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Background Lung cancer is the most common cause of cancer‐related death in the world, however lung cancer screening has not been implemented in most countries at a population level. A previous Cochrane Review found limited evidence for the effectiveness of lung cancer screening with chest radiography (CXR) or sputum cytology in reducing lung cancer‐related mortality, however there has been increasing evidence supporting screening with low‐dose computed tomography (LDCT). Objectives To determine whether screening for lung cancer using LDCT of the chest reduces lung cancer‐related mortality and to evaluate the possible harms of LDCT screening. Search methods We performed the search in collaboration with the Information Specialist of the Cochrane Lung Cancer Group and included the Cochrane Lung Cancer Group Trial Register, Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, current issue), MEDLINE (accessed via PubMed) and Embase in our search. We also searched the clinical trial registries to identify unpublished and ongoing trials. We did not impose any restriction on language of publication. The search was performed up to 31 July 2021. Selection criteria Randomised controlled trials (RCTs) of lung cancer screening using LDCT and reporting mortality or harm outcomes. Data collection and analysis Two review authors were involved in independently assessing trials for eligibility, extraction of trial data and characteristics, and assessing risk of bias of the included trials using the Cochrane RoB 1 tool. We assessed the certainty of evidence using GRADE. Primary outcomes were lung cancer‐related mortality and harms of screening. We performed a meta‐analysis, where appropriate, for all outcomes using a random‐effects model. We only included trials in the analysis of mortality outcomes if they had at least 5 years of follow‐up. We reported risk ratios (RRs) and hazard ratios (HRs), with 95% confidence intervals (CIs) and used the I2statistic to investigate heterogeneity. Main results We included 11 trials in this review with a total of 94,445 participants. Trials were conducted in Europe and the USA in people aged 40 years or older, with most trials having an entry requirement of ≥ 20 pack‐year smoking history (e.g. 1 pack of cigarettes/day for 20 years or 2 packs/day for 10 years etc.). One trial included male participants only. Eight trials were phase three RCTs, with two feasibility RCTs and one pilot RCT. Seven of the included trials had no screening as a comparison, and four trials had CXR screening as a comparator. Screening frequency included annual, biennial and incrementing intervals. The duration of screening ranged from 1 year to 10 years. Mortality follow‐up was from 5 years to approximately 12 years. None of the included trials were at low risk of bias across all domains. The certainty of evidence was moderate to low across different outcomes, as assessed by GRADE. In the meta‐analysis of trials assessing lung cancer‐related mortality, we included eight trials (91,122 participants), and there was a reduction in mortality of 21% with LDCT screening compared to control groups of no screening or CXR screening (RR 0.79, 95% CI 0.72 to 0.87; 8 trials, 91,122 participants; moderate‐certainty evidence). There were probably no differences in subgroups for analyses by control type, sex, geographical region, and nodule management algorithm. Females appeared to have a larger lung cancer‐related mortality benefit compared to males with LDCT screening. There was also a reduction in all‐cause mortality (including lung cancer‐related) of 5% (RR 0.95, 95% CI 0.91 to 0.99; 8 trials, 91,107 participants; moderate‐certainty evidence). Invasive tests occurred more frequently in the LDCT group (RR 2.60, 95% CI 2.41 to 2.80; 3 trials, 60,003 participants; moderate‐certainty evidence). However, analysis of 60‐day postoperative mortality was not significant between groups (RR 0.68, 95% CI 0.24 to 1.94; 2 trials, 409 participants; moderate‐certainty evidence). False‐positive results and recall rates were higher with LDCT screening compared to screening with CXR, however there was low‐certainty evidence in the meta‐analyses due to heterogeneity and risk of bias concerns. Estimated overdiagnosis with LDCT screening was 18%, however the 95% CI was 0 to 36% (risk difference (RD) 0.18, 95% CI ‐0.00 to 0.36; 5 trials, 28,656 participants; low‐certainty evidence). Four trials compared different aspects of health‐related quality of life (HRQoL) using various measures. Anxiety was pooled from three trials, with participants in LDCT screening reporting lower anxiety scores than in the control group (standardised mean difference (SMD) ‐0.43, 95% CI ‐0.59 to ‐0.27; 3 trials, 8153 participants; low‐certainty evidence). There were insufficient data to comment on the impact of LDCT screening on smoking behaviour. Authors' conclusions The current evidence supports a reduction in lung cancer‐related mortality with the use of LDCT for lung cancer screening in high‐risk populations (those over the age of 40 with a significant smoking exposure). However, there are limited data on harms and further trials are required to determine participant selection and optimal frequency and duration of screening, with potential for significant overdiagnosis of lung cancer. Trials are ongoing for lung cancer screening in non‐smokers.&nbsp

