Surgical approaches for lung volume reduction in emphysema

Lung volume reduction surgery (LVRS) for chronic obstructive pulmonary disease (COPD) is recommended in both British and international guidelines because trials have shown improvement in survival in selected patients with poor baseline exercise capacity and upper lobe-predominant emphysema. Despite this, few procedures are carried out, possibly because of historical concerns about high levels of morbidity and mortality associated with the operation. The authors reviewed data on lung volume reduction procedures at their institution between January 2000 and September 2012. There were no deaths within 90 days of unilateral LVRS (n=81), bullectomy (n=20) or intracavity drainage procedures (n=14). These data suggest that concerns about surgical mortality should not discourage LVRS in selected patients with COPD, provided that it is undertaken within a multidisciplinary team environment involving appropriate patient selection. © Royal College of Physicians 2014. All rights reserved

Virtual consultations for patients with Obstructive Sleep Apnoea:systematic review and meta-analysis

Background: The COVID-19 pandemic has accelerated the adoption of virtual care strategies for the management of patients with Obstructive Sleep Apnoea/Hypopnoea Syndrome. Research question: What is the effectiveness of virtual consultations compared to in-person consultations for the management of Continuous Positive Airway Pressure therapy in adult patients with Obstructive Sleep Apnoea/Hypopnoea Syndrome? Methods: A systematic review and meta-analysis (PROSPERO; CRD42022297532) based on six electronic databases plus manually selected journals was conducted in January 2022. Two researchers independently selected, quality appraised, and extracted data. The co-primary outcomes were patient-reported sleepiness, assessed by the Epworth Sleepiness Scale, and reported cost-effectiveness. Findings: 12 studies (n=1823 adults) were included in the review. Seven studies (n=1089) were included in the meta-analysis which showed no difference in the magnitude of improvement in patient-reported sleepiness scores between virtual and in-person consultations (MD [95%CI], -0.39 [-1.38 to 0.60]; p=0.4), though Epworth Sleepiness Scale scores improved in both groups. Virtual care strategies modestly increased Continuous Positive Airway Pressure therapy adherence and were found to be less costly than in-person care strategies in the three Spanish trials that reported cost-effectiveness. Conclusion: The findings of this review suggest that virtual care delivered by telephone or video consultations is as effective as in-person consultations for improving subjective sleepiness in patients with Obstructive Sleep Apnoea/Hypopnoea Syndrome treated with Continuous Positive Airway Pressure. This clinical management strategy may also improve Continuous Positive Airway Pressure adherence without increasing the costs, supporting its potential as a follow-up management strategy, where patients prefer this approach

Mechanisms of improvement of respiratory failure in patients with COPD treated with NIV

Annabel H Nickol1,2, Nicholas Hart1,3, Nicholas S Hopkinson1, Carl-Hugo Hamnegård4, John Moxham5, Anita Simonds1, Michael I Polkey11Respiratory Muscle Laboratory, Royal Brompton Hospital, London, UK; 2Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford, UK; 3The Lane Fox Unit, St Thomas’ Hospital, London, UK; 4Department of Pulmonary Medicine and Clinical Physiology, Sahlgrenska University, Gotenborg, Sweden; 5Respiratory Muscle Laboratory, King’s College London School of Medicine, King’s College Hospital, London, UKBackground: Noninvasive ventilation (NIV) improves gas-exchange and symptoms in selected chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure. We hypothesized NIV reverses respiratory failure by one or all of increased ventilatory response to carbon-dioxide, reduced respiratory muscle fatigue, or improved pulmonary mechanics.Methods: Nineteen stable COPD patients (forced expiratory volume in one second 35% predicted) were studied at baseline (D0), 5–8 days (D5) and 3 months (3M) after starting NIV.Results: Ventilator use was 6.2 (3.7) hours per night at D5 and 3.4 (1.6) at 3M (p = 0.12). Mean (SD) daytime arterial carbon-dioxide tension (PaCO2) was reduced from 7.4 (1.2) kPa to 7.0 (1.1) kPa at D5 and 6.5 (1.1) kPa at 3M (p = 0.001). Total lung capacity decreased from 107 (28) % predicted to 103 (28) at D5 and 103 (27) % predicted at 3M (p = 0.035). At D5 there was an increase in the hypercapnic ventilatory response and some volitional measures of inspiratory and expiratory muscle strength, but not isolated diaphragmatic strength whether assessed by volitional or nonvolitional methods.Conclusion: These findings suggest decreased gas trapping and increased ventilatory sensitivity to CO2 are the principal mechanism underlying improvements in gas-exchange in patients with COPD following NIV. Changes in some volitional but not nonvolitional muscle strength measures may reflect improved patient effort.Keywords: COPD; hypercapnic respiratory failure; NIV; pulmonary mechanics; ventilatory driv

