Positive Airway Pressure for the Treatment of Asthma

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Sleep Apnea
• Intervention / Treatment: Device: Bilevel PAP (4 weeks); Other: Usual Care (4 weeks); Other: Washout Period (4 weeks)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• mild to moderate asthma, diagnosed by a physician, OR
• mild to moderate asthma and CPAP treated OSA. Must be compliant with CPAP therapy (greater than 4 hours per night, at least 4 nights/week)

Exclusion Criteria:

• lung disease other than asthma or OSA
• medications known to affect respiratory function (apart from asthma and rhinitis therapy)
• abnormal nasal anatomy
• current smokers and ex-smokers (quit within the last 3 months, or >10 pack-years)
• pregnant women - women of child bearing age will undergo a urine pregnancy test before enrollment and during the course of the study, as some of the study procedures cannot be performed during pregnancy and because pregnancy often changes asthma symptoms and severity.
• severe asthma - defined as a recent exacerbation (doctor or ER visit for asthma, or oral steroid use, within the previous 4 weeks) or frequent exacerbations (>4 exacerbations in the last year.
• severe obstructive sleep apnea requiring supplemental oxygen in addition to CPAP therapy.
• the regular use of prescription (e.g. zolpidem) or over-the-counter sleep aids (e.g. Benadryl).
• Central sleep apnea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Device: Bilevel PAP (4 weeks); 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.; Other Names: Bilevel positive airway pressure; Other: Usual Care (4 weeks); Subjects will continue with their usual asthma care. Investigators will make no changes to their medications or other habits.; Other: Washout Period (4 weeks); 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.
Experimental: 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.	Device: Bilevel PAP (4 weeks); 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.; Other Names: Bilevel positive airway pressure; Other: Usual Care (4 weeks); Subjects will continue with their usual asthma care. Investigators will make no changes to their medications or other habits.; Other: Washout Period (4 weeks); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Secondary Outcome Measures

Outcome Measure	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)
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)

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Robert L Owens, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 18, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (Estimate): July 1, 2010

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: May 11, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Asthma; Obstructive sleep apnea; Lung volumes; Nocturnal Asthma; Deep inspiration
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Immune System Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Sleep Apnea Syndromes; Asthma
• Other Study ID Numbers: 2009-P-001733/1; 1F32HL097578-01 (U.S. NIH Grant/Contract); 5K23HL105542 (U.S. NIH Grant/Contract)