This is a summary of the presentation on novel methods of ambulatory physiologic monitoring in patients with neuromuscular disease, presented as part of the program on pulmonary management of pediatric patients with neuromuscular disorders at the 30th annual Carrell-Krusen Neuromuscular Symposium on February 20, 2008.
Recently, consensus guidelines were published for the respiratory care of patients with Duchenne muscular dystrophy and spinal muscular atrophy. These were practice-based guidelines, because the ability to generate evidence-based guidelines is limited because of the relatively rare nature of these diseases. The respiratory care guidelines provide precise recommendations for the timing and extent of respiratory examinations and care, from initial diagnosis through end-of-life directives. The process that produced these guidelines and the recent anesthesia and sedation guidelines, reviewed by Birnkrant in this conference, serves as a model for developing consensus practice parameters thataddress the multisystem involvement seen for many of the muscular dystrophies.1–5
In the context of continuous quality improvement, they provided an AIM statement and a clear guide to muscle disorders clinics of the role of pediatric pulmonary evaluation and management (Table 1www.pediatrics.org/content/vol123/Supplement_4).
The welcome shift from hospital ventilation to home ventilation, the emergence of technologic and biomedical advancements, and maximizing the benefits of therapies through appropriate timing have brought about a search for pulmonary outcome measures. Respiratory disease accounts for ∼80% of the mortalities of patients with Duchenne muscular dystrophy. Our current measures consist of spirometry (forced vital capacity, forced expiratory volume at 1 second, oxygen saturation awake and asleep, and peak inspiratory and peak expiratory pressure) and rates of pneumonia, hospitalization, and respiratory failure.6–8 The routine evaluation of sleep has been hindered by the expense associated with technician-monitored studies geared at screening for the justification of expensive home therapies for adults with obstructive sleep apnea syndrome, lack of pediatric sleep laboratories (with the insufficiency made more difficult by the increased recommendations for evaluation of primary snoring with inadequate infrastructure in place), variability in interpretation, and inadequately developed standards of “normal.”9 Home sleep monitoring has been hindered by the frequent need for restudy, which has resulted in the denial of development of a payment structure to foster a business case for innovation.10 The reliance by private payers on Center for Medicare and Medicaid Services approval led to a reevaluation being released in March 2008, spurred by the deluge of obesity-related obstructive sleep apnea in adults with inadequate infrastructure for evaluation before initiation of home continuous positive airway pressure intervention.
In the face of these developments we have sought to adapt and develop home monitoring systems to aid the clinician in assessment of sleep-disordered breathing and relief of sleep deprivation through initiation of nocturnal noninvasive ventilation (NNIV). We have also sought to assess what we have termed “awake disordered breathing” in which we can establish the epidemiology and course of disease through upright and supine ventilation strategies measured with Konno-Mead loops, 24-hour respiratory rate, 24-hour heart rate, level of activity defined with accelerometers, and relation of heart and respiratory rate to moderate-to-high levels of activity. In addition, we have studied what we have termed “life disordered breathing” associated with scoliosis surgery, gastrostomy tube placement, respiratory infection, gastroesophageal reflux, and the disappearance of adequate cough associated with suboptimal physiologic breathing patterns. We have sought to find a diagnostic and therapeutic strategy focused on prevention of progressive respiratory infection through novel methods of home monitoring, assessment of the pulmonary effects of “silent reflux” on the lungs, and assessment of the beneficial effects of mechanical methods of respiratory secretion clearance.
The best available form factor, algorithms, and collection devices for the proposed applications seemed to include the Nonin wrist pulse oximeter with nVision software (Nonin Medical, Plymouth, MN) and the VivoMetrics LifeShirt (VivoMetrics, Ventura, CA), which incorporated respiratory inductive plethysmography. The advantages of respiratory inductive plethysmography are shown in Table 2 (www.pediatrics.org/content/vol123/Supplement_4). In our initial survey, the use of the mechanical insufflator/exsufflator (MI-E), high-frequency chest wall oscillation (HFCWO), and NNIV support were assessed. Data recording used a light-weight respiratory inductive plethysmography device in the home with separate day and sleep algorithm, wrist and wireless oximeter with recording capability, and handheld spirometer. The initial participants were 5 male patients with neuromuscular disease (NMD) who were followed in a muscle disorders clinic and pediatric pulmonary center and were recruited for this pilot study. They were between 8 and 22 years of age and had been introduced to the use of HFCWO, an MI-E device, and NNIV within the previous 18 months. Patients and caretakers reported productive cough, sleep disorders, and anxiety during clinic and home visits. No patient had a tracheostomy or gastrostomy tube. The VivoLogic software (VivoMetrics) collected data with simultaneous screens allowing visual inspection of tidal volume, rib cage movement, abdominal cage movement, electrocardiogram, accelerometers for upright, supine, and lateral positioning and intensity of movement, and oxygen saturation. Figure 1 (www.pediatrics.org/content/vol123/Supplement_4), obtained during NNIV, demonstrates poor synchronization with the ventilator; Fig 2 (www.pediatrics.org/content/vol123/Supplement_4) shows the subsequent synchrony.
On the basis of these initial findings, we undertook further study to establish the utility of the LifeShirt in home sleep testing, with attention to the impact of daily use of HFCWO. As a preliminary assessment, this was a single-site study performed in the home setting. All patients resided within a 1-hour drive from the Pediatric Diagnostic Center in Ventura, California, and they resided in rural agricultural, urban, and suburban settings.
