Treatment of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis: A position statement from the Thoracic Society of Australia and New Zealand 2023 revision.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease leading to significant morbidity and mortality. In 2017 the Thoracic Society of Australia and New Zealand (TSANZ) and Lung Foundation Australia (LFA) published a position statement on the treatment of IPF. Since that time, subsidized anti-fibrotic therapy in the form of pirfenidone and nintedanib is now available in both Australia and New Zealand. More recently, evidence has been published in support of nintedanib for non-IPF progressive pulmonary fibrosis (PPF). Additionally, there have been numerous publications relating to the non-pharmacologic management of IPF and PPF. This 2023 update to the position statement for treatment of IPF summarizes developments since 2017 and reaffirms the importance of a multi-faceted approach to the management of IPF and progressive pulmonary fibrosis.

Quantitative computed tomography predicts outcomes in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Prediction of disease course in patients with progressive pulmonary fibrosis remains challenging. The purpose of this study was to assess the prognostic value of lung fibrosis extent quantified at computed tomography (CT) using data-driven texture analysis (DTA) in a large cohort of well-characterized patients with idiopathic pulmonary fibrosis (IPF) enrolled in a national registry. METHODS: This retrospective analysis included participants in the Australian IPF Registry with available CT between 2007 and 2016. CT scans were analysed using the DTA method to quantify the extent of lung fibrosis. Demographics, longitudinal pulmonary function and quantitative CT metrics were compared using descriptive statistics. Linear mixed models, and Cox analyses adjusted for age, gender, BMI, smoking history and treatment with anti-fibrotics were performed to assess the relationships between baseline DTA, pulmonary function metrics and outcomes. RESULTS: CT scans of 393 participants were analysed, 221 of which had available pulmonary function testing obtained within 90 days of CT. Linear mixed-effect modelling showed that baseline DTA score was significantly associated with annual rate of decline in forced vital capacity and diffusing capacity of carbon monoxide. In multivariable Cox proportional hazard models, greater extent of lung fibrosis was associated with poorer transplant-free survival (hazard ratio [HR] 1.20, p < 0.0001) and progression-free survival (HR 1.14, p < 0.0001). CONCLUSION: In a multi-centre observational registry of patients with IPF, the extent of fibrotic abnormality on baseline CT quantified using DTA is associated with outcomes independent of pulmonary function.

Anti-tumour necrosis factor-α-induced lupus in a patient receiving infliximab for sarcoidosis.

Infliximab is a chimeric monoclonal antibody against tumour necrosis factor (TNF)-α, with a wide variety of uses. Monoclonal antibody therapies specifically targeting TNF-α, have emerged as a novel treatment option for patients with refractory sarcoidosis, with infliximab being the most widely used. This is not true of other TNF-α inhibitors, for example etanercept, which have a different mechanism of action, and are not effective in sarcoidosis. It is well documented that infliximab therapy can result in the production of autoantibodies, however clinical symptoms or disease is rare. In this report, we describe a 37-year-old male with a history of sarcoidosis requiring infliximab therapy, who presented during the course of his treatment with the onset of new migratory joint pain, increasing fatigue and positive serum autoantibodies, heralding the development of infliximab-induced lupus.

Biomarker signatures for progressive idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers have the potential for guiding management in clinical practice. We assessed the prognostic role of serum biomarkers in three independent IPF cohorts: Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE). METHODS: In the AIPFR cohort, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. LASSO (least absolute shrinkage and selection operator) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at 1 year in the AIPFR cohort, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in the PROFILE cohort. Four significantly replicating biomarkers were aggregated into a progression index model based on tertiles of circulating concentrations. RESULTS: 189 participants were included in the AIPFR cohort, 205 participants from the TLF cohort and 122 participants from the PROFILE cohort. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at 1 year. Proteomic data did not replicate. The progression index in the AIPFR, TLF and PROFILE cohorts predicted risk of progression, mortality and progression-free survival. A statistical model incorporating the progression index demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP (gender, age and physiology) score model alone in all cohorts, and significantly so within the incidence-based TLF and PROFILE cohorts. CONCLUSION: A panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.

Diagnosis and management of connective tissue disease-associated interstitial lung disease in Australia and New Zealand: A position statement from the Thoracic Society of Australia and New Zealand.

