Plasma Cathelicidin is Independently Associated with Reduced Lung Function in COPD: Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort

Rm, Burkes; As, Ceppe; Couper, David J.; Comellas, Alejandro P.; Jm, Wells; Sp, Peters; Criner, G.J.; Kanner, R.E.; Paine, Robert; Sa, Christenson; Cb, Cooper; Iz, Barjaktarevic; Ja, Krishnan; Ww, Labaki; Han, M.K.; Curtis, Jeffrey L.; Nn, Hansel; Ra, Wise; Drummond, M. Bradley

doi:10.15326/jcopdf.7.4.2020.0142

Cited by 6 publications

(5 citation statements)

References 48 publications

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“…Two clinical studies (n = 2/19, 11% of all clinical studies included in the review) reported the negative correlation of cathelicidin in plasma [ 42 ] and sputum [ 43 ] with lung function. Both sputum and plasma cathelicidin levels were found to be negatively correlated with lung function [ 42 , 43 ]. Both findings, conducted by Burkes at al.…”

Section: Resultsmentioning

confidence: 99%

“…Both findings, conducted by Burkes at al. and Wright et al, have to be seen as especially thorough, as they derive from clinical studies with a high number of participants, namely exceeding 500 [ 42 ] and 100 individuals [ 43 ]. Furthermore, one study conducted by Jiang et al (5%, n = 19) noted that increased induced sputum LL-37 levels in COPD patients were also associated with airflow limitation [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

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A Scoping Analysis of Cathelicidin in Response to Organic Dust Exposure and Related Chronic Lung Illnesses

Golec

Lemieszek

Dutkiewicz

et al. 2022

IJMS

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Over two billion people worldwide are exposed to organic dust, which can cause respiratory disorders. The discovery of the cathelicidin peptide provides novel insights into the lung’s response to organic dust; however, its role in the lung’s response to organic dust exposure and chronic lung diseases remains limited. We conducted a scoping review to map the current evidence on the role of cathelicidin LL-37/CRAMP in response to organic dust exposure and related chronic lung diseases: hypersensitivity pneumonitis (HP), chronic obstructive pulmonary disease (COPD) and asthma. We included a total of n = 53 peer-reviewed articles in this review, following the process of (i) a preliminary screening; (ii) a systematic MEDLINE/PubMed database search; (iii) title, abstract and full-text screening; (iv) data extraction and charting. Cathelicidin levels were shown to be altered in all clinical settings investigated; its pleiotropic function was confirmed. It was found that cathelicidin contributes to maintaining homeostasis and participates in lung injury response and repair, in addition to exerting a positive effect against microbial load and infections. In addition, LL-37 was found to sustain continuous inflammation, increase mucus formation and inhibit microorganisms and corticosteroids. In addition, studies investigated cathelicidin as a treatment modality, such as cathelicidin inhalation in experimental HP, which had positive effects. However, the primary focus of the included articles was on LL-37’s antibacterial effect, leading to the conclusion that the beneficial LL-37 activity has not been adequately examined and that further research is required.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A Scoping Analysis of Cathelicidin in Response to Organic Dust Exposure and Related Chronic Lung Illnesses

Golec

Lemieszek

Dutkiewicz

et al. 2022

IJMS

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“…We found a negative correlation between sputum SLPI and beta defensin-1 and FEV1. Recently, cathelicidin has also been found to negatively correlate with FEV1 in stable COPD patients, 28 highlighting the potential for these AMPs to identify patients at greater risk of lung function decline.…”

Section: Discussionmentioning

confidence: 99%

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

Cane¹,

Tregidgo²,

Thulborn³

et al. 2021

COPD

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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.

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“…Nevertheless, a few studies on COPD stratification based on exacerbation risk shows that the LL-37 is lower in high-risk exacerbators compared to low-risk counterparts ( 361 , 366 , 367 ). Similarly, COPD stratification based on severity shows that LL-37 is significantly reduced in severe disease compared to mild/moderate disease ( 296 , 348 ). Several authors argue that this observation is most likely driven by a high background of NF-kB activation in severe disease, which has been reported to inhibit LL-37 ( 366 ).…”

Section: Antimicrobial Peptides and Lung Damage In Microbiome-immune ...mentioning

confidence: 96%

“…Besides the known protective effects of LL-37 against invading pathogens at the mucosa, several studies have implicated this peptide in COPD ( 289 , 315 , 336 , 337 , 337 , 338 , 338 , 339 , 339 , 340 , 340 , 341 , 341 , 342 , 342 , 343 , 343 , 344 , 344 , 345 , 345 , 346 , 346 – 351 ). Investigators have demonstrated its association with poor lung function ( 348 , 349 ). In a setting of cigarette-smoke exposure, low levels of LL-37 have been independently associated with lower FEV 1.…”

Section: Antimicrobial Peptides and Lung Damage In Microbiome-immune ...mentioning

confidence: 99%

Airway microbiome-immune crosstalk in chronic obstructive pulmonary disease

et al. 2023

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Chronic Obstructive Pulmonary Disease (COPD) has significantly contributed to global mortality, with three million deaths reported annually. This impact is expected to increase over the next 40 years, with approximately 5 million people predicted to succumb to COPD-related deaths annually. Immune mechanisms driving disease progression have not been fully elucidated. Airway microbiota have been implicated. However, it is still unclear how changes in the airway microbiome drive persistent immune activation and consequent lung damage. Mechanisms mediating microbiome-immune crosstalk in the airways remain unclear. In this review, we examine how dysbiosis mediates airway inflammation in COPD. We give a detailed account of how airway commensal bacteria interact with the mucosal innate and adaptive immune system to regulate immune responses in healthy or diseased airways. Immune-phenotyping airway microbiota could advance COPD immunotherapeutics and identify key open questions that future research must address to further such translation.

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Plasma Cathelicidin is Independently Associated with Reduced Lung Function in COPD: Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort

Abstract: For personal use only. Permission required for all other uses.

Cited by 6 publications

References 48 publications

A Scoping Analysis of Cathelicidin in Response to Organic Dust Exposure and Related Chronic Lung Illnesses

A Scoping Analysis of Cathelicidin in Response to Organic Dust Exposure and Related Chronic Lung Illnesses

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

Airway microbiome-immune crosstalk in chronic obstructive pulmonary disease

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