Publications by authors named "Tamera J Corte"

95 Publications

Contemporary Concise Review 2020: Interstitial lung disease.

Respirology 2021 Apr 28. Epub 2021 Apr 28.

Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

The year 2020 was one like no other, as we witnessed the far-reaching impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic. Yet despite an unprecedented and challenging year, global research in interstitial lung disease (ILD) continued to break new grounds. Research progress has led to an improved understanding in new diagnostic tools and potential biomarkers for ILD. Studies on the role of antifibrotic therapies, newer therapeutic agents, supportive care strategies and the impact of coronavirus disease 2019 (COVID-19) continue to reshape the management landscape of ILD. In this concise review, we aim to summarize the key studies published in 2020, highlighting their impact on the various aspects of ILD.
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http://dx.doi.org/10.1111/resp.14063DOI Listing
April 2021

Baseline Characteristics and Survival of an Australian Interstitial Pneumonia with Autoimmune Features Cohort.

Respiration 2021 Apr 19:1-12. Epub 2021 Apr 19.

Department of Respiratory, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

Background And Objective: The research term "interstitial pneumonia with autoimmune features" (IPAF) encompasses interstitial lung disease (ILD) patients with autoimmune features not meeting diagnostic criteria for a defined connective tissue disease (CTD). It remains unclear if IPAF is a distinct disease entity with implications for management and prognosis. We describe an Australian IPAF population and compare their baseline characteristics and outcomes with distinct cohorts of idiopathic interstitial pneumonia (IIP), CTD-ILD, and unclassifiable ILD.

Methods: Review of 291 consecutive patients attending a specialist ILD clinic was performed. Patients with a diagnosis of IIP, CTD-ILD, and unclassifiable ILD by ILD-multidisciplinary meeting (ILD-MDM) were included. Patients meeting the IPAF criteria were identified. Baseline clinical data, survival, and progression were compared between ILD groups.

Results: 226 patients were included, 36 meeting the IPAF criteria. IPAF patients demonstrated a high prevalence of autoantibodies to tRNA synthetase (35.3%), Ro52 (27.8%), and neutrophilic cytoplasmic antigens (ANCA; 20.0%). IPAF and CTD-ILD patients demonstrated similar clinical characteristics (mean age 66.6 and 63.7 years, respectively, female predominant, frequent CTD-manifestations). Lung function did not differ between ILD groups. Disease severity, pulmonary hypertension (PH), and ILD-MDM diagnosis were strong predictors of worse transplant-free survival (TFS). Meeting the IPAF criteria was not associated with TFS.

Conclusions: We identified IPAF as a heterogeneous phenotype that overlaps considerably with CTD-ILD. Disease severity, PH, and ILD-MDM diagnosis were more powerful predictors of survival outcomes than meeting the IPAF criteria.
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http://dx.doi.org/10.1159/000515396DOI Listing
April 2021

There is detectable variation in the lipidomic profile between stable and progressive patients with idiopathic pulmonary fibrosis (IPF).

Respir Res 2021 Apr 9;22(1):105. Epub 2021 Apr 9.

School of Biomedical Science, University of Western Australia, Crawley, WA, Australia.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by fibrosis and progressive loss of lung function. The pathophysiological pathways involved in IPF are not well understood. Abnormal lipid metabolism has been described in various other chronic lung diseases including asthma and chronic obstructive pulmonary disease (COPD). However, its potential role in IPF pathogenesis remains unclear.

Methods: In this study, we used ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to characterize lipid changes in plasma derived from IPF patients with stable and progressive disease. We further applied a data-independent acquisition (DIA) technique called SONAR, to improve the specificity of lipid identification.

Results: Statistical modelling showed variable discrimination between the stable and progressive subjects, revealing differences in the detection of triglycerides (TG) and phosphatidylcholines (PC) between progressors and stable IPF groups, which was further confirmed by mass spectrometry imaging (MSI) in IPF tissue.

Conclusion: This is the first study to characterise lipid metabolism between stable and progressive IPF, with results suggesting disparities in the circulating lipidome with disease progression.
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http://dx.doi.org/10.1186/s12931-021-01682-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033725PMC
April 2021

Impact of lung morphology on clinical outcomes with riociguat in patients with pulmonary hypertension and idiopathic interstitial pneumonia: A post hoc subgroup analysis of the RISE-IIP study.

J Heart Lung Transplant 2021 Feb 19. Epub 2021 Feb 19.

Interstitial Lung Disease Unit, Royal Brompton Hospital, London, United Kingdom.

