Dyspnea and the Varying Pathophysiologic Manifestations of Chronic Obstructive Pulmonary Disease Evaluated by Cardiopulmonary Exercise Testing With Arterial Blood Analysis

Abstract

Background: Patients with chronic obstructive pulmonary disease (COPD) show varying mechanisms of exertional dyspnea with different exercise capacities. Methods: To investigate the pathophysiologic conditions related to exertional dyspnea, 294 COPD patients were evaluated using cardiopulmonary exercise testing (CPET) with arterial blood analyses, with the patients classified into two groups according to their exercise limitation: the leg fatigue group (n = 58) and the dyspnea group (n = 215). The dyspnea group was further subdivided into four groups based on peak oxygen uptake ( ${\stackrel{°}{\text{V}}}_{\text{O}2}$ in mL/min/kg): group A (< 11), group B (11 to < 15), group C (15 to < 21), and group D (≥21). Results: In the dyspnea group, group A (n = 28) showed the following findings: (i) the forced expiratory volume in 1 s was not correlated with the peak ${\stackrel{°}{\text{V}}}_{\text{O}2}$ (p = 0.288), (ii) the arterial oxygen tension (PaO₂) slope (peak minus resting PaO₂/Δ ${\stackrel{°}{\text{V}}}_{\text{O}2}$ ) was the steepest (p < 0.0001) among all subgroups, (iii) reduced tidal volume (V_T) was negatively correlated with respiratory frequency at peak exercise (p < 0.0001), and (iv) a break point in exertional V_T curve was determined in 17 (61%) patients in group A. In these patients, there was a significant negative correlation between bicarbonate ion ( ${\text{HCO}}_3^{-}$ ) levels at peak exercise and V_T level when the V_T-break point occurred (p = 0.032). In group D (n = 46), ${\text{HCO}}_3^{-}$ levels were negatively correlated with plasma lactate levels (p < 0.0001). In all subgroups, the ${\text{HCO}}_3^{-}$ level was negatively correlated with minute ventilation. The dyspnea subgroups showed no significant differences in the overall mean pH [7.363 (SD 0.039)] and Borg scale scores [7.4 (SD, 2.3)] at peak exercise. Conclusions: During exercise, ventilation is stimulated to avoid arterial blood acidosis and hypoxemia, but ventilatory stimulation is restricted in the setting of reduced respiratory system ability. These conditions provoke the exertional dyspnea in COPD. Although symptom levels were similar, the exertional pathophysiologic conditions differed according to residual exercise performance; moreover, COPD patients showed great inter-individual variability. An adequate understanding of individual pathophysiologic conditions using CPET is essential for proper management of COPD patients.

Keywords: COPD; acidosis; cardiopulmonary exercise testing; dyspnea; exercise tolerance; hypoxemia; norepinephrine.

Figure 1

Distribution of FEV₁ based on exercise tolerance. Patients were divided into seven groups according to increments of 2 mL·min⁻¹·kg⁻¹ in peak ${\stackrel{°}{\text{V}}}_{\text{O}2}$ to confirm the distribution of FEV₁ at different levels of exercise tolerance. The second subdivision of the patients was into four subgroups: group A (< 11 ml·min⁻¹·kg⁻¹); group B (11 to < 15 mL·min⁻¹·kg⁻¹); group C (15 to < 21 mL·min⁻¹·kg⁻¹), and group D (≥21 mL·min⁻¹·kg⁻¹). FEV₁: forced expiratory volume in one second; ${\stackrel{°}{\text{V}}}_{\text{O}2}$: oxygen uptake; ^*p < 0.05, ^**p < 0.01 ^***p < 0.0001 using Tukey–Kramer honestly significant test.

Figure 2

Patient selection flowchart COPD, chronic obstructive pulmonary disease; CPET, cardiopulmonary exercise testing; ECG, electrocardiogram; EL, exercise limitation.

Figure 3

The relationships of the FEV₁ and the V_T at peak exercise during cardiopulmonary exercise testing. (i) relationship of ${\stackrel{°}{\text{V}}}_{\text{E}}$ to FEV₁, (ii) relationship of V_T to FEV₁, (iii) relationship of obtained ${\stackrel{°}{\text{V}}}_{O2}$ to V_T, (iv) relationship of ${\stackrel{°}{\text{V}}}_{\text{E}}$ to V_T, (v) relationship of respiratory frequency to V_T, and (vi) relationship of V_D/V_T to V_T. Group A (< 11 mL·min⁻¹·kg⁻¹); group B (11 to < 15 mL·min⁻¹·kg⁻¹); group C (15 to < 21 mL·min⁻¹·kg⁻¹); and group D (≥21 mL·min⁻¹·kg⁻¹). The dotted lines represent indirect MVV, which was calculated as FEV₁ × 35. EX., exercise; FEV₁, forced expiratory volume in 1 s; MVV, maximum voluntary ventilation; V_D/V_T, physiologic dead space/tidal volume ratio; ${\stackrel{°}{\text{V}}}_{\text{E}}$, minute ventilation; ${\stackrel{°}{\text{V}}}_{\text{O}2}$, oxygen uptake; V_T, tidal volume.

Figure 4

The relationships between the PaO₂-slope and the PaO₂ at peak exercise during cardiopulmonary exercise testing. Group A (< 11 mL·min⁻¹·kg⁻¹); group B (11 to < 15 mL·min⁻¹·kg⁻¹); group C (15 to < 21 mL·min⁻¹·kg⁻¹); and group D (≥21 mL·min⁻¹·kg⁻¹). The horizontal lines represent the standard deviation. The dots between the horizontal lines represent the mean. PaO₂, arterial oxygen tension.

Figure 5

The relationships of the ${\text{HCO}}_3^{-}$ levels at peak exercise during cardiopulmonary exercise testin. (i) relationship between PaO₂ and ${\text{HCO}}_3^{-}$, (ii) relationship between PaCO₂ and ${\text{HCO}}_3^{-}$, (iii) relationship between lactate and ${\text{HCO}}_3^{-}$, and (iv) relationship between ${\stackrel{°}{\text{V}}}_{\text{E}}$ and ${\text{HCO}}_3^{-}$. Group A (< 11 mL·min⁻¹·kg⁻¹); group B (11 to < 15 mL·min⁻¹·kg⁻¹); group C (15 to < 21 mL·min⁻¹·kg⁻¹); and group D (≥21 mL·min⁻¹·kg⁻¹). ${\text{HCO}}_3^{-}$, bicarbonate ion; PaCO₂, arterial carbon dioxide tension; PaO₂, arterial oxygen tension; ${\stackrel{°}{\text{V}}}_{\text{E}}$, minute ventilation.

Figure 6

The relationships of the plasma lactate levels and dyspnea borg scales during exercise. Values are presented as mean (SD) and were analyzed using the Tukey-Kramer honestly significant difference test. Circular symbols show exertional variables at rest, during exercise, and at peak exercise. Square symbols show plasma lactate and dyspnea borg scale break points. Plasma lactate borg scale break points were determined in 15/28 in group A, 43/64 in group B, 55/77 in group C, and 42/46 group D. Dyspnea borg scale break points were determined in 14/28 in group A, 46/64 in group B, 62/77 in group C, and 40/46 group D. A vs. B; ^†p < 0.05, ^††p < 0.01, A vs. D: ^‡p < 0.05, ^‡‡‡‡p < 0.0001; B vs. C: ^§§p < 0.01, B vs. D: ^¶p < 0.05, ^¶¶¶¶p < 0.0001; C vs. D: ^####p < 0.0001.