Systemic Determinants of Exercise Intolerance in PatientsWith Fibrotic Interstitial Lung Disease and Severely Impaired D_LCO

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 (D-LCO < 40% predicted) are not fully understood. Rather than only reflecting impaired O-2 transfer, a severely impaired D-LCO 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 D-LCO < 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 D-LCO < 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-LCO (P <.05). Peak work rate was similar to 45% (vs controls) and similar to 20% (vs D-LCO > 40%) lower in the former group, being associated with lower (and flatter) O-2 pulse, an earlier lactate (anaerobic) threshold, heightened submaximal ventilation, and lower S-pO2. Moreover, critically high inspiratory constrains were reached at lower exercise intensities in the D-LCO < 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 D-LCO 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-LCO < 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.