Fluticasone-based ICS, LABA therapy changes airway microbiome in COPD

Fluticasone-based inhaled corticosteroid treatment substantially changed airway microbiome diversity in patients with COPD, according to new data published in the American Journal of Respiratory and Critical Care Medicine.

“Inhaled corticosteroids, especially potent ones like fluticasone, can change the microbial communities (which are called microbiome) of airways of COPD patients, rendering them more susceptible for pneumonia,” Don D. Sin, MD, director and De Lazzari Family Chair at the Centre for Heart Lung Innovation, Canada Research Chair in COPD and professor of medicine in the division of respiratory medicine in the department of medicine at St. Paul’s Hospital, Vancouver, British Columbia, told Healio. “We were puzzled as to why the use of inhaled corticosteroids increased the risk of pneumonia in COPD patients. We hypothesized that these therapeutics would adversely change the airway microbiome of COPD patients.”

The study enrolled 63 clinically stable patients with COPD. Use of inhaled corticosteroid (ICS) was discontinued and substituted with formoterol (Teva) 12 µg twice daily. Patients were randomly assigned to receive budesonide/formoterol 400/12 µg (n = 20; mean age, 66.3 years; 85% men), fluticasone/salmeterol 250/50 µg (n = 22; mean age, 66 years; 77.3% men) or formoterol only 12 µg (n = 21; mean age, 62.5 years; 85.7% men), all twice daily for 12 weeks.

The primary outcome was the comparison of airway microbiome changes during 12 weeks between the ICS/long-acting beta agonist (LABA) and LABA only groups.

Don D, Sin, MD

A total of 56 patients completed all clinic visits after seven patients withdrew between the first and second bronchoscopy visits. Airway microbiota diversity showed significant differences across groups following the treatment period with the most significant changes observed among those who received fluticasone/salmeterol and formoterol alone.

In addition, longitudinal differential abundance analyses demonstrated more pronounced airway microbial shifts from baseline among those who received fluticasone/salmeterol. These greater shifts were related to reduced abundances of Pasteurellas, Pasteurellaceae and Haemophilus.

According to Sin, it was surprising to find that 3-month LABA therapy improved the airway microbiome in this patient population and that 25% of patients who withdrew from ICS developed breathing troubles and dropped out.

“New corticosteroids are being developed for COPD. We need to find out their effects on the airway microbiome of COPD patients before they are widely deployed in clinical care,” Sin said. “We also need to find out which bacterial organisms are responsible for keeping the airway microbiome healthy and develop novel therapeutics to restore the airway microbiome of COPD patients.”

For more information:

Don D. Sin, MD, can be reached at don.sin@hli.ubc.ca.