Surgical Lung Biopsy Research Articles

Primera experiencia de criobiopsia transbronquial para enfermedad pulmonar intersticial difusa en un hospital nacional de Lima, Perú

Transbronchial cryobiopsy has been described as a new method to obtain lung tissue, demonstrating good correlation with surgical lung biopsies, fewer complications, costs and hospital stay. We describe our first experience carried out successfully in a national hospital. This is a 53-year-old female patient, with a disease duration of five years, characterized by progressive dyspnea. Non-UIP standard tomography. Rheumatological study: mixed positive ANA, speckled nuclear 1/2560 and nucleolar 1/5120. Anti-ENA positive, ANCA negative. Spirometry with FVC 1.83 (69%) and diffusion test 10.39 (67%). After the evaluation of the multidisciplinary committee, a lung biopsy was indicated. After clinical and functional evaluation, cryobiopsy was performed with the use of general anesthesia, prophylactic endobronchial blocker, fluoroscopic guidance and cryoprobe.

Surgical management of pleural complications in lymphangioleiomyomatosis

ObjectiveLymphangioleiomyomatosis (LAM) is a rare cystic lung disease occurring primarily in women. Pneumothorax and chylothorax are common pleural complications in LAM. We aim to explore various options in the surgical management of pleural disease in LAM. MethodsA retrospective chart review of all patients at the Center for LAM and Rare Lung Diseases at Columbia University was performed, and date, type, and indication for surgical procedure were collected. All patients with any cystic lung disease seen between January 1, 2000, and March 1, 2023, were included in the database. ResultsThe charts for 326 patients with possible LAM were reviewed, including 213 with confirmed LAM and 113 women with cystic lung disease consistent suspected to be LAM were reviewed. A total of 40.5% underwent surgical procedures at our institution or at referring hospitals. A total of 15.6% of patients underwent surgical lung biopsies. A total of 16.6% had a history of pneumothoraces, of whom 79.6% underwent chemical and/or mechanical pleurodesis, 14.8% required pleurectomy, and 7.4% were discharged with tunneled indwelling pleural catheters. We found that 5.6% of confirmed LAM patients have history of chylothorax, with thoracic duct ligation, thoracic duct embolization, pleurodesis, and pleurodesis with long-term tunneled indwelling pleural catheter placement all used as treatment strategies. ConclusionsHere we demonstrate the significant burden of pleural disease in patients with LAM. It is imperative that thoracic surgeons understand the high incidence of pneumothorax in this patient population. Tunneled indwelling pleural catheters are underutilized but provide long-term options for chylous management with long-term mechanical pleurodesis and a decrease in hospital length of stay.

Chinese expert consensus on the pathological diagnosis of interstitial lung disease with transbronchial lung cryobiopsy specimens

