BACKGROUND The precise mechanisms driving poor exercise tolerance in patients with fibrotic interstitial lung diseases (fibrotic ILDs) showing a severe impairment in single-breath lung diffusing capacity for carbon monoxide (DLCO < 40% predicted) are not fully understood. Rather than only reflecting impaired O2 transfer, a severely impaired DLCO may signal deranged integrative physiologic adjustments to exercise that jointly increase the burden of exertional symptoms in fibrotic ILD. METHODS Sixty-seven subjects (46 with idiopathic pulmonary fibrosis, 24 showing DLCO < 40%) and 22 controls underwent pulmonary function tests and an incremental cardiopulmonary exercise test with serial measurements of operating lung volumes and 0-10 Borg dyspnea and leg discomfort scores. RESULTS Subjects from the DLCO < 40% group showed lower spirometric values, more severe restriction, and lower alveolar volume and transfer coefficient compared to controls and participants with less impaired DLCO (P < .05). Peak work rate was ∼45% (vs controls) and ∼20% (vs DLCO > 40%) lower in the former group, being associated with lower (and flatter) O2 pulse, an earlier lactate (anaerobic) threshold, heightened submaximal ventilation, and lower SpO2 . Moreover, critically high inspiratory constrains were reached at lower exercise intensities in the DLCO < 40% group (P < .05). In association with the greatest leg discomfort scores, they reported the highest dyspnea scores at a given work rate. Between-group differences lessened or disappeared when dyspnea intensity was related to indexes of increased demand-capacity imbalance, that is, decreasing submaximal, dynamic ventilatory reserve, and inspiratory reserve volume/total lung capacity (P > .05). CONCLUSIONS A severely reduced DLCO in fibrotic ILD signals multiple interconnected derangements (cardiovascular impairment, an early shift to anaerobic metabolism, excess ventilation, inspiratory constraints, and hypoxemia) that ultimately lead to limiting respiratory (dyspnea) and peripheral (leg discomfort) symptoms. DLCO < 40%, therefore, might help in clinical decision-making to indicate the patient with fibrotic ILD who might derive particular benefit from pharmacologic and non-pharmacologic interventions aimed at lessening these systemic abnormalities.

中文翻译：

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纤维化间质性肺病和 DLCO 严重受损患者运动不耐受的全身决定因素。

背景 纤维化间质性肺疾病（纤维化 ILD）患者运动耐量差的确切机制尚不完全清楚，该患者的单次呼吸肺一氧化碳弥散能力严重受损（DLCO <预测值的 40%）。严重受损的 DLCO 不仅反映了 O2 传输受损，还可能表明运动的综合生理调整紊乱，从而共同增加了纤维化 ILD 的运动症状负担。方法 67 名受试者（46 名患有特发性肺纤维化，24 名显示 DLCO < 40%）和 22 名对照者接受了肺功能测试和增量心肺运动测试，连续测量操作肺容量以及 0-10 Borg 呼吸困难和腿部不适评分。结果 与对照组和 DLCO 受损较轻的参与者相比，DLCO < 40% 组的受试者表现出较低的肺量测定值、更严重的限制以及较低的肺泡容积和传输系数 (P < .05)。前一组的峰值工作率分别低约 45%（与对照组相比）和约 20%（与 DLCO > 40% 相比），这与较低（且平坦）的 O2 脉冲、较早的乳酸（无氧）阈值、较高的次最大通气量相关，并降低 SpO2 。此外，DLCO < 40% 组在较低运动强度下达到了极高的吸气受限 (P < .05)。与最大的腿部不适分数相关，他们报告了在给定工作率下最高的呼吸困难分数。当呼吸困难强度与需求能力不平衡指标增加相关时，即次最大动态通气储备和吸气储备量/肺总量的减少（P > .05），组间差异减少或消失。结论 纤维化 ILD 中 DLCO 严重减少预示着多种相互关联的紊乱（心血管损伤、早期转向无氧代谢、通气过度、吸气受限和低氧血症），最终导致限制呼吸（呼吸困难）和外周（腿部不适）症状。因此，DLCO < 40% 可能有助于临床决策，表明患有纤维化 ILD 的患者可能会从旨在减轻这些全身异常的药物和非药物干预中获得特别的益处。