Obstructive Sleep Apnea
Conditions
Keywords
World Trade Center (WTC), nasal symptoms, nasal inflammation, CPAP
Brief summary
The goal of the study is to examine the possible underlying causes of sleep apnea (a disorder in which there are problems with breathing during sleep) in World Trade Center Responders. The study will look at the relationship between sleep apnea and various nose and throat conditions. Specifically, the study will look at upper airway disease (problems with the nose and throat), nasal inflammation, and nasal resistance (the amount of airflow through the nose). Subjects will have a physical exam and answer questions about nasal symptoms and sleeping problems. Nasal lavage (washing the inner nasal passages) will be performed on the subjects and markers of inflammation will be measured in the lavage fluid. Rhinomanometry (measuring the airflow through the nose) will also be performed to measure the degree of airflow obstruction. All subjects will be asked to perform in-home sleep apnea monitoring. Those subjects who are diagnosed with sleep apnea will test two treatment methods. Sleep apnea is treated by using a CPAP (continuous positive airway pressure) device. This device blows air into a mask worn by the patient during sleep. The two treatment methods that will be tested are the fixed pressure CPAP (pressure is constant during use) and CPAP-flex (pressure decreases when the subject exhales). Patients will be randomly assigned to one treatment method for one month then crossed to the other treatment method for the next month. The investigators will determine if patients with certain nasal conditions (high nasal resistance) are more likely to use CPAP-flex rather than CPAP.
Detailed description
Following the World Trade Center (WTC) disaster, an estimated 40,000 individuals were exposed to significant amounts of dust while working in rescue, recovery and debris removal. A significant number of these responders have reported least one new or worsened upper airway respiratory symptom when examined in 2004 with 50% of responders continuing to have symptoms of chronic rhino-sinusitis or upper airway disease (UAD) in 2007. In addition, about 50% of those with UAD referred to our sleep center reported new onset snoring on their questionnaires immediately following their exposure and had unusually high prevalence of obstructive sleep apnea (OSA) that did not appear to be related to obesity, which is the usual risk factor for OSA. This suggests to us that mechanisms other than obesity may be important in the pathogenesis of OSA in these subjects. Given their chronic nasal symptoms they also provide a unique opportunity to examine the relationship between nasal pathology and OSA and test if nasal symptoms reported by the subjects in the WTC Health Program (WTCHP) are an indicator of increased nasal resistance due to nasal inflammation resulting from exposure to the WTC dust. Positive Airway Pressure (CPAP) is the standard therapy for OSA but despite its efficacy has poor adherence. Subjects with high nasal resistance (such as responders with UAD and OSA) may experience additional pressure during expiration at the upper airway resulting in greater difficulty in tolerating CPAP therapy than those who do not have high nasal resistance. Reduction of excess expiratory positive pressure by the modality known as Cflex™ during CPAP therapy (CPAPFlex) may improve comfort and adherence in these subjects without compromising CPAP efficacy. In the present proposal we will study responders enrolled at the Environmental and Occupational Health Sciences Institute of Robert Wood Johnson Medical School (RWJMS) and the NYU School of Medicine Clinical Center of Excellence at Bellevue Hospital
Interventions
Use of the REMstar Auto A-Flex in standard CPAP therapy mode
Use of Philips Respironics REMstar Auto A-Flex in C-Flex mode
Sponsors
Study design
Eligibility
Inclusion criteria
* Member of the World Trade Center Health Program at either the Environmental and Occupational Healthy Sciences Institute at Robert Wood Johnson Medical School in Piscataway, NJ, the New York University School of Medicine Clinical Center of Excellence at Bellevue Hospital in New York, NY, or the Icahn School of Medicine at Mount Sinai.
Exclusion criteria
* Gross skeletal alterations affecting the upper airway (nose and throat) * Unstable chronic medical conditions known to affect Obstructive Sleep Apnea (congestive heart failure, stroke) * Pregnancy or intent to become pregnant * Habitual snoring or diagnosis of obstructive sleep apnea prior to 9/11/2001.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adherence to CPAP Pre-crossover | 5 weeks after initiation of treatment | The use (number of hours per night) will be compared between standard CPAP and CPAP flex. Results are based on the first treatment period only (pre-crossover). |
| Adherence to CPAP Overall Study | 9 weeks after initiation of treatment | The use (number of hours per night) will be compared between standard CPAP and CPAP flex. Results are based on both periods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CPAP Efficacy | 5 weeks after initiation of treatment | Efficacy will be evaluated by measuring the residual apnea and hypopnea index (AHI) while on treatment. The efficacy of standard CPAP and CPAP-flex will be compared. Results are based on the first treatment period only (pre-crossover). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adherence to CPAP Overall Study, Subjects With High Nasal Resistance | 9 weeks after initiation of treatment | The use (number of hours per night) will be compared between standard CPAP and CPAP flex for subjects with high total nasal resistance (logTNR\>0.8). The analysis is based on both periods. |
| Adherence to CPAP Overall Study, Subjects With Low Nasal Resistance | 9 weeks after initiation of treatment | The use (number of hours per night) will be compared between standard CPAP and CPAP flex for subjects with low total nasal resistance (logTNR\<=0.8). The analysis is based on both periods. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited between January 2013 and December 2016 at three World Trade Center Health Program Clinical Centers of Excellence (Rutgers University, Icahn School of Medicine at Mount Sinai, and New York University School of Medicine).
