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| ID | Type | Description | Link |
|---|---|---|---|
| 1F32HL097578-01 | U.S. NIH Grant/Contract | View source | |
| 5K23HL105542 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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Asthma is an extremely common disorder, which is becoming more prevalent. The purpose of this study is to examine how nocturnal lung volumes contribute to asthma severity, which may explain part of the link between asthma and obesity. The investigators seek to test the hypothesis that raising lung volumes during the night will improve asthma symptoms. The investigators work may lead to new targets for therapy.
Asthma is a chronic respiratory disease characterized by airway inflammation and airway hyperresponsiveness, which causes airflow obstruction. It is extremely prevalent, affecting an estimated 22 million Americans, and costly with loss of productivity and direct healthcare costs in the billions of dollars. The incidence and prevalence of asthma are increasing, both in the US and around the world. This increase comes despite greater understanding of the inflammatory and allergic basis for asthma, and despite better antiinflammatory medications. One explanation for the increasing prevalence of asthma is the concomitant increase in obesity, with the majority of Americans now overweight or obese. Numerous studies have convincingly linked asthma and obesity, and demonstrated increased obstruction with weight gain and decreased obstruction with weight loss. However, the mechanisms that underlie this linkage are not known.
We believe that low lung volumes contribute to the pathogenesis and severity of asthma. End-expiratory lung volume is decreased in obesity, and likely falls further during sleep, particularly in overweight and obese patients. Both upper and lower airway resistance increase with decreasing lung volumes, as airways become smaller. However, prior work has shown that lower airway resistance increases out of proportion to the decrease in lung volume that occurs during sleep in asthma patients. This difference between controls and people with asthma has not been further explored, yet may provide insight into asthma pathogenesis and provide potential targets for therapy.
Therefore, we propose a series of experiments to define the impact of lung volumes during sleep on airway resistance. One of these experiments will be to to test the hypothesis that lung stretch can be used therapeutically by tonically and dynamically increasing lung volumes during sleep using bi-level positive airway pressure. This research can help delineate asthma pathogenesis and may help improve therapeutic options in this exceedingly common disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Usual Care first, then Bilevel PAP | Experimental | Subjects will begin the study by continuing their usual care for 4 weeks. They will complete questionnaires and breathing tests at the start and end of this 4 week period. After a "Washout Period" of an additional 4 weeks of usual care, they will then start Bilevel PAP therapy for 4 weeks. Just before and after the Bilevel PAP they will complete questionnaires and breathing tests. |
|
| Bilevel PAP first, then Usual Care | Experimental | Subjects will begin the study by starting on Bilevel PAP for 4 weeks. Just before and after the Bilevel PAP they will complete questionnaires and breathing tests. After a 4 week "Washout Period" of usual care, they will start a Usual Care period for 4 weeks. They will complete questionnaires and breathing tests at the start and end of this 4 week period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bilevel PAP (4 weeks) | Device | Subjects will use bilevel PAP each night for 4 weeks. The pressure levels will be adjusted by the investigators to increase lung volumes during the night. |
| Measure | Description | Time Frame |
|---|---|---|
| Asthma Control Test | Well validated questionnaire of asthma symptoms which includes 5 written questions. Each question is answered on a scale of 1-5, which are summed to report a range of asthma control from 5 to 25 (higher score indicates better asthma control). | Every 4 weeks during the 12 week study (at the start and end of the Usual Care period, and at the start and end of the Bilevel PAP intervention period) |
| Airway Reactivity as Measured by Methacholine Challenge (PC20) | This is a physiological measurement derived from repeated breathing maneuvers which measures airway reactivity. Subjects are exposed to higher and higher concentrations of an airway irritant (in this case methacholine), and between each dose perform spirometry. The test is stopped after the forced expiratory volume in 1 second (FEV1) falls 20% below the baseline. The concentration of methacholine at which this occurs is called the PC20. Methacholine challenges are routinely used in the diagnosis of asthma, and in many asthma research studies to measure changes in airway reactivity. | Every 4 weeks during the 12 week study (at the start and end of the usual care period, and at the start and end of the Bilevel PAP intervention period) |
| Measure | Description | Time Frame |
|---|---|---|
| Epworth Sleepiness Scale (ESS) | 8 item questionnaire to measure daytime sleepiness, with total score reported 0 (less sleepy) to 24 (most sleepy). Scores greater than or equal to 10 are considered excessive daytime sleepiness. | Every 4 weeks during the 12 week study (at the start and end of the usual care period, and at the start and end of the Bilevel PAP intervention period) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert L Owens, MD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
33 subjects were assessed for eligibility (20 asthma only, 13 asthma + OSA).
