Exercise Ventilatory Inefficiency Research Articles

Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal data analysis 34 months post-discharge

BackgroundSARS-CoV-2 infection has raised concerns about long-term health repercussions. Exercise ventilatory inefficiency (EVin) has emerged as a notable long-term sequela, potentially impacting respiratory and cardiovascular health. This study aims to assess the long-term presence of EVin after 34 months and its association with cardiorespiratory health in post-COVID patients.MethodsIn a longitudinal study on 32 selected post-COVID subjects, we performed two cardiopulmonary exercise tests (CPETs) at 6 months (T0) and 34 months (T1) after hospital discharge. The study sought to explore the long-term persistence of EVin and its correlation with respiratory and cardiovascular responses during exercise. Measurements included also V̇O2peak, end-tidal pressure of CO2 (PETCO2) levels, oxygen uptake efficiency slope (OUES) and other cardiorespiratory parameters, with statistical significance set at p < 0.05. The presence of EVin at both T0 and T1 defines a persisting EVin (pEVin).ResultsOut of the cohort, five subjects (16%) have pEVin at 34 months. Subjects with pEVin, compared to those with ventilatory efficiency (Evef) have lower values of PETCO2 throughout exercise, showing hyperventilation. Evef subjects demonstrated selective improvements in DLCO and oxygen pulse, suggesting a recovery in cardiorespiratory function over time. In contrast, those with pEvin did not exhibit these improvements. Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse and OUES, indicating the potential prognostic value of OUES and Evin in post-COVID follow-ups.ConclusionsThe study highlights the clinical importance of long-term follow-up for post-COVID patients, as a significant group exhibit persistent EVin, which correlates with altered and potentially unfavorable cardiovascular responses to exercise. These findings advocate for the continued investigation into the long-term health impacts of COVID-19, especially regarding persistent ventilatory inefficiencies and their implications on patient health outcomes.

The functional consequences in severe and critical covid-19 survivors – A pilot study

PurposeTo perform pulmonary function tests (PFT) in severe COVID-19 survivors one and five months after hospital discharge in order to assess the lung function, as well to identify clinical characteristics and PFT parameters associated with worse cardiopulmonary exercise testing (CPET). Material and methodsA prospective study included 75 patients with severe form of COVID-19. PFT was conducted one and five months after hospital discharge, in addition to CPET in a second assessment. Patients with a previous history of chronic respiratory diseases were excluded from our study. ResultsOne month after hospital discharge, all examined patients had diffusion lung capacity for carbon-monoxide(DLco%) below the 80% of predicted values (in mean 58%), with 40% of patients having a restrictive pattern (total lung capacity(TLC) < 80%). In a repeated assessment after five months, pathological DLco% persisted in 40% of patients, while all other PFT parameters were normal. CPET showed reduced maximum oxygen consumption during exercise testing (VO2peak%) values in 80% of patients (in mean 69%), and exercise ventilatory inefficiency in 60%. Patients with VO2peak < 60% had significantly lower values of examined PFT parameters, both one and five months after hospital discharge. Patients with VO2peak% ≥ 60% had a significantly higher increase after the second assessment for Forced expiratory volume in 1st second (FEV1%), Forced expiratory volume in 1st second and forced vital capacity ratio (FEV1/FVC), DLco% and Diffusion lung capacity for carbon monoxide corrected for alveolar volume (DLco/VA). ConclusionSignificant functional abnormalities, according to PFT and CPET, was present both one and five months in severe COVID-19 survivors, thus emphasizing the importance of a comprehensive follow-up including both resting and dynamic functional assessment in these patients.

Exercise Ventilatory Inefficiency in Post-COVID-19 Syndrome: Insights from a Prospective Evaluation.

Introduction: Coronavirus disease 2019 (COVID-19) is a systemic disease characterized by a disproportionate inflammatory response in the acute phase. This study sought to identify clinical sequelae and their potential mechanism. Methods: We conducted a prospective single-center study (NCT04689490) of previously hospitalized COVID-19 patients with and without dyspnea during mid-term follow-up. An outpatient group was also evaluated. They underwent serial testing with a cardiopulmonary exercise test (CPET), transthoracic echocardiogram, pulmonary lung test, six-minute walking test, serum biomarker analysis, and quality of life questionaries. Results: Patients with dyspnea (n = 41, 58.6%), compared with asymptomatic patients (n = 29, 41.4%), had a higher proportion of females (73.2 vs. 51.7%; p = 0.065) with comparable age and prevalence of cardiovascular risk factors. There were no significant differences in the transthoracic echocardiogram and pulmonary function test. Patients who complained of persistent dyspnea had a significant decline in predicted peak VO2 consumption (77.8 (64–92.5) vs. 99 (88–105); p < 0.00; p < 0.001), total distance in the six-minute walking test (535 (467–600) vs. 611 (550–650) meters; p = 0.001), and quality of life (KCCQ-23 60.1 ± 18.6 vs. 82.8 ± 11.3; p < 0.001). Additionally, abnormalities in CPET were suggestive of an impaired ventilatory efficiency (VE/VCO2 slope 32 (28.1–37.4) vs. 29.4 (26.9–31.4); p = 0.022) and high PETCO2 (34.5 (32–39) vs. 38 (36–40); p = 0.025). Interpretation: In this study, >50% of COVID-19 survivors present a symptomatic functional impairment irrespective of age or prior hospitalization. Our findings suggest a potential ventilation/perfusion mismatch or hyperventilation syndrome.

