An explorative analysis on the optimal cryo-passes and freezing time of the ultrathin cryoprobe in endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy.

EBUS-guided transbronchial mediastinal cryobiopsy (TBMC) has emerged as a promising biopsy tool for diagnosing hilar and mediastinal pathologies. However, several fundamental technical aspects of TBMC remain unexplored. This study aims to determine the optimal number of cryo-passes and freezing time of the ultrathin cryoprobe in EBUS-TBMC concerning specimen size and procedural diagnostic yield. We conducted a retrospective chart review of patients with mediastinal and hilar lesions who underwent EBUS-TBMC between January 2021 and April 2023 across three hospitals in Malaysia. A total of 129 EBUS-TBMC procedures were successfully completed, achieving an overall diagnostic yield of 88.4%. Conclusive TBMC procedures were associated with larger specimen sizes (7.0 vs. 5.0 mm, p < 0.01). Specimen size demonstrated a positive correlation with diagnostic yield (p < 0.01), plateauing at specimen size of 4.1-6.0 mm. A significant positive correlation was also observed between the number of cryo-passes and both specimen size (p < 0.01) and diagnostic yield (p < 0.05). Diagnostic yield plateaued after 2-3 cryo-passes. In contrast, longer freezing times trended towards smaller specimens and lower diagnostic yield, though not reaching statistical significance. The highest diagnostic yield was recorded at the 3.1-4.0 s freezing time. The safety profile of TBMC remains favourable, with one case (0.8%) of pneumothorax and nine cases (7%) of self-limiting bleeding. In our cohort, TBMC performance with 2-3 cryo-passes and a 3.1-4.0 s freezing time to achieve a total aggregate specimen size of 4.1-6.0 mm appeared optimal. Further prospective studies are needed to validate these findings.

Cone-Beam Computed Tomography Improves Location of Transbronchial Cryobiopsy in Interstitial Lung Disease with Limited Extent.

INTRODUCTION: Transbronchial lung cryobiopsy has been recommended as an acceptable alternative to surgical approach for making a histopathological diagnosis in patients with interstitial lung disease (ILD) of undetermined type. In limited diseases (especially if distributed along the subpleural region), sampling the specific area in which the pathological process is more represented could be challenging. Aim of the study was to determine the potential benefit of utilizing cone-beam computed tomography-guided cryobiopsy in patients with limited extent of ILD on CT scan and determine the single impact of each sequential biopsy progressively increasing the total number of biopsies. METHODS: This study is a prospective analysis of patients with undetermined ILD and CT scan extent <15% undergoing cone-beam CT-guided cryobiopsy. Each biopsy sample was collected and processed individually and pathologic interpretations were performed sequentially with the pathologist reformulating a new report with the addition of each sample (cumulative yield). RESULTS: Thirty six patients were enrolled. Pathological diagnostic yield was >90%, with almost 80% of diagnostic samples being the first one; when a second biopsy was performed, mean diagnostic yield increased with only a moderately significant difference. No severe adverse events were observed; pneumothorax was documented in 27.8% of the cases. CONCLUSION: Sequential individual collection and pathologic interpretation of each biopsy sample has confirmed the possibility of obtaining a diagnostic specimen at the first pass if transbronchial cryobiopsy is performed under cone-beam CT.

Transbronchial lung cryobiopsy under real-time radial EBUS: First report on a novel twist of the classical technique.

Transbronchial lung cryobiopsy (TBLC) is a relatively new technique for obtaining lung biopsies, known for being the least invasive method while offering a high diagnostic yield, a favourable safety profile, and a significant reduction in morbidity, mortality, and hospital stay length compared to surgical lung biopsy. Radial-EBUS (r-EBUS) represent a cornerstone modality for accessing 'invisible' peripheral pulmonary lesions. However, a major drawback of these techniques is the lack of 'real-time' visualization of the biopsy being obtained. In this case report, we present a young woman who was referred to us with a cough, haemoptysis, and a non-resolving lung consolidation. She underwent TBLC under real-time rEBUS guidance. This clinical case demonstrates that, in specific clinical scenarios, TBLC with real-time rEBUS is an excellent diagnostic tool.

