Poor Ventilatory Efficiency Research Articles

Uncovering the mechanisms of exertional dyspnoea in combined pulmonary fibrosis and emphysema.

The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxaemia. However, there is little evidence to support these assumptions.We prospectively contrasted the sensory and physiological responses to exercise in 42 CPFE and 16 IPF patients matched by the severity of exertional hypoxaemia. Emphysema and pulmonary fibrosis were quantified using computed tomography. Inspiratory constraints were assessed in a constant work rate test: capillary blood gases were obtained in a subset of patients.CPFE patients had lower exercise capacity despite less extensive fibrosis compared to IPF (p=0.004 and 0.02, respectively). Exertional dyspnoea was the key limiting symptom in 24 CPFE patients who showed significantly lower transfer factor, arterial carbon dioxide tension and ventilatory efficiency (higher minute ventilation (V'E)/carbon dioxide output (V'CO2 ) ratio) compared to those with less dyspnoea. However, there were no between-group differences in the likelihood of pulmonary hypertension by echocardiography (p=0.44). High dead space/tidal volume ratio, low capillary carbon dioxide tension emphysema severity (including admixed emphysema) and traction bronchiectasis were related to a high V'E/V'CO2 ratio in the more dyspnoeic group. V'E/V'CO2 nadir >50 (OR 9.43, 95% CI 5.28-13.6; p=0.0001) and total emphysema extent >15% (2.25, 1.28-3.54; p=0.01) predicted a high dyspnoea burden associated with severely reduced exercise capacity in CPFEContrary to current understanding, hypoxaemia per se is not the main determinant of exertional dyspnoea in CPFE. Poor ventilatory efficiency due to increased "wasted" ventilation in emphysematous areas and hyperventilation holds a key mechanistic role that deserves therapeutic attention.

Poor ventilatory efficiency during exercise may predict prolonged air leak after pulmonary lobectomy.

ClinicalTrials.gov identifier: NCT03498352.

The role of evaluating inspiratory constraints and ventilatory inefficiency in the investigation of dyspnea of unclear etiology.

Exertional dyspnea increases when the mechanical output of the respiratory muscles becomes uncoupled from increases in neural respiratory drive. Combining measurements of inspiratory constraints and ventilatory inefficiency may better uncover the role of mechanical-ventilatory abnormalities on exertional dyspnea than the currently-recommended approach, i.e., a low breathing reserve. We determined the presence of a low breathing reserve (1-(peak ventilation (V̇E)/estimated maximal voluntary ventilation) x 100 < 15%), critical inspiratory constraints (tidal volume (VT)/exercise inspiratory capacity (ICdyn) > 0.7) and ventilatory inefficiency (V̇E/CO2 output (V̇CO2) nadir>34) in 284 subjects (161 males) with "disproportionate dyspnea" (N = 148), "dyspnea with multiple potential causes" (N = 93) and "dyspnea without an apparent cause. The agreement between breathing reserve and assessment of inspiratory constraints was only "fair" (kappa [confidence interval (CI)] = 0.264 [0.169-0.358]). Attainment of critical inspiratory constraints and an upward inflection in dyspnea ratings systematically preceded a low breathing reserve. Of note, ~55% (93/167) of subjects with normal breathing reserve showed critical inspiratory constraints despite largely preserved lung function. Regardless of the breathing reserve, subjects showing critical inspiratory constraints and/or poor ventilatory efficiency reported higher dyspnea and more impaired exercise tolerance compared to their counterparts (p < 0.05). Poor ventilatory efficiency strongly predicted a high dyspnea/work rate in subjects without critical inspiratory constraints regardless of the breathing reserve (odds ratio [95% CI] = 4.21 [2.01-6.42; p < 0.001). An integrated analysis of inspiratory constraints and ventilatory inefficiency is key to uncover physiological abnormalities germane to dyspnea in clinical populations in whom the origins of this distressing symptom are uncertain.

