Impact of a multimodal effort re-education programme on functionality, physical performance, and functional capacity in cancer patients with dyspnoea: a randomised experimental study.

BACKGROUND: In recent years, there has been a significant increase in the survival rates of cancer patients. However, this has also led to an increase in side effects, such as dyspnoea, which can negatively impact of patients. We propose a programme for re-educating effort. The main objective is to test the effectiveness of this programme in improving respiratory symptoms and functionality in cancer patients. METHODOLOGY: Experimental, prospective, longitudinal, randomised study with a parallel fixed-assignment scheme (CG-IG). The patients were selected from the Medical Oncology Service of the University Hospital Complex of Salamanca (CAUSA), Spain. Two parallel intervention programmes were designed for the two study groups (Conventional Clinical Practice-Effort Re-education Programme). Primary variables: dyspnoea (MRC), functionality (Barthel); secondary variables: physical performance (SPPB) and functional capacity (ECOG) and the socio-demographic variables (age, sex, anatomopathological diagnosis, and number of treatment lines). RESULTS: The study sample consisted of 182 patients, with 12 excluded, resulting in a final sample size of n = 170. Sex distribution (CG: 52.9% male and 47.1% female; IG: 49.4% male and 50.6% female). The primary oncological diagnosis was lung cancer, and the most frequent tumour stages were III and IV. Statistically significant differences were found between the IG and CG scores (p < 0.001, d = 0.887, 95% CI) and between the IG and CG scores (p = 0.004, d = 0.358, 95% CI), indicating that the IG performed better. CONCLUSION: The results of this study support the beneficial effects of an exercise re-education programme, carried out by an interdisciplinary team in improving the autonomy of oncology patients with dyspnoea. TRIAL REGISTRATION: The clinical trial was registered in ClinicalTrials.gov (NCT04186754). (03 September 2019).

Dyspnoea relief as an inherent benefit of high flow nasal cannula therapy: A laboratory randomized trial in healthy humans.

BACKGROUND AND OBJECTIVE: Persistent dyspnoea is a public health issue for which the therapeutic arsenal is limited. This study tested high-flow nasal cannula therapy (HFNT) as a means to alleviate experimental dyspnoea. METHODS: Thirty-two healthy subjects underwent an experimental dyspnoea induced by thoracoabdominal elastic loading. HFNT was administered with alternately FiO2 of 100% (HFNT100) or 21% (HFNT21). The sensory (S-VAS) and affective (A-VAS) components of dyspnoea, transcutaneous CO2 pressure (PtcCO2 ), pulse-oximetry oxygen saturation (SpO2 ), heart rate, respiratory rate and skin galvanometry were monitored continuously. Three experimental sessions of 8 min were conducted: the first session consisted in familiarization with the experimental dyspnoea and the next two sessions tested the effects of HFNT100 and HFNT21 alternatively in a randomized order. RESULTS: HFNT21 and HFNT100 significantly reduced dyspnoea, respectively of ∆A-VAS = 0.80 cm [-0.02-1.5]; p = 0.007 and ∆A-VAS = 1.00 cm [0.08-1.75]; p < 0.0001; ∆S-VAS = 0.70 cm [-0.15-1.98]), p < 0.0001 and ∆S-VAS = 0.70 cm [0.08-1.95]), p = 0.0002) with no significant difference between HFNT21 and HFNT100. HFNT did not significantly alter the respiratory rate or the heart rate, reduced PtcCO2 only on room air and GSR under both experimental conditions. CONCLUSION: HFNT was associated with a statistically significant reduction in the intensity of the sensory and affective components of dyspnoea, independent of oxygen addition. This relief of laboratory dyspnoea could result from a reduction of afferent-reafferent mismatch.

