Influence of low-dose dopamine on exercise in fibrosing interstitial lung disease

Fibrotic interstitial lung disease (FILD) is associated with dyspnoea and exercise intolerance. In other cardiorespiratory conditions, heightened carotid body (CB) chemoreflex sensitivity is associated with reduced exercise capacity. We tested the hypothesis that CB chemoreflex inhibition would improve exercise endurance time (EET) and reduce dyspnoea in FILD. In this randomised, single-blind study, 10 FILD patients (four women, 64 ± 8 years) completed the experimental procedures. Low-dose dopamine infusion (2 µg/kg/min) was used to inhibit the CB chemoreflex, and its effectiveness verified by measuring the hypoxic ventilatory response. Participants performed two constant work rate cycle exercise tests (75% of peak work rate) to exhaustion with either dopamine or saline as control. Dopamine suppressed the CB chemoreflex sensitivity in seven of the ten participants. Overall, dopamine reduced chemoreflex sensitivity by 27% relative to control (-0.646 ± 0.344 vs. -0.472 ± 0.410 L/min/%, P = 0.103). EET (saline 460 ± 411 s vs. dopamine 363 ± 182 s, P = 0.305) and exertional dyspnoea scores were similar between the conditions. Among those displaying reduced CB sensitivity with dopamine, there was a positive correlation between the magnitude of reduction in sensitivity and improvement in EET (r_s = 0.943, P = 0.005). Dopamine was associated with reduced blood pressure and increased heart rate. Although low-dose dopamine did not improve exercise capacity or dyspnoea in the group overall, subset analysis of those who achieved CB chemoreflex suppression (n = 7/10) with dopamine demonstrated a strong positive correlation between the reduction in sensitivity and EET improvement. This could suggest that the CB chemoreflex restrains exercise capacity in FILD.