Improvement In Dyspnea Research Articles

Abstract 4123391: CardioMEMS and Mavacamten: A Synergistic Approach in Managing Hypertrophic Obstructive Cardiomyopathy with HFpEF Phenotype

Introduction: Mavacamten is a cardiac myosin inhibitor that has been approved for obstructive hypertrophic cardiomyopathy (oHCM). The CardioMEMS PA (pulmonary artery) sensor allows remote pulmonary artery diastolic (PAD) pressure monitoring to adjust diuresis in heart failure with preserved ejection fraction (HFpEF). We present the case of a patient with oHCM and HFpEF where data extrapolated from CardioMEMS provided valuable insight to the hemodynamic impact of cardiac myosin inhibitors. Case: A 66-year-old female with hypertension, obesity and oHCM presented with worsening dyspnea and was evaluated for septal myectomy. However, surgery was deferred because of decompensated HFpEF, as evidenced by significant leg edema on exam, and severely elevated left and right-side filling pressure, with restrictive physiology on right heart catheterization. A CardioMEMS PA sensor was implanted to guide decongestion, however, escalation of diuresis was limited due to severe left ventricular outflow tract (LVOT) obstruction. PAD remained elevated at 20-30 mmHg. Due to the refractory LVOT obstruction and despite the use of maximally tolerated beta blockers, Mavacamten was initiated and escalated according to protocol. LVOT obstruction resolved on follow up echocardiogram. Without any adjustment in her diuretic regimen, her PAD decreased to 15-20 mmHg. On follow-up visit, the patient reported improvement in dyspnea and reduction in lower extremity edema. Discussion: Managing oHCM is challenging, particularly when complicated by HFpEF. Mavacamten has shown promise in reducing LVOT gradients and improving symptoms in oHCM. However, managing fluid status in these patients can be difficult due to the risk of exacerbating LVOT obstruction while optimizing filling pressures. Our case provides direct evidence that treating LVOT obstruction with a cardiac myosin inhibitor leads to improvement in decompensated heart failure, as evidenced by the reduction in PAD. Conclusion: Addressing LVOT obstruction is key to decongesting and managing heart failure in oHCM patients. In our case, the use of CardioMEMS PA sensor system allowed a novel perspective of assessing hemodynamic impact of cardiac myosin inhibitors.

Exercise interventions for Long COVID: a systematic review of randomised controlled trials

Abstract Background Long COVID is prevalent and costly. There is much debate around the effectiveness and tolerance of exercise among people with Long COVID due to the potential to exacerbate symptoms. Therefore, this systematic review aimed to examine the effectiveness and tolerance of exercise interventions among people with Long COVID as part of a wider project to inform updates to the Irish Health Service Executive’s Long COVID interim model of care. Methods Medline via EBSCOhost, Embase, and CENTRAL were systematically searched on 28 February 2023. Inclusion criteria were: (1) participants with Long COVID; (2) random assignment to either an exercise intervention or a comparison group; (3) a quantitative measure of at least one of 12 core Long COVID outcomes. Two reviewers independently extracted data and assessed study risk of bias using the Cochrane Risk of Bias tool. Results In total, 4,394 studies were identified, 569 full texts were screened, and eight studies were included. Follow up periods ranged from two to 28 weeks (mean=8.5 weeks). Sample sizes ranged from 39 to 119 (mean=56). All studies were in adults (mean age=49.9 years) and both sexes (mean female proportion=53.9%). Four studies were at low risk of bias, two unclear, and two high. The evidence suggests that exercise interventions led to short-term improvements in dyspnoea, fatigue, physical function and the physical domain of quality of life. Of the five studies that reported adverse events, rates were low and, when reported, mild. Of the seven studies that reported sufficient information, one of 252 participants who received exercise discontinued the intervention due to tolerance-related issues. Conclusions Available evidence suggests that exercise interventions may have short-term benefits and be tolerable among some people with Long COVID. However, the evidence base consists of a limited number of studies with small sample sizes and short follow-up periods. Key messages • There is much debate around the effectiveness and safety of exercise among people with Long COVID due to the potential to exacerbate symptoms. • The available evidence suggests that appropriate exercise interventions may have short-term benefits and be tolerable. However, there are notable limitations among the evidence.