Effect of experimental modulation of mood on exertional dyspnoea in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Dyspnoea is a debilitating symptom in individuals with chronic obstructive pulmonary disease (COPD) and a range of other chronic cardiopulmonary diseases and is often associated with anxiety and depression. The present study examined the effect of visually-induced mood shifts on exertional dyspnoea in individuals with COPD. METHODS: Following familiarization, 20 participants with mild to severe COPD (age 57-79 years) attended three experimental sessions on separate days, performing two 5-min treadmill exercise tests separated by a 30-min interval on each day. During each exercise test, participants viewed either a positive, negative or neutral set of images sourced from the International Affective Picture System (IAPS) and rated dyspnoea or leg fatigue (0-10). Heart rate (HR) and peripheral oxygen saturation (SpO2 ) were measured at 1-min intervals during each test. Mood valence ratings were obtained using Self-Assessment Manikin (SAM) scale (1-9). RESULTS: Mood valence ratings were significantly higher when viewing positive (end-exercise mean ± SEM = 7.6 ± 0.3) compared to negative IAPS images (2.4 ± 0.3, p < 0.001). Dyspnoea intensity (mean ± SEM = 5.8 ± 0.4) and dyspnoea unpleasantness (5.6 ± 0.3) when viewing negative images were significantly higher compared to positive images (4.2 ± 0.4, p = 0.004 and 3.4 ± 0.5, p = 0.003). Eighty-five percent of participants (n = 17) met the minimal clinically important difference (MCID) criteria for both dyspnoea intensity and unpleasantness. HR, SpO2 and leg fatigue did not differ significantly between conditions. CONCLUSION: These findings indicate that the negative affective state worsens dyspnoea in COPD, thereby suggesting strategies aimed at reducing the likelihood of negative mood or improving the mood may be effective in managing morbidity associated with dyspnoea in COPD.

Effects of different inspiratory muscle training protocols on functional exercise capacity and respiratory and peripheral muscle strength in patients with chronic kidney disease: a randomized study.

BACKGROUND: Pathological changes were observed in the diaphragm due to abnormal renal function in chronic kidney disease (CKD). Inspiratory muscle training (IMT) has been suggested for patients with CKD; however, the most appropriate intensity for IMT has not been determined. Therefore, this study aimed to investigate the effects of different IMT protocols on respiratory muscle strength, quadriceps femoris muscle strength (QMS), handgrip muscle strength (HGS), functional exercise capacity, quality of life (QoL), pulmonary function, dyspnoea, fatigue, balance, and physical activity (PA) levels in patients with CKD. METHODS: This randomized, controlled, single-blind study included 47 patients and they were divided into three groups: Group 1 (n = 15, IMT with 10% maximal inspiratory pressure (MIP)), Group 2 (n = 16, IMT with 30% MIP), and Group 3(n = 16; IMT with 60% MIP). MIP, maximal expiratory pressure (MEP), 6-min walking test (6-MWT), QMS, HGS, QoL, pulmonary function, dyspnoea, fatigue, balance, and PA levels were assessed before and after eight weeks of IMT. RESULTS: Increases in MIP, %MIP, 6-MWT distance, and %6-MWT were significantly higher in Groups 2 and 3 than in Group 1 after IMT (p < 0.05). MEP, %MEP, FEF25-75%, QMS, HGS, and QoL significantly increased; dyspnoea and fatigue decreased in all groups (p < 0.05). FVC, PEF, and PA improved only in Group 2, and balance improved in Groups 1 and 2 (p < 0.05). CONCLUSIONS: IMT with 30% and 60% MIP similarly improves inspiratory muscle strength and functional exercise capacity. IMT with 30% is more effective in increasing PA. IMT is a beneficial method to enhance peripheral and expiratory muscle strength, respiratory function, QoL and balance, and reduce dyspnoea and fatigue. IMT with %30 could be an option for patients with CKD who do not tolerate higher intensities. TRIAL REGISTRATION: This study was retrospectively registered (NCT06401135, 06/05/2024).

Experiences of living with idiopathic pulmonary fibrosis in relation to physical activity - "How the hills became steeper and steeper": a qualitative interview study.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive disease presenting with symptoms like dyspnoea, dry cough, and fatigue, which affect physical function and quality of life. No earlier qualitative studies have investigated physical activity in IPF. This study aims to explore experiences of living with IPF in relation to physical activity. MATERIALS AND METHODS: Qualitative interviews were conducted with 14 participants living with IPF. The participants were 77 years old (range: 56-86) and diagnosed with IPF between 2 and 9 years ago. The analysis was performed by qualitative content analysis according to Graneheim and Lundman. RESULTS: The results indicated that life and one's ability to be physically active is affected by IPF. Despite this, it seems possible to navigate past obstacles, which was illustrated by an overall theme: "My life is constrained, but I am hanging on". Two major categories cover topics of IPF being a life changing diagnosis with changes in self-image and changed future plans regarding physical activity, as well as life. Physical activity was perceived to be challenging, yet in many ways used as a strategy, developed to manage life. CONCLUSIONS: IPF affects physical activity as well as life, from onset onwards. By developing strategies for facilitating physical activity as well as identifying barriers, it seems possible to maintain an active life despite the disease. The healthcare system needs to create support systems that meet different needs during different phases of the disease. TRIAL REGISTRATION: "FoU in Sweden" Research and Development in Sweden (id: 227081).

