It is well established that failure to apply rhythmic strain to airway smooth muscle leads to a change in the biomechanics of the smooth muscle characterized by shortened resting length, and increased sensitivity to pharmacologic constrictors. Patients with asthma have physiologic airway characteristics that recapitulate this condition - increased airway tone and increased sensitivity to methacholine. It is our underlying hypothesis that asthma is initiated by airway inflammation, but is sustained and promoted by decreased tidal force fluctuations during sleep. If true, then treatments that increase tidal force fluctuations of airways during sleep could reverse these abnormalities. One such proposed treatment is continuous positive airway pressure (CPAP) which prevents the fall in end expiratory lung volume and prevents closure of airways in dependent regions of the lung ~ thereby permitting the stresses of tidal breathing to apply strain to the airways. Preclinical data in rabbit models of asthma treated with CPAP showed significantly reduced sensitivity to acetylcholine-induced airway constriction compared to those treated with sham CPAP or no CPAP. Human data in 15 asthmatics showed that 1 week of 8-10cm H20 nocturnal CPAP was associated with a 2.7-fold increase in the concentration of methacholine causing a 20% fall in FEV1 (PC20). The objective of this study is to conduct a randomized, sham-controlled, multicenter study of 5 and 10 cm H20 nocturnal CPAP in order to confirm these findings;to determine the durability of the effect over 12 weeks;to assess the tolerability and adherence to this treatment;and to explore if CPAP treatment translates into clinically meaningful outcomes. The study will be conducted at 19 centers of the American Lung Association-Asthma Clinical Research Centers (ALA-ACRC) with a data coordinating center (DCC) at Johns Hopkins University.

Public Health Relevance

Asthma is a common chronic disease that affects 23 million Americans and is the most common chronic disease of childhood. Current drugs, aimed at reducing inflammation and airway narrowing are not adequate for many asthma sufferers, and concerns have been raised about long-term safety of these drugs. If CPAP at night is effective, it will represent an entirely new approach to treating asthma.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL108730-02
Application #
8320190
Study Section
Special Emphasis Panel (ZHL1-CSR-H (M1))
Program Officer
Freemer, Michelle M,
Project Start
2011-09-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$1,955,869
Indirect Cost
$465,921
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218