Macrolides
Macrolides exhibit immunomodulatory as well as antibiotic properties and some mixed evidence exists to support long-term use in selected CRS patients 112,113. The presumed mechanism of action is the suppression of pro-inflammatory cytokines 118-120Two randomized, placebo-controlled trials have been performed in CRS.121,122 Post-hoc analysis of treatment response indicated that patients with low serum IgE (and presumably non T2) responded best and these responders exhibited decreased IL-8 levels in the mucus post treatment 121. Later cohort studies demonstrated a lack of efficacy for macrolides in eosinophilic CRSwNP patients 123,124. It remains to be established whether responders exhibit T1, T3, null or mixed endotypes. Studies of whether macrolides might have an additive effect with other medications (e.g. corticosteroids or a biologic) dedicated to suppressing T2 inflammation are worth pursuing 125-127.