The TSANZ and Lung Foundation Australia 2023 landscape survey of lung cancer care across Australia and Aotearoa New Zealand.

BACKGROUND AND OBJECTIVE: Unwarranted variations in lung cancer care have been well described in both Australia and Aotearoa New Zealand, with shortfalls in hospital-based workforce and infrastructure previously demonstrated. A survey of lung cancer clinicians was performed to gain an updated understanding of current workforce and infrastructure. METHODS: An online Qualtrics survey included questions on institutional demographics, estimated lung cancer case load, multidisciplinary team (MDT) characteristics including workforce and local infrastructure. We sought to obtain one response from every institution treating lung cancer in Australia and Aotearoa New Zealand. RESULTS: Responses were received from 89 institutions, estimated to include 85% centres treating lung cancer in Australia and 100% of public hospitals in Aotearoa New Zealand. Lung cancer nurse specialist and Nuclear Medicine are poorly represented in multidisciplinary teams (MDTs) with just 34/88 (38%) institutions fulfilling recommended core workforce for MDT meetings. Case presentation is low with 32/88 (36%) regularly discussing all lung cancer patients at MDT. Metropolitan institutions appear to have a more comprehensive range of services on site, compared to non-metropolitan institutions. Few (4/88) institutions have embedded smoking cessation services. Compared to the previous 2021 Landscape Survey, thoracic surgery representation and core MDT workforce have improved, with modest change in specialist nurse numbers. CONCLUSION: This wide-reaching survey has identified persistent deficiencies and variations in lung cancer workforce and gaps in infrastructure. Multidisciplinary collaboration and care coordination are needed to ensure all patients can access timely and equitable lung cancer care.

Equity of travel to access surgery and radiation therapy for lung cancer in New Zealand.

PURPOSE: Centralisation of lung cancer treatment can improve outcomes, but may result in differential access to care for those who do not reside within treatment centres. METHODS: We used national-level cancer registration and health care access data and used Geographic Information Systems (GIS) methods to determine the distance and time to access first relevant surgery and first radiation therapy among all New Zealanders diagnosed with lung cancer (2007-2019; N = 27,869), and compared these outcomes between ethnic groups. We also explored the likelihood of being treated at a high-, medium-, or low-volume hospital. Analysis involved both descriptive and adjusted logistic regression modelling. RESULTS: We found that Maori tend to need to travel further (with longer travel times) to access both surgery (median travel distance: Maori 57 km, European 34 km) and radiation therapy (Maori 75 km, European 35 km) than Europeans. Maori have greater odds of living more than 200 km away from both surgery (adjusted odds ratio [aOR] 1.83, 95% CI 1.49-2.25) and radiation therapy (aOR 1.41, 95% CI 1.25-1.60). CONCLUSIONS: Centralisation of care may often improve treatment outcomes, but it also makes accessing treatment even more difficult for populations who are more likely to live rurally and in deprivation, such as Maori.

Access to and Timeliness of Lung Cancer Surgery, Radiation Therapy, and Systemic Therapy in New Zealand: A Universal Health Care Context.

PURPOSE: Lung cancer is the biggest cancer killer of indigenous peoples worldwide, including Maori people in New Zealand. There is some evidence of disparities in access to lung cancer treatment between Maori and non-Maori patients, but an examination of the depth and breadth of these disparities is needed. Here, we use national-level data to examine disparities in access to surgery, radiation therapy and systemic therapy between Maori and European patients, as well as timing of treatment relative to diagnosis. METHODS: We included all lung cancer registrations across New Zealand from 2007 to 2019 (N = 27,869) and compared access with treatment and the timing of treatment using national-level inpatient, outpatient, and pharmaceutical records. RESULTS: Maori patients with lung cancer appeared less likely to access surgery than European patients (Maori, 14%; European, 20%; adjusted odds ratio [adj OR], 0.82 [95% CI, 0.73 to 0.92]), including curative surgery (Maori, 10%; European, 16%; adj OR, 0.72 [95% CI, 0.62 to 0.84]). These differences were only partially explained by stage and comorbidity. There were no differences in access to radiation therapy or systemic therapy once adjusted for confounding by age. Although it appeared that there was a longer time from diagnosis to radiation therapy for Maori patients compared with European patients, this difference was small and requires further investigation. CONCLUSION: Our observation of differences in surgery rates between Maori and European patients with lung cancer who were not explained by stage of disease, tumor type, or comorbidity suggests that Maori patients who may be good candidates for surgery are missing out on this treatment to a greater extent than their European counterparts.

Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand.

This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi-disciplinary team that included consumers. The main statements are: Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co-existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease). Confirm bronchiectasis with a chest computed-tomography scan, using age-appropriate protocols and criteria in children. Undertake a baseline panel of investigations. Assess baseline severity, and health impact, and develop individualized management plans that include a multi-disciplinary approach and coordinated care between healthcare providers. Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality-of-life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis. Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules. Treat exacerbations with 14-day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs. Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures. Individualize therapy for long-term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents. Ensure ongoing care with 6-monthly monitoring for complications and co-morbidities. Undertake optimal care of under-served peoples, and despite its challenges, delivering best-practice treatment remains the overriding aim.

Emergency presentation prior to lung cancer diagnosis: A national-level examination of disparities and survival outcomes.

OBJECTIVES: A recent multinational investigation of emergency presentation within 30 days of cancer diagnosis, conducted within the International Cancer Benchmarking Programme (ICBP), observed that New Zealand had the highest rate of emergency presentation prior to lung cancer diagnosis compared to other similar countries. Here we use national-level health data to further investigate these trends, focussing on ethnic disparities in emergency presentation prior to lung cancer diagnosis. We have also compared survival outcomes between those who had an emergency presentation in the preceding 30 days to those who did not. MATERIALS AND METHODS: Our study included all lung cancer registrations between 2007 and 2019 on the New Zealand Cancer Registry (N = 27,869), linked to national hospitalisation and primary healthcare data. We used descriptive (crude and age-standardised proportions) and logistic regression (crude and adjusted odds ratios) analyses to examine primary care access prior to cancer diagnosis, emergency hospitalisation up to and including 30 days prior to diagnosis, and one-year mortality post-diagnosis, both for the total population and between ethnicities. Regression models adjusted for age, sex, deprivation, rurality, comorbidity, tumour type and stage. RESULTS: We found stark disparities by ethnic group, with 62% of Pacific peoples and 54% of Maori having an emergency presentation within 30 days prior to diagnosis, compared to 47% of Europeans. These disparities remained after adjusting for multiple covariates including comorbidity and deprivation (adj. OR: Maori 1.21, 95% CI 1.13-1.30; Pacific 1.50, 95% CI 1.31-1.71). Emergency presentation was associated with substantially poorer survival outcomes across ethnic groups (e.g. 1-year mortality for Maori: no emergency presentation 50%, emergency presentation 79%; adj. OR 2.40, 95% CI 2.10-2.74). CONCLUSIONS: These observations reinforce the need for improvements in the early detection of lung cancer, particularly for Maori and Pacific populations, with a view to preventing diagnosis of these cancers in an emergency setting.

Cryobiopsy with radial-endobronchial ultrasound (Cryo-Radial) has comparable diagnostic yield with higher safety in comparison to computed tomography-guided transthoracic biopsy for peripheral pulmonary lesions: An exploratory randomised study.

