Exhaled breath condensate detects baseline reductions in chloride and increases in response to albuterol in cystic fibrosis patients

Abstract

Impaired ion regulation and dehydration is the primary pathophysiology in cystic fibrosis (CF) lung disease. A potential application of exhaled breath condensate (EBC) collection is to assess airway surface liquid ionic composition at baseline and in response to pharmacological therapy in CF. Our aims were to determine if EBC could detect differences in ion regulation between CF and healthy and measure the effect of the albuterol on EBC ions in these populations. Baseline EBC Cl(-), DLCO and SpO2 were lower in CF (n = 16) compared to healthy participants (n = 16). EBC Cl(-) increased in CF subjects, while there was no change in DLCO or membrane conductance, but a decrease in pulmonary-capillary blood volume in both groups following albuterol. This resulted in an improvement in diffusion at the alveolar-capillary unit, and removal of the baseline difference in SpO2 by 90-minutes in CF subjects. These results demonstrate that EBC detects differences in ion regulation between healthy and CF individuals, and that albuterol mediates increases in Cl(-) in CF, suggesting that the benefits of albuterol extend beyond simple bronchodilation.

Keywords: diffusion capacity of the lungs for carbon monoxide and nitric oxide (DLCO/DLNO); exhaled chloride; exhaled sodium; peripheral oxygen saturation (SpO2).

Figure 1

Timeline of measurements during visit.

Figure 2

Effect of albuterol on EBC Ions in healthy and CF subjects. Panel A: Net EBC Cl⁻ (see methods for equation). Panel B: EBC Na⁺. The open circles represent subjects with CF with the response overtime shown as the broken line. The closed diamonds represent healthy subjects with the response overtime shown as the solid line. The error bars represent the standard error of the mean. Notes: *P < 0.01 healthy vs. CF and ^†P < 0.02 baseline vs. time post in CF subjects.

Figure 3

Bronchodilation in response to albuterol in healthy and CF subjects. The percent change in force expiratory flow at 25–75% of FVC (FEF_25–75) for each time point (30, 60 and 90-minutes post). CF subjects are represented by white bars and healthy subjects are represented by black bars. The error bars represent the standard error of the mean. Note:^†P < 0.02 baseline.

Figure 4

Effect of albuterol on pulmonary capillary blood volume and gas diffusion at the individual alveolar-capillary unit (D_M/V_C) in healthy and CF subjects. Panel A: Pulmonary capillary blood volume (V_C). Panel B: Gas Diffusion at the Individual Alveolar-capillary Unit (D_M/V_C). The open circles represent subjects with CF with the response overtime shown as the broken line. The closed diamonds represent healthy subjects with the response overtime shown as the solid line. The error bars represent the standard error of the mean. Notes:^†baseline vs. time post in CF subjects.