Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Queen's University and Kingston Health Sciences Centre, Kingston General Hospital, Kingston, Ontario, Canada.
Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Queen's University and Kingston Health Sciences Centre, Kingston General Hospital, Kingston, Ontario, Canada; and Centre for Heart Lung Innovation, Providence Health Care Research Institute, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Respir Care. 2023 Nov 25;68(12):1662-1674. doi: 10.4187/respcare.11147.
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 (D < 40% predicted) are not fully understood. Rather than only reflecting impaired O transfer, a severely impaired D may signal deranged integrative physiologic adjustments to exercise that jointly increase the burden of exertional symptoms in fibrotic ILD.
Sixty-seven subjects (46 with idiopathic pulmonary fibrosis, 24 showing D < 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.
Subjects from the D < 40% group showed lower spirometric values, more severe restriction, and lower alveolar volume and transfer coefficient compared to controls and participants with less impaired D ( < .05). Peak work rate was ∼45% (vs controls) and ∼20% (vs D > 40%) lower in the former group, being associated with lower (and flatter) O pulse, an earlier lactate (anaerobic) threshold, heightened submaximal ventilation, and lower S . Moreover, critically high inspiratory constrains were reached at lower exercise intensities in the D < 40% group ( < .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 ( > .05).
A severely reduced D 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. D < 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.
导致弥散功能严重受损（D < 40%预计值）的纤维化间质性肺疾病（fibrotic ILDs）患者运动耐量降低的确切机制尚不完全清楚。弥散功能严重受损并不仅仅反映了 O 转移的受损，它可能还表明了整合生理调节的紊乱，这些紊乱共同增加了纤维化 ILD 中运动性症状的负担。
67 名受试者（46 名特发性肺纤维化患者，24 名 D < 40%）和 22 名对照者接受了肺功能测试和递增心肺运动试验，同时进行了连续的运动肺容量和 0-10 级 Borg 呼吸困难和腿部不适评分测量。
D < 40%组的受试者比对照组和 D > 40%组的患者的肺活量测定值更低，限制性通气障碍更严重，肺泡容积和转移系数更低（< 0.05）。前者的峰值工作率约为对照组的 45%（和 20%），与较低的（和更平坦的）O 脉冲、更早的乳酸（无氧）阈值、更高的亚最大通气量和较低的 S 有关。此外，D < 40%组在较低的运动强度下达到了临界高吸气限制（< 0.05）。与最大腿部不适评分相关，在给定的工作率下，他们报告了最高的呼吸困难评分。当呼吸困难强度与增加的需求-能力失衡指数相关时，组间差异减小或消失，即减少亚最大、动态通气储备和吸气储备量/总肺容量（> 0.05）。
纤维化 ILD 中严重降低的 D 表明存在多种相互关联的紊乱（心血管损伤、早期向无氧代谢的转变、过度通气、吸气限制和低氧血症），这些紊乱最终导致限制呼吸（呼吸困难）和外周（腿部不适）症状。因此，D < 40% 可能有助于临床决策，表明纤维化 ILD 患者可能从旨在减轻这些全身异常的药物和非药物干预中获益。