The association between ibuprofen administration in children and the risk of developing or exacerbating asthma: a systematic review and meta-analysis.

BACKGROUND: Ibuprofen is one of the most commonly used analgesic and antipyretic drugs in children. However, its potential causal role in childhood asthma pathogenesis remains uncertain. In this systematic review, we assessed the association between ibuprofen administration in children and the risk of developing or exacerbating asthma. METHODS: We searched MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and Scopus from inception to May 2022, with no language limits; searched relevant reviews; and performed citation searching. We included studies of any design that were primary empirical peer-reviewed publications, where ibuprofen use in children 0-18 years was reported. Screening was performed in duplicate by blinded review. In total, 24 studies met our criteria. Data were extracted according to PRISMA guidelines, and the risk of bias was assessed using RoB2 and NOS tools. Quantitative data were pooled using fixed effect models, and qualitative data were pooled using narrative synthesis. Primary outcomes were asthma or asthma-like symptoms. The results were grouped according to population (general, asthmatic, and ibuprofen-hypersensitive), comparator type (active and non-active) and follow-up duration (short- and long-term). RESULTS: Comparing ibuprofen with active comparators, there was no evidence of a higher risk associated with ibuprofen over both the short and long term in either the general or asthmatic population. Comparing ibuprofen use with no active alternative over a short-term follow-up, ibuprofen may provide protection against asthma-like symptoms in the general population when used to ease symptoms of fever or bronchiolitis. In contrast, it may cause asthma exacerbation for those with pre-existing asthma. However, in both populations, there were no clear long-term follow-up effects. CONCLUSIONS: Ibuprofen use in children had no elevated risk relative to active comparators. However, use in children with asthma may lead to asthma exacerbation. The results are driven by a very small number of influential studies, and research in several key clinical contexts is limited to single studies. Both clinical trials and observational studies are needed to understand the potential role of ibuprofen in childhood asthma pathogenesis.

A retrospective analysis of patients who underwent tracheal resection and end-to-end anastomosis surgery for benign tracheal stenosis, over a 10-year period.

INTRODUCTION: Laryngotracheal stenosis encompasses a diverse range of diagnoses, encompassing complete or partial narrowing of various subgroups of the upper airways, including the laryngeal structures and trachea, due to pathological scar formation. This increasingly prevalent pathology is of significant importance due to its potential for life-threatening consequences. Among the defined treatment modalities, tracheal resection and end-to-side anastomosis remain a valuable therapeutic alternative in appropriate indications. OBJECTIVE: The objective of this study was to retrospectively evaluate the outcomes of patients who underwent tracheal resection and end-to-end anastomosis at our clinic over the past decade. MATERIAL & METHOD: All patients who underwent tracheal resection and end-to-end anastomosis surgery for benign tracheal stenosis at the Department of Otolaryngology, Mustafa Kemal University Hospital between 2013 and 2023 were included in the study. The diagnosis of tracheal stenosis was based on endoscopic examination and computed tomography results. Interventions without postoperative symptoms and without the need for additional surgical intervention were considered successful. The study was approved by Hatay Mustafa Kemal University Ethics Committee with decision number 2023/27. RESULTS: A total of 29 patients were included in the study. The mean age of the patients was 26.48 years. 3 patients (10.35 %) had a comorbidity. In all patients orotracheal intubation or intubation and tracheotomy was the aetiological cause. There were no intraoperative complications. In the postoperative period, wound infection was observed in 3 patients (10.35 %) and subcutaneous emphysema in 2 patients (6.9 %). In 1 patient (3.45 %) recurrent respiratory distress was observed, restenosis was considered and tracheotomy was performed. Our complication rate was 20.69 %. When all patients were evaluated at the end of the postoperative follow-up period, the surgical success rate was calculated to be 96.55 %. CONCLUSION: With a surgical success rate of 96.55 % and a low complication rate in our study, we believe, in parallel with previous studies, that open surgery is a reliable, physiologically appropriate and successful method among the current treatments for tracheal stenosis.

Heart failure with preserved ejection fraction: relevance of a dedicated dyspnoea clinic.

BACKGROUND AND AIMS: Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous presentation. This study provides an in-;depth description of haemodynamic and metabolic alterations revealed by systematic assessment through cardiopulmonary exercise testing combined with exercise echocardiography (CPETecho) within a dedicated dyspnoea clinic. METHODS AND RESULTS: Consecutive patients (n = 297), referred to a dedicated dyspnoea clinic using a standardized workup including CPETecho, with HFpEF diagnosed through a H2FPEF score ≥6 or HFA-PEFF score ≥5, were evaluated. A median of four haemodynamic/metabolic alterations was uncovered per patient: impaired stroke volume reserve (73%), impaired chronotropic reserve (72%), exercise pulmonary hypertension (65%), and impaired diastolic reserve (64%) were the most frequent cardiac alterations. Impaired peripheral oxygen extraction and a ventilatory limitation were present in 40% and 39%, respectively. In 267 patients (90%), 575 further diagnostic examinations were recommended (median of two tests per patient). Cardiac magnetic resonance imaging, coronary or amyloidosis workup, ventilation-perfusion scanning, and pulmonology referral were each recommended in approximately one out of three patients. In 293 patients (99%), 929 cardiovascular drug optimizations were performed (median of 3 modifications per patient). In 110 patients (37%), 132 cardiovascular interventions were performed, with ablation as the most frequent procedure. CONCLUSION: Holistic workup of HFpEF patients within a multidisciplinary, dedicated dyspnoea clinic, including systematic implementation of CPETecho reveals various haemodynamic/metabolic alterations, leading to further diagnostic testing and potential treatment changes in the majority of cases.

Oral fibrinolytic agent in hyper-coagulopathy in severe COVID - 19 ARDS Patients: two case reports.

Abstract: The use of oral fibrinolytic agent (DLBS1033) has been proven for adjuvant treatment in venous thromboembolism, however until now there is no published report about its uses and effectiveness as an addition to the standard therapy of severe COVID-19 cases and hypercoagulopathy. We present two cases of severe confirmed COVID-19 from PCR tests, seen at Ngimbang Hospital, Lamongan, East Java in October and November, 2020. The first patient was a 51-year-old male who presented to ER with fever, dyspnoea, cough, and oxygen desaturation (SpO2 room air 87%), with comorbids of pulmonary hypertension (PH), atrial fibrillation, heart failure secondary to corpulmonale, and hypercoagulopathy. The second patient was a 56-yearold female who presented with fever, dyspnoea, and oxygen desaturation (Sp02 room air 88%), with comorbid ARDS, hypertension, hyperglycaemia, hypercoagulopathy, heart failure, and CAD. Both of the patients were treated with standard treatment therapy for severe COVID-19 and comorbid therapy, and DLBS1033 in addition to fondaparinux due to limited hospital resources. Both patients showed good clinical outcomes after the course of treatment and had no adverse effects. CONCLUSIONS: Our two case reports were the first that showed good clinical outcome and safety of DLBS1033 treatment in addition to fondaparinux for hypercoagulopathy therapy.

Retractable congestive heart failure due to sinus valsalva rupture with coexisting gerbode defect: a rare case report.

Sinus of Valsalva aneurysm (SoVA) is a rare disease with less than 1% prevalence in the population. Most cases are asymptomatic, however, significant clinical manifestations are possible due to fistula formation and sudden rupture resulting in cardiac shunt. Eventually it may develop into progressive heart failure with high morbidity. We report the case of a 33 year old female patient who presented with shortness of breath, ascites, and recurring hospitalisation. The cardiac examination revealed sinus tachycardia along with loud and continuous murmurs on the left parasternal border. Several standard diagnostic procedures could not be performed due to malignant arrhythmia in supine position. Echocardiography examination revealed SoV rupture with a gerbode defect, which was the underlying cause of severe retractable heart failure.

Low-intensity rehabilitation in persistent post COVID-19 dyspnoea: the value of Spa health resort as appropriate setting.

