Effect of Continuous Positive Airway Pressure on Airway Reactivity in Asthma. A Randomized, Sham-controlled Clinical Trial

Abstract

Rationale: Studies have demonstrated that application of stress suppresses airway smooth muscle contractility. In animal models of asthma, continuous positive airway pressure (CPAP) reduced airway reactivity. Short-term studies of CPAP in patients with asthma showed reductions in airway reactivity.

Objectives: To evaluate whether nocturnal CPAP decreased the provocative concentration of methacholine to reduce FEV₁ by 20% (PC₂₀).

Methods: One hundred ninety-four individuals with asthma were randomized (1:1:1) to use CPAP with warmed, filtered, humidified air at night at pressures either less than 1 cm H₂O (sham) or at 5 cm H₂O or 10 cm H₂O. The primary outcome was change in PC₂₀ after 12 weeks.

Measurements and main results: Adherence to CPAP was low in all groups. Regardless, all groups had a significant improvement in PC₂₀, with 12 weeks/baseline PC₂₀ ratios of 2.12, 1.73, and 1.78 for the sham, 5 cm H₂O, and 10 cm H₂O groups, respectively, and no significant differences between the active and sham groups. Changes in FEV₁ and exhaled nitric oxide were minimal in all groups. The sham group had larger improvements in most patient-reported outcomes measuring asthma symptoms and quality of life, as well as sinus symptoms, than the 5 cm H₂O group. The 10 cm H₂O group showed similar but less consistent improvements in scores, which were not different from improvements in the sham group.

Conclusions: Adherence to nocturnal CPAP was low. There was no evidence to support positive pressure as being effective for reducing airway reactivity in people with well-controlled asthma. Regardless, airway reactivity was improved in all groups, which may represent an effect of participating in a study and/or an effect of warm, humid, filtered air on airway reactivity. Clinical trial registered with www.clinicaltrials.gov (NCT01629823).

Keywords: CPAP; PC20; airway reactivity; asthma; methacholine.

Figure 1.

Study design diagram. Participants were screened at V1 (0–4 d before randomization) and randomized at V2. V3 and V4 were conducted early to troubleshoot problems with continuous positive airway pressure (CPAP) initiation or adherence. Methacholine challenge tests were done at V1, V5 (6 wk), V6 (12 wk), and V7 (14 wk; 2 wk after CPAP use discontinued).

Figure 2.

Consolidated Standards of Reporting Trials diagram of the study. Of the 1,952 participants screened, 1,743 were excluded before enrollment or during the run-in period. Two hundred nine participants were randomized to receive one of the three treatments. Data from one clinic (15 patients) were excluded from the analysis because of data irregularities. Methacholine (MeCh) challenge tests were obtained for 194 participants at baseline, 158 participants at 6 weeks, 158 participants at 12 weeks, and 152 participants after washout. One hundred ninety-four participants were included in the analysis for the trial period, and 165 participants were included in the analysis for the washout period. *Other reasons included those categories with less than 5% (refused or unable to do study procedures [n = 66], previous use of continuous positive airway pressure [CPAP] [n = 44], history or high risk of sleep apnea [≥20% by Multivariable Apnea Prediction Index] [n = 35], sleeps <6 h/night on average [n = 17], not fluent in English or Spanish [n = 14], compensation [n = 6], multiple reasons given [n = 39], and no reason specified [n = 768]). BMI = body mass index; PC₂₀ = concentration of methacholine required to cause a 20% fall in FEV₁.

Figure 3.

Change in concentration of methacholine required to cause a 20% fall in FEV₁ (PC₂₀), by treatment. Median of ratio of PC₂₀ relative to baseline and 95% confidence intervals (CIs) over time by treatment group with 95% CI in the trial period (baseline and Weeks 6 and 12).