12 were excluded, with 11 not meeting inclusion criteria, and 1 declining to participate.
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| ID | Title | Description |
|---|---|---|
| FG000 | Usual Care First, Then Bilevel PAP | Subjects will begin the study by continuing their usual care for 4 weeks. They will complete questionnaires and breathing tests at the start and end of this 4 week period. After a "Washout Period" of an additional 4 weeks of usual care, they will then start Bilevel PAP therapy for 4 weeks. Just before and after the Bilevel PAP they will complete questionnaires and breathing tests. |
| FG001 | Bilevel PAP First, Then Usual Care | Subjects will begin the study by starting on Bilevel PAP for 4 weeks. Just before and after the Bilevel PAP they will complete questionnaires and breathing tests. After a 4 week "Washout Period" of usual care, they will start a Usual Care period for 4 weeks. They will complete questionnaires and breathing tests at the start and end of this 4 week period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (4 Weeks) |
| |||||||||||||||||||
| Washout Period (4 Weeks) |
| |||||||||||||||||||
| Second Intervention |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Asthma Only | Subjects meeting all inclusion criteria and no exclusion criteria with asthma only (no sleep apnea) |
| BG001 | Asthma + OSA | Subjects meeting all inclusion criteria and no exclusion criteria with asthma and obstructive sleep apnea on continuous positive airway pressure (CPAP) treatment |
| 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 | Asthma Control Test | Well validated questionnaire of asthma symptoms which includes 5 written questions. Each question is answered on a scale of 1-5, which are summed to report a range of asthma control from 5 to 25 (higher score indicates better asthma control). | All 21 patients went through usual care and bilevel PAP therapy | Posted | Mean | Standard Deviation | units on a scale | Every 4 weeks during the 12 week study (at the start and end of the Usual Care period, and at the start and end of the Bilevel PAP intervention period) |
|
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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 | Asthma Only | Subjects meeting all inclusion criteria and no exclusion criteria with asthma only (no sleep apnea) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Central Sleep Apnea | Respiratory, thoracic and mediastinal disorders | central sleep apnea | Systematic Assessment | Patients naive to PAP therapy developed central apneas while on bilevel PAP therapy |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Robert L. Owens | University of California San Diego | 8586575258 | rowens@ucsd.edu |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| D012891 | Sleep Apnea Syndromes |
| D020181 | Sleep Apnea, Obstructive |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D045422 | Continuous Positive Airway Pressure |
| ID | Term |
|---|---|
| D011175 | Positive-Pressure Respiration |
| D012121 | Respiration, Artificial |
| D058109 | Airway Management |
| D013812 | Therapeutics |
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|
| Usual Care (4 weeks) | Other | Subjects will continue with their usual asthma care. Investigators will make no changes to their medications or other habits. |
|
| Washout Period (4 weeks) | Other | Subjects will continue with their usual asthma care in between the Usual Care and Bilevel PAP periods. Investigators will make no changes to their medications or other habits. |
|
| Pittsburgh Sleep Quality Index (PSQI) | Well validated questionnaire used frequently to measure sleep quality over the prior 1 month. It consists of 19 individual items that combine to form 7 components summed to create one global score. The overall score is between 0 (better sleep) and 21 (worse sleep). | Every 4 weeks during the 12 week study (at the start and end of the usual care period, and at the start and end of the Bilevel PAP intervention period) |
| Short Form (SF-36) Health Survey | Well validated quality of life questionnaire that measures eight sub-sections, which are summed to yield a score from 0 (maximal disability) to 100 (no disability). The eight subsections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health. | Every 4 weeks during the 12 week study (at the start and end of the usual care period, and at the start and end of the Bilevel PAP intervention period) |
