Pattern of lung function decline in patients with amyotrophic lateral sclerosis: Implications for timing of noninvasive ventilation

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.