Importance of Cardiopulmonary Exercise Testing amongst Subjects Recovering from COVID-19.

The cardiopulmonary exercise test (CPET) provides an objective assessment of ventilatory limitation, related to the exercise minute ventilation (VE) coupled to carbon dioxide output (VCO2) (VE/VCO2); high values of VE/VCO2 slope define an exercise ventilatory inefficiency (EVin). In subjects recovered from hospitalised COVID-19, we explored the methodology of CPET in order to evaluate the presence of cardiopulmonary alterations. Our prospective study (RESPICOVID) has been proposed to evaluate pulmonary damage’s clinical impact in post-COVID subjects. In a subgroup of subjects (RESPICOVID2) without baseline confounders, we performed the CPET. According to the VE/VCO2 slope, subjects were divided into having EVin and exercise ventilatory efficiency (EVef). Data concerning general variables, hospitalisation, lung function, and gas-analysis were also collected. The RESPICOVID2 enrolled 28 subjects, of whom 8 (29%) had EVin. As compared to subjects with EVef, subjects with EVin showed a reduction in heart rate (HR) recovery. VE/VCO2 slope was inversely correlated with HR recovery; this correlation was confirmed in a subgroup of older, non-smoking male subjects, regardless of the presence of arterial hypertension. More than one-fourth of subjects recovered from hospitalised COVID-19 have EVin. The relationship between EVin and HR recovery may represent a novel hallmark of post-COVID cardiopulmonary alterations.

Small airway dysfunction predicts excess ventilation and dynamic hyperinflation during exercise in patients with COPD

IntroductionSmall airway dysfunction (SAD) is a pathophysiological characteristic of chronic obstructive pulmonary disease (COPD). Excess ventilation and dynamic hyperinflation (DH) are two main pathophysiological traits and limiting factors of COPD patients while exercising. We aimed to ascertain whether or not SAD, assessed by the multiple breath nitrogen washout (MBNW), may predict exercise ventilatory inefficiency and DH. MethodsFifty stable COPD patients were prospectively studied and underwent MBNW and incremental cardio-pulmonary exercise test (CPET). Indices of conductive (Scond) and acinar (Sacin) ventilation heterogeneity as well as minute ventilation/CO2 production (VE/VCO2) linear relationship and the change in inspiratory capacity (IC) were analyzed. ResultsSacin was significantly and directly related to VE/VCO2 slope and inversely related to IC change and to peak O2 uptake (p < 0.01 for all correlations). No significant correlation was found between Scond and CPET parameters. The regression equation generated by stepwise multiple regression analysis for the VE/VCO2 slope and IC change, as dependent variables, included only Sacin, as independent variable. This model accounted for 31% and 36% of the total variance for the VE/VCO2 slope and IC change, respectively. ConclusionOur study shows the value of the SAD as determinant of the excess ventilation and DH during exercise in patients with stable COPD.

The value of high-resolution computed tomography (HRCT) to determine exercise ventilatory inefficiency and dynamic hyperinflation in adult patients with cystic fibrosis

IntroductionIn Cystic Fibrosis (CF), exercise ventilatory inefficiency and dynamic hyperinflation (DH) cause exercise limitation and induce poor exercise tolerance. High-resolution computed tomography (HRCT) of the lung can detect pulmonary abnormalities in CF patients. We aimed to identify the determinants of exercise ventilatory inefficiency and DH using HRCT-derived metrics.MethodsFifty-two adult CF patients were prospectively enrolled; all participants underwent cardio-pulmonary exercise test (CPET) and HRCT. Radiological impairment was evaluated by the Brody II scoring system. Slope and intercept of the minute ventilation/CO2 production (V’E/V’CO2) regression line and the ratio of inspiratory capacity/total lung capacity (IC/TLC) at rest and at peak of exercise were measured.ResultsFour groups of patients were identified based on the combination of ventilatory efficiency (Vef) or inefficiency (Vin) and the presence/absence of DH. Compared to other groups, CF adults with Vin and DH had worse functional status and higher total (T), bronchiectasis (B) and air trapping (AT) scores at HRCT. Significant correlations were found between V’E/V’CO2 intercept and V’E/V’CO2 slope (ρ − 0.455, p = 0.001) and between V’E/V’CO2 intercept and Δ inspiratory capacity (IC) (ρ − 0.334, p = 0.015). Regression analysis identified AT score (cut-off 7.9, odds ratio-OR 3.50) as the only independent predictor of Vin and T (cut-off 53.6, OR 4.98), B (cut-off 16.1, OR 4.88), airways wall thickening (AWT) (cut-off 13, OR 3.41), and mucous plugging (MP) scores (cut-off 11.7, OR 4.18) as significant predictors of DH.ConclusionIn adult CF cohort, values of HRCT metrics are determinants of Vin (AT) and DH (T, B, AWT, MP).

