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European Journal of Pharmacology Dec 2023Dapagliflozin may confer additional decongestive and natriuretic benefits to patients with acute heart failure (AHF). Nonetheless, this hypothesis was not clinically... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Dapagliflozin may confer additional decongestive and natriuretic benefits to patients with acute heart failure (AHF). Nonetheless, this hypothesis was not clinically examined. This study aimed primarily to investigate the effect of dapagliflozin on symptomatic relief in those patients.
METHODS
This was a randomized, double-blind study that included 87 patients with AHF presenting with dyspnea. Within 24 h of admission, patients were randomized to receive either dapagliflozin (10 mg/day, N = 45) or placebo (N = 42) for 30 days. The primary outcome was the difference between the two groups in the area under the curve (AUC) of visual analogue scale (VAS) dyspnea score over the first 4 days. Secondary endpoints included urinary sodium (Na) after 2 h of randomization, percent change in NT-proBNP, cumulative urine output (UOP), and differences in mortality and hospital readmission rates.
RESULTS
The results showed that dapagliflozin significantly reduced the AUC of VAS dyspnea score compared to placebo (3192.2 ± 1631.9 mm × h vs 4713.1 ± 1714.9 mm × h, P < 0.001). The relative change of NT-proBNP compared to its baseline was also larger with dapagliflozin (-34.89% vs -10.085%, P = 0.001). Additionally, higher cumulative UOP was found at day 4 (18600 ml in dapagliflozin vs 13700 in placebo, P = 0.031). Dapagliflozin decreased rehospitalization rates within 30 days after discharge, while it did not affect the spot urinary Na concentration, incidence of worsening of heart failure, or mortality rates.
CONCLUSION
Dapagliflozin may provide symptomatic relief and improve diuresis in patients with AHF. Further studies are needed to confirm these findings. https://clinicaltrials.gov/study/NCT05406505.
Topics: Humans; Benzhydryl Compounds; Dyspnea; Glucosides; Heart Failure; Stroke Volume; Double-Blind Method
PubMed: 37923161
DOI: 10.1016/j.ejphar.2023.176179 -
International Journal of Chronic... 2023Chronic obstructive pulmonary disease (COPD) is a disease defined by airflow obstruction with a high morbidity and mortality and significant economic burden. Although... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is a disease defined by airflow obstruction with a high morbidity and mortality and significant economic burden. Although pulmonary function testing is the cornerstone in diagnosis of COPD, it cannot fully characterize disease severity or cause of dyspnea because of disease heterogeneity and variable related and comorbid conditions affecting cardiac, vascular, and musculoskeletal systems. Cardiopulmonary exercise testing (CPET) is a valuable tool for assessing physical function in a wide range of clinical conditions, including COPD. Familiarity with measurements made during CPET and its potential to aid in clinical decision-making related to COPD can thus be useful to clinicians caring for this population. This review highlights pulmonary and extrapulmonary impairments that can contribute to exercise limitation in COPD. Key elements of CPET are identified with an emphasis on measurements most relevant to COPD. Finally, clinical applications of CPET demonstrated to be of value in the COPD setting are identified. These include quantifying functional capacity, differentiating among potential causes of symptoms and limitation, prognostication and risk assessment for operative procedures, and guiding exercise prescription.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Exercise Test; Lung; Respiratory Function Tests; Dyspnea; Exercise Tolerance
PubMed: 38089541
DOI: 10.2147/COPD.S432841 -
Palliative Medicine Oct 2023Opioids are recommended to treat advanced refractory dyspnoea despite optimal therapy by the American Thoracic Society clinical practice guidelines, while newly... (Meta-Analysis)
Meta-Analysis Review
Effectiveness and safety of opioids on breathlessness and exercise endurance in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
Opioids are recommended to treat advanced refractory dyspnoea despite optimal therapy by the American Thoracic Society clinical practice guidelines, while newly published randomised controlled trials of opioids in chronic obstructive pulmonary disease yield conflicting results.
AIM
This study aimed to evaluate the effectiveness and safety of opioids for patients with chronic obstructive pulmonary disease.
DESIGN
Systematic review and meta-analysis (PROSPERO CRD42021272556).
DATA SOURCES
Databases of PubMed, EMBASE and CENTRAL were searched from inception to 2022 for eligible randomised controlled trials.
RESULTS
Twenty-four studies including 975 patients, were included. In cross-over studies, opioids improved breathlessness (standardised mean difference, -0.43; 95% CI, -0.55 to -0.30; = 18%) and exercise endurance (standardised mean difference, 0.22; 95% CI, 0.02-0.41; = 70%). However, opioids failed to improve dyspnoea (standardised mean difference, -0.02; 95% CI, -0.22 to 0.19; = 39%) and exercise endurance (standardised mean difference, 0.00; 95% CI, -0.27 to 0.27; = 0%) in parallel control studies that administered sustained-release opioids for more than 1 week. The opioids used in most crossover studies were short-acting and rarely associated with serious adverse effects. Only minor side effects such as dizziness, nausea, constipation and vomiting were identified for short-acting opioids.
CONCLUSIONS
Sustained-release opioids did not improve dyspnoea and exercise endurance. Short-acting opioids appeared to be safe, have potential to lessen dyspnoea and improve exercise endurance, supporting benefit in managing episodes of breathlessness and providing prophylactic treatment for exertional dyspnoea.
Topics: Humans; Analgesics, Opioid; Delayed-Action Preparations; Pulmonary Disease, Chronic Obstructive; Dyspnea; Exercise; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 37710987
DOI: 10.1177/02692163231194838 -
ESC Heart Failure Aug 2023The HFA-PEFF algorithm (Heart Failure Association-Pre-test assessment, Echocardiography and natriuretic peptide score, Functional testing in cases of uncertainty, Final...
AIMS
The HFA-PEFF algorithm (Heart Failure Association-Pre-test assessment, Echocardiography and natriuretic peptide score, Functional testing in cases of uncertainty, Final aetiology) is a three-step algorithm to diagnose heart failure with preserved ejection fraction (HFpEF). It provides a three-level likelihood of HFpEF: low (score < 2), intermediate (score 2-4), or high (score > 4). HFpEF may be confirmed in individuals with a score > 4 (rule-in approach). The second step of the algorithm is based on echocardiographic features and natriuretic peptide levels. The third step implements diastolic stress echocardiography (DSE) for controversial diagnostic cases. We sought to validate the three-step HFA-PEFF algorithm against a haemodynamic diagnosis of HFpEF based on rest and exercise right heart catheterization (RHC).
METHODS AND RESULTS
Seventy-three individuals with exertional dyspnoea underwent a full diagnostic work-up following the HFA-PEFF algorithm, including DSE and rest/exercise RHC. The association between the HFA-PEFF score and a haemodynamic diagnosis of HFpEF, as well as the diagnostic performance of the HFA-PEFF algorithm vs. RHC, was assessed. The diagnostic performance of left atrial (LA) strain < 24.5% and LA strain/E/E' < 3% was also assessed. The probability of HFpEF was low/intermediate/high in 8%/52%/40% of individuals at the second step of the HFA-PEFF algorithm and 8%/49%/43% at the third step. After RHC, 89% of patients were diagnosed as HFpEF and 11% as non-cardiac dyspnoea. The HFA-PEFF score resulted associated with the invasive haemodynamic diagnosis of HFpEF (P < 0.001). Sensitivity and specificity of the HFA-PEFF score for the invasive haemodynamic diagnosis of HFpEF were 45% and 100% for the second step of the algorithm and 46% and 88% for the third step of the algorithm. Neither age, sex, body mass index, obesity, chronic obstructive pulmonary disease, or paroxysmal atrial fibrillation influenced the performance of the HFA-PEFF algorithm, as these characteristics were similarly distributed over the true positive, true negative, false positive, and false negative cases. Sensitivity of the second step of the HFA-PEFF score was non-significantly improved to 60% (P = 0.08) by lowering the rule-in threshold to >3. LA strain alone had a sensitivity and specificity of 39% and 14% for haemodynamic HFpEF, increasing to 55% and 22% when corrected for E/E'.
CONCLUSIONS
As compared with rest/exercise RHC, the HFA-PEFF score lacks sensitivity: Half of the patients were wrongly classified as non-cardiac dyspnoea after non-invasive tests, with a minimal impact of DSE in modifying HFpEF likelihood.
Topics: Humans; Heart Failure; Stroke Volume; Hemodynamics; Natriuretic Peptides; Dyspnea; Algorithms
PubMed: 37321596
DOI: 10.1002/ehf2.14436 -
Zhonghua Jie He He Hu Xi Za Zhi =... Nov 2023Chronic obstructive pulmonary disease (COPD) is a common respiratory system disease that seriously affects the quality of life and has a high mortality rate. Exertional... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is a common respiratory system disease that seriously affects the quality of life and has a high mortality rate. Exertional dyspnea is the most common symptom in COPD patients with complexed pathogenesis and limited therapeutic drug effects. In this paper, we reviewed the relevant mechanisms and assessment, in order to improve understanding of the pathogenesis of exertional dyspnea in COPD, to emphasize the importance of accurate assessment, and to explore effective interventions that can effectively improve the degree of dyspnea and even delay or reverse the decline in lung function.
