Quantitative micro-CT-derived biomarkers elucidate age-related lung fibrosis in elder mice.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF), prevalently affecting individuals over 60 years of age, has been mainly studied in young mouse models. The limited efficacy of current treatments underscores the need for animal models that better mimic an aged patient population. We addressed this by inducing pulmonary fibrosis in aged mice, using longitudinal micro-CT imaging as primary readout, with special attention to animal welfare. METHODS: A double bleomycin dose was administered to 18-24 months-old male C57Bl/6j mice to induce pulmonary fibrosis. Bleomycin dosage was reduced to as low as 75% compared to that commonly administered to young (8-12 weeks-old) mice, resulting in long-term lung fibrosis without mortality, complying with animal welfare guidelines. After fibrosis induction, animals received Nintedanib once-daily for two weeks and longitudinally monitored by micro-CT, which provided structural and functional biomarkers, followed by post-mortem histological analysis as terminal endpoint. RESULTS: Compared to young mice, aged animals displayed increased volume, reduced tissue density and function, and marked inflammation. This increased vulnerability imposed a bleomycin dosage reduction to the lowest tested level (2.5 µg/mouse), inducing a milder, yet persistent, fibrosis, while preserving animal welfare. Nintedanib treatment reduced fibrotic lesions and improved pulmonary function. CONCLUSIONS: Our data identify a downsized bleomycin treatment that allows to achieve the best trade-off between fibrosis induction and animal welfare, a requirement for antifibrotic drug testing in aged lungs. Nintedanib displayed significant efficacy in this lower-severity disease model, suggesting potential patient stratification strategies. Lung pathology was quantitatively assessed by micro-CT, pointing to the value of longitudinal endpoints in clinical trials.

A formula for predicting emphysema extent in combined idiopathic pulmonary fibrosis and emphysema.

BACKGROUND: No single pulmonary function test captures the functional effect of emphysema in idiopathic pulmonary fibrosis (IPF). Without experienced radiologists, other methods are needed to determine emphysema extent. Here, we report the development and validation of a formula to predict emphysema extent in patients with IPF and emphysema. METHODS: The development cohort included 76 patients with combined IPF and emphysema at the Royal Brompton Hospital, London, United Kingdom. The formula was derived using stepwise regression to generate the weighted combination of pulmonary function data that fitted best with emphysema extent on high-resolution computed tomography. Test cohorts included patients from two clinical trials (n = 455 [n = 174 with emphysema]; NCT00047645, NCT00075998) and a real-world cohort from the Royal Brompton Hospital (n = 191 [n = 110 with emphysema]). The formula is only applicable for patients with IPF and concomitant emphysema and accordingly was not used to detect the presence or absence of emphysema. RESULTS: The formula was: predicted emphysema extent = 12.67 + (0.92 x percent predicted forced vital capacity) - (0.65 x percent predicted forced expiratory volume in 1 second) - (0.52 x percent predicted carbon monoxide diffusing capacity). A significant relationship between the formula and observed emphysema extent was found in both cohorts (R2 = 0.25, P < 0.0001; R2 = 0.47, P < 0.0001, respectively). In both, the formula better predicted observed emphysema extent versus individual pulmonary function tests. A 15% emphysema extent threshold, calculated using the formula, identified a significant difference in absolute changes from baseline in forced vital capacity at Week 48 in patients with baseline-predicted emphysema extent < 15% versus ≥ 15% (P = 0.0105). CONCLUSION: The formula, designed for use in patients with IPF and emphysema, demonstrated enhanced ability to predict emphysema extent versus individual pulmonary function tests. TRIAL REGISTRATION: NCT00047645; NCT00075998.

Progress in the radiologic diagnosis of idiopathic pulmonary fibrosis.

