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Mechanisms of exertional dyspnea in postsurgical patients with non-small cell lung cancer Harper, Megan


Background: Dyspnea is a debilitating symptom reported by patients with non-small cell lung cancer (NSCLC) after pulmonary resection. Reduced ventilatory capacity and respiratory muscle weakness associated with surgery could lead to an imbalance between ventilatory effort and output (a phenomenon known as neuromechanical uncoupling [NMU]) and result in dyspnea. Additionally, augmented pulmonary vascular resistance may impair left ventricular (LV) stroke volume (SV), and contribute to dyspnea and exercise intolerance. It was therefore hypothesized that greater NMU would be associated with dyspnea and exercise intolerance in NSCLC. It was also hypothesized that reduced diastolic filling and decreased LV SV would be associated with dyspnea and exercise intolerance in NSCLC. Methods: Using a cross-sectional design, thirteen post-surgical NSCLC patients performed a pulmonary function test and an incremental cardiopulmonary exercise test, followed by constant-load cycling exercise at 25%, 50%, and 75% Wmax. At 75% Wmax, patients exercised until symptom limitation. The sensory intensity, unpleasantness and sensory qualities of dyspnea were measured during exercise using the modified Borg scale and the multidimensional dyspnea profile. Ventilatory parameters, esophageal pressures, and operational lung volumes were measured continuously; echocardiography was employed during the constant-load trials. Healthy, sedentary age and sex-matched individuals were selected from our database for comparison to the NSCLC group. Results: Patients with NSCLC reported greater intensity of dyspnea for a given power output when compared to controls, particularly during higher intensity exercise. NMU was unchanged throughout exercise despite significant reductions in ventilatory capacity (p<0.05). There was a significant correlation between the resting E/A and exercise tolerance (r² = 0.58; p = 0.035); however, there were no significant correlations observed between ventilatory or cardiovascular parameters and dyspnea or exercise tolerance. Conclusion: In contrast to our hypothesis, we observed no evidence of NMU during exercise in NSCLC. The lack of association between ventilatory parameters and dyspnea suggests that the mechanisms of dyspnea are different from those previously identified in other respiratory diseases. The primary constraint to exercise appeared to be ventilatory limitation secondary to reduced ventilatory capacity and increased ventilatory demand due to peripheral deconditioning. Therapeutic interventions that improve aerobic capacity and reduce ventilatory drive are now warranted with the ultimate aim of reducing dyspnea in this population.

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