Transbronchial lung cryobiopsy (TBLC) is an applicable technique that can provide a histologic diagnosis of interstitial lung disease(ILD). The general sample size of TBLC is much smaller than that of surgical lung biopsy (SLB), which raises more concerns about the procedure's diagnostic accuracy. A guiding consensus and guidelines on the pathological procedure of ILD with TBLC are required to better guide pathologists in diagnostic practice. The Respiratory Pathology Working Group of the Respiratory Physicians Branch of the Chinese Medical Doctor Association and the Thoracic Diseases Group of the Pathological Branch of the Chinese Medical Association, jointly organized by experts, have worked together to discuss and formulated the consensus. The consensus is based on literature review, clinical practice, collection of clinical issues, and discussion during a series of meetings. Experts approved the final proposed consensus with more than 70% of votes in favor (Delphi). The consensus summarized the delivery requirements, quality evaluation and artificial phenomena of TBLC specimens. It also proposed the diagnostic principles and procedures, types of ILD corresponding to major pathological changes, and major corresponding differential diagnoses of TBLC specimens. Finally, the consensus formed 14 recommendations for clinical diagnosis and multidisciplinary discussion.The recommendations are addressed as follows.Recommendation 1: We suggest that the TBLC clinical manipulators should observe and measure the size of the specimen in time. The specimen size should be greater than 5 mm in diameter, and multiple pieces(3 to 5 pieces)are recommended.Recommendation 2: Pathologists should record the number of blocks of tissue submitted for examination and the volume, color, and texture of each specimen. Evaluation of the proportion of alveolar parenchyma/airway components under the microscope, analysis of the type and distribution of lesions will facilitate making diagnostic suggestions.Recommendation 3: The size of TBLC specimens is significantly smaller than SLB and may not show sufficient features of ILD or secondary changes. It is more necessary to combine the evaluation of clinical changes and lesion distribution assessed by HRCT for a comprehensive diagnosis.Recommendation 4: Common microscopic artefacts of TBLC specimen are mass of red blood cells, proteinaceous fluid and fibrin exudation. In the absence of hemosiderin cells or clinical signs of hemoptysis symptoms, the diagnosis of pulmonary hemorrhagic disease should be considered with caution.Recommendation 5: TBLC is not a suggested diagnosis when the pathological changes are mainly located in the pleural or subpleural lung tissues, e.g., pleuroparenchymal fibroelastosis.Recommendation 6: The principle of pathological diagnosis of ILD in TBLC is consistent with SLB, with a description of the main pathological morphological change and a tendentious pathological diagnosis; if the lesion is not fully shown, only a pathological description is given.Recommendation 7: A well-sampled TBLC specimen may show patchy fibrosis and fibroblast foci in UIP, supporting a pathological diagnosis of a probable UIP pattern. TBLC may not display sufficient features of the distribution of subpleural and peripheral lung lesions in UIP, as well as secondary lesions.Recommendation 8: TBLC specimens show diffuse inflammation and fibrosis with well-preserved lung tissue structure, which may support a pathological diagnosis of NSIP; if the distribution of lesions and lung tissue structure are difficult to evaluate, it is recommended that a pathological diagnosis of fibrotic ILD or cellular ILD be made.Recommendation 9: TBLC specimens may show pathological features of NSIP accompanied by organization, but it is difficult to accurately evaluate the proportion of organization area. In this scenario, a descriptive diagnosis of NSIP accompanied by organization is suggested.Recommendation 10: It is recommended to diagnose organizing pneumonia if only distal airway organization is present in TBLC; in addition to organization, if pathological histology is accompanied by obvious interstitial fibrosis and lung tissue remodelling, granuloma formation, obvious neutrophil infiltration or accompanied with abscess formation, obvious eosinophil infiltration, tissue necrosis, hyaline membrane formation or vasculitis, secondary OP should be considered.Recommendation 11: It is recommended to diagnose acute fibrinous and organizing pneumonia (AFOP) if lesions on TBLC show features of organizing pneumonia and fibrin balls.Recommendation 12: A diagnosis of smoking-related ILD (RB-ILD or DIP) is suggested when a good sampling of TBLC shows a significant accumulation of histocytes or smoker's macrophages in the alveolar spaces, and without specific changes sufficient for other diagnoses. If the lesions are confined to the lumen of respiratory bronchioles and the immediate peribronchiolar airspaces, RB-ILD is supported; if the distribution is diffuse, DIP should be considered. If it is difficult to determine the distribution of the lesions, it is necessary to integrate clinical and chest CT imaging findings to differentiate RB-ILD from DIP.Recommendation 13: A well-sampled TBLC specimen can display the pathological features of DAD and then also support such a pathological diagnosis.Recommendation 14: Lymphoid interstitial pneumonia (LIP) should show diffuse lymphocyte infiltration and lymphoid follicle formation in the lung interstitium in TBLC specimens. It is recommended that chest CT imaging be combined to determine whether the lesion is diffuse to differentiate from other lymphoproliferative diseases.

Comment on "Chinese expert consensus on the pathological diagnosis of interstitial lung disease with transbronchial lung cryobiopsy specimens"

As one of the pathological biopsy methods, the transbronchial lung cryobiopsy (TBLC) for interstitial lung disease has been widely used in clinical practice. While TBLC causes less trauma or complications for patients than surgical lung biopsy (SLB), pathologists are sometimes less confident in making diagnosis due to the smaller specimen size of TBLC. In an effort to alleviate the problem, this issue of the journal published "Chinese expert consensus on the pathological diagnosis of interstitial lung disease with transbronchial lung cryobiopsy specimens". The consensus addressed issues related to TBLC delivery, quality evaluation, artificial phenomena, and pathological diagnostic principles. More importantly, physicians and pathologists need to work together to improve the diagnosis of TBLC.

In ILD, a step-up diagnostic strategy vs. immediate surgical biopsy reduced need for unexpected chest tube drainage.

Kalverda KA, Ninaber MK, Wijmans L, et al. 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. Lancet Respir Med. 2024;12:513-522. 38640934.

Acute exacerbation of interstitial lung diseases and mortality post-cryobiopsy: a multicenter cohort study.

Interstitial lung diseases (ILDs) are a group of pulmonary disorders affecting the lung's structure. Acute exacerbation of ILD (AE-ILD) following medical procedures is a significant clinical concern. Lung cryoprobe transbronchial biopsy (cryobiopsy) is a relatively new diagnostic technique for ILD, but data on AE-ILD post-cryobiopsy is limited. This study aims to fill this gap by examining the prevalence, risk factors, and outcomes of AE-ILD following cryobiopsy. This multicenter retrospective study analyzed data from patients who underwent cryobiopsy for ILD diagnosis at three U.S. institutions between January 2014 and August 2022. The study included patients over 18 years with confirmed or suspected ILD, categorized into those who experienced AE-ILD post-cryobiopsy and those who did not. Out of 111 patients, 3.6% experienced AE-ILD, with a 50% mortality rate in these cases. The study cohort was predominantly white, with a median age of 69.0 years. Common comorbidities included tobacco use and hypertension. Patients who developed AE-ILD had an increased median number of biopsies. The overall 30-day mortality was 1.8%. Overall complication rate was 32%, including pneumonia, pneumothorax, AE-ILD, and bleeding requiring intervention. The study findings suggest that bronchoscopic cryobiopsy may be associated with lower overall mortality, particularly in patients with compromised lung function. This study provides significant insights into AE-ILD following cryobiopsy, underscoring the need for careful patient selection and procedural assessment. While cryobiopsy may offer a safer alternative to surgical lung biopsy in specific patient cohorts, the elevated risk of AE-ILD necessitates further research to optimize patient outcomes and procedural safety.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

