Neutrophil elastase correlates with increased sphingolipid content in cystic fibrosis sputum

Cystic fibrosis (CF) airway disease is characterized by chronic microbial infections and infiltration of inflammatory polymorphonuclear (PMN) granulocytes. Staphylococcus aureus (S. aureus) is a major lung pathogen in CF that persists despite the presence of PMNs and has been associated with CF lung function decline. While PMNs represent the main mechanism of the immune system to kill S. aureus, it remains largely unknown why PMNs fail to eliminate S. aureus in CF. The goal of this study was to observe how the CF airway environment affects S. aureus killing by PMNs. PMNs were isolated from the blood of healthy volunteers and CF patients. Clinical isolates of S. aureus were obtained from the airways of CF patients. The results show that PMNs from healthy volunteers were able to kill all CF isolates and laboratory strains of S. aureus tested in vitro. The extent of killing varied among strains. When PMNs were pretreated with supernatants of CF sputum, S. aureus killing was significantly inhibited suggesting that the CF airway environment compromises PMN antibacterial functions. CF blood PMNs were capable of killing S. aureus. Although bacterial killing was inhibited with CF sputum, PMN binding and phagocytosis of S. aureus was not diminished. The S. aureus-induced respiratory burst and neutrophil extracellular trap release from PMNs also remained uninhibited by CF sputum. In summary, our data demonstrate that the CF airway environment limits killing of S. aureus by PMNs and provides a new in vitro experimental model to study this phenomenon and its mechanism.

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Faculty Opinions recommendation of Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.739606469.793590333 ◽

2021 ◽

Author(s):

Robert Palmer

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Cystic Fibrosis Sputum ◽

Current Therapies

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SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum

Journal of Cystic Fibrosis ◽

10.1016/j.jcf.2018.06.002 ◽

2019 ◽

Vol 18 (2) ◽

pp. 244-250 ◽

Cited By ~ 2

Author(s):

Juliana I. Sesma ◽

Bryant Wu ◽

Timothy J. Stuhlmiller ◽

David W. Scott

Keyword(s):

Cystic Fibrosis ◽

Cystic Fibrosis Sputum

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Sputum Neutrophil Elastase in pediatric cystic fibrosis and non-cystic fibrosis bronchiectasis

QJM ◽

10.1093/qjmed/hcab113.027 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Eman M Fouda ◽

Heba A Ali ◽

Mona A. A Salem ◽

Heba H Radwan

Keyword(s):

Cystic Fibrosis ◽

Neutrophil Elastase ◽

Severity Index ◽

Cross Sectional Study ◽

University Hospital ◽

Cross Sectional ◽

Sweat Chloride ◽

Chronic Lung Diseases ◽

Severe Group ◽

Group B

Abstract Objective To assess the value of sputum neutrophil elastase as a biomarker of severity in cases of non-cystic fibrosis bronchectasis & cystic fibrosis. Methods This cross-sectional study was conducted on 50 bronchiectasis patients aged from 1 to 13 years presented to pediatric chest clinic and department of Ain shams university hospital., there were classified into 2 groups; Group A cystic fibrosis patients(30) and group B non-cystic fibrosis bronchiectasis patients(20). Inclusion criteria :children aged from 1 to 16 years, patients were diagnosed with bronchiectasis clinically and with HRCT chest and cystic Fibrosis patients were diagnosed by positive sweat chloride test and genetic study. Exclusion Criteria includes no other known chronic lung diseases. All patients were evaluated by full medical history and full clinical examination, the following lab investigations were done :sweat chloride test, CFTR mutation study, sputum sampling and culture. Quantitative sputum neutrophil elastase assay was done, and the severity of disease was assessed using clinical scores as SK score ,FACED score and bronchiectasis severity index and by using radiological scores as Bhalla and modified Reiff score. Results Steatorrhea was more prevalent among cystic fibrosis patients (80%) than non-CF bronchiectasis patients (0%).(P = 0.00). Clubbing was more prevalent among non -cystic fibrosis bronchectasis (10) (50 %), than cystic fibrosis (2 patients) (6.7 %).(P = 0.00). In cystic fibrosis, neutrophil elastase was significantly higher among severe group (126 ng/mL) than among the moderate (30 ng/mL) and mild (16 ng/mL) groups.(P = 0.00). While in non-CF bronchiectasis patients, neutrophil elastase was significantly higher among severe group (67 ng/mL) than among the moderate (24 ng/mL) and mild (11 ng/mL) groups.(P = 0.00) Conclusion There was a significant correlation between sputum neutrophil elastase and disease severity in bronchiectasis (both cystic fibrosis and non-CF).

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