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Background: Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). To date, clinical practice guidelines regarding treatment for patients with SSc-ILD are primarily consensus based. Methods: An international expert guideline committee composed of 24 individuals with expertise in rheumatology, SSc, pulmonology, ILD, or methodology, and with personal experience with SSc-ILD, discussed systematic reviews of the published evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Predetermined conflict-of-interest management strategies were applied, and recommendations were made for or against specific treatment interventions exclusively by the nonconflicted panelists. The confidence in effect estimates, importance of outcomes studied, balance of desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications for health equity were all considered in making the recommendations. This was in accordance with the American Thoracic Society guideline development process, which is in compliance with the Institute of Medicine standards for trustworthy guidelines. Results: For treatment of patients with SSc-ILD, the committee: 1) recommends the use of mycophenolate; 2) recommends further research into the safety and efficacy of (a) pirfenidone and (b) the combination of pirfenidone plus mycophenolate; and 3) suggests the use of (a) cyclophosphamide, (b) rituximab, (c) tocilizumab, (d) nintedanib, and (e) the combination of nintedanib plus mycophenolate. Conclusions: The recommendations herein provide an evidence-based clinical practice guideline for the treatment of patients with SSc-ILD and are intended to serve as the basis for informed and shared decision making by clinicians and patients.

BackgroundChronic hypersensitivity pneumonitis (CHP) is an immune-mediated interstitial lung disease (ILD) caused by inhalational exposure to environmental antigens, resulting in parenchymal fibrosis. By definition, a diagnosis of CHP assumes a history of antigen exposure, but only half of all patients eventually diagnosed with CHP will have a causative antigen identified. Individual clinician variation in eliciting a history of antigen exposure may affect the frequency and confidence of CHP diagnosis.MethodsA list of potential causative exposures were derived from a systematic review of the literature. A Delphi method was applied to an international panel of ILD experts to obtain consensus regarding technique for the elicitation of exposure to antigens relevant to a diagnosis of CHP. The consensus threshold was set at 80% agreement, and median ≤ 2, interquartile range = 0 on a 5-point Likert scale (1, strongly agree; 2, tend to agree; 3, neither agree nor disagree; 4, disagree; 5, strongly disagree).ResultsIn two rounds, 36/40 experts participated. Experts agreed on 18 exposure items to ask every patient with suspected CHP. Themes included CHP inducing exposures, features that contribute to an exposure's relevance, and quantification of a relevant exposure. Based on the results from the literature review and Delphi process, a CHP exposure assessment instrument was derived. Using cognitive interviews, the instrument was revised by patients with ILD for readability and usability.ConclusionsThis Delphi survey provides items that ILD experts agree are important to ask in all patients presenting with suspected CHP and provides basis for a systematically derived CHP exposure assessment instrument. Clinical utility of this exposure assessment instrument may be affected by different local prevalence patterns of exposures. Ongoing research is required to clinically validate these items and consider their impact in more geographically diverse settings.

The article explores the impact of excessive iron on lung cells in silicosis patients. Topics include the role of iron in alveolar macrophage stress and ferroptosis, the study's use of a multiomic approach to analyze the molecular profile of BAL immune cells, and the alteration of volatile organic compounds (VOCs) in the lungs due to iron-induced oxidative stress.

Hypersensitivity pneumonitis (HP) is an immune‐mediated interstitial lung disease (ILD) relating to specific occupational, environmental or medication exposures. Disease behaviour is influenced by the nature of exposure and the host response, with varying degrees of lung inflammation and fibrosis seen within individuals. The differentiation of HP from other ILDs is important due to distinct causes, pathophysiology, prognosis and management implications. This Thoracic Society of Australia and New Zealand (TSANZ) position statement aims to provide an up‐to‐date summary of the evidence for clinicians relating to the diagnosis and management of HP in adults, in the Australian and New Zealand context. This document highlights recent relevant findings and gaps in the literature for which further research is required. [ABSTRACT FROM AUTHOR]

Chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) is an important potential consequence of venous thromboembolic disease. Untreated CTEPD with pulmonary hypertension (CTEPH) is associated with high rates of morbidity and mortality. Several treatment options are now available for patients with CTEPD and CTEPH, including pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, medical therapy or a combination of therapies. Choice of treatment depends on the location of the thromboembolic disease burden, presence and severity of PH and patient factors, including frailty, parenchymal lung disease and other comorbidities. PEA is a complex surgery that can result in excellent outcomes and resolution of disease, but also comes with the risk of serious perioperative complications. This manuscript examines the history of PEA and its place in Australasia, and reports on outcomes from the main Australasian CTEPH expert centre. It provides a summary of up‐to‐date guidance on how PEA should be utilised in the overall management of these patients and describes opportunities and challenges for the future diagnosis and management of this disease, particularly in the Australasian setting. [ABSTRACT FROM AUTHOR]

Background and Objective: Evidence for the benefit of steroid therapy in acute exacerbations (AEs) of idiopathic pulmonary fibrosis (IPF) is limited; however, they remain a cornerstone of management in other fibrotic interstitial lung diseases. This retrospective observational study assesses the effect of steroid treatment on in‐hospital mortality in patients with acute exacerbation of fibrotic interstitial lung disease (AE‐FILD) including IPF and non‐IPF ILDs. Methods: AE‐FILD cases over a 10‐year period were filtered using a code‐based algorithm followed by individual case evaluation. Binary logistic regression analysis was used to assess the relationship between corticosteroid treatment (defined as ≥0.5 mg/kg/day of prednisolone‐equivalent for ≥3 days within the first 72 h of admission) and in‐hospital mortality or need for lung transplantation. Secondary outcomes included readmission, overall survival, requirement for domiciliary oxygen and rehabilitation. Results: Across two centres a total of 107 AE‐FILD subjects were included, of which 46 patients (43%) received acute steroid treatment. The steroid cohort was of younger age with fewer comorbidities but had higher oxygen requirements. Pre‐admission FVC and DLCO, distribution of diagnoses and smoking history were similar. The mean steroid treatment dose was 4.59 mg/kg/day. Steroid use appeared to be associated with increased risk of inpatient mortality or transplantation (OR 4.11; 95% CI 1.00–16.83; p = 0.049). In the steroid group, there appeared to be a reduced risk of all‐cause mortality in non‐IPF patients (HR 0.21; 95% CI 0.04–0.96; p = 0.04) compared to their IPF counterparts. Median survival was reduced in the steroid group (221 vs. 520.5 days) with increased risk of all‐cause mortality (HR 3.25; 95% CI 1.56–6.77; p < 0.01). Conclusion: In this two‐centre retrospective study of 107 patients, AE‐FILD demonstrates a high risk of mortality, at a level similar to that seen for AE‐IPF, despite steroid treatment. Clinicians should consider other precipitating factors for exacerbations and use steroids judiciously. Further prospective trials are needed to determine the role of corticosteroids in AE‐FILD. This is a multicentre retrospective observational study comparing the outcomes of acute exacerbation of fibrotic ILD between steroid and non‐steroid treatment. Those who were administered steroids were younger, had fewer comorbidities but greater oxygen requirement and lower physiologic reserve. When adjusted for these variables, there appeared no survival benefit and potential increased risk of death in those who were given steroids. See relatededitorial [ABSTRACT FROM AUTHOR]

Background and Objective: Chest x‐ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. Methods: Paired CXR and high‐resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. Results: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29–68) and specificity 97% (90–100). Conclusion: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry. The use of CXR to screen artificial stone benchtop industry workers for silicosis has low sensitivity compared to HRCT chest, especially for early‐stage disease. Reliance on chest x‐ray for screening will fail to identify many workers with artificial stone silicosis and underestimate the prevalence of respiratory disease in this industry. [ABSTRACT FROM AUTHOR]

Background: The American Thoracic Society convened an international multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis–associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with nintedanib alone or with the combination of nintedanib plus mycophenolate. Data Sources: Literature searches were conducted across MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases through June 2022 for studies using nintedanib or nintedanib plus mycophenolate to treat patients with SSc-ILD. Data Extraction: Mortality, disease progression, quality of life, and adverse event data were extracted, and meta-analysis was performed when possible. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group method was used to assess the quality of evidence. Synthesis: For nintedanib therapy alone, the systematic review included three total studies and revealed that disease progression was less in the nintedanib arm (the annual rate of decline in forced vital capacity [FVC] was 44.5 ml less, the absolute change from baseline was 46.4 ml less, and FVC% predicted was 1.2% less in the nintedanib arm) compared with placebo. However, gastrointestinal side effects and treatment discontinuation were double in the nintedanib arm compared with placebo. For combination therapy, the systematic review also included three total studies and revealed that changes in the annual rate of decline in FVC favored combination therapy over placebo (mean difference, 79.1 ml). Combination therapy was, however, associated with increased gastrointestinal adverse effects compared with placebo. The quality of evidence for all outcomes was very low as per GRADE. Conclusions: The use of nintedanib alone and in combination with mycophenolate in patients with SSc-ILD is associated with a significant reduction in disease progression compared with placebo but at the cost of increased gastrointestinal side effects and treatment discontinuation. The quality of evidence is very low. [ABSTRACT FROM AUTHOR]

