An Australian COVID-19 respiratory care unit experience.

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a heterogeneous presentation ranging from severe pneumonitis to asymptomatic infection. International studies have demonstrated the utility of respiratory care units (RCUs) to facilitate the delivery of non-invasive ventilation techniques to patients with COVID-19 pneumonitis. AIMS: This study aims to describe the patient characteristics, flow and outcomes of admissions to the Royal Melbourne Hospital (RMH) COVID-19 RCU (CRCU) during its initial period of operation. METHODS: Single-centre retrospective cohort study, all patients admitted to CRCU between 17 September and 10 December 2021 were included in this study. Patient demographics, including comorbidities and limitations of medical treatment, were analysed. Admission source and discharge destination were reviewed. Length of stay was recorded. Finally, in-hospital and CRCU mortality were analysed. RESULTS: Ninety-seven patients, comprising 111 admissions, occurred during the study period with median age of 65 years (48% female). Most patients were admitted from and discharged to the ward. Twenty patients died in hospital (21%), with age, 4C score, comorbidity and presence of obstructive lung disease predicting mortality (area under the curve (AUC) 0.85, P < 0.001). Mortality was significantly higher in those over 65 years of age compared to those under 65 (P < 0.001), or those deemed not for intubation compared to those for intubation (P = 0.0019). CONCLUSIONS: This study demonstrates the feasibility of operating a CRCU within an Australian tertiary healthcare setting.

Bullous lung disease due to marijuana.

BACKGROUND AND OBJECTIVE: In contrast to the well-described effects of tobacco smoking upon pulmonary emphysema, with approximately 15% of smokers being affected at the age of 65 years, the effects of marijuana smoking are rarely reported and poorly understood. METHODS: We report a series of 10 patients (mean age 41 +/- 9 years, eight male, two female), who presented over a period of 12 months to our respiratory unit with new respiratory symptoms, and who admitted to regular chronic marijuana smoking (>1 year continuously). Symptoms on presentation were dyspnoea (n = 4), pneumothorax (n = 4) and chest infection (n = 2). RESULTS: High-resolution CT revealed asymmetrical, variably sized, emphysematous bullae in the upper and mid zones. However, the CXR was normal in four patients and lung function was normal in five. CONCLUSIONS: Marijuana smoking leads to asymmetrical bullous disease, often in the setting of normal CXR and lung function. In subjects who smoke marijuana, these pathological changes occur at a younger age (approximately 20 years earlier) than in tobacco smokers.

The importance of the airway microvasculature in asthma.

PURPOSE OF REVIEW: The microvasculature in asthma has been known to contribute to airway-wall thickening and oedema from early post-mortem series. Current concepts of airway inflammation in asthma highlight the importance of the role of the Th2 lymphocyte in the atopic response to aeroallergens, the importance of mast-cell mediators in airway remodelling, potential actions of the vascular response in determining airway thickness and mechanisms of angiogenesis involving endogenous as well as homing progenitor cells with angioblastic potential. RECENT FINDINGS: The development of animal models of asthmatic airway inflammation and remodelling have given new insight into mechanisms of angiogenesis in asthma. The central role of vascular endothelial growth factor in angiogenesis, vessel leakage and vascular homeostasis is now recognized. A more recent finding is the influence of this factor in enhancing the Th2 response in airway inflammation. The ability of bone marrow-derived angioblasts to migrate to sites of inflammation and contribute to angiogenesis indicates a pivotal role of stem cells in this process. SUMMARY: These findings now provide logical links between the inflammatory response, stem-cell mobilization, angiogenesis and airflow obstruction in the remodelled airway of asthma. Future studies examining airway-wall thickness will be able to account for the contribution of the vasculature and airway-wall oedema. Therapies aimed at vascular mechanisms may be useful adjuncts to current treatments and the recognition of stem cells as key players in airway remodelling may provide strategies to reduce fixed airflow obstruction in severe disease.

Loss of PKR activity in chronic lymphocytic leukemia.

There are a number of observations that suggest the dsRNA-activated protein kinase, PKR, may play an active role in formation and maintenance of leukemia, including nonrandom chromosomal deletions in acute leukemia as well as truncations and deletions of the PKR gene in some leukemia cell lines. However, there is little direct evidence from patient material that this is so. Here we show that full-length PKR is present but not active in 21 of 28 patient samples from B-cell chronic lymphocytic leukemia (B-CLL). PKR from these patients was unable to auto-activate or phosphorylate substrates but was able to bind dsRNA. Furthermore, the lack of PKR activation was not due to differing levels of the PKR activator, PACT nor of the PKR inhibitor, p58(IPK). We compared PKR status with clinical parameters and disease staging. No differences were found between the 2 groups in terms of staging (modified Rai or Binet), age, CD38 status, p53 status, 11q23 deletion status or CEP12 deletion status. However, there was a significant correlation between deletion in 13q14.3 and lack of PKR activity. We show that B-CLL cells appear to contain a soluble inhibitor of PKR, as lysates from cells lacking PKR activity were able to inhibit exogenous PKR in mixing experiments. Finally, we show suppression of PKR activity was still present following ultrafilitration through a 10,000 Da cutoff filter but was lost upon extraction with phenol/chloroform or by high salt washing. This data suggests loss of PKR activity may contribute to the formation and/or maintenance of CLL.