The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxaemia. However, there is little evidence 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 hypoxaemia. Emphysema and pulmonary fibrosis were quantified using computed tomography. Inspiratory constraints were assessed in a constant work rate test: capillary blood gases were obtained in a subset 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, arterial carbon dioxide tension and ventilatory efficiency (higher minute ventilation (V′E)/carbon dioxide output (V′CO2) ratio) compared to those with less dyspnoea. However, there were no between-group differences in the likelihood of pulmonary hypertension by echocardiography (p=0.44). High dead space/tidal volume ratio, low capillary carbon dioxide tension emphysema severity (including admixed emphysema) and traction bronchiectasis were related to a high V′E/V′CO2 ratio in the more dyspnoeic group. V′E/V′CO2 nadir >50 (OR 9.43, 95% CI 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, hypoxaemia 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. Exertional dyspnoea is related to poor ventilatory efficiency rather than hypoxaemia or inspiratory constraints in CPFE. Lessening patients' excessive ventilation might prove particularly beneficial to mitigate the burden of this disabling symptom. http://bit.ly/2MRn6az

中文翻译：

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揭示合并肺纤维化和肺气肿的劳力性呼吸困难的机制

普遍的观点是，特发性肺纤维化 (IPF) 和肺气肿 (CPFE) 合并患者的劳力性呼吸困难在很大程度上可以用严重的低氧血症来解释。然而，几乎没有证据支持这些假设。我们前瞻性地对比了与劳力性低氧血症严重程度相匹配的 42 名 CPFE 和 16 名 IPF 患者对运动的感觉和生理反应。使用计算机断层扫描量化肺气肿和肺纤维化。在恒定工作速率测试中评估了吸气限制：获得了一部分患者的毛细血管血气。尽管与 IPF 相比，CPFE 患者的纤维化程度较低，但其运动能力较低（分别为 p=0.004 和 0.02）。劳力性呼吸困难是 24 名转移因子显着降低的 CPFE 患者的主要限制性症状，与呼吸困难较少的患者相比，动脉二氧化碳张力和通气效率（每分钟通气量 (V'E)/二氧化碳输出量 (V'CO2) 比率更高）。然而，超声心动图显示肺动脉高压的可能性没有组间差异（p=0.44）。高死腔/潮气量比、低毛细血管二氧化碳张力肺气肿严重程度（包括混合性肺气肿）和牵引性支气管扩张与呼吸困难组的高 V'E/V'CO2 比值有关。V'E/V'CO2 最低点 >50（OR 9.43, 95% CI 5.28–13.6；p=0.0001）和总肺气肿范围 >15%（2.25, 1.28–3.54；p=0.01）预测与呼吸困难相关的高呼吸困难负担CPFE 运动能力严重降低 与目前的理解相反，低氧血症本身并不是 CPFE 劳力性呼吸困难的主要决定因素。由于肺气肿区域“浪费”的通气量增加导致通气效率低下，过度通气具有重要的机械作用，值得治疗关注。在 CPFE 中，劳力性呼吸困难与通气效率低下有关，而不是低氧血症或吸气受限。减少患者过度通气可能特别有益于减轻这种致残症状的负担。http://bit.ly/2MRn6az