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Chronic P. Aeruginosa Infection Greatly Raises Risk of Flares in Non-CF Bronchiectasis, Study Shows

People with non-cystic fibrosis (CF) bronchiectasis are at a significantly greater risk of exacerbations if they have chronic infections caused by Pseudomonas aeruginosa, a common bacteria that produces specific virulence factors, according to researchers in China.

P. aeruginosa is often found in people with chronic lung diseases, including CF, non-CF bronchiectasis, and chronic obstructive pulmonary disease (COPD).

After colonizing the respiratory tract, the bacteria can become established and convert to its mucoid form, which produces alginate — a gelatinous molecule that improves the bacteria’s survival and growth — and is associated with chronic infection, stronger inflammation, and a worsening in lung function.

The bacteria has a tendency to persist in bronchiectatic airways, due to its ability to produce virulence factors and modulate the host’s immune responses. About one-third of non-CF bronchiectasis patients have chronic P. aeruginosa infections.

Two virulence factors in P. aeruginosa, called exoU and pldA, have been shown to induce toxicity — exoU to the host’s cells and pldA to harmless bacteria in the respiratory tract.

But the potential link between their presence and clinical outcomes in non-CF bronchiectasis patients remains unknown.

Researchers with Shanghai Pulmonary Hospital at Tongji University School of Medicine evaluated whether non-CF bronchiectasis patients infected with mucoid P. aeruginosa that tested positive for exoU and pldA had more exacerbations.

They enrolled 147 patients (101 women and 46 men) who were hospitalized for non-CF bronchiectasis with mucoid P. aeruginosa from October 2012 and January 2015 at Shanghai Pulmonary Hospital, a specialized center focused on lung diseases.

The presence of the two virulence factors was assessed in the mucoid P. aeruginosa collected from the lung fluid of these patients, who had a mean age of about 58 and were followed for a median of 18 months.

Among these 147 people, 17 were positive for pldA, nine were positive for exoU, and seven were positive for both factors.

Results showed that a lower body mass index (lower than 18.5 kg/m2), a longer hospitalization stay (more than eight days), and testing positive for either of the virulence factors were associated with an increased risk of exacerbations.

Patients who were positive for either of the virulence factors had significantly more flare per year (mean of 2.37) than those who were negative for these factors (mean of 0.79).

A significantly higher number of patients with virulence factors (93.94%) had exacerbations compared to those without them (64.91%).

The team found that the chance of patients having exoU or pldA in mucoid P. aeruginosa increased as the frequency of exacerbations rose.

Researchers also noted that the presence of pldA was associated with a higher frequency of exacerbations and greater mucus production than the presence of exoU, suggesting that it might be a more important virulence factor. Additional studies are necessary to explore its role in lung diseases, they said.

These findings suggest that the presence of the virulence factors exoU and pldA in mucoid P. aeruginosa are “significant risk factors for exacerbations in patients with non-CF bronchiectasis,” the researchers wrote.

“We hope this could be used as a biomarker to help physicians identify patients with bronchiectasis at higher risk for exacerbations and take stronger [preventive] and therapeutic strategies for these patients,” they added.

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