Background: Riociguat in Patients with Symptomatic Pulmonary Hypertension associated with Idiopathic Interstitial Pneumonias (RISE-IIP), a randomized, controlled, phase 2b trial of riociguat for pulmonary hypertension associated with idiopathic interstitial pneumonia, was terminated early due to increased mortality in riociguat-treated patients. Baseline characteristics of enrolled patients demonstrated a low diffusing capacity of the lung for carbon monoxide (DL) with preserved lung volumes at baseline, suggesting the presence of combined pulmonary fibrosis and emphysema (CPFE) in some patients. This post hoc analysis of RISE-IIP was undertaken to explore lung morphology, assessed by high-resolution computed tomography, and associated clinical outcomes.

Methods: Available baseline/pre-baseline high-resolution computed tomography scans were reviewed centrally by 2 radiologists. The extent of emphysema and fibrosis was retrospectively scored and combined to provide the total CPFE score.

Results: Data were available for 65/147 patients (44%), including 15/27 fatal cases (56%). Of these, 41/65 patients (63%) had CPFE. Mortality was higher in patients with CPFE (12/41; 29%) than those without (3/24; 13%). Fourteen patients with CPFE had emphysema > fibrosis (4 died). No relationship was observed between CPFE score, survival status, and treatment assignment. A low DL, short 6-min walking distance, and high forced vital capacity:DL ratio at baseline also appeared to be risk factors for mortality.

Conclusions: High parenchymal lung disease burden and the presence of more emphysema than fibrosis might have predisposed patients with pulmonary hypertension associated with idiopathic interstitial pneumonia to poor outcomes in RISE-IIP. Future studies of therapy for group 3 pulmonary hypertension should include centrally adjudicated imaging for morphologic phenotyping and disease burden evaluation during screening.
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http://dx.doi.org/10.1016/j.healun.2021.02.006DOI Listing
February 2021

Are serum biomarkers useful in the management of systemic sclerosis-associated interstitial lung disease?

Respirology 2021 May 20;26(5):406-408. Epub 2021 Feb 20.

Centre of Research Excellence for Pulmonary Fibrosis, University of Sydney, Sydney, NSW, Australia.

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http://dx.doi.org/10.1111/resp.14017DOI Listing
May 2021

Untargeted metabolomics of human plasma reveal lipid markers unique to chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

Proteomics Clin Appl 2021 Feb 13:e2000039. Epub 2021 Feb 13.

Separation Science and Metabolomics Laboratory, Murdoch University, Murdoch, WA, Australia.

Chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation and progressive airflow limitation, whereas idiopathic pulmonary fibrosis (IPF) is characterised by a restrictive pattern due to fibrosis and impaired gas exchange. We undertook metabolomic analysis of blood samples in IPF, COPD and healthy controls (HC) to determine differences in circulating molecules and identify novel pathogenic pathways. An untargeted metabolomics using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) was performed to profile plasma of patients with COPD (n = 21), and IPF (n = 24) in comparison to plasma from healthy controls (HC; n = 20). The most significant features were identified using multiple database matching. One-way ANOVA and variable importance in projection (VIP) scores were also used to highlight metabolites that influence the specific disease groups. Non-polar metabolites such as fatty acids (FA) and membrane lipids were well resolved and a total of 4805 features were identified. The most prominent metabolite composition differences in lipid mediators identified at ∼2-3 fold higher in both diseases compared to HC were palmitoleic acid, oleic acid and linoleic acid; and dihydrotestosterone was lower in both diseases. We demonstrated that COPD and IPF were characterised by systemic changes in lipid constituents such as essential FA sampled from circulating plasma.
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http://dx.doi.org/10.1002/prca.202000039DOI Listing
February 2021

Nutritional status and quality of life in interstitial lung disease: a prospective cohort study.

BMC Pulm Med 2021 Feb 5;21(1):51. Epub 2021 Feb 5.

Nutrition and Dietetics, University of Sydney, Sydney, NSW, 2006, Australia.

Background: Malnutrition and altered body composition are well-documented in chronic pulmonary diseases; however, investigation of nutritional status in interstitial lung disease (ILD) is limited. This study aimed to describe the nutritional status of ILD patients within three diagnostic groups and explore the relationship between nutritional status and quality of life (QoL).

Methods: Consecutive patients attending an ILD clinic within a tertiary referral hospital in Sydney, Australia were studied. Weight, body-mass-index, anthropometrics, handgrip strength (HGS), subjective global assessment and QoL questionnaires (EQ-5D-5L and King's-Brief Interstitial-Lung-Disease 'K-BILD') were collected. Associations between nutritional status and QoL were analysed.

Results: Ninety participants were recruited and categorised: (1) Idiopathic Pulmonary Fibrosis (IPF) (2) Connective-Tissue Disease associated-ILD (CTD-ILD) or (3) Other (non-IPF/non-CTD ILD). Median age was 66.5 (18) years. Four-percent of patients were underweight and 50% were overweight or obese. Median HGS was 71%-(25.3) of predicted and was correlated to all measures of QoL including EQ-5D health-state index (r = 0.376, p < 0.0001), patient-reported EQ-5D-5L Visual Analogue Score (r = 0.367, p < 0.0001) and K-BILD total score (r = 0.346, p = 0.001). Twenty-three percent of the variance in K-BILD total score (F = 12.888, p < 0.0001) was explained by HGS (ß = 0.273, p = 0.006) and forced vital capacity % predicted (ß = 0.331, p = 0.001).

Conclusions: Although a small number of ILD patients were malnourished, a large proportion of the cohort were overweight or obese. Handgrip strength was compromised and correlated to QoL. Future research with a larger cohort is required to explore the role of HGS as a predictor of QoL.
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http://dx.doi.org/10.1186/s12890-021-01418-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863253PMC
February 2021

Home spirometry in patients with idiopathic pulmonary fibrosis: data from the INMARK trial.

Eur Respir J 2021 Jan 8. Epub 2021 Jan 8.

National Heart and Lung Institute, Imperial College London, London, UK.

Data from the INMARK trial were used to investigate the feasibility and validity of home spirometry as a measure of lung function decline in patients with idiopathic pulmonary fibrosis (IPF).Subjects with IPF and preserved forced vital capacity (FVC) were randomised to receive nintedanib or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Clinic spirometry was conducted at baseline and weeks 4, 8, 12, 16, 20, 24, 36 and 52. Subjects were asked to perform home spirometry at least once a week and ideally daily. Correlations between home- and clinic-measured FVC and rates of change in FVC were assessed using Pearson correlation coefficients.In total, 346 subjects were treated. Mean adherence to weekly home spirometry decreased over time but remained above 75% in every 4-week period. Over 52 weeks, mean adherence was 86%. Variability in change from baseline in FVC was greater when measured by home rather than clinic spirometry. Strong correlations were observed between home- and clinic-measured FVC at all time-points (r=0.72 to 0.84), but correlations between home- and clinic-measured rates of change in FVC were weak (r=0.26 for rate of decline in FVC over 52 weeks).Home spirometry was a feasible and valid measure of lung function in patients with IPF and preserved FVC, but estimates of the rate of FVC decline obtained using home spirometry were poorly correlated with those based on clinic spirometry.
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http://dx.doi.org/10.1183/13993003.01518-2020DOI Listing
January 2021

Cryobiopsy for Identification of Usual Interstitial Pneumonia and Other Interstitial Lung Disease Features: Further Lessons from COLDICE, a Prospective Multi-Center Study.

Am J Respir Crit Care Med 2020 Dec 7. Epub 2020 Dec 7.

Royal Prince Alfred Hospital, 2205, Respiratory Medicine, Sydney, New South Wales, Australia.

Rationale: Transbronchial lung cryobiopsy (TBLC) is an emerging technique for interstitial lung disease (ILD) diagnosis. Good histopathologic agreement between TBLC and surgical lung biopsy (SLB) was demonstrated in the COLDICE Study, however diagnostic confidence was frequently lower for TBLC than SLB. This secondary analysis aimed to characterize specific features of TBLC predictive of usual interstitial pneumonia (UIP) in corresponding SLB and to identify clinical indices predictive of biopsy concordance.

Methods: COLDICE was a prospective, multicenter study investigating diagnostic agreement between TBLC and SLB. Participants underwent both procedures, with blinded pathologist analysis of specimens, applying international guideline criteria. TBLC features predictive of UIP in the paired SLB and predictive features of overall concordance were analyzed.

Results: 65 patients (66·1±9·3yrs; FVC 84·7±14·2%; DLCO 63·4±13·8%) participated in the COLDICE Study. UIP was identified in 33/65 (50.8%) SLB, and 81.5% were concordant with corresponding TBLC (κ 0.61, 95% CI 0.38-0.77). The UIP guideline criteria of "predominantly subpleural or paraseptal fibrosis" was infrequently reported in TBLC (8/33, 24.2%), while "patchy fibrosis", "fibroblast foci" and "absence of alternative diagnostic features" were frequently observed in TBLC. The combination of these three features strongly predicted UIP in paired SLB (OR 23.4, 95%CI 6.36-86.1, p<0.0001). Increased numbers of TBLC samples predicted histopathologic concordance with SLB (OR 1.8, 95% CI 1.08-3.01, p=0.03). Predictors of discordance included older age, family history and radiologic asymmetry.