PURPOSE OF REVIEW: To discuss the most recent applications of radiological imaging, from conventional to quantitative, in the setting of idiopathic pulmonary fibrosis (IPF) diagnosis. RECENT FINDINGS: In this article, current concepts on radiological diagnosis of IPF, from high-resolution computed tomography (CT) to other imaging modalities, are reviewed. In a separate section, advances in quantitative CT and development of novel imaging biomarkers, as well as current limitations and future research trends, are described. SUMMARY: Radiological imaging in IPF, particularly quantitative CT, is an evolving field which holds promise in the future to allow for an increasingly accurate disease assessment and prognostication of IPF patients. However, further standardization and validation studies of alternative imaging applications and quantitative biomarkers are needed.

The pros and cons of lung cancer screening.

Several trials have shown that low-dose computed tomography-based lung cancer screening (LCS) allows a substantial reduction in lung cancer-related mortality, carrying the potential for other clinical benefits. There are, however, some uncertainties to be clarified and several aspects to be implemented to optimize advantages and minimize the potential harms of LCS. This review summarizes current evidence on LCS, discussing some of the well-established and potential benefits, including lung cancer (LC)-related mortality reduction and opportunity for smoking cessation interventions, as well as the disadvantages of LCS, such as overdiagnosis and overtreatment. CLINICAL RELEVANCE STATEMENT: Different perspectives are provided on LCS based on the updated literature. KEY POINTS: Lung cancer is a leading cancer-related cause of death and screening should reduce associated mortality. This review summarizes current evidence related to LCS. Several aspects need to be implemented to optimize benefits and minimize potential drawbacks of LCS.

Coronary inflammation on chest computed tomography and COVID-19 mortality.

OBJECTIVES: The main factors associated with coronavirus disease-19 (COVID-19) mortality are age, comorbidities, pattern of inflammatory response, and SARS-CoV-2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri-coronary adipose tissue attenuation (PCAT), available from high-resolution chest computed tomography (HRCT) in COVID-19 patients with severe disease requiring hospitalization. METHODS: Two distinct groups of patients were admitted to Parma University Hospital in Italy with COVID-19 in March 2020 and March 2021 (first- and third-wave peaks of the COVID-19 pandemic in Italy, with the prevalence of wild-type and B.1.1.7 SARS-CoV-2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in-hospital mortality. Demographic, clinical, laboratory, HRCT data, and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to show which variables were associated with mortality. RESULTS: Among the 769 patients enrolled, 555 (72%) were discharged alive, and 214 (28%) died. In multivariable logistic regression analysis age (p < 0.001), number of chronic illnesses (p < 0.001), smoking habit (p = 0.006), P/F ratio (p = 0.001), platelet count (p = 0.002), blood creatinine (p < 0.001), non-invasive mechanical ventilation (p < 0.001), HRCT visual score (p < 0.001), and PCAT (p < 0.001), but not the calcium score, were independently associated with in-hospital mortality. CONCLUSION: Coronary inflammation, measured with PCAT on non-triggered HRCT, appeared to be independently associated with higher mortality in patients with severe COVID-19, while the pre-existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates. CLINICAL RELEVANCE STATEMENT: The current study demonstrates that a relatively simple measurement, peri-coronary adipose tissue attenuation (PCAT), available ex-post from standard high-resolution computed tomography, is strongly and independently associated with in-hospital mortality. KEY POINTS: • Coronary inflammation can be measured by the attenuation of peri-coronary adipose tissue (PCAT) on high-resolution CT (HRCT) without contrast media. • PCAT is strongly and independently associated with in-hospital mortality in SARS-CoV-2 patients. • PCAT might be considered an independent prognostic marker in COVID-19 patients if confirmed in other studies.

ESR Essentials: imaging in fibrotic lung diseases-practice recommendations by the European Society of Thoracic Imaging.