BACKGROUND: Computed tomography-guided transthoracic biopsy (CT-TTB) is the 'gold standard' biopsy for lung nodules. Radial-endobronchial ultrasound (R-EBUS) bronchoscopy is another recommended biopsy but carries a lower diagnostic yield. Addition of cryobiopsy with R-EBUS (Cryo-Radial) has shown promising results. There are no studies comparing CT-TTB with Cryo-Radial biopsy. AIM: The co-primary aims were the diagnostic yeild and safety. The secondary aim: ability to test epidermal growth factor receptor (EGFR). METHODS: A randomised controlled, multicentre exploratory study was conducted at three tertiary hospitals. Patients with nodules >1 cm on CT of the chest were randomised to CT-TTB or Cryo-Radial. With Cryo-Radial, patients had 1-3 cryo-biopsies in addition to at least one R-EBUS biopsy through the 2.6 mm guide sheath. RESULTS: Forty-eight patients were randomised: 22 to CT-TTB and 26 to Cryo-Radial. Sixteen in the CT-TTB and 20 in the Cryo-Radial received the allocated biopsy. The diagnostic yield was CT-TTB 93.8% (15/16) versus Cryo-Radial 85% (17/20) P = 0.61 and the odds ratio was 0.37. For 5/13 (38%), a diagnosis was solely made on cryobiopsy. Eleven (78%) of 14 in CT-TTB versus 7/10 (70%) Cryo-Radial were suitable for EGFR testing P = 0.66, with odds ratio 0.63. Pneumothorax occurrence was 44% (7/16) in CT-TTB versus 4.2% (1/24) in Cryo-Radial. Two (12.5%) of 16 CT-TTB required chest drain insertion. CONCLUSION: Cryo-Radial is comparable in diagnostic yield and ability to perform EGFR testing with a significantly lower risk of pneumothorax, compared with CT-TTB. Cryo-Radial has the additional advantage of mediastinal staging during the same procedure with Linear-EBUS and is a promising first-line tool in the diagnostic method of lung cancer.

A survey of adult respiratory and sleep services in Aotearoa New Zealand: inequities in the provision of adult respiratory and sleep services.

AIMS: The New Zealand "Standards for Adult Respiratory and Sleep Services" were published by the Ministry of Health in 2004. A 2006 survey demonstrated major gaps in the staffing and service provision and significant variation between district health boards (DHBs). We repeated this survey in 2019/20 in order to highlight issues which should be addressed as part of health service reforms. METHODS: Survey of all adult DHB respiratory services assessing staffing and service provision. RESULTS: There is marked regional variation in staffing levels for all specialist clinicians. There are 1.18 FTE/100,000 population respiratory physicians, which is well below Australian and United Kingdom levels. Two hundred thousand people in New Zealand do not have access to a local respiratory physician. For provided services we found a four-fold variation between DHBs for CPAP treatments, six-fold for oxygen services, and eight-fold for pulmonary rehabilitation. CONCLUSION: The place of residence of New Zealanders determines access to respiratory services. There are inequities in access, with little progress made since 2006. Data on health outcomes are required. The restructure of the health service must rectify this situation. The need to end a "postcode lottery" is demonstrated when reviewing current respiratory services in New Zealand.

An International Consensus on Actions to Improve Lung Cancer Survival: A Modified Delphi Method Among Clinical Experts in the International Cancer Benchmarking Partnership.

BACKGROUND: Research from the International Cancer Benchmarking Partnership (ICBP) demonstrates that international variation in lung cancer survival persists, particularly within early stage disease. There is a lack of international consensus on the critical contributing components to variation in lung cancer outcomes and the steps needed to optimise lung cancer services. These are needed to improve the quality of options for and equitable access to treatment, and ultimately improve survival. METHODS: Semi-structured interviews were conducted with 9 key informants from ICBP countries. An international clinical network representing 6 ICBP countries (Australia, Canada, Denmark, England, Ireland, New Zealand, Northern Ireland, Scotland & Wales) was established to share local clinical insights and examples of best practice. Using a modified Delphi consensus model, network members suggested and rated recommendations to optimise the management of lung cancer. Calls to Action were developed via Delphi voting as the most crucial recommendations, with Good Practice Points included to support their implementation. RESULTS: Five Calls to Action and thirteen Good Practice Points applicable to high income, comparable countries were developed and achieved 100% consensus. Calls to Action include (1) Implement cost-effective, clinically efficacious, and equitable lung cancer screening initiatives; (2) Ensure diagnosis of lung cancer within 30 days of referral; (3) Develop Thoracic Centres of Excellence; (4) Undertake an international audit of lung cancer care; and (5) Recognise improvements in lung cancer care and outcomes as a priority in cancer policy. CONCLUSION: The recommendations presented are the voice of an expert international lung cancer clinical network, and signpost key considerations for policymakers in countries within the ICBP but also in other comparable high-income countries. These define a roadmap to help align and focus efforts in improving outcomes and management of lung cancer patients globally.

