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The purpose for this research protocol was to examine the role of breathing control mechanisms that determine the development of sleep-disordered breathing in the elderly. This proposal focused on key factors that contribute to the control of ventilation in elderly adults during sleep. The investigators studied the age-specific changes in ventilatory control in older and young adults during NREM sleep.
Sleep apnea-hypopnea syndrome (SAS) is a relatively common disorder in the US population with significant adverse health consequences. Despite the high prevalence of SAS in elderly individuals, the underlying mechanisms have remained elusive. Specifically, the investigators do not know whether the high prevalence of sleep apnea in older adults is due to increased central breathing instability. This proposal focused on investigating age-specific differences in the susceptibility to central breathing instability in adults.
This project had the following specific objectives:
Procedure: The investigators determined the susceptibility to central breathing instability by mechanically ventilating the subjects during NREM sleep using non-invasive pressure support ventilation. The investigators compared the hypocapnic apneic threshold in old (age>60 years) and young (age 18-50 years) individuals who were healthy. The investigators also measured the parameters over a continuum of age from 18 to 89 years.
- The investigators investigated whether there was a difference in the susceptibility to long term facilitation of ventilation between young and old healthy individuals in response to episodic hypoxia, while maintaining isocapnia.
Sleep apnea is very common in older Veterans and is associated with significant cardiovascular complications. Greater insight into the pathogenesis will have a positive impact on the health of Veterans suffering from this condition. This study furthers the understanding of the pathogenesis of breathing instability leading to sleep-disordered breathing during sleep. The investigators anticipate findings will provide a basis for new approaches to prevention and management of SAS in Veterans.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Other | Determine the apneic threshold and carbon- dioxide reserve using noninvasive positive pressure ventilation during NREM sleep and determine the effect effect of episodic hypoxia on ventilatory long-term facilitation during NREM sleep in Young adults. |
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| Arm 2 | Experimental | Determine the apneic threshold and carbon- dioxide reserve using noninvasive positive pressure ventilation during NREM sleep and determine the effect of episodic hypoxia on ventilatory long-term facilitation during NREM sleep in Older adults. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 1) hyperventilation via noninvasive positive pressure ventilation 2) multiple trials of episodic hypoxia | Other | 1) noninvasive hyperventilation to determine apneic threshold; 2) episodic hypoxia to determine ventilatory long term facilitation |
| Measure | Description | Time Frame |
|---|---|---|
| Apneic Threshold (AT) and Carbon-dioxide (CO2) Reserve | The AT was defined as the end-tidal (PETCO2) that demarcated the central apnea closest to the eupneic PETCO2. The CO2 reserve was defined as the difference in PETCO2 between eupnea and AT. | 4-6 wks for each participant |
| Long-term Facilitation (LTF) of Ventilation, Minute Ventilation Was Measured in Older Adults Only | Episodic hypoxia (EH) leads to sustained elevation of the ventilatory motor output, referred to as LTF, an excitatory mechanism characterized by a sustained elevation in ventilatory motor output following EH. Minute ventilation during recovery period after multiple trials of EH. This is reported in older adults on this grant. | 4-6 wks for each participant |
| Measure | Description | Time Frame |
|---|---|---|
| Hypoxic Ventilatory Response | Hypoxic ventilatory response was calculated as the change in minuted ventilation for a change in oxygen saturation during each hypoxia trial. | 4-6 wks for each participant |
| Brief Hyperoxia Response |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Susmita Chowdhuri, MD | John D. Dingell VA Medical Center, Detroit, MI | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| John D. Dingell VA Medical Center, Detroit, MI | Detroit | Michigan | 48201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26316510 | Result | Chowdhuri S, Pranathiageswaran S, Franco-Elizondo R, Jayakar A, Hosni A, Nair A, Badr MS. Effect of age on long-term facilitation and chemosensitivity during NREM sleep. J Appl Physiol (1985). 2015 Nov 15;119(10):1088-96. doi: 10.1152/japplphysiol.00030.2015. Epub 2015 Aug 27. |
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Participants were recruited by posting fliers at the sites approved by the Detroit VA clinical investigations committee and Wayne State IRB (institution review board). They completed a phone interview. If they qualified based on the inclusion/exclusion criteria they completed an informed consent. Dates 2008 to 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1 | Young adults, age 18-59yrs hyperventilation and episodic hypoxia: a) noninvasive hyperventilation to determine apneic threshold; b) episodic hypoxia to determine ventilatory long term facilitation |