Fibrotic lung diseases (FLDs) represent a subgroup of interstitial lung diseases (ILDs), which can progress over time and carry a poor prognosis. Imaging has increased diagnostic discrimination in the evaluation of FLDs. International guidelines have stated the role of radiologists in the diagnosis and management of FLDs, in the context of the interdisciplinary discussion. Chest computed tomography (CT) with high-resolution technique is recommended to correctly recognise signs, patterns, and distribution of individual FLDs. Radiologists may be the first to recognise the presence of previously unknown interstitial lung abnormalities (ILAs) in various settings. A systematic approach to CT images may lead to a non-invasive diagnosis of FLDs. Careful comparison of serial CT exams is crucial in determining either disease progression or supervening complications. This 'Essentials' aims to provide radiologists a concise and practical approach to FLDs, focusing on CT technical requirements, pattern recognition, and assessment of disease progression and complications. Hot topics such as ILAs and progressive pulmonary fibrosis (PPF) are also discussed. KEY POINTS: Chest CT with high-resolution technique is the recommended imaging modality to diagnose pulmonary fibrosis. CT pattern recognition is central for an accurate diagnosis of fibrotic lung diseases (FLDs) by interdisciplinary discussion. Radiologists are to evaluate disease behaviour by accurately comparing serial CT scans.

CT-Guided Core Needle Biopsy of Pulmonary Lesions Associated With Cystic Airspaces: A Case-Control Study.

BACKGROUND. Concern may exist that pulmonary lesions associated with cystic airspaces are at risk of increased biopsy complications or lower biopsy accuracy given challenges in targeting tissue abutting or intermingled with the cystic airspaces. OBJECTIVE. The purpose of this study was to evaluate the safety and diagnostic performance of CT-guided core needle biopsy (CNB) of pulmonary lesions associated with cystic airspaces. METHODS. This retrospective study included 90 patients (median age, 69.5 years; 28 women, 62 men) who underwent CT-guided CNB of pulmonary lesions associated with cystic airspaces (based on review of procedural images) from February 2010 to December 2022 and a matched control group (2:1 ratio) of 180 patients (median age, 68.0 years; 56 women, 124 men) who underwent CNB of noncystic noncavitary lesions during the same period. The groups were compared in terms of complications, nondiagnostic biopsies (i.e., nonspecific benignities, atypical cells, or insufficient specimens), and CNB diagnostic performance for detecting malignancy using as reference the final diagnosis from a joint review of all available records. For lesions associated with cystic airspaces that underwent surgical resection after CNB, histologic slides were reviewed to explore the nature of the cystic airspace. RESULTS. The final diagnosis was malignant in 90% (81/90) of lesions associated with cystic airspaces and 92% (165/180) of noncystic noncavitary lesions. Patients with lesions associated with cystic airspaces and patients with noncystic noncavitary lesions showed no significant difference in frequency of complications (overall: 40% [36/90] vs 38% [68/180], p = .79; major: 4% [4/90] vs 6% [10/180], p = .78; minor: 36% [32/90] vs 32% [58/180], p = .59), frequency of nondiagnostic biopsies (12% [11/90] vs 9% [16/180], p = .40), or diagnostic performance (accuracy: 94% [85/90] vs 97% [175/180], p = .50; sensitivity: 94% [76/81] vs 97% [160/165], p = .50; specificity: 100% [9/9] vs 100% [15/15]; p > .99), respectively. All false-negative results for malignancy in both groups occurred in patients with nondiagnostic CNB results. Among lesions associated with cystic airspaces that were resected after CNB (all malignant), the cystic airspaces most commonly represented tumor degeneration (22/31 [71%]). CONCLUSION. CT-guided CNB is safe and accurate for assessing pulmonary lesions associated with cystic airspaces. CLINICAL IMPACT. CNB may help avoid a missed or delayed cancer diagnosis in pulmonary lesions with cystic airspaces.

Study rationale and design of the PEOPLHE trial.

PURPOSE: Lung cancer screening (LCS) by low-dose computed tomography (LDCT) demonstrated a 20-40% reduction in lung cancer mortality. National stakeholders and international scientific societies are increasingly endorsing LCS programs, but translating their benefits into practice is rather challenging. The "Model for Optimized Implementation of Early Lung Cancer Detection: Prospective Evaluation Of Preventive Lung HEalth" (PEOPLHE) is an Italian multicentric LCS program aiming at testing LCS feasibility and implementation within the national healthcare system. PEOPLHE is intended to assess (i) strategies to optimize LCS workflow, (ii) radiological quality assurance, and (iii) the need for dedicated resources, including smoking cessation facilities. METHODS: PEOPLHE aims to recruit 1.500 high-risk individuals across three tertiary general hospitals in three different Italian regions that provide comprehensive services to large populations to explore geographic, demographic, and socioeconomic diversities. Screening by LDCT will target current or former (quitting < 10 years) smokers (> 15 cigarettes/day for > 25 years, or > 10 cigarettes/day for > 30 years) aged 50-75 years. Lung nodules will be volumetric measured and classified by a modified PEOPLHE Lung-RADS 1.1 system. Current smokers will be offered smoking cessation support. CONCLUSION: The PEOPLHE program will provide information on strategies for screening enrollment and smoking cessation interventions; administrative, organizational, and radiological needs for performing a state-of-the-art LCS; collateral and incidental findings (both pulmonary and extrapulmonary), contributing to the LCS implementation within national healthcare systems.

Prior CT Improves Deep Learning for Malignancy Risk Estimation of Screening-detected Pulmonary Nodules.

Background Prior chest CT provides valuable temporal information (eg, changes in nodule size or appearance) to accurately estimate malignancy risk. Purpose To develop a deep learning (DL) algorithm that uses a current and prior low-dose CT examination to estimate 3-year malignancy risk of pulmonary nodules. Materials and Methods In this retrospective study, the algorithm was trained using National Lung Screening Trial data (collected from 2002 to 2004), wherein patients were imaged at most 2 years apart, and evaluated with two external test sets from the Danish Lung Cancer Screening Trial (DLCST) and the Multicentric Italian Lung Detection Trial (MILD), collected in 2004-2010 and 2005-2014, respectively. Performance was evaluated using area under the receiver operating characteristic curve (AUC) on cancer-enriched subsets with size-matched benign nodules imaged 1 and 2 years apart from DLCST and MILD, respectively. The algorithm was compared with a validated DL algorithm that only processed a single CT examination and the Pan-Canadian Early Lung Cancer Detection Study (PanCan) model. Results The training set included 10 508 nodules (422 malignant) in 4902 trial participants (mean age, 64 years ± 5 [SD]; 2778 men). The size-matched external test sets included 129 nodules (43 malignant) and 126 nodules (42 malignant). The algorithm achieved AUCs of 0.91 (95% CI: 0.85, 0.97) and 0.94 (95% CI: 0.89, 0.98). It significantly outperformed the DL algorithm that only processed a single CT examination (AUC, 0.85 [95% CI: 0.78, 0.92; P = .002]; and AUC, 0.89 [95% CI: 0.84, 0.95; P = .01]) and the PanCan model (AUC, 0.64 [95% CI: 0.53, 0.74; P < .001]; and AUC, 0.63 [95% CI: 0.52, 0.74; P < .001]). Conclusion A DL algorithm using current and prior low-dose CT examinations was more effective at estimating 3-year malignancy risk of pulmonary nodules than established models that only use a single CT examination. Clinical trial registration nos. NCT00047385, NCT00496977, NCT02837809 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Horst and Nishino in this issue.

A fully automated micro­CT deep learning approach for precision preclinical investigation of lung fibrosis progression and response to therapy.