Bronchoscopy with and without needle-based confocal laser endomicroscopy for peripheral lung nodule diagnosis: protocol for a multicentre randomised controlled trial (CLEVER trial).

INTRODUCTION: Despite many technological advances, the diagnostic yield of bronchoscopic peripheral lung nodule analysis remains limited due to frequent mispositioning. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic feedback on needle positioning, potentially improving the sampling location and diagnostic yield. Previous studies have defined and validated nCLE criteria for malignancy, airway and lung parenchyma. Larger studies demonstrating the effect of nCLE on diagnostic yield are lacking. We aim to investigate if nCLE-imaging integrated with conventional bronchoscopy results in a higher diagnostic yield compared with conventional bronchoscopy without nCLE. METHODS AND ANALYSIS: This is a parallel-group randomised controlled trial. Recruitment is performed at pulmonology outpatient clinics in universities and general hospitals in six different European countries and one hospital in the USA. Consecutive patients with a for malignancy suspected peripheral lung nodule (10-30 mm) with an indication for diagnostic bronchoscopy will be screened, and 208 patients will be included. Web-based randomisation (1:1) between the two procedures will be performed. The primary outcome is diagnostic yield. Secondary outcomes include diagnostic sensitivity for malignancy, needle repositionings, procedure and fluoroscopy duration, and complications. Pathologists will be blinded to procedure type; patients and endoscopists will not. ETHICS AND DISSEMINATION: Primary approval by the Ethics Committee of the Amsterdam University Medical Center. Dissemination involves publication in a peer-reviewed journal. SUPPORT: Financial and material support from Mauna Kea Technologies. TRIAL REGISTRATION NUMBER: NCT06079970.

Endobronchial ultrasound-guided cryobiopsy for diagnosing a case of granulomatosis with polyangiitis.

EBUS-TBNA has represented a revolution in the diagnosis of intrathoracic pathologies, particularly in lung cancer staging, replacing more invasive methods such as mediastinoscopy. However, its role in diagnosing rare benign or malignant mediastinal disorders is still a matter of debate. Over the past few years, the role of EBUS-guided cryobiopsy has been increasingly emerging as an innovative and minimally invasive technique in diagnosing these disorders, with an excellent safety profile. In this case report, we present the case of a young man brought to our attention after already undergoing a non-diagnostic trans thoracic needle aspiration (TTNA) procedure for lung consolidations. In our department, he underwent an initial EBUS-TBNA procedure with inconclusive rapid on-site evaluation (ROSE), leading to the decision to perform an EBUS-guided cryobiopsy, which yielded a diagnosis of granulomatosis with polyangiitis without complications. This clinical case demonstrates that in specific contexts, EBUS-cryobiopsy represents an excellent diagnostic tool.

Transbronchial cryobiopsy followed by as-needed surgical lung biopsy versus immediate surgical lung biopsy for diagnosing interstitial lung disease (the COLD study): a randomised controlled trial.