The protocol was reviewed by the institutional review board of the Ventura County Medical Center. All patients gave written informed consent or assent before any study-related procedures were performed. Patients with NMD that affected the musculature of the oropharynx and the upper airway or the respiratory musculature who were aged ≥7 years were identified from the pediatric pulmonary clinic of the Pediatric Diagnostic Center. Patients were required to attend a clinic visit to complete the case-report form including medical history, treatments for NMD, and adverse effects of treatment. This was a single-site study.
Eight patients with NMD and a history of restrictive lung disease were enrolled in a 90-day trial of HFCWO therapy. Demographic information including diagnosis, gender, age at initiation of MI-E, HFCWO, and NNIV, use of antireflux medications and/or presence of fundoplication, and need for mechanical ventilatory support were recorded (see Table 3www.pediatrics.org/content/vol123/Supplement_4). In addition, pulmonary function data, including the most recent spirometry results and measurements of respiratory muscle strength before the initiation of therapies (HFCWO, MI-E, and NNIV), were recorded. Data then were collected to determine the safety, tolerance, and efficacy of the LifeShirt in this patient population. Safety was assessed by noting the occurrence of pulmonary, cardiac, or gastrointestinal complications (eg, pneumothorax, pulmonary hemorrhage, cardiac dysrhythmias, nausea, or vomiting) associated with use of the device. The use of the LifeShirt was considered to be well tolerated if the patient used the device at the prescribed frequency. The patient was classified as intolerant of the device if the patient or caregiver expressed the desire to discontinue use of the LifeShirt for any reason.
Patients were fitted with the wearable LifeShirt system (Fig 3www.pediatrics.org/content/vol123/Supplement_4), which incorporates respiratory inductance plethysmography for the noninvasive measurement of volume and timing ventilatory variables. The system also incorporates a single-channel electrocardiogram and a centrally located, 3-axis accelerometer. Data were processed and stored on a compact flash card that was housed within the recorder unit. Patients were fitted at home with a single-lead electroencephalogram (EEG) attached through a serial expansion module at baseline and 30, 60, and 90 days. The subjects slept at home wearing the 8-oz, 260-g shirt that captures ventilation, electrocardiography, pulse oxygen saturation, posture, and EEG data. Sleep studies were scored by certified sleep technicians using VivoLogic software (R and K standard criteria), and the studies underwent independent certified sleep technician reading by using a sleep-scoring protocol incorporating respiratory, cardiac, and oximetry data. All studies were reviewed by the principal investigator.
A registered respiratory therapist trained the patients and caregivers in the use of the LifeShirt and in HFCWO therapy with the Vest airway-clearance system (model 104; Hill-Rom, St Paul, MN). The target Vest settings included a frequency of 12 Hz and a pressure setting of 4, adjusted for patient comfort. The subject was monitored throughout the therapy. The subject and caregiver were instructed to interrupt therapy to allow the subject to cough or to clear secretions, if required, and to clear secretions through coughing or suctioning at the completion of therapy. Therapy was performed 3 times per day for 12 minutes per treatment.
Clinical end points included type, frequency, and time distribution of sleep-disordered breathing events such as apneas, hypopneas, arousals, periods of oxygen desaturation, measures of sleep time, stages of sleep, accelerometry, and cardiac and respiratory data.
Subjects were studied at baseline and 30, 60, and 90 days after the initiation of airway-clearance therapy with HFCWO per protocol. Evaluations were performed at 1, 2, and 3 months for pulse oximetry, spirometry, negative inspiratory flow force, and 24-hour wake and sleep continuous ambulatory physiologic monitoring. A central-lead sleep EEG was obtained and integrated with physiologic measures of rapid eye movement (REM) and non-REM sleep.
Subject 5 was withdrawn after 60 days because of reluctance to follow the measurement and intervention protocol, and subject 8 withdrew after 30 days because of anxiety. Both subjects had excessive sweating at night, which led to difficulties in maintaining the EEG leads. Each individual served as his or her own control.
Median respiratory rate over 24 hours improved by 10% within 1 month, and improvement was sustained at the 3-month exit evaluation. Sleep latency and sleep-organization parameters of slow-wave sleep, low delta, theta, and alpha activity, showed continuous improvement over the 90-day trial. One patient had an aspiration-related pneumonia during the 90-day study, with a return to improvement from baseline after resolution of the pulmonary exacerbation.
It is my hope that, with a source of funding for home sleep testing, the expanded data set available to the NMD clinician will become part of the standard of care in assessing epidemiology, progression of disease, and the impact of current and new therapies. A proposed outline for assessment and intervention is shown in Table 4 (www.pediatrics.org/content/vol123/Supplement_4).
- Accepted January 5, 2009.
- Address correspondence to Chris Landon, MD, FAAP, FCCP, CMD, Pediatric Diagnostic Center, 3160 Loma Vista Road, Ventura, CA 93003. E-mail:
Dr Landon serves on an advisory board for Hill-Rom Services Inc.
All tables and figures for this article appear online at: www.pediatrics.org/content/vol123/Supplement_4
- Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol.2007;22 (8):1027– 1047
- ↵Birnkrant DJ. The assessment and management of the respiratory complications of pediatric neuromuscular diseases. Clin Pediatr (Phila).2002;41 (5):301– 308
- ↵Flemons WW, Littner MR, Rowley JA, et al. Home diagnosis of sleep apnea: a systematic review of the literature—an evidence review cosponsored by the American Academy of Sleep Medicine, the American College of Chest Physicians, and the American Thoracic Society. Chest.2003;124 (4):1543– 1579
- Copyright © 2009 by the American Academy of Pediatrics