Ana ; Keir, Holly R. ; Oriano, Martina ; Ong, Samantha ; Vidal, Silvia ; Blasi, Francesco ; Aliberti, Stefano ; Chalmers, James D. / Antimicrobial peptides, disease severity and exacerbations in bronchiectasis. In: Thorax. 2019.
@article{56e30d3909d543f28a183958b84ab01e,
title = "Antimicrobial peptides, disease severity and exacerbations in bronchiectasis",
abstract = "Rationale: Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease.Objectives: To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis.Methods: A total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk.Measurements and main results: AMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months.Conclusions: Patients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis.",
keywords = "Bronchiectasis, pseudomonas aeruginosa, LL-37, SLPI, elastase activity",
author = "Oriol Sibila and L{\'i}dia Perea and Elisabet Cant{\'o} and Amelia Shoemark and Diane Cassidy and Smith, {Alexandria Holly} and Guillermo Suarez-cuartin and Ana Rodrigo-troyano and Keir, {Holly R.} and Martina Oriano and Samantha Ong and Silvia Vidal and Francesco Blasi and Stefano Aliberti and Chalmers, {James D.}",
note = "Funding European Respiratory Society through the EMBARC2 consortium, Instituto de Salud Carlos III (PI18/00311), Fundaci{\'o} Catalana de Pneumologia (FUCAP), Sociedad Espa{\~n}ola de Neumolog{\'i}a y Cirug{\'i}a Tor{\'a}cica (SEPAR) and a research Grant from Zambon. OS is supported by PERIS. JDC is supported by the GSK/British Lung Foundation Chair of Respiratory Research.",
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Sibila, O, Perea, L, Cantó, E, Shoemark, A, Cassidy, D, Smith, AH, Suarez-cuartin, G, Rodrigo-troyano, A, Keir, HR, Oriano, M, Ong, S, Vidal, S, Blasi, F, Aliberti, S & Chalmers, JD 2019, 'Antimicrobial peptides, disease severity and exacerbations in bronchiectasis', Thorax. https://doi.org/10.1136/thoraxjnl-2018-212895

Antimicrobial peptides, disease severity and exacerbations in bronchiectasis. / Sibila, Oriol (Lead / Corresponding author); Perea, Lídia; Cantó, Elisabet; Shoemark, Amelia; Cassidy, Diane; Smith, Alexandria Holly; Suarez-cuartin, Guillermo; Rodrigo-troyano, Ana; Keir, Holly R.; Oriano, Martina; Ong, Samantha; Vidal, Silvia; Blasi, Francesco; Aliberti, Stefano; Chalmers, James D.

In: Thorax, 05.07.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antimicrobial peptides, disease severity and exacerbations in bronchiectasis

AU - Sibila, Oriol

AU - Perea, Lídia

AU - Cantó, Elisabet

AU - Shoemark, Amelia

AU - Cassidy, Diane

AU - Smith, Alexandria Holly

AU - Suarez-cuartin, Guillermo

AU - Rodrigo-troyano, Ana

AU - Keir, Holly R.

AU - Oriano, Martina

AU - Ong, Samantha

AU - Vidal, Silvia

AU - Blasi, Francesco

AU - Aliberti, Stefano

AU - Chalmers, James D.

N1 - Funding European Respiratory Society through the EMBARC2 consortium, Instituto de Salud Carlos III (PI18/00311), Fundació Catalana de Pneumologia (FUCAP), Sociedad Española de Neumología y Cirugía Torácica (SEPAR) and a research Grant from Zambon. OS is supported by PERIS. JDC is supported by the GSK/British Lung Foundation Chair of Respiratory Research.

PY - 2019/7/5

Y1 - 2019/7/5

N2 - Rationale: Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease.Objectives: To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis.Methods: A total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk.Measurements and main results: AMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months.Conclusions: Patients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis.

AB - Rationale: Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease.Objectives: To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis.Methods: A total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk.Measurements and main results: AMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months.Conclusions: Patients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis.

KW - Bronchiectasis

KW - pseudomonas aeruginosa

KW - LL-37

KW - SLPI

KW - elastase activity

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U2 - 10.1136/thoraxjnl-2018-212895

DO - 10.1136/thoraxjnl-2018-212895

M3 - Article

JO - Thorax

JF - Thorax

SN - 0040-6376

ER -