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BACKGROUND: High-flow nasal oxygen therapy (HFNO) is used in diverse hospital settings to treat patients with acute respiratory failure (ARF). This systematic review aims to summarise the evidence regarding any benefits HFNO therapy has compared with conventional oxygen therapy (COT) for patients with ARF. METHODS: Three databases (Embase, Medline and CENTRAL) were searched on 22 March 2023 for studies evaluating HFNO compared with COT for the treatment of ARF, with the primary outcome being hospital mortality and secondary outcomes including (but not limited to) escalation to invasive mechanical ventilation (IMV) or non-invasive ventilation (NIV). Risk of bias was assessed using the Cochrane risk-of-bias tool (randomised controlled trials (RCTs)), ROBINS-I (non-randomised trials) or Newcastle-Ottawa Scale (observational studies). RCTs and observational studies were pooled together for primary analyses, and secondary analyses used RCT data only. Treatment effects were pooled using the random effects model. RESULTS: 63 studies (26 RCTs, 13 cross-over and 24 observational studies) were included, with 10 230 participants. There was no significant difference in the primary outcome of hospital mortality (risk ratio, RR 1.08, 95% CI 0.93 to 1.26; p=0.29; 17 studies, n=5887) between HFNO and COT for all causes ARF. However, compared with COT, HFNO significantly reduced the overall need for escalation to IMV (RR 0.85, 95% CI 0.76 to 0.95 p=0.003; 39 studies, n=8932); and overall need for escalation to NIV (RR 0.70, 95% CI 0.50 to 0.98; p=0.04; 16 studies, n=3076). In subgroup analyses, when considering patients by illness types, those with acute-on-chronic respiratory failure who received HFNO compared with COT had a significant reduction in-hospital mortality (RR 0.58, 95% CI 0.37 to 0.91; p=0.02). DISCUSSION: HFNO was superior to COT in reducing the need for escalation to both IMV and NIV but had no impact on the primary outcome of hospital mortality. These findings suppo

This Thoracic Society of Australia and New Zealand Guideline on the provision of home oxygen therapy in adults updates a previous Guideline from 2015. The Guideline is based upon a systematic review and meta-analysis of literature to September 2022 and the strength of recommendations is based on GRADE methodology. Long-term oxygen therapy (LTOT) is recommended for its mortality benefit for patients with COPD and other chronic respiratory diseases who have consistent evidence of significant hypoxaemia at rest (PaO2 ≤ 55 mm Hg or PaO2 ≤59 mm Hg in the presence of hypoxaemic sequalae) while in a stable state. Evidence does not support the use of LTOT for patients with COPD who have moderate hypoxaemia or isolated nocturnal hypoxaemia. In the absence of hypoxaemia, there is no evidence that oxygen provides greater palliation of breathlessness than air. Evidence does not support the use of supplemental oxygen therapy during pulmonary rehabilitation in those with COPD and exertional desaturation but normal resting arterial blood gases. Both positive and negative effects of LTOT have been described, including on quality of life. Education about how and when to use oxygen therapy in order to maximize its benefits, including the use of different delivery devices, expectations and limitations of therapy and information about hazards and risks associated with its use are key when embarking upon this treatment.

BACKGROUND AND OBJECTIVE: Inhalation of high concentrations of respirable crystalline silica (RCS) can lead to silicosis. RCS contains varying levels of iron, which can cause oxidative stress and stimulate ferritin production. This study evaluated iron-related and inflammatory markers in control and silicosis patients. METHODS: A cohort of stone benchtop industry workers (n = 18) were radiologically classified by disease severity into simple or complicated silicosis. Peripheral blood and bronchoalveolar lavage (BAL) were collected to measure iron, ferritin, C-reactive protein, serum amyloid A and serum silicon levels. Ferritin subunit expression in BAL and transbronchial biopsies was analysed by reverse transcription quantitative PCR. Lipid accumulation in BAL macrophages was assessed by Oil Red O staining. RESULTS: Serum iron levels were significantly elevated in patients with silicosis, with a strong positive association with serum ferritin levels. In contrast, markers of systemic inflammation were not increased in silicosis patients. Serum silicon levels were significantly elevated in complicated disease. BAL macrophages from silicosis patients were morphologically consistent with lipid-laden foamy macrophages. Ferritin light chain (FTL) mRNA expression in BAL macrophages was also significantly elevated in simple silicosis patients and correlated with systemic ferritin. CONCLUSION: Our findings suggest that elevated iron levels during the early phases of silicosis increase FTL expression in BAL macrophages, which drives elevated BAL and serum ferritin levels. Excess iron and ferritin were also associated with the emergence of a foamy BAL macrophage phenotype. Ferritin may represent an early disease marker for silicosis, where increased levels are independent of inflammation and may contribute to fibrotic lung remodelling.

