Partitioning of pulmonary responses to inhaled methacholine in subjects with asymptomatic asthma

To partition the central and peripheral airway resistance, a catheter-tip micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a bronchus with a 3 mm inner diameter in 10 patients with asymptomatic asthma. We simultaneously measured mouth flow, transpulmonary pressure (PL) and intra-airway lateral pressure during tidal breathing. Total pulmonary resistance (RL) was calculated from PL and mouth flow, and central airway resistance (RC) was calculated from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by subtraction of RC from RL. Therefore, our measurement of Rp included lung tissue resistance. The technique permitted identification of the site of changes in airway resistance. The baseline values of resistances were 2.3 ± 0.2 cm H₂O/L/s in RL, 1.5 ± 0.1 cm H₂O/L/s in RC, and 0.8 ± 0.1 cm H₂O/L/s in Rp, respectively. To determine the site of airway hyperresponsiveness, dose- response curves of central, peripheral, and total airways to inhaled methacholine were separately constructed. Bronchial responsiveness was evaluated by a log methacholine unit requiring a 35% decrease (PC₃₅) and a 50% decrease (PC₅₀) in pulmonary conductance (a reciprocal of RL). We calculated the increase of resistances in total (ΔRL), central (ΔRC), and peripheral (ΔRp) airways from the baseline values at either PC₃₅ or PC₅₀. Both PC₃₅ and PC₅₀ negatively correlated to the ratio of ΔRp to ΔRL (r = -0.86, p < 0.01 and r = -0.68, p < 0.05, respectively), and they positively correlated to the ratio of ΔRC to ΔRL (r = 0.86, p < 0.01 and r = 0.68, p < 0.05, respectively). These results imply that peripheral airways, including lung tissue, are an important site for development of bronchial hyperresponsiveness in patients with asymptomatic asthma.