Exercise ventilatory inefficiency in heart failure and chronic obstructive pulmonary disease

BackgroundDyspnea on exertion is common to both heart failure (HF) and chronic obstructive pulmonary disease (COPD), and it is important to discriminate whether symptoms are caused by HF or COPD in clinical practice. The ventilatory equivalent for carbon dioxide (V̇E/V̇CO2) slope and V̇E intercept (a reflection of pulmonary dead space) are two candidate non-invasive indices that could be used for this purpose. Thus, we compared non-invasive indexes of ventilatory efficiency in patients with HF and preserved or reduced ejection fraction (HFpEF and HFrEF, respectively) or COPD. MethodsPatients with HFpEF (n = 21), HFrEF (n = 20), and COPD (n = 22) patients performed cardiopulmonary exercise testing to volitional fatigue. V̇E and gas exchange were measured via breath-by-breath open circuit spirometry. All data from rest to peak exercise were used to calculate V̇E/V̇CO2 slope and V̇E intercept using linear regression. Receiver operating characteristic (ROC) curves were constructed to determine optimized cutoffs for V̇E/V̇CO2 slope and V̇E intercept to discriminate HFpEF and HFrEF from COPD. ResultsHFrEF patients had a greater V̇E/V̇CO2 slope than HFpEF and COPD patients (HFrEF: 40 ± 9; HFpEF: 32 ± 7; COPD: 32 ± 7) (p < 0.01). COPD patients had a greater V̇E intercept than HFpEF and HFrEF patients (COPD: 3.32 ± 1.66; HFpEF: 0.77 ± 1.23; HFrEF: 1.28 ± 1.19 L/min) (p < 0.01). A V̇E intercept of 2.64 L/min discriminated COPD from HF patients (AUC: 0.88, p < 0.01), while V̇E/V̇CO2 slope did not (p = 0.11). ConclusionThese findings demonstrate that V̇E intercept, not V̇E/V̇CO2 slope, may discriminate COPD from both HFpEF and HFrEF patients.

Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure.

Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (V̇E /V̇CO2 ) slope. The physiological correlates of the V̇E /V̇CO2 slope remain unclear in the two HF phenotypes. We hypothesized that changes in the physiological dead space to tidal volume ratio (VD /VT ) and arterial CO2 tension (PaCO2 ) differentially contribute to the V̇E /V̇CO2 slope in HFrEF vs. HFpEF. Adults with HFrEF (n = 32) and HFpEF (n = 27) [mean ± standard deviation (SD) left ventricular ejection fraction: 22 ± 7% and 61 ± 9%, respectively; mean ± SD body mass index: 28 ± 4 kg/m2 and 33 ± 6 kg/m2 , respectively; P < 0.01] performed cardiopulmonary exercise testing with breath-by-breath ventilation and gas exchange measurements. PaCO2 was measured via radial arterial catheterization. We calculated the V̇E /V̇CO2 slope via linear regression, and VD /VT = 1 - [(863 × V̇CO2 )/(V̇E × PaCO2 )]. Resting VD /VT (0.48 ± 0.08 vs. 0.41 ± 0.11; P = 0.04), but not PaCO2 (38 ± 5 mmHg vs. 40 ± 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak exercise VD /VT (0.39 ± 0.08 vs. 0.32 ± 0.12; P = 0.02) and PaCO2 (33 ± 6 mmHg vs. 38 ± 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The V̇E /V̇CO2 slope was higher in HFrEF compared with HFpEF (44 ± 11 vs. 35 ± 8; P < 0.01). Variance associated with the V̇E /V̇CO2 slope in HFrEF and HFpEF was explained by peak exercise VD /VT (R2 = 0.30 and R2 = 0.50, respectively) and PaCO2 (R2 = 0.64 and R2 = 0.28, respectively), but the relative contributions of each differed (all P < 0.01). Relationships between the V̇E /V̇CO2 slope and both VD /VT and PaCO2 are robust, but differ between HFpEF and HFrEF. Increasing V̇E /V̇CO2 slope appears to be strongly explained by mechanisms influential in regulating PaCO2 in HFrEF, which contrasts with the strong role of increased VD /VT in HFpEF.

