Isolation and loneliness are related to various aspects of health. Physical performance is a central component of health. However, its relationship with isolation and loneliness is not well ...understood. We therefore assessed the relationship between loneliness, different aspects of social isolation, and physical performance over time. 8,780 participants from the English Longitudinal Study of Ageing, assessed three times over 8 years of follow-up, were included. Measures included physical performance (Short Physical Performance Battery), loneliness (modified UCLA Loneliness Scale), and isolation considered in three ways (domestic isolation, social disengagement, low social contact). Fixed effects regression models were used to estimate the relationship between changes in these parameters. Missing data were imputed to account for variable response and ensure a representative sample. Loneliness, domestic isolation and social disengagement were longitudinally associated with poorer physical performance when accounting for both time-invariant and time-variant confounders (loneliness: coef = - 0.06, 95% CI - 0.09 to - 0.02; domestic isolation: coef = - 0.32, 95% CI - 0.46 to - 0.19; social disengagement: coef = - 0.10, 95% CI - 0.12 to - 0.07). Low social contact was not associated with physical performance. These findings suggest social participation and subjectively meaningful interpersonal interactions are related to physical performance, and highlight additional considerations regarding social distancing related to COVID-19 control measures.
Polkey et al discuss the study by Regmi and colleagues on diaphragm dysfunction as a contributor to breathlessness after COVID-19 infection. They studied a group of COVID survivors for a mean of 15 ...months after their illness who had required ventilation and a second group who had been admitted to the hospital but had required oxygen therapy alone. The control group was age-matched control subjects without illness studied prepandemic; the paper would have been strengthened, of course, had they also studied patients with mild or asymptomatic disease and also if they had studied patients with acute lung injury due to non-COVID causes. They found that both groups of patients had reduced diaphragm strength, expiratory muscle strength (measured as Twitch T10 gastric pressure Tw T10 Pga), and contractility, but the weakness was not different between the ventilated group and those who required oxygen alone.
: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of ...expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.
: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.
: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations:
) a strong recommendation for the use of long-acting β
-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance;
) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year;
) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year;
) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy;
) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and
) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.
: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.
Severe obesity causes respiratory morbidity and mortality. The impact of obesity on the mechanics of breathing is not fully understood.
We undertook a comprehensive observational study of lung ...volumes and elasticity in nine obese and nine normal weight subjects, seated and supine, during spontaneous breathing. Seated and supine total lung capacity (TLC) and subdivisions were measured by multibreath helium dilution method. Using balloon catheters, oesophageal (Poes) and gastric (Pgas) pressures were recorded. Transpulmonary pressure (PL) was calculated as mouth pressure (Pmouth)-Poes, and complete expiratory PL volume curves were measured.
The obese group had a body mass index (BMI) of 46.8 (17.2) kg/m(2), and the normal group had a BMI of 23.2 (1.6) kg/m(2) (p=0.001). Obese and normals were matched for age (p=0.233), gender (p=0.637) and height (p=0.094). The obese were more restricted than the normals (TLC 88.6 (16.9) vs 104.4 (12.3) %predicted, p=0.033; FEV1/FVC 79.6 (7.3) vs 82.5 (4.2) %, p=0.325), had dramatically reduced expiratory reserve volume (ERV 0.4 (0.4) vs 1.7 (0.6) L, p<0.001) and end-tidal functional residual capacity (FRC) was smaller (37.5 (6.9) vs 46.9 (4.6) %TLC, p=0.004) when seated, but was similar when supine (39.4 (7.7) vs 41.5 (4.3) %TLC, p=0.477). Gastric pressures at FRC were significantly elevated in the obese (seated 19.1 (4.7) vs 12.1 (6.2) cm H2O, p=0.015; supine 14.3 (5.7) vs 7.1 (2.6) cm H2O, p=0.003), as were end-expiratory oesophageal pressures at FRC (seated 5.2 (6.9) vs -2.0 (3.5) cm H2O, p=0.013; supine 14.0 (8.0) vs 5.4 (3.1) cm H2O, p=0.008). BMI correlated with end-expiratory gastric (seated R(2)=0.43, supine R(2)=0.66, p<0.01) and oesophageal pressures (seated R(2)=0.51, supine R(2)=0.62, p<0.01).
Obese subjects have markedly increased gastric and oesophageal pressures, both when upright and supine, causing dramatically reduced FRC and ERV, which increases work of breathing.