Background: Post COVID-19 syndrome is a frequent disabling outcome, leading to a delay in social reintegration and return to working life. Study design: This was a prospective observational cohort study. The main objective was to explore the effectiveness of a Spa rehabilitation treatment on the improvement of post COVID-19 dyspnoea and fatigue, also analyzing the relationship between such symptoms. Additionally, it was assessed if different clinical characteristics could predispose patients in experiencing post COVID-19 symptoms or could influence the effectiveness of a Spa intervention. Methods: From July to November 2021, 187 post COVID-19 patients were enrolled in the study. All the patients complained persi-sting dyspnoea, whose impact on daily activities was assessed using the modified Medical Research Council dyspnoea scale. 144 patients (77.0%) reported also fatigue. The Spa treatment was started at least 3 months after COVID-19 acute phase. At the end of the treatment, patients were asked to rate the improvement in the dyspnoea and fatigue sensation. 118 patients also underwent the modified Borg Dyspnoea Scale for severity estimation of Exertion Dyspnoea and the Barthel index for severity estimation of Physical Limitation. Results: 165 out of 187 patients (88.2%) reported an improvement in dyspnoea, while 116 out 144 patients (80.6%) reported an improvement in both dyspnoea and fatigue. On a total of 118 subjects, a clinically significant improvement in the modified Borg Dyspnoea Scale (i.e. Delta Borg equal or more than -2.0 points) was reached by the 50.8% of patients, while a clinically significant improvement in the Barthel index (i.e. Delta Barthel equal or more than +10.0 points) was reached by the 51.7% of them. The 31.4% of patients reached a minimal clinically important improvement in both the modified Borg Dyspnoea Scale and the Barthel index. No risk factors were associated to a clinically impacting dyspnoea at entry, while a BMI>30 Kg/m2 was the main risk factor for chronic fatigue. Presence of respiratory comorbidities, obesity and severe acute COVID-19 (phenotype 4) configured risk factors for the lack of improvement of dyspnoea after the treatment, while no risk factors were associated to a lack of improvement for fatigue. Older age, obesity and comorbidities seemed to make more difficult to reach a clinically meaningful improvement in the modified Borg Dyspnoea Scale and the Barthel index after treatment. Female gender may imply more physical limitation at entry, while male patients seem to show less improvement in the Barthel index after treatment. Conclusions: Dyspnoea and fatigue were confirmed to be important post COVID-19 symptoms even in younger subjects of wor-king age and subjects with absent or modest pulmonary alterations at distance from acute COVID-19. A Spa health resort seems to be an effective "low-intensity" setting for a rehabilitation program of such patients. There is a strong relationship in terms of improvement between dyspnoea and fatigue, even if risk factors for their occurrence appear to be different. The improvement in exertion dyspnoea and physical limitation seemed to be less mutually related, probably due to a greater complexity in the asses-sment questionnaires. Some risk factors may predict a lack of improvement in symptoms after treatment.

Patient-Controlled Therapy with Intravenous Oxycodone in Breathlessness due to Advanced Cancer: A Case Report.

Dyspnoea is a debilitating symptom in medicine, especially in palliative care. Opioids are the pharmacological agents of choice in the treatment of dyspnoea in palliative medicine. Morphine is the best-studied opioid, and recent literature on oxycodone is encouraging. In refractory cases, opioid infusion and palliative sedation may have to be used. We present a case that used oxycodone in a patient-controlled device specifically for dyspnoea and its effects in relieving dyspnoea in a fast and timely manner. This helped in meeting the demands of the patient and relieving suffering rapidly with less sedation. This case report is unique in the use of an oxycodone patient-controlled device specifically for dyspnoea.

Hepatopulmonary syndrome is associated with low sphingosine-1-phosphate levels and can be ameliorated by the functional agonist fingolimod.

BACKGROUND & AIMS: Hepatopulmonary syndrome (HPS) is characterised by a defect in arterial oxygenation induced by pulmonary vascular dilatation in patients with liver disease. Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, suppresses vasodilation by reducing nitric oxide (NO) production. We investigated the role of S1P in patients with HPS and the role of fingolimod as a therapeutic option in an experimental model of HPS. METHODS: Patients with cirrhosis with HPS (n = 44) and without HPS (n = 89) and 25 healthy controls were studied. Plasma levels of S1P, NO, and markers of systemic inflammation were studied. In a murine model of common bile duct ligation (CBDL), variations in pulmonary vasculature, arterial oxygenation, liver fibrosis, and inflammation were estimated before and after administration of S1P and fingolimod. RESULTS: Log of plasma S1P levels was significantly lower in patients with HPS than in those without HPS (3.1 ± 1.4 vs. 4.6 ± 0.2; p <0.001) and more so in severe intrapulmonary shunting than in mild and moderate intrapulmonary shunting (p <0.001). Plasma tumour necrosis factor-α (76.5 [30.3-91.6] vs. 52.9 [25.2-82.8]; p = 0.02) and NO (152.9 ± 41.2 vs. 79.2 ± 29.2; p = 0.001) levels were higher in patients with HPS than in those without HPS. An increase in Th17 (p <0.001) and T regulatory cells (p <0.001) was observed; the latter inversely correlated with plasma S1P levels. In the CBDL HPS model, fingolimod restored pulmonary vascular injury by increasing the arterial blood gas exchange and reducing systemic and pulmonary inflammation, resulting in improved survival (p = 0.02). Compared with vehicle treatment, fingolimod reduced portal pressure (p <0.05) and hepatic fibrosis and improved hepatocyte proliferation. It also induced apoptotic death in hepatic stellate cells and reduced collagen formation. CONCLUSIONS: Plasma S1P levels are low in patients with HPS and even more so in severe cases. Fingolimod, by improving pulmonary vascular tone and oxygenation, improves survival in a murine CBDL HPS model. IMPACT AND IMPLICATIONS: A low level of plasma sphingosine-1-phosphate (S1P) is associated with severe pulmonary vascular shunting, and hence, it can serve as a marker of disease severity in patients with hepatopulmonary syndrome (HPS). Fingolimod, a functional agonist of S1P, reduces hepatic inflammation, improves vascular tone, and thus retards the progression of fibrosis in a preclinical animal model of HPS. Fingolimod is being proposed as a potential novel therapy for management of patients with HPS.