BACKGROUND Low-dose computed tomography (LDCT) screening can reduce lung cancer deaths in high-risk individuals, yet current Australian guidelines do not recommend screening. Little is known about current screening practices in Australia. AIM To evaluate the proportion of general practitioners who report ordering lung cancer screening for their patients, identify factors associated with ordering lung cancer screening and assess general practitioners (GP) rationale for recommending screening and preference of composition of any future national targeted screening programme. METHODS A survey was distributed to a nationally representative sample of 4000 Australian GP. The questionnaire included respondent demographics, self-reported screening practices, knowledge of screening recommendations, recent screening education, preference for recruitment methodologies for potential screening programmes and potential factors influencing the screening practices of GP. Two logistic regression models identified factors associated with self-reported chest X-ray (CXR) and LDCT screening within the past 12 months. RESULTS A total of 323 GP completed the survey (participation rate 8.1%). Participants were mostly females (50.6%), from collective/group (79.1%) and metropolitan-based practices (73.5%). Despite the majority of responders understanding that screening is not recommended by Australian professional societies (71.2%), a substantial proportion of participants requested a CXR or LDCT screening (46.4% and 20.8% respectively). A variety of shared (GP reassurance, affordability of screening, believing screening is funded) and unique practice, educational and cognitive factors were associated with self-reported LDCT and CXR screening, with the strongest association being recent education about screening from radiology practices (odds ratio (aOR) for LDCT screening 10.4, P

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.

Lung cancer screening is effective at reducing lung cancer deaths when individuals at greatest risk are screened. Recruitment initiatives target all current and former smokers, of whom only some are eligible for screening, potentially leading to discordance between screening preference and eligibility in ineligible individuals. The objective of the present study was to identify factors associated with preference for screening among ever-smokers. Ever-smokers aged 55–80 years attending outpatient clinics at three Australian hospitals were invited. The survey recorded: 1) demographics; 2) objective lung cancer risk and screening eligibility using the Prostate Lung Colon Ovarian 2012 risk model; and 3) perceived lung cancer risk, worry about and seriousness of lung cancer using a validated questionnaire. Multivariable ordinal logistic regression identified predictors of screening preference. The survey was completed by 283 individuals (response rate 27%). Preference for screening was high (72%) with no significant difference between low-dose computed tomography screening-eligible and -ineligible individuals (77% versus 68%, p=0.11). Worry about lung cancer (adjusted-proportional odds ratio (adj-OR) 1.31, 95% CI 1.08–1.58; p=0.007) and perceived seriousness of lung cancer (adj-OR 1.31, 95% CI 1.05–1.64; p=0.02) were associated with higher preference for lung cancer screening while screening eligibility was not. The concept of “early detection” was the most important driver to have screening while practical obstacles like difficulty travelling to the scan or taking time off work were the least important barriers to screening. Most current or former smokers prefer to undergo screening. Worry about lung cancer and perceived seriousness of the diagnosis are more important drivers for screening preference than eligibility status., Preference for lung cancer screening is high among Australian current and former smokers. Worry about lung cancer and perceived seriousness of the disease are associated with screening preference, while eligibility based on lung cancer risk is not. http://bit.ly/36PZlYA

Background Chronic obstructive pulmonary disease (COPD) is a disorder linked with a multitude of extra pulmonary manifestations (also known as treatable traits), including low bone mineral density (BMD). To date, no specific guidelines exist for the management of BMD in this population. Impact loading exercise has been identified as an intervention that improves or maintains BMD in other populations. However, the feasibility of and tolerance to impact loading exercise has not been tested in people with COPD. The aim of the proposed study will be to investigate the feasibility and tolerance of adding impact loading exercise to a standard pulmonary rehabilitation programme (PRP) in people with COPD and report its effects on bone health, balance and falls risk. Methods This is a protocol for a pilot feasibility and tolerance randomised controlled trial (RCT). Fifty-eight people with COPD will be randomly allocated, on a 1:1 ratio, to either the experimental or control group. Initially, participants in both groups will complete a standard 8-week (twice-weekly) PRP followed by a 32-week period of maintenance exercises. Over the initial 8-week period, participants allocated to the experimental group will also undertake targeted lower limb resistance exercises and commence a programme of impact loading exercises (e.g. bounding and drop jumps). On completion of the initial 8-week PRP, in addition to the standard maintenance exercises, participants in the experimental group will continue with home-based impact loading exercises, four times a week, for the extra 32 weeks. The primary outcome of this study is feasibility of and tolerance to impact loading exercises. Feasibility will be measured using data collected pertaining to recruitment, withdrawal and completion. Adherence to the exercises will be collected using exercise logs. Tolerance to the exercises will be determined using outcomes to assess pain, recording any adverse effects such as a fall and feedback from the participants in semi-structured interviews on completing of the trial. The effects of the 40-week experimental intervention on bone health, balance and falls risk will be reported. Discussion This pilot RCT will test the feasibility and tolerance of an intervention that has never been trialed in people with COPD. It will also provide initial information regarding the size of the effect this intervention has on outcomes such as BMD, balance and falls risk. These data will be critical when designing a definitive RCT to advance this area of research. Trial registration Australian and New Zealand Clinical Trials Registry (ANZCTR): 12620001085965 (20/10/2020)

Lung cancer screening of high-risk individuals with computed tomography is a promising intervention to reduce lung cancer mortality. Patient Decision Aids (PtDAs) may assist eligible individuals assess the risks and benefits associated with screening. Screening preference is high among lower-risk, screening-ineligible individuals and strategies are needed to reduce screening demand among this group. We developed and evaluated a resource comprising a recruitment pamphlet combined with either a PtDA for screening-eligible individuals or an education pamphlet for screening-ineligible individuals. Quasi-experimental pre-post pamphlet exposure design. Ever-smokers aged 55–80 years attending hospital outpatient clinics were invited. Among screening-eligible participants, the assessed outcome was change in score on the Decisional Conflict Scale (DCS). Among screening-ineligible participants, the assessed outcomes were change in screening preference. In the study 51% (55/107) of invited individuals participated, with mean ± standard deviation age 66.9 ± 6.4 years, 53% (29/55) male, and 65% (36/55) eligible for screening. Median (interquartile range) DCS among screening-eligible participants reduced from 28.9 (22.7–45.3) pre-PtDA to 25 (1.6–29.7) post-PtDA (p < .001), but there was no significant change in the proportion that reached the accepted threshold for decisional certainty (DCS < 25, 10/36 [28%] pre-exposure vs. 14/36 [39%] post-exposure, p = .1). Screening preference among screening-ineligible individuals reduced after viewing the screening-ineligible brochure (pre-exposure median of “Prefer” to post-exposure median of “Unsure,” p = .001). Our consumer information pamphlets about lung cancer screening may reduce decisional conflict and improve alignment of screening preference with eligibility.

Incidental findings, including pulmonary nodules, on computed tomography coronary angiography (CTCA) are common. Previous authors have suggested CTCA could allow opportunistic screening for lung cancer, though the lung cancer risk profile of this patient group has not previously been established. Smoking histories of 229 patients undergoing CTCA at two tertiary hospitals were reviewed and only 25% were current or former smokers aged 55-80 years old. Less than half of this group were eligible for screening based on the PLCOm2012 risk model. We conclude that routine screening in the form of full thoracic field imaging, of individuals undergoing CTCA is not appropriate as it would likely result in net harm.

Introduction: Data on device-measured physical activity (PA) and sedentary behaviour (SB) in the period before treatment commencement in people with inoperable lung cancer could help guide PA goals during and after treatment. However, the feasibility of collecting these data during such a stressful (and often short) period has not been reported. Aim: In people with inoperable lung cancer, to (i) examine compliance to accelerometry in the period before treatment; and (ii) describe their time spent in PA and SB. Method: People diagnosed with inoperable lung cancer, with Eastern Cooperative Oncology Group (ECOG) performance status 0-2, without brain metastases, wore an accelerometer (Actigraph GT9X) on their waist for 7 days before treatment. Compliance was measured as the percent of people who had ≥4 valid days (i.e. 10 h/day of wear-time). Results: Sixty-eight participants consented (44 males; 71±11yr), 62 were provided with the accelerometer, and 60 of them (97%) returned the device. No complications were reported on accelerometer use. Fifty-seven (95%) had ≥4 valid days of wear-time. Participants mean step count was 7,633±3,569 steps/day and they spent 600±116 min/day in SB. Compared to those with better performance status (ECOG 0/1; n=47), participants with poorer performance status (ECOG 2; n=10) had a lower step count (mean difference [95% CI] 2,480 [112; 4847] steps/day) and spent more time in SB (61 [7; 115] min/day). Conclusion: Compliance to accelerometry before lung cancer treatment was high. Participants with poorer performance status were less active and 1 h/day more sedentary than those with better performance status. Such data could guide PA and SB goal setting during and after treatment.

Following publication of the original article [1], the authors flagged that the article had gone to publishing with errors in Tables 1-3.

Use of non-invasive ventilation (NIV) in patients with hypercapnic respiratory failure has clear benefits over invasive ventilation. Existing risk prediction models are complex and difficult to apply in the acute setting. We developed the Midland NIV score comprising only five parameters for use to predict NIV failure (in-hospital death or intubation) at initiation. Individuals with Midland NIV score of ≤11 (average 13% NIV failure) may be suitable for general ward care, compared to intensive care for those with Midland NIV score ≥12 (average 66% NIV failure rate). Prospective external validation is required.

Background Lung cancer is the leading cause of cancer mortality in Australia. Guidelines suggest that patients with suspected lung cancer on thoracic imaging be referred for urgent specialist review. However, the term “suspected” is broad and includes the common finding of lung nodules, which often require periodic surveillance rather than urgent invasive investigation. The British Thoracic Society recommends that a lung nodule with a PanCan risk > 10% be considered for invasive investigation. This study aimed to assess which factors influence general practitioners (GPs) to request urgent review for a lung nodule and if these factors concur with PanCan risk prediction model variables. Methods A discrete choice experiment was developed that produced 32 individual case vignettes. Each vignette contained eight variables, four of which form the parsimonious PanCan risk prediction model. Two additional vignettes were created that addressed haemoptysis with a normal chest computed tomography (CT) scan and isolated mediastinal lymphadenopathy. The survey was distributed to 4160 randomly selected Australian GPs and they were asked if the patients in the vignettes required urgent (less than two weeks) specialist review. Multivariate logistic regression identified factors associated with request for urgent review. Results Completed surveys were received from 3.7% of participants, providing 152 surveys (1216 case vignettes) for analysis. The factors associated with request for urgent review were nodule spiculation (adj-OR 5.57, 95% CI 3.88–7.99, p p p Conclusion Future lung cancer investigation pathways may benefit from the addition of a risk prediction m9odel to reduce variations in referral behavior for low risk lung nodules.

Lung cancer screening with computerised tomography holds promise, but optimising the balance of benefits and harms via selection of a high risk population is critical. PLCOm2012 is a logistic regression model based on U.S. data, incorporating sociodemographic and health factors, which predicts 6-year lung cancer risk among ever-smokers, and thus may better predict those who might benefit from screening than criteria based solely on age and smoking history. We aimed to validate the performance of PLCOm2012 in predicting lung cancer outcomes in a cohort of Australian smokers. Predicted risk of lung cancer was calculated using PLCOm2012 applied to baseline data from 95,882 ever-smokers aged ≥45 years in the 45 and Up Study (2006-2009). Predictions were compared to lung cancer outcomes captured to June 2014 via linkage to population-wide health databases; a total of 1035 subsequent lung cancer diagnoses were identified. PLCOm2012 had good discrimination (area under the receiver-operating-characteristic-curve; AUC 0.80, 95%CI 0.78-0.81) and excellent calibration (mean and 90th percentiles of absolute risk difference between observed and predicted outcomes: 0.006 and 0.016, respectively). Sensitivity (69.4%, 95%CI, 65.6-73.0%) of the PLCOm2012 criteria in the 55-74 year age group for predicting lung cancers was greater than that using criteria based on ≥30 pack-years smoking and ≤15 years quit (57.5%, 53.3-61.3%; p

The correlation between ultra low dose computed tomography (ULDCT)-detected parenchymal lung changes and pulmonary function abnormalities is not well described. This study aimed to determine the relationship between ULDCT-detected interstitial lung disease (ILD) and measures of pulmonary function in an asbestos-exposed population. Two thoracic radiologists independently categorised prone ULDCT scans from 143 participants for ILD appearances as absent (score 0), probable (1) or definite (2) without knowledge of asbestos exposure or lung function. Pulmonary function measures included spirometry and diffusing capacity to carbon monoxide (DLCO). Participants were 92% male with a median age of 73.0 years. CT dose index volume was between 0.6 and 1.8 mGy. Probable or definite ILD was reported in 63 (44.1%) participants. Inter-observer agreement was good (k = 0.613, p