Development of an Australia and New Zealand Lung Cancer Clinical Quality Registry: a protocol paper.

INTRODUCTION: Lung cancer is the leading cause of cancer mortality, comprising the largest national cancer disease burden in Australia and New Zealand. Regional reports identify substantial evidence-practice gaps, unwarranted variation from best practice, and variation in processes and outcomes of care between treating centres. The Australia and New Zealand Lung Cancer Registry (ANZLCR) will be developed as a Clinical Quality Registry to monitor the safety, quality and effectiveness of lung cancer care in Australia and New Zealand. METHODS AND ANALYSIS: Patient participants will include all adults >18 years of age with a new diagnosis of non-small-cell lung cancer (NSCLC), SCLC, thymoma or mesothelioma. The ANZLCR will register confirmed diagnoses using opt-out consent. Data will address key patient, disease, management processes and outcomes reported as clinical quality indicators. Electronic data collection facilitated by local data collectors and local, state and federal data linkage will enhance completeness and accuracy. Data will be stored and maintained in a secure web-based data platform overseen by registry management. Central governance with binational representation from consumers, patients and carers, governance, administration, health department, health policy bodies, university research and healthcare workers will provide project oversight. ETHICS AND DISSEMINATION: The ANZLCR has received national ethics approval under the National Mutual Acceptance scheme. Data will be routinely reported to participating sites describing performance against measures of agreed best practice and nationally to stakeholders including federal, state and territory departments of health. Local, regional and (bi)national benchmarks, augmented with online dashboard indicator reporting will enable local targeting of quality improvement efforts.

The impact of COVID-19 on lung cancer detection, diagnosis and treatment for Maori in Aotearoa New Zealand.

AIM: The purpose of this article is to examine disparities in the impact of the COVID-19 pandemic on access to lung cancer diagnosis and access to clinical services between Maori and non-Maori. METHODS: Using national-level data, we examined age-standardised lung cancer registrations, diagnostic procedures (bronchoscopy) and lung surgeries separately by ethnic group for the years 2018-2020, as well as patterns of stage of diagnosis. RESULTS: We found a trend toward a reduction in rates of lung cancer registration in Maori (but not non-Maori/non-Pacific) New Zealanders in 2020 compared to 2018 and 2019, but no apparent shift in the distribution of stage at diagnosis. We found a trend toward a reduction in rates of bronchoscopy for both Maori and non-Maori/non-Pacific patients, with the largest reduction observed for Maori. Rates of lung cancer surgery appeared to have reduced for Maori patients, although this was based on a small number of procedures. CONCLUSIONS: We observed disparities between Maori and non-Maori/non-Pacific patients in lung cancer registration and bronchoscopy as a result of the COVID-19 pandemic.

Lung cancer screening in Australia and New Zealand: the evidence and the challenge.

Lung cancer remains the commonest cause of cancer death in Australia and New Zealand. Targeted screening of individuals at highest risk of lung cancer aims to detect early stage disease, which may be amenable to potentially curative treatment. While current policy recommendations in Australia and New Zealand have acknowledged the efficacy of lung cancer screening in clinical trials, there has been no implementation of national programmes. With the recent release of findings from large international trials, the evidence and experience in lung cancer screening has broadened. This article discusses the latest evidence and implications for Australia and New Zealand.