Inspiratory Constraints and Ventilatory Inefficiency Are Superior to Breathing Reserve in the Assessment of Exertional Dyspnea in COPD

Combining measurements of impaired lung mechanics (inspiratory constraints) with an index of increased respiratory stimuli to metabolic demand (poor ventilatory efficiency) might enhance the ability of cardiopulmonary exercise testing (CPET) in exposing a mechanistic role for ventilation on exertional dyspnea in COPD. In addition to the standard approach to suggest ventilatory limitation to exercise – a low breathing reserve (1−(peak ventilation (V̇E)/maximal voluntary ventilation × 100 < 20%) – we assessed the presence of critical inspiratory constraints (end-inspiratory lung volume (EILV)/total lung capacity (TLC) ≥ 0.9) and ventilatory inefficiency (V̇E/CO2 output (V̇CO2) nadir > 34) in 288 patients with mild to very severe COPD (FEV1 ranging from 18 to 121% predicted). We found that ∼50% of the patients with preserved breathing reserve developed critical inspiratory constraints. A low breathing reserve was weakly related to a lower peak O2 uptake (V̇O2) and/or a higher dyspnea burden; for instance, patients with low breathing reserve but without critical inspiratory constraints had similar dyspnea and peak V̇O2 than those with preserved breathing reserve (p > 0.05). In contrast, critical inspiratory constraints and ventilatory inefficiency were strongly associated with a negative outcome (likelihood ratio = 42.3 and 47.7, respectively; p < 0.001). A multiple logistic regression analysis revealed that only EILV/TLC ≥ 0.9 and V̇E/V̇CO2 nadir >34 predicted a severely reduced peak V̇O2 due to a high dyspnea burden (p < 0.001). Measurements of dynamic mechanical constraints and ventilatory inefficiency during incremental CPET are key to determine the impact of COPD on dyspnea and exercise tolerance across the spectrum of disease severity.

Is Cardiorespiratory Fitness Related to Cardiometabolic Health and All-Cause Mortality Risk in Patients with Coronary Heart Disease? A CARE CR Study

BackgroundHigher cardiorespiratory fitness (CRF) is associated with lower morbidity and mortality in patients with coronary heart disease (CHD). The mechanisms for this are not fully understood. A more favourable cardiometabolic risk factor profile may be responsible; however, few studies have comprehensively evaluated cardiometabolic risk factors in relation to CRF amongst patients with CHD. We aimed to explore differences in cardiometabolic risk and 5-year all-cause mortality risk in patients with CHD who have low, moderate, and high levels of CRF.MethodsPatients with CHD underwent maximal cardiopulmonary exercise testing, echocardiogram, carotid intima-media thickness measurement, spirometry, and dual X-ray absorptiometry assessment. Full blood count, biochemical lipid profiles, high-sensitivity (hs) C-reactive protein, and NT-proBNP were analysed. Patients were defined as having low, moderate, or high CRF based on established prognostic thresholds.ResultsSeventy patients with CHD (age 63.1 ± 10.0 years, 86% male) were recruited. Patients with low CRF had a lower ventilatory anaerobic threshold, peak oxygen pulse, post-exercise heart rate recovery, and poor ventilatory efficiency. The low CRF group also had higher NT pro-BNP, hs-CRP, non-fasting glucose concentrations, and lower haemoglobin and haematocrit. Five-year mortality risk (CALIBER risk score) was also greatest in the lowest CRF group (14.9%).ConclusionsPractitioners should interpret low CRF as an important clinical risk factor associated with adverse cardiometabolic health and poor prognosis, study registry; www.researchregistry.com.

Excess Ventilation in Chronic Obstructive Pulmonary Disease-Heart Failure Overlap. Implications for Dyspnea and Exercise Intolerance.

