Exertional oscillatory ventilation in subjects without heart failure reporting chronic dyspnoea.

Oscillatory ventilation detected on incremental cardiopulmonary exercise testing might be found in subjects without heart failure reporting exertional dyspnoea despite the best available therapy for their underlying cardiopulmonary disease https://bit.ly/3Tyl7bE.

Comparing hospital admissions, comorbidities, and biomarkers between severe asthma and Gold III-IV chronic obstructive pulmonary disease.

INTRODUCTION: In spite of difficulties in differentiating asthma from chronic obstructive pulmonary disease (COPD), physicians should strive for accurate diagnosis because outcomes may be different. OBJECTIVES: Our aims were to compare the frequency of hospital admissions (HA) between severe asthmatic (SA) and Gold III-IV COPD subjects receiving disease-specific guideline recommended therapy and to depict the frequency of prevalent chronic disorders and the laboratorial profile suggesting allergic and eosinophilic phenotypes. METHODS: This cross-sectional study comprises one group of SA subjects and another group of Gold III-IV COPD subjects. Subjects answered standard questionnaires, underwent spirometry, and provided a peripheral blood sample. We validated the HA that have occurred during the preceding year by review of the report emitted by the hospital. We detected comorbidities by review of current pharmacological therapies. RESULTS: We enrolled 160 SA and 41 Gold III-IV COPD subjects. As compared with Gold III-IV COPD subjects, SA subjects had lower odds of HA (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.05-0.74) and higher odds of obesity (OR 9.17, 95%CI 2.68-31.37), hypertension (OR 2.54, 95%CI 1.16-5.57), and diabetes mellitus (OR 5.71, 95%CI 1.56-20.85). The frequency of atopic and eosinophilic phenotypes was similar between study groups. CONCLUSIONS: Our results demonstrated that Gold III-IV COPD subjects had worse outcomes as compared with SA subjects. We also observed that the frequency of atopy and high peripheral blood eosinophil count were similar between study groups. Finally, we exposed aspects of comorbidities related to asthma and COPD that indicate the need of close monitoring the cardiovascular risk in SA subjects above 40 years of age.

Modified BODE Index to Predict Mortality in Individuals With COPD: The Role of 4-Min Step Test.

BACKGROUND: The BODE (body mass index, air-flow obstruction, dyspnea, exercise capacity) index is a composite prognostic marker that predicts mortality in COPD. It includes body mass index, air-flow obstruction, dyspnea score, and exercise capacity by using the 6-min walk distance. However, a 30-m-long corridor is necessary to perform the test and this limits its use in clinical practice. Step tests may elicit distinct physiologic responses compared with the 6-min walk test but are easy to perform in the office setting. We sought to investigate whether a 4-min step test would be a suitable surrogate of the 6-min walk test, in a modified BODE step index (simplified BODE index), to predict mortality in COPD. METHODS: Individuals with COPD performed a self-paced 4-min step test, and the simplified BODE index was calculated by replacing the 6-min walk distance by the number of steps climbed. Cutoff values were determined by receiver operating characteristic curve analysis as follows: score 0 for >60 steps; score 1 for 50-60 steps; score 2 for 40-49 steps; and score 3 for <40 steps. RESULTS: A total of 186 individuals with COPD were enrolled from 2011 to 2016 (60% males; mean ± SD age, 65 ± 9 y; mean ± SD FEV1, 50 ± 17 L). There were 36 deaths among the study cohort. The simplified BODE index was a prognostic marker, independent of cardiovascular comorbidities and oxygen desaturation (HR 1.12, confidence interval (CI) [1.03-1.22]). Individuals with simplified BODE index scores ≥ 7 were at higher risk of death from any cause (P < .001, log-rank test). CONCLUSIONS: This was the first study, to our knowledge, to show that the 4-min step test as a surrogate of exercise capacity in the BODE index (simplified BODE index) is an independent predictor of mortality in COPD and may help to spread its use among practicing physicians.

Effects of bi-level positive airway pressure on ventilatory and perceptual responses to exercise in comorbid heart failure-COPD.

This study tested the hypothesis that, by increasing the volume available for tidal expansion (inspiratory capacity, IC), bi-level positive airway pressure (BiPAP™) would lead to greater beneficial effects on dyspnea and exercise intolerance in comorbid heart failure (HF)-chronic obstructive pulmonary disease (COPD) than HF alone. Ten patients with HF and 9 with HF-COPD (ejection fraction = 30 ± 6% and 35 ± 7%; FEV1 = 83 ± 12% and 65 ± 15% predicted, respectively) performed a discontinuous exercise protocol under sham ventilation or BiPAP™. Time to intolerance increased with BiPAP™ only in HF-COPD (p < 0.05). BiPAP™ led to higher tidal volume and lower duty cycle with longer expiratory time (p < 0.05). Of note, BiPAP™ improved IC (by ∼0.5 l) across exercise intensities only in HF-COPD. These beneficial consequences were associated with lower dyspnea scores at higher levels of ventilation (p < 0.05). By improving the qualitative" (breathing pattern and operational lung volumes) and sensory (dyspnea) features of exertional ventilation, BiPAP™ might allow higher exercise intensities to be sustained for longer during cardiopulmonary rehabilitation in HF-COPD.

