The macrolide clarithromycin could be an effective therapy for both steroid sensitive and severe steroid-insensitive asthma, largely because of its anti-inflammatory properties, finds an Australian study published in Thorax.
Carried out at the University of Newcastle, the study by Professor Philip Hansbro and colleagues used a new mouse model to replicate the symptoms of severe steroid-insensitive (SSI) asthma.
“We gave the mice asthma and then we gave them an infection, and that turned their asthma into a more severe form that was steroid resistant,” says Hansbro.
Clarithromycin treatment of the mice with SSI asthma, induced by either Chlamydia pneumonia or Haemophilus influenza infection, suppressed inflammation and reduced airway hyper-responsiveness.
Similar improvements with the macrolide were seen in mice that were not infected and had steroid-sensitive allergic airways disease.
Amoxicillin treatment was used as a comparator, and although, like clarithromycin, it cleared the infection, it was not an effective treatment for either steroid-sensitive or SSI asthma.
“It looks as if you get a ‘double whammy’ from using clarithromycin,” says Hansbro, it kills the bacteria but also suppresses inflammation, which is important in asthma.”
Clarithromycin seems to reduce the dominant source of inflammation in the different types of allergic airways disease: targeting T-helper lymphocyte type 2 responses in steroid-sensitive disease, TNF-α in Chlamydia-induced SSI asthma, and T-helper lymphocyte type 17 responses in Haemophilus-induced SSI disease, the authors say.
The data also showed that steroids reactivated infection, suggesting they may be detrimental in steroid-insensitive SSI asthma, they add.
Numerous clinical studies have linked Chlamydia pneumoniae and Haemophilus influenza infection to steroid-insensitive endotypes such as neutrophilic asthma, says Hansbro, who suspects that SSI asthma is produced by bacterial colonisation in people with asthma.
The AMAZES clinical trial, investigating the effectiveness of another macrolide (azithromycin) for asthma is currently underway, led by Professor Peter Gibson of the Hunter New England Area Health Service, who co-authored the clarithromycin paper.