CT pectoralis muscle area is associated with DXA lean mass and correlates with emphysema progression in a tobacco-exposed cohort.

INTRODUCTION: Muscle loss is an important extrapulmonary manifestation of COPD. Dual energy X-ray absorptiometry (DXA) is the method of choice for body composition measurement but is not widely used for muscle mass evaluation. The pectoralis muscle area (PMA) is quantifiable by CT and predicts cross-sectional COPD-related morbidity. There are no studies that compare PMA with DXA measures or that evaluate longitudinal relationships between PMA and lung disease progression. METHODS: Participants from our longitudinal tobacco-exposed cohort had baseline and 6-year chest CT (n=259) and DXA (n=164) data. Emphysema was quantified by CT density histogram parenchymal scoring using the 15th percentile technique. Fat-free mass index (FFMI) and appendicular skeletal mass index (ASMI) were calculated from DXA measurements. Linear regression model relationships were reported using standardised coefficient (ß) with 95% CI. RESULTS: PMA was more strongly associated with DXA measures than with body mass index (BMI) in both cross-sectional (FFMI: ß=0.76 (95% CI 0.65 to 0.86), p<0.001; ASMI: ß=0.76 (95% CI 0.66 to 0.86), p<0.001; BMI: ß=0.36 (95% CI 0.25 to 0.47), p<0.001) and longitudinal (ΔFFMI: ß=0.43 (95% CI 0.28 to 0.57), p<0.001; ΔASMI: ß=0.42 (95% CI 0.27 to 0.57), p<0.001; ΔBMI: ß=0.34 (95% CI 0.22 to 0.46), p<0.001) models. Six-year change in PMA was associated with 6-year change in emphysema (ß=0.39 (95% CI 0.23 to 0.56), p<0.001) but not with 6-year change in airflow obstruction. CONCLUSIONS: PMA is an accessible measure of muscle mass and may serve as a useful clinical surrogate for assessing skeletal muscle loss in smokers. Decreased PMA correlated with emphysema progression but not lung function decline, suggesting a difference in the pathophysiology driving emphysema, airflow obstruction and comorbidity risk.

The Royal College of surgeons multidisciplinary guidelines on elective tracheostomy insertion in COVID-19 ventilated patients.

BACKGROUND: The current COVID-19 pandemic has placed enormous strain on healthcare systems worldwide. Understanding of COVID-19 is rapidly evolving. Pneumonia associated with COVID-19 may lead to respiratory failure requiring mechanical ventilation. The rise in patients requiring mechanical ventilation may lead to an increase in tracheostomies being performed in patients with COVID-19. Performing tracheostomy in patients with active SARS-CoV-2 infection poses a number of challenges. METHODS: These guidelines were written following multidisciplinary agreement between Otolaryngology, Head and Neck Surgery, Respiratory Medicine and the Department of Anaesthetics and Critical Care Medicine in the Royal College of Surgeons in Ireland. A literature review was performed and a guideline for elective tracheostomy insertion in patients with COVID-19 proposed. CONCLUSION: The decision to perform tracheostomy in patients with COVID-19 should be undertaken by senior members of the multidisciplinary team. Steps should be taken to minimise risks to healthcare workers.

Prolonged Cold Ischemia Induces Necroptotic Cell Death in Ischemia-Reperfusion Injury and Contributes to Primary Graft Dysfunction after Lung Transplantation.

Primary graft dysfunction (PGD) is a major cause of morbidity and mortality after lung transplantation. Ischemia-reperfusion injury (IRI) is a key event that contributes to PGD, though complex interactions affect donor lungs status, such as preceding brain death (BD), hemorrhagic shock (HS), and pre-engraftment lung management, the latter recognized as important risk factors for PGD. We hypothesized that a multi-hit isogenic mouse model of lung transplantation is more closely linked to PGD than IRI alone. Left lung transplants were performed between inbred C57BL/6 mice. A one-hit model of IRI was established by inducing cold ischemia (CI) of the donor lungs at 0°C for 1, 72, or 96 hours before engraftment. Multi-hit models were established by inducing 24 hours of HS and/or 3 hours of BD before 24 hours of CI. The recipients were killed at 24 hours after transplant and lung graft samples were analyzed. In the one-hit model of IRI, up to 72-hour CI time resulted in minimal cellular infiltration near small arteries after 24-hour reperfusion. Extension of CI time to 96 hours led to increased cellular infiltration and necroptotic pathway activation, without evidence of apoptosis, after 24-hour reperfusion. In a multi-hit model of PGD, "HS + BD + IRI" demonstrated increased lung injury, cellular infiltration, and activation of necroptotic and apoptotic pathways compared with IRI alone. Treatment with an inhibitor of receptor-interacting protein kinase 1 kinase, necrostatin-1, resulted in a significant decrease of downstream necroptotic pathway activation in both single- and multi-hit models of IRI. Thus, activation of necroptosis is a central event in IRI after prolonged CI, though it may not be sufficient to cause PGD alone. Pathological evaluation of donor lungs after CI-induced IRI, in conjunction with pre-engraftment donor lung factors in our multi-hit model, demonstrated early evidence of lung injury consistent with PGD. Our findings support the premise that pre-existing donor lung status is more important than CI time alone for inflammatory pathway activation in PGD, which may have important clinical implications for donor lung retrieval.