Pulmonary complications in CTD are common and can involve the interstitium, airways, pleura and pulmonary vasculature. ILD can occur in all CTD (CTD-ILD), and may vary from limited, non-progressive lung involvement, to fulminant, life-threatening disease. Given the potential for major adverse outcomes in CTD-ILD, accurate diagnosis, assessment and careful consideration of therapeutic intervention are a priority. Limited data are available to guide management decisions in CTD-ILD. Autoimmune-mediated pulmonary inflammation is considered a key pathobiological pathway in these disorders, and immunosuppressive therapy is generally regarded the cornerstone of treatment for severe and/or progressive CTD-ILD. However, the natural history of CTD-ILD in individual patients can be difficult to predict, and deciding who to treat, when and with what agent can be challenging. Establishing realistic therapeutic goals from both the patient and clinician perspective requires considerable expertise. The document aims to provide a framework for clinicians to aid in the assessment and management of ILD in the major CTD. A suggested approach to diagnosis and monitoring of CTD-ILD and, where available, evidence-based, disease-specific approaches to treatment have been provided.

Does face-to-face pre-operative joint replacement education reduce hospital costs in a regional Australian hospital? A descriptive retrospective clinical audit.

OBJECTIVE: To evaluate whether attending a face-to-face pre-operative joint replacement education in a regional setting reduces overall hospital costs and length of stay (LOS) following total knee replacement (TKR) or total hip replacement (THR). METHODS: A retrospective clinical audit reviewed the medical records of all patients who underwent an elective THR or TKR at Rockhampton Hospital in regional Queensland, Australia, between 03/2015 and 12/2016 (22 months). The pre-operative joint replacement education class was provided by a multidisciplinary team that included a physiotherapist, an occupational therapist, a dietician, a pharmacist and a social worker. In addition to demographic data, we extracted and analysed data related to total acute care and total healthcare cost, prevalence of post-operative complications, discharge destination and comorbidities (using the Functional Comorbidity Index). RESULTS: Out of 326 cases that were included in the analysis, 115 cases with TKR and 51 cases with THR attended a pre-operative education class. Demographic characteristics between those attending and not attending the class were largely similar, except from more females attending in the THR group. There was no difference in hospital costs or LOS between those who attended the class compared to those who did not for both the TKR and THR groups. Outcomes related to total acute stay costs, total cost including travel and education and score for Functional Comorbidities Index were similar between those who attended the class and those who did not. CONCLUSION: Pre-operative education does not reduce hospital costs (surgery and hospital stay) in Central Queensland.

Invasive tracheal aspergillosis after chemoradiotherapy treatment.

Invasive tracheobronchial aspergillosis is a rare disease with most reported cases in the literature occurring in immunocompromised hosts. We report an unusual case of a patient with persistent cough and dyspnoea in the context of prior chemoradiotherapy for primary lung cancer. Chest computed tomography (CT) demonstrated an abnormal soft tissue mass surrounding the trachea and carina, with focal moderate fluorodeoxyglucose (FDG) activity on positron emission tomography (PET) scan. Bronchoscopic biopsy revealed fungal hyphae associated with necrosis and cartilage invasion, subsequently confirmed to be Aspergillus fumigatus complex. The patient was commenced on antifungal therapy promptly and had a good clinical response to treatment.

Gastroesophageal reflux and antacid therapy in IPF: analysis from the Australia IPF Registry.

BACKGROUND AND OBJECTIVE: Gastroesophageal reflux disease (GORD) is highly prevalent in idiopathic pulmonary fibrosis (IPF) and may play a role in its pathogenesis. Recent IPF treatment guidelines suggest that all patients with IPF be considered for antacid therapy. However, emerging evidence suggests that antacid therapy does not improve IPF patient outcomes and may increase the risk of pulmonary infection. METHODS: Using prospectively collected data from the Australian IPF Registry including use of antacid therapy, GORD diagnosis and GORD symptoms, the relationship of these GORD variables to survival and disease progression was assessed. The severity of GORD symptoms using the frequency scale for symptoms of GORD (FSSG) and its relationships to outcomes was also assessed for the first time in an IPF cohort. RESULTS: Five hundred eighty-seven (86%) of the 684 patients in the Australian IPF Registry were eligible for inclusion. Patients were mostly male (69%), aged 71.0 ± 8.5 years with moderate disease (FVC 81.7 ± 21.5%; DLco 48.5 ± 16.4%). Most patients were taking antacids (n = 384; 65%), though fewer had a diagnosis of GORD (n = 243, 41.4%) and typical GORD symptoms were even less common (n = 171, 29.1%). The mean FSSG score was 8.39 ± 7.45 with 43% (n = 251) having a score > 8. Overall, there was no difference in survival or disease progression, regardless of antacid treatment, GORD diagnosis or GORD symptoms. CONCLUSIONS: Neither the use of antacid therapy nor the presence of GORD symptoms affects longer term outcomes in IPF patients. This contributes to the increasing evidence that antacid therapy may not be beneficial in IPF patients and that GORD directed therapy should be considered on an individual basis to treat the symptoms of reflux.

