A 61-year-old previously healthy man presented to hospital with acute type 1 respiratory failure after five days of coryzal symptoms and a positive coronavirus disease 2019 (COVID-19) rapid antigen test. Within 24 hours, the patient became progressively hypoxic, was rapidly intubated and transferred to Alfred Health in December 2022, a tier one Victorian extracorporeal membrane oxygenation (ECMO) service site, for veno-venous ECMO (Avalon Elite bi-caval dual lumen catheter). The patient was born in Chile and migrated to Australia at 5 years of age. His medical history was significant for mild asthma. The patient was a distant ex-smoker with a less than five pack-year smoking history. At the time of admission, he had received three COVID-19 vaccines (Comirnaty Original; Pfizer–BioNTech). The patient was treated with broad-spectrum antibiotics, antifungals and COVID-19-specific therapies, including baricitinib, remdesivir and dexamethasone. Initial COVID polymerase chain reaction (PCR) analysis identified the Omicron variant with a cycle threshold value of 29.8. In accordance with hospital guidelines, the patient was cleared of isolation precautions on Day 20 with a cycle threshold value of 30.7. Multiple complications occurred during hospitalisation, including deep venous thrombosis, ventilator-associated pneumonia, Pseudomonas aeruginosa bacteraemia, pancreatitis, cytomegalovirus viraemia and localised herpes simplex virus type 1 infection. A failed attempt at de-cannulation occurred two months after presentation, where the patient required re-cannulation within 48 hours due to respiratory distress. The patient remained awake on ECMO and participated in treatment decision discussions and rehabilitation. Lung transplantation assessment and waitlisting occurred four months after the patient started ECMO. Transplantation was delayed due to human leukocyte antigen (HLA) sensitisation following multiple platelet transfusions for bleeding after endoscopic retrograde cholangiopancreatography for investigation of pancreatitis. An HLA single antigen bead Luminex test was positive for 53 Class I HLA antibodies with a peak mean fluorescence intensity of 24 000. After three months, the test was repeated and results had improved to 33 Class I HLA antibodies with a peak mean fluorescence intensity of 15 072. Due to the patient's Chilean heritage, he was tested for Chagas disease (nucleic acid test) and returned a positive result. However, the result was negative on blood smear, indicating a chronic-phase infection. A computed tomography scan was performed at this point and showed evidence of COVID-related pulmonary fibrosis (Box, A). The patient underwent bilateral sequential lung transplantation in June 2023, six months after admission. ECMO de-cannulation occurred the day after transplantation. He was discharged home 20 days post-transplantation with no oxygen requirement. At follow-up six months post-transplantation, the patient was functionally independent with clear lung fields on imaging (Box, B) and normal spirometry. Given the risk of reactivation of Chagas disease post-transplantation, monitoring with clinical and blood film surveillance was performed up until 100 weeks post-transplant. As of November 2024, there has not been reactivation of Chagas disease or allograft dysfunction and the patient continues a routine post-transplant immunosuppression regimen of prednisolone, tacrolimus and mycophenolate. This is the first reported case of lung transplantation as curative treatment for irreversible COVID-19 lung injury in Australia. Although lung transplantation for COVID-19 has been increasingly practised internationally, this indication is not well established in Australia.1, 2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections continue to result in patients requiring prolonged ventilation for acute respiratory distress syndrome (ARDS) and pulmonary fibrosis.3 In addition to the International Society for Heart and Lung Transplantation 2021 consensus document for the selection of lung transplant candidates,4 an international case series suggested that potential lung transplant candidates with COVID-19 ARDS require two negative COVID-19 PCR results at least 24 hours apart and at least four to six weeks with no signs of recovery despite optimal medical therapy.5 Recovery was defined by improvement in lung compliance, radiography and gas exchange. As seen in the patient (Box, A), post-acute COVID-19 pneumonia can progress to fibrotic lung disease with traction bronchiectasis, interlobular septal thickening, and ground glass with reticulation.6 Short term outcomes of COVID-19 lung transplantation appear promising. Studies have found that lung transplantation for COVID-19 has acceptable one-year outcomes and no significant difference in survival outcomes compared with non-COVID-19 lung transplantation.7, 8 These studies also showed that ECMO treatment pre-transplant resulted in adequate functional status. As experienced with the patient, ECMO may reduce sedation to allow engagement in discussions and participation in physiotherapy to reduce risk of critical illness myopathy.9 Pre-transplant allo-sensitisation creates a barrier to transplant candidacy by limiting available donors.10 Highly sensitised lung transplant candidates are often declined due to increased risk of graft rejection and reduced survival after transplantation.11 Use of erythropoietin and iron supplementation can help moderate blood loss and anaemia without increasing the risk of sensitisation.12 This article demonstrates lung transplantation as a life-saving therapy for irreversible COVID-19 lung injury requiring prolonged ECMO. Further evidence is required to determine long term survival outcomes and best practice principles for lung transplantation in COVID-19 related respiratory failure in Australia. The patient provided written consent for publication. No relevant disclosures. Not commissioned; externally peer reviewed.

BACKGROUND:Transbronchial lung cryobiopsy (TBLC) is an alternative to surgical lung biopsy for histopathological evaluation of unclassifiable interstitial lung disease (ILD) or ILD diagnosed with low confidence. This meta-analysis synthesised current literature regarding cryobiopsy diagnostic performance and safety, focusing on procedural and sampling techniques. METHODS:Medline and Embase were searched on 11 April 2022. Studies included adults with unclassifiable ILD, reporting diagnostic yield, complications and methodological techniques of TBLC. Meta-analyses were performed for diagnostic yield, pneumothorax and bleeding. Subgroup analyses and meta-regression assessed methodological variables. PROSPERO registration: CRD42022312386. RESULTS:70 studies were included with 6183 participants. Diagnostic yield of TBLC was 81% (95% CI 79-83%, I2=97%), with better yield being observed with general anaesthesia (p=0.007), ILD multidisciplinary meeting prior to cryobiopsy (p=0.02), 2.4 mm cryoprobe (p=0.04), higher mean forced vital capacity (p=0.046) and higher mean diffusing capacity for carbon monoxide (p=0.023). Pneumothorax rate was 5% (95% CI 4-5%, I2=91%), with higher rates associated with a 2.4 mm cryoprobe (p<0.00001), routine post-procedure imaging (p<0.00001), multiple lobe sampling (p<0.0001), reduced mean diffusing capacity for carbon monoxide (p=0.028) and general anaesthesia (p=0.05). Moderate-to-severe bleeding rate was 12% (11-14%, I2=95%) and higher rates were associated with a 2.4 mm cryoprobe (p=0.001) and bleeding score selection (p=0.04). INTERPRETATION:Patient characteristics and modifiable factors, including procedural methods and anaesthetic techniques, impacted diagnostic yield and safety outcomes of TBLC in people with unclassifiable ILD and contributed to heterogeneity of clinical outcomes. These variables should be considered for individualised clinical decision making and guideline development and warrant routine reporting in future research.

Pulmonary arterial hypertension (PAH) is a rare condition for which a remarkable change has been witnessed in the epidemiology, assessment and treatment landscape over the last three decades. Well-established registries from the Western world have not only highlighted the shift in the epidemiology to an older, more comorbid cohort but have also identified markers of prognosis that have been validated as part of risk stratification scores in multiple cohorts. The emphasis on early identification through a systematic assessment pathway and the option of upfront combination therapy with serial risk stratification assessment has laid the foundation for the standard of care and improved prognosis. This review provides an update on the assessment and newer therapies for PAH.

Chronic eosinophilic pneumonia (CEP) is a rare, idiopathic interstitial lung disease characterised by the accumulation of eosinophils in the pulmonary interstitia and alveoli. Patients with CEP respond well to systemic corticosteroid therapy and infrequently progress to end-stage lung disease. We report a case of a woman in her 40s with previously stable, steroid-responsive CEP who experienced a critical deterioration of her CEP at 25 weeks of gestation during her third pregnancy. The patient was admitted to the intensive care unit due to respiratory failure requiring intubation and mechanical ventilation. Follow-up investigation revealed advanced fibrotic lung disease requiring long-term oxygen therapy and referral for double lung transplantation. While CEP infrequently advances to permanent parenchymal damage, this case demonstrates the potential for severe exacerbations in the setting of pregnancy and highlights pregnancy as a potential risk factor for disease progression, reinforcing the need for further research to define optimal monitoring and treatment strategies.