Exercise intolerance in comorbid COPD and heart failure: the role of impaired aerobic function.

Impaired aerobic function is a potential mechanism of exercise intolerance in patients with combined cardiorespiratory disease. We investigated the pathophysiological and sensory consequences of a low change in oxygen uptake (ΔV'O2 )/change in work rate (ΔWR) relationship during incremental exercise in patients with coexisting chronic obstructive pulmonary disease (COPD) and systolic heart failure (HF).After clinical stabilisation, 51 COPD-HF patients performed an incremental cardiopulmonary exercise test to symptom limitation. Cardiac output was non-invasively measured (impedance cardiography) in a subset of patients (n=18).27 patients presented with ΔV'O2 /ΔWR below the lower limit of normal. Despite similar forced expiratory volume in 1 s and ejection fraction, the low ΔV'O2 /ΔWR group showed higher end-diastolic volume, lower inspiratory capacity and lower transfer factor compared to their counterparts (p<0.05). Peak WR and peak V'O2 were ∼15% and ∼30% lower, respectively, in the former group: those findings were associated with greater symptom burden in daily life and at a given exercise intensity (leg discomfort and dyspnoea). The low ΔV'O2 /ΔWR group presented with other evidences of impaired aerobic function (sluggish V'O2 kinetics, earlier anaerobic threshold) and cardiocirculatory performance (lower oxygen pulse, lower stroke volume and cardiac output) (p<0.05). Despite similar exertional hypoxaemia, they showed worse ventilatory inefficiency and higher operating lung volumes, which led to greater mechanical inspiratory constraints (p<0.05).Impaired aerobic function due to negative cardiopulmonary-muscular interactions is an important determinant of exercise intolerance in patients with COPD-HF. Treatment strategies to improve oxygen delivery to and/or utilisation by the peripheral muscles might prove particularly beneficial to these patients.

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

RATIONALE: 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. OBJECTIVES: 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. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

BACKGROUND: Exercise 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. METHODS: Ventilatory, gas exchange and sensory responses to incremental exercise were contrasted in 68 heart failure-COPD patients (12 EOV+). EOV was established by standard criteria. RESULTS: Compared 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). CONCLUSIONS: Dyspnea 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.

Exercise Ventilation in COPD: Influence of Systolic Heart Failure.

Systolic heart failure is a common and disabling co-morbidity of chronic obstructive pulmonary disease (COPD) which may increase exercise ventilation due to heightened neural drive and/or impaired pulmonary gas exchange efficiency. The influence of heart failure on exercise ventilation, however, remains poorly characterized in COPD. In a prospective study, 98 patients with moderate to very severe COPD [41 with coexisting heart failure; 'overlap' (left ventricular ejection fraction < 50%)] underwent an incremental cardiopulmonary exercise test (CPET). Compared to COPD, overlap had lower peak exercise capacity despite higher FEV1. Overlap showed lower operating lung volumes, greater ventilatory inefficiency and larger decrements in end-tidal CO2 (PETCO2) (P < 0.05). These results were consistent with those found in FEV1-matched patients. Larger areas under receiver operating characteristic curves to discriminate overlap from COPD were found for ventilation ([Formula: see text]E)-CO2 output [Formula: see text]CO2) intercept, [Formula: see text]E-[Formula: see text]CO2 slope, peak [Formula: see text]E/[Formula: see text]CO2 ratio and peak PETCO2. Multiple logistic regression analysis revealed that [Formula: see text]CO2 intercept ≤ 3.5 L/minute [odds ratios (95% CI) = 7.69 (2.61-22.65), P < 0.001] plus [Formula: see text]E-[Formula: see text]CO2 slope ≥ 34 [2.18 (0.73-6.50), P = 0.14] or peak [Formula: see text]E/[Formula: see text]CO2 ratio ≥ 37 [5.35 (1.96-14.59), P = 0.001] plus peak PETCO2 ≤ 31 mmHg [5.73 (1.42-23.15), P = 0.01] were indicative of overlapping. Heart failure increases the ventilatory response to metabolic demand in COPD. Variables reflecting excessive ventilation might prove useful to assist clinical interpretation of CPET responses in COPD patients presenting heart failure as co-morbidity.

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

Severity 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.

Heart Failure Impairs Muscle Blood Flow and Endurance Exercise Tolerance in COPD.

