The role of evaluating inspiratory constraints and ventilatory inefficiency in the investigation of dyspnea of unclear etiology

Abstract Background Exertional dyspnoea increases when the mechanical output of the respiratory muscles becomes uncoupled from increases in neural respiratory drive. Combining measurements of inspiratory constraints and ventilatory inefficiency may better uncover the role of mechanical-ventilatory abnormalities on exertional dyspnoea than the currently-recommended approach, i.e., a low breathing reserve. Methods We determined the presence of a low breathing reserve (1-(peak ventilation (VE)/estimated maximal voluntary ventilation) x 100   0.7) and ventilatory inefficiency (VE/CO2 output (VCO2) nadir>34) in 284 subjects (161 males) with “disproportionate dyspnoea” (N = 148), “dyspnea with multiple potential causes” (N = 93) and “dyspnea without an apparent cause. Results The agreement between breathing reserve and assessment of inspiratory constraints was only “fair” (kappa [confidence interval (CI)] = 0.264 [0.169–0.358]). Attainment of critical inspiratory constraints and an upward inflection in dyspnea ratings systematically preceded a low breathing reserve. Of note, ∼55% (93/167) of subjects with normal breathing reserve showed critical inspiratory constraints despite largely preserved lung function. Regardless of the breathing reserve, subjects showing critical inspiratory constraints and/or poor ventilatory efficiency reported higher dyspnea and more impaired exercise tolerance compared to their counterparts (p  Conclusion An integrated analysis of inspiratory constraints and ventilatory inefficiency is key to uncover physiological abnormalities germane to dyspnoea in clinical populations in whom the origins of this distressing symptom are uncertain.