Eligibility for anti-fibrotic treatment in idiopathic pulmonary fibrosis depends on the predictive equation used for pulmonary function testing.

BACKGROUND AND OBJECTIVE: Publicly funded therapy for idiopathic pulmonary fibrosis (IPF) relies on percentage predicted values from pulmonary function testing, for example Australian patients must have a forced vital capacity ≥50% (%FVC), transfer factor of the lung for carbon monoxide ≥ 30% (%TLco) and forced expiratory volume in 1 s (FEV1 )/FVC ratio > 0.7. Despite defined cut-off values, no jurisdiction prescribes a reference equation for use; multiple equations exist. We hypothesized that access to subsidized treatment varies depending on the chosen equation. The %FVC and %TLco from different commonly used reference equations across general respiratory patients, and IPF-specific patients, were compared. METHODS: FVC and TLco measurements from a large general respiratory laboratory and the Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR) database were analysed using multiple equations. Differences between %FVC and %TLco for each equation were calculated, with particular interest in classification of patients (%) at the threshold for subsidized treatment. RESULTS: A total of 20 378 general respiratory database results were analysed. The %FVC ≥ 50% increased from 86% with the Roca equation to 96% with Quanjer (European Coal and Steal Community, ECSC) and %TLco≥30% increased from 91% with Paoletti to 98% with Thompson. However, overall increase in eligibility for subsidized treatment was modest, varying from 48.2% to 49.2%. A total of 545 AIPFR database results were analysed. The %FVC ≥ 50% increased from 73% with Roca to 94% with Quanjer (ECSC) and %TLco≥30% increased from 87% with Paoletti to 96% with Miller. Overall eligibility for subsidized treatment in the AIPFR group varied from 73.6% to 82.8% between surveyed interstitial lung disease (ILD) centres based entirely on the equation used. CONCLUSION: Substantial variability exists between reference equations, impacting access to subsidized treatment. Treating clinicians should be aware of this when assessing patients around public funding thresholds.

Implications of the diagnostic criteria of idiopathic pulmonary fibrosis in clinical practice: Analysis from the Australian Idiopathic Pulmonary Fibrosis Registry.

BACKGROUND AND OBJECTIVE: Current guidelines for the diagnosis of idiopathic pulmonary fibrosis (IPF) provide specific criteria for diagnosis in the setting of multidisciplinary discussion (MDD). We evaluate the utility and reproducibility of these diagnostic guidelines, using clinical data from the Australian IPF Registry. METHODS: All patients enrolled in the registry undergo a diagnostic review whereby international IPF guidelines are applied via a registry MDD. We investigated the clinical applicability of these guidelines with regard to: (i) adherence to guidelines, (ii) Natural history of IPF diagnostic categories and (iii) Concordance for diagnostic features. RESULTS: A total of 417 participants (69% male, 70.6 ± 8.0 years) with a clinical diagnosis of IPF underwent MDD. The 23% of participants who did not meet IPF diagnostic criteria displayed identical disease behaviour to those with confirmed IPF. Honeycombing on radiology was associated with a worse prognosis and this translated into poorer prognosis in the 'definite' IPF group. While there was moderate agreement for IPF diagnostic categories, agreement for specific radiological features, other than honeycombing, was poor. CONCLUSION: In clinical practice, physicians do not always follow IPF diagnostic guidelines. We demonstrate a cohort of IPF patients who do not meet IPF diagnostic guideline criteria, based largely on their radiology and lack of lung biopsy, but who have outcomes identical to those with IPF.

Diagnosis and management of idiopathic pulmonary fibrosis: Thoracic Society of Australia and New Zealand and Lung Foundation Australia position statements summary.

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.

