Asthma
Conditions
Keywords
obesity, asthma
Brief summary
The purpose of this study is to test the effect of increasing lung volume with a simple hand-held device to both prevent, and also to relieve, airway constriction in people with asthma and a BMI ≥ 30 kg/m2. Twenty people with late onset non-allergic asthma and a BMI of ≥ 30 kg/m2 will be recruited. The efficacy of elevating lung volume on both preventing and reversing bronchoconstriction will be tested. Lung volume will be modulated by breathing out against a small level of resistance (positive expiratory pressure).
Detailed description
This study will investigate whether PEEP can prevent and/or reverse bronchoconstriction in asthmatics with a BMI \> 30 kg/m2. People with late-onset non-allergic asthma that develops in the setting of obesity do not respond well to conventional asthma medications, likely because all treatments for asthma have been developed to treat early-onset allergic disease in lean patients. There is a critical need to understand the pathophysiology of airway disease in late-onset, non-allergic obese asthmatics, in order to develop therapies to target this disease. Airway hyperresponsiveness (AHR) is a defining characteristic in asthma. Lung function tests in individuals with late onset asthma in the setting of obesity are suggestive of distal airway closure rather than airway narrowing as a cause of hyperresponsiveness; these individuals tend to have more collapsible lung peripheries than obese individuals who do not develop asthma. If late onset asthma in obesity is related to a tendency of airways to close, it should respond to therapies designed to keep airways open, such as Positive End-Expiratory Pressure (PEEP). The purpose of this study is to investigate the efficacy of PEEP on prevention and reversal of bronchoconstriction in obese people with asthma. This will be achieved by investigating the efficacy of PEEP therapy on preventing and reversing bronchoconstriction in response to the inhalation of methacholine, while measuring changes in respiratory impedance using the forced oscillation method. Participants will initially perform a conventional methacholine challenge test. Participants will return for 2 visits in which methacholine will be administered concurrently with varying levels of PEEP (using PEEP to prevent bronchoconstriction) while measuring changes in respiratory impedance using the forced oscillation method. Participants will return for another 2 visits in which PEEP will be administered subsequent to methacholine challenge (using PEEP to reverse bronchoconstriction) while measuring changes in respiratory impedance using the forced oscillation method. These studies will be completed over 5 visits.
Interventions
Patient will exhale against positive expiratory pressure 0 mm or 10 mm while inhaling methacholine
Sponsors
University of Vermont
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* PC20 to methacholine \< 16 mg/ml * Asthma diagnosis when ≥ 18 years of age * Serum Immunoglobulin E \< 100 IU/ml * Ages ≥ 18 years * BMI ≥ 30 kg/m2
Exclusion criteria
* Asthma exacerbation (defined as a hospitalization, ED visit, urgent care visit for asthma or new corticosteroids for asthma) in prior 6 weeks. * Forced Expiratory Volume in 1 second \< 60 % predicted * Other significant disease that in the opinion of the investigator would interfere with study * Inability to perform required testing. * Smoking within last 6 months. * ≥ 20 pack year smoking history * Inability to provide informed consent * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Central and Peripheral Elastance | The end of the experiment (at the 8-min time point) | Investigators compare changes in respiratory system elastance to methacholine. Respiratory system impedance was measured at the 8-min time point and fit with the two-compartment series model of respiratory mechanics. The elastances of the central and distal compartments obtained from good quality fits of this model are reported for each of the following conditions: V2: PEP of 0 was administered during (0-4.5 min) and after (4.5-8 min) methacholine administration. V3: PEP of 0 was administered during (0-4.5 min) and PEP of 10 cmH2O after (4.5-8 min) methacholine administration. V4: This is a repeat of V2 above to test for stability of the response. V5: PEP of 10 cmH2O was administered both during (0-4.5 min) and after (4.5-8 min) methacholine administration. V1 was a baseline visit to establish physiologic parameters required for conducting Visits 2-5. There are no outcome measures for Visit 1. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled between 2016-2019. There was a minor delay to the enrollment timeline relative to the proposed starting date due to staffing changes. The uploaded protocol is an IRB approved document. Given that the study is now complete, the IRB record has been closed out and further modification of this protocol is not possible.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Assigned to Intervention in Cross Over Design participants underwent the following studies and intervention
1\. PEP 10 after methacholine 3. PEP 10 during methacholine 3. PEP 0 | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | All Study Participants Assigned to Intervention in Cross Over Design |
|---|---|
| Age, Continuous | 52 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
Central and Peripheral Elastance
Investigators compare changes in respiratory system elastance to methacholine. Respiratory system impedance was measured at the 8-min time point and fit with the two-compartment series model of respiratory mechanics. The elastances of the central and distal compartments obtained from good quality fits of this model are reported for each of the following conditions: V2: PEP of 0 was administered during (0-4.5 min) and after (4.5-8 min) methacholine administration. V3: PEP of 0 was administered during (0-4.5 min) and PEP of 10 cmH2O after (4.5-8 min) methacholine administration. V4: This is a repeat of V2 above to test for stability of the response. V5: PEP of 10 cmH2O was administered both during (0-4.5 min) and after (4.5-8 min) methacholine administration. V1 was a baseline visit to establish physiologic parameters required for conducting Visits 2-5. There are no outcome measures for Visit 1.
Time frame: The end of the experiment (at the 8-min time point)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Visit 2 | Central and Peripheral Elastance | Peripheral Elastance | 103 cmH2O/L | Standard Error 50 |
| Visit 2 | Central and Peripheral Elastance | Central Elastance | 391 cmH2O/L | Standard Error 86 |
| Visit 3 | Central and Peripheral Elastance | Central Elastance | 461 cmH2O/L | Standard Error 82 |
| Visit 3 | Central and Peripheral Elastance | Peripheral Elastance | 82 cmH2O/L | Standard Error 16 |
| Visit 4 | Central and Peripheral Elastance | Central Elastance | 587 cmH2O/L | Standard Error 299 |
| Visit 4 | Central and Peripheral Elastance | Peripheral Elastance | 162 cmH2O/L | Standard Error 33 |
| Visit 5 | Central and Peripheral Elastance | Peripheral Elastance | 42 cmH2O/L | Standard Error 16 |
| Visit 5 | Central and Peripheral Elastance | Central Elastance | 334 cmH2O/L | Standard Error 60 |