Interstitial lung disease is fast becoming one of the most common indications for lung transplantation (LTx); however, LTx for Goodpasture's syndrome with pulmonary involvement has not been previously described in the literature. In this report, we outline the case of a young male with undifferentiated rapidly progressive interstitial lung disease who ultimately received a bilateral sequential LTx after deterioration requiring extracorporeal membrane oxygenation. The original disease soon recurred in the graft, and unfortunately, the patient did not survive. The diagnosis of Goodpasture's syndrome was made postmortem and was not clearly evident on examination of the native explanted tissue, nor was there an elevated titer of antiglomerular basement membrane antibodies during his initial work-up. We hypothesize that the donor and recipient's HLA profile made him more susceptible to aggressive disease. In hindsight, active Goodpasture's disease would have been a contraindication to proceed to transplantation. This case is a cautionary reminder of the high stakes of performing LTx without a certain diagnosis.

With the continuation of the COVID-19 pandemic, focus has been on vaccination rates and pharmacological treatment options. We believe it is important to highlight a commonly forgotten aspect of health – sleep disturbance, its relationship on the immune system and the impact on outcomes in COVID-19. Dysfunctional sleep impacts immunity and increases the risk of poorer outcomes from respiratory infections. In addition, an increased incidence of cardiovascular diseases, such as coronary artery disease, hypertension, arrythmias and obesity, are observed with deprived sleep. These studies suggest the lowest morbidity and mortality generally occurred among patients achieving 7–8 h of sleep per night. Consequently, in COVID-19-positive patients, poor sleep behaviour burden, including insomnia, daytime sleepiness and late chronotype was associated with needing hospitalisation and greater mortality. Sleep apnoea has also been identified as another risk factor for COVID-19-related death. Overall poor outcomes from sleep disturbances and sleep-related conditions are now evident and perhaps accentuated by COVID-19. The possible explanation for this lies in the evidence of bidirectional interaction between sleep and the immune system. Sleep is part of a hormonal milieu that supports immune function, and any disturbance of this equilibrium promotes a chronic inflammatory state. Normal sleep promotes immunity and Th1 response. Slow wave sleep downregulates hypothalamic–pituitary–adrenal axis and sympathetic nervous system to reduce cortisol, adrenaline and noradrenaline, while simultaneously raising substances promoting cell activation, growth and differentiation. The peak differentiation of immune cells in lymph nodes and peripheral blood peaks occurs during sleep. Following sleep deprivation, elevated levels of pro-inflammatory cytokines and activation signals are observed. The Th2 pathway is favoured over the Th1, which leads to an increase infection risk and alteration in vaccination response. Robertson and Goldin recently stressed the potential detrimental effects of sleep on vaccine efficacy, particularly in a time where vaccination rates are the cornerstone of public healthcare. Alternatively, in response to infection or stress, the body has an increased drive to sleep to counteract pathology and enhance removal of neurotoxic waste products. Certainly, prior to the pandemic, multiple institutional factors were present to affect sleep in both intensive care and hospital ward settings. One of the most common contributing factors to sleep disturbance is noise from alarms, staff interactions and patient care interventions. The lack of natural light in negatively ventilated rooms abolishes the physiological regulation of melatonin secretion critical for the TH1 response. Further COVID-19-specific management therapies exist to aggravate this issue. Pronation is a technique encouraged to improve oxygenation and reduce intubation. However, prone is the least common body position during sleep and healthy controls change sleeping positions up to 40 times per night. Last, dexamethasone, a potent glucocorticoid that is prescribed for up to 10 days to reduce mortality, commonly leads to steroid-induced sleep disruption. All these facets of COVID19 care ultimately lead to the immune dysregulation from metabolic consequences of disrupted sleep. Unfortunately, the problem of sleep and COVID-19 exists outside of inpatient care. Following hospital discharge, critically ill patients experience sleep disturbance for up to 12 months. Public health measures of repeated lockdown and travel restrictions have led to a negative impact on mental health. Psychosocial distress, anxiety and depression have been associated with sleep disturbances and contributed to the high prevalence of sleep problems observed during the pandemic at 40%. During the COVID-19 pandemic, when sleep is arguably needed the most, the chance of a good night’s rest is not favourable. Hospital systems have been presented the opportunity to promote sleep health through the implementation of quiet time. Interventions such as noise and light reduction strategies and minimising interaction might lead to the improvement of sleep quality and physiological parameters. Evaluating the impact of such changes could lead to a better understanding of the influence of sleep on COVID-19 and immunity.

Patients with idiopathic pulmonary fibrosis (IPF) have reduced levels of daily physical activity (DPA); however, little is known about how DPA changes as disease progresses. We aimed to (i) describe change in DPA over 12 months, (ii) analyse its association with conventional markers of disease severity and quality of life and (iii) assess DPA as a prognostic tool.

BackgroundPhysical inactivity is associated with poor outcomes in patients with many chronic lung diseases, however little is known about physical activity in patients with idiopathic pulmonary fibrosis (IPF). Our aim was to describe daily physical activity (DPA) in patients with a confirmed diagnosis of IPF and analyse its associations with traditional markers of disease severity and quality of life.MethodsFifty-nine patients with IPF had DPA parameters and sedentary time assessed with the Sensewear armband for seven consecutive days. Participants completed the Hospital Anxiety and Depression scale (HADS), St Georges Respiratory Questionnaire (SGRQ) and Leicester Cough Questionnaire (LCQ). Data on current markers of disease severity; forced vital capacity (FVC), carbon monoxide diffusion capacity (DLCO) and 6-minute walk test (6MWT) as well as prognostic markers; composite physiologic index (CPI) and gender age and physiology (GAP) was collected.ResultsPatients had a median daily step count of 3957 (300–7614), mean daily moderate to vigorous (MV) physical activity duration of 8.6 minutes (-13.1 to 30.3) and mean total daily sedentary time of 1234.6 minutes (± 122.8). Patients with early stages of IPF according to GAP stage had significantly higher daily step count than those with more severe disease (p < 0.003). Age, BMI and DLCO accounted for 54% variability in physical activity duration. The 6-minute walk distance and DLCO accounted for 44% variability in daily step count. Patient reported outcomes had weak association with daily step count and MV physical activity duration.ConclusionIn IPF, increasing disease severity is associated with reduced DPA. DPA may be a meaningful outcome for future trials of therapies designed to enhance patient functioning and wellbeing.Trial Registration: please note that a request has been made for retrospective registration with the Australian New Zealand Clinical Trial Registry with the request number being 381161. Due to holiday period closure, this is yet to be processed. I will supply this as soon as accepted.

Introduction Interstitial lung diseases are characterised by scarring of lung tissue that leads to reduced transfer of oxygen into the blood, decreased exercise capacity and premature death. Ambulatory oxygen therapy may be used to treat exertional oxyhaemoglobin desaturation, but there is little evidence to support its efficacy and there is wide variation in clinical practice. This study aims to compare the clinical efficacy and cost-effectiveness of ambulatory oxygen versus ambulatory air in people with fibrotic interstitial lung disease and exertional desaturation.Methods and analysis A randomised, controlled trial with blinding of participants, clinicians and researchers will be conducted at trial sites in Australia and Sweden. Eligible participants will be randomised 1:1 into two groups. Intervention participants will receive ambulatory oxygen therapy using a portable oxygen concentrator (POC) during daily activities and control participants will use an identical POC modified to deliver air. Outcomes will be assessed at baseline, 3 months and 6 months. The primary outcome is change in physical activity measured by number of steps per day using a physical activity monitor (StepWatch). Secondary outcomes are functional capacity (6-minute walk distance), health-related quality of life (St George Respiratory Questionnaire, EQ-5D-5L and King’s Brief Interstitial Lung Disease Questionnaire), breathlessness (Dyspnoea-12), fatigue (Fatigue Severity Scale), anxiety and depression (Hospital Anxiety and Depression Scale), physical activity level (GENEActive), oxygen saturation in daily life, POC usage, and plasma markers of skeletal muscle metabolism, systematic inflammation and oxidative stress. A cost-effectiveness evaluation will also be undertaken.Ethics and dissemination Ethical approval has been granted in Australia by Alfred Hospital Human Research Ethics Committee (HREC/18/Alfred/42) with governance approval at all Australian sites, and in Sweden (Lund Dnr: 2019-02963). The results will be published in peer-reviewed scientific journals, presented at conferences and disseminated to consumers in publications for lay audiences.Trial registration number ClinicalTrials.gov Registry (NCT03737409).