Emphysema on Thoracic CT and Exercise Ventilatory Inefficiency in Mild-to-Moderate COPD

ABSTRACTThere is growing evidence that emphysema on thoracic computed tomography (CT) is associated with poor exercise tolerance in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that an excessive ventilatory response to exercise (ventilatory inefficiency) would underlie these abnormalities. In a prospective study, 19 patients (FEV1 = 82 ± 13%, 12 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1) and 26 controls underwent an incremental exercise test. Ventilatory inefficiency was assessed by the ventilation (E)/CO2 output (CO2) nadir. Pulmonary blood flow (PBF) in a submaximal test was calculated by inert gas rebreathing. Emphysema was quantified as % of attenuation areas below 950 HU. Patients typically presented with centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/total lung ratio = 0.82 ± 0.04). They had lower peak oxygen uptake (O2), higher E/CO2 nadir, and greater dyspnea scores than controls (p < 0.05). Lower peak O2 and worse dyspnea were found in patients with higher E/CO2 nadirs (≥30). Patients had blunted increases in PBF from rest to iso-O2 exercise (p < 0.05). Higher E/CO2 nadir in COPD was associated with emphysema severity (r = 0.63) which, in turn, was related to reduced lung diffusing capacity (r = −0.72) and blunted changes in PBF from rest to exercise (r = −0.69) (p < 0.01). Ventilation “wasted” in emphysematous areas is associated with impaired exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (DLCO) to a key clinical outcome (poor exercise tolerance) in COPD patients with only modest spirometric abnormalities.

Does Exercise Ventilatory Inefficiency Predict Poor Outcome in Heart Failure Patients With COPD?

To investigate whether the opposite effects of heart failure (HF) and chronic obstructive pulmonary disease (COPD) on exercise ventilatory inefficiency (minute ventilation [(Equation is included in full-text article.)E]-carbon dioxide output [(Equation is included in full-text article.)CO2] relationship) would negatively impact its prognostic relevance. After treatment optimization and an incremental cardiopulmonary exercise test, 30 male patients with HF-COPD (forced expiratory volume in 1 second [FEV1] = 57% ± 17% predicted, ejection fraction = 35% ± 6%) were prospectively followed up during 412 ± 261 days for major cardiac events. Fourteen patients (46%) had a negative outcome. Patients who had an event had lower echocardiographically determined right ventricular fractional area change (RVFAC), greater ventilatory inefficiency (higher (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir), and lower end-tidal CO2 (PETCO2) (all P < .05). Multivariate Cox models revealed that (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir >36, ΔPETCO2(PEAK-REST)≥2 mm Hg, and PETCO2PEAK≤33 mm Hg added prognostic value to RVFAC≤45%. Kaplan-Meyer analyses showed that although 18% of patients with RVFAC>45% had a major cardiac event after 1 year, no patient with RVFAC>45% and (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir ≤36 (or PETCO2PEAK>33 mm Hg) had a negative event. Conversely, although 69% of patients with RVFAC≤45% had a major cardiac event after 1 year, all patients with RVFAC≤45% and ΔPETCO2(PEAK-REST)≥2 mm Hg had a negative event. Ventilatory inefficiency remains a powerful prognostic marker in HF despite the presence of mechanical ventilatory constraints induced by COPD. If these preliminary findings are confirmed in larger studies, optimal thresholds for outcome prediction are likely greater than those traditionally recommended for HF patients without COPD.

Exercise Ventilatory Inefficiency Adds to Lung Function in Predicting Mortality in COPD

ABSTRACTSeverity of resting functional impairment only partially predicts the increased risk of death in chronic obstructive pulmonary disease (COPD). Increased ventilation during exercise is associated with markers of disease progression and poor prognosis, including emphysema extension and pulmonary vascular impairment. Whether excess exercise ventilation would add to resting lung function in predicting mortality in COPD, however, is currently unknown. After an incremental cardiopulmonary exercise test, 288 patients (forced expiratory volume in one second ranging from 18% to 148% predicted) were followed for a median (interquartile range) of 57 (47) months. Increases in the lowest (nadir) ventilation to CO2 output (VCO2) ratio determined excess exercise ventilation. Seventy-seven patients (26.7%) died during follow-up: 30/77 (38.9%) deaths were due to respiratory causes. Deceased patients were older, leaner, had a greater co-morbidity burden (Charlson Index) and reported more daily life dyspnea. Moreover, they had poorer lung function and exercise tolerance (p < 0.05). A logistic regression analysis revealed that ventilation/VCO2 nadir was the only exercise variable that added to age, body mass index, Charlson Index and resting inspiratory capacity (IC)/total lung capacity (TLC) ratio to predict all-cause and respiratory mortality (p < 0.001). Kaplan–Meier analyses showed that survival time was particularly reduced when ventilation/VCO2 nadir > 34 was associated with IC/TLC ≤ 0.34 or IC/TLC ≤ 0.31 for all-cause and respiratory mortality, respectively (p < 0.001). Excess exercise ventilation is an independent prognostic marker across the spectrum of COPD severity. Physiological abnormalities beyond traditional airway dysfunction and lung mechanics are relevant in determining the course of the disease.