| FG001 | Arm 2 | Older adults, age >/=60 yrs hyperventilation and episodic hypoxia: a) noninvasive hyperventilation to determine apneic threshold; b) episodic hypoxia to determine ventilatory long term facilitation |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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We studied normal subjects. Subjects were assigned to two age categories, 'young' between 18 and 50 years, and 'elderly' >55-60 years respectively. Participants with data available were included in the analysis Normal participants (controls) will have apnea hypopnea index, AHI<5/hour, respiratory events /hour of sleep
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| ID | Title | Description |
|---|---|---|
| BG000 | Health Young Adults | Health Young adults, age 18-50 yrs hyperventilation and episodic hypoxia: noninvasive hyperventilation to determine apneic threshold; episodic hypoxia to determine long term facilitation |
| BG001 | Healthy Older Adults |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Apneic Threshold (AT) and Carbon-dioxide (CO2) Reserve | The AT was defined as the end-tidal (PETCO2) that demarcated the central apnea closest to the eupneic PETCO2. The CO2 reserve was defined as the difference in PETCO2 between eupnea and AT. | Older adults : n=10, 6 females/4 males Young n=15, 8 females/ 7 males; participants with data available were included in the analysis | Posted | Mean | Standard Error | mm Hg | 4-6 wks for each participant |
|
The participants were monitored throughout the study 2008 to 2013. Safety monitoring board also reviewed the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Young Adults | Young adults, age 18-50 yrs hyperventilation and episodic hypoxia: noninvasive hyperventilation to determine apneic threshold; episodic hypoxia to determine long term facilitation |
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Participants who could not maintain stable sleep could not be included in the analyses. Participants also dropped out after the initial diagnostic sleep study as they did not want to continue the experimental arms.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Susmita Chowdhuri | John D. Dingell VA Medical Center | 313 576 1000 | 3685 | susmita.chowdhuri@va.gov |
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| ID | Term |
|---|---|
| D012891 | Sleep Apnea Syndromes |
| D020182 | Sleep Apnea, Central |
| D053120 | Respiratory Aspiration |
| ID | Term |
|---|---|
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
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Brief hyperoxia response was the nadir minute ventilation achieved immediately upon exposure to brief hyperoxia expressed as a percent of eupneic minuted ventilation.
| 4-6 wks for each participant |
Healthy Older adults, age >55-60yrs hyperventilation and episodic hypoxia: noninvasive hyperventilation to determine apneic threshold; episodic hypoxia to determine long term facilitation |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex/Gender, Customized | Participants with data available were included in the analysis | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Region of Enrollment | Number | participants |
|
| Body mass index | Mean | Standard Deviation | kg/m2 |
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Older adults, age >60 yrs hyperventilation and episodic hypoxia: noninvasive hyperventilation to determine apneic threshold; episodic hypoxia to determine long term facilitation |
|
|
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| Primary | Long-term Facilitation (LTF) of Ventilation, Minute Ventilation Was Measured in Older Adults Only | Episodic hypoxia (EH) leads to sustained elevation of the ventilatory motor output, referred to as LTF, an excitatory mechanism characterized by a sustained elevation in ventilatory motor output following EH. Minute ventilation during recovery period after multiple trials of EH. This is reported in older adults on this grant. | Older adults 8 women/6 men;participants with data available were included in the analysis | Posted | Mean | Standard Error | percentage of control minute ventilation | 4-6 wks for each participant |
|
|
|
|
| Secondary | Hypoxic Ventilatory Response | Hypoxic ventilatory response was calculated as the change in minuted ventilation for a change in oxygen saturation during each hypoxia trial. | older adults: 7 women/6 men; young adults: 6 women/4 men;participants with data available were included in the analysis | Posted | Mean | Standard Error | Liter/minute/%saturation | 4-6 wks for each participant |
|
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|
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| Secondary | Brief Hyperoxia Response | Brief hyperoxia response was the nadir minute ventilation achieved immediately upon exposure to brief hyperoxia expressed as a percent of eupneic minuted ventilation. | young adults: 3 women/6 men; older adults: 6 women/4 men; participants with data available were included in the analysis | Posted | Mean | Standard Error | percentage of eupneic minute ventilaion | 4-6 wks for each participant |
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|
|
| 0 |
| 50 |
| 0 |
| 50 |
| EG001 | Healthy Older Adults | Older adults, age >55-60 years hyperventilation and episodic hypoxia: noninvasive hyperventilation to determine apneic threshold; episodic hypoxia to determine long term facilitation | 0 | 42 | 0 | 42 |
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| D020920 |
| Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Male |
|
| Male |
|
| Male |
|