Aerobic capacity and mitochondrial function in bipolar disorder: a longitudinal study during acute phases and after clinical remission.

Background: Aerobic capacity has shown to predict physical and mental health-related quality of life in bipolar disorder (BD). However, the correlation between exercise respiratory capacity and mitochondrial function remains understudied. We aimed to assess longitudinally intra-individual differences in these factors during mood episodes and remission in BD. Methods: This study included eight BD patients admitted to an acute psychiatric unit. Incremental cardiopulmonary exercise test (CPET) was conducted during acute episodes (T0), followed by constant work rate cycle ergometry (CWRCE) to evaluate endurance time, oxygen uptake at peak exercise (VO2peak) and at the anaerobic threshold. The second test was repeated during remission (T1). Mitochondrial respiration rates were assessed at T0 and T1 in peripheral blood mononuclear cells. Results: Endurance time, VO2peak, and anaerobic threshold oxygen consumption showed no significant variations between T0 and T1. Basal oxygen consumption at T1 tended to inversely correlate with maximal mitochondrial respiratory capacity (r=-0.690, p=0.058), and VO2peak during exercise at T1 inversely correlated with basal and minimum mitochondrial respiration (r=-0.810, p=0.015; r=-0.786, p=0.021, respectively). Conclusions: Our preliminary data showed that lower basal oxygen consumption may be linked to greater mitochondrial respiratory capacity, and maximum oxygen uptake during the exercise task was associated with lower basal mitochondrial respiration, suggesting that lower oxygen requirements could be associated with greater mitochondrial capacity. These findings should be replicated in larger samples stratified for manic and depressive states.

Six-minute walking distance and desaturation-distance ratio in allogeneic stem cell transplantation.

BACKGROUND: Most patients with haematological malignancies who undergo allogeneic haematopoietic stem cell transplant (HSCT) receive chemotherapy before the transplant to control the disease. Certain chemotherapy drugs can cause lung toxicity. Conversely, in patients with chronic respiratory conditions, the 6-min walking test (6MWT) and the desaturation-distance ratio (DDR) have demonstrated prognostic significance. Our objective was to determine whether the 6MWD and DDR, assessed prior to HSCT, have a prognostic impact on survival at 24 months post-HSCT. METHODS: A prospective experimental study was conducted in consecutive patients referred for allogeneic HSCT at Hospital Clinic, Barcelona, Spain. A complete functional respiratory study, including the 6MWT and DDR, was conducted prior to admission. The area under the curve (AUC) and cut-off points were calculated. Data on patients' characteristics, HSCT details, main events, with a focus on lung complications, and survival at 24 months were analysed. RESULTS: One hundred and seventy-five patients (39% women) with mean age of 48 ± 13 years old were included. Before HSCT, forced vital capacity and forced expiratory volume in the first second were 96% ± 13% predicted and 92% ± 14% predicted, respectively; corrected diffusing capacity for carbon monoxide 79% ± 15% predicted; 6MWD was 568 ± 83 m and DDR of .27 (.20-.41). The cut-off points for 6MWD and DDR were 566 m, [.58 95% CI (.51-.64)], p = .024 and .306, [.63 95% CI (.55-.70)], p = .0005, respectively. The survival rate at 24 months was 55%. CONCLUSION: Our results showed that individuals who exhibit a 6MWD shorter than 566 ms or a decline in DDR beyond .306 experienced reduced survival rates at 24 months after HSCT.

Reduced mitochondrial respiratory capacity in patients with acute episodes of bipolar disorder: Could bipolar disorder be a state-dependent mitochondrial disease?