Exercise ventilatory inefficiency in mild to end-stage COPD.

Ventilatory inefficiency during exercise is a key pathophysiological feature of chronic obstructive pulmonary disease. Currently, it is unknown how this physiological marker relates to clinically relevant outcomes as resting ventilatory impairment progresses across disease stages. Slope and intercept of the linear region of the ventilation-carbon dioxide output relationship and the ratio between these variables, at the lowest point (nadir), were contrasted in 316 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-4 (forced expiratory volume in 1 s, ranging from 148% pred to 12% pred) and 69 aged- and gender-matched controls, Compared to controls, slope and intercept were higher in GOLD stages 1 and 2, leading to higher nadirs (p<0.05). Despite even larger intercepts in GOLD stages 3 and 4, slopes diminished as disease evolved (from mean±sd 35±6 in GOLD stage 1 to 24±5 in GOLD stage 3, p<0.05). As a result, there were no significant differences in nadirs among patient groups. Higher intercepts, across all stages (p<0.01), and to a lesser extent lower slopes in GOLD stages 2-4 (p<0.05), were related to greater mechanical constraints, worsening pulmonary gas exchange, higher dyspnoea scores, and poorer exercise capacity. Increases in the ventilation intercept best indicate the progression of exercise ventilatory inefficiency across the whole spectrum of chronic obstructive pulmonary disease severity.

Ventilation Distribution Heterogeneity at Rest as a Marker of Exercise Impairment in Mild-to-Advanced COPD

The difference between total lung capacity (TLC) by body plethysmography and alveolar volume (VA) from the single-breath lung diffusing capacity measurement provides an index of ventilation distribution inequalities in COPD. The relevance of these abnormalities to dyspnea and exercise intolerance across the continuum of disease severity remains unknown. Two-hundred and seventy-six COPD patients distributed across GOLD grades 1 to 4 and 67 healthy controls were evaluated. The “poorly communicating fraction” (PCF) of the TLC was estimated as the ratio (%) of TLC to VA. Healthy subjects showed significantly lower PCF values compared to GOLD grades 1 to 4 (10 ± 3% vs. 17 ± 8% vs. 27 ± 10% vs. 37 ± 10% vs. 56 ± 11%, respectively; p < 0.05). Pulmonary gas exchange impairment, mechanical ventilatory constraints and ventilation-corrected dyspnea scores worsened across PCF tertiles (p < 0.05). Of note, GOLD grades 1 and 2 patients with the highest PCF values had pronounced exercise ventilatory inefficiency and dyspnea as a limiting symptom. In fact, dyspnea was a significant contributor to exercise limitation only in those with “moderate” or “extensive” PCF (p < 0.05). A receiver operating characteristics curve analysis revealed that PCF was a better predictor of severely reduced maximal exercise capacity than traditional pulmonary function indexes including FEV1 (area under the curve (95% confidence interval) = 0.85 (0.81–0.89), best cutoff = 33.4%; p < 0.01). In conclusion, PCF is a readily available functional marker of gas exchange and mechanical abnormalities relevant to dyspnea and exercise intolerance across the COPD grades.

Exercise ventilatory inefficiency and mortality in patients with chronic obstructive pulmonary disease undergoing surgery for non-small-cell lung cancer

