Anthracosis, usually regarded as a benign and uncommon bronchoscopic finding, was identified in 108 (9.9%) of 1154 bronchoscopy procedures at two Australian hospitals, with almost a third showing bronchial narrowing consistent with anthracofibrosis. Anthracofibrosis was rarely anticipated before bronchoscopy, and most procedures were undertaken to investigate suspected tuberculosis or malignancy, which were ultimately confirmed in only a minority of cases. Frequent readmissions, often for respiratory infection, support anthracofibrosis as a chronic airways disease and highlight the need to improve awareness, optimise investigation pathways and prioritise long-term respiratory and infection-prevention care.

BACKGROUND AND OBJECTIVE:In 2022, the American Thoracic and European Respiratory Societies recommended a shift to race-neutral equations for reporting and interpreting lung function tests. The impact of this change in the Australian population has not been comprehensively evaluated. METHODS:We conducted a cross-sectional study of adults evaluated at a multi-centre lung function laboratory in Australia between 2014 and 2024. Adults aged 40-70 years referred with respiratory symptoms or suspected obstructive airways disease were included (n = 6109). We compared the classification and severity of obstructive, restrictive, and mixed ventilatory defects using the race-neutral versus race-specific Global Lung Initiative reference equations. RESULTS:Lung function tests from 6109 individuals with a mean (SD) age of 51.0 (13.7) years were evaluated (71% Caucasian, 9% South East (SE) Asian, 19% Other). Using race-neutral instead of race-specific equations resulted in 93% (5702 of 6109) remaining in the same classification. Among Caucasians, race-neutral equations increased the prevalence of obstruction (11%-13%), decreased restriction (8%-4%), and decreased mixed (4%-3%). Among SE Asians, race-neutral equations decreased the prevalence of obstruction (15%-10%) and increased restriction (6%-8%), and mixed was unchanged (2%). Among Others, race-neutral equations decreased the prevalence of obstruction (8%-7%), decreased restriction (21% to 17%) and decreased mixed (6% to 5%). CONCLUSION:While race-neutral and race-specific equations had concordant classifications for most individuals, the change resulted in a relative decrease in the prevalence of restriction in Caucasians by 53% and obstruction in SE Asians by 35%.

Infection by influenza A virus (IAV) and other viruses causes disease exacerbations in chronic obstructive pulmonary disease (COPD). Immune responses are blunted in COPD, a deficit compounded by current standard-of-care glucocorticosteroids (GCS) to further predispose patients to life-threatening infections. The immunosuppressive effects of elevated transforming growth factor-β (TGF-β) in COPD may amplify lung inflammation during infections while advancing fibrosis. In the present study, we investigated potential repurposing of pirfenidone, currently used as an antifibrotic for idiopathic pulmonary fibrosis, as a nonsteroidal treatment for viral exacerbations of COPD. Murine models of lung-specific TGF-β overexpression or chronic cigarette smoke exposure with IAV infection were used. Pirfenidone was administered daily by oral gavage commencing pre- or postinfection, and inhaled pirfenidone and GCS treatment preinfection were also compared. Tissue and BAL were assessed for viral replication, inflammation, and immune responses. Overexpression of TGF-β enhanced the severity of IAV infection, contributing to unrestrained airway inflammation. Mechanistically, TGF-β reduced innate immune responses to IAV by blunting IFN-regulated gene expression and suppressing production of antiviral proteins. Prophylactic pirfenidone administration opposed these actions of TGF-β, curbing IAV infection and airway inflammation associated with TGF-β overexpression and cigarette smoke-induced COPD. Notably, inhaled pirfenidone caused greater inhibition of viral loads and inflammation than inhaled GCS. These proof-of-concept studies demonstrate that repurposing pirfenidone and employing a preventative strategy may yield substantial benefit over antiinflammatory GCS in COPD. Pirfenidone can mitigate damaging viral exacerbations without attendant immunosuppressive actions and merits further investigation, particularly as an inhaled formulation.

Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: (i) the ability to fight infections; (ii) the activation of blood coagulation or blood clot lysis systems; (iii) the activation of digestive enzymes; and (iv) reproduction. Serine protease activity is highly regulated by multiple families of protease inhibitors, known collectively as the SERine Protease INhibitor (SERPIN). The serpins use a conformational change mechanism to inhibit proteases in an irreversible way. The unusual conformational change required for serpin function provides an elegant opportunity for allosteric regulation by the binding of cofactors, of which the most well-studied is heparin. The goal of this review is to discuss some of the clinically relevant serine protease–serpin interactions that may be enhanced by heparin or other negatively charged polysaccharides. The paired serine protease–serpin in the framework of heparin that we review includes the following: thrombin–antithrombin III, plasmin–anti-plasmin, C1 esterase/kallikrein–C1 esterase inhibitor, and furin/TMPRSS2 (serine protease Transmembrane Protease 2)–alpha-1-antitrypsin, with the latter in the context of COVID-19 and prostate cancer.

Extracellular traps made by neutrophils (NETs) and other leukocytes such as macrophages and eosinophils have a key role in the initial immune response to infection but are highly inflammatory and may contribute to tissue damage. They are particularly relevant to lung disease, with the pulmonary anatomy facilitating their ability to fully extend into the airways/alveolar space. There has been a rapid expansion in the number of published studies demonstrating their role in a variety of important respiratory diseases including chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis, asthma, pneumonia, COVID-19, rhinosinusitis, interstitial lung disease and lung cancer. The expression of NETs and other traps is a specific process, and diagnostic tests need to differentiate them from other inflammatory pathways/causes of cell death that are also characterised by the presence of extracellular DNA. The specific targeting of this pathway by relevant therapeutics may have significant clinical benefit; however, current clinical trials/evidence are at a very early stage. This review will provide a broad overview of the role of NETs and their possible treatment in respiratory disease.

Background Although airway clearance techniques (ACTs) and physical exercise are recommended for adults with bronchiectasis, there is little data on current practice and limited guidance predicting clinical approach. Objective This study aimed to describe current ACT and exercise practice recorded by patients, and identify predictors of regular ACTs, ACT modalities and exercise. Methods Physiotherapy-specific interventions, quality of life (Quality-of-Life Bronchiectasis questionnaire, QOL-B), demographics and disease severity were extracted from the Australian Bronchiectasis Registry. Multivariate analyses were undertaken to identify predictors of undertaking ACTs or exercise. Results We included 461 patients; median age of 72 years (interquartile range 64-78 years). Regular ACT use was recorded by 266 (58%) patients; the active cycle of breathing technique (n=175, 74%) was the most common technique. Regular exercise use was recorded by 213 (46%) patients, with walking the most common form of exercise. A pulmonary rehabilitation referral was made for 90 (19.5%) of patients. Regular ACT use was associated with a higher treatment burden on QOL-B (Odds ratio (OR)=0.97, 95% confidence interval (CI) 0.96 to 0.99). Regular exercise was more likely amongst patients with severe bronchiectasis compared to those with mild disease (OR=9.46, 95% CI 1.94 to 67.83) and in those with greater physical function on the QOL-B (OR=1.02, 95% CI 1.01 to 1.04). Conclusion Approximately half the adults in the registry report regular ACT or exercise; QOL and disease severity predict this engagement. This knowledge may guide the tailoring of ACTs and exercise prescription to optimise physiotherapy management in adults with bronchiectasis.

Background: Impaired diffusing capacity of the lung (DLCO) in the absence of post-bronchodilator (BD) airflow obstruction has been proposed as a marker of 'PreCOPD'. However, the relationship between impaired DLCO and subsequent lung function decline and COPD incidence has not been examined in-depth. Methods: We conducted an observational study of adults aged between 40 and 70 years who were evaluated at a multi-centre lung function laboratory in Australia between 2014 and 2024. Adults referred with respiratory symptoms or a clinical suspicion of obstructive airways disease with follow-up spirometry obtained >= 12 months after the initial assessment were included. The relationship between impaired DLCO and subsequent lung function decline and COPD incidence was assessed among those with normal spirometry at baseline. Results: A total of 266 patients with a mean age of 53.2 (SD 12.8) years were evaluated after a median follow-up of 2.3 [IQR 1.5 to 3.3] years. We found no evidence of an association between impaired DLCO (below the lower limit of normal) and annualised rate of decline in post-BD FEV1 1 (MD-0.1 % predicted per-year, 95%CI-1.3 to 1.2), FVC (-0.4 % predicted, 95%CI-1.6 to 0.8) or FEV1/FVC 1 /FVC (-0.1 % per-year, 95%CI-0.1 to 0.1). The sensitivity of impaired DLCO for COPD incidence was 40 %, and specificity 82 %. Findings were similar in sub-samples limited to current and former smokers, and when impaired DLCO was defined as < 80 % predicted. Conclusion: Impaired DLCO was not an effective discriminator of lung function decline or COPD incidence in this real-world cohort.