BACKGROUND: Bipolar disorder (BD) is a chronic and recurrent disease characterized by acute mood episodes and periods of euthymia. The available literature postulates that a biphasic dysregulation of mitochondrial bioenergetics might underpin the neurobiology of BD. However, most studies focused on inter-subject differences rather than intra-subject variations between different mood states. To test this hypothesis, in this preliminary proof-of-concept study, we measured in vivo mitochondrial respiration in patients with BD during a mood episode and investigated differences compared to healthy controls (HC) and to the same patients upon clinical remission. METHODS: This longitudinal study recruited 20 patients with BD admitted to our acute psychiatric ward with a manic (n = 15) or depressive (n = 5) episode, and 10 matched HC. We assessed manic and depressive symptoms using standardized psychometric scales. Different mitochondrial oxygen consumption rates (OCRs: Routine, Leak, electron transport chain [ETC], Rox) were assessed during the acute episode (T0) and after clinical remission (T1) using high-resolution respirometry at 37°C by polarographic oxygen sensors in a two-chamber Oxygraph-2k system in one million of peripheral blood mononuclear cells (PMBC). Specific OCRs were expressed as mean ± SD in picomoles of oxygen per million cells. Significant results were adjusted for age, sex, and body mass index. RESULTS: The longitudinal analysis showed a significant increase in the maximal oxygen consumption capacity (ETC) in clinical remission (25.7 ± 16.7) compared to the acute episodes (19.1 ± 11.8, p = 0.025), and was observed separately for patients admitted with a manic episode (29.2 ± 18.9 in T1, 22.3 ± 11.9 in T0, p = 0.076), and at a trend-level for patients admitted with a depressive episode (15.4 ± 3.9 in T1 compared to 9.4 ± 3.2 in T0, p = 0.107). Compared to HC, significant differences were observed in ETC in patients with a bipolar mood episode (H = 11.7; p = 0.003). Individuals with bipolar depression showed lower ETC than those with a manic episode (t = -3.7, p = 0.001). Also, significant differences were observed in ETC rates between HC and bipolar depression (Z = 1.000, p = 0.005). CONCLUSIONS: Bioenergetic and mitochondrial dysregulation could be present in both manic and depressive phases in BD and, importantly, they may restore after clinical remission. These preliminary results suggest that mitochondrial respiratory capacity could be a biomarker of illness activity and clinical response in BD. Further studies with larger samples and similar approaches are needed to confirm these results and identify potential biomarkers in different phases of the disease.

Pulmonary rehabilitation in sarcoidosis: A systematic review and meta-analysis.

BACKGROUND: Exercise intolerance, muscle weakness, dyspnoea, and fatigue are frequent complications in symptomatic sarcoidosis patients. Pulmonary rehabilitation improves exercise capacity, symptoms, and quality of life in patients with chronic respiratory diseases. Our objective was to systematically determine the effects of pulmonary rehabilitation in patients with sarcoidosis. METHODS: A systematic review was conducted in seven databases. Studies that applied pulmonary rehabilitation in patients with sarcoidosis were reviewed. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence. RESULTS: Of the 406 reports returned by the initial search, five articles reporting on 184 patients were included in the data synthesis. Two studies included multi-component exercise, one inspiratory muscle training, one a physical activity incentivisation programme, and one a telerehabilitation program. In the intervention group (IG), we found significant improvement in exercise capacity (SMD 1.65, 95%CI 0.45, 2.86 points, p = 0.006). If we only analyse the studies that performed the 6-min walking test, the IG walked 40.3 (CI95% 20.3, 60.2) m higher than the control group (CG) (p < 0.001). Additionally, dyspnoea score was reduced (MD -0.42 95%CI -0.75, -0.10, p = 0.002). However, fatigue, quality of life and pulmonary function did not show any change. CONCLUSION: Pulmonary rehabilitation could improve exercise capacity and dyspnoea perception in patients with sarcoidosis.

Blood Immunophenotypes of Idiopathic Pulmonary Fibrosis: Relationship with Disease Severity and Progression.

