Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma (CPAP)
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional

Summary: 
      The CPAP trial is a 3-arm parallel design randomized sham-controlled trial. Participants are
      randomly assigned in equal allocation to one of three treatments: CPAP 10 cm water (H₂O)
      (high) vs. CPAP 5 cm H₂O (medium) vs. CPAP Sham (less than 1 cm H₂O, Low). The treatment
      period is 12 weeks with airways reactivity assessed at baseline, 6 and 12 weeks of treatment
      and after a 2 week washout.
    

Detailed description: 
      It is now well established that failure to rhythmically apply strain to airway smooth muscle
      leads to 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,
      although it may be initiated by allergic airway inflammation, is promoted by decreased tidal
      force fluctuations during recumbent sleep. If this is true, then treatments that increase
      tidal force fluctuations of airways should reverse these abnormalities. One treatment that
      increases tidal force fluctuations is continuous positive airway pressure (CPAP). CPAP
      prevents a 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
      airways. Preliminary data in 15 asthmatics showed that 1 week of 10cm H₂O nocturnal CPAP was
      associated with a remarkable 2.7-fold increase in the concentration of methacholine causing a
      20% fall in forced expiratory volume in 1 second (FEV₁) (PC20). The objective of this study
      is to conduct a randomized, sham-controlled, multicenter study of 5 and 10 cm H₂O CPAP in
      order to verify these findings; to assess the effect of nocturnal CPAP on airways reactivity;
      to determine the durability of the effect over 12 weeks; to assess the safety, tolerability
      and adherence to this treatment; and to explore if there are clinically meaningful benefits.
      The study will be conducted at 18 centers of the American Lung Association-Asthma Clinical
      Research Centers (ALA-ACRC) with the Data Coordinating Center (DCC) at Johns Hopkins
      University.

      A substudy of High Resolution Computed Tomography (HRCT) will also be conducted at a subset
      of the ACRC clinics. A total of 54 subjects (18 per arm)who are randomized in the main study
      will be voluntarily enrolled in the substudy to compare the structural changes in the airways
      across treatment groups and to correlate structural changes with the physiological changes. A
      total of two visits will be conducted. HRCT Visit 1 will be performed after randomization in
      the main CPAP study, and prior to initiation of CPAP. HRCT Visit 2 will be performed between
      weeks 10 and 12 of CPAP, at a different day or prior of methacholine challenge testing.Two CT
      scans will be performed each at different lung volume at each visit (Total of 4 scans for the
      study duration). The first volume will be at Total Lung Capacity (TLC), followed by another
      CT scan at Functional Residual Capacity (FRC).
    

Intervention name(s): Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)
Intervention type(s): Device
Intervention description(s): Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
Other intervention name(s): ResMed CPAP S9 series: Elite & Escape; Masks: Swift FX, Mirage FX
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment