Project description:BackgroundExercise ventilatory inefficiency is usually defined as high ventilation ([Formula: see text]) versus low CO2 output ([Formula: see text]). The inefficiency may be lowered when airflow obstruction is severe because [Formula: see text] cannot be adequately increased in response to exercise. However, the ventilatory inefficiency-airflow obstruction relationship differs to a varying degree. This has been hypothesized to be affected by increased dead space fraction of tidal volume (VD/VT), acidity, hypoxemia, and hypercapnia.MethodsA total of 120 male patients with chronic obstructive pulmonary disease were enrolled. Lung function and incremental exercise tests were conducted, and [Formula: see text] versus [Formula: see text] slope ([Formula: see text]) and intercept ([Formula: see text]) were obtained by linear regression. Arterial blood gas analysis was also performed in 47 of the participants during exercise tests. VD/VT and lactate level were measured.ResultsVD/VTpeak was moderately positively related to [Formula: see text] (r = 0.41) and negatively related to forced expired volume in 1 sec % predicted (FEV1%) (r = - 0.27), and hence the FEV1%- [Formula: see text] relationship was paradoxical. The higher the [Formula: see text], the higher the pH and PaO2, and the lower the PaCO2 and exercise capacity. [Formula: see text] was marginally related to VD/VTrest. The higher the [Formula: see text], the higher the inspiratory airflow, work rate, and end-tidal PCO2peak.Conclusion1) Dead space ventilation perturbs the airflow- [Formula: see text] relationship, 2) increasing ventilation thereby increases [Formula: see text] to maintain biological homeostasis, and 3) the physiology- [Formula: see text]- [Formula: see text] relationships are inconsistent in the current and previous studies.Trial registrationMOST 106-2314-B-040-025 .
Project description: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. 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. 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). 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.
Project description:BackgroundVentilatory inefficiency contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). The intercept of the minute ventilation (V˙ E) vs. carbon dioxide output (V˙ CO2) plot is a key ventilatory inefficiency parameter. However, its relationships with lung hyperinflation (LH) and airflow limitation are not known. This study aimed to evaluate correlations between the V˙ E/V˙ CO2 intercept and LH and airflow limitation to determine its physiological interpretation as an index of functional impairment in COPD.MethodsWe conducted a retrospective analysis of data from 53 COPD patients and 14 healthy controls who performed incremental cardiopulmonary exercise tests (CPETs) and resting pulmonary function assessment. Ventilatory inefficiency was represented by parameters reflecting the V˙ E/V˙ CO2 nadir and slope (linear region) and the intercept of V˙ E/V˙ CO2 plot. Their correlations with measures of LH and airflow limitation were evaluated.ResultsCompared to control, the slope (30.58±3.62, P<0.001) and intercept (4.85±1.11 L/min, P<0.05) were higher in COPDstages1-2, leading to a higher nadir (31.47±4.47, P<0.01). Despite an even higher intercept in COPDstages3-4 (7.16±1.41, P<0.001), the slope diminished with disease progression (from 30.58±3.62 in COPDstages1-2 to 26.84±4.96 in COPDstages3-4, P<0.01). There was no difference in nadir among COPD groups and higher intercepts across all stages. The intercept was correlated with peak V˙ E/maximal voluntary ventilation (MVV) (r=0.489, P<0.001) and peak V˙ O2/Watt (r=0.354, P=0.003). The intercept was positively correlated with residual volume (RV) % predicted (r=0.571, P<0.001), RV/total lung capacity (TLC) (r=0.588, P<0.001), peak tidal volume (VT)/FEV1 (r=0.482, P<0.001) and negatively correlated with rest inspiratory capacity (IC)/TLC (r=-0.574, P<0.001), peak VT/TLC (r=-0.585, P<0.001), airflow limitation forced expiratory volume in 1 s (FEV1) % predicted (r=-0.606, P<0.001), and FEV1/forced vital capacity (FVC) (r=-0.629, P<0.001).ConclusionsV˙ E/V˙ CO2 intercept was consistently correlated with worsening static and dynamic LH, pulmonary gas exchange, and airflow limitation in COPD. The V˙ E/V˙ CO2 intercept emerged as a useful index of ventilatory inefficiency in COPD patients.