Micro-computed tomography (µCT)-based imaging plays a key role in monitoring disease progression and response to candidate drugs in various animal models of human disease, but manual image processing is still highly time-consuming and prone to operator bias. Focusing on an established mouse model of bleomycin (BLM)-induced lung fibrosis we document, here, the ability of a fully automated deep-learning (DL)-based model to improve and speed-up lung segmentation and the precise measurement of morphological and functional biomarkers in both the whole lung and in individual lobes. µCT-DL whose results were overall highly consistent with those of more conventional, especially histological, analyses, allowed to cut down by approximately 45-fold the time required to analyze the entire dataset and to longitudinally follow fibrosis evolution and response to the human-use-approved drug Nintedanib, using both inspiratory and expiratory µCT. Particularly significant advantages of this µCT-DL approach, are: (i) its reduced experimental variability, due to the fact that each animal acts as its own control and the measured, operator bias-free biomarkers can be quantitatively compared across experiments; (ii) its ability to monitor longitudinally the spatial distribution of fibrotic lesions, thus eliminating potential confounding effects associated with the more severe fibrosis observed in the apical region of the left lung and the compensatory effects taking place in the right lung; (iii) the animal sparing afforded by its non-invasive nature and high reliability; and (iv) the fact that it can be integrated into different drug discovery pipelines with a substantial increase in both the speed and robustness of the evaluation of new candidate drugs. The µCT-DL approach thus lends itself as a powerful new tool for the precision preclinical monitoring of BLM-induced lung fibrosis and other disease models as well. Its ease of operation and use of standard imaging instrumentation make it easily transferable to other laboratories and to other experimental settings, including clinical diagnostic applications.

Walking the path of treatable traits in interstitial lung diseases.

Interstitial lung diseases (ILDs) are complex and heterogeneous diseases. The use of traditional diagnostic classification in ILD can lead to suboptimal management, which is worsened by not considering the molecular pathways, biological complexity, and disease phenotypes. The identification of specific "treatable traits" in ILDs, which are clinically relevant and modifiable disease characteristics, may improve patient's outcomes. Treatable traits in ILDs may be classified into four different domains (pulmonary, aetiological, comorbidities, and lifestyle), which will facilitate identification of related assessment tools, treatment options, and expected benefits. A multidisciplinary care team model is a potential way to implement a "treatable traits" strategy into clinical practice with the aim of improving patients' outcomes. Multidisciplinary models of care, international registries, and the use of artificial intelligence may facilitate the implementation of the "treatable traits" approach into clinical practice. Prospective studies are needed to test potential therapies for a variety of treatable traits to further advance care of patients with ILD.

Unsupervised machine learning identifies predictive progression markers of IPF.

OBJECTIVES: To identify and evaluate predictive lung imaging markers and their pathways of change during progression of idiopathic pulmonary fibrosis (IPF) from sequential data of an IPF cohort. To test if these imaging markers predict outcome. METHODS: We studied radiological disease progression in 76 patients with IPF, including overall 190 computed tomography (CT) examinations of the chest. An algorithm identified candidates for imaging patterns marking progression by computationally clustering visual CT features. A classification algorithm selected clusters associated with radiological disease progression by testing their value for recognizing the temporal sequence of examinations. This resulted in radiological disease progression signatures, and pathways of lung tissue change accompanying progression observed across the cohort. Finally, we tested if the dynamics of marker patterns predict outcome, and performed an external validation study on a cohort from a different center. RESULTS: Progression marker patterns were identified and exhibited high stability in a repeatability experiment with 20 random sub-cohorts of the overall cohort. The 4 top-ranked progression markers were consistently selected as most informative for progression across all random sub-cohorts. After spatial image registration, local tracking of lung pattern transitions revealed a network of tissue transition pathways from healthy to a sequence of disease tissues. The progression markers were predictive for outcome, and the model achieved comparable results on a replication cohort. CONCLUSIONS: Unsupervised learning can identify radiological disease progression markers that predict outcome. Local tracking of pattern transitions reveals pathways of radiological disease progression from healthy lung tissue through a sequence of diseased tissue types. KEY POINTS: • Unsupervised learning can identify radiological disease progression markers that predict outcome in patients with idiopathic pulmonary fibrosis. • Local tracking of pattern transitions reveals pathways of radiological disease progression from healthy lung tissue through a sequence of diseased tissue types. • The progression markers achieved comparable results on a replication cohort.

MR-based simplified extraprostatic extension evaluation: comparison of performances of different predictive models.