Unilateral arytenoid chondroplasty combined with minimally invasive mucosal flap plasty for bilateral vocal cord paralysis--clinical analysis of 66 cases

Objective: To analyze the efficacy of unilateral arytenoid chondroplasty combined with minimally invasive mucosal flap plasty in the management bilateral vocal cord paralysis. Methods: A total of 66 patients with bilateral vocal cord paralysis hospitalized in the First Hospital of Sun Yat-sen University from January 2018 to December 2023 were retrospectively analyzed, among whom there were 8 males and 58 females, with ages ranging from 35 to 86 years old(mean age (57.8±11.6) years). All patients underwent suspension laryngoscopic CO2 laser unilateral arytenoid chondroplasty and mucosal flap under general anesthesia. Postoperative follow-up period extended from 6 months to 6 years, with a median duration of 28 months. The study compared the degree of dyspnea and voice quality (subjective and objective evaluation) of the patients pre- and post-operatively, and analyzed the clinical differences between patients with and without preoperative or intraoperative tracheotomy, the extubation rate of tracheotomized patients, the recurrence rate, and the complication rate. Continuous variables conforming to normal distribution were tested by t-test and categorical variables by χ² test,the Wilcoxon rank-sum test was used to analyze the improvement in dyspnea before and after surgery. Results: Compared with the preoperative period, 59 patients showed improvement in postoperative dyspnea (U=161.5, P<0.01); there was no significant difference in voice disorder index 10, subjective auditory-perceptual assessment, and maximal vocalization time (P>0.05), all of which remained within the relative normal range. Tracheotomy was performed in 32 out of 66 patients, with predominantly degree Ⅲ- dyspnea (46.9%, 15/32), including 26 patients with preoperative tracheotomy and 6 patients with intraoperative tracheotomy. Among the 34 patients who did not undergo tracheotomy, the majority presented with degree Ⅱ-dyspnea (82.4%, 28/34). All patients achieved successful extubation following surgery, with a mean median time to extubation of 1 month. Conclusions: The combination of unilateral arytenoid chondroplasty and minimally invasive mucosal flap plasty represents a refined and effective therapeutic approach for bilateral vocal cord paralysis. This minimally invasive technique has the potential to reduce the rate of tracheotomy.

Bronchial asthma with normal forced expiratory volume in 1 second (FEV1) compared with low FEV1.

Cough variant asthma (CVA) is characterized by cough as a sole symptom and normal pulmonary function. However, it is unclear whether CVA really common among asthmatic patients with normal forced expiratory volume in 1 second (FEV1). The aim of this study was to evaluate the incidence of cough alone symptom among the subjects with normal FEV1 and to evaluate their differences from ordinary asthmatic subjects. We defined normal FEV1 as ≥90% predicted based on the article of Kotti GH. Of the patients with normal FEV1, we chose subjects without wheeze, and the duration of cough was not to ask, since the symptoms often occurred with acute exacerbation and timing of visiting a doctor depended on each patient's perception. Test for airway hyperresponsiveness was not performed in this study. Visual analogue scale (VAS) scores for cough and dyspnea, FEV1, and fractional exhaled nitric oxide (FeNO) responsiveness to inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) treatment were compared in patients with normal FEV1 and with low FEV1 <90%. Correlations of changes in symptoms with changes of FEV1, FeNO, peripheral eosinophil count, and serum immunoglobulin E (IgE) at single time point were also examined in each group and in overall patients. The participants were 329 physician-diagnosed treatment-naive patients with asthma who were divided into 187 in normal FEV1 and 142 in low FEV1 groups. Cough without dyspnea was present in 16 patients (8.6%) in the normal FEV1 group, suggesting candidates for CVA in this analysis were quite few. Improvement in symptoms after treatment was similar between both groups. But VAS scores of dyspnea were still higher in the low FEV1 group. The degree of improvement in FEV1 after ICS/LABA treatment was less in the normal FEV1 group than in the low FEV1 group, but was still evident. Peripheral eosinophil count, serum IgE, and FeNO values before treatment were lower in the normal FEV1 group. In overall patients, improvements of symptoms after treatment were significantly correlated with FEV1 changes. Improvement of dyspnea was also significantly related to peripheral eosinophil count and change of FeNO, whereas improvement of cough was not related to these T helper 2 (Th2) response markers. Candidates for CVA among the patients with asthma with predicted FEV1 ≥90% were few. Participants with normal FEV1 respond well to ICS/LABA treatment for improvement of symptom. The change of FEV1 after treatment, and the pre-treatment blood eosinophil count, serum IgE, and FeNO were lower in normal FEV1 cases than in low FEV1 cases. These observations suggest asthmatic patients with normal FEV1, including candidates for CVA having just common mild asthma. In overall participants, symptoms of cough and dyspnea were similar, but were not identical in relation to the Th2 background.

