Inflammation may persist in kids with early CF despite P. aeruginosa eradication

Cystic fibrosis

By Michael Woodhead

25 Feb 2021

Anti-inflammatory approaches are needed in early CF because some children have a propensity for persistent inflammation and bronchiectasis progression despite successful P. aeruginosa eradication, Australian research shows.

A study involving 88 infants enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) database found that more than a third continued to have high levels of activity of the neutrophil proteases known to cause airway tissue damage, even after successful antibiotic treatment (tobramycin and ciprofloxacin) to eradicate P. aeruginosa.

Researchers at the Respiratory Research Centre, Telethon Kids Institute, University of WA, conducted the study in infants aged from three months to six years old who had P. aeruginosa cultured from their routine annual bronchoalveolar lavage (BAL) fluid.

Eradication was successful in 84% of episodes on first treatment, and there was an overall decline in neutrophilic inflammation as measured by  neutrophil elastase (NE) activity at three months follow up.

However NE activity persisted in 33 subjects post-eradication, and these high levels were associated with an increased risk for P. aeruginosa infection in the next annual visit (Odds Ratio = 1.7).

Children with persistently elevated NE activity were also at increased risk for structural lung disease progression on CT imaging within one year (backward stepwise linear regression model, R 2 = 0.608, P < 0.001), independent of P. aeruginosa eradication.

The study investigators said high NE activity in patients with CF was a well-documented risk factor for worse pulmonary outcomes, and in the current study the persistently elevated NE levels were found to be most consistently related to baseline neutrophilic inflammation, older age and worse baseline bronchiectasis score, “possibly indicating a predisposition for persistent inflammation in patients with more severe lung disease.”

They said their findings confirmed other reports that factors other than P. aeruginosa infection – including inflammation –  were likely to have a strong relationship to decreased lung function in CF.

They also supported the mechanism of action in which neutrophilic inflammation – as NE activity – promoted bacterial colonisation in the lungs by obstructing bacterial recognition and clearance through altering airway mucus composition and degrading immune components.

“Collectively, these findings suggest that management of early P. aeruginosa infections should also include strategies to diminish neutrophilic inflammation as part of the eradication protocol,” they wrote.

The next step should be to validate whether NE-related lung inflammation may be an important clinical biomarker to monitor CF lung health in addition to eradication of germs like P. aeruginosa, they said.

“Additional studies to confirm whether for these individuals [with persistent inflammation], treatments that mitigate inflammation or protease activity can reduce or prevent progressive structural disease from their P. aeruginosa infection are warranted,” they suggested.

The findings are published in the Journal of Cystic Fibrosis.

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