Radial-probe endobronchial ultrasound outcomes in the investigation of peripheral pulmonary lesions: a New Zealand perspective.

BACKGROUND: Radial-probe endobronchial ultrasound (radial-EBUS) is becoming an important investigation for peripheral pulmonary lesions (PPL). A key advantage of radial-EBUS is the favourable risk profile compared with current gold-standard computerised tomography-guided biopsy. AIM: To investigate the diagnostic yield, predictors of positive yield and radial-EBUS safety in a New Zealand institution. We also determined whether molecular analysis was possible on the same tissue samples. METHODS: We performed a retrospective analysis of all patients (n = 68) from Middlemore Hospital, Auckland, undergoing radial-EBUS with guide-sheath for PPL from March 2015 to August 2016. Clinical, radiological and procedural data were collected. Radial-EBUS diagnostic yield was determined for malignant and benign diagnoses, and molecular analysis yield was determined on appropriate malignant samples. Logistic regression was used to determine factors predicting successful radial-EBUS. RESULTS: Overall diagnostic yield of radial-EBUS was 55.9% (95% confidence interval (CI): 44.3-67.9). Malignant diagnostic sensitivity was 60.8% (95% CI: 46.1-74.2) and benign diagnostic sensitivity was 50% (95% CI: 23-77). Lesions close to the hilum (P = 0.039), concentric radial-probe positioning (P = 0.008) and the use of forceps as first instrument (P = 0.0049) significantly predicted successful diagnostic yield. Of the malignant cases 81.0% (95% CI: 58.1-94.6) were sufficient for molecular analysis. Pneumothorax occurred in 4.4% (95% CI: 0.9-12.4), none required chest drain intervention. There were no cases of significant pulmonary haemorrhage. CONCLUSION: Radial-EBUS was shown to be safe with diagnostic yield similar to international reports. Important predictors of success include distance from hilum, probe position and forceps as first instrument. We also demonstrated that molecular analysis is possible in radial-EBUS obtained samples.

Deletion of Serpina1a, a murine α1-antitrypsin ortholog, results in embryonic lethality.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States Approximately 1% to 2% of COPD patients suffer from α(1)-antitrypsin (A1AT) deficiency, the major inheritable predisposition to COPD/emphysema. To further study the role of A1AT deficiency in the pathogenesis of COPD/emphysema, the authors attempted to generate null-mutant mice for Serpina1a, 1 of 2 A1AT orthologs in mice. Here the authors show that targeted deletion of Serpina1a results in embryonic lethality prior to 8.5 days post conception (dpc). The results are surprising given that A1AT-null humans exist and therefore do not require this gene product for normal development. The Serpina1 gene cluster is substantially different between mouse and man. Through gene duplication, mice have 3 to 5 (depending on the strain) highly homologous proteinase inhibiting (Pi) genes, 2 of which inhibit neutrophil elastase. Despite the abundance of Pi genes in mice, Serpina1a serves a critical, nonredundant function during early mouse development. A1AT-deficient mice have been highly sought after to study emphysema, cancer, and liver disease, and as a model to perfect gene replacement therapy. These results highlight important differences between human and murine serpins and point to the difficulty inherent to using gene-targeted mice to study this common human genetic disease.

Studies of gamma-glutamyl transferase in alpha-1 antitrypsin deficiency.

