Determinants of Age Related Breathing Instability During Non-Rapid-Eye-Movement (NREM) Sleep

Determinants of Age-specific Breathing Instability During Sleep

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.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea; Age
• Intervention / Treatment: Other: 1) hyperventilation via noninvasive positive pressure ventilation 2) multiple trials of episodic hypoxia

Detailed Description

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:

• To determine age-specific changes in the hypocapnic apneic threshold during NREM sleep in elderly vs young individuals.
• To determine age-specific changes in long-term facilitation during sleep in elderly versus young individuals.

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.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • John D. Dingell VA Medical Center, Detroit, MI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy older and young adults

Exclusion Criteria:

• Pregnancy,
• history of active coronary artery disease-including stable and unstable angina,
• recent myocardial infarction,
• history of congestive heart failure,
• stroke,
• excessive daytime sleepiness with Epworth Sleepiness Scale of >15
• patient with OSA- (Obstructive sleep apnea) on therapy
• depression,
• schizophrenia,
• untreated hypothyroidism,
• diabetes on insulin,
• seizure disorder,
• intrinsic renal and liver disorders,
• failure to give informed consent,
• patients with evidence of pulmonary diseases based on history and abnormal pulmonary function testing, including obstructive (ratio of predicted forced expiratory volume to forced vital capacity, <80% predicted) or restrictive lung disorders (total lung capacity <80% predicted) with resting oxygen saturation of <96% and kyphoscoliosis (chest wall deformities)
• patients on certain medications including, opiates derivatives, stimulants, antidepressants, tranquilizers, anti-psychotic agents, theophylline and other central nervous system altering medications
• history of alcohol or recreational drug use will also serve as grounds for exclusion,
• patients with body mass index (BMI) >34kg/m2
• subjects with sleep apnea are already using continuous positive airway pressure for more than 7 days as therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm 1; 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.	Other: 1) hyperventilation via noninvasive positive pressure ventilation 2) multiple trials of episodic hypoxia; 1) noninvasive hyperventilation to determine apneic threshold; 2) episodic hypoxia to determine ventilatory long term facilitation
Experimental: Arm 2; 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.	Other: 1) hyperventilation via noninvasive positive pressure ventilation 2) multiple trials of episodic hypoxia; 1) noninvasive hyperventilation to determine apneic threshold; 2) episodic hypoxia to determine ventilatory long term facilitation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Susmita Chowdhuri, MD, John D. Dingell VA Medical Center, Detroit, MI

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: August 7, 2008
• First Submitted That Met QC Criteria: August 8, 2008
• First Posted (Estimate): August 11, 2008

Study Record Updates

• Last Update Posted (Actual): June 28, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: aging; ventilation; chemoresponsiveness; apneic threshold; carbon-dioxide reserve; intermittent hypoxia; central apnea
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes
• Other Study ID Numbers: CDA-2-019-07F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO