ERS International Congress 2023: highlights from the Thoracic Oncology Assembly.

Lung cancer is the leading cause of cancer mortality in the world. It greatly affects the patients' quality of life, and is thus a challenge for the daily practice in respiratory medicine. Advances in the genetic knowledge of thoracic tumours' mutational landscape, and the development of targeted therapies and immune checkpoint inhibitors, have led to a paradigm shift in the treatment of lung cancer and pleural mesothelioma. During the 2023 European Respiratory Society Congress in Milan, Italy, experts from all over the world presented their high-quality research and reviewed best clinical practices. Lung cancer screening, management of early stages of lung cancer, application of artificial intelligence and biomarkers were discussed and they will be summarised here.

Prevalence and clinical characteristics of non-malignant CT detected incidental findings in the SUMMIT lung cancer screening cohort.

BACKGROUND: Pulmonary and extrapulmonary incidental findings are frequently identified on CT scans performed for lung cancer screening. Uncertainty regarding their clinical significance and how and when such findings should be reported back to clinicians and participants persists. We examined the prevalence of non-malignant incidental findings within a lung cancer screening cohort and investigated the morbidity and relevant risk factors associated with incidental findings. We quantified the primary and secondary care referrals generated by our protocol. METHODS: The SUMMIT study (NCT03934866) is a prospective observational cohort study to examine the performance of delivering a low-dose CT (LDCT) screening service to a high-risk population. Spirometry, blood pressure, height/weight and respiratory history were assessed as part of a Lung Health Check. Individuals at high risk of lung cancer were offered an LDCT and returned for two further annual visits. This analysis is a prospective evaluation of the standardised reporting and management protocol for incidental findings developed for the study on the baseline LDCT. RESULTS: In 11 115 participants included in this analysis, the most common incidental findings were coronary artery calcification (64.2%) and emphysema (33.4%). From our protocolised management approach, the number of participants requiring review for clinically relevant findings in primary care was 1 in 20, and the number potentially requiring review in secondary care was 1 in 25. CONCLUSIONS: Incidental findings are common in lung cancer screening and can be associated with reported symptoms and comorbidities. A standardised reporting protocol allows systematic assessment and standardises onward management.

The SUMMIT Study: Utilising a written 'Next Steps' information booklet to prepare participants for potential lung cancer screening results and follow-up.

OBJECTIVES: Low-Dose Computed Tomography (LDCT) screening for lung cancer can result in several potential outcomes of varying significance. Communication methods used in Lung Cancer Screening (LCS) programmes must, therefore, ensure that participants are prepared for the range of possible results and follow-up. Here, we assess perceptions of a written preparatory information booklet provided to participants in a large LCS cohort designed to convey this information. MATERIALS AND METHODS: All participants in the SUMMIT Study (NCT03934866) were provided with a results preparation information booklet, entitled 'The SUMMIT Study: Next Steps' at their baseline appointment which outlined potential results, their significance, and timelines for follow up. Results from the LDCT scan and Lung Health Check were subsequently sent by letter. Perceptions of this booklet were assessed among participants with indeterminate pulmonary findings when they attended a face-to-face appointment immediately before their three-month interval scan. Specifically, questions assessed the perceived usefulness of the booklet and the amount of information contained in it. RESULTS: 70.1% (n = 1,412/2,014) participants remembered receiving the booklet at their appointment. Of these participants, 72.0% (n = 1,017/1,412) found it quite or very useful and 68.0% (n = 960/1,412) reported that it contained the right amount of information. Older participants, those from the least deprived socioeconomic quintile and those of Black ethnicity were less likely to report finding the booklet either quite or very useful, or that it contained the right amount of information. Participants who remembered receiving the booklet were more likely to be satisfied with the process of results communication by letter. CONCLUSION: Providing written information that prepares participants for possible LDCT results and their significance appears to be a useful resource and a helpful adjunct to a written method of results communication for large scale LCS programmes.

Multi-center evaluation of baseline neutrophil-to-lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in IPF. Methods: We adopted a two-stage discovery (n = 71) and validation (n = 134) design using patients from the UCL partners (UCLp) cohort. We then combined discovery and validation cohorts and included an additional 794 people with IPF, using real-life data from 5 other UK centers, to give a combined cohort of 999 patients. Data were collected from patients presenting over a 13-year period (2006-2019) with mean follow up of 3.7 years (censoring: 2018-2020). Findings: In the discovery analysis, we showed that high values of NLR (>/ = 2.9 vs < 2.9) were associated with increased risk of mortality in IPF (HR 2.04, 95% CI 1.09-3.81, n = 71, p = 0.025). This was confirmed in the validation (HR 1.91, 95% CI 1.15-3.18, n = 134, p = 0.0114) and combined cohorts (HR 1.65, n = 999, 95% CI 1.39-1.95; p < 0·0001). NLR correlated with GAP stage and GAP index (p < 0.0001). Stratifying patients by NLR category (low/high) showed significant differences in survival for GAP stage 2 (p < 0.0001), however not for GAP stage 1 or 3. In a multivariate analysis, a high NLR was an independent predictor of mortality/progression after adjustment for individual GAP components and steroid/anti-fibrotic use (p < 0·03). Furthermore, incorporation of baseline NLR in a modified GAP-stage/index, GAP-index/stage-plus, refined prognostic ability as measured by concordance (C)-index. Interpretation: We have identified NLR as a widely available test that significantly correlates with lung function, can predict outcomes in IPF and refines cohort staging with GAP. NLR may allow timely prioritisation of at-risk patients, even in the absence of lung function. Funding: Breathing Matters, GSK, CF Trust, BLF-Asthma, MRC, NIHR Alpha-1 Foundation.

Growing small solid nodules in lung cancer screening: safety and efficacy of a 200 mm3 minimum size threshold for multidisciplinary team referral.

The optimal management of small but growing nodules remains unclear. The SUMMIT study nodule management algorithm uses a specific threshold volume of 200 mm3 before referral of growing solid nodules to the multidisciplinary team for further investigation is advised, with growing nodules below this threshold kept under observation within the screening programme. Malignancy risk of growing solid nodules of size >200 mm3 at initial 3-month interval scan was 58.3% at a per-nodule level, compared with 13.3% in growing nodules of size ≤200 mm3 (relative risk 4.4, 95% CI 2.17 to 8.83). The positive predictive value of a combination of nodule growth (defined as percentage volume change of ≥25%), and size >200 mm3 was 65.9% (29/44) at a cancer-per-nodule basis, or 60.5% (23/38) on a cancer-per-participant basis. False negative rate of the protocol was 1.9% (95% CI 0.33% to 9.94%). These findings support the use of a 200 mm3 minimum volume threshold for referral as effective at reducing unnecessary multidisciplinary team referrals for small growing nodules, while maintaining early-stage lung cancer diagnosis.

The reporting of pulmonary nodule results by letter in a lung cancer screening setting.

OBJECTIVES: Pulmonary nodules are commonly found in Lung Cancer Screening (LCS), with results typically communicated by face-to-face or telephone consultation. Providing LCS on a population basis requires resource efficient and scalabe communication methods. Written communication provides one such method. Here, we assess participant satisfaction with this approach in a LCS setting and investigate characteristics associated with dissatisfaction. MATERIALS AND METHODS: The SUMMIT Study is a prospective observational cohort study which aims to assess the implementation of Low-Dose Computed Tomography (LDCT) scanning for LCS in a high-risk population and validate a multi-cancer early detection blood test (NCT03934866). Participants with indeterminate pulmonary nodules requiring a three-month interval LDCT were informed of their result by postal letter and given a face-to-face appointment with a study practitioner at their interval LDCT appointment. At this appointment, having previously received their results letter, participants were verbally asked questions to assess their satisfaction with, and preferences for, methods of results communication. RESULTS: 1,900 participants were included in the analysis. 82.8% (n = 1573) were satisfied with receiving their results by letter, with 2.9% (n = 55) reporting dissatisfaction. 86.3% (n = 1640) stated it was their preferred communication method and 77.3% (n = 1469) reported that their letter contained the right amount of information. Participants from less deprived socioeconomic quintiles were more likely to report that the letter contained insufficient information and individuals aged ≥ 70 years were less likely to do so. Although 13.7% (n = 261) participants had discussed their results with their General Practitioner (GP) prior to the study visit, 83.9% (n = 219) of these participants were satisfied with receiving results by letter, with the same proportion preferring this communication method. CONCLUSION: We report high participant satisfaction with the reporting of pulmonary nodule results by letter in a LCS setting. We believe this provides a feasible route forward for large-scale screening programmes.

Use of peripheral neutrophil to lymphocyte ratio and peripheral monocyte levels to predict survival in fibrotic hypersensitivity pneumonitis (fHP): a multicentre retrospective cohort study.

The factors determining disease course and survival in fibrotic hypersensitivity pneumonitis (fHP) have not been fully elucidated.The aim of this study was to describe the characteristics of patients with fHP in a real-world cohort and investigate factors associated with worse outcomes. We aimed to explore the use of neutrophil to lymphocyte ratio (NLR) and peripheral blood monocyte levels in predicting mortality. METHODS: A retrospective, multicentre, observational UK cohort study. RESULTS: Patients with fHP were significantly younger than those with idiopathic pulmonary fibrosis (IPF) (median age fHP 73 vs IPF 75 years) and were much more likely to be woman (fHP 61% vs IPF 26%). In almost half of all fHP cases (49%, n=104/211), no causative antigen was identified from either the history or specific antigen testing. Overall, fHP was associated with a better survival than IPF, although median survival of both groups was poor (fHP 62 months vs IPF 52 months).IPF survival in patients with a high NLR was significantly lower than those with a low NLR (44 vs 83 months). A monocyte count ≥0.95 K/uL also predicted significantly poorer outcomes for patients with IPF compared with <0.95 K/uL (33 vs 57 months). In contrast, NLR and monocyte count did not predict survival in the fHP cohort. CONCLUSIONS: Although fHP has a statistically lower mortality than IPF, absolute survival time of both conditions is poor. High baseline NLR and absolute monocyte counts predict worse survival in IPF but not in fHP, highlighting the potential for divergence in their pathogenic mechanisms.

Prognostic factors in chronic hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease resulting from exposure to inhaled environmental antigens. Prognosis is variable, with a subset of patients developing progressive fibrosis leading to respiratory failure and death. Therefore, there is an urgent need to identify factors which predict prognosis and survival in patients with HP. We undertook a narrative review of existing evidence to identify prognostic factors in patients with chronic HP. Patient demographics, smoking history, extent of antigen exposure and comorbidities all have reported associations with disease outcome, and physiological, radiological and laboratory markers have been shown to predict overall survival. While no single marker has been demonstrated to accurately and reliably predict prognosis, older age, more severe impairment of pulmonary function at baseline and established fibrosis on either biopsy or high-resolution computed tomography are consistently associated with worse survival. The vast majority of existing studies are retrospective, and this review identifies a need for prospective longitudinal studies with serial assessment of respiratory health to ascertain factors associated with nonfatal deterioration. Future developments, including the development of HP-specific composite scores may help further improve our ability to predict outcomes for individual patients.

Procalcitonin in respiratory disease: use as a biomarker for diagnosis and guiding antibiotic therapy.

Procalcitonin (PCT) is a peptide measurable in serum which becomes elevated in response to bacterial infection. Multiple trials have explored the safety and efficacy of using PCT as a biomarker to guide decisions about starting or stopping antibiotic therapy in a wide variety of situations, and PCT assays have recently been approved by the Federal Drug Administration (FDA) in the US for use in both sepsis and respiratory tract infections. While there have been a number of promising results particularly in acute respiratory tract infections and intensive care unit settings, problems including adherence to protocol, cost of the assay and improved antimicrobial stewardship more generally, have limited more widespread adoption. This educational article summarises the evidence for the use of procalcitonin as a biomarker of bacterial infection across the spectrum of respiratory disease and reviews how the use of procalcitonin-guided antibiotic therapy is reflected in current major international guidelines. KEY POINTS: Procalcitonin has been widely investigated as a biomarker of bacterial infection to aid diagnosis and decisions to start or stop antibiotics in a range of conditions, including in diseases of the lower respiratory tract.Meta-analysis suggests that the use of procalcitonin to guide antibiotic therapy in acute respiratory tract infections can reduce duration of antibiotic therapy and hospital admission without adversely affecting outcomes - however, there was significant heterogeneity in methodology and population in the included studies, and more recent studies have failed to show such significant benefits.The use of procalcitonin to guide stopping or shortening antibiotic therapy in sepsis/septic shock is suggested in the international guidelines for the management of sepsis (2016), but this is a "weak" recommendation, with a low quality of evidence recognised. Major international guidelines do not support a role for procalcitonin in the management of acute exacerbations of COPD, bronchiectasis, interstitial lung disease or pleural infection.Regardless of situation, decisions on initiating, altering, or discontinuing antimicrobial therapy should never be made solely on the basis of changes in any biomarker - while biomarkers such as procalcitonin may provide supportive information, they should only be used alongside regular and robust clinical assessment. EDUCATIONAL AIMS: To understand the principles of using procalcitonin to guide decisions regarding antibiotic use (procalcitonin-guided antibiotic therapy).To review important research studies into the use of procalcitonin as a biomarker of bacterial infection across the spectrum of diseases of the lower respiratory tract.To understand the current international guidelines regarding procalcitonin use in disease of the lower respiratory tract.

Does ambulatory oxygen improve quality of life in patients with fibrotic lung disease? Results from the AmbOx trial.

The AmbOx trial provides RCT evidence for ambulatory oxygen therapy improving HRQoL in patients with fibrotic ILD http://ow.ly/uHC030nEzsz.