Topics: Humans; Quality of Life; Pulmonary Disease, Chronic Obstructive; Dyspnea
PubMed: 37914428
DOI: 10.3760/cma.j.cn112147-20230823-00104 -
Respiratory Medicine 2023This systematic review summarized the evidence on the effects (benefits and harms) of pulmonary rehabilitation for individuals with acute exacerbations of chronic...
INTRODUCTION AND OBJECTIVES
This systematic review summarized the evidence on the effects (benefits and harms) of pulmonary rehabilitation for individuals with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).
MATERIAL AND METHODS
We included randomized controlled trials comparing pulmonary rehabilitation to either active interventions or usual care regardless of setting. In March 2022, we searched MEDLINE, Scopus, CENTRAL, CINAHL and Web of Sciences, and trial registries. Record screening, data extraction and risk of bias assessment were undertaken by two reviewers. We assessed the certainty of the evidence using the GRADE approach.
RESULTS
This systematic review included 18 studies (n = 1465), involving a combination of mixed settings (8 studies), inpatient settings (8 studies), and outpatient settings (2 studies). The studies were at high risk of performance, detection, and reporting biases. Compared to usual care, pulmonary rehabilitation probably improves AECOPD-related hospital readmissions (relative risk 0.56, 95% CI 0.36 to 0.86; moderate certainty evidence) and cardiovascular submaximal capacity (standardized mean difference 0.73, 95% CI 0.48 to 0.99; moderate certainty evidence). Low certainty evidence suggests that pulmonary rehabilitation may be beneficial on re-exacerbations, dyspnoea, and impact of disease. The evidence regarding the effects of pulmonary rehabilitation on health-related quality of life and mortality is very uncertain (very low certainty evidence).
CONCLUSION
Our results indicate that pulmonary rehabilitation may be an effective treatment option for individuals with AECOPD, irrespective of setting. Our certainty in this evidence base was limited due to small studies, heterogeneous rehabilitation programs, numerous methodological weaknesses, and a poor reporting of findings that were inconsistent with each other. Trialists should adhere to the latest reporting standards to strengthen this body of evidence.
REGISTRATION
The study protocol was registered in Open Science Framework (https://osf.io/amgbz/).
Topics: Humans; Quality of Life; Pulmonary Disease, Chronic Obstructive; Patient Readmission; Dyspnea; Treatment Outcome
PubMed: 37858727
DOI: 10.1016/j.rmed.2023.107425 -
Annals of the American Thoracic Society Nov 2023Subjects with preserved ratio impaired spirometry (PRISm) experience increased respiratory symptoms, although they present heterogeneous characteristics. However, the...
Subjects with preserved ratio impaired spirometry (PRISm) experience increased respiratory symptoms, although they present heterogeneous characteristics. However, the longitudinal changes in these symptoms and respiratory function are not well known. To investigate PRISm from the viewpoint of respiratory symptoms in a longitudinal, large-scale general population study. The Nagahama study included 9,789 inhabitants, and a follow-up evaluation was conducted after 5 years. Spirometry and self-administered questionnaires regarding respiratory symptoms, including prolonged cough, sputum and dyspnea, and comorbidities were conducted. In total, 9,760 subjects were analyzed, and 438 subjects had PRISm. Among the subjects with PRISm, 53% presented with respiratory symptoms; dyspnea was independently associated with PRISm. Follow-up assessment revealed that 73% of the subjects with PRISm with respiratory symptoms were consistently symptomatic, whereas 39% of the asymptomatic subjects with PRISm developed respiratory symptoms within 5 years. In addition, among subjects with respiratory symptoms without airflow limitation at baseline, PRISm was a risk factor for the development of airflow limitation independent of smoking history and comorbidities. This study demonstrated that 53% of the subjects with PRISm had respiratory symptoms; dyspnea was a distinct characteristic of PRISm. Approximately three-fourths of the symptomatic subjects with PRISm consistently complained of respiratory symptoms within 5 years. Together with our result that PRISm itself is an independent risk factor for the development of chronic obstructive pulmonary disease among subjects with respiratory symptoms, the clinical course of subjects with PRISm with symptoms requires careful monitoring.
