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.

Cardiorespiratory responses to muscle metaboreflex activation in fibrosing interstitial lung disease.

NEW FINDINGS: What is the central question of this study? We determined whether sensory feedback from metabolically sensitive skeletal muscle afferents (metaboreflex) causes a greater ventilatory response and higher dyspnoea ratings in fibrosing interstitial lung disease (FILD). What is the main finding and its importance? Ventilatory responses and dyspnoea ratings during handgrip exercise and metaboreflex isolation were not different in FILD and control groups. Blood pressure and heart rate responses to handgrip were attenuated in FILD but not different to controls during metaboreflex isolation. These findings suggest that the muscle metaboreflex contribution to the respiratory response to exercise is not altered in FILD. ABSTRACT: Exercise limitation and dyspnoea are hallmarks of fibrosing interstitial lung disease (FILD); however, the physiological mechanisms are poorly understood. In other respiratory diseases, there is evidence that an augmented muscle metaboreflex may be implicated. We hypothesized that metaboreflex activation in FILD would result in elevated ventilation and dyspnoea ratings compared to healthy controls, due to augmented muscle metaboreflex. Sixteen FILD patients (three women, 69±14 years; mean±SD) and 16 age-matched controls (four women, 67±7 years) were recruited. In a randomized cross-over design, participants completed two min of rhythmic handgrip followed by either (i) two min of post-exercise circulatory occlusion (PECO trial) to isolate muscle metaboreflex activation, or (ii) rested for four min (Control trial). Minute ventilation ( V̇E$\dot{V}_E$ ; pneumotachometer), dyspnoea ratings (0-10 Borg scale), mean arterial pressure (MAP; finger photoplethysmography) and heart rate (HR; electrocardiogram) were measured. V̇E$\dot{V}_E$ was higher in the FILD group at baseline and exercise increased V̇E$\dot{V}_E$ similarly in both groups. V̇E$\dot{V}_E$ remained elevated during PECO, but there was no between-group difference in the magnitude of this response (Δ V̇E$\dot{V}_E$ FILD 4.2 ± 2.5 L·min-1  vs. controls 3.6 ± 2.4 L·min-1 , P = 0.596). At the end of PECO, dyspnoea ratings in FILD were similar to controls (1.0 ± 1.3 units vs. 0.5 ± 1.1 units). Exercise increased MAP and HR (P < 0.05) in both groups; however, responses were lower in FILD. Collectively, these findings suggest that there is not an augmented effect of the muscle metaboreflex on breathing and dyspnoea in FILD, but haemodynamic responses to handgrip are reduced relative to controls.

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.

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.

Ethnicity, socioeconomic status and the severity and course of non-cystic fibrosis bronchiectasis.

BACKGROUND AND AIMS: This study evaluated whether there are ethnic factors which affect the severity and progression of bronchiectasis in our adult multi-ethnic population in Auckland, New Zealand. METHODS: Clinical records were reviewed from patients attending the outpatient facilities of our institution between 2007 and 2010. Data collected included demographics, clinical features, smoking status, self-reported ethnicity, socioeconomic status (NZDep), pulmonary function and sputum microbiology. RESULTS: A total of 437 patients was identified: median age 65 years, 66% female, mean forced expiratory volume in the first second (FEV1 ) 62.4% predicted, and 10.5% of patients had recurrent growth of Pseudomonas aeruginosa. Patients of Maori and Pacific ethnicity were overrepresented compared to the institution population catchment and had more severe impairment of lung function: mean % predicted FEV1 for Pacific 52.0, Maori 58.6, European 68.6, Asian 64.2 (P < 0.0001). This was independent of socioeconomic status. However, no overall decline was seen in serial lung function measurements, either across the whole cohort or in any particular ethnic group. CONCLUSIONS: Patients of Maori and Pacific ethnicity are both overrepresented and have more severe bronchiectasis in this cohort, independent of socioeconomic status. Ethnicity did not predict decline in pulmonary function. Further studies into genetic predisposition to bronchiectasis in Maori or Pacific people may be warranted.

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.

The relationships among dyspnoea, health-related quality of life and psychological factors in sarcoidosis.

BACKGROUND AND OBJECTIVES: Dyspnoea is a common symptom in sarcoidosis and is not predictably related to pulmonary function or radiology. A subjective symptom of dyspnoea is likely to be influenced by patient perception and experience. The aim of this study was to determine the prevalence and nature of dyspnoea in sarcoidosis and describe the relationship of dyspnoea to psychological factors and health-related quality of life (HRQL). METHODS: Fifty-six subjects (31 men, mean age 51 years) with sarcoidosis completed an HRQL measure, St George's Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS) and Nijmegen questionnaire. The presence of symptoms of dyspnoea was noted and qualitative descriptors for dyspnoea were chosen at peak exercise. Resting pulmonary function was performed. RESULTS: Sixty-four per cent of the subjects reported dyspnoea. Those with symptoms were older, had a longer duration of disease and with lower forced expiratory volume in 1 s (FEV1 ) and FEV1 /forced vital capacity (FVC) (all P < 0.05). Symptoms of dyspnoea were associated with worse HRQL (P < 0.005) and higher scores on the Nijmegen questionnaire (P < 0.05). Anxiety was not associated with dyspnoea and only a trend to greater depression was observed (P = 0.066). In multivariate analysis, SGRQ and Nijmegen scores predicted dyspnoea independent of demographic factors and resting pulmonary function. CONCLUSION: Dyspnoea is common in sarcoidosis and is associated with worse HRQL irrespective of baseline pulmonary function. Hyperventilation appears to be a factor contributing to dyspnoea and the Nijmegen questionnaire may be helpful in assessing dyspnoea and hyperventilation in sarcoidosis patients.

