Polkey Michael I, Lyall Rebecca A, Yang Ke, Johnson Erin, Leigh P Nigel, Moxham John
1 National Institute for Heath Research Respiratory Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College, London, United Kingdom.
2 Department of Respiratory Medicine, King's College Hospital, London, United Kingdom.
Am J Respir Crit Care Med. 2017 Jan 1;195(1):86-95. doi: 10.1164/rccm.201604-0848OC.
Biomarkers for survival in amyotrophic lateral sclerosis (ALS) would facilitate the development of novel drugs. Although respiratory muscle weakness is a known predictor of poor prognosis, a comprehensive comparison of different tests is lacking.
To compare the predictive power of invasive and noninvasive respiratory muscle strength assessments for survival or ventilator-free survival, up to 3 years.
From a previously published report respiratory muscle strength measurements were available for 78 patients with ALS. Time to death and/or ventilation were ascertained. Receiver operating characteristic analysis was used to determine the cutoff point of each parameter.
Each respiratory muscle strength assessment individually achieved statistical significance for prediction of survival or ventilator-free survival. In multivariate analysis sniff trans-diaphragmatic and esophageal pressure, twitch trans-diaphragmatic pressure (Tw Pdi), age, and maximal static expiratory mouth pressure were significant predictors of ventilation-free survival and Tw Pdi and maximal static expiratory mouth pressure for absolute survival. Although all measures had good specificity, there were differing sensitivities. All cutoff points for the VC were greater than 80% of normal, except for prediction of 3-month outcomes. Sequential data showed a linear decline for direct measures of respiratory muscle strength, whereas VC showed little to no decline until 12 months before death/ventilation.
The most powerful biomarker for mortality stratification was Tw Pdi, but the predictive power of sniff nasal inspiratory pressure was also excellent. A VC within normal range suggested a good prognosis at 3 months but was of little other value.
肌萎缩侧索硬化症（ALS）患者生存的生物标志物将有助于新型药物的研发。尽管呼吸肌无力是预后不良的已知预测指标，但缺乏对不同检测方法的全面比较。
比较有创和无创呼吸肌力量评估对长达3年生存或无呼吸机生存的预测能力。
从之前发表的一份报告中获取了78例ALS患者的呼吸肌力量测量数据。确定了死亡和/或通气时间。采用受试者操作特征分析来确定每个参数的临界值。
每项呼吸肌力量评估单独对生存或无呼吸机生存的预测均具有统计学意义。在多变量分析中，嗅吸跨膈压和食管压、膈肌抽搐压（Tw Pdi）、年龄以及最大静态呼气口腔压是无呼吸机生存的显著预测指标，而Tw Pdi和最大静态呼气口腔压是绝对生存的显著预测指标。尽管所有测量指标都有良好的特异性，但敏感性有所不同。除了预测3个月的结果外，肺活量（VC）的所有临界值均大于正常的80%。连续数据显示呼吸肌力量直接测量值呈线性下降，而VC在死亡/通气前12个月之前几乎没有下降。
用于死亡率分层的最有力生物标志物是Tw Pdi，但嗅吸鼻吸气压力的预测能力也很出色。正常范围内的VC在3个月时提示预后良好，但其他价值不大。