Summary Background Lung volume reduction surgery improves survival in selected patients with emphysema, and has generated interest in bronchoscopic approaches that might achieve the same effect with ...less morbidity and mortality. Previous trials with endobronchial valves have yielded modest group benefits because when collateral ventilation is present it prevents lobar atelectasis. Methods We did a single-centre, double-blind sham-controlled trial in patients with both heterogeneous emphysema and a target lobe with intact interlobar fissures on CT of the thorax. We enrolled stable outpatients with chronic obstructive pulmonary disease who had a forced expiratory volume in 1 s (FEV1 ) of less than 50% predicted, significant hyperinflation (total lung capacity >100% and residual volume >150%), a restricted exercise capacity (6 min walking distance <450 m), and substantial breathlessness (MRC dyspnoea score ≥3). Participants were randomised (1:1) by computer-generated sequence to receive either valves placed to achieve unilateral lobar occlusion (bronchoscopic lung volume reduction) or a bronchoscopy with sham valve placement (control). Patients and researchers were masked to treatment allocation. The study was powered to detect a 15% improvement in the primary endpoint, the FEV1 3 months after the procedure. Analysis was on an intention-to-treat basis. The trial is registered at controlled-trials.com , ISRCTN04761234. Findings 50 patients (62% male, FEV1 % predicted mean 31·7% SD 10·2) were enrolled to receive valves (n=25) or sham valve placement (control, n=25) between March 1, 2012, and Sept 30, 2013. In the bronchoscopic lung volume reduction group, FEV1 increased by a median 8·77% (IQR 2·27–35·85) versus 2·88% (0–8·51) in the control group (Mann-Whitney p=0·0326). There were two deaths in the bronchoscopic lung volume reduction group and one control patient was unable to attend for follow-up assessment because of a prolonged pneumothorax. Interpretation Unilateral lobar occlusion with endobronchial valves in patients with heterogeneous emphysema and intact interlobar fissures produces significant improvements in lung function. There is a risk of significant complications and further trials are needed that compare valve placement with lung volume reduction surgery. Funding Efficacy and Mechanism Evaluation Programme, funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership.
Frailty is an important clinical syndrome that is consistently associated with adverse outcomes in older people. The relevance of frailty to chronic respiratory disease and its management is unknown.
...To determine the prevalence of frailty among patients with stable COPD and examine whether frailty affects completion and outcomes of pulmonary rehabilitation.
816 outpatients with COPD (mean (SD) age 70 (10) years, FEV
% predicted 48.9 (21.0)) were recruited between November 2011 and January 2015. Frailty was assessed using the Fried criteria (weight loss, exhaustion, low physical activity, slowness and weakness) before and after pulmonary rehabilitation. Predictors of programme non-completion were identified using multivariate logistic regression, and outcomes were compared using analysis of covariance, adjusting for age and sex.
209/816 patients (25.6%, 95% CI 22.7 to 28.7) were frail. Prevalence of frailty increased with age, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) score and age-adjusted comorbidity burden (all p≤0.01). Patients who were frail had double the odds of programme non-completion (adjusted OR 2.20, 95% CI 1.39 to 3.46, p=0.001), often due to exacerbation and/or hospital admission. However, rehabilitation outcomes favoured frail completers, with consistently better responses in MRC score, exercise performance, physical activity level and health status (all p<0.001). After rehabilitation, 71/115 (61.3%) previously frail patients no longer met case criteria for frailty.
Frailty affects one in four patients with COPD referred for pulmonary rehabilitation and is an independent predictor of programme non-completion. However, patients who are frail respond favourably to rehabilitation and their frailty can be reversed in the short term.
This European Respiratory Society (ERS) statement provides a comprehensive overview on physical activity in patients with chronic obstructive pulmonary disease (COPD). A multidisciplinary Task Force ...of experts representing the ERS Scientific Group 01.02 "Rehabilitation and Chronic Care" determined the overall scope of this statement through consensus. Focused literature reviews were conducted in key topic areas and the final content of this Statement was agreed upon by all members. The current knowledge regarding physical activity in COPD is presented, including the definition of physical activity, the consequences of physical inactivity on lung function decline and COPD incidence, physical activity assessment, prevalence of physical inactivity in COPD, clinical correlates of physical activity, effects of physical inactivity on hospitalisations and mortality, and treatment strategies to improve physical activity in patients with COPD. This Task Force identified multiple major areas of research that need to be addressed further in the coming years. These include, but are not limited to, the disease-modifying potential of increased physical activity, and to further understand how improvements in exercise capacity, dyspnoea and self-efficacy following interventions may translate into increased physical activity. The Task Force recommends that this ERS statement should be reviewed periodically (e.g. every 5-8 years).