| FEV1 %Predicted | Performed as part of spirometry | Every 4 weeks during the 12 week study (at the start and end of the usual care period, and at the start and end of the Bilevel PAP intervention period) |
| Subjects With Asthma + OSA |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| Subjects With Asthma + OSA |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (kg/m2) | Mean | Standard Deviation | kg/m2 |
|
| FEV1% predicted | Mean | Standard Deviation | % |
|
| FEV1/FVC | Mean | Standard Deviation | ratio |
|
| PC20 (mg/mL) | Geometric Mean | Standard Deviation | mg/mL |
|
| AHI (events/hour) | Mean | Standard Deviation | events per hour |
|
| CPAP Pressure | Subjects with ASTHMA only do not use CPAP | Mean | Standard Deviation | cm of water |
|
| CPAP Usage | Subjects with asthma ONLY do not use CPAP | Mean | Standard Deviation | minutes |
|
Subjects will wear Bilevel PAP for 4 weeks. Just before and after the Bilevel PAP they will complete questionnaires and breathing tests. |
|
|
|
| Primary | Airway Reactivity as Measured by Methacholine Challenge (PC20) | This is a physiological measurement derived from repeated breathing maneuvers which measures airway reactivity. Subjects are exposed to higher and higher concentrations of an airway irritant (in this case methacholine), and between each dose perform spirometry. The test is stopped after the forced expiratory volume in 1 second (FEV1) falls 20% below the baseline. The concentration of methacholine at which this occurs is called the PC20. Methacholine challenges are routinely used in the diagnosis of asthma, and in many asthma research studies to measure changes in airway reactivity. | All subjects completed the crossover study design | Posted | Geometric Mean | Standard Error | mg/mL | Every 4 weeks during the 12 week study (at the start and end of the usual care period, and at the start and end of the Bilevel PAP intervention period) |
|
|
|
|
| Secondary | Epworth Sleepiness Scale (ESS) | 8 item questionnaire to measure daytime sleepiness, with total score reported 0 (less sleepy) to 24 (most sleepy). Scores greater than or equal to 10 are considered excessive daytime sleepiness. | All subjects completed both arms of this crossover study. | Posted | Mean | Standard Deviation | units on a scale | Every 4 weeks during the 12 week study (at the start and end of the usual care period, and at the start and end of the Bilevel PAP intervention period) |
|
|
|
|
| Secondary | Pittsburgh Sleep Quality Index (PSQI) | Well validated questionnaire used frequently to measure sleep quality over the prior 1 month. It consists of 19 individual items that combine to form 7 components summed to create one global score. The overall score is between 0 (better sleep) and 21 (worse sleep). | All subjects completed both arms of this crossover study. | Posted | Mean | Standard Deviation | units on a scale | Every 4 weeks during the 12 week study (at the start and end of the usual care period, and at the start and end of the Bilevel PAP intervention period) |
|
|
|
|
| Secondary | Short Form (SF-36) Health Survey | Well validated quality of life questionnaire that measures eight sub-sections, which are summed to yield a score from 0 (maximal disability) to 100 (no disability). The eight subsections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health. | All subjects completed both arms of the study | Posted | Mean | Standard Deviation | units on a scale | Every 4 weeks during the 12 week study (at the start and end of the usual care period, and at the start and end of the Bilevel PAP intervention period) |
|
|
|
|
| Secondary | FEV1 %Predicted | Performed as part of spirometry | All subjects completed both arms of this crossover study. | Posted | Mean | Standard Deviation | percentage of predicted FEV1 | Every 4 weeks during the 12 week study (at the start and end of the usual care period, and at the start and end of the Bilevel PAP intervention period) |
|
|
|
|
| 0 |
| 13 |
| 3 |
| 13 |
| EG001 | Asthma + OSA | Subjects meeting all inclusion criteria and no exclusion criteria with asthma and obstructive sleep apnea on continuous positive airway pressure (CPAP) treatment | 0 | 8 | 0 | 8 |
|
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D012138 |
| Respiratory Therapy |