(1) The role of the immune response in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remains controversial. We hypothesized that peripheral blood immune phenotypes will be different in IPF patients and may relate to the disease severity and progression. (2) Whole blood flow cytometry staining was performed at diagnosis in 32 IPF patients, and in 32 age- and smoking-matched healthy controls. Thirty-one IPF patients were followed up for one year and categorized as stable or progressors based on lung function, deterioration and/or death. At 18-60 months, immunophenotypes were characterized again. (3) The main results showed that: (1) compared to matched controls, at diagnosis, patients with IPF showed more neutrophils, CD8+HLA-DR+ and CD8+CD28- T cells, and fewer B lymphocytes and naïve T cells; (2) in IPF, circulating neutrophils, eosinophils and naïve T cells were associated with lung function abnormalities; (3) patients whose disease progressed during the 12 months of follow-up showed evidence of cytotoxic dysregulation, with increased CD8+CD28- T cells, decreased naïve T cells and an inverted CD4/CD8 ratio at baseline; and (4) blood cell alterations were stable over time in survivors. (4) IPF is associated with abnormalities in circulating immune cells, particularly in the cytotoxic cell domain. Patients with progressive IPF, despite antifibrotic therapy, present an over-activated and exhausted immunophenotype at diagnosis, which is maintained over time.

Assessment of Exercise Capacity in Post-COVID-19 Patients: How Is the Appropriate Test Chosen?

There is a wide range of sequelae affecting COVID-19 survivors, including impaired physical capacity. These sequelae can affect the quality of life and return to work of the active population. Therefore, one of the pillars of following-up is the evaluation of physical capacity, which can be assessed with field tests (such as the six-minute walk test, the one-minute standing test, the Chester step test, and the shuttle walking test) or laboratory tests (such as the cardiopulmonary exercise test). These tests can be performed in different contexts and have amply demonstrated their usefulness in the assessment of physical capacity both in post-COVID-19 patients and in other chronic respiratory, metabolic, cardiologic, or neurologic diseases. However, when traditional tests cannot be performed, physical function can be a good substitute, especially for assessing the effects of an intervention. For example, the Short Physical Performance Battery assessment and the Timed Up and Go assessment are widely accepted in older adults. Thus, the test should be chosen according to the characteristics of each subject.

Does arterial oxygenation during exercise add prognostic value in pulmonary arterial hypertension?

BACKGROUND: The 6-min walking distance (6MWD) is often used to assess prognosis in pulmonary arterial hypertension (PAH) patients. Whether or not changes in arterial oxygen saturation (SpO2) during exercise add prognostic value to the 6MWD in these patients is unclear. The objective of this study was to investigate if SpO2 changes during exercise adds prognostic value to the 6MWD in PAH patients. METHODS: Ambispective study that includes 137 patients with PAH: 38 idiopathic/heritable (i/h PAH), 42 with connective tissue disease (CTD-PAH), 34 with porto-pulmonary hypertension (PoPH), 21 with HIV-associated PAH and 2 with pulmonary venous occlusive disease (PVOD). Patients were characterized and, treated according to international recommendations, and were followed-up for 5 years. To integrate SpO2 changes during exercise, we calculated the desaturation distance ratio (DDR) either in its original form (from a maximal theoretical value of 100%) or the actual resting SpO2 value of the patient (new DDR) as well as the distance saturation product (DSP). RESULTS: (1) during follow-up, 40 patients died (29.2%); (2) results confirmed the prognostic value of the 6MWD (AUC 0.913 [IQR 0.868-0.958]; p < 0.0001), original DDR (AUC 0.923 [0.881-0.966]; p < 0.001), New DDR (AUC 0.917 [0.872-0.961], p < 0.001), and DSP (AUC 0.914 [0.869-0.959], p < 0.001); and, (3) neither the original or new DDR or DSP added significant prognostic value to 6MWD in these patients. CONCLUSIONS: Consideration of three different composite indices of arterial oxygenation changes during exercise does not add prognostic value to that of the 6MWD in patients with PAH.