Background: Patients with bronchiectasis often require hospitalisation for the administration of intravenous antibiotics for the management of acute exacerbations. Increasingly, Outpatient Parenteral Antibiotic Therapy (OPAT) services have become available as a potential alternative for domiciliary management.Aims: This study assessed outcomes in both cystic fibrosis (CF) and non-CF bronchiectasis patients who received OPAT for the management of an acute exacerbation of bronchiectasis.Methods: A retrospective study of consecutive subjects was done in both CF and non-CF groups in a large metropolitan Health Service in Australia from 2016 to 2022.Results: There were 51 episodes of care in the non-CF group (22 subjects) and 73 episodes in the CF group (13 subjects). The non-CF group were nearly all treated with once daily domiciliary intravenous (IV) ceftriaxone (49/51 episodes) for a duration of 9.1 +/- 3.0 days (mean and stan-dard deviation (SD)) via a peripherally inserted venous canula (84% of episodes). In contrast, the CF group generally received dual IV antibiotics (64% of episodes), with an average duration of 16.8 +/- 6.3 days via central venous access (100%). In the non-CF group, the admission rate to hospital after 1 month was 9.6% and in the CF group was 0%. At 3 and 6 months the readmission rate for the non-CF group was 15.7% and 19.6% and CF group was 21.9% and 31.5%. There was a low rate of complications for the OPAT admissions (2% for the non-CF group and 7% for CF group).Conclusions: OPAT is a viable alternative for the management of bronchiectasis exacerbations.

A series of studies has reported weight gain in association with COVID-19 lockdowns; typically, this research has had short-term follow-up in populations that tended to gain weight. In this study, the effect of prolonged lockdowns on weight was assessed in a population of patients with chronic obstructive pulmonary disease. Before lockdown subjects gained an average of 0.022 kg per month; after lockdown this trend reversed with subjects losing weight at 0.032 kg per month, a trend that was highly significant (P < 0.001).

Background and Objective: Raised blood lactate secondary to high dose beta(2)-agonist treatment has been reported in asthma exacerbations but has not been investigated during acute exacerbations of COPD (AECOPD). We explored associations of blood lactate measurements with disease outcomes and beta(2)-agonist treatments during AECOPD. Methods: Retrospective (n = 199) and prospective studies (n = 142) of patients hospitalized with AECOPD were conducted. The retrospective cohort was identified via medical records and the prospective cohort was recruited during hospitalization for AECOPD. Baseline demographics, comorbidities, beta(2)-agonist treatment, biochemical measurements and clinical outcomes were compared between patients with normal (<= 2.0 mmol/L) versus elevated lactate (>2.0 mmol/L). Regression analyses examined associations of lactate measurements with beta(2)-agonist dosages. Results: Demographic data and comorbidities were similar between high versus normal lactate groups in both cohorts. The populations were elderly (mean >70 years), predominantly male (>60%) with reduced FEV1 (%) 48.2 +/- 19 (prospective cohort). Lactate was elevated in approximately 50% of patients during AECOPD and not related to evidence of sepsis. In the prospective cohort, patients with high lactate had more tachypnoea, tachycardia, acidosis and hyperglycaemia (p < 0.05) and received more non-invasive ventilation (37% vs. 9.7%, p < 0.001, prospective cohort). There was a trend to longer hospitalization (6 vs. 5 days, p = 0.06, prospective cohort). Higher cumulative beta(2)-agonist dosages were linked to elevated lactate levels (OR 1.04, p = 0.01). Conclusion: Elevated lactate during AECOPD was common, unrelated to sepsis and correlated with high cumulative doses of beta(2)-agonists. Raised lactate may indicate excessive beta(2)-agonist treatment and should now be investigated as a possible biomarker.