Utilization of Pulmonary Clearance Devices in Amyotrophic Lateral Sclerosis
Phase: NA
Conditions: Amyotrophic Lateral Sclerosis
Sponsor: Cedars-Sinai Medical Center

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Pulmonary Clearance Devices in ALS 
Utilization of Pulmonary Clearance Devices in Amyotrophic Lateral Sclerosis 
Background: 
ALS: 
Amyotrophic lateral sclerosis (ALS) is a progressive degenerative neuromuscular disease with no known 
cause or cure. ALS causes weakness in many muscles in the body, including the muscles involved in 
respiration and swallowing. Weakness in these muscles can cause respiratory problems, making 
breathing more difficult. Respiratory problems are among the most serious symptoms of ALS and should 
not be ignored. Shortness of breath may be the first respiratory symptom that some patients 
experience. Patients may notice shortness of breath when engaged in vigorous physical activities like 
running, exercising, walking long distances, or climbing stairs. They may also have difficulty breathing at 
night which can interfere with sleep and cause fatigue or morning headaches. Patients often find 
themselves waking frequently throughout the night. Difficulty breathing at night occurs when the chest 
muscles relax too much to assist with breathing during the dreaming phase of sleep. 
Problems with swallowing can also interfere with breathing. When the swallowing muscles are 
weakened, food and saliva are more easily inhaled (aspirated) into the windpipe which leads to choking. 
Aspiration of food or saliva can also introduce bacteria into the lungs, increasing the risk of respiratory 
infection and pneumonia.  
High Frequency Chest Compression Devices (HFCC): 
Disease conditions, such as cystic fibrosis (CF), chronic bronchitis, bronchiectasis, and immotile cilia 
syndrome, can lead to abnormal airway clearance which is a source of increased sputum production, 
often purulent or tenacious.  The underlying pathology of the decline in mucociliary clearance varies 
with the given disease.  Chest physical therapy (CPT), which is also referred to as percussion and 
postural drainage (P/PD), is the standard treatment program that attempts to compensate for abnormal 
airway clearance.  By improving the clearance of lung secretions, which may often be tenacious, 
complications of infection, atelectasis, and hyperinflation are reduced, and the decline in respiratory 
function is slowed in these types of diseases.  Depending on the severity of the disease and any 
presence of infection, CPT sessions can be from 1-3 times per day for 20-30 minutes.  A physical 
therapist or another trained adult in the home, typically a parent if the affected individual is a child, may 
administer CPT.  The need for regular therapy can be particularly burdensome for adolescents or adults 
who wish to lead independent lifestyles.  CPT is time consuming and requires the assistance of a skilled 
caregiver. 
Different types of airway clearance techniques and devices have been developed in an attempt to 
address the problem of convenience and compliance with CPT.  Airway clearance techniques or systems 
have been most often associated and studied in the treatment of CF.  Of these techniques, daily P/PD 
and HFCC devices, such as the Vest™ Airway Clearance System and Incourage Airway Clearance System, 