Conclusion: Subpleural and/or paraseptal fibrosis were not essential for diagnosing UIP in TBLC, provided other guideline criteria features were present. Diagnostic accuracy of TBLC was strengthened when increased numbers of samples were taken.
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http://dx.doi.org/10.1164/rccm.202009-3688OCDOI Listing
December 2020

Top 10 research priorities for people living with pulmonary fibrosis, their caregivers, healthcare professionals and researchers.

Thorax 2020 Dec 4. Epub 2020 Dec 4.

Department of Allergy, Immunology and Respiratory Medicine, Monash University, Melbourne, Victoria, Australia

Introduction: People with pulmonary fibrosis (PF) experience a high symptom burden, reduced quality of life and a shortened lifespan. Treatment options are limited and little is known about what patients, caregivers and healthcare professionals (HCPs)/researchers consider as the most important research priorities. This study aimed to identify the top 10 research priorities for PF across all stakeholders.

Methods: Participants included people with PF, caregivers and HCPs/researchers involved with PF. The research priority setting exercise involved three stages: (1) identifying priorities using an open-ended questionnaire and thematic analysis, (2) development of specific research questions at a face-to-face workshop, and (3) online ranking of research questions to identify the top 10 research priorities using nominal group ranking method.

Results: 196 participants completed stage 1 generating 560 questions and 14 research themes were identified. Stage 2 involved 32 participants and generated 53 indicative questions from which 39 were used for the final ranking. Stage 3 was completed by 270 participants. The top ranked priorities focussed on medications to reverse scarring in the lungs (ranked 1), improving lung function (ranked 2, 6 and 8), interventions aimed at alleviating symptoms (ranked 5 and 7), prevention of PF (ranked 3 and 4) and the best exercise programme for PF (ranked 10). There was good consensus among patients/carers and HCPs/researchers on the top 10 priorities, however, causes of acute exacerbations and early diagnosis for improving survival, was ranked higher by HCPs/researchers.

Conclusion: Interventions for preserving lung health and alleviation of symptom burden were top research priorities for PF stakeholders.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215731DOI Listing
December 2020

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.

Respirology 2021 Jan 24;26(1):23-51. Epub 2020 Nov 24.

Department of Respiratory Medicine, Princess Alexandra Hospital, Brisbane, QLD, Australia.

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.
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http://dx.doi.org/10.1111/resp.13977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894187PMC
January 2021

Health-related quality of life of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

Eur Respir Rev 2020 Dec 5;29(158). Epub 2020 Nov 5.

Menzies Institute for Medical Research, University of Tasmania, Tasmania, Australia

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease presenting in persons 50 years and older. Through a comprehensive review of available studies, we aimed to assess health-related quality of life (HRQoL) of people living with IPF and the instruments used in this assessment.Searches were conducted up to May, 2020. Quality appraisal and data extraction were performed using pre-designed forms. Narrative synthesis approach was used to report results of the systematic review and a random effects model was used for the meta-analysis. A leave-one-out sensitivity analysis was performed, and a trim and fill method was used to assess publication bias.The review included 134 studies. The most used instruments to measure HRQoL were St George's Respiratory Questionnaire (SGRQ), Short Form 36 (SF36) and EuroQoL (EQ5D). Standardised mean scores (95% confidence interval) for these instruments were as follows: SGRQ total score: 44.72 (42.21-47.22); SF36 physical component score (PCS): 37.00 (34.74-39.26) SF36 mental component score (MCS): 50.18 (48.41-51.95); King's Brief Interstitial Lung Disease questionnaire total score: 58.38 (55.26-61.51); and EQ5D utility: 0.73 (0.68-0.79). Analysis of standardised means for both SGRQ and SF36 demonstrated worse scores in physical health domains as compared to mental health domains.This systematic review confirms that IPF negatively affected HRQoL, mostly impacting the physical health domains. This study also demonstrated that a diverse number of instruments are used to evaluate HRQoL. In view of this diversity, a standardised approach to measurement of HRQoL for IPF is important to ensure that comparisons made are reliable.
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http://dx.doi.org/10.1183/16000617.0154-2020DOI Listing
December 2020

Australasian interstitial lung disease registry (AILDR): objectives, design and rationale of a bi-national prospective database.

BMC Pulm Med 2020 Oct 2;20(1):257. Epub 2020 Oct 2.

Royal Prince Alfred Hospital, Sydney, NSW, Australia.

Background: Interstitial Lung Disease (ILD) is a group of respiratory conditions affecting the lung interstitium often associated with progressive respiratory failure. There is increasing recognition of the need for improved epidemiological data to help determine best practice and improve standardisation of care. The Australasian ILD Registry (AILDR) is a bi-national registry of patients with all ILD subtypes designed to establish a clinically meaningful database reflecting real world practice in Australasia with an objective to improve diagnostic and treatment pathways through research and collaboration.

Methods: AILDR is a prospective observational registry recruiting patients attending ILD clinics at centres around Australia and New Zealand. Core and non-core data are stored on a secure server. The pilot phase was launched in 2016 consisting of four sites in Australia. Currently in its second phase a further 16 sites have been recruited, including three in New Zealand.

Results: A total of 1061 participants were consented during the pilot phase. Baseline data demonstrated a mean age 68.3 ± 12.5 (SD) years, mean FVC (%predicted) 79.1 ± 20.4 (SD), mean DLCO (%predicted) 58.5 ± 17.9 (SD) and nadir exertional SpO2 (%) 91 ± 6.9 (SD). Idiopathic pulmonary fibrosis (31%) and connective-tissue disease related ILD (21.7%) were the two most common subtypes. Baseline demographics and physiology were not significantly different across the four centres.

Conclusion: AILDR is an important clinical and research tool providing a platform for epidemiological data that will prove essential in promoting understanding of a rare cohort of lung disease and provide foundations for our aspiration to standardise investigation and treatment pathways of ILD across Australasia.
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http://dx.doi.org/10.1186/s12890-020-01297-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532571PMC
October 2020

Priorities and expectations of patients attending a multidisciplinary interstitial lung disease clinic.

Respirology 2021 Jan 17;26(1):80-86. Epub 2020 Aug 17.

Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.

Background And Objective: The significant and progressive morbidity associated with ILD mean that patients often struggle with the impact of this disease on their QOL and independence. To date, no studies have investigated the importance of multidisciplinary care on patient experience in ILD. We aimed to determine the expectations and priorities of patients attending a tertiary referral centre multidisciplinary ILD clinic. In particular, we sought to learn how important the multidisciplinary element of the clinic was to patients and which aspects of the clinic were most valued.

Methods: An 18-item patient questionnaire was developed in conjunction with expert physicians and specialist nurses involved in the ILD clinic and sent to all patients on the centre's ILD registry at the time of the study (n = 240). Patients rated the importance of different aspects of their experience of attending the clinic. Data collected were analysed using descriptive statistics. Comparisons across disease severity were made using two-sided Z-tests for independent proportions.

Results: A total of 100 respondents comprised the study group. Almost all respondents valued the multidisciplinary aspect of the clinic. Obtaining an accurate diagnosis and improving their disease understanding was most important to respondents. The importance of the ILD specialist nurse for both education and support increased with worsening disease severity.

Conclusion: Our results suggest that a multidisciplinary approach to the management of ILD with additional focus on patient education, as well as tailoring care to disease severity, is a plausible pathway to improving the patient experience with ILD.
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http://dx.doi.org/10.1111/resp.13913DOI Listing
January 2021

First risk, next reward? A new clinico-radiological risk model predicts mortality in rheumatoid arthritis-associated interstitial lung disease.

Respirology 2020 12 30;25(12):1225-1226. Epub 2020 Jul 30.

Central Clinical School, University of Sydney, Sydney, NSW, Australia.

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http://dx.doi.org/10.1111/resp.13924DOI Listing
December 2020

Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.

Am J Respir Crit Care Med 2020 08;202(3):e36-e69

This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax. Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions. The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.
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http://dx.doi.org/10.1164/rccm.202005-2032STDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397797PMC
August 2020

Occupational and environmental risk factors for idiopathic pulmonary fibrosis in Australia: case-control study.

Thorax 2020 10 13;75(10):864-869. Epub 2020 Jul 13.

School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a lung disease of unknown cause characterised by progressive scarring, with limited effective treatment and a median survival of only 2-3 years. Our aim was to identify potential occupational and environmental exposures associated with IPF in Australia.

Methods: Cases were recruited by the Australian IPF registry. Population-based controls were recruited by random digit dialling, frequency matched on age, sex and state. Participants completed a questionnaire on demographics, smoking, family history, environmental and occupational exposures. Occupational exposure assessment was undertaken with the Finnish Job Exposure Matrix and Australian asbestos JEM. Multivariable logistic regression was used to describe associations with IPF as ORs and 95% CIs, adjusted for age, sex, state and smoking.

Results: We recruited 503 cases (mean±SD age 71±9 years, 69% male) and 902 controls (71±8 years, 69% male). Ever smoking tobacco was associated with increased risk of IPF: OR 2.20 (95% CI 1.74 to 2.79), but ever using marijuana with reduced risk after adjusting for tobacco: 0.51 (0.33 to 0.78). A family history of pulmonary fibrosis was associated with 12.6-fold (6.52 to 24.2) increased risk of IPF. Occupational exposures to secondhand smoke (OR 2.1; 1.2 to 3.7), respirable dust (OR 1.38; 1.04 to 1.82) and asbestos (OR 1.57; 1.15 to 2.15) were independently associated with increased risk of IPF. However occupational exposures to other specific organic, mineral or metal dusts were not associated with IPF.

