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.

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.

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.

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.

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.

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.