PEEP as Rescue Therapy for Asthmatics With Elevated BMI

Phase 1

Completed

• Conditions: Asthma
• Interventions: Device: Positive Expiratory Pressure

• Registration Number: NCT02696980
• Lead Sponsor: University of Vermont

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.

Study Timeline

• Study First Submitted: 2016-02-23
• Study First Submitted QC: 2016-03-01
• Study First Posted: 2016-03-02
• Study Start: 2016-04
• Primary Completion: 2019-04
• Study Completion: 2019-06
• Results First Submitted: 2022-01-21
• Status Verified: 2024-06
• Results First Submitted QC: 2024-06-21
• Last Update Submitted: 2024-06-21
• Results First Posted: 2024-07-17
• Last Update Posted: 2024-07-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Rescue	Positive Expiratory Pressure	Intervention: Positive expiratory pressure (PEEP) 10 will be applied after the administration of methacholine
Prophylaxis	Positive Expiratory Pressure	Intervention: Positive expiratory pressure (PEEP) 10 will be applied during the administration of methacholine
No PEEP	Positive Expiratory Pressure	Intervention: Positive expiratory pressure (PEEP) 0 will be applied during the administration of methacholine

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Vermont Lung Center; 🇺🇸 Colchester, Vermont, United States