BACKGROUND: An adequate diagnosis for interstitial lung disease (ILD) is important for clinical decision making and prognosis. In most patients with ILD, an accurate diagnosis can be made by clinical and radiological data assessment, but in a considerable proportion of patients, a lung biopsy is required. Surgical lung biopsy (SLB) is the most common method to obtain tissue, but it is associated with high morbidity and even mortality. More recently, transbronchial cryobiopsy has been introduced, with fewer adverse events but a lower diagnostic yield than SLB. The aim of this study is to compare two diagnostic strategies: a step-up strategy (transbronchial cryobiopsy, followed by SLB if the cryobiopsy is insufficiently informative) versus immediate SLB. METHODS: The COLD study was a multicentre, randomised controlled trial in six hospitals across the Netherlands. We included patients with ILD with an indication for lung biopsy as assessed by a multidisciplinary team discussion. Patients were randomly assigned in a 1:1 ratio to the step-up or immediate SLB strategy, with follow-up for 12 weeks from the initial procedure. Patients, clinicians, and pathologists were not masked to the study treatment. The primary endpoint was unexpected chest tube drainage, defined as requiring any chest tube after transbronchial cryobiopsy, or prolonged (>24 h) chest tube drainage after SLB. Secondary endpoints were diagnostic yield, in-hospital stay, pain, and serious adverse events. A modified intention-to-treat analysis was performed. This trial is registered with the Dutch Trial Register, NL7634, and is now closed. FINDINGS: Between April 8, 2019, and Oct 24, 2021, 122 patients with ILD were assessed for study participation; and 55 patients were randomly assigned to the step-up strategy (n=28) or immediate SLB (n=27); three patients from the immediate SLB group were excluded. Unexpected chest tube drainage occurred in three of 28 patients (11%; 95% CI 4-27%) in the step-up group, and the number of patients for whom the chest tube could not be removed within 24 h was 11 of 24 patients (46%; 95% CI 2-65%) in the SLB group, with an absolute risk reduction of 35% (11-56%; p=0·0058). In the step-up strategy, the multidisciplinary team diagnostic yield after transbronchial cryobiopsy alone was 82% (64-92%), which increased to 89% (73-96%) when subsequent SLB was performed after inconclusive transbronchial cryobiopsy. In the immediate surgery strategy, the multidisciplinary team diagnostic yield was 88% (69-97%). Total in-hospital stay was 1 day (IQR 1-1) in the step-up group versus 5 days (IQR 4-6) in the SLB group. One (4%) serious adverse event occurred in step-up strategy versus 12 (50%) in the immediate SLB strategy. INTERPRETATION: In ILD diagnosis, if lung tissue assessment is required, a diagnostic strategy starting with transbronchial cryobiopsy, followed by SLB when transbronchial cryobiopsy is inconclusive, appears to result in a significant reduction of patient burden and in-hospital stay with a similar diagnostic yield versus immediate SLB. FUNDING: Netherlands Organisation for Health Research and Development (ZonMW) and Amsterdam University Medical Centers.

COVID-19. Biology, pathophysiology, and immunology: a pathologist view.

Even if the SARS-CoV-2 pandemic has been declared over, several risks and clinical problems remain to be faced, including long-COVID sequelae and possible outbreaks of pathogenic variants. Intense research on COVID-19 has provided in these few years a striking amount of data covering different fields and disciplines, which can help to provide a knowledge shield against new potential infective spreads, and may also potentially be applied to other fields of medicine, including oncology and neurology. Nevertheless, areas of uncertainty still remain regarding the pathogenic mechanisms that subtend the multifaceted manifestations of the disease. To better clarify the pathogenesis of the disease, a systematic multidisciplinary evaluation of the many mechanisms involved in COVID-19 is mandatory, including clinical, physiological, radiological, immunological and pathological studies. In COVID-19 syndrome the pathological studies have been mainly performed on autopsy cases, and only a few studies are available on biopsies. Nevertheless, these studies have provided relevant information that can substantially contribute to decipher the complex scenario characterizing the different forms of COVID-19 and long-COVID-19. In this review the data provided by pathological investigations are recapitulated and discussed, in the light of different hypothesis and data provided by clinical, physiological and immunological data.

Historical eye on IPF: a cohort study redefining the mortality scenario.

Rationale: Therapies that slow idiopathic pulmonary fibrosis (IPF) progression are now available and recent studies suggest that the use of antifibrotic therapy may reduce IPF mortality. Objectives: The aim of the study was to evaluate whether, to what extent, and for which factors the survival of IPF in a real-life setting has changed in the last 15 years. Methods: Historical eye is an observational study of a large cohort of consecutive IPF patients diagnosed and treated in a referral center for ILDs with prospective intention. We recruited all consecutive IPF patients seen at GB Morgagni Hospital, Forlì, Italy between January 2002 and December 2016 (15 years). We used survival analysis methods to describe and model the time to death or lung transplant and Cox regression to model prevalent and incident patient characteristics (time-dependent Cox models were fitted). Measurements and main results: The study comprised 634 patients. The year 2012 identifies the time point of mortality shift (HR 0.58, CI 0.46-0.63, p < 0.001). In the more recent cohort, more patients had better preserved lung function, underwent cryobiopsy instead of surgery, and were treated with antifibrotics. Highly significant negative prognostic factors were lung cancer (HR 4.46, 95% CI 3.3-6, p < 0.001), hospitalizations (HR 8.37, 95% CI 6.5-10.7, p < 0.001), and acute exacerbations (HR 8.37, 95% CI 6.52-10.7, p < 0.001). The average antifibrotic treatment effect estimated using propensity score matching showed a significant effect in the reduction of all-cause mortality (ATE coeff -0.23, SE 0.04, p < 0.001), acute exacerbations (ATE coeff -0.15, SE 0.04, p < 0.001), and hospitalizations (ATE coeff -0.15, SE 0.04, p < 0.001) but no effect on lung cancer risk (ATE coeff -0.03, SE 0.03, p = 0.4). Conclusion: Antifibrotic drugs significantly impact hospitalizations, acute exacerbations, and IPF survival. After the introduction of cryobiopsy and antifibrotic drugs, the prognosis of IPF patients has significantly improved together with our ability to detect IPF at an earlier stage.

Association between Parenchymal B-Cell Follicles and CT-Proven Enlarged Mediastinal Lymph Nodes in Patients with Pulmonary Fibrosis.

BACKGROUND: Mediastinal lymph node enlargement (MLNE) is a finding described in a subset of patients with idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs) and is associated with accelerated disease progression and increased mortality. The cause of MLNE is still not known. Our hypothesis is that there is an association between MLNE and B-cell follicles in lung tissue, another aspect detectable in the lung tissue of patients with IPF and other ILDs. OBJECTIVES: The aim of this study was to assess if there is an association between MLNE and B-cell follicles in lung tissue in patients with IPF and other ILDs. METHOD: Patients having transbronchial cryobiopsies performed as part of an investigation for ILD were included in this prospective observational study. MLNE (smallest diameter ≥10 mm) were assessed in station 7, 4R, and 4L on high-resolution computed tomography scans. B-cell follicles were assessed on haematoxylin-eosin-stained specimens. Lung function, 6-minute walk test, acute exacerbation, and mortality were registered after 2 years. In addition, we investigated if the finding of B-cell follicles was consistent in patients who underwent both surgical lung biopsies (SLBs) and cryobiopsies. RESULTS: In total, 93 patients were included for analysis (46% diagnosed with IPF, 54% diagnosed with other ILDs). MLNE was found in 26 (60%) of the IPF patients and in 23 (46%) of the non-IPF patients (p = 0.164). Diffusing capacity for carbon monoxide was significantly lower (p = 0.03) in patients with MLNE compared to patients without MLNE. B-cell follicles were found in 11 (26%) of the IPF patients and in 22 (44%) of the non-IPF patients (p = 0.064). Germinal centres were not seen in any of the patients. There was no association between MLNE and B-cell follicles (p = 0.057). No significant difference in change of pulmonary function test was seen at 2-year follow-up when comparing the patients with and without MLNE or B-cell follicles. In 13 patients, both SLBs and cryobiopsies were performed. The presence of B-cell follicles was not consistent when comparing the two different methods. CONCLUSION: MLNE is evident in a substantial part of patients with ILD and is associated with lower DLCO at inclusion. We could not demonstrate an association between histological B-cell follicles in biopsies and MLNE. A possible explanation for this is that the cryobiopsies might not have captured the changes we sought.

Is there any role for medical thoracoscopy in the treatment of empyema in children?

It is still controversial whether surgical or nonsurgical treatment approaches are most appropriate for empyema in children, and there are no data regarding the role of medical thoracoscopy in this population. The aim of this study was to describe our experience with medical thoracosocpy in children with multiloculated and organizing pneumonia. We retrospectively reviewed children admitted to our hospital with a diagnosis of empyema from 2011 to 2021 and treated with medical thoracoscopy. A total of six patients with empyema were treated by medical thoracoscopy; empyema was multiloculated in five cases and organized in one case; all children in the study recovered completely with full lung expansion after chest X-rays, and no disease sequelae were reported after clinical follow-up. Our small case series suggests that in selected cases, medical thoracoscopy could safely and effectively treat pleural empyema in children, with less invasiveness and reduced psychological consequences.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Treatment with COLchicine in hospitalized patients affected by COVID-19: The COLVID-19 trial.

OBJECTIVE: To evaluate whether the addition of colchicine to standard of care (SOC) results in better outcomes in hospitalized patients with COVID-19. DESIGN: This interventional, multicenter, randomized, phase 2 study, evaluated colchicine 1.5 mg/day added to SOC in hospitalized COVID-19 patients (COLVID-19 trial) and 227 patients were recruited. The primary outcome was the rate of critical disease in 30 days defined as need of mechanical ventilation, intensive care unit (ICU), or death. RESULTS: 152 non-anti-SARS-CoV-2-vaccinated patients (colchicine vs controls: 77vs75, mean age 69.1±13.1 vs 67.9±15 years, 39% vs 33.3% females, respectively) were analyzed. There was no difference in co-primary end-points between patients treated with colchicine compared to controls (mechanical ventilation 5.2% vs 4%, ICU 1.3% vs 5.3%, death 9.1% vs 6.7%, overall 11 (14.3%) vs 10 (13.3%) patients, P=ns, respectively). Mean time to discharge was similar (colchicine vs controls 14.1±10.4 vs 14.7±8.1 days). Older age (>60 years, P=0.025), P/F<275 mmHg (P=0.005), AST>40 U/L (P<0.001), pre-existent heart (P=0.02), lung (P=0.003), upper-gastrointestinal (P=0.014), lower-gastrointestinal diseases (P=0.009) and cancer (P=0.008) were predictive of achieving the primary outcome. Diarrhoea (9.1% vs 0%, p=0.0031) and increased levels of AST at 6 days (76.9±91.8 vs 33.5±20.7 U/l, P=0.016) were more frequent in the colchicine group. CONCLUSION: Colchicine did not reduce the rate and the time to the critical stage. Colchicine was relatively safe although adverse hepatic effects require caution. We confirm that older (>60 years) patients with comorbidities are characterized by worse outcome.

Medical Thoracoscopy and Intrapleural Fibrinolytic Therapy for the Management of Pleural Empyema: A Cohort Study.

BACKGROUND: Pleural empyema is associated with relevant morbidity and mortality, and it may be classified, according to evolution and ultrasound, into three stages: stage I (free-flowing effusion), stage II (viscous effusion with the tendency to loculate), and stage III (organizing phase). According to guidelines, antibiotic therapy and pleural drainage are recommended, with surgery being performed when patients fail and/or in case of organized empyema. OBJECTIVES: The aim of the study was to report the efficacy and safety of medical thoracoscopy in patients with pleural empyema stratified by chest ultrasound. METHOD: Observational retrospective cohort study analyzing patients with pleural empyema treated with medical thoracoscopy. Procedure success and mortality were evaluated at 30 days and 90 days after the procedure; complications were also reported. RESULTS: 131 patients were included. Intrapleural fibrinolytic therapy was performed thereafter in the majority of cases. Medical thoracoscopy was considered successful without subsequent intervention in 99 patients (76%); 19 patients (15%) underwent a second procedure (drainage, thoracoscopy, video-assisted thoracic surgery, or thoracotomy); and 6 patients (5%) died of the evolution of empyema. Patients treated in stages I and II showed significantly better post-procedure results compared with patients treated in stage III (100%, 83.3%, and 58.1%, respectively). Thoracoscopy complications were observed in 18 patients and were reversible in all cases. CONCLUSIONS: Patients with pleural empyema treated in earlier stages (free-flowing or multiloculated effusion) with medical thoracoscopy show significantly better results than patients treated in later stages (organized empyema). This approach is safe, minimally invasive, and efficient in these patients with disease having relevant mortality; however, patient selection remains essential.

Lung cancer in patients with idiopathic pulmonary fibrosis: A retrospective multicentre study in Europe.