Prognostication tools are developed to assist clinical decision making and provide valid diagnostic and prognostic outcomes including mortality. Given significant disease and demographic heterogeneity, these tools have to be generally applicable to different patient populations. Therefore, once a model is developed it is internally and externally validated with subsequent clinical impact analyses after which its performance is evaluated and that particular model is then established., A retrospective single-centre study suggesting that patients with higher SAPS3-CNIV scores may be monitored in an ICU setting in order to reduce adverse patient events and optimal utilisation of resources http://ow.ly/F5qp30o2OT7

Lung cancer screening with computerised tomography holds promise, but optimising the balance of benefits and harms via selection of a high risk population is critical. PLCO

Background: The proportion of people eligible for lung cancer screening in Australia is unknown. Risk prediction models used for screening eligibility, such as the PLCO m2012 , use self-reported Chronic Obstructive Pulmonary Disease (COPD) as a variable. Measured airflow obstruction has been advocated as part of eligibility assessment but this needs patient contact. The change in the proportion of people eligible if COPD is self-reported, defined by symptoms or airflow obstruction is unknown. Aim: To estimate the proportion of people eligible for lung cancer screening in Australia and to measure the effect of spirometry to identify COPD on the proportion eligible. Methods: Cross-sectional study of 2523 people aged 55-68 years who live in the Busselton Shire of Western Australia. Eligibility was based on United States Preventative Services Task Force (USPSTF) criteria or PLCO m2012 lung cancer risk >1.5%. Results: Using USPSTF criteria, 20.1%, (95%CI 17.9-22.3) of ever-smokers would be eligible for screening. Using PLCO m2012 criteria, fewer ever-smokers would be eligible (17.9%, 95%CI 15.8-20.0, p m2012 risk (p=0.06). Conclusions: The proportion of ever-smokers eligible for lung cancer screening in this population is 17.9-20.1%. Up to 450,000 people in Australia may benefit from lung cancer screening. Using symptoms to identify COPD is an appropriate surrogate for spirometry when determining presence of COPD in this population.

OBJECTIVES To estimate the proportion of ever-smokers who are eligible for lung cancer screening in an Australian cohort, and to evaluate the effect of spirometry in defining chronic obstructive pulmonary disease (COPD) when assessing screening eligibility. DESIGN Cross-sectional study of 3586 individuals aged 50-68 years who live in the Busselton Shire of Western Australia. OUTCOMES Proportion of ever-smokers eligible for lung cancer screening based on United States Preventive Services Task Force (USPSTF) criteria, and PLCOm2012 lung cancer risk > 1.5%. The effect of using self-reported COPD, symptoms consistent with COPD, or spirometry to define COPD for screening eligibility according to the PLCOm2012 criteria. RESULTS Of ever-smokers aged 55-68 years, 254 (20.1%) would be eligible for screening according to USPSTF criteria; fewer would be eligible according to PLCOm2012 criteria (225, 17.9%; P = 0.004). This is equivalent to 8.9-10.0% of the total population aged 55-68 years, which suggests about 450 000 individuals in Australia may be eligible for lung cancer screening. The proportions of eligible participants were not significantly different whether spirometry results or symptoms consistent with COPD were used to determine PLCOm2012 risk. CONCLUSIONS The proportion of ever-smokers in this population who were eligible for lung cancer screening was 17.9-20.1%. Using symptoms to define COPD is an appropriate surrogate measure for spirometry when determining the presence of COPD in this population. There are significant challenges for policy makers on how to identify and recruit these eligible individuals from the wider population.

Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29 ± 12 mM min(-1), CV(inter-subject) = 42%) as compared with PF (46 ± 20 mM min(-1), CV(inter-subject) = 44%) and tended to be higher in FF (43 ± 35 mM min(-1), CV(inter-subject) = 80%). The coefficient of variation (CV) of oxidative capacity between muscles within the group was 59 ± 24%. PCr recovery time constant was correlated with end-exercise pH in Q (p0.01), FF (p0.05) and PF (p0.05) as well as proton efflux rate in FF (p0.01), PF (p0.01) and Q (p = 0.12). We also observed a steeper slope of the relationship between end-exercise acidosis and PCr recovery kinetics in FF compared with either PF or Q muscles. Overall, this study supports the concept of skeletal muscle heterogeneity by revealing a comparable inter- and intra-individual variability in oxidative capacity across three skeletal muscles in untrained individuals. These findings also indicate that the sensitivity of mitochondrial respiration to the inhibition associated with cytosolic acidosis is greater in the finger flexor muscles compared with locomotor muscles, which might be related to differences in permeability in the mitochondrial membrane and, to some extent, to proton efflux rates.