Project description:AimsThe minute ventilation-carbon dioxide production relationship (VE/VCO2 slope) is widely used for prognostication in heart failure (HF) with reduced left ventricular ejection fraction (LVEF). This study explored the prognostic value of VE/VCO2 slope across the spectrum of HF defined by ranges of LVEF.Methods and resultsIn this single-centre retrospective observational study of 1347 patients with HF referred for cardiopulmonary exercise testing, patients with HF were categorized into HF with reduced (HFrEF, LVEF < 40%, n = 598), mid-range (HFmrEF, 40% ≤ LVEF < 50%, n = 164), and preserved (HFpEF, LVEF ≥ 50%, n = 585) LVEF. Four ventilatory efficiency categories (VC) were defined: VC-I, VE/VCO2 slope ≤ 29; VC-II, 29 < VE/VCO2 slope < 36; VC-III, 36 ≤ VE/VCO2 slope < 45; and VC-IV, VE/VCO2 slope ≥ 45. The associations of these VE/VCO2 slope categories with a composite outcome of all-cause mortality or HF hospitalization were evaluated for each category of LVEF. Over a median follow-up of 2.0 (interquartile range: 1.9, 2.0) years, 201 patients experienced the composite outcome. Compared with patients in VC-I, those in VC-II, III, and IV demonstrated three-fold, five-fold, and eight-fold increased risk for the composite outcome. This incremental risk was observed across HFrEF, HFmrEF, and HFpEF cohorts.ConclusionsHigher VE/VCO2 slope is associated with incremental risk of 2 year all-cause mortality and HF hospitalization across the spectrum of HF defined by LVEF. A multilevel categorical approach to the interpretation of VE/VCO2 slope may offer more refined risk stratification than the current binary approach employed in clinical practice.
Project description:Study objectivesThere are few studies evaluating (1) exercise capacity as assessed by the 6-minute walking distance (6MWD) test in large populations with obstructive sleep apnea (OSA); and (2) correlations with patients' comorbidities.MethodsThis study presents a cluster analysis performed on the data of 1,228 patients. Severity of exercise limitation was defined on the basis of 6MWD.ResultsSixty-one percent showed exercise limitation (29.2% and 31.9% mild and severe exercise limitation, respectively). About 60% and 40% of patients were included in cluster 1 (CL1) and 2 (CL2), respectively. CL1 included younger patients with high prevalence of apneas, desaturations, and hypertension with better exercise tolerance. CL2 included older patients, all with chronic obstructive pulmonary disease (COPD), high prevalence of chronic respiratory failure (CRF), fewer apneas but severe mean desaturation, daytime hypoxemia, more severe exercise limitation, and exercise-induced desaturations. Only CRF and COPD significantly (P < .001) correlated with 6MWD < 85% of predicted value. 6MWD correlated positively with apnea-hypopnea index, oxygen desaturation index, nocturnal pulse oxygen saturation (SpO₂), resting arterial oxygen tension, mean SpO₂ on exercise, and negatively with age, body mass index, time spent during night with SpO₂ < 90%, mean nocturnal desaturation, arterial carbon dioxide tension, and number of comorbidities. Patients without severe comorbidities had higher exercise capacity than those with severe comorbidities, (P < .001). Exercise limitation was significantly worse in OSA severity class I when compared to other classes (P < .001).ConclusionsA large number of patients with OSA experience exercise limitation. Older age, comorbidities such as COPD and CRF, OSA severity class I, severe mean nocturnal desaturation, and daytime hypoxemia are associated with worse exercise tolerance.
