Assessing the performance of the HAS-BLED score: is the C statistic sufficient?

We thank Dr Vos and colleagues for providing important additional studies that support the use of long-term azithromycin therapy to treat and, possibly, prevent posttransplant bronchiolitis obliterans syndrome (BOS). These studies should have been included in our review of chronic macrolide therapy in infl ammatory airways disease 1 but were not available at the time of submission. Their recently published retrospective observational study 2 is the largest to date and confi rms previous fi ndings that a dichotomy exists in the clinical spectrum of BOS, with neutrophilic allograft dysfunction being macrolide responsive, whereas fi broproliferative BOS is not. Importantly, their study supports the fi nding observed by Jain et al 3 showing better long-term survival in responders compared with nonresponders. Given these more recent studies, we wish to change our grading recommendation to 2A in favor of the use of long-term azithromycin therapy in a subgroup of patients with established BOS (neutrophilic). We believe that the recently published randomized controlled trial of azithromycin prophylaxis in lung transplant recipients by Vos et al 4 is the fi rst to demonstrate that long-term macrolide therapy may prevent BOS. Additionally, this study supports the immunomodulatory effects seen with certain macrolides therapy, even when given at low doses, as discussed in our review. We agree that this is good evidence supporting the use of long-term, low-dose azithromycin therapy to prevent BOS. However, additional placebo-controlled randomized trials are necessary to further defi ne the potential adverse effects of this therapy.