Sensitization in Medically Unexplained Dyspnea: Differential Effects on Intensity and Unpleasantness

Background The present study investigated alterations in both the sensory (intensity) and the affective (unpleasantness) components of dyspnea in patients with medically unexplained dyspnea during repeated hypercapnic challenges. Methods The sensory and affective components were assessed every 20 s during the baseline, rebreathing, and recovery phases of three subsequent trials in patients (n = 17) and matched healthy control subjects (n = 5). Fractional end-tidal carbon dioxide was monitored simultaneously and continuously. Peak intensity and unpleasantness were compared, and intraindividual linear regression slopes between the dyspnea components and fractional end-tidal carbon dioxide were calculated. Results Both intensity and unpleasantness of dyspnea perception were higher in patients than in healthy control subjects. Additionally, the regression slopes were steeper, but this was more prominent for the affective than for the sensory component in patients. Moreover, across-trial increases in unpleasantness of peak dyspnea and slopes of both components were observed in patients. Conclusions Patients with medically unexplained dyspnea are particularly hypersensitive to the unpleasantness of dyspnea. The elevated breathlessness further increases across repeated challenges, documenting sensitization and suggesting that basic learning mechanisms contribute to exaggerated response to respiratory challenges.