This was a retrospective study to clarify if we could use the respiratory rate and thoracic movement as preliminary clinical signs for the development of significant respiratory insufficiency in ALS patients. The main finding in our study was that patients who received NIV within six months of the diagnosis of ALS had higher respiratory rates and smaller thoracic movement at diagnosis compared with patients who received NIV later.
Among healthy subjects, a respiratory rate under 15 BPM allows a physiologically optimal level of work of breathing [18, 19]. In advanced ALS, thoracic compliance is usually decreased, resulting in decreased tidal volume , increased respiratory rate and work of breathing [18, 19]. NIV can help patients compensate for the decreased thoracic compliance and thus decrease the respiratory frequency and the work of breathing [20, 21]. Although the retrospective study design and small number of patients did not allow the calculation of positive and negative predictive values and cut-off values for respiratory rate and thoracic movement in the assessment of respiratory insufficiency in ALS, it appears that NIV was initiated within six months from diagnosis for those patients who had a respiratory rate at least of 20 BPM at the moment of diagnosis.
Another result of interest was that we failed to show any difference in dyspnoea between the two study groups (Table 2). The patients scored only mild symptoms of dyspnoea and morning headaches at the moment of diagnosis in both groups. The same was true for sleep disturbances and daytime sleepiness. In a previous study with 36 ALS patients, respiratory complaints did not occur until the vital capacity, MIP, or MEP were severely impaired . In that study, the strongest correlation with dyspnoea was a decline in vital capacity. The authors suggested that a small reduction in vital capacity does not cause any symptoms except in heavy exercise. The patients decrease their physical activity because of skeletal muscle weakness, and thus may not feel dyspnoeic during their daily activities unless more strenuous exercise is required. Our results are similar as our patients complained of very little dyspnoea at the time of diagnosis. Nevertheless, as our patients were aware of the possibility of initiating NIV, they might have been reluctant to disclose the severity of their symptoms and intentionally underestimated their response in our VAS query. A larger sample size might show a difference in dyspnoea.
FVC and FEV 1 are commonly used to assess pulmonary function in lung diseases  and in ALS patients. Previously, FVC, SNP, MIP and MEP were determined in 16 ALS patients monthly over a period of 18 ± 10 months . The SNP, MIP and MEP were severely reduced even though the FVC remained normal. In addition, the measurement of MIP and MEP was difficult in these advanced ALS patients because they had difficulties tightly holding the mouthpiece of the recording device. This led to air leaks and reduced the values of MIP and MEP. A reduced SNP of under 40 cmH2O has been suggested as the most sensitive and easiest test to perform in ALS patients [9, 10, 24]. However, although we found that the SNP was severely reduced in both groups, only those with an increased respiratory rate in Group 1 were ready to start NIV (Table 2).
Our study has limitations. First, the retrospective design compared the respiratory measurements between two different patient groups at one single time point. Thus, we cannot draw definitive conclusions for the cut-off values for respiratory rate or thoracic movement to indicate the need for NIV. Further studies are needed. In addition, the only inclusion criterion was the respiratory assessment within three months from diagnosis. Thus, we did not evaluate other pulmonary or heart diseases which might have biased the results. Second, the ideal is a randomized prospective trial in which the initiation of NIV is blinded and the subjects are observed from an asymptomatic stage until severe hypoventilation occurs. However, because NIV is established in palliative care in ALS [9, 10], ethical aspects have to be considered in randomized study designs, especially if the initiation of NIV is somehow blinded. Moreover, the diagnosis of ALS is often delayed and the patients often have reduced ventilation capacity at the time of diagnosis [22, 25]. We saw this in our patients as the median time from the first symptoms until diagnosis ranged from 11 to 13 months (Table 1). During this time, the patients’ symptoms were evaluated at the primary care level or not at all. Thus, when we met the patients, half already showed moderately to severely reduced FVC (60%), SNP (24 cmH2O), MIP (29 cmH2O), or MEP (41 cmH2O) and NIV was recommended based on a single measurement without follow-up. Third, we dealt with severely ill patients, whose NIV initiation was based on both the clinical measurements and the patient’s own desire. The fact that NIV was based on the patient’s own desire may have biased the answers in the hypoventilation questionnaire if the patients reported no or only mild symptoms of hypoventilation even if they had severely reduced respiratory measurements.