Pre-assignment details
Subjects without OSA were excluded from the trial.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who were randomized to receive either standard CPAP or CPAP-Flex. | 317 |
| Total | 317 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 - Initial Assignment | Lost to Follow-up | 18 | 27 |
| Period 1 - Initial Assignment | Physician Decision | 2 | 3 |
| Period 1 - Initial Assignment | Withdrawal by Subject | 19 | 20 |
| Period 2 -Cross to Alternate Arm | Lost to Follow-up | 13 | 17 |
| Period 2 -Cross to Alternate Arm | Physician Decision | 1 | 1 |
| Period 2 -Cross to Alternate Arm | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 29 Participants |
| Age, Categorical Between 18 and 65 years | 288 Participants |
| Age, Continuous | 53.29 years STANDARD_DEVIATION 8.23 |
| Apnea and Hypopnea Index (AHI4%) | 17.01 Events/hour STANDARD_DEVIATION 14.42 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 264 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants |
| Race (NIH/OMB) More than one race | 33 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 227 Participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 282 Participants |
| Total Nasal Resistance High Nasal Resistance (LogTNR>0.8) | 132 Participants |
| Total Nasal Resistance Low Nasal Resistance (LogTNR<=0.8) | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 267 | 0 / 278 |
| other Total, other adverse events | 0 / 267 | 0 / 278 |
| serious Total, serious adverse events | 0 / 267 | 0 / 278 |
Outcome results
Adherence to CPAP Overall Study
The use (number of hours per night) will be compared between standard CPAP and CPAP flex. Results are based on both periods.
Time frame: 9 weeks after initiation of treatment
Population: Subjects who received the allocated treatment (i.e., turned on the PAP device) in either the first treatment period or the second treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard CPAP | Adherence to CPAP Overall Study | 1.03 Hours/night |
| CPAP-Flex | Adherence to CPAP Overall Study | 0.8 Hours/night |
Adherence to CPAP Pre-crossover
The use (number of hours per night) will be compared between standard CPAP and CPAP flex. Results are based on the first treatment period only (pre-crossover).
Time frame: 5 weeks after initiation of treatment
Population: Subjects who received the allocated treatment (i.e., turned on the PAP device). The difference between the number allocated and the number of analyzed is the result of some subjects (n=11 in CPAP and n=16 in C-Flex) who did not turn on the device despite taking it home. These were assumed to have NOT received the allocated treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard CPAP | Adherence to CPAP Pre-crossover | 1 Hours/night |
| CPAP-Flex | Adherence to CPAP Pre-crossover | 0.89 Hours/night |
CPAP Efficacy
Efficacy will be evaluated by measuring the residual apnea and hypopnea index (AHI) while on treatment. The efficacy of standard CPAP and CPAP-flex will be compared. Results are based on the first treatment period only (pre-crossover).
Time frame: 5 weeks after initiation of treatment
Population: Subjects who received treatment (turned on the PAP device). An additional 48 subjects on CPAP and 53 on CPAP-FLex were not analyzed as an AHI could not be generated during the analysis period due to insufficient use.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard CPAP | CPAP Efficacy | 2.89 Events/hour | Standard Deviation 3.06 |
| CPAP-Flex | CPAP Efficacy | 3.12 Events/hour | Standard Deviation 2.95 |
CPAP Efficacy
Efficacy will be evaluated by measuring the residual apnea and hypopnea index (AHI) while on treatment. The efficacy of standard CPAP and CPAP-flex will be compared. Results are based on both treatment periods.
Time frame: 9 weeks after initiation of treatment
Population: Subjects who received the allocated treatment (i.e., turned on the PAP device; N=239 for CPAP and N=249 for CPAP Flex). An additional 82 subjects on CPAP and 102 subjects on CPAP-Flex were not analyzed as an AHI could not be generated during the analysis period due to insufficient use.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard CPAP | CPAP Efficacy | 2.71 events/hour | Standard Deviation 2.76 |
| CPAP-Flex | CPAP Efficacy | 2.94 events/hour | Standard Deviation 2.65 |
Adherence to CPAP Overall Study, Subjects With High Nasal Resistance
The use (number of hours per night) will be compared between standard CPAP and CPAP flex for subjects with high total nasal resistance (logTNR\>0.8). The analysis is based on both periods.
Time frame: 9 weeks after initiation of treatment
Population: Subjects with high total nasal resistance who received the allocated treatment (i.e., turned on the PAP device) in either the first treatment period or in the second treatment period.Total nasal resistance data are missing for 8 subjects.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Standard CPAP | Adherence to CPAP Overall Study, Subjects With High Nasal Resistance | 2.08 Hours/night |
| CPAP-Flex | Adherence to CPAP Overall Study, Subjects With High Nasal Resistance | 1.75 Hours/night |
Adherence to CPAP Overall Study, Subjects With Low Nasal Resistance
The use (number of hours per night) will be compared between standard CPAP and CPAP flex for subjects with low total nasal resistance (logTNR\<=0.8). The analysis is based on both periods.
Time frame: 9 weeks after initiation of treatment
Population: Subjects with low total nasal resistance who received the allocated treatment (i.e., turned on the PAP device) in either the first treatment period or in the second treatment period. Total nasal resistance data are missing for 8 subjects.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Standard CPAP | Adherence to CPAP Overall Study, Subjects With Low Nasal Resistance | 1.81 Hours/night |
| CPAP-Flex | Adherence to CPAP Overall Study, Subjects With Low Nasal Resistance | 1.55 Hours/night |