BACKGROUND AND OBJECTIVE: There remains a paucity of large databases for patients with idiopathic pulmonary fibrosis (IPF) and lung cancer. We aimed to create a European registry. METHODS: This was a multicentre, retrospective study across seven European countries between 1 January 2010 and 18 May 2021. RESULTS: We identified 324 patients with lung cancer among 3178 patients with IPF (prevalence = 10.2%). By the end of the 10 year-period following IPF diagnosis, 26.6% of alive patients with IPF had been diagnosed with lung cancer. Patients with IPF and lung cancer experienced increased risk of all-cause mortality than IPF patients without lung cancer (HR: 1.51, [95% CI: 1.22-1.86], p < 0.0001). All-cause mortality was significantly lower for patients with IPF and lung cancer with a monocyte count of either <0.60 or 0.60-<0.95 K/µl than patients with monocyte count ≥0.95 K/µl (HR [<0.60 vs. ≥0.95 K/µl]: 0.35, [95% CI: 0.17-0.72], HR [0.60-<0.95 vs. ≥0.95 K/µl]: 0.42, [95% CI: 0.21-0.82], p = 0.003). Patients with IPF and lung cancer that received antifibrotics presented with decreased all cause-mortality compared to those who did not receive antifibrotics (HR: 0.61, [95% CI: 0.42-0.87], p = 0.006). In the adjusted model, a significantly lower proportion of surgically treated patients with IPF and otherwise technically operable lung cancer experienced all-cause mortality compared to non-surgically treated patients (HR: 0.30 [95% CI: 0.11-0.86], p = 0.02). CONCLUSION: Lung cancer exerts a dramatic impact on patients with IPF. A consensus statement for the management of patients with IPF and lung cancer is sorely needed.

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.

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.

Genetic testing in interstitial lung disease: An international survey.

BACKGROUND AND OBJECTIVE: Genetic analysis is emerging for interstitial lung diseases (ILDs); however, ILD practices are not yet standardized. We surveyed patients', relatives' and pulmonologists' experiences and needs on genetic testing in ILD to evaluate the current situation and identify future needs. METHODS: A clinical epidemiologist (MT) together with members of the ERS taskforce and representatives of the European Idiopathic Pulmonary Fibrosis and related disorders Federation (EU-IPFF) patient organisation developed a survey for patients, relatives and pulmonologists. Online surveys consisted of questions on five main topics: awareness of hereditary ILD, the provision of information, genetic testing, screening of asymptomatic relatives and clinical impact of genetic analysis in ILD. RESULTS: Survey respondents consisted of 458 patients with ILD, 181 patients' relatives and 352 pulmonologists. Most respondents think genetic testing can be useful, particularly for explaining the cause of disease, predicting its course, determining risk for developing disease and the need to test relatives. Informing patients and relatives on genetic analysis is primarily performed by the pulmonologist, but 88% (218) of pulmonologists identify a need for more information and 96% (240) ask for guidelines on genetic testing in ILD. A third of the pulmonologists who would offer genetic testing currently do not offer a genetic test, primarily because they have limited access to genetic tests. Following genetic testing, 72% (171) of pulmonologists may change the diagnostic work-up and 57% (137) may change the therapeutic approach. CONCLUSION: This survey shows that there is wide support for implementation of genetic testing in ILD and a high need for information, guidelines and access to testing among patients, their relatives and pulmonologists.

Lung cancer in patients with fibrosing interstitial lung diseases: an overview of current knowledge and challenges.

Patients with progressive fibrosing interstitial lung diseases (fILD) have increased morbidity and mortality. Lung fibrosis can be associated with lung cancer. The pathogenesis of both diseases shows similarities, although not all mechanisms are understood. The combination of the diseases is challenging, due to the amplified risk of mortality, and also because lung cancer treatment carries additional risks in patients with underlying lung fibrosis. Acute exacerbations in fILD patients are linked to increased mortality, and the risk of acute exacerbations is increased after lung cancer treatment with surgery, chemotherapy or radiotherapy. Careful selection of treatment modalities is crucial to improve survival while maintaining acceptable quality of life in patients with combined lung cancer and fILD. This overview of epidemiology, pathogenesis, treatment and a possible role for antifibrotic drugs in patients with lung cancer and fILD is the summary of a session presented during the virtual European Respiratory Society Congress in 2021. The review summarises current knowledge and identifies areas of uncertainty. Most current data relate to patients with combined idiopathic pulmonary fibrosis and lung cancer. There is a pressing need for additional prospective studies, required for the formulation of a consensus statement or guideline on the optimal care of patients with lung cancer and fILD.