Topics: Humans; Lung; Pulmonary Disease, Chronic Obstructive; Spirometry; Dyspnea; Risk Factors; Forced Expiratory Volume
PubMed: 37560979
DOI: 10.1513/AnnalsATS.202301-050OC -
Respiratory Medicine Aug 2023Cardiopulmonary exercise testing (CPET) remains poorly understood and, consequently, largely underused in respiratory medicine. In addition to a widespread lack of... (Review)
Review
Cardiopulmonary exercise testing (CPET) remains poorly understood and, consequently, largely underused in respiratory medicine. In addition to a widespread lack of knowledge of integrative physiology, several tenets of CPET interpretation have relevant controversies and limitations which should be appropriately recognized. With the intent to provide a roadmap for the pulmonologist to realistically calibrate their expectations towards CPET, a collection of deeply entrenched beliefs is critically discussed. They include a) the actual role of CPET in uncovering the cause(s) of dyspnoea of unknown origin, b) peak O uptake as the key metric of cardiorespiratory capacity, c) the value of low lactate ("anaerobic") threshold to differentiate cardiocirculatory from respiratory causes of exercise limitation, d) the challenges of interpreting heart rate-based indexes of cardiovascular performance, e) the meaning of peak breathing reserve in dyspnoeic patients, f) the merits and drawbacks of measuring operating lung volumes during exercise, g) how best interpret the metrics of gas exchange inefficiency such as the ventilation-CO output relationship, h) when (and why) measurements of arterial blood gases are required, and i) the advantages of recording submaximal dyspnoea "quantity" and "quality". Based on a conceptual framework that links exertional dyspnoea to "excessive" and/or "restrained" breathing, I outline the approaches to CPET performance and interpretation that proved clinically more helpful in each of these scenarios. CPET to answer clinically relevant questions in pulmonology is a largely uncharted research field: I, therefore, finalize by highlighting some lines of inquiry to improve its diagnostic and prognostic yield.
Topics: Humans; Exercise Test; Pulmonary Medicine; Dyspnea; Anaerobic Threshold; Exercise; Exercise Tolerance
PubMed: 37100256
DOI: 10.1016/j.rmed.2023.107249 -
European Journal of Applied Physiology Mar 2024Research describes the existence of a relationship between cortical activity and the regulation of bulbar respiratory centers through the evaluation of the... (Review)
Review
PURPOSE
Research describes the existence of a relationship between cortical activity and the regulation of bulbar respiratory centers through the evaluation of the electroencephalographic (EEG) signal during respiratory challenges. For example, we found evidences of a reduction in the frequency of the EEG (alpha band) in both divers and non-divers during apnea tests. For instance, this reduction was more prominent in divers due to the greater physiological disturbance resulting from longer apnea time. However, little is known about EEG adaptations during tests of maximal apnea, a test that voluntarily stops breathing and induces dyspnea.
RESULTS
Through this mini-review, we verified that a protocol of successive apneas triggers a significant increase in the maximum apnea time and we hypothesized that successive maximal apnea test could be a powerful model for the study of cortical activity during respiratory distress.
CONCLUSION
Dyspnea is a multifactorial symptom and we believe that performing a successive maximal apnea protocol is possible to understand some factors that determine the sensation of dyspnea through the EEG signal, especially in people not trained in apnea.
Topics: Humans; Apnea; Breath Holding; Dyspnea; Electroencephalography; Respiratory Distress Syndrome; Diving
PubMed: 38105311
DOI: 10.1007/s00421-023-05379-x -
Journal of Cardiac Failure Sep 2023Prior studies indicate significant physiological differences between obese and nonobese patients with heart failure (HF), but none have evaluated differences in...
BACKGROUND
Prior studies indicate significant physiological differences between obese and nonobese patients with heart failure (HF), but none have evaluated differences in hemodynamic patterns in these patient populations during treatment for acute decompensated HF (ADHF).
OBJECTIVES
In this study, we assessed differences in hemodynamic trends between obese and nonobese patients during treatment for ADHF.
METHODS
Obese (body mass index (BMI) >30, n = 63) and nonobese (BMI < 25, n = 69) patients with ADHF in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) study who had pulmonary artery catheterization data available through the duration of treatment were evaluated. Hemodynamics were analyzed at baseline and optimal day. Changes in BNP levels, weight, creatinine, BUN, 6MWT, orthopnea and dyspnea scores were assessed.
RESULTS
Despite similar baseline hemodynamics, obese patients had significantly less absolute and relative pulmonary arterial wedge pressure (PAWP) reduction (-16 ± 28 vs -32 ± 29%; P = 0.03) during treatment. Obese patients also had higher PAWPs (19.9 + 8 vs 15.5 + 6.8 mmHg; P = 0.01) and PA pressures at optimization compared with nonobese patients. Obese and nonobese patients had similar relative improvements in weight, BNP, 6-minute walk test distance, dyspnea and orthopnea scores, and similar changes in creatinine and BUN levels.
CONCLUSIONS
Obese patients treated for ADHF display less reduction in invasively measured left heart filling pressures, despite similar improvements in symptoms, weight loss, and noninvasive surrogates of congestion. Our findings suggest a degree of decoupling between left heart filling pressures and congestive symptoms in obese patients undergoing treatment for ADHF.
Topics: Humans; Heart Failure; Creatinine; Obesity; Hemodynamics; Dyspnea
PubMed: 36963608
DOI: 10.1016/j.cardfail.2023.02.016