Santos Jesse, Hays Steven R, Golden Jeffrey A, Calabrese Daniel R, Kolaitis Nicholas, Kleinhenz Mary Ellen, Shah Rupal, Estrada Aida Venado, Leard Lorriana E, Kukreja Jasleen, Singer Jonathan P, Greenland John R
San Francisco Department of Medicine, University of California, San Francisco, CA.
Medical Service, San Francisco VA Health Care System, San Francisco, CA.
Transplant Direct. 2023 Aug 9;9(9):e1495. doi: 10.1097/TXD.0000000000001495. eCollection 2023 Sep.
Large-airway lymphocytic inflammation (LB), assessed on endobronchial biopsies, has been associated with acute cellular rejection and chronic lung allograft dysfunction (CLAD). Azithromycin (AZI) prophylaxis has been used to prevent airway inflammation and subsequent CLAD, with inconsistent results. We hypothesized that AZI prophylaxis would be associated with reduced LB, changes in bronchoalveolar lavage (BAL) immune cell populations, and improved CLAD-free survival.
We compared frequencies of LB from endobronchial biopsies before (N = 1856) and after (N = 975) protocolized initiation of AZI prophylaxis at our center. LB was classified as none, minimal, mild, or moderate by histopathologic analysis. LB grades were compared using ordinal mixed-model regression. Corresponding automated BAL leukocyte frequencies were compared using mixed-effects modeling. The effect of AZI prophylaxis on CLAD-free survival was assessed by a Cox proportional hazards model adjusted for age, sex, ethnicity, transplant indication, and cytomegalovirus serostatus.
Biopsies in the pre-AZI era had 2-fold increased odds (95% confidence interval, 1.5-2.7; < 0.001) of higher LB grades. LB was associated with BAL neutrophilia in both eras. However, there was no difference in risk for CLAD or death between AZI eras (hazard ratio 1.3; 95% confidence interval, 0.7-2.0; = 0.45).
Decreased airway inflammation in the era of AZI prophylaxis may represent a direct effect of AZI therapy or reflect other practices or environmental changes. In this cohort, AZI prophylaxis was not associated with improved CLAD-free survival.
通过支气管活检评估的大气道淋巴细胞炎症（LB）与急性细胞排斥反应和慢性肺移植功能障碍（CLAD）相关。阿奇霉素（AZI）预防已用于预防气道炎症及随后的CLAD，但结果不一致。我们假设AZI预防与LB减少、支气管肺泡灌洗（BAL）免疫细胞群体变化及无CLAD生存期改善相关。
我们比较了在本中心按方案开始AZI预防之前（N = 1856）和之后（N = 975）支气管活检中LB的频率。通过组织病理学分析将LB分为无、极少、轻度或中度。使用有序混合模型回归比较LB分级。使用混合效应模型比较相应的自动BAL白细胞频率。通过针对年龄、性别、种族、移植指征和巨细胞病毒血清状态进行调整的Cox比例风险模型评估AZI预防对无CLAD生存期的影响。
在AZI预防前时代的活检中，LB分级较高的几率增加了2倍（95%置信区间，1.5 - 2.7；< 0.001）。在两个时代，LB均与BAL中性粒细胞增多相关。然而，AZI时代之间CLAD或死亡风险没有差异（风险比1.3；95%置信区间，0.7 - 2.0； = 0.45）。
AZI预防时代气道炎症的减少可能代表AZI治疗的直接作用，或反映其他实践或环境变化。在这个队列中，AZI预防与无CLAD生存期的改善无关。