Heart failure, a prevalent and disabling co-morbidity of COPD, may impair cardiac output and muscle blood flow thereby contributing to exercise intolerance. To investigate the role of impaired central and peripheral hemodynamics in limiting exercise tolerance in COPD-heart failure overlap, cycle ergometer exercise tests at 20% and 80% peak work rate were performed by overlap (FEV1 = 56.9 ± 15.9% predicted, ejection fraction = 32.5 ± 6.9%; N = 16), FEV1-matched COPD (N = 16), ejection fraction-matched heart failure patients (N = 15) and controls (N = 12). Differences (Δ) in cardiac output (impedance cardiography) and vastus lateralis blood flow (indocyanine green) and deoxygenation (near-infrared spectroscopy) between work rates were expressed relative to concurrent changes in muscle metabolic demands (ΔO2 uptake). Overlap patients had approximately 30% lower endurance exercise tolerance than COPD and heart failure (p < 0.05). ΔBlood flow was closely proportional to Δcardiac output in all groups (r = 0.89-0.98; p < 0.01). Overlap showed the largest impairments in Δcardiac output/ΔO2 uptake and Δblood flow/ΔO2 uptake (p < 0.05). Systemic arterial oxygenation, however, was preserved in overlap compared to COPD. Blunted limb perfusion was related to greater muscle deoxygenation and lactate concentration in overlap (r = 0.78 and r = 0.73, respectively; p < 0.05). ΔBlood flow/ΔO2 uptake was related to time to exercise intolerance only in overlap and heart failure (p < 0.01). In conclusion, COPD and heart failure add to decrease exercising cardiac output and skeletal muscle perfusion to a greater extent than that expected by heart failure alone. Treatment strategies that increase muscle O2 delivery and/or decrease O2 demand may be particularly helpful to improve exercise tolerance in COPD patients presenting heart failure as co-morbidity.

Exercise ventilation in COPD: influence of systolic heart failure

Systolic heart failure is a common and disabling co-morbidity of chronic obstructive pulmonary disease (COPD) which may increase exercise ventilation due to heightened neural drive and/or impaired pulmonary gas exchange efficiency. The influence of heart failure on exercise ventilation, however, remains poorly characterized in COPD. In a prospective study, 98 patients with moderate to very severe COPD [41 with coexisting heart failure; 'overlap' (left ventricular ejection fraction < 50%)] underwent an incremental cardiopulmonary exercise test (CPET). Compared to COPD, overlap had lower peak exercise capacity despite higher FEV1. Overlap showed lower operating lung volumes, greater ventilatory inefficiency and larger decrements in end-tidal CO2 (PETCO2) (P < 0.05). These results were consistent with those found in FEV1-matched patients. Larger areas under receiver operating characteristic curves to discriminate overlap from COPD were found for ventilation ([Formula: see text]E)-CO2 output [Formula: see text]CO2) intercept, [Formula: see text]E-[Formula: see text]CO2 slope, peak [Formula: see text]E/[Formula: see text]CO2 ratio and peak PETCO2. Multiple logistic regression analysis revealed that [Formula: see text]CO2 intercept ≤ 3.5 L/minute [odds ratios (95% CI) = 7.69 (2.61-22.65), P < 0.001] plus [Formula: see text]E-[Formula: see text]CO2 slope ≥ 34 [2.18 (0.73-6.50), P = 0.14] or peak [Formula: see text]E/[Formula: see text]CO2 ratio ≥ 37 [5.35 (1.96-14.59), P = 0.001] plus peak PETCO2 ≤ 31 mmHg [5.73 (1.42-23.15), P = 0.01] were indicative of overlapping...

Heart Failure Impairs Muscle Blood Flow and Endurance Exercise Tolerance in COPD

Heart failure, a prevalent and disabling co-morbidity of COPD, may impair cardiac output and muscle blood flow there by contributing to exercise intolerance. To investigate the role of impaired central and peripheral hemodynamics in limiting exercise tolerance in COPD-heart failure overlap, cycle ergometer exercise tests at20% and 80% peak work rate were performed by overlap (FEV1 = 56.9 ± 15.9% predicted, ejection fraction =32.5 ± 6.9%; N = 16), FEV1-matched COPD (N = 16), ejection fraction-matched heart failure patients (N =15) and controls (N = 12). Differences () in cardiac output (impedance cardiography) and vastus lateralis blood flow (indocyanine green) and deoxygenation (near-infrared spectroscopy) between work rates were expressed relative to concurrent changes in muscle metabolic demands (O2 uptake). Overlap patientshad approximately 30% lower endurance exercise tolerance than COPD and heart failure (p < 0.05). Blood flow was closely proportional to cardiac output in all groups (r = 0.89–0.98; p < 0.01). Overlap showedthe largest impairments in cardiac output/O2 uptake and blood flow/O2 uptake (p < 0.05). Systemicarterial oxygenation, however, was preserved in overlap compared to COPD. Blunted limb perfusion wasrelated to greater muscle deoxygenation and lactate concentration in overlap (r = 0.78 and r = 0.73, respectively;p < 0.05). Blood flow/O2 uptake was related to time to exercise intolerance only in overlap andheart failure (p < 0.01). In conclusion, COPD and heart failure add to decrease exercising cardiac output andskeletal muscle perfusion to a greater extent than that expected by heart failure alone. Treatment strategiesthat increase muscle O2 delivery and/or decrease O2 demand may be particularly helpful to improveexercise tolerance in COPD patients presenting heart failure as co-morbidity...

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. METHODS: 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.RESULTS: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 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...

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.