BACKGROUND AND OBJECTIVE: People living with pulmonary fibrosis (PF) report unmet needs for information and support. Lung Foundation Australia (LFA) have developed the Peer Connect Service to facilitate telephone support for people with PF across Australia. This project documented the experiences of participants and the resources required to support the service. METHODS: Consenting participants took part in semi-structured interviews by telephone. Primary peers (peers who agreed to initiate contact) and secondary peers (eligible patients who sought a peer match) were interviewed. Thematic analysis was undertaken by two independent researchers. Data were collected on the number of matches and contacts required to establish each match. RESULTS: Interviews were conducted with 32 participants (16 primary peers, 15 secondary peers and 1 who was both), aged from 53 to 89 years with 56% being male. Major themes included the value of shared experiences, providing mutual support and the importance of shared personal characteristics (e.g. gender and hobbies) in allowing information and emotional support needs to be met. Participants saw face-to-face contact with peers as highly desirable whilst acknowledging the practical difficulties. Primary peers were cognizant that their role was not to provide medical advice but to listen and share experiences. In the 12-month period, 60 peer matches were made, each match requiring a minimum of seven staff contacts. CONCLUSION: The Peer Connect Service provides a unique opportunity for people with PF to share experiences and offer mutual support. This telephone matching model may be useful in providing peer support for individuals with rare diseases who are geographically dispersed.

In addition to facilitating healthcare delivery planning, reliable information about prognosis is essential for treatment decisions in patients with idiopathic pulmonary fibrosis (IPF). This review aimed to evaluate the prognosis of patients with IPF without anti-fibrotic therapy. We included all cohort studies and the placebo arms of randomised controlled trials (RCTs) in IPF and follow-up of ≥12 months. Two reviewers independently evaluated studies for inclusion, assessed risk of bias and extracted data. A total of 154 cohort studies and 16 RCTs were included. The pooled proportions of mortality were 0.12 (95% CI 0.09-0.14) at 1-2 years, 0.38 (95% CI 0.34-0.42) between 2-5 years, and 0.69 (95% CI 0.59-0.78) at ≥5 years. The pooled mean overall survival was 4 years (95% CI 3.7-4.6) for studies with a follow-up duration of 10 years. At <2 years, forced vital capacity and diffusing capacity of the lung for carbon monoxide declined by a mean of 6.76% predicted (95% CI -8.92 -4.61) and 3% predicted (95% CI -5.14 -1.52), respectively. Although heterogeneity was high, subgroup analyses revealed lower pooled proportions of mortality at 1 year in the RCT participants (0.07 (95% CI 0.05-0.09)) versus cohort study participants (0.14 (95% CI 0.12-0.17)). This review provides comprehensive information on the prognosis of IPF, which can inform treatment discussions with patients and comparisons for future studies with new therapies.

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: 2

BACKGROUND: People with pulmonary fibrosis often experience a protracted time to diagnosis, high symptom burden and limited disease information. This review aimed to identify the supportive care needs reported by people with pulmonary fibrosis and their caregivers. METHODS: A systematic review was conducted according to PRISMA guidelines. Studies that investigated the supportive care needs of people with pulmonary fibrosis or their caregivers were included. Supportive care needs were extracted and mapped to eight pre-specified domains using a framework synthesis method. RESULTS: A total of 35 studies were included. The most frequently reported needs were in the domain of information/education, including information on supplemental oxygen, disease progression and prognosis, pharmacological treatments and end-of-life planning. Psychosocial/emotional needs were also frequently reported, including management of anxiety, anger, sadness and fear. An additional domain of "access to care" was identified that had not been specified a priori; this included access to peer support, psychological support, specialist centres and support for families of people with pulmonary fibrosis. CONCLUSION: People with pulmonary fibrosis report many unmet needs for supportive care, particularly related to insufficient information and lack of psychosocial support. These data can inform the development of comprehensive care models for people with pulmonary fibrosis and their loved ones.

Domiciliary oxygen therapy is often prescribed for patients with hypoxaemia due to advanced lung disease, most commonly chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Long-term oxygen therapy (LTOT) trials conducted in patients with COPD in the 1980s remain the basis for clinical decisions and guideline recommendations regarding LTOT for patients with non-COPD conditions as there is a lack of high-quality evidence concerning its use in the non-COPD population. There is also a lack of evidence for the use of ambulatory and nocturnal oxygen therapy in patients with isolated exertional and nocturnal hypoxaemia. These deficiencies pose significant challenges in patient care, with consequent discrepancies in guideline recommendations and clinical approaches. In recent years, new studies have been and are currently being conducted to fill the gaps in our understanding and use of domiciliary oxygen therapy for other indications, including ILD. This article provides a comparison of the epidemiology and significance of hypoxaemia in patients with COPD and ILD, with an up-to-date review of current evidence regarding the role of different types of domiciliary oxygen therapy in these conditions.

