title: Identification of three exercise-induced mortality risk factors in patients with COPD.
abstract: The survival rate of chronic obstructive pulmonary disease (COPD) patients with severely reduced exercise capacity is extremely low. We recently identified three life-threatening pathophysiological conditions during cardiopulmonary exercise testing (CPET): (1) exercise-induced hypoxemia, (2) sympathetic overactivity, and (3) progressive respiratory acidosis at low-intensity exercise. The present prospective observation study aimed to determine whether these parameters constitute risk factors of mortality in moderate-to-very severe COPD. Ninety-six COPD patients were followed-up, monthly, for >3 years. Subsequently, spirometry and CPET were performed to examine parameters of exercise-induced hypoxemia ([PaO2 slope, mmHg/L · min(-1)] = Decrease in PaO2/ΔV˙ O2 (Difference in ΔV˙ O2 between at rest and at peak exercise)), progression of acidosis ([ΔpH/ΔV˙ O2,/L · min(-1)] = Decrease in pH/ΔV˙ O2), and sympathetic overactivity ([Δnorepinephrine (NE)/ΔV˙ O2, ng/mL/L · min(-1)] = Increase in NE/ΔV˙ O2). Univariate analysis revealed a significant association between the three conditions with increased mortality. Kaplan-Meier analysis showed that the quartile combining the steepest PaO2 slope (≤-55 mmHg/ΔV˙ O2 [L/min]), steepest decrease in arterial blood pH (≤ -1.72/ΔV˙ O2 [L/min]), and most rapid increase in plasma NE level (≥ 5.2 ng/VO2 [L/min]) during incremental exercise was associated with higher all-cause mortality. These conditions showed cumulative effects on COPD patients' survival. Multivariate analyses revealed that these three life-threatening factors are also independent predictors of mortality based on age, heart rate and PaO2 at rest, body mass index, and forced expiratory volume in 1 s. Thus, these new exercise-induced mortality risk factors may lead to more efficient pulmonary rehabilitation programs for COPD patients based on patient-specific exercise-induced pathophysiological profiles.
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Toneyama Hospital , Toyonaka-city, Osaka , Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Ryoji
authors.initials: R
authors.lastname: Maekura
authors.forename: Toru
authors.initials: T
authors.lastname: Hiraga
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miki
authors.forename: Seigo
authors.initials: S
authors.lastname: Kitada
authors.forename: Mari
authors.initials: M
authors.lastname: Miki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tateishi
authors.forename: Masahide
authors.initials: M
authors.lastname: Mori
mesh_terms: D000142:Acidosis, Respiratory / Q000209:etiology / Q000503:physiopathology; D000368:Aged; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption; D010313:Partial Pressure; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000401:mortality* / Q000503:physiopathology*; D012307:Risk Factors; D012720:Severity of Illness Index; D015996:Survival Rate; D013564:Sympathetic Nervous System / Q000503:physiopathology
chemical_list: D009638:Norepinephrine
keywords: Exercise capacity; exercise-induced hypoxemia; progressive respiratory acidosis; survival rate; sympathetic overactivity