OBJECTIVES: To test reproducibility and predictive value of a simplified score for assessment of extraprostatic tumor extension (sEPE grade). METHODS: Sixty-five patients (mean age ± SD, 67 years ± 6.3) treated with radical prostatectomy for prostate cancer who underwent 1.5-Tesla multiparametric magnetic resonance imaging (mpMRI) 6 months before surgery were enrolled. sEPE grade was derived from mpMRI metrics: curvilinear contact length > 15 mm (CCL) and capsular bulging/irregularity. The diameter of the index lesion (dIL) was also measured. Evaluations were independently performed by seven radiologists, and inter-reader agreement was tested by weighted Cohen K coefficient. A nested (two levels) Monte Carlo cross-validation was used. The best cut-off value for dIL was selected by means of the Youden J index to classify values into a binary variable termed dIL*. Logistic regression models based on sEPE grade, dIL, and clinical scores were developed to predict pathologic EPE. Results on validation set were assessed by the main metrics of the receiver operating characteristics curve (ROC) and by decision curve analysis (DCA). Based on our findings, we defined and tested an alternative sEPE grade formulation. RESULTS: Pathologic EPE was found in 31/65 (48%) patients. Average κw was 0.65 (95% CI 0.51-0.79), 0.66 (95% CI 0.48-0.84), 0.67 (95% CI 0.50-0.84), and 0.43 (95% CI 0.22-0.63) for sEPE grading, CLL ≥ 15 mm, dIL*, and capsular bulging/irregularity, respectively. The highest diagnostic yield in predicting EPE was obtained by combining both sEPE grade and dIL*(ROC-AUC 0.81). CONCLUSIONS: sEPE grade is reproducible and when combined with the dIL* accurately predicts extraprostatic tumor extension. KEY POINTS: • Simple and reproducible mpMRI semi-quantitative scoring system for extraprostatic tumor extension. • sEPE grade accurately predicts extraprostatic tumor extension regardless of reader expertise. • Accurate pre-operative staging and risk stratification for optimized patient management.

Implementation of artificial intelligence in thoracic imaging-a what, how, and why guide from the European Society of Thoracic Imaging (ESTI).

This statement from the European Society of Thoracic imaging (ESTI) explains and summarises the essentials for understanding and implementing Artificial intelligence (AI) in clinical practice in thoracic radiology departments. This document discusses the current AI scientific evidence in thoracic imaging, its potential clinical utility, implementation and costs, training requirements and validation, its' effect on the training of new radiologists, post-implementation issues, and medico-legal and ethical issues. All these issues have to be addressed and overcome, for AI to become implemented clinically in thoracic radiology. KEY POINTS: • Assessing the datasets used for training and validation of the AI system is essential. • A departmental strategy and business plan which includes continuing quality assurance of AI system and a sustainable financial plan is important for successful implementation. • Awareness of the negative effect on training of new radiologists is vital.

Deep Learning-based Outcome Prediction in Progressive Fibrotic Lung Disease Using High-Resolution Computed Tomography.

