Using patient-reported symptoms of dyspnea for screening reduced respiratory function in patients with motor neuron diseases

Journal of Neurology https://doi.org/10.1007/s00415-020-10003-5 ORIGINAL COMMUNICATION Using patient‑reported symptoms of dyspnea for screening reduced respiratory function in patients with motor neuron diseases Jochem Helleman1,2 · Esther T. Kruitwagen‑van Reenen1,2 · J. Bakers1 · Willeke J. Kruithof1 · Annerieke C. van Groenestijn4 · Rineke J. H. Jaspers Focks5 · Arthur de Grund6 · Leonard H. van den Berg3 · Johanna M. A. Visser‑Meily1,2 · Anita Beelen1,2 Received: 27 March 2020 / Revised: 10 June 2020 / Accepted: 16 June 2020 © The Author(s) 2020 Abstract Background Poor monitoring of respiratory function may lead to late initiation of non-invasive ventilation (NIV) in patients with motor neuron diseases (MND). Monitoring could be improved by remotely assessing hypoventilation symptoms between clinic visits. We aimed to determine which patient-reported hypoventilation symptoms are best for screening reduced respiratory function in patients with MND, and compared them to the respiratory domain of the amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). Methods This prospective multi-center study included 100 patients with MND, who were able to perform a supine vital capacity test. Reduced respiratory function was defined as a predicted supine vital capacity ≤ 80%. We developed a 14-item hypoventilation symptom questionnaire (HYSQ) based on guidelines, expert opinion and think-aloud interviews with patients. Symptoms of the HYSQ were related to dyspnea, sleep quality, sleepiness/fatigue and pneumonia. The diagnostic performances of these symptoms and the ALSFRS-R respiratory domain were determined from the receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, specificity, predictive values and accuracy. Results Dyspnea-related symptoms (dyspnea while eating/talking, while lying flat and during light activity) were combined into the MND Dyspnea Scale (MND-DS). ROC curves showed that the MND-DS had the best diagnostic performance, with the highest AUC = 0.72, sensitivity = 75% and accuracy = 71%. Sleep-quality symptoms, sleepiness/fatigue-related symptoms and the ALSFRS-R respiratory domain showed weak diagnostic performance. Conclusion The diagnostic performance of the MND-DS was better than the respiratory domain of the ALSFRS-R for screening reduced respiratory function in patients with MND, and is, therefore, the preferred method for (remotely) monitoring respiratory function. Keywords Motor neuron disease · Amyotrophic lateral sclerosis · Dyspnea · Vital capacity · Respiratory function · Patientreported outcome measure Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00415-020-10003-5) contains supplementary material, which is available to authorized users. * Anita Beelen 1 Department of Rehabilitation, Physical Therapy Science and Sports, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands 2 Center of Excellence for Rehabilitation Medicine, UMC Utrecht Brain Center, University Medical Center Utrecht, and De Hoogstraat Rehabilitation, Utrecht, The Netherlands 3 Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands 4 Department of Rehabilitation, Amsterdam UMC, University of Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands 5 Roessingh, Center for Rehabilitation, Enschede, The Netherlands 6 Basalt, Center for Rehabilitation, Den Haag, The Netherlands 13 Vol.:(0123456789) Journal of Neurology Introduction Motor neuron diseases (MND) are rapidly progressive neurodegenerative diseases, which include amyotrophic lateral sclerosis (ALS), progressive muscular atrophy (PMA) and primary lateral sclerosis (PLS). The main cause of death is respiratory failure due to diaphragm weakness [1]. One of the first signs of diaphragm weakness is nocturnal hypoventilation. Prolonged hypoventilation leads to hypercapnia, which causes clinical symptoms, such as sleep disturbances and daytime fatigue [2]. These symptoms may negatively affect patients’ quality of life. Non-invasive ventilation (NIV) is the most effective intervention for improving quality of life and relieving symptoms in patients with MND (2). The effect of NIV on the rate of respiratory decline and survival has been shown to be associated with the timing of NIV initiation [3, 4]. The guidelines for MND specify a number of criteria for the timing of NIV initiation, based on pulmonary function tests, blood gas analysis and respiratory symptoms [5–7]. Despite these guidelines, NIV is often initiated late, which could lead to reduced compliance and worse survival [8]. Literature suggests that poor monitoring of respiratory function as a result of lacking pulmonary function tests, may be one of the causes of late NIV initiation [9–13]. One way to improve the monitoring of respiratory function is by remotely monitoring respiratory symptoms that are indicative of a reduced pulmonary function test score. This approach enables more frequent assessments of respiratory function compared to usual care, may facilitate early detection of respiratory dysfunction and allows patients to stay at home, saving travel time and costs. Unlike performing pulmonary function tests, the remote assessment of respiratory symptoms is simple, not requiring a medical device or skill to complete. Currently, the respiratory domain of the revised amyotrophic lateral sclerosis functional rating scale (ALSFRSR) is commonly used for assessing respiratory symptoms in patients with MND. However, there has been some criticism about the screening value of this domain [14, 15]. For this reason, it would be valuable to know which symptoms are better than the respiratory domain of the ALSFRS-R for screening a reduced pulmonary function test score. In clinical care, the vital capacity (VC) test is the most used pulmonary function test for assessing respiratory function in patients with MND. Knowing which symptoms are best for screening a reduced VC will help healthcare professionals to remotely identify those who may need to be referred to a pulmonologist for comprehensive assessment. We, therefore, developed a hypoventilation symptom questionnaire (HYSQ), based on guidelines, expert opinion and think-aloud interviews with patients, and 13 compared the diagnostic performance of the HYSQ with the respiratory domain of the ALSFRS-R. Methods Hypoventilation symptom questionnaire The patient-reported hypoventilation symptom questionnaire (HYSQ) was developed to standardize the assessment of hypoventilation symptoms. Recent literature has provided evidence that patient-reported outcome measures are feasible and of added value in routine ALS care [16]. A preliminary questionnaire of 19 items was created based on literature, expert opinion and guidelines for management of MND [5, 6]. It assessed the extent to which patients experienced the symptoms (...truncated)