Department of Medicine and.
Department of Medicine, University of California, San Francisco, San Francisco, California.
Ann Am Thorac Soc. 2022 Dec;19(12):2013-2020. doi: 10.1513/AnnalsATS.202204-332OC.
Human immunodeficiency virus (HIV) infection is associated with chronic lung disease and impaired pulmonary function; however, longitudinal pulmonary function phenotypes in HIV are undefined. To identify pulmonary function trajectories, their determinants, and outcomes. We used data from participants with HIV in the Pittsburgh HIV Lung Cohort with three or more pulmonary function tests between 2007 and 2020. We analyzed post-bronchodilator forced expiratory volume in 1 second (FEV), forced vital capacity (FVC), and FEV/FVC, and diffusing capacity of the lung for carbon monoxide (Dl) using group-based trajectory modeling to identify subgroups of individuals whose measurements followed a similar pattern over time. We examined the association between participant characteristics and trajectories using multivariable logistic regression. In exploratory adjusted analyses restricted to individuals with available plasma cytokine data, we investigated the association between 18 individual standardized cytokine concentrations and trajectories. We compared mortality, dyspnea prevalence, respiratory health status, and 6-minute-walk distance between phenotypes. A total of 265 participants contributed 1,606 pulmonary function measurements over a median follow-up of 8.1 years. We identified two trajectories each for FEV and FVC: "low baseline, slow decline" and "high baseline, rapid decline." There were three trajectory groups for FEV/FVC: "rapid decline," "moderate decline," and "slow decline." Finally, we identified two trajectories for Dl: "baseline low" and "baseline high." The low baseline, slow decline FEV and FVC, rapid decline, and moderate decline FEV/FVC, and baseline low Dl phenotypes were associated with increased dyspnea prevalence, worse respiratory health status, and decreased 6-minute-walk distance. The baseline low Dl phenotype was also associated with worse mortality. Current smoking and pack-years of smoking were associated with the adverse FEV, FEV/FVC, and Dl phenotypes. Detectable viremia was the only HIV marker associated with the adverse Dl phenotype. C-reactive protein and endothelin-1 were associated with the adverse FEV and FVC phenotypes, and endothelin-1 trended toward an association with the adverse Dl phenotype. We identified novel, distinct longitudinal pulmonary function phenotypes with significant differences in characteristics and outcomes. These findings highlight the importance of lung dysfunction over time in people with HIV and should be validated in additional cohorts.
人类免疫缺陷病毒 (HIV) 感染与慢性肺部疾病和肺功能受损有关；然而，HIV 患者的纵向肺功能表型尚不清楚。为了确定肺功能轨迹、其决定因素和结果。我们使用了 2007 年至 2020 年期间匹兹堡 HIV 肺队列中 HIV 患者的参与者数据，这些患者有三次或更多次支气管扩张后用力呼气量 (FEV)、用力肺活量 (FVC) 和 FEV/FVC，以及一氧化碳弥散量 (Dl) 的检测结果。我们使用基于群组的轨迹建模来分析 FEV 和 FVC 以及 FEV/FVC 的测量值，以确定随着时间的推移测量值遵循相似模式的个体亚组。我们使用多变量逻辑回归来检查参与者特征与轨迹之间的关系。在对有可用血浆细胞因子数据的个体进行的探索性调整分析中，我们研究了 18 种个体标准化细胞因子浓度与轨迹之间的关系。我们比较了表型之间的死亡率、呼吸困难发生率、呼吸健康状况和 6 分钟步行距离。共有 265 名参与者在中位数为 8.1 年的随访期间提供了 1606 次肺功能测量值。我们为 FEV 和 FVC 各确定了两个轨迹：“低基线、缓慢下降”和“高基线、快速下降”。FEV/FVC 有三个轨迹组：“快速下降”、“中度下降”和“缓慢下降”。最后，我们确定了 Dl 的两个轨迹：“基线低”和“基线高”。低基线、缓慢下降的 FEV 和 FVC、快速下降、中度下降的 FEV/FVC 和基线低的 Dl 表型与呼吸困难发生率增加、呼吸健康状况恶化和 6 分钟步行距离降低有关。低基线 Dl 表型也与死亡率增加有关。目前吸烟和吸烟包年数与不良 FEV、FEV/FVC 和 Dl 表型有关。可检测到的病毒血症是唯一与不良 Dl 表型相关的 HIV 标志物。C 反应蛋白和内皮素-1 与不良 FEV 和 FVC 表型相关，内皮素-1 与不良 Dl 表型呈趋势相关。我们确定了具有显著特征和结果差异的新型、独特的纵向肺功能表型。这些发现强调了 HIV 患者随时间推移肺功能障碍的重要性，应该在其他队列中得到验证。