Effectiveness of TheraPEP Versus Conventional Breathing Techniques in Managing Acute COPD Exacerbations

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, often complicated by acute exacerbations that impair lung function and quality of life. Effective airway clearance techniques are essential in managing exacerbations, but the comparative effectiveness of different methods remains unclear. This study aimed to evaluate the short-term effectiveness of TheraPEP, a positive expiratory pressure (PEP) device, versus the Active Cycle of Breathing Technique (ACBT) in managing acute COPD exacerbations. Methods: A randomized controlled trial (RCT) was conducted with 60 patients (≥40 years) admitted with acute exacerbations of COPD. Participants were randomly assigned to either the TheraPEP group (n=30) or the ACBT group (n=30). Each group received three daily sessions of their assigned therapy throughout their hospital stay. Primary outcomes included dyspnea, measured by the modified Borg Dyspnea Scale, and secondary outcomes included sputum clearance, lung function (FEV1, FVC, and FEV1/FVC ratio), oxygen saturation (SpO₂), and quality of life, measured by the Breathlessness, Cough, and Sputum Scale (BCSS). Data were collected at baseline, discharge, and 14-day follow-up. A two-way repeated-measures ANOVA was used to examine changes in dyspnea, lung function, sputum clearance, SpO₂, and BCSS scores over time (baseline, discharge, and 14-day follow-up) within and between groups. The main effects of time (within-subject factor) and group (between-subject factor) were assessed, along with the interaction effects (time × group). Results: Both groups demonstrated significant improvements in dyspnea, lung function, and quality of life from baseline to discharge and follow-up. However, the TheraPEP group showed significantly greater improvements in sputum clearance (p=0.01), oxygen saturation (p=0.03), and BCSS scores (p=0.03) compared to the ACBT group. No significant between-group differences were found for FEV1, FVC, or FEV1/FVC ratio (p &gt; 0.05). Conclusions: Both TheraPEP and ACBT are effective in managing acute COPD exacerbations, but TheraPEP offers additional benefits in terms of sputum clearance and oxygenation. These findings suggest that TheraPEP may be more suitable for patients with severe mucus hypersecretion. Further research is warranted to assess the long-term effects of these therapies on COPD progression and patient outcomes.

Patient-reported outcomes in patients with metastatic non-squamous non-small cell lung cancer from the randomized Phase II PERLA trial comparing first-line chemotherapy plus dostarlimab or pembrolizumab

BackgroundPERLA (NCT04581824) compared efficacy and safety of dostarlimab (DCT) or pembrolizumab (PCT) plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer. Here, we report patient-reported outcomes (PROs; exploratory analysis) from PERLA. MethodsPatients were randomized 1:1 to receive DCT or PCT every 3 weeks (Q3W) for ≤ 35 cycles [C]. PROs (EORTC QLQ-C30 and QLQ-LC13, PRO-CTCAE, FACT-GP5) were collected at baseline, Q3W until C4, Q9W until C16, Q12W until end of treatment and at 30-day safety follow-up. Change from baseline and time to deterioration (TTD) in QLQ-C30 and QLQ-LC13 were analyzed using longitudinal mixed models and Kaplan–Meier estimators, respectively. ResultsThe PRO (DCT/PCT) datasets included 102/99 patients for QLQ-C30, 96/90 for QLQ-LC13, 96/88 for PRO-CTCAE, and 95/87 for FACT-GP5. Completion rates were > 80 % to C4, then decreased in both arms. For QLQ-C30 and QLQ-LC13, most patients reported stable/improved responses at C13 (∼ 9 months on treatment), with similar responses between arms except more patients reported improvements in dyspnea (QLQ-C30: 36.4 % vs 13.0 %; QLQ-LC13: 40.6 % vs 25.0 %) and chest pain (QLQ-LC13: 34.4 % vs 10.0 %) with DCT vs PCT. TTD per QLQ-C30 and QLQ-LC13 were similar between arms, although TTD in dyspnea was longer with DCT vs PCT (QLQ-LC13: 4.24 vs 1.54 months; p = 0.0168). Most patients in both arms reported that adverse events occurred occasionally/rarely/never with moderate/mild severity. Overall, patients reported little/no bother from treatment side effects. ConclusionsDCT maintained health-related quality of life similarly to PCT and was well tolerated, supporting the PERLA primary results and dostarlimab use in future regimens.

Pro-Resolving Inflammatory Effects of a Marine Oil Enriched in Specialized Pro-Resolving Mediators (SPMs) Supplement and Its Implication in Patients with Post-COVID Syndrome (PCS).

This study aimed to evaluate the eicosanoid and pro-resolutive parameters in patients with Post-COVID Syndrome (PCS) during a 12-week supplementation with a marine oil enriched in specialized pro-resolving mediators (SPMs). This study was conducted on 53 adult patients with PCS. The subjects included must have had a positive COVID-19 test (PCR, fast antigen test, or serologic test) and persistent symptoms related to COVID-19 at least 12 weeks before their enrolment in the study. The following parameters were evaluated: polyunsaturated fatty acids EPA, DHA, ARA, and DPA; specialized pro-resolving mediators (SPMs), 17-HDHA, 18-HEPE, 14-HDHA, resolvins, maresins, protectins, and lipoxins. The eicosanoids group included prostaglandins, thromboxanes, and leukotrienes. The development of the clinical symptoms of fatigue and dyspnea were evaluated using the Fatigue Severity Scale (FSS) and the Modified Medical Research Council (mMRC) Dyspnea Scale. Three groups with different intake amounts were evaluated (daily use of 500 mg, 1500 mg, and 3000 mg) and compared to a control group not using the product. In the serum from patients with PCS, an increase in 17-HDHA, 18-HEPE, and 14-HDHA could be observed, and a decrease in the ratio between the pro-inflammatory and pro-resolutive lipid mediators was detected; both differences were significant (p < 0.05). There were no differences found between the three treatment groups. Fatigue and dyspnea showed a trend of improvement after supplementation in all groups. A clear enrichment in the serum of the three monohydroxylated SPMs could be observed at a dosage of 500 mg per day. Similarly, a clear improvement in fatigue and dyspnea was observed with this dosage.

408. IS DYSPNOEA IN PARAOESOPHAGEAL HERNIA ONLY POST PRANDIAL? RELEVANCE TO THE POST TOOL DEVELOPMENT

Abstract Background Paraoesophageal hernia (POH) presents with a unique symptomatology that may mimic respiratory and cardiovascular disease. Dyspnoea is increasingly recognised as a predominant symptom of POH. Post-prandial dyspnoea was included in a POH specific symptom reporting tool (POST). We have prospectively recorded the type of dyspnoea among patients with POH, and whether surgery improves dyspnoea. Methods Consecutive patients with POH managed in our service from 2009 to 2022 were identified. Preoperative dyspnoea was documented as 'post prandial' or 'with ordinary physical activity' on a symptom recording proforma. Post operative improvement in dyspnoea was evaluated. Results A total of 520 consecutive patients were diagnosed with POH between January 2009 to November 2022. 514 patients were included in the analysis; there were 383 females (75%) and mean age was 70. Improvement in dyspnoea was reported in 308 out of 355 (95%) patients. Pre-operative dyspnoea was categorised into activity induced (89%) and post-prandial (3%) or both (8%). Patients with both activity induced and post-prandial dyspnoea were 0.26 times less likely to report improvement in dyspnoea postoperatively than those with only activity induced dyspnoea (OR=0.26, 95% CI 0.07-0.94, P=0.041). Conclusion Symptom assessment of POH should include both post-prandial and activity induced dyspnoea, as both type of dyspnoea are associated with the presence of POH and is improved following surgical repair. There are multiple possible causes for dyspnoea including post prandial cardiac inflow obstruction, pulmonary aspiration, as well as anaemia (with or without iron deficiency) associated with the hernia. Any dyspnoea should be considered related to POH and therefore both post-prandial and activity induced dyspnoea should be included in diagnostic algorithm designed to evaluate POH.

Exploring Functional Improvements by Sex in Six-Minute Walk Test, Exertional Angina, and Dyspnea After Enhanced External Counterpulsation Therapy.

The objective of this study was to explore functional improvements by sex for patients with refractory angina pectoris using a 6-min walk test (6MWT) after enhanced external counterpulsation (EECP) therapy. All patients who completed EECP from 2015 to 2023 were identified for analysis retrospectively, utilizing the electronic medical record. Patients completed 35 1-hr EECP sessions 5 d/wk over 7wk. All baseline and post-EECP intervention 6MWT, exertional angina, and dyspnea measurements were assessed on the first and last sessions, respectively. Paired and unpaired t tests and linear and stepwise multivariable regression analyses were performed. The cohort consisted of 116 patients (24 female) with a mean age of 69±13yr. After EECP, there was a mean improvement of 128 m (72%) in distance walked during the 6MWT ( P <.001) with 126±91 m improvement in males and 134±73 m in females. The improvement in angina and dyspnea scores was 3.5±2.1 and 4.2±2.4, respectively. There were no differences between the sexes for improvements in 6MWT distance, angina, or dyspnea. Univariate associations for change in 6MWT distance included body mass index (BMI; adjusted R2 =.05) and being a nonsmoker (adjusted R2 =.03). The only independent predictor for increasing distance during 6MWT was BMI (adjusted R2 =.1; P =.001). Patients who have refractory angina pectoris can improve their functional capacity while simultaneously decreasing exertional angina and dyspnea using EECP. This study highlights the equal efficacy of EECP therapy for females.

Acute effects of manual breathing assist technique on lung volume and dyspnea in individuals with severe chronic obstructive pulmonary disease: A quasi-experimental study.

