The development of early progressive hypoventilation affects the natural history of ALS, and time for admitting patients to NPPV represents a crucial dilemma for neurologists and pulmonologists. The use of noninvasive positive pressure ventilation has yet been demonstrated to improve survival in ALS patients [2, 4, 23], although the most useful indicator of chronic respiratory decline and dead risk was previously considered a baseline FVC < 50% [6–8]. Our findings show that ALS patients who receive noninvasive positive pressure ventilation when Forced Vital Capacity at baseline is less than 75% have a significant survival improvement at 1 year, as compared to those, with similar FVC, who refused or can not tolerate NPPV (p = 0.02). In addition, the median rate of FVC decline was slower in survived patients who tolerated NPPV than in patients who were intolerant to NPPV (p < 0.0001). These results are independent by differences in sex, age, BMI, bulbar or spinal onset, pulmonary functions, arterial blood gas analysis, ALSFRS-R questionnaire score, riluzole treatment, and polysomnographic characteristics, including saturation % per minute, total sleep time, and AHI. Recent papers showed contrasting data about disease progression and survival indicators in patients with ALS. While a study established that chronic hypoventilation requiring mechanical ventilation can rapidly occur, in a small number of patients, independently of their initial respiratory function degree (median FVC% 87) [9], a recent paper revealed the FVC value > 75%, as an early positive predictor of survival in a large number (1034) of ALS patients[10]. Very lately, in a randomised controlled trial, Bourke and co-workers showed that application of noninvasive ventilation when orthopnea occurred, associated to reduction of maximal inspiratory pressure < 60% of the predicted, improved survival, as compared to standard care, in ALS patients [24]. Our data, already published as preliminary results [25], are similar to the findings of Lechtzin and colleagues, who admitted ALS patients with FVC < 65% to mechanical ventilation and observed a significant prolongation of survival [26].
Our study provides additional data about the role of sleep disorders, which actively participate to respiratory failure in ALS. Indeed, the respiratory failure may be present in the absence of breathlessness at rest, or orthopnoea [27], while, it has been observed that sleep disturbance appears at an early stage of disease [12], when respiratory muscle weakness is not sufficient to cause daytime orthopnea. Sleep-disordered breathing might be likely the earliest indication of respiratory insufficiency [17]. In addition, in ALS patients with nocturnal insufficiency, NPPV has been demonstrated to correct sleep-disordered breathing, enhancing quality of life[16].
This study supports the hypothesis that NPPV should be immediately prescribed to ALS patients with mild respiratory dysfunction (FVC < 75%) and polysomnographic signs of nocturnal hypoventilation, for at least 4 hours per day, in order to delay the rapid progression toward chronic respiratory failure. In particular, NPPV treatment significantly decreased the mortality rate of ALS patients with FVC < 75%, as well as the median FVC% rate decline, resulting much slower when compared to the slope of vital capacity of ALS patients with FVC < 50%, treated with 4 hours per day with bi-level intermittent positive pressure, as earlier reported [23].
Although in the present study, the small number of patients treated with noninvasive mechanical ventilation can not give significance for a definitive conclusion, our findings encourage the early use of NPPV, in order to extend survival and to reduce the decline of lung volumes and compliance, thus ameliorating the respiratory function and quality of life of these patients.
In conclusion, this preliminary report demonstrates that early treatment with NPPV prolongs survival in ALS patients, indicating for the first time that NPPV should be introduced when FVC drops below 75% and not 50%, as considered standard care for these patients previously, although further multicentric studies must be conducted to well establish it.