Sleep disordered breathing (SDB) in heart failure (HF) is a common co-morbidity with an estimated prevalence of 50%. The high prevalence of mood disorders (anxiety and depression) in individuals with obstructive sleep apnoea (OSA) is well described. Little is known about the prevalence of mood disorders in central sleep apnoea (CSA). Aim: In patients with HF who had a polysomnography, our aim was to, (i) characterise the prevalence of SDB (OSA vs CSA) & (ii) assess anxiety & depression scores (14 question Hospital Anxiety and Depression Scale (HADS)) with a significant HADS A & D score of 8 & 11 respectively. Method: A retrospective record analysis of patients coded with a diagnosis of heart failure who underwent a polysomnography & transthoracic echocardiogram at a tertiary hospital between 2013-2019 were included. Results: 200 patients (68% males, median age 58 years) were included. 49% of patients had at least moderate OSA (AHI >15) & 5% had moderate CSA (AHI > 15). 24% of patients with OSA (AHI > 15) had an elevated HADS D score, however this was not statistically significant when compared to CSA (AHI >15) p=0.88. Similarly, 11% of patients reported a high HADS A score in the OSA group however was not significant compared to CSA (p=0.33). There was a trend towards higher HADS D scores for patients with SDB vs no SDB, however this was not statistically significant (25% vs 14%). Conclusion: HF patients with SDB report higher HADS D scores & lower HADS A scores compared to patients with no SDB. There was no significant difference in depression or anxiety scores between OSA & CSA patients. Further studies are needed to understand the strong interplay of mood disorders with HF & SDB.

Background: Bronchoscopic transbronchial cryobiopsy is increasingly used for the histological assessment of diffuse parenchymal lung disease. Diagnostic performance may be improved by more accurate targeting of biopsy to radiologic abnormalities, and complication rates may be reduced by avoiding biopsy of pleura or larger vessels. Objectives: To report the preliminary experience of using CT-fluoroscopic guidance for accurate targeting of bronchoscopic transbronchial cryobiopsy. Methods: Bronchoscopic cryobiopsy was performed in a hybrid CT theatre. 3D CT images were acquired following positioning of the cryoprobe in a distal airway segment. Where cryoprobe position was observed to be too close to the chest wall/diaphragm pleura, or not within the region of interest within the lung parenchyma, re-positioning of probe was undertaken and repeat 3D images were acquired to confirm positioning prior to cryobiopsy. Results: CT-fluoroscopic transbronchial cryobiopsy was successfully performed in 4 patients: 3 patients with interstitial lung infiltrates, and one with an enlarging left upper lobe mass. Images were reviewed following each acquisition to accurately assess the probe position within the lung parenchyma, and relative to other thoracic structures. Intra-procedural imaging was of sufficient quality to allow the accurate positioning of the cryoprobe tip with respect to both the parenchymal region of interest and pleural surfaces. No complications were experienced, and all procedures yielded diagnostic specimens. Conclusions: Our preliminary experience confirms the feasibility of performing transbronchial cryobiopsy under CT-fluoroscopic guidance. Accurate targeting of transbronchial cryobiopsy may be achieved using CT-fluoroscopic guidance. Positioning of the probe tip, both with respect to parenchymal region of interest and to pleural surfaces, can be established with high accuracy.

Interstitial lung diseases (ILD) are a diverse group of pulmonary diseases for which accurate diagnosis is critical for optimal treatment outcomes. Diagnosis of ILD can be challenging and a multidisciplinary approach is recommended in international guidelines. The purpose of this position paper is to review the evidence for the use of the multidisciplinary meeting (MDM) in ILD and suggest an approach to its governance and constitution, in an attempt to provide a standard methodology that could be applied across Australia and New Zealand. This position paper is endorsed by the Thoracic Society of Australia and New Zealand (TSANZ) and the Lung Foundation Australia (LFA).

INTRODUCTION:Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with debilitating symptoms of dyspnoea and cough, resulting in respiratory failure, impaired quality of life and ultimately death. Diagnosing IPF can be challenging, as it often shares many features with other interstitial lung diseases. In this article, we summarise recent joint position statements on the diagnosis and management of IPF from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia, specifically tailored for physicians across Australia and New Zealand. Main suggestions: A comprehensive multidisciplinary team meeting is suggested to establish a prompt and precise IPF diagnosis. Antifibrotic therapies should be considered to slow disease progression. However, enthusiasm should be tempered by the lack of evidence in many IPF subgroups, particularly the broader disease severity spectrum. Non-pharmacological interventions including pulmonary rehabilitation, supplemental oxygen, appropriate treatment of comorbidities and disease-related symptoms remain crucial to optimal management. Despite recent advances, IPF remains a fatal disease and suitable patients should be referred for lung transplantation assessment.

Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.