A low diversity of bacterial species in the lungs of adults with bronchiectasis is linked with higher levels of an enzyme called active neutrophil elastase (NE), as well as greater disease severity and worse lung function, a study discovered.
High levels of neutrophil elastase were specifically related to infections by Pseudomonas aeruginosa.
The study, “Sputum Neutrophil Elastase associates with microbiota and P. aeruginosa in bronchiectasis,” was published in the journal European Respiratory Journal.
Airway inflammation caused by immune cells called neutrophils is thought to be one of the major drivers of bronchiectasis. In fact, up to 80% of bronchiectasis patients experience inflammation related to neutrophils.
These cells secrete NE, which usually destroys invading bacteria, and has been suggested as a promising biomarker of inflammatory lung damage in bronchiectasis. NE detected in sputum has also been linked to disease severity, lung function, exacerbations, and quality of life.
Although many studies have investigated the association between NE activity and the presence of chronic bacterial infection, an analysis of the diversity of bacteria — called the microbiome — in the airways of bronchiectasis patients has yet to be reported.
Researchers in Italy, the U.S., and the U.K. analyzed bacterial diversity and active NE levels in sputum samples from 185 bronchiectasis patients, ages 51 to 71.
Bacteria were identified by genetic analysis. Patients underwent clinical assessments, including radiological and functional evaluation.
Based on active enzyme levels, they were divided into two groups; 109 with active neutrophil elastase levels below 20 micrograms (mcg)/mL, and 76 with levels of 20 mcg/mL and above.
Patients with higher levels of NE showed more disease severity, greater daily sputum protection, and lower forced expiratory volume in one second, a measure of lung function.
Most patients had a chronic infection. Genetic analysis found the bacteria P. aeruginosa in 43.2% of cases, Staphylococcus aureus in 38.4%, Streptococcus pneumoniae in 36.2%, and Haemophilus influenzae in 30.3% of patients.
The team found a strong link between lower bacterial diversity and higher levels of active NE. Patients in the high NE group had significantly less diverse bacteria than those with lower NE levels.
“The correlation between [active NE] and a reduced microbiota diversity in sputum is a novel finding in bronchiectasis patients,” the scientists wrote.
Specifically, greater levels of active NE correlated with having a higher P. aeruginosa load in sputum. In contrast, increases in Streptococcus species was linked with low levels of the active enzyme.
Chronic bacterial infection was more prevalent in the high than in the low NE group (67.1% vs. 40.2%), as were P. aeruginosa infections (45.2% vs. 23.5%). No differences were found in the distribution of the other bacteria species.
A statistical analysis then found that P. aeruginosa was the only significant variable associated with active NE.
“P. aeruginosa appears to be the most potent bacterial stimulus of neutrophil recruitment and release of NE in the bronchiectasis airways,” the scientists wrote.
“High levels of active neutrophil elastase are associated to low microbiome diversity and specifically to P. aeruginosa infection,” they added. The scientists also said that the link between P. aeruginosa, active NE and decreased bacteria diversity suggest that the microbiome in the lung could be a future treatment target.
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