Pathogenesis and Outcomes of Sleep Disordered Breathing in Chronic Obstructive Pulmonary Disease (COPD)

Pathogenesis and Outcomes of Sleep Disordered Breathing in COPD

This research is being conducted to examine the effects of nasal insufflation of warm and humidified air through a small nasal cannula on sleep, breathing pulmonary function, and daytime exercise capability.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Other: Oxygen; Other: High flow of room air

Detailed Description

Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity including substantial daytime fatigue exertional intolerance and ventilatory impairment, which hits a nadir in the morning. Nocturnal disturbances in sleep and breathing are common in COPD, although the impact of these disturbances on COPD morbidity remains largely unknown. The hypothesis is that COPD induces specific sleep and breathing disturbances that remain a substantial source of morbidity in this disorder.

Current therapy for treating nocturnal disturbances in sleep and breathing in COPD including nocturnal oxygen has failed to improve morning fatigue and pulmonary function. This study promises to significantly alter our approach to the diagnosis and management of sleep disordered breathing in COPD.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Consenting adults over the age of 21
• BMI < 40 kg/m2

Exclusion Criteria:

• Diagnosed with sleep apnea (apnea and hypopneas of >10 events/hr).
• A sleep efficiency of <30%, or a prior diagnosis of disorders that impair sleep architecture.
• Unstable cardiovascular disease (decompensated heart failure, myocardial infarction within the past 3 months, revascularization procedure within the past 3 months, unstable arrhythmias, uncontrolled hypertension (BP > 190/110)).
• Severe renal insufficiency requiring dialysis.
• Liver cirrhosis.
• A recent acute illness in a 6 weeks period prior to the sleep studies.
• We will exclude subjects with severe daytime hypoxemia (Oxyhemoglobin saturation (SaO2) <80% or partial pressure of oxygen (PaO2) <55 mmHg at rest).
• Chronic use of sedatives or respiratory depressants that would affect sleep quality (e.g., benzodiazepines or other hypnotics or narcotics).
• Pregnancy.
• Tracheostomy or other significant oropharyngeal or nasopharyngeal surgery, in the last 6 months.
• Narcolepsy and other neurological disorders such as Parkinson's Disease.
• Severe hepatic insufficiency.
• Bleeding disorders or Coumadin use.
• Allergy to lidocaine or benzocaine.
• Language/dementia/psychiatric issues - the participant must be able to provide consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: oxygen; nocturnal oxygen of 2 L/min	Other: Oxygen; oxygen at a rate of 2 L/min will be delivered through a small nasal cannula throughout sleep.; Other Names: supplemental oxygen; nocturnal oxygen
Experimental: High Flow of room air; Warm and humidified air at a rate of 20 L/min through a small nasal cannula (similar to oxygen cannula)	Other: High flow of room air; Warm and humidified air at rates of 20 L/min will be delivered through a small nasal cannula throughout sleep; Other Names: Optiflow; TNI: Transnasal insufflation; Open CPAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The evening to morning differences in expiratory airflow obstruction (FEV1/FVC)	Lung function declines over the course of the night. We hypothesize that delivering warm and humidified air at a rate of 20 L/min over the entire night improves morning FEV1 compared to oxygen.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percent rate of inspiratory flow limitation.	Patients with COPD often exhibit inspiratory air flow limitation during sleep. We hypothesize that delivering warm and humidified air at a rate of 20 L/min reduces the degree of inspiratory air flow limitation compared to oxygen.	4 Years
Effect of High flow nasal insufflation of air on exercise capacity (6 minute walk test).	Patients with COPD have impaired exercise tolerance in the morning. We hypothesize that delivering warm and humidified air at a rate of 20 L/min over the entire night extends morning 6 minute walk length.	One Year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep efficiency	We hypothesize that delivering warm and humidified air at a rate of 20 L/min over the entire night improves sleep efficiency compared to oxygen treatment.	4 years
Episodes of dynamic hyperinflation	The combination of in- and expiratory flow limitation can lead to dynamic hyperinflation during sleep. We hypothesize that compared to oxygen, high flow nasal insufflation of warm and humidified air at a rate of 20 L/min will reduce the number of breaths associated with dynamic hyperinflation.	4 years

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Hartmut Schneider, M.D., Ph.D., Johns Hopkins University

Publications and helpful links

General Publications

• Schneider H, Krishnan V, Pichard LE, Patil SP, Smith PL, Schwartz AR. Inspiratory duty cycle responses to flow limitation predict nocturnal hypoventilation. Eur Respir J. 2009 May;33(5):1068-76. doi: 10.1183/09031936.00063008. Epub 2009 Jan 7.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: July 16, 2010
• First Submitted That Met QC Criteria: January 7, 2013
• First Posted (Estimate): January 9, 2013

Study Record Updates

• Last Update Posted (Estimate): October 5, 2016
• Last Update Submitted That Met QC Criteria: October 4, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: COPD; Sleep; Supplemental oxygen; Breathing mechanics; nasal insufflation
• 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: R01HL105546-01 (U.S. NIH Grant/Contract); NA_00040333 (Other Identifier: Johns Hopkins Medicine-IRB 5)