Respiratory Muscle Strength as a Predictive Biomarker for Survival in Amyotrophic Lateral Sclerosis.
RATIONALE
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.


OBJECTIVES
To compare the predictive power of invasive and noninvasive respiratory muscle strength assessments for survival or ventilator-free survival, up to 3 years.


METHODS
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.


MEASUREMENTS AND MAIN RESULTS
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.


CONCLUSIONS
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.
['Polkey|Michael I|MI|', 'Lyall|Rebecca A|RA|', 'Yang|Ke|K|', 'Johnson|Erin|E|', 'Leigh|P Nigel|PN|', 'Moxham|John|J|']
D000690:Amyotrophic Lateral Sclerosis D015415:Biomarkers D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D053580:Muscle Strength D011379:Prognosis D016016:Proportional Hazards Models D012372:ROC Curve D012132:Respiratory Muscles
survival amyotrophic lateral sclerosis sniff nasal inspiratory pressure diaphragm maximal inspiratory pressure