Gamma-glutamyl transferase (GGT) is a clinical marker of biliary disease, but is also of importance in anti-oxidant metabolic pathways and, consequently, is a potential biomarker of oxidative stress in COPD. Serum GGT is increased in alpha-1 antitrypsin deficiency (AATD) but this could reflect a hepatic, systemic or pulmonary origin. We aimed to investigate the relationship between serum GGT, lung disease, liver disease and mortality in subjects with AATD. Serum GGT was measured at the baseline assessment in 334 PiZ subjects from the UK AATD registry, and related to static lung function, chronic bronchitis, sputum purulence, history of acute exacerbations, smoking status, mortality, alcohol consumption, cirrhosis and serum markers of liver disease. GGT correlated with airflow obstruction and was associated with chronic bronchitis. GGT levels were higher in current smokers compared with ex-smokers and never smokers, and in non-survivors compared with survivors. Although GGT related to alcohol consumption and established liver disease, it was independently related to FEV(1), mortality, smoking history and male gender. In conclusion, although serum GGT reflects the presence of liver disease it is independently associated with airflow obstruction and mortality. Further studies are needed to establish the role of GGT in oxidative lung injury, and its use as a potential biomarker in chronic inflammatory lung disease.

Mortality in alpha-1-antitrypsin deficiency in the United Kingdom.

BACKGROUND: Four hundred and eighty-eight PiZ alpha-1-antitrypsin deficient patients, who had joined the UK registry over a 9-year period, were followed in an observational study to determine mortality. None had received A1AT augmentation therapy. METHODS: Cause of death was confirmed from death certification and medical records. Patients were censored according to length of time on the program or until they withdrew from the program. RESULTS: There were 56 deaths of which 30 were attributed to respiratory causes. Of the remaining 26 deaths, 4 were due to complications from lung transplant, 6 due to liver disease (including 2 post-liver transplant) and the other 16 due to a variety of causes. Kaplan-Meier plots indicated a cumulative hazard for mortality of 18.1% in 9 years, correcting for time of follow up. When categorised for FEV1 percent-predicted, the group with severe impairment had increased mortality (p = <0.001) compared with the mild group and there was a direct relationship between severity and mortality. The severe group had increased mortality compared with the mild group when categorised for KCO percent-predicted (p<0.001), RV/TLC ratio (p<0.001) or emphysema score on CT scan (p<0.001 upper zone). Cox regression analyses indicated that these relationships remained when corrected for age. There were no differences in mortality after categorisation for educational level or occupational group. CONCLUSION: Mortality in a cohort of A1AT deficient patients (PiZ phenotype) in the UK was 2% per year and was associated with lung function impairment and emphysema severity on CT scan, but not social status.

An outbreak of extrinsic alveolitis at a car engine plant.

BACKGROUND: Twelve workers from a car engine-manufacturing plant presented with extrinsic allergic alveolitis (EAA), with heterogeneous clinical, radiological and pathological findings. They were exposed to metalworking fluids (MWF) that cooled, lubricated and cleaned the machines. METHODS: They were characterized by history, examination, lung function testing, radiology, bronchoscopic lavage, lung biopsy and serology. Sera were tested for precipitins to a crude extract of used MWF and to reference cultures of bacteria suspected to be implicated. RESULTS: All were males and none were current smokers. All had dyspnoea, many had weight loss and cough, but only half had influenza-like symptoms. Only half had auscultatory crackles. Five had peak flow variability, four with an occupational component. There was overall restrictive spirometry, decreased lung volumes and reduced gas transfers. Ten had radiological evidence of interstitial lung disease. Seven (of eight) had lymphocytosis on bronchial lavage, including the two with inconclusive radiology. Seven (of 11) had lung biopsies showing inflammatory infiltrates, two with fibrosis and one with granulomas. Three (of 11) had strong positive precipitins to an extract of the used MWF from the plant. Molecular biological analysis of the MWF revealed Acinetobacter and Ochrobactrum. Precipitins to Acinetobacter were detected in seven of 11 workers tested (and four of 11 control workers). Precipitins to Ochrobactrum were detected in three of 11 workers tested (and three of 11 control workers). CONCLUSION: This is the largest series reported in Europe of EAA due to an aerosol of microbiologically contaminated MWF in heavy manufacturing industry.