Project description:ObjectiveOriginator intravenous rituximab is an important rheumatology treatment but is costly, and administration requires several hours. Because biosimilar rituximab may cost less and subcutaneous rituximab requires a shorter visit, both may reduce costs and increase treatment capacity (infusions per year).MethodsWe implemented time-driven activity-based costing (TDABC), a method to assess costs and opportunities to increase capacity, throughout the care pathway for 26 patients receiving a total of 30 rituximab infusions. Using the TDABC estimates, we created a base case, which included provider time, salaries, infusion rates and times, and drug formulation, to simulate an induction cycle (two infusions). We varied these parameters in sensitivity analyses and assessed the impact of infusion rates and formulation (biosimilar vs. subcutaneous) on capacity before and after assuming a fixed budget.ResultsThe base-case cost was $19 452; more than 90% was due to drug cost. In sensitivity analyses, varying projected biosimilar cost led to the greatest cost savings ($8,988 per cycle). Faster infusion rates and subcutaneous rituximab increased annual capacity (300% and 800%, respectively). With a fixed budget, subcutaneous rituximab led to a relative increase in capacity over biosimilar rituximab except when biosimilar cost savings relative to originator rituximab exceeded 40%; faster biosimilar infusion rates did not meaningfully affect these findings.ConclusionUsing TDABC, we demonstrate that rituximab cost is the primary driver of treatment cost, but capacity is largely driven by treatment time. Subcutaneous rituximab leads to higher capacity than biosimilar rituximab across a range of plausible costs; its use in rheumatology should be studied.
Project description:Due to the currently ongoing pandemic of coronavirus disease 2019 (COVID-19), it is strongly recommended to wear facemasks to minimize transmission risk. Wearing a facemask may have the potential to increase dyspnea and worsen cardiopulmonary parameters during exercise; however, research-based evidence is lacking. We investigated the hypothesis that wearing facemasks affects the sensation of dyspnea, pulse rate, and percutaneous arterial oxygen saturation during exercise. Healthy adults (15 men, 9 women) underwent a progressive treadmill test under 3 conditions in randomized order: wearing a surgical facemask, cloth facemask, or no facemask. Experiment was carried out once daily under each condition, for a total of 3 days. Each subject first sat on a chair for 30 minutes, then walked on a treadmill according to a Bruce protocol that was modified by us. The experiment was discontinued when the subject's pulse rate exceeded 174 beats/min. After discontinuation, the subject immediately sat on a chair and was allowed to rest for 10 minutes. Subjects were required to rate their levels of dyspnea perception on a numerical scale. Pulse rate and percutaneous arterial oxygen saturation were continuously monitored with a pulse oximeter. These parameters were recorded in each trial every 3 minutes after the start of the exercise; the point of discontinuation; and 5 and 10 minutes after discontinuation. The following findings were obtained. Wearing a facemask does not worsen dyspnea during light to moderate exercise but worsens dyspnea during vigorous exercise. Wearing a cloth facemask increases dyspnea more than wearing a surgical facemask during exercise and increases pulse rate during vigorous exercise, but it does not increase pulse rate during less vigorous exercise. Wearing a surgical facemask does not increase pulse rate at any load level. Lastly, wearing a facemask does not affect percutaneous arterial oxygen saturation during exercise at any load level regardless of facemask type.
Project description:BACKGROUND:Bronchiectasis is common in patients with advanced chronic obstructive pulmonary disease (COPD) and adversely affects the patients' clinical condition. This study aimed to investigate the effects of bronchiectasis on exercise capacity, dyspnea perception, disease-specific quality of life, and psychological status in patients with COPD and determine the extent of these adverse effects by the severity of bronchiectasis. METHODS:A total of 387 COPD patients (245 patients with only COPD [Group 1] and 142 COPD patients with accompanying bronchiectasis [Group 2]) were included in the study. The patients in Group 2 were divided into three subgroups as mild, moderate, and severe using the Bronchiectasis Severity Index. Six-minute walk distance, dyspnea perception, St. George's Respiratory Questionnaire (SGRQ), and hospital anxiety and depression scores were compared between the groups. RESULTS:In Group 2, dyspnea perception, SGRQ total scores, depression score were higher, and walking distance was lower (P = 0.001, P = 0.007, P = 0.001, and P = 0.011, respectively). Group 2 had significantly worse arterial blood gas values. Dyspnea perception increased with the increasing severity in Group 2 (P < 0.001). Walking distance was lower in patients with severe bronchiectasis (P < 0.001). SGRQ total score, anxiety, and depression scores were significantly higher in the severe subgroup (P < 0.001, P = 0.003, and P = 0.002, respectively). CONCLUSIONS:In patients with Stage 3 and 4 COPD, the presence of bronchiectasis adversely affects the clinical status of the patients, decreases their exercise capacity, deteriorates their quality of life, and disrupts their psychological status. Investigating the presence of bronchiectasis in COPD patients is crucial for early diagnosis and proper treatment.