Manual breathing assist technique (MBAT) is a common physical therapy technique used to facilitate airway clearance and improve ventilation and oxygenation. The effects during and immediately after intervention in individuals with chronic obstructive pulmonary disease (COPD) are unknown. This study aimed to investigate the acute effects and potential mechanisms of MBAT on lung volume, dyspnea, and oxygenation in individuals with COPD. This non-randomized quasi-experimental pre-test/post-test study included participants from pulmonary rehabilitation programs at Tagami Hospital (COPD group) and a community exercise program (Healthy group). During a single session, MBAT was applied during the expiration of every breath for 10 minutes. Dyspnea and lung volumes (tidal volume; VT, inspiratory capacity; IC, inspiratory reserved capacity; IRV, expiratory reserve capacity; ERV) were collected at baseline and after MBAT. Pulse oximetry (SpO2), skeletal muscle oxygenation (SmO2), and oxy- and deoxy-hemoglobin (O2Hb and HHb) using near-infrared spectroscopy (NIRS) were collected at baseline, during, and after MBAT. Between-group comparisons were conducted using the Mann-Whitney U-test and chi-square analyses. Within-group changes before and after MBAT were analyzed using the Wilcoxon signed-rank test. The Kruskal-Wallis test was used to detect differences in NIRS variables in each phase and over time. Thirty participants with COPD, matched for age and sex, were included, with 15 individuals per group. The difference scores of VT, IRV, and IC were significantly higher in the Healthy group than in the COPD group, but improvements in dyspnea and SpO2 were significantly higher in the COPD group. Compared to baseline, ERV decreased significantly in both groups, with dyspnea and SpO2 improving significantly only in the COPD group. Inspiratory accessory muscle ΔO2Hb and ΔHHb were significantly higher and lower (respectively) during MBAT in the COPD group compared to the Healthy group. Additionally, only the COPD group had increased SmO2 during and after MBAT compared to baseline. MBAT in patients with COPD had acute physiological effects in reducing dyspnea by facilitating expiration and decreasing the recruitment of accessory respiratory muscles. MBAT may help individuals with COPD reduce dyspnea before exercise therapy in a pulmonary rehabilitation program.

Effect of a polyherbal Unani formulation on left ventricular diastolic dysfunction in hypertensive patients- a randomized single blind placebo controlled clinical trial.

Diastolic dysfunction represents an important pathophysiological intermediate between hypertension and heart failure. In the last two decades, the prevalence of heart failure patients having normal or near normal ejection fraction (EF) has increased to around 60 %. It thus poses a great morbidity and mortality risk to the population. In view of present scenario of high prevalence, lack of evidence-based therapy, and limited clinical trials, this study aimed to evaluate how a Unani formulation affects the improvement of the left ventricular diastolic function. This clinical trial was set up as a randomized, placebo-controlled study involving 35 participants, with 18 individuals in the test group and 17 in the control group. Test group received 3.5 g of a polyherbal Unani formulation in capsule form along with 35 mL of an extract of Borago officinalis L. (Arq-e-Gaozaban), divided into two doses after meals. Meanwhile, the control group received a placebo in the same manner over an eight-week period. Follow-ups were conducted every 15days to assess both subjective and objective parameters in all participants. The test formulation shows significant improvement in dyspnea and diastolic function from baseline to the end of trial (p<0.05), slight improvement in palpitations (p>0.05) and highly significant improvement in easy fatigability (p=0.001) as compared to the control. The present study shows the effectiveness of the test drug in enhancing the diastolic function of left ventricle and alleviating other symptoms associated with ventricular diastolic dysfunction. Nevertheless, additional research with longer follow-up durations is necessary to clarify its efficacy and establish optimal treatment approaches for ventricular diastolic dysfunction in Unani medicine.

Effects of home-based telerehabilitation-assisted inspiratory muscle training in patients with idiopathic pulmonary fibrosis: A randomized controlled trial.

There are few studies that have used inspiratory muscle training (IMT) as an intervention for patients with isolated idiopathic pulmonary fibrosis (IPF). This study aimed to investigate and interpret the effects of home-based telerehabilitation-assisted IMT in patients with IPF. Twenty-eight participants with IPF took part in the study. Lung function tests, functional exercise capacity by 6-min walk distance (6MWD), dyspnoea perception by modified medical research council dyspnoea scale (mMRC), and inspiratory muscle strength by maximal inspiratory pressure (MIP) were assessed. IMT was performed twice a day, 7 days/week, for 8 weeks. The intervention group (n = 14) performed IMT at 50% of their baseline MIP while the control group (n = 14) performed IMT without applied resistance. Loading intensity was progressed by keeping the load at 4-6 on a modified Borg scale for the highest tolerable perceived respiratory effort for each patient. Dyspnoea based on mMRC score (p < 0.001, η2 effect size = 0.48) significantly decreased within the intervention group compared with the control group. There were significant increases in the intervention group compared to the control group based on 6MWD (p < 0.001, η2 effect size = 0.43), MIP (p = 0.006, η2 effect size = 0.25) and MIP % predicted (p = 0.008, η2 effect size = 0.25). The findings of this study suggest that an 8-week home-based telerehabilitation-assisted IMT intervention produced improvements in inspiratory muscle strength, leading to improvements in functional exercise capacity and dyspnoea.