Ventilatory response to peripheral chemoreflex and muscle metaboreflex during static handgrip in healthy humans: evidence of hyperadditive integration.

NEW FINDINGS: What is the central question of this study? What is the effect of peripheral chemoreflex and muscle metaboreflex integration on ventilation regulation, and what is the effect of integration on breathing-related sensations and emotions? What is the main finding and its importance? Peripheral chemoreflex and muscle metaboreflex coactivation during isocapnic static handgrip exercise appeared to elicit a hyperadditive effect with regard to ventilation and an additive effect with regard to breathing-related sensations and emotions. These findings reveal the nature of the integration between two neural mechanisms that operate during small-muscle static exercise performed under hypoxia. ABSTRACT: Exercise augments the hypoxia-induced ventilatory response in an exercise intensity-dependent manner. A mutual influence of hypoxia-induced peripheral chemoreflex activation and exercise-induced muscle metaboreflex activation might mediate the augmentation phenomenon. However, the nature of these reflexes' integration (i.e., hyperadditive, additive or hypoadditive) remains unclear, and the coactivation effect on breathing-related sensations and emotions has not been explored. Accordingly, we investigated the effect of peripheral chemoreflex and muscle metaboreflex coactivation on ventilatory variables and breathing-related sensations and emotions during exercise. Fourteen healthy adults performed 2-min isocapnic static handgrip, first with the non-dominant hand and immediately after with the dominant hand. During the dominant hand exercise, we (a) did not manipulate either reflex (control); (b) activated the peripheral chemoreflex by hypoxia; (c) activated the muscle metaboreflex in the non-dominant arm by post-exercise circulatory occlusion (PECO); or (d) coactivated both reflexes by simultaneous hypoxia and PECO use. Ventilation response to coactivation of reflexes (mean ± SD, 13 ± 6 l/min) was greater than the sum of responses to separated activations of reflexes (mean ± SD, 8 ± 8 l/min, P = 0.005). Breathing-related sensory and emotional responses were similar between coactivation of reflexes and the sum of separate activations of reflexes. Thus, the peripheral chemoreflex and muscle metaboreflex integration during exercise appeared to be hyperadditive with regard to ventilation and additive with regard to breathing-related sensations and emotions in healthy adults.

Histopathology, immunoenzyme activity and transcriptome analysis of immune response in silver pomfret infected by cryptokaryon (Cryptorchidism irritant).

Cryptorchidism irritant (CI) infection is a major problem in the culturing process of silver pomfret (Pampus argenteus), which can result in rapid and massive death. However, there is limited information available on the immune response of silver pomfret infected by CI. To address this gap, we sampled naturally infected fish and observed milky white translucent oval CI trophozoites on the gills, body surface, and fin rays. Histological analysis showed that CI infection led to vacuolation of epithelial cells and a decrease in blood cells in the gills. We also performed transcriptome profiling of the gill, kidney complex, and spleen, generating 399,616,194 clean reads that assembled into 101,228 unigenes, which were annotated based on public databases. We detected 14,369 differentially expressed genes, and selected several key immune-related genes for further validation using RT-qPCR. The Graft-versus-host pathway and Allograft rejection pathway were enriched in the gills, leading to inflammation and ulceration. CI infection activated the immune system, increasing levels of interleukin-1 beta and MHC class II antigen, and also activated innate and acquired immune genes in silver pomfret. Furthermore, we measured the activities of five immune-related enzymes (SOD, AKP, CAT, CSH and ACP), which all increased to varying degrees after CI infection. Our findings enhance our understanding of the immune response of fish to parasitic infection and may contribute to the development of strategies to prevent high mortality in CI-stimulated fish in aquaculture.