Tracheostomy insertion in COVID-19: insertion practice and factors leading to unplanned tube exchange.

Background: Tracheostomy insertion in patients with coronavirus disease 2019 (COVID-19) presents unique challenges. Patients frequently have high ventilatory requirements, and as an aerosol generating procedure, tracheostomy insertion creates the potential for staff transmission. Problems with tracheostomies contribute to morbidity and mortality, and tracheostomy changes may increase risks of staff transmission. We sought to quantify the incidence of clinically necessitated tracheostomy changes, establish the indications for change and investigate the incidence of staff transmission. Methods: We conducted a single institution, retrospective, observational cohort study of all intensive care unit (ICU) patients with COVID-19 who had a tracheostomy between March 2020 and April 2021. The institution is a large tertiary referral centre in Ireland. Results: Forty-three patients had a tracheostomy during the study period. All were a Shiley™ Flexible Adult Taperguard or Shiley™ XLT Tracheostomy. 14 patients (33%) required a tracheostomy change, with the majority (57%) involving a change from a standard size to an extended length tracheostomy. Persistent leak was the most common indication for change (71.6%). Other indications included patient-ventilator dyssynchrony, persistent cough and accidental decannulation. No staff transmission of COVID-19 occurred during this study. Conclusions: The incidence of tracheostomy change was 33%, highlighting the importance of selecting the right tracheostomy for each patient. We discuss how key characteristics of tracheostomies such as type, size, length and inner diameter may impact flow, resistance and work of breathing, leading to unplanned tracheostomy change. No staff transmission occurred arising from tracheostomy insertion, adding to increasing evidence that tracheostomy insertion in COVID-19 appears safe with adherence to guidelines describing the correct use of personal protective equipment.

Integrating hospital and community care: using a community virtual ward model to deliver combined specialist and generalist care to patients with severe chronic respiratory disease in their homes.

BACKGROUND: Chronic respiratory diseases are responsible for significant patient morbidity, mortality, and healthcare use. Community virtual ward (CVW) models of care have been successfully implemented to manage patients with complex medical conditions. AIMS: To explore the feasibility and clinical outcomes of a CVW model of care in patients with chronic respiratory disease. METHODS: Patients known to specialist respiratory services with Chronic Obstructive Pulmonary Disease (COPD) and/or asthma were admitted to the CVW for disease optimisation and exacerbation management. Individualised management plans were delivered in the patients' home by hospital-based respiratory and community nursing teams, incorporating remote technology to monitor vital signs. Symptoms and health status at admission and discharge were compared. RESULTS: Twenty patients were admitted. One-quarter of patients had asthma, 50% COPD, and 25% combined asthma/COPD. Patients had severe disease, mean (SD) FEV1 50(20) % predicted, and an average 6.4(5.7) exacerbations of disease in the previous 12 months. Patients received personalised disease and self-management education. All acute exacerbations (n = 11) were successfully treated in the community. The average length of CVW admission was 10(4) days. By discharge, 60% of COPD and 66% of asthma patients recorded improvements in symptoms score exceeding the minimal clinically important difference. Fifty percent had clinically meaningful improvements in health status. CONCLUSION: A CVW model facilitates the delivery of combined specialist and generalist care to patients with chronic respiratory disease in the community and improves symptoms and health status. The principles of the model are transferable to other conditions to improve overall health and reduce emergency hospital care.

Proteomic analysis of bronchoalveolar lavage fluid (BALF) from lung cancer patients using label-free mass spectrometry.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC). METHODS: Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC). Validation of candidate biomarkers identified in BALF was performed in a larger cohort of plasma samples by detection with enzyme-linked immunoassay. RESULTS: Four proteins (Cystatin-C, TIMP-1, Lipocalin-2 and HSP70/HSPA1A) were selected as a representative group from discovery phase mass spectrometry BALF analysis. Plasma levels of TIMP-1, Lipocalin-2 and Cystatin-C were found to be significantly elevated in AD and SqCC compared to control. CONCLUSION: The results presented in this study indicate that BALF is an important proximal biofluid for the discovery and identification of candidate lung cancer biomarkers. GENERAL SIGNIFICANCE: There is good correlation between the trend of protein abundance levels in BALF and that of plasma which validates this approach to develop a blood biomarker to aid lung cancer diagnosis, particularly in the era of lung cancer screening. The protein signatures identified also provide insight into the molecular mechanisms associated with lung malignancy.