Comparison of the modified shuttle walk test and cardiopulmonary exercise test in sarcoidosis.

BACKGROUND AND OBJECTIVE: Dyspnoea and exercise intolerance are common in sarcoidosis and are often poorly correlated with resting lung function. Measurement of peak exercise capacity is likely to be helpful in assessing and monitoring disease. The aim of this study was to compare the modified shuttle walk test (MSWT) to cardiopulmonary exercise test (CPET) as a measure of peak exercise capacity in sarcoidosis. METHODS: Thirty-three (17 male, mean age 48 years) patients with sarcoidosis completed a standardized exponential exercise protocol cycle ergometer CPET and a single corridor MSWT in random order. RESULTS: Subjects has a mean forced expiratory volume in 1 s (FEV1) 2.4 L (75.7%predicted), forced vital capacity (FVC) 3.43 L (88.7%predicted) and diffusing capacity for carbon monoxide (DLCO) 20.3 mL/min/mm Hg (71.4%predicted). There was a strong correlation between MSWT distance and peak oxygen uptake (VO2) during CPET (r = 0.87; P < 0.0001), and between maximum heart rate during MSWT and CPET (r = 0.82; P < 0.0001). There was a moderate correlation between FEV1 , FVC and DLCO with MSWT distance (r = 0.55, r = 0.61, r = 0.61, respectively; all P < 0.001) and with peak VO2 (r = 0.62, r = 0.63, r = 0.62, respectively; all P < 0.0001). CONCLUSIONS: Peak VO2 achieved during CPET strongly correlated with MSWT distance. MSWT is a measure of peak exercise capacity in sarcoidosis that does not require equipment and can be readily available in the clinic.

Sex- and Race-Based Differences in the Treatment of Interstitial Lung Diseases in North America and Australasia.

BACKGROUND: Biological sex, gender, and race are important considerations in patients with interstitial lung diseases (ILDs). RESEARCH QUESTION: Does a patient's sex assigned at birth, and race, influence ILD treatment initiation? STUDY DESIGN AND METHODS: Patients with ILD from three longitudinal prospective registries were compared in this observational study. ILD-related medications included antifibrotics and immunomodulating medications. Race was dichotomized as "White" vs "non-White." Time to treatment initiation was determined from the date of the initial ILD registry visit to the date of first medication initiation. Proportions of treated patients were compared between groups by χ2 test. Cox proportional analysis was used to determine how sex and race were associated with time to treatment initiation stratified by ILD diagnosis. RESULTS: A total of 4,572 patients were included across all cohorts. The proportion of men who received treatment was higher than for women in the Canadian cohort (47% vs 40%; P < .001), and the proportion of White patients who received treatment was also higher compared with non-White patients (46% vs 36%; P < .001). In contrast, the proportion of treated men in the Chicago cohort was lower compared with women (56% vs 64%; P = .005), and that of White patients was lower compared with non-White patients (56% vs 69%; P < .001). No sex- or race-based differences in proportions of patients treated were found in the Australasian cohort. White race was significantly associated with earlier treatment initiation compared with non-White race across diagnoses in the Canadian cohort, whereas the opposite association was found in the Australasian cohort. INTERPRETATION: Sex- and race-based differences exist in the initiation of ILD treatment, with variability across different cohorts in different countries. Reasons for these differences need to be further explored in future studies.

Validation of the Sarcoidosis Health Questionnaire in a non-US population.

BACKGROUND AND OBJECTIVE: Sarcoidosis is a multi-system disease with an unpredictable course and variable clinical manifestations that are often associated with impaired quality of life. The Sarcoidosis Health Questionnaire (SHQ), which was developed for an 80% African American population, assesses health-related quality of life in sarcoidosis patients. The aim of this study was to validate the SHQ in a predominantly European population of sarcoidosis patients. METHODS: Consecutive outpatients (n = 92) with sarcoidosis, who were attending a teaching hospital clinic, completed three questionnaires (SHQ, Short Form (SF) 36, Fatigue Assessment Scale (FAS)) and pulmonary function tests were performed. RESULTS: The mean age of the patients was 51 years, 52% were males and 74% were of European ethnicity. The mean number of organs involved was 1.3, with pulmonary involvement in 95% of patients (mean forced expiratory volume in 1 s 74.4%, forced vital capacity 84.6%). Seventy percent of patients had current symptoms and 26.5% were receiving immunosuppressant therapy. The SHQ total score (mean 5.13) was significantly correlated with the SF 36 physical component score (46.7, r = 0.78) and the FAS (20.8, r = -0.7) but only weakly correlated with pulmonary function. There were significant differences in SHQ scores when patients were stratified according to symptoms, oral therapy, health status (P < 0.0001 for all), forced expiratory volume in 1 s ≥70% (P = 0.008) and forced vital capacity ≥70% (P = 0.01). CONCLUSIONS: The SHQ correlated well with health-related quality of life and fatigue measures in a predominantly European population of sarcoidosis patients, despite differences in organ involvement and disease burden, when compared with the development study.