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are passive techniques that do not require the participation of the affected person.  Although there have 
been a range of studies on these alternatives, there remains a lack of scientific evidence to support any 
secretion clearance technique over another.   
HFCC devices have shown improved lung function and sputum clearance in many who are afflicted with 
CF with few adverse effects.  However, the therapy has not been shown to be superior to conventional 
CPT in short-term studies, and its impact on long-term prognosis is unknown.  In addition, it is not clear 
from the clinical studies which subjects would derive the most benefit from this therapy, or at what time 
during the course of the disease HFCC should be initiated.  Interpretations of the data derived from the 
clinical trials of HFCC for CF are complicated by issues in study design, small sample sizes, inadequate 
length of follow-up, heterogeneity of study subjects, and lack of control for confounding variables, such 
as concurrent treatment, disease severity, respiratory functions variability, and age.  Moreover, there 
remain questions of the validity and reliability of outcomes measures, such as sputum weight and 
respiratory function indexes for the determination of therapeutic efficacy. 
The FDA cleared the original Vest Airway clearance system in 1998.  The currently approved indications 
are "To promote airway clearance or improve bronchial drainage by enhancing mobilization of bronchial 
secretions where external manipulation of the thorax is the physician's choice of treatment.  The 
indications typically follow the Clinical Practice Guideline published by the American Association for 
Respiratory Care (AARC) in 1991.  In addition, the device is also indicated for the purpose of collecting 
mucus for diagnostic evaluation."  Several earlier versions included the THAIRapy®Vest System and the 
ABI Vest®Airway Clearance System, amongst others (Advanced Respiratory, Inc. St. Paul, MN). A similar 
device, the Medpulse Respiratory Vest System (Electromed, Inc., Minnetonka, MN) also obtained FDA 
clearance through the 510(k) approval process (1999), and others have also been cleared by the FDA.  In 
2007, a similar device, the FREQUENCER™ (DYMEDSO, Inc., Boisbriand, Quebec Canada) obtained FDA 
clearance as substantially equivalent to the THAIRapy device.  It produces sound wave stimulation to 
oscillate and loosen mucous secretions in the chest. 
Cough Assist: 
Normal clearance of airways rests on three (3) basic components: a patent airway, mucociliary 
clearance, and an adequate cough. Patients with spinal cord injuries or a variety of neuromuscular 
diseases or chest wall deformities may have impaired cough responses, which may lead to respiratory 
failure during respiratory tract infections due to the inability to clear the profuse respiratory secretions. 
Chest wall deformities may include kyphosis, scoliosis, or lordosis, while neuromuscular diseases include 
muscular dystrophy, poliomyelitis, spinal muscle atrophy, myasthenia gravis, amyotrophic lateral 
sclerosis, or cerebral palsy. The great majority of neuromuscular disease morbidity and mortality is 
related to respiratory muscle weakness, and the vast majority of episodes of respiratory failure occur 
during otherwise benign episodes of respiratory tract infections. Chest infections may result in repeated 
episodes of pneumonia, repeated hospitalizations, and finally, in tracheostomy with mechanical 
ventilation. The normal cough consists of 4 stages: 1) A precough inspiration to about 85% of total lung 
capacity; 2) Followed by closure of the glottis; 3) Development of thoracoabdominal pressure sufficient 

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to generate an explosive decompression of the chest at glottic opening; and 4) Opening of the glottis 
with exsufflation. The peak cough expiratory force typically exceeds 5L/sec, with total expiratory volume 
of about 2.3L. In general, an impaired ability to cough has been defined as a peak cough expiratory flow 
of less than 2-3L per second. A variety of techniques have been developed to enhance each of these 
stages. For example, manually assisted coughing is designed to enhance exsufflation and consists of 
abdominal pressure delivered by a caregiver timed with the glottic opening. Manual assisted coughing 
may be offered to patients with a peak cough expiratory flow of less than 5L/ sec, but is less effective in 
the presence of scoliosis or obesity or after meals. Glossopharyngeal breathing is a technique to 
increase inspiratory flow and is commonly used in patients with a decreased vital capacity due to 
inspiratory muscle paralysis. This breathing technique involves the use of the tongue and pharyngeal 
muscles to add to an inspiratory effort by projecting (gulping) boluses of air past the glottis. Mechanical 
insufflation-exsufflation is designed to deliver alternative cycles of positive and negative pressure. One 
such device, the CoughAssist, is a portable electric device which utilizes a blower and valve to alternately 
apply a positive and then a negative pressure to a patient’s airway in order to assist the patient in 
clearing retained broncho pulmonary secretions. Air is delivered to and from the patient via a breathing 
circuit incorporating a flexible tube, a bacterial filter and either a facemask, a mouthpiece or an adapter 
to a tracheostomy or endotracheal tube. Physicians, respiratory therapists, nurses, and trained family 
members may administer this therapy. Mechanical insufflation (MI-E) has been used in a variety of 
patient populations as an adjunct to noninvasive ventilation using intermittent positive pulmonary 
ventilation (IPPV) delivered nasally or orally. For example, many patients with neuromuscular disease or 
chest wall deformities with progressive ventilator failure will use noninvasive IPPV either nocturnally or 
throughout the day, depending on such parameters as vital capacity and oxygenation levels. Patients 
managed at home with noninvasive IPPV may monitor oxygen desaturation levels. A sudden decrease in 
oxygen desaturation may prompt the use of MI-E to eliminate the presumed offending mucus plug. 
Advocates of MI-E state that even patients requiring 24 hour IPPV can be managed noninvasively for 
prolonged periods of time without hospitalization using this technique. In patients with tracheostomies, 
MI-E has been used as an alternative or complement to suctioning. In addition, it is suggested that MI-E 
is more comfortable to the patient than suctioning. MI-E may either be offered on a temporary basis in 
patients with noninvasive IPPV who are suffering from a respiratory tract illness, or may be used on a 
more chronic basis in an attempt to avoid the option of invasive tracheostomy and suctioning. 
 
