Ventilatory Inefficiency and Exertional Dyspnea in Early Chronic Obstructive Pulmonary Disease

Abstract

Exertional dyspnea is present across the spectrum of chronic obstructive pulmonary disease (COPD) severity. However, without realizing it themselves, patients may decrease daily physical activity to avoid distressing respiratory sensations. Dyspnea also may be associated with deconditioning. Cardiopulmonary exercise testing can uncover exertional dyspnea and its physiological determinants in patients with preserved or only mildly reduced FEV. Dyspnea in mild COPD can largely be explained by increased "wasted" ventilation in the physiological dead space, which heightens the drive to breathe and worsens the inspiratory mechanical constraints. During incremental exercise testing, this is readily identified as an excessive ventilation-to-metabolic demand, that is, a high ventilation ([Formula: see text]e) to carbon dioxide output ([Formula: see text]co) relationship. Linking increases in [Formula: see text]e/[Formula: see text]co to exertional dyspnea may provide objective evidence that a patient's poor exercise tolerance is not just a consequence of deconditioning. This information should prompt a proactive therapeutic approach to increase the available ventilatory reserve by, for example, giving inhaled bronchodilators. Considering that the structural determinants of ventilatory inefficiency (early emphysema, ventilation-perfusion mismatching, and microvascular disease) may progress despite only modest changes in FEV, serial [Formula: see text]e/[Formula: see text]co measurements might also prove valuable to track disease progression in these symptomatic patients.

Dyspnea in COPD: New Mechanistic Insights and Management Implications

“…In COPD, ventilation-perfusion mismatch in the lung leads to inefficient pulmonary gas exchange. Dysfunction of the lung microvasculature occurs to a variable extent across the entire severity spectrum of COPD [27][28][29]. In mild COPD during exercise, physiological dead space, the ventilatory equivalent for CO 2 (V E /VCO 2 )-a measure of ventilatory efficiency-and alveolar ventilation (V A ) are all elevated, compared with healthy controls [27].…”

Non‐COPD smokers: The occult face behind exercise physiology in heart failure

“…The 11 ± 3 pack‐years (the number of packs of cigarettes smoked per day, multiplied by years of consumption) intensity of smoking could cover up more severe pulmonary disease, because it was recently shown that smoking duration alone is more important to estimate chronic parenchymal pulmonary disease compared with pack‐years (Bhatt et al., ). Non‐COPD smokers can develop ventilatory constraints, gas trapping, dynamic hyperinflation (DH) and increased ventilatory inefficiency (Neder et al., ) besides dead‐space augmentation (Gläser et al., ). In a small sample such as this, ∼50% of smokers could well lead to very heterogeneous responses, partly explaining the strongly significant calculated expiratory reserve volume (ERV, as a percentage of predicted Forced Vital Capacity) and inspiratory capacity (IC, as a percentage of predicted) correlations with alveolar volume or dead‐space fraction of tidal volume, caused by a statistical ‘effect of the extremes’, supposing a worse superimposed detrimental effect of tobacco‐associated small airway disease.…”

Reply to Barbosa and Müller

“…Importantly, the percent predicted physiological dead space of the HFrEF patients was substantially greater than that of the CTL participants during submaximal exercise (HFrEF, 134 ± 38% versus CTL, 96 ± 41%, P < 0.05). Furthermore, there and ventilatory constraints during exercise (Neder et al, 2017), this additional analysis indicates that HFrEF-induced pathophysiological mechanisms were largely responsible for the elevated physiological dead space compared with CTL participants. However, we do agree with Barbosa and Müller (2019) that future studies are necessary to determine how smoking history and/or duration influences the integrative cardiopulmonary response to exercise in HFrEF patients with and without concurrent COPD.…”

“…Furthermore, there was a negative relationship between percent predicted physiological dead space and percent predicted IC during submaximal exercise in the HFrEF patients ( r = −0.74, P < 0.01), suggesting that ventilatory constraints contribute to the elevated physiological dead space in HFrEF patients when smoking status is accounted for. Although smoking history can have a negative influence on pulmonary function and ventilatory constraints during exercise (Neder et al., ), this additional analysis indicates that HFrEF‐induced pathophysiological mechanisms were largely responsible for the elevated physiological dead space compared with CTL participants. However, we do agree with Barbosa and Müller () that future studies are necessary to determine how smoking history and/or duration influences the integrative cardiopulmonary response to exercise in HFrEF patients with and without concurrent COPD.…”