Short-term intermittent hypoxia exposure for dyspnea and fatigue in post-acute sequelae of COVID-19: A randomized controlled study

BackgroundPost-acute sequelae of COVID-19 (PASC) is incurring a huge health and economic burden worldwide. There is currently no effective treatment or recommended drug for PASC. MethodsThis prospective randomized controlled study was conducted in a hospital in China. The effect of intermittent hypoxia exposure (IHE; 5-min hypoxia alternating with 5-min normal air, repeated five times) on dyspnea and fatigue was investigated in patients meeting the NICE definition of PASC. Patients were computationally randomized to receive normoxia exposure (NE) and routine therapy or IHE and routine therapy. Six-minute walk distance (6MWD) and spirometry were tested before and after the interventions; the Borg Dyspnea Scale (Borg) and the modified Medical Research Council Dyspnea Scale (mMRC) were used to assess dyspnea; and the Fatigue Assessment Scale (FAS) and the Chalder Fatigue Scale-11 (CFQ-11) were used to assess fatigue. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2300070565). FindingsNinety-five participants (33 males and 62 females) were recruited between March 1, 2023 and December 30, 2023. Forty-seven patients in the IHE group received 10.0 (9.0, 15.0) days of IHE, and 48 patients in NE group received 10.0 (8.0, 12.0) days of NE. 6MWD, forced vital capacity (FVC), FVC %pred, forced expiratory volume in 1 s (FEV1), FEV1 %pred, tidal volume (VT), and dyspnea and fatigue scales markedly improved after IHE (p < 0.05), and improvements were greater than in the NE group (all p < 0.05). Furthermore, participants in IHE group had better subjective improvements in dyspnea and fatigue than those in the NE group (p < 0.05). Compared with <10 days of IHE, ≥10 days of IHE had a greater impact on 6MWD, FVC, FEV1, FEV1 %pred, VT, FAS, and CFQ-11. No severe adverse events were reported. InterpretationIHE improved spirometry and 6MWD and relieved dyspnea and fatigue in PASC patients. Larger prospective studies are now needed to verify these findings.

Endovascular Treatment for Peripheral Pulmonary Arterial Stenosis in RNF213-Related Vasculopathy

This brief report reviews the clinical, procedural, and imaging data of 7 patients with p.Arg4810Lys variant of the ring finger protein 213 (RNF213) gene–related peripheral pulmonary arterial stenosis who underwent percutaneous transluminal pulmonary angioplasties (PTPAs) for demographics, clinical presentation, indications for angioplasty, and procedural and clinical outcomes. During median follow-up of 64.4 months since the first confirmed diagnosis, PTPA was performed for 62 segmental pulmonary arteries with 38 sessions of the procedure in 7 patients. Vascular stent placement because of resistance to balloon dilation and immediate elastic recoil was performed in 48 of 62 procedures (77%). Except for 1 death, 6 patients showed an improvement in dyspnea and 5 patients showed a decrease in mean pulmonary arterial pressure (mean, 55.5–42.7 mm Hg) and increase in 6-minute walk distance (mean, 415.5–484.3 m). Reperfusion edema occurred in 4 of 7 patients (57%), which was 6 of 38 sessions (16%).

Gravity- vs Wall Suction-Driven Large-Volume Thoracentesis: A Randomized Controlled Study

Prior studies have found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative-pressure gradient generated by wall suction has not been investigated. Does wall suction drainage result in more chest discomfort compared with gravity drainage in patients undergoing large-volume thoracentesis? In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of≥ 500mL were assigned at a 1:1 ratio to wall suction or gravity drainage. Wall suction was performed with a suction system attached to the suction tubing and with vacuum pressure adjusted to full vacuum. Gravity drainage was performed with a drainage bag placed 100cm below the catheter insertion site and connected via straight tubing. Patients rated chest discomfort on a 100-mm visual analog scale before, during, and after drainage. The primary outcome was postprocedural chest discomfort at 5 min. Secondary outcomes included measures of postprocedure chest discomfort, breathlessness, procedure time, volume of fluid drained, and complication rates. Of the 228 patients initially randomized, 221 were included in the final analysis. The primary outcome of procedural chest discomfort did not differ significantly between the groups (P= .08), nor did the secondary outcomes of postprocedural discomfort and dyspnea. Similar volumes were drained in both groups, but the procedure duration was longer in the gravity arm by approximately 3 min. No differences in rate of pneumothorax or reexpansion pulmonary edema were noted between the two groups. Thoracentesis via wall suction and gravity drainage results in similar levels of procedural discomfort and dyspnea improvement. ClinicalTrials.gov; No.: NCT05131945; URL: www. gov.