Objectives: 
Primary Aim 
The primary objective of this pilot study is to determine the potential clinical effect of airway clearance 
devices in patients with ALS over a period of 180 days (25.7 weeks). 
Secondary Aim 

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The secondary aim is to determine the potential effectiveness of HFCC as a stand-alone airway clearance 
therapy as compared to HFCC in conjunction with a Cough Assist Device over a period of 180 days (25.7 
weeks).   
Study Design: 
This 180 day (25.7 weeks) pilot study is designed to evaluate the effectiveness of airway clearance 
devices in adults with ALS. Subjects will be randomized in a 1:1 ratio to one of two treatment groups: 
treatment with an HCFF device alone or treatment with both an HFCC device and a cough assist device.  
This outpatient study includes a screening/baseline visit followed by a 180 day (25.7 weeks) treatment 
period with three scheduled clinic visits (day 30, day 90, day 180). Pulmonary assessments and ALS 
outcome measures will be collected at each visit in addition to quality of life assessments and device 
usage diaries. 
Informed consent will be obtained from all subjects prior to any study procedures, including screening 
and baseline assessments. Institutional standard of care for ALS will be maintained for each subject. 
 Study Population:   
Inclusion criteria  
1. Suspected, possible, probable, Probable (Lab-Supported), or Definite ALS according to El Escorial 
Criteria  
2. Males and females age 18 and above  
3. Novel to airway clearance device use 
4. Forced vital capacity ≤ 75% of predicted 
 
Exclusion criteria  
1. Any contraindication for pulmonary ventilation or perfusion scan including allergy to 
radioisotopes  
2. Any contraindication for use of a pulmonary clearance device  
a. Susceptibility to pneumothorax  
b. Recent (within 30 days) barotrauma  
c. Unstable head or neck injury  
d. Active hemorrhage with hemodynamic instability 
Sample size 
20 male and female subjects aged 18 and older will be randomized into one of two treatment groups in 
a 1:1 randomization ratio (10 subjects per group). 
Intervention  

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After completing the screening and baseline assessments subjects will be randomized. 
Treatment group A –Subjects randomized to group A will be fitted for and issued a HFCC device for 
home use. Subjects will be instructed to use the HFCC device 2-3 times per day for 15-30 minutes each. 
Subjects will be instructed to keep a device usage, concomitant medication, and adverse event diary.  
Treatment group B – Subjects randomized to group B will be fitted for and issued a HFCC device and will 
also be issued a cough assist device. Subjects will be instructed in the use of both devices. The HFCC 
device should be utilized 2-3 times per day for 15-30 minutes each followed by sessions with the cough 
assist until secretions have been cleared. Subjects will be instructed to keep a device usage, concomitant 
medication, and adverse event diary.  
Outcome Measures 
Pulmonary Function Testing - Spirometry is the most common of the pulmonary function tests and 
measures lung function, specifically the measurement of the amount (volume) and/or speed (flow) of air 
that can be inhaled and exhaled.  
FVC – Forced Vital Capacity: the determination of the vital capacity from a maximally forced 
expiratory effort 
 
FEV-1 – Volume of air that has been exhaled at the end of the first second of forced expiration 
MIP/MEP – Maximum Inspiratory Pressure/Maximum Expiratory Pressure: MIP is the pressure 
generated during maximal inspiratory effort against a closed system. MEP is the pressure 
generated during maximal expiratory effort against a closed system 
Diffusion capacity – measures the transfer of gas from the air in the lung to the lung blood 
vessels. 
Chest X-Ray – a projection radiograph of the chest used to diagnose conditions affecting the chest 
Lung Ventilation Scan – a nuclear scanning test commonly used to detect abnormalities in air flow. A 
radioactive tracer gas or mist is inhaled into the lungs. Pictures from the scan indicate areas of the lungs 
that are not receiving enough air or that retain too much air. Areas of the lung that retain too much air 
are brighter spots on the film and areas not receiving enough air are dark. 
Lung Perfusion Scan— a nuclear scanning test commonly used to detect abnormalities in blood flows. A 
radioactive tracer is injected into a vein. Pictures from the scan indicate areas of the lungs that are not 
receiving enough blood or that retain too much blood. Areas of the lung that retain too much blood are 
brighter spots on the film and areas not receiving enough blood are dark.  
McGill Single item quality of life question – Assess the improvement of/ rate of deterioration of the 
subject’s quality of life. 
Follow-up Schedule 

