Effects of Obstructive Sleep Apnea on Airway Immunity and Susceptibility to Respiratory Infections.

Obstructive sleep apnea is a prevalent sleep disorder characterized by recurrent episodes of partial or complete upper airway collapse during sleep, leading to disrupted breathing patterns and intermittent hypoxia. OSA results in systemic inflammation but also directly affects the upper and lower airways leading to upregulation of inflammatory pathways and alterations of the local microbiome. These changes result in increased susceptibility to respiratory infections such as influenza, COVID-19, and bacterial pneumonia. This relationship is more complex and bidirectional in individuals with chronic lung disease such as chronic obstructive lung disease, interstitial lung disease and bronchiectasis.

Ventilator Weaning in Prolonged Mechanical Ventilation-A Narrative Review.

Patients requiring mechanical ventilation (MV) beyond 21 days, usually referred to as prolonged MV, represent a unique group with significant medical needs and a generally poor prognosis. Research suggests that approximately 10% of all MV patients will need prolonged ventilatory care, and that number will continue to rise. Although we have extensive knowledge of MV in the acute care setting, less is known about care in the post-ICU setting. More than 50% of patients who were deemed unweanable in the ICU will be liberated from MV in the post-acute setting. Prolonged MV also presents a challenge in care for medically complex, elderly, socioeconomically disadvantaged and marginalized individuals, usually at the end of their life. Patients and their families often rely on ventilator weaning facilities and skilled nursing homes for the continuation of care, but home ventilation is becoming more common. The focus of this review is to discuss recent advances in the weaning strategies in prolonged MV, present their outcomes and provide insight into the complexity of care.

Mechanical Ventilator Liberation of Patients With COVID-19 in Long-term Acute Care Hospital.

BACKGROUND: Mechanical ventilation (MV) via tracheostomy is performed commonly for patients who are in long-term acute care hospitals (LTACHs) after respiratory failure. However, the outcome of MV in COVID-19-associated respiratory failure in LTACHs is not known. RESEARCH QUESTION: What is the ventilator liberation rate of patients who have received tracheostomy with COVID-19-associated respiratory failure compared with those with respiratory failure unrelated to COVID-19 in LTACHs? STUDY DESIGN AND METHODS: In this retrospective cohort study, we examined mechanically ventilated patients discharged between June 2020 and March 2021. Of 242 discharges, 165 patients who had undergone tracheostomy arrived and were considered for ventilator liberation. One hundred twenty-eight patients did not have COVID-19 and 37 patients were admitted for COVID-19. RESULTS: The primary outcome of the study was ventilator liberation; secondary outcomes were functional recovery, length of stay (LOS) at the LTACH, and discharge disposition. After controlling for demographics, the number of comorbidities, hemodialysis, vasopressor need, thrombocytopenia, and the LOS at the short-term acute care hospital, our results indicated that patients with COVID-19 showed a higher adjusted ventilator liberation rate of 91.4% vs 56.0% in those without COVID-19. Functional ability was assessed with the change of Functional Status Score for the Intensive Care Unit (FSS-ICU) between admission and discharge. The adjusted mean change in FSS-ICU was significantly higher in the COVID-19 group than in the non-COVID-19 group: 9.49 (95% CI, 7.38-11.6) vs 2.08 (95% CI, 1.05-3.11), respectively (P < .001). Patients with COVID-19 experienced a shorter adjusted LOS at the LTACH with an adjusted hazard ratio of 1.57 (95% CI, 1.0-2.46; P = .05) compared with patients without COVID-19. We did not observe significant differences between the two groups regarding discharge location, but a trend toward need for lower level of care was found in patients with COVID-19. INTERPRETATION: Our study suggests that patients with COVID-19 requiring MV and tracheostomy have a higher chance for recovery than those without COVID-19.

Quantitative image analysis in COVID-19 acute respiratory distress syndrome: a cohort observational study.

