Background: The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied. Methods: We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO. Findings: The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (P a O2/FiO 2 ) was 68 (54À92) in 293 enroled patients. Of these, 137/293 (47%) of patients [P a O2/FiO 2 76 (63À93)] were successfully weaned from HFNO. The median duration of HFNO was 6 (3À9) in those successfully treated versus 2 (1À5) days in those who failed (p<0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31À0.60), as was use of steroids (AHR 0.35, 95%CI 0.19À0.64). A ROX-6 score of 3.7 was 80% predictive of successful weaning whilst ROX-6 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%). Interpretation: In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation.

Background There is a paucity of knowledge about pulmonary hypertension (PH) in sub-Saharan Africa and an urgent need for its investigation in this context. The impact of HIV infection in PH is also unknown. Objectives To determine the aetiology, clinical presentation, severity and current management of PH at a tertiary-level hospital in Cape Town, South Africa (SA). Methods Demographic and clinical data, including from special investigations, were captured retrospectively for all patients referred to the Groote Schuur Hospital Pulmonary Hypertension Clinic between October 2015 and November 2017 (n=58) and entered into an online registry. Descriptive statistics were used to present the baseline data at enrolment. Results Patients were mainly young and female and almost half (48.3%) had severe symptoms according to World Health Organization classification. The main aetiologies were pulmonary arterial hypertension (PAH) and chronic thromboembolic PH. More than a fifth of the patients were HIV-positive, with nine patients presenting with HIV-associated PAH. The median time from initial presentation to referral to a specialist centre was 227 days (interquartile range: 72 - 625 days). Only a small number of patients were on PH-specific treatment at enrolment and a notable number never underwent right-heart catheterisation. Conclusion PH diagnosis is often delayed and even at a tertiary institution with a dedicated clinic and access to special investigations, PH is suboptimally investigated and managed. Expansion of this registry to better understand the phenotype of this disease in SA can improve outcomes for these patients through awareness, early identification and effective management.

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication associated with a high mortality. However, evidence and guidance on management is sparse. The aim of this international survey was to assess differences in prevention, diagnostic and treatment strategies for AE-IPF in specialised and non-specialised ILD centres worldwide.Material and Methods: Pulmonologists working in specialised and non-specialised ILD centres were invited to participate in a survey designed by an international expert panel. Responses were evaluated in respect to the physicians' institutions.Results: Three hundred and two (65%) of the respondents worked in a specialised ILD centre, 134 (29%) in a non-specialised pulmonology centre. Similarities were frequent with regards to diagnostic methods including radiology and screening for infection, treatment with corticosteroids, use of high-flow oxygen and non-invasive ventilation in critical ill patients and palliative strategies. However, differences were significant in terms of the use of KL-6 and pathogen testing in urine, treatments with cyclosporine and recombinant thrombomodulin, extracorporeal membrane oxygenation in critical ill patients as well as antacid medication and anaesthesia measures as preventive methods.Conclusion: Despite the absence of recommendations, approaches to the prevention, diagnosis and treatment of AE-IPF are comparable in specialised and non-specialised ILD centres, yet certain differences in the managements of AE-IPF exist. Clinical trials and guidelines are needed to improve patient care and prognosis in AE-IPF.

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Lung transplantation (LT) is a robust therapy for advanced lung disease, which offers recipients extended and good-quality survival. In South Africa (SA), patients have historically had limited access to this therapy, particularly if unfunded. LT has been used as a successful therapeutic intervention for a wide variety of end-stage pulmonary parenchymal and vascular diseases, but the most common diseases that lead to LT are chronic obstructive pulmonary disease, interstitial lung disease, cystic fibrosis, alpha-1-antitrypsin deficiency and pulmonary arterial hypertension. Timing of referral for LT can be challenging and is disease specific, influenced by the rate of progression of the disease, the development of associated comorbidities, and access and response to advanced therapies. Advances in recipient and donor selection, surgical technique and postoperative management have improved early survival, but mortality remains higher than for other solid organ transplants. Rejection and infection remain major causes of early posttransplant death, while chronic rejection is the major cause of death after the first year. Survival is heavily influenced by the underlying lung disease. In this review, we summarise the indications and contraindications for LT, remind pulmonologists of the availability of this therapy in SA and offer guidelines for the timely referral of suitable candidates.

Background Few studies detail the evolution of COVID-19 associated coagulopathy. We performed serial thromboelastography (TEG) and laboratory coagulation studies in 40 critically-ill, mechanically ventilated COVID-19 patients over a 14-day period and analysed differences between 30-day survivors and non-survivors. Methods Single-center prospective, observational study including 40 patients with severe COVID-19 pneumonia admitted to the intensive care unit (ICU) for mechanical ventilation. TEG analysis was performed on days 1, 7 and 14 of ICU admission and laboratory coagulation studies were performed on days 1 and 14. Coagulation variables were evaluated for change over the 14-day observation period. Differences between survivors and non-survivors at 30-days were analysed and compared. Results On admission, TEG maximum amplitude (MA) with heparinase correction was above the upper limit of the reference range in 32 (80%) patients while 33 (82.5%) presented with absent clot lysis at 30 min. The functional fibrinogen MA was also elevated above the upper limit of the reference range in 37 (92.5%) patients. All patients had elevated D-dimer and fibrinogen levels, mildly prolonged prothrombin times (PT), normal platelet counts and normal activated partial thromboplastin times (aPTT). The heparinase MA decreased significantly with time and normalised after 14 days (p = < 0.001) while the increased fibrin contribution to clot strength persisted with time (p = 0.113). No significant differences in TEG analysis were noted between 30-day survivors and non-survivors at all time points. No patients developed disseminated intravascular coagulopathy (DIC) after 14-days, however thrombosis and bleeding were each reported in 3 (7.5%) patients. Conclusion Critically-ill patients with COVID-19 present in a hypercoagulable state characterised by an increased clot strength. This state normalises after 14 days despite a persistently increased fibrin contribution to clot strength. We were unable to demonstrate any significant differences in TEG parameters between 30-day survivors and non-survivors at all time points.

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