Reduced exercise tolerance in mild chronic obstructive pulmonary disease: The contribution of combined abnormalities of diffusing capacity for carbon monoxide and ventilatory efficiency

Abstract

Background and objective: The combination of both reduced resting diffusing capacity of the lung for carbon monoxide (DL CO ) and ventilatory efficiency (increased ventilatory requirement for CO 2 clearance [ _ V E / _ VCO 2 ]) has been linked to exertional dyspnoea and exercise intolerance in chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are poorly understood. The current study examined if low resting DL CO and higher exercise ventilatory requirements were associated with earlier critical dynamic mechanical constraints, dyspnoea and exercise limitation in patients with mild COPD. Methods: In this retrospective analysis, we compared _ V E / _ VCO 2 , dynamic inspiratory reserve volume (IRV), dyspnoea and exercise capacity in groups of patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 COPD with (1) a resting DL CO at or greater than the lower limit of normal (≥LLN; Global Lung Function Initiative reference equations [n = 44]) or (2) below the <LLN (n = 33), and age-and sex-matched healthy controls (n = 81). Results: Spirometry and resting lung volumes were similar in the two COPD groups. During exercise, _ V E / _ VCO 2 (nadir and slope) was consistently higher in the DL CO < LLN compared with the other groups (all p < 0.05). The DL CO < LLN group had lower IRV and greater dyspnoea intensity at standardized submaximal work rates and lower peak work rate and oxygen uptake than the other two groups (all p < 0.05). Conclusion: Reduced exercise capacity in patients with DL CO < LLN was related to higher ventilatory requirements, a faster rate of decline in dynamic IRV and greater dyspnoea during exercise. These simple measurements should be considered for the clinical evaluation of unexplained exercise intolerance in individuals with ostensibly mild COPD.

Out-of-proportion dyspnea and exercise intolerance in mild COPD

“… 4 Such impairment in gas exchange efficiency is frequently reflected on ↓DL CO ( Figure 1 A). 5 The excess ventilation is associated with a high drive to the respiratory muscles, leading to increased dyspnea at a given exercise intensity ( Figure 1 B, second graph). Because the ventilatory pump can still respond to such a high drive, dyspnea remains proportional to the heightened ∙ V E .…”

“…Esse comprometimento da eficiência das trocas gasosas frequentemente se reflete em DL CO ↓ (Figura 1A). (5) A ventilação excessiva está relacionada com um alto estímulo dos músculos respiratórios, o que leva ao aumento da dispneia para uma determinada intensidade de exercício (Figura 1B, segundo gráfico). Como a bomba ventilatória ainda é capaz de responder a esse estímulo tão alto, a dispneia permanece proporcional à…”

Journal Club: Impaired Ventilatory Efficiency and Exercise Intolerance in Former/Current Smokers With Dyspnea Disproportionate to Their Lung Function: Pathophysiological Insights Gained Through Cardiopulmonary Exercise Testing

“…12,14,17,[22][23][24][25][26] Other studies have examined the ventilatory efficiency--(minute ventilation [VE] to carbon dioxide production [VCO2]) VE/VCO2 nadir: the lowest ventilatory rate able to remove 1 liter of CO2 per minute during graded cardiopulmonary exercise testing (CPET). [27][28][29][30][31] While many clinicians are familiar with the concept of dynamic hyperinflation that can lead to breath stacking and dyspnea, fewer non-pulmonary physicians are familiar with the assessment of ventilatory efficiency.…”

“…Abnormally high nadir VE/VCO2 during exercise has been independently linked to dyspnea and low volume of oxygen consumed (VO2peak) and mortality in COPD. 28,30,32,34,35 Correlations have been found between a high nadir VE/VCO2 and lower resting diffusing capacity of the lungs for carbon monoxide (DLCO) 28,36 which is considered a surrogate marker of pulmonary vascular disease.…”

Exercise tolerance in mild chronic obstructive pulmonary disease: Finding the missing link is what provides clinical value in pulmonary function tests

“…Moreover, how do we distil this information and link it to help guide treatment? In a recent publication in Respirology , Phillips et al 4 provide a very important link between various pieces of physiological information observed in patients with mild COPD. The authors ask a very simple question: In patients with mild (GOLD stage 1) COPD, do patients with a TLCO below the limit of normal have heightened VE/VCO 2 , faster decline in dynamic inspiratory reserve volume and corresponding heightened dyspnoea intensity.…”