Singing teaching as a therapy for chronic respiratory disease - a randomised controlled trial and qualitative evaluation

<p>Abstract</p> <p>Background</p> <p>Despite optimal pharmacological therapy and pulmonary rehabilitation, patients with COPD continue to be breathless. There is a need to develop additional strategies to alleviate symptoms. Learning to sing requires control of breathing and posture and might have benefits that translate into daily life.</p> <p>Methods</p> <p>To test this hypothesis we performed a randomised controlled trial, comparing a six week course of twice weekly singing classes to usual care, in 28 COPD patients. The experience of singing was assessed in a qualitative fashion, through interviews with a psychologist. In addition, we surveyed patients with chronic respiratory conditions who participated in a series of open singing workshops.</p> <p>Results</p> <p>In the RCT, the physical component score of the SF36 improved in the singers (n = 15) compared to the controls (n = 13); +7.5(14.6) vs. -3.8(8.4) p = 0.02. Singers also had a significant fall in HAD anxiety score; -1.1(2.7) vs. +0.8(1.7) p = 0.03. Singing did not improve single breath counting, breath hold time or shuttle walk distance. In the qualitative element, 8 patients from the singing group were interviewed. Positive effects on physical sensation, general well-being, community/social support and achievement/efficacy emerged as common themes. 150 participants in open workshops completed a questionnaire. 96% rated the workshops as "very enjoyable" and 98% thought the workshop had taught them something about breathing in a different way. 81% of attendees felt a "marked physical difference" after the workshop.</p> <p>Conclusion</p> <p>Singing classes can improve quality of life measures and anxiety and are viewed as a very positive experience by patients with respiratory disease; no adverse consequences of participation were observed.</p> <p>Trial Registration</p> <p>Current Controlled Trials - ISRCTN17544114.</p

Central and peripheral quadriceps fatigue in congestive heart failure

AbstractAimsThe clinical syndrome of heart failure includes exercise limitation that is not directly linked to measures of cardiac function. Quadriceps fatigability may be an important component of this and this may arise from peripheral or central factors.Methods and resultsWe studied 10 men with CHF and 10 healthy age-matched controls. Compared with a rest condition, 10min after incremental maximal cycle exercise, twitch quadriceps force in response to supramaximal magnetic femoral nerve stimulation fell in both groups (CHF 14.1%±18.1%, p=0.037; Control: 20.8±11.0%, p<0.001; no significant difference between groups). There was no significant change in quadriceps maximum voluntary contraction voluntary force. The difference in the motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex between rest and exercise conditions at 10min, normalised to the peripheral action potential, also fell significantly in both groups (CHF: 27.3±38.7%, p=0.037; Control: 41.1±47.7%, p=0.024). However, the fall in MEP was sustained for a longer period in controls than in patients (p=0.048).ConclusionsThe quadriceps is more susceptible to fatigue, with a similar fall in TwQ occurring in CHF patients at lower levels of exercise. This is associated with no change in voluntary activation but a lesser degree of depression of quadriceps motor evoked potential

Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the licenseRATIONALE: Muscle atrophy confers a poor prognosis in patients with chronic obstructive pulmonary disease (COPD), yet the molecular pathways responsible are poorly characterised. Muscle-specific microRNAs and serum response factor (SRF) are important regulators of muscle phenotype that contribute to a feedback system to regulate muscle gene expression. The role of these factors in the skeletal muscle dysfunction that accompanies COPD is unknown. METHODS: 31 patients with COPD and 14 healthy age-matched controls underwent lung and quadriceps function assessments, measurement of daily activity and a percutaneous quadriceps muscle biopsy. The expression of muscle-specific microRNAs, myosin heavy chains and components of the serum response factor signalling pathway were determined by qPCR. RESULTS: A reduction in expression of miR-1 (2.5-fold, p=0.01) and the myocardin-related transcription factors (MRTFs) A and B was observed in patients compared with controls (MRTF-A mRNA: twofold, p=0.028; MRTF-B mRNA: fourfold, p=0.011). miR-1 expression was associated with smoking history, lung function, fat-free mass index, 6 min walk distance and percentage of type 1 fibres. miR-133 and miR-206 were negatively correlated with daily physical activity. Insulin-like growth factor 1 mRNA was increased in the patients and miR-1 was negatively correlated with phosphorylation of the kinase Akt. Furthermore, the protein levels of histone deacetylase 4, another miR-1 target, were increased in the patients. CONCLUSIONS: Downregulation of the activity of the MRTF-SRF axis and the expression of muscle-specific microRNAs, particularly miR-1, may contribute to COPD-associated skeletal muscle dysfunction.BBSRC, Wellcome Trust and the National Institute for Health Research (NIHR) Respiratory Biomedical Unit at the Royal Brompton Hospital and Imperial College. AL is a BBSRC PhD student, SAN received a Wellcome Trust Fellowship, AD received a NIHR Respiratory Biomedical Unit fellowship and WM is a NIHR Clinician Scientist. NSH is a HEFCE Clinical Senior Lecturer. MIP's salary is part funded by the NIHR Respiratory Biomedical Unit at the Royal Brompton Hospital and National Heart & Lung Institute

The Impact of Homogeneous Versus Heterogeneous Emphysema on Dynamic Hyperinflation in Patients With Severe COPD Assessed for Lung Volume Reduction

Dynamic hyperinflation (DH) is a pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to investigate the impact of emphysema distribution on DH during a maximal cardiopulmonary exercise test (CPET) in patients with severe COPD. This was a retrospective analysis of prospectively collected data among severe COPD patients who underwent thoracic high-resolution computed tomography, full lung function measurements and maximal CPET with inspiratory manouvers as assessment for a lung volume reduction procedure. ΔIC was calculated by subtracting the end-exercise inspiratory capacity (eIC) from resting IC (rIC) and expressed as a percentage of rIC (ΔIC %). Emphysema quantification was conducted at 3 predefined levels using the syngo PULMO-CT (Siemens AG); a difference >25% between best and worse slice was defined as heterogeneous emphysema. Fifty patients with heterogeneous (62.7% male; 60.9 ± 7.5 years old; FEV(1)% = 32.4 ± 11.4) and 14 with homogeneous emphysema (61.5% male; 62.5 ± 5.9 years old; FEV(1)% = 28.1 ± 10.3) fulfilled the enrolment criteria. The groups were matched for all baseline variables. ΔIC% was significantly higher in homogeneous emphysema (39.8% ± 9.8% vs.31.2% ± 13%, p = 0.031), while no other CPET parameter differed between the groups. Upper lobe predominance of emphysema correlated positively with peak oxygen pulse, peak oxygen uptake and peak respiratory rate, and negatively with ΔIC%. Homogeneous emphysema is associated with more DH during maximum exercise in COPD patients

Surrogate Markers of Cardiovascular Risk and Chronic Obstructive Pulmonary Disease: A Large Case-Controlled Study.

Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease. A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes. We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors. A total of 458 patients with a diagnosis of chronic obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers) with no airflow limitation were matched for age, sex, and body mass index. All individuals underwent assessments of carotid-femoral (aortic) pulse wave velocity, augmentation index, and carotid intima-media thickness. The mean age of the cohort was 67±8 years and 58% were men. Patients with chronic obstructive pulmonary disease had increased aortic pulse wave velocity (9.95±2.54 versus 9.27±2.41 m/s; P<0.001), augmentation index (28±10% versus 25±10%; P<0.001), and carotid intima-media thickness (0.83±0.19 versus 0.74±0.14 mm; P<0.001) compared with controls. Chronic obstructive pulmonary disease was associated with increased levels of each vascular biomarker independently of physiological confounders, smoking, and other cardiovascular risk factors. In this large case-controlled study, chronic obstructive pulmonary disease was associated with increased arterial stiffness, wave reflections, and subclinical atherosclerosis, independently of traditional cardiovascular risk factors. These findings suggest that the cardiovascular burden observed in this condition may be mediated through these mechanisms and supports the concept that chronic obstructive pulmonary disease is an independent risk factor for cardiovascular disease

Risk assessment for hospital admission in patients with COPD; a multi-centre UK prospective observational study.

In chronic obstructive pulmonary disease (COPD), acute exacerbation of COPD requiring hospital admission is associated with mortality and healthcare costs. The ERICA study assessed multiple clinical measures in people with COPD, including the short physical performance battery (SPPB), a simple test of physical function with 3 components (gait speed, balance and sit-to-stand). We tested the hypothesis that SPPB score would relate to risk of hospital admissions and length of hospital stay. Data were analysed from 714 of the total 729 participants (434 men and 280 women) with COPD. Data from this prospective observational longitudinal study were obtained from 4 secondary and 1 tertiary centres from England, Scotland, and Wales. The main outcome measures were to estimate the risk of hospitalisation with acute exacerbation of COPD (AECOPD and length of hospital stay derived from hospital episode statistics (HES). In total, 291 of 714 individuals experienced 762 hospitalised AECOPD during five-year follow up. Poorer performance of SPPB was associated with both higher rate (IRR 1.08 per 1 point decrease, 95% CI 1.01 to 1.14) and increased length of stay (IRR 1.18 per 1 point decrease, 95% CI 1.10 to 1.27) for hospitalised AECOPD. For the individual sit-to-stand component of the SPPB, the association was even stronger (IRR 1.14, 95% CI 1.02 to 1.26 for rate and IRR 1.32, 95% CI 1.16 to 1.49 for length of stay for hospitalised AECOPD). The SPPB, and in particular the sit-to-stand component can both evaluate the risk of H-AECOPD and length of hospital stay in COPD. The SPPB can aid in clinical decision making and when prioritising healthcare resources

Respiratory muscle strength as a predictive biomarker for survival in amyotrophic lateral sclerosis

Rationale: Biomarkers for survival in amyotrophic lateral sclerosis (ALS) would facilitate the development of novel drugs. Although respiratory muscle weakness is a known predictor of poor prognosis, a comprehensive comparison of different tests is lacking. Objectives: To compare the predictive power of invasive and noninvasive respiratory muscle strength assessments for survival or ventilator-free survival, up to 3 years. Methods: From a previously published report respiratory muscle strength measurements were available for 78 patients with ALS. Time to death and/or ventilation were ascertained. Receiver operating characteristic analysis was used to determine the cutoff point of each parameter. Measurements and Main Results: Each respiratory muscle strength assessment individually achieved statistical significance for prediction of survival or ventilator-free survival. In multivariate analysis sniff trans-diaphragmatic and esophageal pressure, twitch trans-diaphragmatic pressure (Tw Pdi), age, and maximal static expiratory mouth pressure were significant predictors of ventilation-free survival and Tw Pdi and maximal static expiratory mouth pressure for absolute survival. Although all measures had good specificity, there were differing sensitivities. All cutoff points for the VC were greater than 80% of normal, except for prediction of 3-month outcomes. Sequential data showed a linear decline for direct measures of respiratory muscle strength, whereas VC showed little to no decline until 12 months before death/ventilation. Conclusions: The most powerful biomarker for mortality stratification was Tw Pdi, but the predictive power of sniff nasal inspiratory pressure was also excellent. A VC within normal range suggested a good prognosis at 3 months but was of little other value