Uncovering the mechanisms of exertional dyspnoea in combined pulmonary fibrosis and emphysema

The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxemia. There is little evidence, however, to support these assumptions. We prospectively contrasted the sensory and physiological responses to exercise in 42 CPFE and 16 IPF patients matched by the severity of exertional hypoxemia. Emphysema and PF were quantified by computed tomography. Inspiratory constraints were assessed in a constant work rate test: capillary (c) blood gases were obtained in a sub-set of patients. CPFE patients had lower exercise capacity despite less extensive fibrosis compared to IPF (p=0.004 and 0.02, respectively). Exertional dyspnoea was the key limiting symptom in 24 CPFE patients who showed significantly lower transfer factor, PaCO2 and ventilatory efficiency (higher ventilation (VE)/CO2 output (VCO2) ratio) compared to those with less dyspnoea. There were, however, no between-group differences in the likelihood of pulmonary hypertension by echocardiography (p=0.44). High dead space/tidal volume ratio, low PcCO2, emphysema severity (including admixed emphysema) and traction bronchiectasis were related to a high VE/VCO2 in the more dyspnoeic group. VE/VCO2 nadir >50 (odds ratio (95% confidence interval)=9.43 (5.28–13.6), p=0.0001) and total emphysema extent >15% (2.25 (1.28–3.54), p=0.01) predicted a high dyspnoea burden associated with severely-reduced exercise capacity in CPFE Contrary to current understanding, hypoxemia per se is not the main determinant of exertional dyspnoea in CPFE. Poor ventilatory efficiency due to increased “wasted” ventilation in emphysematous areas and hyperventilation holds a key mechanistic role that deserves therapeutic attention.