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 language | English |
|---|---|
| Pages (from-to) | 835-842 |
| Journal | Thorax |
| Volume | 74 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- elastase activity
- LL-37
- pseudomonas aeruginosa
- SLPI
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
Antimicrobial peptides, disease severity and exacerbations in bronchiectasis. / 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.
In: Thorax, Vol. 74, No. 9, 01.01.2019, p. 835-842.Research output: Contribution to journal › Article
}
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.
PY - 2019/1/1
Y1 - 2019/1/1
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 - elastase activity
KW - LL-37
KW - pseudomonas aeruginosa
KW - SLPI
UR - http://www.scopus.com/inward/record.url?scp=85068582336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068582336&partnerID=8YFLogxK
U2 - 10.1136/thoraxjnl-2018-212895
DO - 10.1136/thoraxjnl-2018-212895
M3 - Article
VL - 74
SP - 835
EP - 842
JO - Thorax
JF - Thorax
SN - 0040-6376
IS - 9
ER -