Surgical resection is the treatment of choice to cure patients with non-small-cell lung cancer (NSCLC); nevertheless, the assessment of the lower limit of surgical tolerance remains difficult. Ventilatory inefficiency (measured as the ventilation to CO(2) production ratio (V'(E)/V'(CO2) slope) is a survival predictor in pulmonary hypertension (PH) and chronic heart failure (CHF) and is considered a marker of PH in chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the role of V'(E)/V'(CO2) slope as preoperative mortality and morbidity predictor in COPD patients submitted to lung resection for NSCLC and considered operable according to current standards. A retrospective analysis was performed in 145 consecutive COPD patients with lung cancer (128 males and 17 females), with a mean age of 64 years (range: 41-82 years) who were referred for preoperatory evaluation. Because of bronchial obstruction or reduced pulmonary diffusion capacity for carbon monoxide (D(L,CO)), all these patients were considered operable only after a cardiopulmonary exercise test showed a preserved cardiopulmonary function. A total of 98 lobectomies, eight bilobectomies and 39 pneumonectomies (13 left and 26 right) were performed. Twenty-one patients (14.5%) suffered severe cardio-respiratory complications; 15/106 patients (14.2%) after lobectomy/bilobectomy and 6/39 (15.4%) after pneumonectomy. Five patients (3.4%) died within 30 days after surgery (3/106 after lobectomy/bilobectomy (2.8%) and 2/39 after pneumonectomy (5.1%)). Considering all functional parameters before surgery and the postoperative predicted values, a logistic regression analysis individuated the V'(E)/V'(CO2) slope as the only independent mortality predictor (odds ratio (OR): 1.24 z=2.77; p<0.007). The V'(O2 peak) was instead the best predictor for the occurrence of severe cardiopulmonary postoperative complications (OR: 0.05, z=-2.39, p<0.02). In COPD patients, a high V'(E)/V'(CO2) slope before lung resection is an independent mortality predictor even in the presence of an acceptable cardiopulmonary performance. COPD patients with high V'(E)/V'(CO2) slope before surgery must be carefully screened to exclude pulmonary hypertension, especially before surgical procedures with large parenchymal exeresis.

Skeletal muscle ergoreflex overactivity is not related to exercise ventilatory inefficiency in non-hypoxaemic patients with COPD

Increased ventilatory response to the metabolic demand ("ventilatory inefficiency") is commonly found during dynamic exercise in patients with chronic obstructive pulmonary disease (COPD). However, the role of enhanced muscle ergoreflex activity on this phenomenon is yet unknown. Ten non-hypoxaemic patients with varying degrees of disease severity (median and range of post-bronchodilator FEV(1) = 37.5 (27 to 70%) predicted) and 7 age- and gender-matched controls were studied. Subjects were submitted to wrist flexion tests to the limit of tolerance (Tlim) with and without post-exercise regional circulatory occlusion (PE-RCO) for 3 min. The muscle ergoreflex activity was quantified as the difference in ventilation between PE-RCO and control recovery periods corrected for the resting values (ergoreflex Delta). In addition, the area under the ventilatory curve in the recovery period was calculated in both conditions. We found that Tlim and the physiological stress associated with localized exercise did not differ between patients and controls. However, patients had increased ventilatory response to a given metabolic demand (VCO(2)), either at rest or during exercise (P < 0.05). There were no significant differences in ergoreflex Delta in patients and controls (-2.2 to 2.4 (0.2) vs. -0.6 to 1.8 (0.3) l/min, respectively). In addition, the area under the ventilatory curve in the recovery period did not differ between control and PE-RCO tests in patients and healthy subjects (P > 0.05). We conclude that increased muscle ergoreflex activity did not contribute to an excessive ventilatory response to exercise in patients with COPD-at least in non-hypoxaemic and non-cachetic subjects.

Exercise ventilation inefficiency in heart failure: pathophysiological and clinical significance

Heart failure (HF) is a complex syndrome characterized by myocardial dysfunction and a poor prognosis. Among multiple markers of severity, an exercise ventilation inefficiency has important clinical and prognostic value. The pathophysiology determining exercise ventilatory inefficiency is complex and not definitively clarified. Three different mechanisms have been identified: (i) increased dead space, (ii) early occurrence of lactic acidosis, and (iii) abnormal chemoreflex and/or metaboreflex activity. Besides its prognostic value, abnormal ventilation can be influenced by pharmacological and non-pharmacological therapies such as beta-blockers, selective cyclic 3'-5' guanosine monosphosphate phosphodiesterase inhibitors, physical training, and nocturnal continuous positive airway pressure. There is an increasing interest for the exercise periodic breathing, which is frequently associated with HF syndrome and has prognostic importance. The precise mechanisms sustaining exercise periodic breathing are not fully defined but ventilatory and metabo-haemodynamic hypotheses have been proposed.

Validation of open-circuit method for the determination of oxygen consumption.