Project description:Study objectivesPatients with congestive heart failure (CHF) frequently exhibit an elevated ratio of minute ventilation over CO2 output (VE/VCO2 slope) while undergoing exercise tests. One of the factors contributing to this elevated slope is an increased chemosensitivity to CO2 in that this slope significantly correlates with the slope of the ventilatory response to CO2 rebreathing at rest. A previous study in patients with CHF and central sleep apnea showed that the highest VE/VCO2 slope during exercise was associated with the most severe central sleep apnea. In the current study, we tested the hypothesis that in patients with CHF and obstructive sleep apnea (OSA), the highest VE/VCO2 slope is also associated with the most severe OSA. If the hypothesis is correct, then it implies that in CHF, augmented instability in the negative feedback system controlling breathing predisposes to both OSA and central sleep apnea.MethodsThis preliminary study involved 70 patients with stable CHF and a spectrum of OSA severity who underwent full-night polysomnography, echocardiography, and cardiopulmonary exercise testing. Peak oxygen consumption and the VE/VCO2 slope were calculated.ResultsThere was significant positive correlation between the apnea-hypopnea index and the VE/VCO2 slope (r = .359; P = .002). In the regression model, involving the relevant variables of age, body mass index, sex, VE/VCO2 slope, peak oxygen consumption, and left ventricular ejection fraction, the apnea-hypopnea index retained significance with VE/VCO2.ConclusionsIn patients with CHF, the VE/VCO2 slope obtained during exercise correlates significantly to the severity of OSA, suggesting that an elevated CO2 response should increase suspicion for the presence of severe OSA, a treatable disorder that is potentially associated with excess mortality.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Comparison Between Exercise Training and CPAP Treatment for Patients With Heart Failure and Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/record/NCT01538069; Identifier: NCT01538069.CitationBittencourt L, Javaheri S, Servantes DM, Pelissari Kravchychyn AC, Almeida DR, Tufik S. In patients with heart failure, enhanced ventilatory response to exercise is associated with severe obstructive sleep apnea. J Clin Sleep Med. 2021;17(X):1875-1880.
Project description:BackgroundWhether individuals with non-obstructive spirometry-defined small airway dysfunction (SAD) have impaired exercise capacity is unclear, particularly in never-smokers. This study clarifies the degree of impaired exercise capacity and its potential cause in individuals with non-obstructive SAD.MethodsThis community-based, multiyear cross-sectional study analyzed data collected in Guangdong, China from 2012-2019 by the National Science and Technology Support Plan Program. Measurements of exercise capacity [peak work rate and peak oxygen uptake ( V˙O2peak )] in participants with non-obstructive spirometry-defined SAD (n=157) were compared with those in controls (n=85) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) I patients (n=239). Subgroup analyses were performed by smoking status.ResultsThe risk of impaired exercise capacity was significantly higher in participants with non-obstructive SAD [ V˙O2peak <84%predicted, adjusted odds ratio (aOR) =2.53; 95% confidence interval (CI): 1.42-4.52] than in controls but was not significantly different from that in GOLD I patients. Results were consistent within subgroups of smoking status (ever-smokers: non-obstructive SAD vs. controls, aOR =2.44; 95% CI: 1.08-5.51; never-smokers: non-obstructive SAD vs. controls, aOR =2.38, 95% CI: 1.02-5.58). Participants with non-obstructive SAD had a significantly lower peak work rate (β=-10.5; 95% CI: -16.3 to -4.7) and V˙O2peak (%predicted, β=-4.0; 95% CI: -7.7 to -0.2) and tended to have higher ventilatory equivalents for carbon dioxide at the ventilatory threshold ( V˙E/V˙CO2AT , β=1.1; 95% CI: -0.1 to 2.3) when compared with controls. Both peak work rate and V˙O2peak were negatively correlated with V˙E/V˙CO2AT .ConclusionsAlthough not meeting the current criteria for chronic obstructive pulmonary disease, individuals with non-obstructive SAD have impaired exercise capacity that may be associated with ventilatory inefficiency regardless of smoking status.