Important immunomodulatory properties of 14- and 15-membered
macrolides may benefit patients with
respiratory diseases associated with chronic
inflammation. These properties include decreased neutrophil chemotaxis and infiltration into the respiratory epithelium, inhibition of
transcription factors leading to decreased proinflammatory
cytokine production, downregulation of adhesion molecule expression, inhibition of microbial
virulence factors including biofilm formation, reduced generation of
oxygen-
free radicals, enhanced neutrophil apoptosis, and decreased mucus hypersecretion with improved mucociliary clearance. Chronic, low-dose
macrolides have dramatically improved survival in patients with
diffuse panbronchiolitis (DPB). Given the overlap in pathogenesis between DPB and other chronic
respiratory diseases,
macrolides are being investigated for
cystic fibrosis,
asthma,
chronic bronchitis, chronic
sinusitis, and
chronic obstructive pulmonary disease. Preliminary data (largely from open-label trials) are promising, but conclusive results are needed.