ArticleValidation of open-circuit method for the determination of oxygen consumption.J A Wagner, S M Horvath, T E Dahms, and S ReedJ A Wagner, S M Horvath, T E Dahms, and S ReedPublished Online:01 Jun 1973https://doi.org/10.1152/jappl.1973.34.6.859MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByOn the winter enhancement of adaptive humoral immunity: hypothesis testing in desert hamsters ( Phodopus roborovskii : Cricetidae, Rodentia) kept under long‐day and short‐day photoperiod22 April 2020 | Integrative Zoology, Vol. 15, No. 3Frontiers in Physiology, Vol. 11Alveolar Air and O2 Uptake During Exercise in Patients With Heart FailureJournal of Cardiac Failure, Vol. 24, No. 10Indirect Calorimetry: History, Technology, and Application19 September 2018 | Frontiers in Pediatrics, Vol. 6Basal metabolic rate in free-living tropical birds: the influence of phylogenetic, behavioral, and ecological factors24 March 2017 | Current Zoology, Vol. 64, No. 1Determinants of Exercise Ventilatory Inefficiency in Heart Failure With Reduced or Preserved Ejection Fraction: Application of Classical and Emerging Integrative Physiology ConceptsStable isotope analysis of CO2 in breath indicates metabolic fuel shifts in torpid arctic ground squirrelsComparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, Vol. 209Metabolism of Glucose and Methods of Investigation in the Fetus and NewbornThermoregulation and energetics in hibernating black bears: metabolic rate and the mystery of multi-day body temperature cycles4 February 2015 | Journal of Comparative Physiology B, Vol. 185, No. 4Resting metabolic rate, stress, testosterone, and induced immune response in spring- and fall-born males of Campbell’s dwarf hamsters: Maintenance in long-day conditions23 May 2014 | Biology Bulletin Reviews, Vol. 4, No. 3Metabolic Rate and Prehibernation Fattening in Free-Living Arctic Ground SquirrelsPhysiological and Biochemical Zoology, Vol. 86, No. 5Automated open flow respirometry in continuous and long-term measurements: design and principlesØivind Tøien15 April 2013 | Journal of Applied Physiology, Vol. 114, No. 8Energiehaushalt von Tieren26 October 2012Metabolism of Glucose and Methods of Investigation in the Fetus and NewbornEnergetics of arousal episodes in hibernating arctic ground squirrels11 March 2009 | Journal of Comparative Physiology B, Vol. 179, No. 6Elevated expression of protein biosynthesis genes in liver and muscle of hibernating black bears (Ursus americanus)Vadim B. Fedorov, Anna V. Goropashnaya, Øivind Tøien, Nathan C. Stewart, Andrew Y. Gracey, Celia Chang, Shizhen Qin, Geo Pertea, John Quackenbush, Louise C. Showe, Michael K. Showe, Bert B. Boyer, and Brian M. Barnes1 April 2009 | Physiological Genomics, Vol. 37, No. 2Metabolism of Glucose and Methods of Investigation in the Fetus and NewbornAutomated Metabolic Gas Analysis SystemsSports Medicine, Vol. 31, No. 12A method for estimating respiratory muscle efficiency using an automated metabolic cartRespiration Physiology, Vol. 106, No. 2MRATE: A Pascal program for on-line calculation of metabolic rate using wet gasesComputer Methods and Programs in Biomedicine, Vol. 36, No. 1Effects of different exercise training intensities on lipoprotein cholesterol fractions in healthy middle-aged menAmerican Heart Journal, Vol. 119, No. 2Physiologic and metabolic response of exercising horses to added dietary fatJournal of Equine Veterinary Science, Vol. 9, No. 4Effect of Diet and Metabolic Rate on Open Circuit Calculations of [Vdot]O 2 and [Vdot]CO 217 March 2013 | Research Quarterly. American Alliance for Health, Physical Education and Recreation, Vol. 47, No. 4Nitrogen exchange across the lungs in resting manRespiration Physiology, Vol. 24, No. 3EQUALITY OF INSPIRED AND EXPIRED N2 IN MAN27 April 2009 | Nutrition Reviews, Vol. 32, No. 4 More from this issue > Volume 34Issue 6June 1973Pages 859-63 https://doi.org/10.1152/jappl.1973.34.6.859PubMed4711599History Published online 1 June 1973 Published in print 1 June 1973 Metrics

Alveolar-arterial gas tension differences during graded exercise.

Alveolar-arterial gas tension differences during graded exercise.

Interaction of physiological mechanisms during exercise.