Acetazolamide Therapy in Patients with Heart Failure: A Meta analysis

Background: Acute heart failure (AHF) is a sudden worsening of chronic HF necessitating hospitalization. It involves complex pathophysiology including activation of multiple pathways (inflammatory, neurohumoral, immune) in multiple organs leading to unfavorable short and long-term prognosis. Impaired diuretic response caused by sodium reabsorption is associated with increased rehospitalization and mortality. Since a large amount of sodium is reabsorbed in the proximal tubule, acetazolamide induces natriuresis and may facilitate further diuresis. We performed this meta-analysis to assess the effects of acetazolamide therapy on natriuresis and clinical symptoms of congestion including rales and dyspnea. Methods: A literature search was conducted using EMBASE, MEDLINE, and Google Scholar Database from inception through 17th April 2023 to identify studies evaluating the use of acetazolamide in AHF. Search terms included ‘acetazolamide’ and ‘acute heart failure’. Additional relevant articles were evaluated using references of included articles. Eligible studies were randomized clinical trials, published in English, that assessed the effects of addition of acetazolamide to standard diuretic therapy as compared to placebo on natriuresis at 24-48 hours and decongestion. Study quality was assessed by Cochrane risk of bias tool. RevMan 5.4 was used for the analyses. Study results were analyzed using a random effects model. I2 statistics were applied to assess the between-study heterogeneity. Results: Three eligible RCTs of 66 screened studies enrolled a total of 284 heart failure patients who received Acetazolamide in addition to their background diuretics treatment. Of the excluded 63 studies, 33 were reviews, 16 study design was not RCT, two duplicate studies, 6 studies had other outcomes of interest and seven studies compared acetazolamide with other diuretics. Most studies compared acetazolamide with other add on diuretics including spironolactone, metolazone, etc. One study was identified by cross reference and one study Verbrugge et al 2014 that met all the criteria could not be included since it reported natriuretic effects in with standard error without sample size. The results showed that when compared to a placebo, Acetazolamide significantly increased natriuresis at the end of 24 to 48 hours, with a standardized mean difference (SMD) of 0.40 (95% CI, 0.24 to 0.57, p value &lt;0.00001, I2=0). Two of three studies evaluated the effect of addition of Acetazolamide on clinical symptoms of HF, including dyspnea and rales. However, in this 259 patients, addition of Acetazolamide did not demonstrate a significant improvement in dyspnea or rales compared to standard treatment, with an OR of 1.34 (95% CI, 0.37 to 4.91, p = 0.66 I2=70). Cochrane risk of bias showed low risk for two studies and low to moderate for one study with uncertainty in allocation. Conclusions: Our study demonstrates a significant increase in natriuresis but no improvements in clinical symptoms of congestion with use of acetazolamide among HF patients. Multiple strategies to overcome diuretic resistance are being explored to improve in-hospital AHF.

Long-term outcomes of surgical reconstruction for post-tuberculosis tracheobronchial stenosis: a 7-year follow-up in a tuberculosis-endemic region.

Surgical reconstruction is often necessary for severe tracheobronchial stenosis resulting from tuberculosis (TB). However, the long-term efficacy of this approach remains unclear. This study investigated the safety and long-term outcomes of surgery for severe post-TB tracheobronchial stenosis. We conducted a retrospective study of 48 patients with severe post-TB tracheobronchial stenosis who underwent surgical reconstruction between 2015 and 2018 in a TB-endemic region. Pre- and postoperative evaluations included Karnofsky performance status, modified Medical Research Council (mMRC) dyspnea scale, spirometry, chest computed tomography (CT) scan, and bronchoscopy. The primary outcome was intervention-requiring restenosis over the long term. The mean patient age was 30.6±9.9 years, with 91.7% females. Airway fibrosis was the predominant lesion (93.8%), affecting the bronchi (93.8%) and trachea (6.2%). All the patients underwent resection and anastomosis, and 56.2% required lobectomy. Postoperative complications occurred in 13 patients (27.1%), with prolonged air leaks being the most prevalent (12.5%). All complications resolved with conservative management. Significant improvements in performance status, dyspnea, and lung function were observed postoperatively and sustained for over 5 years. Within a median follow-up of 69 months, five cases of intervention-requiring restenosis occurred within the first year. The freedom from restenosis rate was 90% from 1 year onwards. Surgical reconstruction is safe and effective in treating severe post-TB tracheobronchial stenosis. Larger studies are required to validate these findings.