Conclusion: The burden of IPF could be reduced by intensified tobacco control, occupational dust control measures and elimination of asbestos at work.
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http://dx.doi.org/10.1136/thoraxjnl-2019-214478DOI Listing
October 2020

Diagnosing idiopathic pulmonary fibrosis: Has the time for surgical lung biopsy passed?

Respirology 2020 11 9;25(11):1112-1113. Epub 2020 Jul 9.

Interstitial Lung Diseases Unit, Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.

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http://dx.doi.org/10.1111/resp.13909DOI Listing
November 2020

The supportive care needs of people living with pulmonary fibrosis and their caregivers: a systematic review.

Eur Respir Rev 2020 Jun 29;29(156). Epub 2020 Apr 29.

Physiotherapy, La Trobe University, Melbourne, Australia

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 ; 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.
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http://dx.doi.org/10.1183/16000617.0125-2019DOI Listing
June 2020

Nonspecific Interstitial Pneumonia.

Semin Respir Crit Care Med 2020 Apr 12;41(2):184-201. Epub 2020 Apr 12.

Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

Nonspecific interstitial pneumonia (NSIP) is a complex disorder commonly associated with other conditions such as connective tissue diseases (CTDs) and environmental exposures. Although idiopathic NSIP has been recognized as a separate clinical entity, recent studies have suggested that a proportion of these cases have autoimmune features suggestive of underlying CTDs. The diagnosis of NSIP usually carries a better prognosis compared with idiopathic pulmonary fibrosis but has an unpredictable natural history. Its pathogenesis is thought to be an inflammatory-driven process involving multiple pathways, including a genetic predisposition. The lack of specific clinical features often makes the diagnosis of NSIP difficult. The huge variability of radiological and histological features seen in NSIP adds to the complexity of achieving an accurate diagnosis of NSIP and a multidisciplinary approach is often required. There is a lack of consensus on the optimal management strategy of NSIP. Early clarification of the goals of therapy and close monitoring for the progression of disease is important across the spectrum of NSIP irrespective of its etiology. Although immunosuppressive and immunomodulatory agents are commonly used for severe and progressive disease, the therapeutic landscape of NSIP is constantly evolving as the role of newer agents such as antifibrotic therapies is being explored.
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http://dx.doi.org/10.1055/s-0040-1708499DOI Listing
April 2020

Peer Connect Service for people with pulmonary fibrosis in Australia: Participants' experiences and process evaluation.

Respirology 2020 10 23;25(10):1053-1059. Epub 2020 Mar 23.

Department of Allergy, Immunology and Respiratory Medicine, Monash University, Melbourne, VIC, Australia.

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.
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http://dx.doi.org/10.1111/resp.13807DOI Listing
October 2020

Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial.

Lancet Respir Med 2020 02 29;8(2):147-157. Epub 2019 Sep 29.

National Reference Coordinating Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Lyon, France; Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France.

Background: At present, no approved pharmacotherapies are available for unclassifiable interstitial lung disease (ILD), which is characterised by progressive fibrosis of the lung. We aimed to assess the efficacy and safety of pirfenidone in patients with progressive fibrosing unclassifiable ILD.

Methods: We did a multicentre, double-blind, randomised, placebo-controlled phase 2 trial at 70 centres in Australia, Belgium, Canada, Czech Republic, Denmark, Germany, Greece, Ireland, Israel, Italy, Poland, Portugal, Spain, and the UK. Eligible patients (aged ≥18-85 years) had progressive fibrosing unclassifiable ILD, a percent predicted forced vital capacity (FVC) of 45% or higher and percent predicted carbon monoxide diffusing capacity (DLco) of 30% or higher, more than 10% fibrosis on high-resolution CT, and a high-resolution CT from the previous 12 months. Patients were randomly assigned (1:1) to 2403 mg oral pirfenidone daily or placebo using a central validated interactive voice or web-based response system, stratified by concomitant mycophenolate mofetil use and presence or absence of interstitial pneumonia with autoimmune features. Investigators, site personnel, and patients were masked to treatment assignment. The primary endpoint was mean predicted change in FVC from baseline over 24 weeks, measured by daily home spirometry. Secondary endpoints were change in FVC measured by site spirometry, proportion of patients who had a more than 5% or more than 10% absolute or relative decline in percent predicted FVC measured by clinic-based spirometry, change in percent predicted DLco, change in 6-min walk distance (6MWD), change in University of California San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) score, change in Leicester Cough Questionnaire score, change in cough visual analogue scale, and changes in total and subscores of the St George's Respiratory Questionnaire (SGRQ), all of which were compared with baseline. Additional secondary endpoints included proportion of patients who had non-elective hospitalisation (respiratory and all-cause) and acute exacerbations, and progression-free survival. Efficacy was analysed in the intention-to-treat (ITT) population, which included all randomly assigned patients. Safety was assessed in the safety analysis set, which included all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03099187, and is no longer recruiting.

