Survival in amyotrophic lateral sclerosis patients on non-invasive ventilation. What can we do more?

Abstract

Poor prognosis in amyotrophic lateral sclerosis (ALS) is primarily caused by the development of acute respiratory failure (ARF). Despite the recent proposal of a scoring system for early prediction of patient survival (1), this remains challenging due to the clinical heterogeneity of the disease. Non-invasive ventilation (NIV) may counterbalance the progression of ARF; however, the optimal strategies for applying NIV, including patient selection and timing, remain controversial (2). On this issue, we read with interest the article by N. Gonzalez Calzada et al., which focused on defining potential survival factors in ALS (3). In a large cohort of ALS patients, the author confirmed that the severity of bulbar involvement and the ALSFRS-R score at the time of NIV initiation strongly predict patient survival. A key topic in assessing patient survival is the definition of survival time as time to death or to tracheostomy. We think that the clinical protocol used by the authors to propose tracheostomy and invasive mechanical ventilation, and the percentage of patients in which it was performed, should be reported and discussed in the letter. We agree with the authors that a better assessment of bulbar involvement, including evaluation of the upper airways, and a careful titration of NIV are necessary to improve the efficacy of the treatment. However, we would like to point out an important unresolved issue, which is how respiratory evaluation should be performed. Respiratory symptoms may be under-perceived and arterial blood gas analysis usually begins to alter only late in the progression of the disease. Authors have considered spirometry with the generally accepted cut-off of forced vital capacity (FVC) of less than 50% of the predicted value as the threshold to start NIV. In spite of this, spirometry remains the reference test to assess overall ventilatory function; in this cohort a valid spirometry was available only for half to onethird of patients with moderate to severe bulbar dysfunction. Thus, this cohort highlights a gap in evaluating respiratory function in patients with advanced disease. If it is true that pulmonary function tests are affected by diaphragmatic dysfunction as shown by a decrease in vital capacity, due to the non-linear relationship between lung volume and muscle force, the decrease in lung volumes occurs relatively late compared to the development of muscle dysfunction. Moreover, spirometry requires patient cooperation and may not be reliable in the presence of facial weakness and mouth leaks during forced manoeuvre, which is frequently the case with ALS patients. Performing the test becomes more challenging in patients with bulbar dysfunction who tend to rapidly progress towards ARF and, thus, would require frequent monitoring. Sleep studies may help show nocturnal desaturation. However, what it is needed is a test focused on measuring respiratory muscles. Ultrasonography is a non-invasive, non-ionizing imaging technique that directly assesses the