Supplementary Material for: Long-Term Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease: Association between Clinical Phenotypes and Survival

Background: Long-term noninvasive ventilation (LTNIV) is widely used in patients with chronic hypercapnic respiratory failure (CHRF) related to COPD. Prognosis of these patients is however poor and heterogenous. Research Question: In COPD patients under LTNIV for CHRF, is it possible to identify specific phenotypes which are predictive of probability of pursuing NIV and survival? Study Design and Methods: A latent class analysis was performed in a COPD population under LTNIV included in a comprehensive database of patients in the Geneva Lake area, to determine clinically relevant phenotypes. The observation period of this subgroup of COPD was extended to allow assessment of survival and/or pursuit of NIV for at least 2 years after inclusion. A logistic regression was conducted to generate an equation accurately attributing an individual patient to a defined phenotype. The identified phenotypes were compared on a series of relevant variables, as well as for probability of pursuing NIV or survival. A competitive risk analysis allowed to distinguish death from other causes of cessation of NIV. Results: Two phenotypes were identified: a “respiratory COPD” profile with very severe airway obstruction, a low or normal body mass index, and a low prevalence of comorbidities and a “systemic COPD” profile of obese COPDs with moderate airway obstruction and a high rate of cardiovascular and metabolic comorbidities. The logistic regression correctly classified 95.7% of patients studied. Probability of pursuing NIV and survival were significantly related to these phenotypes, with a poorer prognosis for “respiratory COPD.” Probability of death 5 years after implementing NIV was 22.3% (95% CI: 15.4–32.2) for “systemic COPD” versus 47.2% (37.4–59.6) for “respiratory COPD” (p = 0.001). Conclusion: The two distinct phenotypes of COPD under LTNIV for CHRF identified appear to be strongly related to prognosis and require further validation in other cohort studies.

背景：长期无创通气（long-term noninvasive ventilation, LTNIV）被广泛应用于慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease, COPD）相关慢性高碳酸血症性呼吸衰竭（chronic hypercapnic respiratory failure, CHRF）患者的治疗。然而此类患者的预后不佳且存在异质性。研究问题：针对接受LTNIV治疗的COPD合并CHRF患者，能否识别出可预测其持续NIV治疗概率及生存概率的特定表型？研究设计与方法：本研究对纳入日内瓦湖地区患者综合数据库的、接受LTNIV治疗的COPD人群开展潜在类别分析（latent class analysis），以确定具有临床意义的表型。延长该COPD亚组患者的观察周期，使其至少能被随访至入组后2年，以评估其生存情况及/或持续NIV治疗的情况。通过逻辑回归（logistic regression）分析构建可准确将个体患者归类至既定表型的预测方程。对已识别的表型，就一系列相关临床变量、持续NIV治疗概率及生存情况进行对比分析。采用竞争风险分析（competitive risk analysis）区分死亡与其他导致NIV治疗终止的病因。结果：本研究共识别出两种表型：其一为“呼吸型COPD”表型，表现为极重度气道阻塞、体质量指数偏低或正常、合并症患病率较低；其二为“全身型COPD”表型，表现为肥胖型COPD、中度气道阻塞，且心血管与代谢类合并症发生率较高。逻辑回归模型对受试患者的分类准确率达95.7%。持续NIV治疗概率与生存情况均与上述表型显著相关，“呼吸型COPD”表型患者的预后更差。启动NIV治疗后5年的死亡率，“全身型COPD”表型为22.3%（95%置信区间：15.4~32.2），“呼吸型COPD”表型为47.2%（37.4~59.6）（p=0.001）。结论：本研究识别出的、接受LTNIV治疗的CHRF相关COPD患者的两种独特表型，似乎与患者预后密切相关，需在其他队列研究中进一步验证其有效性。