BACKGROUND AND OBJECTIVE: Patients with interstitial lung disease (ILD) are often prescribed disease-targeted and symptomatic therapies, both of which can cause significant treatment burden due to polypharmacy and drug-disease interactions. This study aimed to evaluate medication regimen complexity before and after introduction of ILD-specific therapies. Potential drug-disease interactions were evaluated for patients who were prescribed prednisolone. METHODS: In this study, 214 patients with ILD were assessed for demographic information, co-morbidities and medication use. Medication lists were reviewed prior to and after the introduction of ILD-specific therapies. Complexity of treatment regimen was examined using the validated Medication Regimen Complexity Index (MRCI). RESULTS: Of the 214 patients, 75 had idiopathic pulmonary fibrosis (IPF) while the rest had inflammatory ILD (chronic hypersensitivity pneumonitis: 45; connective tissue disease-related ILD: 41). Polypharmacy was common at baseline (IPF: 51%, inflammatory ILD: 63%). Following introduction of ILD-specific therapies, median total MRCI scores significantly increased from 8 (interquartile range (IQR) = 8-15) to 22.5 (17.5-27.5) and 14.5 (8.5-21) to 21.5 (16-30) for IPF and inflammatory ILD groups, respectively (P < 0.0001 for both). Complex dosing instructions contributed the most to total MRCI scores for ILD-specific therapies. Among patients receiving prednisolone (n = 113), 88% had ≥1 co-morbidity which may be impacted. Common co-morbidities included gastrointestinal diseases (56%), obesity (37%), osteoporosis (24%) and diabetes mellitus (18%). CONCLUSION: Polypharmacy and complex medication regimen are common in patients with ILD of different aetiologies. There is a high frequency of potential drug-disease interactions among patients who are prescribed systemic corticosteroids. These findings highlight the need for careful evaluation of the impact of therapeutic complexity and burden in patients wit

© 2018, Springer Nature Switzerland AG. Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship.

© 2018, Springer Nature Switzerland AG. Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship.

BACKGROUND AND OBJECTIVE: Ambulatory oxygen therapy is often provided to patients with interstitial lung disease (ILD). Lightweight portable oxygen concentrators (POCs) provide an alternative to traditional portable systems such as compressed oxygen cylinders; however, their efficacy in patients with ILD has not been assessed. This study aimed to evaluate the clinical performance of three ambulatory oxygen systems (two different POCs and a compressed oxygen cylinder) during 6-min walk tests (6MWTs) in patients with ILD and exertional desaturation. METHODS: A total of 20 participants with ILD of varying aetiologies who demonstrated exertional desaturation to <90% on room air during 6MWT were recruited. Each participant performed two 6MWTs while breathing room air. On a subsequent day, two further 6MWTs were performed, in random order: one breathing oxygen via a POC (either the Inogen One G2 POC or the EverGo POC at the setting of 6) and one with a compressed oxygen cylinder (at 5 L/min). RESULTS: There were no significant differences in nadir oxygen saturation (SpO2 ) during 6MWTs using different portable oxygen devices (Trial 1: mean SpO2 for Inogen One G2 POC: 82.3 ± 3.5% vs oxygen cylinder: 80.3 ± 2.2%, P = 0.14; Trial 2: mean SpO2 for EverGo POC: 85.7 ± 7.7% vs oxygen cylinder: 86.1 ± 6.1%, P = 0.79). The mean 6-min walk distances were not significantly different among the three devices. CONCLUSION: The performance of the Inogen One G2 POC and the EverGo POC had comparable performance with that of the compressed oxygen cylinder during walking in patients with ILD and exertional desaturation.

Background Back-titration of inhaled corticosteroid (ICS) dose in well-controlled asthma patients is emphasized in clinical guidelines, but there are few published data on the airway cell and cytokine changes in relation to ICS reduction. In our study, 20 mild-to-moderate persistent (inspite of low-moderate dose ICS treatment) asthmatic subjects prospectively rendered largely asymptomatic by high-dose ICS were assessed again by clinical, physiological, and airway inflammatory indices after 4–8 weeks of reduced ICS treatment.We aimed at assessing the underlying pathological changes in relation to clinical deterioration. Methods Patients recorded daily symptom scores and peak expiratory flows (PEF). Spirometry and airways hyperreactivity (AHR) were measured and bronchoscopy was performed with assessment of airway biopsies (mast cells, eosinophils, neutrophils, and T lymphoctyes), bronchoalveolar lavage (BAL) IL-5 and eotaxin levels and cellular profiles at the end of highdose ICS therapy and again after ICS dose reduction. Baseline data were compared with symptomatic steroid-free asthmatics (n = 42) and non-asthmatic controls (n = 28). Results After ICS reduction, subjects experienced a variable but overall significant increase in symptoms and reductions in PEF and forced expiratory volume in 1 s. There were no corresponding changes in AHR or airways eosinophilia. The most relevant pathogenic changes were increased CD41/CD81 T cell ratio, and decreased sICAM-1 and CD18 macrophage staining (potentially indicating ligand binding). However, there was no relationship between the spectrum of clinical deterioration and the changes in cellular profiles or BAL cytokines. Conclusions These data suggest that clinical markers remain the most sensitive measures of early deterioration in asthma during back-titration of ICS, occurring at a time when AHR and conventional indices of asthmatic airway inflammation appear unchanged. These findings have major relevance to management and