An increased ventilatory response to exertional metabolic demand (high [Formula: see text]e/[Formula: see text]co2 relationship) is a common finding in patients with coexistent chronic obstructive pulmonary disease and heart failure. We aimed to determine the mechanisms underlying high [Formula: see text]e/[Formula: see text]co2 and its impact on operating lung volumes, dyspnea, and exercise tolerance in these patients. Twenty-two ex-smokers with combined chronic obstructive pulmonary disease and heart failure with reduced left ventricular ejection fraction undertook, after careful treatment optimization, a progressive cycle exercise test with capillary (c) blood gas collection. Regardless of the chosen metric (increased [Formula: see text]e-[Formula: see text]co2 slope, [Formula: see text]e/[Formula: see text]co2 nadir, or end-exercise [Formula: see text]e/[Formula: see text]co2), ventilatory inefficiency was closely related to PcCO2 (r values from -0.80 to -0.84; P < 0.001) but not dead space/tidal volume ratio. Ten patients consistently maintained exercise PcCO2 less than or equal to 35 mm Hg (hypocapnia). These patients had particularly poor ventilatory efficiency compared with patients without hypocapnia (P < 0.05). Despite the lack of between-group differences in spirometry, lung volumes, and left ventricular ejection fraction, patients with hypocapnia had lower resting PaCO2 and lung diffusing capacity (P < 0.01). Excessive ventilatory response in this group was associated with higher exertional PcO2. The group with hypocapnia, however, had worse mechanical inspiratory constraints and higher dyspnea scores for a given work rate leading to poorer exercise tolerance compared with their counterparts (P < 0.05). Heightened neural drive promoting a ventilatory response beyond that required to overcome an increased "wasted" ventilation led to hypocapnia and poor exercise ventilatory efficiency in chronic obstructive pulmonary disease-heart failure overlap. Excessive ventilation led to better arterial oxygenation but at the expense of earlier critical mechanical constraints and intolerable dyspnea.

Physiological and clinical relevance of exercise ventilatory efficiency in COPD.

Exercise ventilation (V'E) relative to carbon dioxide output (V'CO2 ) is particularly relevant to patients limited by the respiratory system, e.g. those with chronic obstructive pulmonary disease (COPD). High V'E-V'CO2 (poor ventilatory efficiency) has been found to be a key physiological abnormality in symptomatic patients with largely preserved forced expiratory volume in 1 s (FEV1). Establishing an association between high V'E-V'CO2 and exertional dyspnoea in mild COPD provides evidence that exercise intolerance is not a mere consequence of detraining. As the disease evolves, poor ventilatory efficiency might help explaining "out-of-proportion" breathlessness (to FEV1 impairment). Regardless, disease severity, cardiocirculatory co-morbidities such as heart failure and pulmonary hypertension have been found to increase V'E-V'CO2 In fact, a high V'E-V'CO2 has been found to be a powerful predictor of poor outcome in lung resection surgery. Moreover, a high V'E-V'CO2 has added value to resting lung hyperinflation in predicting all-cause and respiratory mortality across the spectrum of COPD severity. Documenting improved ventilatory efficiency after lung transplantation and lung volume reduction surgery provides objective evidence of treatment efficacy. Considering the usefulness of exercise ventilatory efficiency in different clinical scenarios, the V'E-V'CO2 relationship should be valued in the interpretation of cardiopulmonary exercise tests in patients with mild-to-end-stage COPD.

Physiological and sensory consequences of exercise oscillatory ventilation in heart failure-COPD

BackgroundExercise oscillatory ventilation (EOV) is associated with poor ventilatory efficiency and higher operating lung volumes in heart failure. These abnormalities may be particularly deleterious to dyspnea and exercise tolerance in mechanically-limited patients, e.g. those with coexistent COPD. MethodsVentilatory, gas exchange and sensory responses to incremental exercise were contrasted in 68 heart failure-COPD patients (12 EOV+). EOV was established by standard criteria. ResultsCompared to EOV−, EOV+ had lower exercise capacity, worse ventilatory inefficiency and higher peak dyspnea scores (p<0.05). Peak capillary PCO2 (PcCO2) was higher and end-tidal CO2 (PETCO2) was lower in EOV+. Thus, greater (i.e., more positive) P(c-ET)CO2 and dead space/tidal volume values were found in these patients compared to EOV− (p<0.05). Ventilatory inefficiency was related to increased dead space/tidal volume in EOV+ (r=0.74; p<0.01). Owing to higher operating lung volumes, inspiratory reserve volume (IRV) decreased to a greater extent in EOV+. Tidal volume oscillations consistently ceased when a “critical” IRV was reached (~0.3–0.5L); thereafter, PcCO2 stabilized or increased and dyspnea scores rose sharply. Exercise capacity was closely related to IRV decrements and peak dyspnea in EOV+ (r=−0.78 and 0.84, respectively; p<0.01). ConclusionsDyspnea and exercise tolerance are negatively influenced by EOV in heart failure patients presenting with COPD as co-morbidity. Pharmacological and non-pharmacological interventions known to decrease EOV might prove particularly valuable to mitigate symptom burden and exercise intolerance in this specific heart failure group.

