Abstract
Background The course of lung function decline in amyotrophic lateral sclerosis (ALS) and the effect of noninvasive positive-pressure ventilation (NIPPV) on that decline are uncertain. We sought to model lung function decline, determine when NIPPV is initiated along that course, and assess its impact on the course of decline.
Methods An observed sigmoid pattern of forced vital capacity decline was reproduced with a four-parameter nonlinear mixed-effects logistic model.
Results Analyses were performed on 507 patients overall and in 353 patients for whom a determination of adherence to NIPPV was ascertained. A sigmoid bi-asymptotic model provided a statistical fit of the data and showed a period of stable vital capacity, followed by an accelerated decline, an inflection point, then a slowing in decline to a plateau. By the time NIPPV was initiated in accordance with reimbursement guidelines, vital capacity had declined by ≥85% of the total range. Nearly half of the total loss of vital capacity occurred over 6.2 months centred at an inflection point occurring 17 months after disease onset and 5.2 months before initiation of NIPPV at a vital capacity of about 60%. Fewer bulbar symptoms and a faster rate of decline of lung function predicted adherence to NIPPV, but the intervention had no impact on final vital capacity.
Conclusions In patients with ALS, vital capacity decline is rapid but slows after an inflection point regardless of NIPPV. Initiating NIPPV along reimbursement guidelines occurs after ≥85% of vital capacity loss has already occurred.
Abstract
In patients with amyotrophic lateral sclerosis, vital capacity decline is rapid but slows after an inflection point regardless of NIPPV. Initiation of NIPPV according to guidelines occurs when >85% of vital capacity loss has already occurred. http://bit.ly/2JOiEZG
Footnotes
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Author contributions: T.S. Panchabhai, E. Mireles Cabodevila and E.P. Pioro contributed substantially to the study design, data collection, interpretation of analysis and writing of the manuscript. X. Wang and X. Han contributed substantially to the statistical analysis, interpretation of the analysis and writing the corresponding sections of the manuscript. L.S. Aboussouan contributed substantially to the study design, data collection, analysis of results, interpretation of analysis and the manuscript writing, had full access to all of the data in the study, and takes responsibility for the integrity of the data.
Conflict of interest: T.S. Panchabhai has nothing to disclose.
Conflict of interest: E. Mireles Cabodevila reports book royalties from Bartlett and Jones Publishers, honoraria for a book chapter and questions from the American College of Physicians and honoraria for lectures from Dong'e People's Hospital, China, outside the submitted work.
Conflict of interest: E.P. Pioro reports grants from the NIH/CDC, the ALS Association and Iron Horse Diagnostics, Inc., and personal fees from Avanir Pharmaceuticals, Inc., Cytokinetics, Inc., ITF Pharma, Inc., and MT Pharma America, Inc., outside the submitted work.
Conflict of interest: X. Wang has nothing to disclose.
Conflict of interest: X. Han has nothing to disclose.
Conflict of interest: L.S. Aboussouan reports personal fees from UpToDate Wolters Kluwer outside the submitted work.
- Received March 25, 2019.
- Accepted July 20, 2019.
- Copyright ©ERS 2019
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.