Rationale: Reliable outcome prediction in patients with fibrotic lung disease using baseline high-resolution computed tomography (HRCT) data remains challenging. Objectives: To evaluate the prognostic accuracy of a deep learning algorithm (SOFIA [Systematic Objective Fibrotic Imaging Analysis Algorithm]), trained and validated in the identification of usual interstitial pneumonia (UIP)-like features on HRCT (UIP probability), in a large cohort of well-characterized patients with progressive fibrotic lung disease drawn from a national registry. Methods: SOFIA and radiologist UIP probabilities were converted to Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED)-based UIP probability categories (UIP not included in the differential, 0-4%; low probability of UIP, 5-29%; intermediate probability of UIP, 30-69%; high probability of UIP, 70-94%; and pathognomonic for UIP, 95-100%), and their prognostic utility was assessed using Cox proportional hazards modeling. Measurements and Main Results: In multivariable analysis adjusting for age, sex, guideline-based radiologic diagnosis, anddisease severity (using total interstitial lung disease [ILD] extent on HRCT, percent predicted FVC, DlCO, or the composite physiologic index), only SOFIA UIP probability PIOPED categories predicted survival. SOFIA-PIOPED UIP probability categories remained prognostically significant in patients considered indeterminate (n = 83) by expert radiologist consensus (hazard ratio, 1.73; P < 0.0001; 95% confidence interval, 1.40-2.14). In patients undergoing surgical lung biopsy (n = 86), after adjusting for guideline-based histologic pattern and total ILD extent on HRCT, only SOFIA-PIOPED probabilities were predictive of mortality (hazard ratio, 1.75; P < 0.0001; 95% confidence interval, 1.37-2.25). Conclusions: Deep learning-based UIP probability on HRCT provides enhanced outcome prediction in patients with progressive fibrotic lung disease when compared with expert radiologist evaluation or guideline-based histologic pattern. In principle, this tool may be useful in multidisciplinary characterization of fibrotic lung disease. The utility of this technology as a decision support system when ILD expertise is unavailable requires further investigation.

Syndrome of Combined Pulmonary Fibrosis and Emphysema: An Official ATS/ERS/JRS/ALAT Research Statement.

Background: The presence of emphysema is relatively common in patients with fibrotic interstitial lung disease. This has been designated combined pulmonary fibrosis and emphysema (CPFE). The lack of consensus over definitions and diagnostic criteria has limited CPFE research. Goals: The objectives of this task force were to review the terminology, definition, characteristics, pathophysiology, and research priorities of CPFE and to explore whether CPFE is a syndrome. Methods: This research statement was developed by a committee including 19 pulmonologists, 5 radiologists, 3 pathologists, 2 methodologists, and 2 patient representatives. The final document was supported by a focused systematic review that identified and summarized all recent publications related to CPFE. Results: This task force identified that patients with CPFE are predominantly male, with a history of smoking, severe dyspnea, relatively preserved airflow rates and lung volumes on spirometry, severely impaired DlCO, exertional hypoxemia, frequent pulmonary hypertension, and a dismal prognosis. The committee proposes to identify CPFE as a syndrome, given the clustering of pulmonary fibrosis and emphysema, shared pathogenetic pathways, unique considerations related to disease progression, increased risk of complications (pulmonary hypertension, lung cancer, and/or mortality), and implications for clinical trial design. There are varying features of interstitial lung disease and emphysema in CPFE. The committee offers a research definition and classification criteria and proposes that studies on CPFE include a comprehensive description of radiologic and, when available, pathological patterns, including some recently described patterns such as smoking-related interstitial fibrosis. Conclusions: This statement delineates the syndrome of CPFE and highlights research priorities.

Drug-induced interstitial lung disease.

Interstitial lung disease (ILD) secondary to drug-induced lung injury is an increasingly common cause of morbidity and mortality. The number of drugs associated with the development of ILD continues to rise, mainly due to the use of novel monoclonal antibodies and biologicals for neoplastic and rheumatological diseases, and includes, among others, chemotherapeutics, molecular targeting agents, immune checkpoint inhibitors, antibiotics, antiarrhythmics and conventional or biological disease-modifying antirheumatic drugs. Drug-induced ILD (DI-ILD) manifests with a variety of clinical patterns, ranging from mild respiratory symptoms to rapidly progressive respiratory failure and death. In most cases, there are no pathognomonic clinical, laboratory, radiological or pathological features and the diagnosis of DI-ILD is suspected in the presence of exposure to a drug known to cause lung toxicity and after exclusion of alternative causes of ILD. Early identification and permanent discontinuation of the culprit drug are the cornerstones of treatment with systemic glucocorticoids being used in patients with disabling or progressive disease. However, for certain drugs, such as checkpoint inhibitors, the frequency of lung toxicity is such that mitigation strategies are put in place to prevent this complication, and occurrence of DI-ILD is not necessarily synonymous with permanent drug discontinuation, particularly in the absence of valid therapeutic alternatives.