Disease progression in idiopathic pulmonary fibrosis with mild physiological impairment: analysis from the Australian IPF registry.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrosing lung disease of unknown cause. The advent of anti-fibrotic medications known to slow disease progression has revolutionised IPF management in recent years. However, little is known about the natural history of IPF patients with mild physiological impairment. We aimed to assess the natural history of these patients using data from the Australian IPF Registry (AIPFR). METHODS: Using our cohort of real-world IPF patients, we compared FVC criteria for mild physiological impairment (FVC ≥ 80%) against other proposed criteria: DLco ≥ 55%; CPI ≤40 and GAP stage 1 with regards agreement in classification and relationship with disease outcomes. Within the mild cohort (FVC ≥ 80%), we also explored markers associated with poorer prognosis at 12 months. RESULTS: Of the 416 AIPFR patients (mean age 70.4 years, 70% male), 216 (52%) were classified as 'mild' using FVC ≥ 80%. There was only modest agreement between FVC and DLco (k = 0.30), with better agreement with GAP (k = 0.50) and CPI (k = 0.48). Patients who were mild had longer survival, regardless of how mild physiologic impairment was defined. There was, however, no difference in the annual decline in FVC% predicted between mild and moderate-severe groups (for all proposed criteria). For patients with mild impairment (n = 216, FVC ≥ 80%), the strongest predictor of outcomes at 12 months was oxygen desaturation on a 6 min walk test. CONCLUSION: IPF patients with mild physiological impairment have better survival than patients with moderate-severe disease. Their overall rate of disease progression however, is comparable, suggesting that they are simply at different points in the natural history of IPF disease.

Mortality Reduction Associated With ß-Adrenoceptor Inhibition in Chronic Heart Failure Is Greater in Patients With Diabetes.

OBJECTIVE: Diabetes increases mortality in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction. Studies have questioned the safety of ß-adrenoceptor blockers (ß-blockers) in some patients with diabetes and reduced left ventricular ejection fraction. We examined whether ß-blockers and ACE inhibitors (ACEIs) are associated with differential effects on mortality in CHF patients with and without diabetes. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of 1,797 patients with CHF recruited between 2006 and 2014, with mean follow-up of 4 years. ß-Blocker dose was expressed as the equivalent dose of bisoprolol (mg/day) and ACEI dose as the equivalent dose of ramipril (mg/day). Cox regression analysis was used to examine the interaction between diabetes and drug dose on all-cause mortality. RESULTS: Patients with diabetes were prescribed larger doses of ß-blockers and ACEIs than were patients without diabetes. Increasing ß-blocker dose was associated with lower mortality in patients with diabetes (8.9% per mg/day; 95% CI 5-12.6) and without diabetes (3.5% per mg/day; 95% CI 0.7-6.3), although the effect was larger in people with diabetes (interaction P = 0.027). Increasing ACEI dose was associated with lower mortality in patients with diabetes (5.9% per mg/day; 95% CI 2.5-9.2) and without diabetes (5.1% per mg/day; 95% CI 2.6-7.6), with similar effect size in these groups (interaction P = 0.76). CONCLUSIONS: Increasing ß-blocker dose is associated with a greater prognostic advantage in CHF patients with diabetes than in CHF patients without diabetes.

Treatment of idiopathic pulmonary fibrosis in Australia and New Zealand: A position statement from the Thoracic Society of Australia and New Zealand and the Lung Foundation Australia.

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease (ILD) of unknown aetiology with a median survival of only 2-5 years. It is characterized by progressive dyspnoea and worsening lung function, ultimately resulting in death. Until recently, there were no effective therapies for IPF; however, with the publication of two landmark clinical trials in 2014, the anti-fibrotic therapies, nintedanib and pirfenidone, have gained widespread approval. This position paper aims to highlight the current evidence for the treatment of IPF, with particular application to the Australian and New Zealand population. We also consider areas in which evidence is currently lacking, especially with regard to the broader IPF severity spectrum and treatment of co-morbid conditions. The utility of non-pharmacological therapies including pulmonary rehabilitation, oxygen as well as symptom management thought to be important in the holistic care of IPF patients are also discussed.

Health-related quality of life in idiopathic pulmonary fibrosis: Data from the Australian IPF Registry.

