Assessment of Dystussia in Traumatic Brain Injury

Recovery of people with mild, moderate, or severe swallowing, speech, hearing, and
cognitive-communication impairments is best facilitated by a team of multidisciplinary
specialists. Symptoms associated with traumatic brain injury (TBI) include disordered
swallowing (dysphagia), ataxia and, frequently, but not inevitably, dysarthria or disorder
of speech. Airway compromise also exists in the form of impaired cough, or dystussia. In
view of the frequency of oral intake problems in individuals with TBI and the presence of
weakened cough, or absence of cough, along with the added challenge of the
cognitive-communicative problems, further studies are needed to increase our understanding
of the degree of disordered airway protection. From this work appropriate intervention
strategies can be designed along with an understanding of the compensations that may be used
to assist with improving swallow and airway safety, oral intake and management.

Informed Consent Process:

Investigators working with subjects with TBI, and who are also aware of this study, will
have the ability to provide potential participants with a business card containing only the
name of the study coordinator (Dr. Erin Silverman) as well as her email and telephone
numbers. The individual participants will be responsible for contacting Dr. Silverman if
they wish to participate. Additional participants will be recruited via face to face methods
and by the previously IRB-approved study flyer at local brain injury support groups and
Shands Rehabilitation Hospital.The staff member consenting (Dr. Silverman) has completed
University of Florida training on HIPAA and privacy issues. Subjects do not have to give an
immediate response about enrolling and may freely discuss the study with people of their
choice before making a decision. Capacity to consent will be decided by the consenting staff
member (Dr. Silverman). The study will be explained to the subject, any questions answered,
and a written and signed consent completed along with a HIPAA authorization. Written consent
will be obtained prior to collection of any health history or study data. Once written
informed consent is obtained, Dr. Silverman will conduct an extensive interview in order to
insure the subject meets all required inclusionary/exclusionary criteria.

Neuropsychological Testing: The MOCA (Montreal Cognitive Assessment) will be administered by
Dr. Silverman, on each participant, upon entry into the study.

Measures of TBI severity: Multiple studies have correlated severity of TBI upon initial
admission related to the TBI with swallowing function. The Glasgow Coma Scale (GCS) and
Rancho Los Amigos Scale (RLAS) are commonly administered upon admission of TBI patients.
When available (availability may vary depending on the hospital at initial admission) we
will record the GCS and/or RLAS scores from admission. As well, the investigators will
administer the RLAS upon enrollment in the study. These measures will be incorporated into
our statistical model to better understand the heterogeneity of cognitive impairment on
swallow and cough function.

Cough and respiratory measures: Pulmonary status screening measures: The forced expired
volume in the first second (FEV1) of a forced vital capacity (FVC) exhalation are measures
used to screen pulmonary function (American Thoracic Society). Spirometry is used to derive
FVC, FEV1 and the ratio FEV1/FVC measures (Spirovision 3+m, Futuremed). Alternatively, if
the subject is unable to perform the cognitive voluntary spirometric task, upper airway
respiratory resistance will be measured with impulse oscillometry (lOS, Jaeger Instruments).

Maximum Respiratory Pressures: Maximum inspiratory and expiratory pressures are an indirect
measure of inspiratory and expiratory muscle strength, respectively. The ability to generate
high expiratory airflows is essential to producing high expiratory airflow, and subsequently
cough production and will be measured at the initial assessment in all studies.

Cough: The participant will be instrumented for the measurement of the respiratory airflow
pattern during spontaneous breathing, voluntary cough and reflex capsaicin induced cough. A
facemask with a pneumotachograph will be used to record the airflow changes associated with
spontaneous breathing and cough. The mouth airflow signal will be digitized and recorded on
a desktop computer (Chart, ADinstruments, Inc). Inspiratory and expiratory muscle EMG will
be recorded to provide a neuromuscular motor assessment of cough strength. The computer
signals will be analyzed to determine inspiratory breath phase, expiratory breath phase,
inspiratory cough phase, cough compression phase, and expiratory cough phase. Because it has
been reported that brain injury differentially affects the neuromuscular motor pattern of
voluntary and reflex elicited coughs, it is essential to elicit coughs with both peripheral
afferent stimulation (capsaicin; reflexive cough) and voluntary induced cough in these TBI
participants.

Capsaicin administration: After the participant is instrumented with the facemask, he/she
will be seated comfortably in a chair in front of an airflow fume hood. The airflow fume
hood prevents exposure of the participant and experimenter to the nebulized solution except
when the participant inhales for the capsaicin challenge. Participants will inspire deeply
through the nebulizer (containing the capsaicin or a vehicle solution) coupled to the
facemask and pneumotachograph. The outflow nebulizer gas will be passed through an isopropyl
alcohol solution to remove capsaicin from the air vented into the fume hood. Cough threshold
and sensitivity will be determined using our established randomized block presentation
method of graded capsaicin concentrations (0-2001-JM). The investigators have an FDA IND #
76866 for the use of capsaicin in the study of cough motor pattern. This will take 10-15
minutes to complete.

Design and Procedures: This project will address the Specific Aim over a 1-year time period.
Our Specific Aim will focus on characterizing the mechanical features of swallow and cough
motor function in subjects with TBI and the swallow and cough reconfiguration of respiratory
pattern. Our Specific Aim will allow us to determine the relationship between TBI and both
swallow and cough dysfunction.

Study Protocol: Subjects with a medical history of TBI will be recruited from community TBI
support groups and through face to face recruitment procedures. Once informed consent has
been obtained, relevant medical history will be reviewed, and the participants will complete
screening procedures to determine inclusionary/exclusionary criteria. If inclusionary and
exclusionary criteria are met, participants will complete the following tests:

- MIP and MEP measurement

- Reflex and voluntary cough assessments

Timeframe: This is a one-time visit study. Therefore, participants will be followed only on
the day they present for study procedures. There will be no follow up beyond this day.

Inclusion Criteria:

1. TBI within 5 years - may have accompanying neck injury but not extensive
reconstruction of oral structures.

2. Pulmonary function screening: FEV1 >75%, FVC > 75% and FEV1/FVC ratio of >75% of age,
sex and ethnicity corrected predicted values, impulse oscillometry R5 resistance
measurement within 15% of age, sex and ethnicity corrected predicted values.

3. Medical status permits participation.

4. Cognitive status permits participation.

Exclusion Criteria:

1. Refuses consent.

2. Cognitively incapable of informed consent

3. Active substance dependence/use (from clinical interview/record review)

4. Diagnosis of moderate to very severe chronic obstructive pulmonary disease (COPD;
from patient interview)

5. History of chronic cough and/or cough syncope (From clinical interview)

6. History of cancer in the head or neck (From clinical interview)

7. History of radiation to the head or neck (From clinical interview)

8. History of stroke or other neurodegenerative disease (From clinical interview)
Participants will be enrolled without regard for sex, ethnicity, or age.