Ventilatory inefficiency: a key physiopathological mechanism increasing dyspnea and reducing exercise capacity in chronic obstructive pulmonary disease.
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ABSTRACT:
SUBMITTER: Caviedes I
PROVIDER: S-EPMC8339755 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
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Ventilatory inefficiency: a key physiopathological mechanism increasing dyspnea and reducing exercise capacity in chronic obstructive pulmonary disease.
Journal of thoracic disease 20210701 7
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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 .
| S-EPMC7409645 | biostudies-literature
Project description:IntroductionCoronavirus 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.MethodsWe 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.ResultsPatients 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).InterpretationIn 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.
| S-EPMC8230788 | biostudies-literature
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.
| S-EPMC8024855 | biostudies-literature
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.
| S-EPMC8788025 | biostudies-literature
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.
| S-EPMC7161454 | biostudies-literature
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.
| S-EPMC7231514 | biostudies-literature
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.
| S-EPMC8483295 | biostudies-literature
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.
| S-EPMC6967141 | biostudies-literature
Project description:RationaleOpioids are commonly used to relieve dyspnea, but clinical data are mixed and practice varies widely.ObjectivesEvaluate the effect of morphine on dyspnea and ventilatory drive under well-controlled laboratory conditions.MethodsSix healthy volunteers received morphine (0.07 mg/kg) and placebo intravenously on separate days (randomized, blinded). We measured two responses to a CO(2) stimulus: (1) perceptual response (breathing discomfort; described by subjects as "air hunger") induced by increasing partial pressure of end-tidal carbon dioxide (Pet(CO2)) during restricted ventilation, measured with a visual analog scale (range, "neutral" to "intolerable"); and (2) ventilatory response, measured in separate trials during unrestricted breathing.Measurements and main resultsWe determined the Pet(CO2) that produced a 60% breathing discomfort rating in each subject before morphine (median, 8.5 mm Hg above resting Pet(CO2)). At the same Pet(CO2) after morphine administration, median breathing discomfort was reduced by 65% of its pretreatment value; P < 0.001. Ventilation fell 28% at the same Pet(CO2); P < 0.01. The effect of morphine on breathing discomfort was not significantly correlated with the effect on ventilatory response. Placebo had no effect.Conclusions(1) A moderate morphine dose produced substantial relief of laboratory dyspnea, with a smaller reduction of ventilation. (2) In contrast to an earlier laboratory model of breathing effort, this laboratory model of air hunger established a highly significant treatment effect consistent in magnitude with clinical studies of opioids. Laboratory studies require fewer subjects and enable physiological measurements that are difficult to make in a clinical setting. Within-subject comparison of the response to carefully controlled laboratory stimuli can be an efficient means to optimize treatments before clinical trials.
| S-EPMC3208656 | biostudies-literature
Project description:BACKGROUND: Chronic obstructive pulmonary disease (COPD) reduces exercise capacity, but lung function parameters do not fully explain functional class and lung-heart interaction could be the explanation. We evaluated echocardiographic predictors of mortality and six minutes walking distance (6MWD), a marker for quality of life and mortality in COPD. METHODS: Ninety COPD patients (GOLD criteria) were evaluated by body plethysmography, 6MWD and advanced echocardiography parameters (pulsed wave tissue Doppler and speckle tracking). RESULTS: Mean 6MWD was 403 (± 113) meters. All 90 subjects had preserved left ventricular (LV) ejection fraction 64.3%?±?8.6%. Stroke volume decreased while heart rate increased with COPD severity and hyperinflation. In 66% of patients, some degree of diastolic dysfunction was present. Mitral tissue Doppler data in COPD could be interpreted as a sign of low LV preload and not necessarily an intrinsic impairment in LV relaxation/compliance. Tricuspid regurgitation (TR) increased with COPD severity and hyperinflation. Age (p?<?0.001), BMI (p <?0.001), DLCO SB (p <?0.001) and TR (p 0.005) were independent predictors of 6MWD and a multivariable model incorporating heart function parameters (adjusted r2?=?.511) compared well to a model with lung function parameters alone (adjusted r2?=?.475). LV global longitudinal strain (p?=?0.034) was the only independent predictor of mortality among all baseline, body plethysmographic and echocardiographic variables. CONCLUSIONS: Among subjects with moderate to severe COPD and normal LVEF, GLS independently predicted all-cause mortality. Exercise tolerance correlated with standard lung function parameters only in univariate models; in subsequent models including echocardiographic parameters, longer 6MWD correlated independently with milder TR, better DLCO SB, younger age and lower BMI. We extended the evidence on COPD affecting cardiac chamber volumes, LV preload, heart rate, as well as systolic and diastolic function. Our results highlight lung-heart interaction and the necessity of cardiac evaluation in COPD.
| S-EPMC3852306 | biostudies-literature