1 Centre for Sports Medicine and Human Performance, Brunel University, Uxbridge; and 2 Respiratory Muscle Laboratory, Royal Brompton Hospital, and National Heart and Lung Institute, London, United ...Kingdom
It is commonly held that the respiratory system has ample capacity relative to the demand for maximal O 2 and CO 2 transport in healthy humans exercising near sea level. However, this situation may not apply during heavy-intensity, sustained exercise where exercise may encroach on the capacity of the respiratory system. Nerve stimulation techniques have provided objective evidence that the diaphragm and abdominal muscles are susceptible to fatigue with heavy, sustained exercise. The fatigue appears to be due to elevated levels of respiratory muscle work combined with an increased competition for blood flow with limb locomotor muscles. When respiratory muscles are prefatigued using voluntary respiratory maneuvers, time to exhaustion during subsequent exercise is decreased. Partially unloading the respiratory muscles during heavy exercise using low-density gas mixtures or mechanical ventilation can prevent exercise-induced diaphragm fatigue and increase exercise time to exhaustion. Collectively, these findings suggest that respiratory muscle fatigue may be involved in limiting exercise tolerance or that other factors, including alterations in the sensation of dyspnea or mechanical load, may be important. The major consequence of respiratory muscle fatigue is an increased sympathetic vasoconstrictor outflow to working skeletal muscle through a respiratory muscle metaboreflex, thereby reducing limb blood flow and increasing the severity of exercise-induced locomotor muscle fatigue. An increase in limb locomotor muscle fatigue may play a pivotal role in determining exercise tolerance through a direct effect on muscle force output and a feedback effect on effort perception, causing reduced motor output to the working limb muscles.
respiratory muscles; exercise; diaphragm; abdominals; magnetic stimulation; metaboreflex
Address for reprint requests and other correspondence: L. M. Romer, Centre for Sports Medicine and Human Performance, Brunel Univ., Uxbridge UB8 3PH, United Kingdom (e-mail: lee.romer{at}brunel.ac.uk )
Loss of skeletal muscle mass and function is a common consequence of critical illness and a range of chronic diseases, but the mechanisms by which this occurs are unclear.
To identify microRNAs ...(miRNAs) that were increased in the quadriceps of patients with muscle wasting and to determine the molecular pathways by which they contributed to muscle dysfunction.
miRNA-542-3p/5p (miR-542-3p/5p) were quantified in the quadriceps of patients with chronic obstructive pulmonary disease and intensive care unit-acquired weakness (ICUAW). The effect of miR-542-3p/5p was determined on mitochondrial function and transforming growth factor-β signaling in vitro and in vivo.
miR-542-3p/5p were elevated in patients with chronic obstructive pulmonary disease but more markedly in patients with ICUAW. In vitro, miR-542-3p suppressed the expression of the mitochondrial ribosomal protein MRPS10 and reduced 12S ribosomal RNA (rRNA) expression, suggesting mitochondrial ribosomal stress. miR-542-5p increased nuclear phospho-SMAD2/3 and suppressed expression of SMAD7, SMURF1, and PPP2CA, proteins that inhibit or reduce SMAD2/3 phosphorylation, suggesting that miR-542-5p increased transforming growth factor-β signaling. In mice, miR-542 overexpression caused muscle wasting, and reduced mitochondrial function, 12S rRNA expression, and SMAD7 expression, consistent with the effects of the miRNAs in vitro. Similarly, in patients with ICUAW, the expression of 12S rRNA and of the inhibitors of SMAD2/3 phosphorylation were reduced, indicative of mitochondrial ribosomal stress and increased transforming growth factor-β signaling. In patients undergoing aortic surgery, preoperative levels of miR-542-3p/5p were positively correlated with muscle loss after surgery.
Elevated miR-542-3p/5p may cause muscle atrophy in intensive care unit patients through the promotion of mitochondrial dysfunction and activation of SMAD2/3 phosphorylation.
Moving from sitting to standing is a common activity of daily living. The five-repetition sit-to-stand test (5STS) is a test of lower limb function that measures the fastest time taken to stand five ...times from a chair with arms folded. The 5STS has been validated in healthy community-dwelling adults, but data in chronic obstructive pulmonary disease (COPD) populations are lacking.
To determine the reliability, validity and responsiveness of the 5STS in patients with COPD.
Test-retest and interobserver reliability of the 5STS was measured in 50 patients with COPD. To address construct validity we collected data on the 5STS, exercise capacity (incremental shuttle walk (ISW)), lower limb strength (quadriceps maximum voluntary contraction (QMVC)), health status (St George's Respiratory Questionnaire (SGRQ)) and composite mortality indices (Age Dyspnoea Obstruction index (ADO), BODE index (iBODE)). Responsiveness was determined by measuring 5STS before and after outpatient pulmonary rehabilitation (PR) in 239 patients. Minimum clinically important difference (MCID) was estimated using anchor-based methods.
Test-retest and interobserver intraclass correlation coefficients were 0.97 and 0.99, respectively. 5STS time correlated significantly with ISW, QMVC, SGRQ, ADO and iBODE (r=-0.59, -0.38, 0.35, 0.42 and 0.46, respectively; all p<0.001). Median (25th, 75th centiles) 5STS time decreased with PR (Pre: 14.1 (11.5, 21.3) vs Post: 12.4 (10.2, 16.3) s; p<0.001). Using different anchors, a conservative estimate for the MCID was 1.7 s.
The 5STS is reliable, valid and responsive in patients with COPD with an estimated MCID of 1.7 s. It is a practical functional outcome measure suitable for use in most healthcare settings.
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