Breathlessness limiting exertion in very old adults: findings from the Newcastle 85+ study.

INTRODUCTION: Long-term breathlessness is more common with age. However, in the oldest old (>85 years), little is known about the prevalence, or impact of breathlessness. We estimated breathlessness limiting exertion prevalence and explored (i) associated characteristics; and (ii) whether breathlessness limiting exertion explains clinical and social/functional outcomes. METHODS: Health and socio-demographic characteristics were extracted from the Newcastle 85+ Study cohort. Phase 1 (baseline) and follow-up data (18 months, Phase 2; 36 months, Phase 3; 60 months, Phase 4 after baseline) were examined using descriptive statistics and cross-sectional regression models. RESULTS: Eight hundred seventeen participants provided baseline breathlessness data (38.2% men; mean 84.5 years; SD 0.4). The proportions with any limitation of exertion, or severe limitation by breathlessness were 23% (95% confidence intervals (CIs) 20-25%) and 9% (95%CIs 7-11%) at baseline; 20% (16-25%) and 5% (3-8%) at Phase 4. Having more co-morbidities (odds ratio (OR) 1.34, 1.18-1.54; P < 0.001), or self-reported respiratory (OR 1.88, 1.25-2.82; P = 0.003) or cardiovascular disease (OR 2.38, 1.58-3.58; P < 0.001) were associated with breathlessness limiting exertion. Breathlessness severely limiting exertion was associated with poorer self-rated health (OR 0.50, 029-0.86; P = 0.012), depression (beta-coefficient 0.11, P = 0.001), increased primary care contacts (beta-co-efficient 0.13, P = 0.001) and number of nights in hospital (OR 1.81; 1.02-3.20; P = 0.042). CONCLUSIONS: Breathlessness limiting exertion appears to become less prevalent over time due to death or withdrawal of participants with cardio-respiratory illness. Breathlessness severely limiting exertion had a wide range of service utilisation and wellbeing impacts.

The use of respiratory muscle training in patients with pulmonary dysfunction, internal diseases or central nervous system disorders: a systematic review with meta-analysis.

OBJECTIVE: The aim of this systematic review with meta-analysis was to evaluate the effectiveness of RMT in internal and central nervous system disorders, on pulmonary function, exercise capacity and quality of life. METHODS: The inclusion criteria were (1) publications designed as Randomized Controlled Trial (RCT), with (2) participants being adults with pulmonary dysfunction caused by an internal disease or central nervous system disorder, (3) an intervention defined as RMT (either IMT or EMT) and (4) with the assessment of exercise capacity, respiratory function and quality of life. For the methodological quality assessment of risk of bias, likewise statistical analysis and meta-analysis the RevMan version 5.3 software and the Cochrane Risk of Bias Tool were used. Two authors independently analysed the following databases for relevant research articles: PubMed, Scopus, Cochrane Library, Web of Science, and Embase. RESULTS: From a total of 2200 records, the systematic review includes 29 RCT with an overall sample size of 1155 patients. Results suggest that patients with internal and central nervous system disorders who underwent RMT had better quality of life and improved significantly their performance in exercise capacity and in respiratory function assessed with FVC and MIP when compared to control conditions (i.e. no intervention, sham training, placebo or conventional treatments). CONCLUSION: Respiratory muscle training seems to be more effective than control conditions (i.e. no intervention, sham training, placebo or conventional treatment), in patients with pulmonary dysfunction due to internal and central nervous system disorders, for quality of life, exercise capacity and respiratory function assessed with MIP and FVC, but not with FEV1.

Contribution of obesity to breathlessness in a large nationally representative sample of Australian adults.