Findings: Between May 15, 2017, and June 5, 2018, 253 patients were randomly assigned to receive 2403 mg pirfenidone (n=127) or placebo (n=126) and were included in the ITT analysis set. Analysis of the primary endpoint was affected by intraindividual variability in home spirometry values, which prevented application of the prespecified statistical model. Over 24 weeks, predicted median change in FVC measured by home spirometry was -87·7 mL (Q1-Q3 -338·1 to 148·6) in the pirfenidone group versus -157·1 mL (-370·9 to 70·1) in the placebo group. Over 24 weeks, predicted mean change in FVC measured by site spirometry was lower in patients given pirfenidone than placebo (treatment difference 95·3 mL [95% CI 35·9 to 154·6], p=0·002). Compared with the placebo group, patients in the pirfenidone group were less likely to have a decline in FVC of more than 5% (odds ratio [OR] 0·42 [95% CI 0·25 to 0·69], p=0·001) or more than 10% (OR 0·44 [0·23 to 0·84], p=0·011). At week 24, mean change in DLco from baseline was -0·7% (SD 7·1) for the pirfenidone group and -2·5% (8·8) for the placebo group, and mean change in 6MWD from baseline was -2·0 m (68·1) for the pirfenidone group and -26·7 m (79·3) for the placebo group. Changes from baseline in UCSD-SOBQ, Leicester Cough Questionnaire score, cough visual analogue scale, and SGRQ scores were similar between the pirfenidone and placebo groups at week 24. Analysis of acute exacerbations, hospital admissions, and time to death from respiratory causes during the study yielded no meaningful results due to a small number of events. No differences in progression-free survival were identified between the pirfenidone and placebo groups, irrespective of the definition of progression-free survival used. Treatment-emergent adverse events were reported in 120 (94%) of 127 patients in the pirfenidone group and 101 (81%) of 124 patients in the placebo group. Serious treatment-emergent adverse events were reported in 18 (14%) patients in the pirfenidone group and 20 (16%) patients in the placebo group. The most common treatment-related treatment-emergent adverse events were gastrointestinal disorders (60 [47%] in the pirfenidone group vs 32 [26%] in the placebo group), fatigue (16 [13%] vs 12 [10%]), and rash (13 [10%] vs nine [7%]).

Interpretation: Although the planned statistical model could not be applied to the primary endpoint data, analysis of key secondary endpoints suggests that patients with progressive fibrosing unclassifiable ILD could benefit from pirfenidone treatment, which has an acceptable safety and tolerability profile. These findings support further investigation of pirfenidone as an effective treatment for patients with progressive fibrotic unclassifiable ILD.

Funding: F Hoffmann-La Roche.
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http://dx.doi.org/10.1016/S2213-2600(19)30341-8DOI Listing
February 2020

Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study.

Lancet Respir Med 2020 02 29;8(2):171-181. Epub 2019 Sep 29.

Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

Background: Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease diagnosis. The aim of this study was to establish the diagnostic accuracy of TBLC compared with surgical lung biopsy (SLB), in the context of increasing use of TBLC in clinical practice as a less invasive biopsy technique.

Methods: COLDICE was a prospective, multicentre, diagnostic accuracy study investigating diagnostic agreement between TBLC and SLB, across nine Australian tertiary hospitals. Patients with interstitial lung disease aged between 18 and 80 years were eligible for inclusion if they required histopathological evaluation to aid diagnosis, after detailed baseline evaluation. After screening at a centralised multidisciplinary discussion (MDD), patients with interstitial lung disease referred for lung biopsy underwent sequential TBLC and SLB under one anaesthetic. Each tissue sample was assigned a number between 1 and 130, allocated in a computer-generated random sequence. Encoded biopsy samples were then analysed by masked pathologists. At subsequent MDD, de-identified cases were discussed twice with either TBLC or SLB along with clinical and radiological data, in random non-consecutive order. Co-primary endpoints were agreement of histopathological features in TBLC and SLB for patterns of definite or probable usual interstitial pneumonia, indeterminate for usual interstitial pneumonia, and alternative diagnosis; and for agreement of consensus clinical diagnosis using TBLC and SLB at MDD. Concordance and κ values were calculated for each primary endpoint. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12615000718549.