Background Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury commonly associated with pneumonia, including coronavirus disease-19 (COVID-19). The resultant effect can be persistent lung damage, but its extent is not known. We used quantitative high resolution computed tomography (QHR-CT) lung scans to radiographically characterize the lung damage in COVID-19 ARDS (CARDS) survivors. Methods Patients with CARDS (N=20) underwent QHR-CT lung scans 60 to 90 days after initial diagnosis, while hospitalized at a long-term acute care hospital (LTACH). QHR-CT assessed for mixed disease (QMD), ground glass opacities (QGGO), consolidation (QCON) and normal lung tissue (QNL). QMD was correlated with respiratory support on admission, tracheostomy decannulation and supplementary oxygen need on discharge. Results Sixteen patients arrived with tracheostomy requiring invasive mechanical ventilation. Four patients arrived on nasal oxygen support. Of the patients included in this study 10 had the tracheostomy cannula removed, four remained on invasive ventilation, and two died. QHR-CT showed 45% QMD, 28.1% QGGO, 3.0% QCON and QNL=23.9%. Patients with mandatory mechanical ventilation had the highest proportion of QMD when compared to no mechanical ventilation. There was no correlation between QMD and tracheostomy decannulation or need for supplementary oxygen at discharge. Conclusions Our data shows severe ongoing lung injury in patients with CARDS, beyond what is usually expected in ARDS. In this severely ill population, the extent of mixed disease correlates with mechanical ventilation, signaling formation of interstitial lung disease. QHR-CT analysis can be useful in the post-acute setting to evaluate for interstitial changes in ARDS.

Post-COVID recovery: characteristics of chronically critically ill patients admitted to a long-term acute care hospital.

Background: Survivors of COVID-19 pneumonia often suffer from chronic critical illness (CCI) and require long-term hospitalization. Long-term acute care (LTAC) hospitals are vital in the care of CCI patients, but their role for patients post COVID-19 infection is not known. Barlow Respiratory Hospital (BRH) is a 105-bed, LTAC hospital network serving ventilator-dependent and medically-complex patients transferred from the ICUs of hospitals in southern California. We report patient characteristics of our first series of COVID-19 survivors admitted to the post-acute venue of an LTAC hospital. Methods: Single-center observational descriptive report of patients recovering from acute infectious complications of COVID-19 pneumonia requiring long-term respiratory support. Results: From 28 April to 7 September 2020, 41 patients were admitted to BRH for continued recovery from COVID-19 pneumonia. Median age: 68 [44-94] years, 25/41 (61%) male, 33/41 (80.5%) with tracheostomy, 21/41 (51.2%) on invasive mechanical ventilation, 9/41 (22%) receiving hemodialysis. All mechanical ventilation and hemodialysis interventions were initiated at the transferring hospital. Conclusions: To our knowledge, this is the first report to characterize CCI and medically complex COVID-19 patients transferred to the post-acute venue of an LTAC hospital. Patients on average spent over six weeks in the transferring hospital mostly in the ICU, are largely elderly, carry the known risk factors for COVID-19 infection, and experienced respiratory failure necessitating prolonged mechanical ventilation via tracheostomy. Our findings suggest that these patients will continue to require considerable medical interventions and treatments, including weaning from mechanical ventilation, owing to the numerous sequelae of the infection and the burden of acute-on-chronic diseases. As ICU survival rates improve, this research further emphasizes the important role of the LTAC hospital in responding to the COVID-19 crisis.

Clodronate liposomes improve metabolic profile and reduce visceral adipose macrophage content in diet-induced obese mice.

BACKGROUND: Obesity-related adipose inflammation has been thought to be a causal factor for the development of insulin resistance and type 2 diabetes. Infiltrated macrophages in adipose tissue of obese animals and humans are an important source for inflammatory cytokines. Clodronate liposomes can ablate macrophages by inducing apoptosis. In this study, we aim to determine whether peritoneal injection of clodronate liposomes has any beneficial effect on systemic glucose homeostasis/insulin sensitivity and whether macrophage content in visceral adipose tissue will be reduced in diet-induced obese (DIO) mice. METHODOLOGY/PRINCIPAL FINDINGS: Clodronate liposomes were used to deplete macrophages in lean and DIO mice. Macrophage content in visceral adipose tissue, metabolic parameters, glucose and insulin tolerance, adipose and liver histology, adipokine and cytokine production were examined. Hyperinsulinemic-euglycemic clamp study was also performed to assess systemic insulin sensitivity. Peritoneal injection of clodronate liposomes significantly reduced blood glucose and insulin levels in DIO mice. Systemic glucose tolerance and insulin sensitivity were mildly improved in both lean and DIO mice treated with clodronate liposomes by intraperitoneal (i.p.) injection. Hepatosteatosis was dramatically alleviated and suppression of hepatic glucose output was markedly increased in DIO mice treated with clodronate liposomes. Macrophage content in visceral adipose tissue of DIO mice was effectively decreased without affecting subcutaneous adipose tissue. Interestingly, levels of insulin sensitizing hormone adiponectin, including the high molecular weight form, were significantly elevated in circulation. CONCLUSIONS/SIGNIFICANCE: Intraperitoneal injection of clodronate liposomes reduces visceral adipose tissue macrophages, improves systemic glucose homeostasis and insulin sensitivity in DIO mice, which can be partially attributable to increased adiponectin levels.