obtained from such studies is often difficult to interpret because the precise work intensity is not known and/or the duration of the exercise is too short for cardiorespiratory function to stabilize and a “Steady state” of exercise to be achieved. WASSERMAN, KARLMAN, ANTONIUS L. VAN KESSEL, AND GEORGE G. BURTON. Interaction of physiological mechanisms during exercise. J. Appl. Physiol. 22(1): 71-85. rg67.-The effects of work intensity and duration on the metabolic circulatory and ventilatory response to exercise are quantitated in healthy male subjects during cycle ergometer exercise. There is a wellordered relationship between work rate and oxidatve energy sources. Steady-state time for 02 consumption (Vo,) is dependent on work intensity (the time arterial blood lactate concentration stops increasing). At moderate work, anaerobic metabolism is a very small part of credit oxidation, while at very heavy work, the pyruvate-lactate mechanism is the major creditor. The increase in gas exchange ratio (R) reflecting the production of CO2 from bicarbonate (buffering of lactic aid) is transient. After the steady state is reached, R decreases. The heart rate increase during constant-load exercise parallels the increase in vo,. Physiological dead space/tidal volume ratio decreases from .33 to .17 during exercise. The reduction is independent of work duration and only slightly reduced as work intensity increases. Arterial 02 tension does not decrease during exercise at sea level even at maximal rates of 02 transport. Arterial-end tidal CO2 tension differences suggest a fluctuation in pulmonary capillary CO2 tension of approximately 8 mm Hg during the respiratory cycle of the exercising subject. Changes in minute ventilation are best predicted from the rate of CO2 production and the extent of respiratory compensation for metabolic acidosis.

A THEORETICAL STUDY OF THE COMPOSITION OF THE ALVEOLAR AIR AT ALTITUDE

ArticleA THEORETICAL STUDY OF THE COMPOSITION OF THE ALVEOLAR AIR AT ALTITUDEWallace O. Fenn, Hermann Rahn, and Arthur B. OtisWallace O. FennFrom the Department of Physiology, The School of Medicine and Dentistry of the University of Rochester, Rochester, N. Y., Hermann RahnFrom the Department of Physiology, The School of Medicine and Dentistry of the University of Rochester, Rochester, N. Y., and Arthur B. OtisFrom the Department of Physiology, The School of Medicine and Dentistry of the University of Rochester, Rochester, N. Y.Published Online:01 Aug 1946https://doi.org/10.1152/ajplegacy.1946.146.5.637MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByTeaching an intuitive derivation of the clinical alveolar equations: mass balance as a fundamental physiological principleMichael C. Wang, Thomas C. Corbridge, Donald R. McCrimmon, and James M. Walter28 February 2020 | Advances in Physiology Education, Vol. 44, No. 2Determinants of Exercise Ventilatory Inefficiency in Heart Failure With Reduced or Preserved Ejection Fraction: Application of Classical and Emerging Integrative Physiology ConceptsCombined effects of inspired oxygen, carbon dioxide, and carbon monoxide on oxygen transport and aerobic capacityGeorge H. Crocker, Balazs Toth, and James H. Jones1 September 2013 | Journal of Applied Physiology, Vol. 115, No. 5Recognition of American Physiological Society members whose research publications had a significant impact on the discipline of physiologyCharles M. Tipton1 March 2013 | Advances in Physiology Education, Vol. 37, No. 1The physiological legacy of the Fenn, Rahn, and Otis schoolJohn B. West15 November 2012 | American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 303, No. 10Comments on Point:Counterpoint: Hypobaric hypoxia induces/does not induce different responses from normobaric hypoxia15 May 2012 | Journal of Applied Physiology, Vol. 112, No. 10O2-CO2 diagram as a tool for comprehension of blood gas abnormalitiesSathya Subramani, Praghalathan Kanthakumar, Delinda Maneksh, Anita Sidharthan, Shoma V. Rao, Vinodh Parasuraman, and Elizabeth Tharion1 September 2011 | Advances in Physiology Education, Vol. 35, No. 3A classic learning opportunity from Fenn, Rahn, and Otis (1946): the alveolar gas equationDouglas Curran-Everett1 June 2006 | Advances in Physiology Education, Vol. 30, No. 2The physiological challenges of the 1952 Copenhagen poliomyelitis epidemic and a renaissance in clinical respiratory physiologyJohn B. West1 August 2005 | Journal of Applied Physiology, Vol. 99, No. 2Understanding pulmonary gas exchange: ventilation-perfusion relationshipsJohn B. West1 December 2004 | American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 287, No. 6Understanding pulmonary gas exchange: ventilation-perfusion relationshipsJohn B. West1 November 2004 | Journal of Applied Physiology, Vol. 97, No. 5Imaging obstructed ventilation with NMR using inert fluorinated gasesDean O. Kuethe, Arvind Caprihan, H. Michael Gach, Irving J. Lowe, and Eiichi Fukushima1 June 2000 | Journal of Applied Physiology, Vol. 88, No. 6Pulmonary gas-exchange analysis by using simultaneous deposition of aerosolized and injected microspheresWilliam A. Altemeier, H. Thomas Robertson, and Robb W. Glenny1 December 1998 | Journal of Applied Physiology, Vol. 85, No. 6 More from this issue > Volume 146Issue 5August 1946Pages 637-653 Copyright & PermissionsCopyright © 1946 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1946.146.5.637PubMed20996488History Received 7 March 1946 Published online 1 August 1946 Published in print 1 August 1946 Metrics