Findings: Between March 15, 2016, and April 15, 2019, we enrolled 65 patients (31 [48%] men, 34 [52%] women; mean age 66·1 years [SD 9·3]; forced vital capacity 83·7% [SD 14·2]; diffusing capacity for carbon monoxide 63·4% [SD 12·8]). TBLC (7·1 mm, SD 1·9) and SLB (46·5 mm, 14·9) samples were each taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70·8% (weighted κ 0·70, 95% CI 0·55-0·86); diagnostic agreement at MDD was 76·9% (κ 0·62, 0·47-0·78). For TBLC with high or definite diagnostic confidence at MDD (39 [60%] of 65 cases), 37 (95%) were concordant with SLB diagnoses. In the 26 (40%) of 65 cases with low-confidence or unclassifiable TBLC diagnoses, SLB reclassified six (23%) to alternative high-confidence or definite MDD diagnoses. Mild-moderate airway bleeding occurred in 14 (22%) patients due to TBLC. The 90-day mortality was 2% (one of 65 patients), following acute exacerbation of idiopathic pulmonary fibrosis.

Interpretation: High levels of agreement between TBLC and SLB for both histopathological interpretation and MDD diagnoses were shown. The TBLC MDD diagnoses made with high confidence were particularly reliable, showing excellent concordance with SLB MDD diagnoses. These data support the clinical utility of TBLC in interstitial lung disease diagnostic algorithms. Further studies investigating the safety profile of TBLC are needed.

Funding: University of Sydney, Hunter Medical Research Institute, Erbe Elektromedizin, Medtronic, Cook Medical, Rymed, Karl-Storz, Zeiss, and Olympus.
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http://dx.doi.org/10.1016/S2213-2600(19)30342-XDOI Listing
February 2020

Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study.

Lancet Respir Med 2019 09 12;7(9):780-790. Epub 2019 Aug 12.

Royal Brompton Hospital, London, UK.

Background: Idiopathic interstitial pneumonias are often complicated by pulmonary hypertension, increasing morbidity and mortality. There are no approved treatments for pulmonary hypertension associated with idiopathic interstitial pneumonia (PH-IIP). We aimed to evaluate the efficacy and safety of riociguat in patients with PH-IIP.

Methods: RISE-IIP was a double-blind, randomised, placebo-controlled study done at 65 pulmonary hypertension and interstitial lung disease centres in 19 countries to evaluate the efficacy and safety of riociguat in patients with PH-IIP. Eligible patients were adults (aged 18-80 years) diagnosed with idiopathic interstitial pneumonia (as per American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines), forced vital capacity (FVC) of at least 45%, 6MWD of 150-450 m, WHO functional classes II-IV, precapillary pulmonary hypertension confirmed by right heart catheterisation, systolic blood pressure of at least 95 mm Hg, and no signs or symptoms of hypotension. Patients were randomly allocated (1:1) using an interactive voice and web response system to riociguat (0·5-2·5 mg three times daily) or placebo for 26 weeks (main study), after which they could enter an open-label extension in which all patients received riociguat. The primary endpoint was change in 6-min walking distance (6MWD) in the intention-to-treat population. Prespecified safety variables included adverse events and serious adverse events, laboratory parameters, and adverse events of special interest (haemoptysis and symptomatic hypotension), assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02138825.

Findings: Between June 4, 2014, and May 5, 2016, we enrolled 229 participants. After the exclusion of 82 participants, 147 were randomly allocated to treatment (73 to riociguat, 74 to placebo). The study was terminated early (median treatment duration 157 days [range 6-203]) at the request of the data monitoring committee owing to increased serious adverse events (main study: 27 [37%] of 73 participants in the riociguat group vs 17 [23%] of 74 in the placebo group) and mortality in patients receiving riociguat, and the absence of efficacy signals in the riociguat group. 11 patients died in the main study (eight in the riociguat group, three in the placebo group), and nine died in the extension phase (one in the riociguat group, eight in the former placebo group; all received riociguat). In the main study, the most common adverse events were peripheral oedema (16 [22%] of 73 in the riociguat group vs seven [9%] of 74 in the placebo group) and diarrhoea (11 [15%] vs seven [9%]). The most common serious adverse events were worsening of interstitial lung disease (main study: six [8%] of 73 in the riociguat group vs five [7%] of 74 in the placebo group) and pneumonia (four [5%] vs one [1%]). Riociguat did not improve 6MWD versus placebo at 26 weeks (least-squares mean difference 21 m; 95% CI -9 to 52).

Interpretation: In patients with PH-IIP, riociguat was associated with increased serious adverse events and mortality, and an unfavourable risk-benefit profile. Riociguat should not be used in patients with PH-IIP.

Funding: Bayer AG and Merck & Co.
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http://dx.doi.org/10.1016/S2213-2600(19)30250-4DOI Listing
September 2019