Safety and Patient-Reported outcomes of atezolizumab plus chemotherapy with or without bevacizumab in stage IIIB/IV non-squamous non-small cell lung cancer with EGFR mutation, ALK rearrangement or ROS1 fusion progressing after targeted therapies (GFPC 06–2018 study)

BackgroundIn an open-label multicenter non-randomized non-comparative phase II study in patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC), oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine-kinase inhibitor and no prior chemotherapy (NCT04042558), atezolizumab, carboplatin, pemetrexed with or without bevacizumab showed some promising result. Beyond the clinical evaluation, we assessed safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in this population. MaterialsPatients received platinum-pemetrexed-atezolizumab-bevacizumab (PPAB cohort) or, if not eligible, platinum-pemetrexed-atezolizumab (PPA cohort). The incidence, nature, and severity of adverse events (AEs) were assessed. PROs were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-Core 30 and EORTC QLQ-Lung Cancer 13). ResultOverall, 68 (PPAB) and 72 (PPA) patients were evaluable for safety. Grade 3–4 AEs occurred in 83.8% (PPAB) and 63.9% (PPA). Grade 3–4 atezolizumab-related AEs occurred in 29.4% and 19.4%, respectively. Grade 3–4 bevacizumab-related AEs occurred in 36.8% (PPAB). Most frequent grade 3–4 AEs were neutropenia (19.1% in PPAB; 23.6% in PPA) and asthenia (16.2% in PPAB; 9.7% in PPA). In PPAB, we observed a global stability in global health security (GHS) score, fatigue and dyspnea with a constant tendency of improvement, and a significant improvement in cough. In PPA, we observed a significant improvement in GHS score with a significant improvement in fatigue, dyspnea and cough. At week 54, we observed an improvement from baseline in GHS score for 49.2% of patients. In both cohorts, patients reported on average no clinically significant worsening in their overall health or physical functioning scores. ConclusionPPAB and PPA combinations seem tolerable and manageable in patients with stage IIIB/IV non-squamous NSCLC with oncogenic addiction (EGFR mutation or ALK/ROS1 fusion) after targeted therapies.

Outpatient management of Post-COVID syndrome – single center experience

BackgroundCOVID patients continue to experience unremitting symptoms that extend far beyond the initial illness. While there is rapid accumulation of data on acute COVID treatment in hospitalized patients, little is known regarding post-COVID management. ObjectivesTo describe our center's experience treating post-COVID sub-syndromes encountered in Post-COVID Lung Clinic. MethodsWe retrospectively reviewed data on 98 post-COVID patients evaluated in our clinic between 07/01/2020–12/31/2022. We encountered three distinct post-COVID subtypes: 1) respiratory complaints associated with increased O2 requirements and abnormal CT findings (post-COVID interstitial lung disease [ILD]), 2) respiratory complaints associated with tachycardia (post-COVID dyspnea-tachycardia syndrome [DTS]). Post-COVID ILD patients (n = 28) received steroids in combination with cell cycle inhibitor (mycophenolate mofetil-MMF). Post-COVID DTS patients (n = 16) were treated with metoprolol. 3) A third, undifferentiated group presented with mild respiratory complaints and normal spirometry (n = 17) and was followed in clinic without initiation of a specific treatment. ResultsIn treated post-COVID ILD patients, mean oxygen requirements at rest (1.96 ± 1.79 L/NC) decreased to 0.89 ± 1.29 L/NC at 6 months follow-up, p = 0.005. In patients with post-COVID DTS, mean heart rate at rest decreased (98 ± 15 bpm to 79 ± 11 bpm) at 6 months follow-up, p = 0.023. 60 % of patients reported an improvement in exertional dyspnea. ConclusionsOur descriptive study presents a single center outpatient COVID-19 clinic experience. We encountered 3 post-COVID sub-syndromes and describe their treatments: post-COVID interstitial lung disease [ILD] treated with a novel regimen of MMF and steroids, post COVID dyspnea-tachycardia syndrome [DTS] treated with metoprolol, and a third subgroup with mild undifferentiated symptoms without specific treatment.

The Effect of Physiotherapy on Dyspnea, Muscle Strength and Functional Status in Patients with Long COVID Syndrome.

Patients who were infected with COVID-19 may experience Long COVID syndrome. We examined the effectiveness of physiotherapy on dyspnea, muscle strength, and functional status in Long COVID syndrome. The exercise group underwent an 8-week supervised physiotherapeutic program consisting of interval aerobic exercise and strengthening exercises, each lasting 30 min. The control group did not engage in any exercise. Dyspnea, muscle strength, and functional status were assessed at the beginning and end of the intervention in both groups. No significant baseline differences were found between the two groups. The exercise group demonstrated improvements compared to baseline in dyspnea, quadriceps muscle strength, and functional status. Specifically, there was a significant increase of 3.7 lifts in the 60-s sit-to-stand test (p = 0.01), an increase of 5.86 kg in right quadriceps muscle strength (p = 0.03), an increase of 8.26 kg in left quadriceps muscle strength (p = 0.01), and a decrease in dyspnea score by 0.95 points (p = 0.02). Similar studies have reported improvements in dyspnea, muscle strength, and functional status in the exercise group. However, further research with larger sample sizes is needed to confirm these findings.