A Prospective Observational Study of Physical Activity Levels and Physical Fitness of People at High Risk for Lung Cancer.

Introduction: Physical activity (PA) is a potentially modifiable risk factor for lung cancer, with previous research revealing that people who engage in more PA have lower risk of developing lung cancer. PA levels of lung cancer screening participants have not previously been explored. Methods: Participants at a single Australian International Lung Screen Trial site were eligible for assessment of self-reported PA levels (International Physical Activity Questionnaire and Physical Activity Scale for the Elderly) and physical assessments (6-min walk distance, hand grip muscle strength, daily step count, and body composition) at a single time point during lung cancer screening. Statistics were predominantly descriptive, with parametric data presented as mean and SD and nonparametric data presented as median and interquartile range (IQR). Results: A total of 178 participants were enrolled in this study, with a median age of 61 years. Of the participants, 61% were men and 51% were people who currently smoke. The median total International Physical Activity Questionnaire score was 1756 MET/min/wk (IQR 689, 4049). Mean total Physical Activity Scale for the Elderly score was 160 (SD 72), higher than described in healthy sedentary adults. The median daily step count was 7237 steps (IQR 5353, 10,038) and mean 6-minute walk distance was 545 m (SD 92). Median grip strengths were within predicted normal range, with an elevated median percentage body fat and low skeletal muscle mass found on body composition. Conclusion: Almost a quarter of International Lung Screen Trial participants assessed reported low levels of PA and have a potentially modifiable risk factor to improve health outcomes. Larger studies are needed to characterize the burden of inactivity among high-risk lung cancer screening populations.

Critical deterioration of chronic eosinophilic pneumonia during pregnancy.

Chronic eosinophilic pneumonia (CEP) is a rare, idiopathic interstitial lung disease characterised by the accumulation of eosinophils in the pulmonary interstitia and alveoli. Patients with CEP respond well to systemic corticosteroid therapy and infrequently progress to end-stage lung disease. We report a case of a woman in her 40s with previously stable, steroid-responsive CEP who experienced a critical deterioration of her CEP at 25 weeks of gestation during her third pregnancy. The patient was admitted to the intensive care unit due to respiratory failure requiring intubation and mechanical ventilation. Follow-up investigation revealed advanced fibrotic lung disease requiring long-term oxygen therapy and referral for double lung transplantation. While CEP infrequently advances to permanent parenchymal damage, this case demonstrates the potential for severe exacerbations in the setting of pregnancy and highlights pregnancy as a potential risk factor for disease progression, reinforcing the need for further research to define optimal monitoring and treatment strategies.

Validation of the psychosocial consequences of screening in lung cancer questionnaire in the international lung screen trial Australian cohort.

BACKGROUND: Evaluation of psychosocial consequences of lung cancer screening with LDCT in high-risk populations has generally been performed using generic psychometric instruments. Such generic instruments have low coverage and low power to detect screening impacts. This study aims to validate an established lung cancer screening-specific questionnaire, Consequences Of Screening Lung Cancer (COS-LC), in Australian-English and describe early results from the baseline LDCT round of the International Lung Screen Trial (ILST). METHODS: The Danish-version COS-LC was translated to Australian-English using the double panel method and field tested in Australian-ILST participants to examine content validity. A random sample of 200 participants were used to assess construct validity using Rasch item response theory models. Reliability was assessed using classical test theory. The COS-LC was administered to ILST participants at prespecified timepoints including at enrolment, dependent of screening results. RESULTS: Minor linguistic alterations were made after initial translation of COS-LC to English. The COS-LC demonstrated good content validity and adequate construct validity using psychometric analysis. The four core scales fit the Rasch model, with only minor issues in five non-core scales which resolved with modification. 1129 Australian-ILST participants were included in the analysis, with minimal psychosocial impact observed shortly after baseline LDCT results. CONCLUSION: COS-LC is the first lung cancer screening-specific questionnaire to be validated in Australia and has demonstrated excellent psychometric properties. Early results did not demonstrate significant psychosocial impacts of screening. Longer-term follow-up is awaited and will be particularly pertinent given the announcement of an Australian National Lung Cancer Screening Program. TRIAL REGISTRATION: NCT02871856.

Prevalence of subclinical lung cancer detected at autopsy: a systematic review.

BACKGROUND: Lung cancer screening in high-risk populations with low-dose computed tomography is supported by international associations and recommendations. Overdiagnosis is considered a risk of screening with associated harms. The aim of this paper is to determine the prevalence of subclinical lung cancer diagnosed post-mortem to better understand the reservoir of subclinical lung cancer. METHODS: We searched EMBASE, PubMed, and MEDLINE databases from inception until March 2022 with no language restrictions. We considered all studies with ≥100 autopsies in adults. Two reviewers independently assessed eligibility of studies, extracted data, and assessed risk of bias of included studies. We performed a meta-analysis using a random-effects model for prevalence of subclinical lung cancer diagnosed post-mortem with sensitivity and subgroup analyses. RESULTS: A total of 13 studies with 16 730 autopsies were included. Pooled prevalence was 0.4% (95% CI 0.20 to 0.82%, I2 = 84%, tau2 = 1.19, low certainty evidence,16 730 autopsies). We performed a sensitivity analysis excluding studies which did not specify exclusion of children in their cohort, with a pooled prevalence of subclinical lung cancer of 0.87% (95% CI 0.48 to 1.57%, I2 = 71%, tau2 = 0.38, 6998 autopsies, 8 studies). CONCLUSIONS: This is the first published systematic review to evaluate the prevalence of post-mortem subclinical lung cancer. Compared to autopsy systematic reviews in breast, prostate and thyroid cancers, the pooled prevalence is lower in lung cancer for subclinical cancer. This result should be interpreted with caution due to the included studies risk of bias and heterogeneity, with further high-quality studies required in target screening populations.

Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality.

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 I2 statistic 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.

COVID-19 pandemic 2020: a tertiary Melbourne hospital's experience.

BACKGROUND: The COVID-19 pandemic has affected different parts of Australia in distinct ways across 2020 and 2021. In 2020, Melbourne was the epicentre of COVID-19. As one of the key tertiary centres caring for the patients affected by the outbreaks, the Royal Melbourne Hospital (RMH) managed the majority of the Victorian inpatient caseload. AIMS: To review the demographics, management and outcomes of patients with COVID-19 cared for by the RMH services in 2020. METHODS: A single health service retrospective cohort analysis of demographics, interventions and outcomes was conducted to characterise the RMH experience in 2020. RESULTS: From January to December 2020, 433 patients required admission more than 24 h. The demographics of affected patients and outcomes changed over the course of the study. Overall, 47% (203/433) required oxygen, most frequently (36%; 154/433) with low-flow devices (nasal prongs or hudson mask), and 11% (47/433) of patients required admission to intensive care. We recorded a 30-day mortality of 24% (104/433) mortality overall, rising to over 50% in patients aged over 80 years. CONCLUSIONS: The experience of this health service in 2020 demonstrated changing demographics over time, with associated differences in outcomes; notably marked mortality in older populations, frequent complications and limited inter-site transfer possible with mobilised resources.

Predicting Lymph Node Metastasis in Non-small Cell Lung Cancer: Prospective External and Temporal Validation of the HAL and HOMER Models.

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers? STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. RESULTS: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. INTERPRETATION: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.

Correlation of positron emission tomography ventilation-perfusion matching with CT densitometry in severe emphysema.

BACKGROUND: Emphysema severity is frequently measured on CT via densitometry. Correlation with scintigraphic and spirometric functional measures of ventilation or perfusion varies widely, and no prior study has evaluated correlation between densitometry and lobar ventilation/perfusion in patients with severe emphysema. The aim of this study was to evaluate the utility and findings of gallium-68 (68Ga) ventilation/perfusion positron emission tomography-CT (68Ga-VQ/PET-CT) in severe emphysema assessment. METHODS: Fourteen consecutive patients undergoing evaluation for bronchoscopic lung volume reduction between March 2015 and March 2018 underwent 68Ga-VQ/PET-CT assessment for lobar functional lung mapping, in addition to CT densitometry. Correlations between CT densitometry and 68Ga-VQ/PET-CT parameters for individual lobar lung function were sought. RESULTS: CT densitometry assessment of emphysema correlated only weakly (R2 = 0.13) with lobar perfusion and was not correlated with ventilation (R2 = 0.04). Densitometry was moderately (R2 = 0.67) correlated with V/Q units in upper lobes, though poorly reflected physiological function in lower lobes (R2 = 0.19). Emphysema severity, as measured by CT densitometry, was moderately correlated with proportion of normal V/Q units and matched V/Q defects in individual lobes. CONCLUSIONS: Assessment of lobar pulmonary function by 68Ga-VQ/PET-CT provides physiologic information not evident on CT densitometry such as ventilation and perfusion specifics and matched defects. Further research is needed to see if the discordant findings on 68Ga-VQ/PET-CT provide prognostic information or can be used to modify patient management and improve outcomes.

The feasibility of molecular testing on cell blocks created from brush tip washings in the assessment of peripheral lung lesions.