BACKGROUND AND OBJECTIVE: Breathlessness is prevalent and associated with medical consequences. Obesity is related to breathlessness. However, the magnitude of its contribution has not been clearly documented. This investigation aimed to determine the contribution of obesity to breathlessness by estimating the population attributable fraction (PAF) in a representative sample of Australian adults. METHODS: A cross-sectional, nationally representative survey of Australian residents aged ≥18 years was conducted in October 2019. Breathlessness was defined as modified Medical Research Council (mMRC) dyspnoea scale grade ≥2. BMI was calculated from self-reported height and weight. Adjusted relative risks (aRRs) were estimated using a generalized linear model with Poisson distribution, adjusted for age group and/or participant-reported diagnosed illnesses. Adjusted PAFs were estimated using aRR and obesity prevalence in Australian adults. RESULTS: Among those who completed the National Breathlessness Survey, 9769 participants (51.4% female) were included in the analysis; 28.1% of participants were obese. The prevalence of breathlessness was 9.54%. The aRR of obesity for breathlessness was 2.04, adjusted for age. Adjusting for various co-morbid conditions, the aRR was slightly attenuated to around 1.85-1.98. The PAF, adjusted only for age, was 24.6% (95% CI 20.1-29.1) and after further adjustment for co-morbid conditions, the PAF ranged from 21.1% to 23.6%. Obesity accounted for a higher proportion of breathlessness in women than in men. CONCLUSION: Our results demonstrate that obesity accounts for around a quarter of breathlessness symptoms in Australian adults. This has important implications for health policy in light of the global trend in increasing obesity.

Palliative care for interstitial lung disease: A nationwide survey of pulmonary specialists.

BACKGROUND AND OBJECTIVE: Interstitial lung disease (ILD) is progressive with high symptom burdens and poor prognosis. Patients with ILD need optimal palliative care to maintain their quality of life, however, few nationwide surveys have addressed palliative care for ILD. METHODS: A nationwide, self-administered questionnaire was conducted. Questionnaires were sent by mail to pulmonary specialists certified by the Japanese Respiratory Society (n = 3423). The current practices of PC for ILD, end-of-life communication, referral to a PC team, barriers to PC for ILD, and comparison of PC between ILD and lung cancer (LC). RESULTS: 1332 (38.9%) participants completed the questionnaire, and the data of 1023 participants who had cared for ILD patients in the last year were analysed. Most participants reported that ILD patients often or always complained of dyspnoea and cough, but only 25% had referred them to a PC team. The timing of end-of-life communication tended to be later than the physician-perceived ideal timing. The participants experienced significantly greater difficulty in symptomatic relief and decision-making in PC for ILD compared to LC. Prescription of opioids for dyspnoea was less frequent for ILD than for LC. ILD-specific barriers in PC included an 'inability to predict prognosis', 'lack of established treatments for dyspnoea', 'shortage of psychological and social support', and 'difficulty for patients/families to accept the disease's poor prognosis'. CONCLUSION: Pulmonary specialists experienced more difficulty in providing PC for ILD compared to LC and reported considerable ILD-specific barriers in PC. Multifaceted clinical studies are needed to develop optimal PC for ILD.

TARGET-HF: developing a model for detecting incident heart failure among symptomatic patients in general practice using routine health care data.

BACKGROUND: Timely diagnosis of heart failure (HF) is essential to optimize treatment opportunities that improve symptoms, quality of life, and survival. While most patients consult their general practitioner (GP) prior to HF, the early stages of HF may be difficult to identify. An integrated clinical support tool may aid in identifying patients at high risk of HF. We therefore constructed a prediction model using routine health care data. METHODS: Our study involved a dynamic cohort of patients (≥35 years) who consulted their GP with either dyspnoea and/or peripheral oedema within the Amsterdam metropolitan area from 2011 to 2020. The outcome of interest was incident HF, verified by an expert panel. We developed a regularized, cause-specific multivariable proportional hazards model (TARGET-HF). The model was evaluated with bootstrapping on an isolated validation set and compared to an existing model developed with hospital insurance data as well as patient age as a sole predictor. RESULTS: Data from 31,905 patients were included (40% male, median age 60 years) of whom 1,301 (4.1%) were diagnosed with HF over 124,676 person-years of follow-up. Data were allocated to a development (n = 25,524) and validation (n = 6,381) set. TARGET-HF attained a C-statistic of 0.853 (95% CI, 0.834 to 0.872) on the validation set, which proved to provide a better discrimination than C = 0.822 for age alone (95% CI, 0.801 to 0.842, P < 0.001) and C = 0.824 for the hospital-based model (95% CI, 0.802 to 0.843, P < 0.001). CONCLUSION: The TARGET-HF model illustrates that routine consultation codes can be used to build a performant model to identify patients at risk for HF at the time of GP consultation.