Key unanswered questions on the mechanisms and consequences of minute ventilation (V′E)/carbon dioxide output (V′CO2) abnormalities in COPD
| Exercise intolerance | What are the structural determinants of increased VD/VTphys in milder disease? What is the relevance of alveolar hyperventilation to increase V′E/V′CO2? Does it change with disease severity? What is the physiological meaning (if any) of the V′E–V′CO2 intercept? Is the V′E/V′CO2 consistently associated with specific disease phenotypes? How does very severe, end-stage disease influence V′E/V′CO2? Is resting V′E/V′CO2 useful to predict exercise intolerance and dyspnoea in patients unable to exercise? |
| Influence of comorbidities | Do emphysema severity and COPD phenotype influence V′E/V′CO2 in COPD-HF? Do HF aetiology and HF with preserved ejection fraction influence V′E/V′CO2 in COPD-HF? What is the effect of exertional hypoxia on V′E/V′CO2 in hypoxaemic patients with COPD-HF? Does V′E/V′CO2 relate to right ventricular–pulmonary arterial coupling in COPD? How does the severity of restriction influence V′E/V′CO2 in CPFE? |
| Risk assessment/prognosis | Why does a high V′E/V′CO2 predict poor peri-operative outcome in lung resection surgery? What is the best V′E/V′CO2 parameter to predict poor surgical outcome across the spectrum of disease severity? Does V′E/V′CO2 independently predict poor outcome in severe to very severe patients? How to best associate V′E/V′CO2 with clinical data to determine prognosis? Does the longitudinal assessment of V′E/V′CO2 improve prognosis estimation? |
| Effects of interventions | What is the most sensitive parameter to detect improvement in V′E/V′CO2? Can exercise training and/or inspiratory muscle training improve V′E/V′CO2 in selected patients? Do interventions aimed to improve pulmonary vascular function impact on V′E/V′CO2? Is there any beneficial effect of specific pharmacological interventions on V′E/V′CO2 in COPD-HF and disproportionate pulmonary hypertension? Can long-term bronchodilation improve V′E/V′CO2 in selected patients? |
VD/VTphys: physiological dead space; HF: heart failure; CPFE: combined pulmonary fibrosis and emphysema.