A New and More Sensitive Method to Integrate the Desaturation Distance Ratio During a 6-Minute Walking Test in Chronic Respiratory Diseases: Physiological Correlates / Un método nuevo y más sensible para integrar la relación entre distancia y desaturación durante la prueba de la marcha de seis minutos en las enfermedades respiratorias crónicas: correlaciones fisiológicas

No disponible

Prevalence of potential respiratory symptoms in survivors of hospital admission after coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

Knowledge on the sequelae of Coronavirus Disease 2019 (COVID-19) remains limited due to the relatively recent onset of this pathology. However, the literature on other types of coronavirus infections prior to COVID-19 reports that patients may experience persistent symptoms after discharge. To determine the prevalence of respiratory symptoms in survivors of hospital admission after COVID-19 infection. A living systematic review of five databases was performed in order to identify studies which reported the persistence of respiratory symptoms in COVID-19 patients after discharge. Two independent researchers reviewed and analysed the available literature, and then extracted and assessed the quality of those articles. Of the 1,154 reports returned by the initial search nine articles were found, in which 1,816 patients were included in the data synthesis. In the pooled analysis, we found a prevalence of 0.52 (CI 0.38-0.66, p < 0.01, I2 = 97%), 0.37 (CI 0.28-0.48, p < 0.01, I2 = 93%), 0.16 (CI 0.10-0.23, p < 0.01, I2 = 90%) and 0.14 (CI 0.06-0.24, p < 0.01, I2 = 96%) for fatigue, dyspnoea, chest pain, and cough, respectively. Fatigue, dyspnoea, chest pain, and cough were the most prevalent respiratory symptoms found in 52%, 37%, 16% and 14% of patients between 3 weeks and 3 months, after discharge in survivors of hospital admission by COVID-19, respectively.

Cost-effectiveness of a technology-supported multimodal prehabilitation program in moderate-to-high risk patients undergoing lung cancer resection: randomized controlled trial protocol.

BACKGROUND: Multimodal prehabilitation is a preoperative intervention with the objective to enhance cancer patients' functional status which has been showed to reduce both postoperative morbidity and hospital length of stay in digestive oncologic surgery. However, in lung cancer surgery patients further studies with higher methodological quality are needed to clarify the benefits of prehabilitation. The main aim of the current protocol is to evaluate the cost-effectiveness of a multimodal prehabilitation program supported by information and communication technologies in moderate-to-high risk lung cancer patients undergoing thoracic surgery. METHODS: A Quadruple Aim approach will be adopted, assessing the prehabilitation program at the following levels: i) Patients' and professionals' experience outcomes (by means of standardized questionnaires, focus groups and structured interviews); ii) Population health-based outcomes (e.g. hospital length of stay, number and severity of postoperative complications, peak oxygen uptake and levels of systemic inflammation); and, iii) Healthcare costs. DISCUSSION: This study protocol should contribute not only to increase the scientific basis on prehabilitation but also to detect the main factors modulating service adoption. TRIAL REGISTRATION: NCT04052100 (August 9, 2019).

Automated Spirometry Quality Assurance: Supervised Learning From Multiple Experts.

Forced spirometry testing is gradually becoming available across different healthcare tiers including primary care. It has been demonstrated in earlier work that commercially available spirometers are not fully able to assure the quality of individual spirometry manoeuvres. Thus, a need to expand the availability of high-quality spirometry assessment beyond specialist pulmonary centres has arisen. In this paper, we propose a method to select and optimise a classifier using supervised learning techniques by learning from previously classified forced spirometry tests from a group of experts. Such a method is able to take into account the shape of the curve as an expert would during visual inspection. We evaluated the final classifier on a dataset put aside for evaluation yielding an area under the receiver operating characteristic curve of 0.88 and specificities of 0.91 and 0.86 for sensitivities of 0.60 and 0.82. Furthermore, other specificities and sensitivities along the receiver operating characteristic curve were close to the level of the experts when compared against each-other, and better than an earlier rules-based method assessed on the same dataset. We foresee key benefits in raising diagnostic quality, saving time, reducing cost, and also improving remote care and monitoring services for patients with chronic respiratory diseases in the future if a clinical decision support system with the encapsulated classifier is to be integrated into the work-flow of forced spirometry testing.