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All subjects regardless of treatment group will undergo the following: 
Screening/Baseline (all procedures to be completed within + 7 days of screening/baseline visit) 
Informed consent 
Physical/Pulmonary Examination 
Medical history review/ Demographics 
Vital signs 
Pulmonary Function Testing 
 
FVC 
 
FEV-1 
 
MIP/MEP 
 
Diffusion capacity 
Chest X-ray 
Lung Ventilation Scan 
Lung Perfusion Scan 
McGill single item QOL question 
Adverse event review 
Concomitant medication review 
Post use survey 
Review usage diary 
Randomization 
 
Equipment Delivery and Instruction visit – After subject has been randomized, the appropriate 
equipment will be ordered and delivered to the patient’s home. Equipment representatives will instruct 
subjects in appropriate use of the equipment.  
 
Visit 1 (30 days ±7 days after baseline- all procedures to be completed within this window) 
Vital signs 
Pulmonary Function Testing 
 
FVC 
 
FEV-1 
 
MIP/MEP 
 
Diffusion capacity 
Chest X-ray 
Lung Ventilation Scan 
Lung Perfusion Scan  
McGill single item QOL question 
Adverse event review 
Concomitant medication review 
Diary usage review 
Post use survey 

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Visit 2 (90 days ±7 days after baseline- all procedures to be completed within this window) 
Vital signs 
Pulmonary Function Testing 
 
FVC 
 
FEV-1 
 
MIP/MEP 
 
Diffusion capacity 
Chest X-ray 
Lung Ventilation Scan 
Lung Perfusion Scan  
McGill single item QOL question 
Adverse event review 
Concomitant medication review 
Diary usage review 
Post use survey 
 
Visit 3 (180 days ±7 days after baseline- all procedures to be completed within this window)/Early 
Termination 
Physical/Pulmonary examination 
Vital signs 
Pulmonary Function Testing 
 
FVC 
 
FEV-1 
 
MIP/MEP 
 
Diffusion capacity 
Chest X-ray 
Lung Ventilation Scan 
Lung Perfusion Scan 
McGill single item QOL question 
Adverse event review 
Concomitant medication review 
Diary usage review 
Post use survey 
Risks:  
As with any electronic device, there is a rare risk for both the vest and cough assist of electrocution, fire, 
personal injury or equipment damage. However, these risks are minimized when following all 
instructions in the user manuals. 
Data Analysis 

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Changes in Pulmonary function testing results, lung ventilation scan results, and lung perfusion scan 
results will be compared across the two treatment groups for each time point. Changes from baseline 
measurements to the study endpoint will also be analyzed. Descriptive statistics will be utilized for 
analysis of adverse events and quality of life assessments. 
Stopping Rules 
All research activities are completely voluntary. Subjects may discontinue their participation in the study 
at any time. The Investigator may stop a subject’s participation secondary to safety issues, intolerance of 
the airway clearance devices, and/or noncompliance with study protocol including airway clearance 
device usage. 
Study Organization:  
Cedars Sinai Medical Center  
127 South San Vicente Blvd.  
LA, CA 90048 
Investigators 
Principle Investigator:  Ashraf Elsayegh MD 
Co-Investigators: 
Robert Baloh, MD PhD 
 
 
 
Richard Lewis, MD 
Abirami Muthukumaran, MD 
 
 
 
Peggy Allred, PT DPT 
Collaborating Departments 
Pulmonary Medicine 
 
 
 
 
 
Nuclear Medicine 
Sponsor:  
RespirTech  
2896 Centre Pointe Drive  
St. Paul, MN 55113 800-793-1261