Idiopathic Pulmonary Fibrosis (IPF): An Overview.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterised by chronic, progressive scarring of the lungs and the pathological hallmark of usual interstitial pneumonia. Current paradigms suggest alveolar epithelial cell damage is a key initiating factor. Globally, incidence of the disease is rising, with associated high morbidity, mortality, and economic healthcare burden. Diagnosis relies on a multidisciplinary team approach with exclusion of other causes of interstitial lung disease. Over recent years, two novel antifibrotic therapies, pirfenidone and nintedanib, have been developed, providing treatment options for many patients with IPF, with several other agents in early clinical trials. Current efforts are directed at identifying key biomarkers that may direct more customized patient-centred healthcare to improve outcomes for these patients in the future.

Data Management Rubric for Video Data in Organismal Biology.

SYNOPSIS: Standards-based data management facilitates data preservation, discoverability, and access for effective data reuse within research groups and across communities of researchers. Data sharing requires community consensus on standards for data management, such as storage and formats for digital data preservation, metadata (i.e., contextual data about the data) that should be recorded and stored, and data access. Video imaging is a valuable tool for measuring time-varying phenotypes in organismal biology, with particular application for research in functional morphology, comparative biomechanics, and animal behavior. The raw data are the videos, but videos alone are not sufficient for scientific analysis. Nearly endless videos of animals can be found on YouTube and elsewhere on the web, but these videos have little value for scientific analysis because essential metadata such as true frame rate, spatial calibration, genus and species, weight, age, etc. of organisms, are generally unknown. We have embarked on a project to build community consensus on video data management and metadata standards for organismal biology research. We collected input from colleagues at early stages, organized an open workshop, "Establishing Standards for Video Data Management," at the Society for Integrative and Comparative Biology meeting in January 2017, and then collected two more rounds of input on revised versions of the standards. The result we present here is a rubric consisting of nine standards for video data management, with three levels within each standard: good, better, and best practices. The nine standards are: (1) data storage; (2) video file formats; (3) metadata linkage; (4) video data and metadata access; (5) contact information and acceptable use; (6) camera settings; (7) organism(s); (8) recording conditions; and (9) subject matter/topic. The first four standards address data preservation and interoperability for sharing, whereas standards 5-9 establish minimum metadata standards for organismal biology video, and suggest additional metadata that may be useful for some studies. This rubric was developed with substantial input from researchers and students, but still should be viewed as a living document that should be further refined and updated as technology and research practices change. The audience for these standards includes researchers, journals, and granting agencies, and also the developers and curators of databases that may contribute to video data sharing efforts. We offer this project as an example of building community consensus for data management, preservation, and sharing standards, which may be useful for future efforts by the organismal biology research community.

Headache in an HIV positive patient: diagnostic challenges and approach to treatment .

Headaches are a common complaint in HIV positive patients attending emergency services. A thorough understanding of the differential diagnoses, initial investigations and empirical management of this presentation is essential for the assessing physician. We discuss a case of a patient with known advanced HIV infection presenting with headache to the emergency department. Given the range of possible diagnoses, broad-spectrum antimicrobial therapy was initially commenced. This was stopped when magnetic resonance imaging confirmed a diagnosis of venous sinus thrombosis. Anticoagulation therapy was started in accordance with current clinical guidelines after discussing the rationale and options for treatment with the patient. Here, we review the guidelines and supporting evidence for management of venous sinus thrombosis, and consider the challenges and strategies for engaging a patient with previous poor attendance in their ongoing care.

Improving smoking cessation policy by assessing user demand for an inpatient smoking cessation service in adult psychiatric wards.

Smoking rates are higher among people with mental health conditions compared to the general population. Smoking reduces physical, mental and financial well-being, and interacts with psychotropic drugs. An inpatient admission provides an opportunity to engage and support smokers in smoking cessation. Compliance with Trust/NICE smoking cessation guidelines was assessed in two inpatient wards, and a questionnaire evaluated user demand for an inpatient smoking cessation service. A need for improved documentation of smoking status to identify and treat smokers routinely was revealed. A new electronic health form was designed and introduced, and a clear pathway for onward referrals was developed. This intervention preceded the introduction of the Trust-wide smoke free policy from October 2014. The intervention doubled rates of documentation of smoking status, cessation advice and offer of NRT/referral. There were large differences between the two wards, highlighting the need for a tailored approach.

Widespread skin rash following travel to South-East Asia.

A 21-year-old man presented with a widespread, intensely pruritic skin rash, which developed acutely 5 days after returning from a backpacking holiday in Thailand. On initial presentation to his general practitioner, an erythematous, papular rash was noted in the upper right back, with smaller clusters of lesions on the buttocks and right arm. Based on the anatomical distribution of the lesions, a preliminary diagnosis of shingles was made. Over the following 2 weeks, the lesions failed to improve, and new snake-like lesions appeared. A dermatologist made the diagnosis of cutaneous larva migrans. The skin lesions rapidly resolved following oral albendazole therapy.