European Respiratory Society statement on long COVID follow-up.

Patients diagnosed with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently experience symptom burden post-acute infection or post-hospitalisation. We aimed to identify optimal strategies for follow-up care that may positively impact the patient's quality of life (QoL). A European Respiratory Society (ERS) Task Force convened and prioritised eight clinical questions. A targeted search of the literature defined the timeline of "long COVID" as 1-6 months post-infection and identified clinical evidence in the follow-up of patients. Studies meeting the inclusion criteria report an association of characteristics of acute infection with persistent symptoms, thromboembolic events in the follow-up period, and evaluations of pulmonary physiology and imaging. Importantly, this statement reviews QoL consequences, symptom burden, disability and home care follow-up. Overall, the evidence for follow-up care for patients with long COVID is limited.

Scan-based competing death risk model for re-evaluating lung cancer computed tomography screening eligibility.

BACKGROUND: A baseline computed tomography (CT) scan for lung cancer (LC) screening may reveal information indicating that certain LC screening participants can be screened less, and instead require dedicated early cardiac and respiratory clinical input. We aimed to develop and validate competing death (CD) risk models using CT information to identify participants with a low LC risk and a high CD risk. METHODS: Participant demographics and quantitative CT measures of LC, cardiovascular disease and chronic obstructive pulmonary disease were considered for deriving a logistic regression model for predicting 5-year CD risk using a sample from the National Lung Screening Trial (n=15 000). Multicentric Italian Lung Detection data were used to perform external validation (n=2287). RESULTS: Our final CD model outperformed an external pre-scan model (CD Risk Assessment Tool) in both the derivation (area under the curve (AUC) 0.744 (95% CI 0.727-0.761) and 0.677 (95% CI 0.658-0.695), respectively) and validation cohorts (AUC 0.744 (95% CI 0.652-0.835) and 0.725 (95% CI 0.633-0.816), respectively). By also taking LC incidence risk into consideration, we suggested a risk threshold where a subgroup (6258/23 096 (27%)) was identified with a number needed to screen to detect one LC of 216 (versus 23 in the remainder of the cohort) and ratio of 5.41 CDs per LC case (versus 0.88). The respective values in the validation cohort subgroup (774/2287 (34%)) were 129 (versus 29) and 1.67 (versus 0.43). CONCLUSIONS: Evaluating both LC and CD risks post-scan may improve the efficiency of LC screening and facilitate the initiation of multidisciplinary trajectories among certain participants.

A fully automated deep learning pipeline for micro-CT-imaging-based densitometry of lung fibrosis murine models.

Idiopathic pulmonary fibrosis, the archetype of pulmonary fibrosis (PF), is a chronic lung disease of a poor prognosis, characterized by progressively worsening of lung function. Although histology is still the gold standard for PF assessment in preclinical practice, histological data typically involve less than 1% of total lung volume and are not amenable to longitudinal studies. A miniaturized version of computed tomography (µCT) has been introduced to radiologically examine lung in preclinical murine models of PF. The linear relationship between X-ray attenuation and tissue density allows lung densitometry on total lung volume. However, the huge density changes caused by PF usually require manual segmentation by trained operators, limiting µCT deployment in preclinical routine. Deep learning approaches have achieved state-of-the-art performance in medical image segmentation. In this work, we propose a fully automated deep learning approach to segment right and left lung on µCT imaging and subsequently derive lung densitometry. Our pipeline first employs a convolutional network (CNN) for pre-processing at low-resolution and then a 2.5D CNN for higher-resolution segmentation, combining computational advantage of 2D and ability to address 3D spatial coherence without compromising accuracy. Finally, lungs are divided into compartments based on air content assessed by density. We validated this pipeline on 72 mice with different grades of PF, achieving a Dice score of 0.967 on test set. Our tests demonstrate that this automated tool allows for rapid and comprehensive analysis of µCT scans of PF murine models, thus laying the ground for its wider exploitation in preclinical settings.