El-Kersh K, Bag R, Bhatt N, King C, Waxman A, Rischard F, Kim H, Cella D, Shen E, Nathan S D
University of Arizona College of Medicine, Phoenix.
Mayo Clinic.
JHLT Open. 2025 Jan 7;7:100206. doi: 10.1016/j.jhlto.2025.100206. eCollection 2025 Feb.
Pulmonary hypertension due to interstitial lung disease (ILD-PH) portends very poor clinical outcomes, with a median survival time of 1.5 to 2 years. Currently, there is no tool to assess the risk of clinical worsening in patients with ILD-PH. Our aim was to derive a simple and practical risk calculator that could be used to predict risk of clinical worsening in patients with ILD-PH.
The INCREASE study was a 16-week study that evaluated inhaled treprostinil in patients with ILD-PH. Baseline data from patients who were randomized to the placebo arm (n=163) and thus untreated with any approved pulmonary artery vasodilators were used to derive a risk calculator. The endpoint of interest was the time to clinical worsening. Stepwise regression, Harrell's c-index, and clinician input were used to derive 2 multivariable Cox PH models from a set of candidate variables. The models were then simplified by applying a point-scoring system to the predictors and refitting with total point score as the covariate. Total point scores were grouped into 3 risk strata (lower, intermediate, and higher).
Two versions of a risk calculator were derived. The first was a non-invasive risk calculator which included NT-proBNP and FVC%/DLCO%, and a second adds cardiac index, an invasive parameter, to the above two parameters. For the total point score models, the estimated c-indices were 0.703 (95% CI: 0.635, 0.783) and 0.683 (95% CI: 0.612, 0.761) for the invasive and non-invasive model, respectively.
These two risk calculators provide a simple way to risk stratify ILD-PH patients with clinically useful discrimination. The calculators are easy to employ in clinical practice, since they utilize assessments commonly collected in the care of patients with ILD-PH. Moreover, the calculators can provide clinicians with important prognostic information which can be used to reinforce the benefits of therapy. The risk calculators may also find utility as part of the composite allocation score of ILD-PH patients listed for lung transplant. Future research in this area could include incorporating longer-term outcomes as well as validating the risk models in a separate patient population.
间质性肺疾病所致肺动脉高压（ILD-PH）的临床预后非常差，中位生存时间为1.5至2年。目前，尚无工具可评估ILD-PH患者临床恶化的风险。我们的目的是得出一个简单实用的风险计算器，用于预测ILD-PH患者临床恶化的风险。
INCREASE研究是一项为期16周的研究，评估吸入性曲前列尼尔治疗ILD-PH患者的效果。将随机分配至安慰剂组（n = 163）且未接受任何已批准的肺动脉血管扩张剂治疗的患者的基线数据用于得出风险计算器。感兴趣的终点是临床恶化时间。采用逐步回归、Harrell c指数和临床医生的意见，从一组候选变量中得出2个多变量Cox PH模型。然后通过对预测因子应用评分系统并以总分作为协变量重新拟合来简化模型。总分分为3个风险分层（低、中、高）。
得出了两个版本的风险计算器。第一个是无创风险计算器（包括NT-proBNP和FVC%/DLCO%），第二个在上述两个参数的基础上增加了有创参数心脏指数。对于总分模型，有创模型和无创模型的估计c指数分别为0.703（95%CI：0.635，0.783）和0.683（95%CI：0.612，0.761）。
这两个风险计算器提供了一种简单的方法对ILD-PH患者进行风险分层，具有临床实用的鉴别能力。这些计算器在临床实践中易于使用，因为它们利用了ILD-PH患者护理中通常收集的评估数据。此外，这些计算器可以为临床医生提供重要的预后信息，可用于强化治疗的益处。风险计算器还可能作为列入肺移植名单的ILD-PH患者综合分配评分的一部分发挥作用。该领域未来的研究可能包括纳入长期结局以及在另一独立患者群体中验证风险模型。
