Disparity Between Proximal and Distal Airway Reactivity During Methacholine Challenge

Abstract

There is an increasing awareness of the role of distal airways in the pathophysiology of obstructive lung diseases including asthma and chronic obstructive pulmonary disease. We hypothesize that during induced bronchoconstriction: 1) disparity between distal and proximal airway reactivity may occur; and 2) changes in distal airway function may explain symptom onset in subjects with minimal FEV₁ change. 185 subjects underwent methacholine challenge testing (MCT). In addition to spirometry, oscillometry was performed at baseline and after maximum dose of methacholine; 33/185 also underwent oscillometry after each dose. Oscillometric parameters included resistance at 5 and 20 Hz (R_5, R₂₀) and heterogeneity of distal airway mechanics assessed by frequency dependence of resistance 5–20 Hz (R_5–20) and reactance area (AX). R₅ varied widely during MCT (range -0.8 – 11.3 cmH₂O/L/s) and correlated poorly with change in FEV₁ (r = 0.17). Changes in R₅ reflected changes in both R₂₀ and R_5–20 (r = 0.59, p<0.05; r = 0.87, p<0.0001). However, R₂₀ increased only 0.3 cmH₂O/L/s, while R_5–20 increased 0.7 cmH₂O/L/s for every 1cmH₂O/L/s change in R_5, indicating predominant effect of distal airway mechanics. 9/33 subjects developed symptoms despite minimal FEV₁ change (<5%), while R₅ increased 42% due to increased distal airway heterogeneity. These data indicate disparate behavior of proximal airway resistance (FEV₁ and R₂₀) and distal airway heterogeneity (R_5–20 and AX). Distal airway reactivity may be associated with methacholine-induced symptoms despite absence of change in FEV₁. This study highlights the importance of disparity between proximal and distal airway behavior, which has implications in understanding pathophysiology of obstructive pulmonary diseases and their response to treatment.

Keywords::

• Bronchial Provocation Tests
• Small airways physiology
• Airway Resistance
• Oscillometry