BACKGROUND: With the rapid development of genotype-guided therapies, molecular testing is becoming important in the management of lung cancer. Bronchoscopy is one of the most common investigations performed to diagnose and investigate lung cancer. Given the limited samples often produced by bronchoscopy, this study aims to evaluate the feasibility of performing molecular testing on cell blocks created from bronchoscope cytology brush tip washings (BTW). METHODS: Patients with positive brush cytology for tumour cells had cell blocks created from the BTW. Mutations were detected using amplicon-based massively parallel sequencing of targeted regions of EGFR, KRAS, and BRAF genes. RESULTS: A total of 45 patients were included in this study. Of those, 91% had adequate specimens for molecular analysis and 66% of patients with adenocarcinoma had mutations detected. Bronchial brush tip wash cell blocks were the sole specimen available for molecular testing in 27 (60%) patients. CONCLUSIONS: The findings of this study demonstrate that molecular testing can be performed on cell blocks created from BTW and this technique may allow for an increase in bronchoscope specimens amenable to molecular testing without further increasing morbidity and mortality.

Diagnostic Utility of Bronchial Brush-Tip Washings for the Immunohistochemical Assessment of Peripheral Lung Lesions.

OBJECTIVES: Immunohistochemistry (IHC) is an important component of lung cancer diagnosis and management, although performance can be limited due to tissue availability. We describe a novel technique for processing brush-tip washings (BTW) and evaluate the feasibility of IHC testing on these samples. STUDY DESIGN: All patients who had cell blocks (CB) created from BTW following bronchoscopic investigation of peripheral lung lesions were included. CB were assessed for adequate material before undergoing IHC staining. RESULTS: 75 patients were included in the study, with bronchoscopic diagnosis of malignancy achieved in 77%. Sixty-seven samples (89%) had sufficient cells for diagnosis on CB and 56 of these (84%) proved amenable to IHC. CB created from BTW were the sole specimens available for IHC subtyping in 7 patients (9%). CONCLUSIONS: CB are easily created from BTW and are a simple method for increasing the diagnostic utility of bronchoscopic specimens without increasing the risk or duration of bronchoscopy. IHC can be easily performed in a high proportion of cases, increasing the likelihood of accurate sub-typing of tumours following diagnostic bronchoscopy.

Sequential multimodality bronchoscopic investigation of peripheral pulmonary lesions.

Multiple guidance modalities may be combined during bronchoscopic investigation of peripheral pulmonary lesions (PPLs). The relative contribution of each modality to diagnostic performance remains uncertain.Endobronchial ultrasound (EBUS) with virtual bronchoscopy (VB) was routinely performed, with electromagnetic navigation (EMN) utilised only where EBUS was unable to locate PPLs or where the probe was adjacent to the lesion and on-site cytologic examination was nondiagnostic.236 consecutive patients with 245 PPLs had lesion size 22.8±12.4 mm (mean±sd). PPLs were localised using EBUS+VB alone in 188 (77%) and was diagnostic in 134 of these (71.3%). EBUS localisation was predicted by PPL size (23.7±10.5 versus 19.7±9.8 mm, p=0.003), but not by bronchus sign, PPL-hilum distance or PPL-pleura distance. EMN in 57 patients achieved EBUS localisation in a further 17 patients (30.9%), improving overall visualisation yield to 85%. Nine of these 57 procedures achieved a definitive diagnosis (16%), improving overall diagnostic yield to 58.4%. Probe position and lesion type influenced overall diagnostic yield. Sensitivity for diagnosis of lung cancer was 70% (131/188; 95% CI 63-76%).Localisation rate and diagnostic sensitivity of radial probe EBUS+VB alone for diagnosis of PPLs is high. EBUS localisation rates and procedural yield are improved only modestly (by 8% and 4%, respectively) with addition of EMN. Sampling following EMN should include all available methods to maximise diagnostic yield.

Antihistamines for children with otitis media.

QUESTION: Otitis media is a very common condition in pediatrics and can be quite distressing for children and their parents. Is there a role for antihistamines and decongestants in the management of acute otitis media orotitis media with effusion in children? ANSWER: Traditionally, antihistamines and decongestants have been used in the treatment of otitis media;however, recent guidelines, which are based on study findings with negative results, recommend against routine use. No antihistamine-decongestant combination has been shown to be of clinically significant benefit,and there are potential adverse events that need to be taken into account.

Laundry detergent capsules and pediatric poisoning.

QUESTION: A 4-year-old girl was brought into the emergency department vomiting after having had ingested a laundry detergent capsule (LDC) from under the sink at her house. What is the risk of LDC poisoning? What can be done to treat these children? ANSWER: Laundry detergent capsules are relatively new to supermarket shelves in North America, and there has been an emergence of case reports in the literature describing LDC poisoning, which is worse than poisoning from other laundry detergents. Very little is known about the mechanisms causing these severe reactions, which include airway compromise and esophageal perforation, but the attractive appearance of these capsules and easy access at home has governments and health officials concerned about an increase in poisoning. No residual problems have been associated with these cases to date; however, further research is needed to assess long-term effects.