Background: The American Thoracic Society (ATS) convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis--associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine the impact of treating patients with SSc-ILD with tocilizumab on prespecified critical and important outcomes determined by the ATS guideline panel. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through June 2022 for studies using tocilizumab to treat patients with SSc-ILD. Data Extraction: Mortality and disease progression were determined to be critical outcomes of focus, with quality of life and adverse events important outcomes. Data on these outcomes were extracted and meta-analyses performed using the generic inverse variance method when possible. The Grading of Recommendations, Assessment, Development, and Evaluation Working Group method was used to assess the quality of evidence. Synthesis: The literature review resulted in five studies for inclusion. The absolute decrease from baseline in forced vital capacity (FVC) for the tocilizumab arm was 118ml, 241ml, and 129ml less than the placebo arm at 24, 48, and 96weeks, respectively, favoring tocilizumab. The mean decrease in FVC% predicted at 48weeks was 6.50% less and the risk of decrease .10% was 66% less in the tocilizumab arm, whereas patients were 1.97 times more likely to have any increase in FVC% predicted if they received tocilizumab in place of placebo. When the placebo arm was given tocilizumab from 48 to 96weeks, the mean change in absolute FVC was 54.90ml less and the mean change in FVC% predicted was 1.30% less. For diffusing capacity of the lung for carbon monoxide (DLCO)% predicted, at 48weeks there was 1.50% less change and from 48 to 96weeks there was 5.40% less change in the tocilizumab arm. Quantitative Interstitial Lung Disease scores and Quantitative Lung Fibrosis scores at 48weeks and modified Rodnan skin scores at 72weeks all favored the tocilizumab arm, as did several adverse event parameters, including serious adverse events (mean difference, 227.40; 95% confidence interval, 230.10 to 224.70). The quality of evidence was very low grade. Conclusions: Tocilizumab use in patients with SSc-ILD is associated with less disease progression and a better toxicity profile than placebo. However, the quality of evidence is very low, and large prospective studies dedicated to assessing tocilizumab specifically for SSc-ILD are needed. [ABSTRACT FROM AUTHOR]

Background: The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis--associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with rituximab. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through June 2022 for studies using rituximab to treat patients with SSc-ILD. Data Extraction: Disease progression, quality of life, mortality, and adverse event data were extracted. The intervention was rituximab. The standard-of-care comparator group was decided a priori by consensus of the panel as either placebo or mycophenolate. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Synthesis: Three relevant studies were selected. Rituximab significantly improved the forced vital capacity % predicted (mean difference, 3.13; 95% confidence interval [CI], 0.37 to 5.90) and the modified Rodnan Skin Score (mean difference, 27.01; 95% CI, 11.46 to 22.56) at 24--48 weeks. Conclusions: Rituximab use in patients with SSc-ILD is associated with stabilization of lung function. The quality of evidence for study outcomes was considered to be very low, as defined by the GRADE approach. Additional research on treatment with rituximab is imperative. [ABSTRACT FROM AUTHOR]

The article reports a systematic review and meta-analysis on the use of cyclophosphamide in patients with systemic sclerosis-associated interstitial lung disease. Key topics include risk of bias in randomized controlled trials, summary of evidence for cyclophosphamide versus placebo, and important outcomes such as adverse events and changes in pulmonary function.

Background and Objective: Identification of an exposure is integral to the diagnosis, management, and prognostication of chronic hypersensitivity pneumonitis (CHP). Standardized questionnaires may aid in the identification of exposures, however, there currently are no evidence‐based patient‐validated questionnaires available. Key qualifiers (including duration and frequency) which indicate exposure relevance are also poorly defined. This study assessed the use of a standardized CHP exposure questionnaire in the identification of exposures and diagnostic confidence of CHP. Methods: People with a multi‐disciplinary meeting (MDM) diagnosis from five Australian interstitial lung disease (ILD) expert centres who provided informed consent were included. Participants completed a previously developed standardized CHP Exposure Questionnaire. Responses were collected with the participant's MDM data, including diagnosis, diagnostic confidence, and clinician‐elicited exposures. Results: One hundred thirty participants (IPF = 58, CHP = 24, CTD‐ILD = 17, unclassifiable = 19, other = 12) were included. In 33% of CHP participants, a standardized questionnaire elicited an exposure where the clinician did not. 63% of these had provisional low confidence CHP; and an exposure history would have increased the diagnostic confidence in these cases. Using the standardized questionnaire, 96% of CHP participants reporting any exposure, compared with 75% of non‐HP ILD participants. CHP participants were 3.5 times more likely (p = 0.004) to report their symptoms improved on avoidance, and 2.3 times more likely (p = 0.018) to report daily frequent exposure, compared with non‐HP ILDs. Conclusion: A standardized questionnaire which elicits exposure characteristics in addition to presence or absence of relevant exposures can increase the diagnostic confidence of CHP and reduce the proportion of antigen‐indeterminate CHP. This case–control study found that a standardized evidence‐based chronic hypersensitivity pneumonitis (CHP) exposure questionnaire increased the diagnostic confidence of CHP and reduced the proportion of antigen‐indeterminate CHP. See relatedEditorial [ABSTRACT FROM AUTHOR]