What underlies NYHA class in elderly patients with heart failure? role of diastolic dysfunction, functional mitral regurgitation and abnormal ventilation during exercise

Color-Doppler ecocardiography and cardiopulmonary stress test are pivotal in the evaluation of patients with heart failure. Besides determining systolic function through left ventricular ejection fraction (EF), color-Doppler ecocardiography evaluates the presence and degree of functional mitral regurgitation and the severity of diastolic dysfunction. Moreover, in addition to the aerobic capacity indicated by peak O2 consumption, other parameters of cardiopulmonary stress have proven useful for diagnostic purposes, such as the peak VE/VCO2 ratio or ventilatory efficiency. Since in elderly patients with heart failure the functional impairment often is a combination of the effects of aging with those of disease, the relationship between symptoms, i.e. the NYHA class, ventricular pump function and aerobic performance is sometimes difficult to estabilish. In 60 elderly with systolic heart failure (75 +/- 3 years, EF 30 +/- 6%), we correlated symptoms (i.e. NYHA class) with [1] degree of functional mitral regurgitation (FMR) determined by color-Doppler echocardiography; [2] degree of left ventricular diastolic dysfunction, measured by Doppler analysis of transmitralic and pulmonary veins flow; [3] VO2 and VE/VCO2 at peak exercise at cardiopulmonary test. In all patients, NYHA class was only weakly related with EF and peak VO2, with wide overlap of individual values among patients with different NYHA class. Instead, we observed a tight relationship between NYHA class, FMR degree, and severity of diastolic dysfunction and VE/VCO2 ratio at peak exercise (p<0.001), with a more evident partition among patients in different NYHA classes. In elderly heart failure patients, the reduced effort tolerance expressed by the NYHA classification is only weakly associated with reduced aerobic capacity and pump function, but rather is related with the presence of mitral regurgitation, left ventricular diastolic dysfunction, and a poor ventilatory efficiency during exercise.

Exercise capacity and ventilatory efficiency with afferent blockade in heart failure (884.3)

Increased locomotor muscle afferent feedback may be linked to the reduced exercise capacity (peak VO2) and poor ventilatory efficiency (high VE/VCO2 slope) observed in heart failure (HF). We examined the relationship between peak VO2 and change in VE/VCO2 with afferent inhibition during exercise in HF. 9 HF (60±6 yr) and 9 controls (CTL) (63±7 yr) completed 3 visits. Visit 1: cycle exercise to volitional exhaustion. Visits 2‐ 3: 5 min constant‐load cycling (65% of peak work) randomized to lumbar intrathecal fentanyl injection (afferent block) or placebo. VO2, ventilation (VE), carbon dioxide production (VCO2), and end‐tidal CO2 (PETCO2) were measured. In HF, peak work (120±34 vs 176±54 W, p&lt;0.05) and VO2 (18.4±2.7 vs 27.2±4.7 ml/kg/min, p&lt;0.05) were reduced, whereas VE/VCO2 slope was elevated (39.7±1.8 vs 35.3±0.8, p&lt;0.05) compared with CTL. With afferent inhibition, HF patients had a greater reduction in VE/VCO2 (‐18.8±8.1 vs ‐5.4±13.3%, p&lt;0.05) and increase in PETCO2 (20.3±10.5 vs 6.1±9.5%, p&lt;0.01) during constant‐load cycling. Lower VO2peak was related to a greater decline in VE/VCO2 and rise in PETCO2 after afferent inhibition in HF (r=0.82, p&lt;0.01 and r=‐0.69, p&lt;0.05, respectively) but not CTL (p&gt;0.05). Our data demonstrate that patients with the lowest VO2peak have the greatest improvement in VE/VCO2, suggesting a close link between afferent feedback, ventilatory efficiency and exercise capacity in HF.Grant Funding Source: Supported by AHA 12GRNT11630027 and National Center for Advancing Translational Science KL2TR000136.

P131 CT emphysema score, dynamic hyperinflation and ventilatory efficiency during exercise in patients with COPD

BackgroundVolumetric CT scan is used for evaluating the severity of emphysema in COPD patients. The aim of this study was to ascertain whether volumetric CT scan of emphysema may provide...