BACKGROUND AND OBJECTIVE: Studies analysing the effect of worsening pulmonary physiological impairment in idiopathic pulmonary fibrosis (IPF) with respect to quality of life have been limited to single centres or highly selected trial populations. The aim of this study was to determine the principal determinants of baseline and longitudinal health-related quality of life (HRQoL) in a large unselected IPF population. METHODS: We used the Australian IPF Registry to examine the relationship between HRQoL, measured using the St George Respiratory Questionnaire (SGRQ), and demographic features, physiological features, co-morbidities and symptoms. Linear regression analysis was performed to identify predictors of baseline HRQoL, linear mixed model analysis to determine the effect of time and forced vital capacity (FVC) on SGRQ and Cox proportional hazards regression to examine the relationship between HRQoL and all-cause mortality. RESULTS: Baseline data from 516 patients were available (347 males; mean (SD) age: 71.3 ± 8.6 years). Univariate analysis showed significant associations between HRQoL and demographic, clinical and physiological features. However, multivariate analysis demonstrated independent associations only between SGRQ and dyspnoea (University of California San Diego Shortness of Breathlessness Questionnaire (UCSD-SOBQ); R2 = 0.71, P < 0.0001), cough severity (visual analogue scale; R2 = 0.06, P < 0.0001) and depression (Hospital Anxiety and Depression Scale; R2 = 0.04, P < 0.0001). Linear mixed-effects modelling of combined baseline and longitudinal data confirmed these associations, as well as for FVC% predicted (P = 0.005). Multivariate Cox proportionate-proportional hazards regression analysis demonstrated no association between HRQoL and risk of mortality. CONCLUSION: Cough, dyspnoea and depression are major symptomatic determinants of HRQoL in IPF. FVC decline is associated with worsening HRQoL.

Baseline characteristics of idiopathic pulmonary fibrosis: analysis from the Australian Idiopathic Pulmonary Fibrosis Registry.

7The prevalence of idiopathic pulmonary fibrosis (IPF), a fatal and progressive lung disease, is estimated at 1.25-63 out of 100 000, making large population studies difficult. Recently, the need for large longitudinal registries to study IPF has been recognised.The Australian IPF Registry (AIPFR) is a national registry collating comprehensive longitudinal data of IPF patients across Australia. We explored the characteristics of this IPF cohort and the effect of demographic and physiological parameters and specific management on mortality.Participants in the AIPFR (n=647, mean age 70.9±8.5 years, 67.7% male, median follow up 2 years, range 6 months-4.5 years) displayed a wide range of age, disease severity and co-morbidities that is not present in clinical trial cohorts. The cumulative mortality rate in year one, two, three and four was 5%, 24%, 37% and 44% respectively. Baseline lung function (forced vital capacity, diffusing capacity of the lung for carbon monoxide, composite physiological index) and GAP (gender, age, physiology) stage (hazard ratio 4.64, 95% CI 3.33-6.47, p<0.001) were strong predictors of mortality. Patients receiving anti-fibrotic medications had better survival (hazard ratio 0.56, 95% CI 0.34-0.92, p=0.022) than those not on anti-fibrotic medications, independent of underlying disease severity.The AIPFR provides important insights into the understanding of the natural history and clinical management of IPF.

Current Australasian practice for diagnosis and management of idiopathic pulmonary fibrosis: Where are we now?

BACKGROUND AND OBJECTIVE: Recent international consensus statements have refined evidence-based guidelines for the diagnosis and management of idiopathic pulmonary fibrosis (IPF). This study sought to investigate how closely these guidelines are adhered to and to compare current practices with those of a similar cohort 15 years ago. METHODS: A questionnaire on IPF diagnosis and management was distributed to respiratory physicians practising in Australia and New Zealand, in 2012-2013, and results were compared with a similar survey conducted in 1999. RESULTS: A total of 172 and 144 questionnaires were completed in 1999 and 2012-2013, respectively. The most important investigations in both survey populations were high-resolution computed tomography scans, spirometry, diffusing capacity for carbon monoxide, chest X-ray, static lung volumes and autoimmune serology. In 1999, physicians were more likely to perform arterial blood gases, bronchoalveolar lavage and transbronchial lung biopsy. In the 2012-2013 cohort, 6-min walk tests and pulse oximetry were more widely utilized. Treatment choices differed considerably between the two survey populations. In 1999, the majority would offer a steroid-based regimen, whereas most would not use any specific treatment or would refer for trial participation in 2012-2013. CONCLUSIONS: Approach to IPF diagnosis and management is not uniform and has changed over 15 years. Surveyed respiratory physicians were generally practising in accordance with clinical guidelines, although significant variation in practice was identified in both cohorts. This study identifies the need to standardize care of IPF patients across Australia and New Zealand.