Usefulness of Right-to-Left Shunting and Poor Exercise Gas Exchange for Predicting Prognosis in Patients With Pulmonary Arterial Hypertension

We hypothesized that the longitudinal changes in peak oxygen uptake, ventilatory efficiency, and exercise-induced right-to-left shunting in patients with pulmonary arterial hypertension (PAH) would predict outcomes better than baseline measurements alone. Patients with PAH die prematurely. Identifying prognostic markers is critical for treating patients with PAH; however, longitudinal prognostic information of PAH is limited. We enrolled 103 patients with PAH into a long-term, prospective outcome study using serial cardiopulmonary exercise testing to measure the peak oxygen uptake, ventilatory efficiency (ratio of ventilation to carbon dioxide output at the anaerobic threshold), right-to-left shunting, and other factors in patients treated with optimal therapy. The patients were followed up for a mean of 4.7 years. During the study period, 20 patients died, and 3 underwent lung transplantation. The baseline peak oxygen uptake and ventilatory efficiency was 0.79 L/min and 49 (normal <34), respectively, reflecting severe disease. Poorer ventilatory efficiency and greater New York Heart Association classification were associated with poor outcome at baseline and at follow-up. On multivariate analysis, the persistence or development of an exercise-induced right-to-left shunt strongly predicted death or transplantation (p <0.0001), independent of the hemodynamics and all other exercise measures, including peak oxygen uptake and ventilatory efficiency. The absence of a shunt at baseline was associated with a 20% rate of nonsurvival, which decreased to 7% at follow-up. A poorer ventilatory efficiency appeared to be associated with a poor outcome in patients without a shunt. In conclusion, a persistent exercise-induced right-to-left shunt and poor ventilatory efficiency were highly predictive of poor outcomes in patients with pulmonary arterial hypertension.

Prognostic Value of BNP and Cardiopulmonary Exercise Testing in Patients With Systolic Heart Failure on Beta-Blocker Therapy

The long-term prognostic value of the B-type natriuretic peptide (BNP) level and cardiopulmonary exercise testing in patients with heart failure (HF) who are receiving beta-blocker therapy is not well established. The study involved 80 outpatients (78% male, age 50 [11] years) with stable HF, severe systolic dysfunction (left ventricular ejection fraction 25 [9]%), and intermediate functional impairment (New York Heart Association functional class 2.4 [0.6]) who were receiving optimum therapy, including beta-blockers. Their BNP levels (pg/mL) were measured and cardiopulmonary exercise testing was carried out to determine maximal oxygen uptake (VO2max) and ventilatory efficiency (VE/VCO2 slope). Patients were followed up for 2.7 (0.8) years. The study endpoints were cardiovascular death, heart transplantation, and HF hospitalization. The BNP level and VE/VCO2 slope were greater in patients who died (n=7), at 211 pg/mL (51-266 pg/mL) vs. 46 pg/mL (16-105 pg/mL) (P=.017) and 39 (3) vs. 33.8 (5.5) (P=.018), respectively, or who had an adverse event (n=19), at 139 pg/mL (88-286 pg/mL) vs. 40 pg/mL (13-81 pg/mL) (P< .001) and 38.7 (4.3) vs. 32.9 (5.2) (P< .001), respectively. Only the combined endpoint was associated with a significant difference in VO2max (19.7 [5.4] vs. 16.8 [3.9] mL/kg per min, P=.016). On multivariate analysis, BNP >102 pg/mL (P=.002; hazard ratio [HR]=5.2; 95% confidence interval [CI], 1.8-14.8) and VE/VCO2 slope >35 (P=.012; HR =4.3; 95% CI, 1.4-13.2) were the best predictors of an adverse event. In patients who satisfied neither, one or both criteria, 36-month cumulative adverse event rates were 2%, 25% and 63%, respectively (log rank, P< .001). In ambulatory HF patients with intermediate functional impairment who are receiving optimum beta-blocker therapy, the persistence of a high BNP level (>102 pg/mL) combined with poor ventilatory efficiency (VE/VCO2 slope >35) identify those with a poor long-term prognosis.