Application of the 2022 American Thoracic/European Respiratory Society/Japanese Respiratory Society/Associatión Latinoamericana de Tórax (ATS/ERS/JRS/ALAT) idiopathic pulmonary fibrosis and progressive pulmonary fibrosis clinical practice guideline to a Canadian population: An opinion piece

In 2022, the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Associatión Latinoamericana de Tórax (ALAT) produced an updated clinical practice guideline on the diagnosis and management of idiopathic pulmonary fibrosis (IPF), also defining and making treatment recommendations for progressive pulmonary fibrosis (PPF). In this review, we summarize and highlight aspects of this guideline that are most relevant to Canadians. New recommendations in IPF include the use of transbronchial lung cryobiopsy as an alternative to surgical lung biopsy and a recommendation against antacid medications in asymptomatic patients. The guideline also recommends treating PPF with nintedanib, an antifibrotic currently approved for IPF. The guideline definition of PPF should be adopted in Canada, although with flexibility in physiologic parameters of the PPF definition and increased support for community respirologists to care for these patients. Although pirfenidone was not recommended in the guideline for the treatment of PPF, there are multiple clinical trials that support its use as a second-line treatment for PPF. It is imperative that Canadian resources continue to support knowledge generation of this complex group of patients and that Canadians continue to have ongoing involvement in the development of future international clinical practice guidelines.

Demographic and Clinical Factors Associated With Diagnostic Confidence in Interstitial Lung Disease: Findings From the Pulmonary Fibrosis Foundation Patient Registry

BACKGROUNDAccurate diagnosis of interstitial lung disease (ILD) can be challenging. Accordingly, clinicians may attribute a diagnostic certainty based on guideline criteria and clinical judgment. However, further research is needed to refine this approach and improve diagnostic clarity. RESEARCH QUESTIONWhat are the real-world factors associated with diagnostic confidence in fibrotic ILD? STUDY DESIGN AND METHODSData were included from all patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry from March 2016 to August 2018. Baseline demographic and clinical characteristics were collected at enrollment, or at the test date closest to the date of consent for longitudinal measures. Descriptive analyses were performed separately for all participants, as well as for subgroup participants with idiopathic pulmonary fibrosis (IPF) and participants with non-IPF ILD, stratified by the level of investigator diagnostic confidence (High vs Medium/Low) assigned at registry enrollment. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression, with the aforementioned characteristics as predictors. RESULTSData up to April 2022 from 1,992 participants were included. In adjusted logistic regression analyses among all participants, antifibrotic use (OR [95% CI], 1.51 [1.09-2.07]), longer time since diagnosis (0.94 [0.89-0.98]) at the research unit of 365 days, and diabetes (2.56 [1.01-6.44]) were significantly associated with higher diagnostic confidence, and non-IPF idiopathic interstitial pneumonia (vs IPF; 0.36 [0.24-0.55]), insurance - others (0.65 [0.43-0.97]), and Hispanic ethnicity (0.54 [0.31-0.94]) were significantly associated with lower diagnostic confidence. Factors associated with diagnostic confidence in the IPF and/or non-IPF ILD groups included age, male sex, region, immunomodulatory medication, multidisciplinary team discussion, surgical lung biopsy, and definite high-resolution computed tomography pattern. INTERPRETATIONThese findings suggest that certain demographic and clinical factors may influence physicians’ confidence in diagnosis of IPF and non-IPF ILD. Tailored physician education may help to reduce biases and improve consistency in diagnosis.

Correlation of CT-based radiomics analysis with pathological cellular infiltration in fibrosing interstitial lung diseases

PurposeWe aimed to identify computed tomography (CT) radiomics features that are associated with cellular infiltration and construct CT radiomics models predictive of cellular infiltration in patients with fibrotic ILD.Materials and methodsCT images of patients with ILD who underwent surgical lung biopsy (SLB) were analyzed. Radiomics features were extracted using artificial intelligence-based software and PyRadiomics. We constructed a model predicting cell counts in histological specimens, and another model predicting two classifications of higher or lower cellularity. We tested these models using external validation.ResultsOverall, 100 patients (mean age: 62 ± 8.9 [standard deviation] years; 61 men) were included. The CT radiomics model used to predict cell count in 140 histological specimens predicted the actual cell count in 59 external validation specimens (root-mean-square error: 0.797). The two-classification model’s accuracy was 70% and the F1 score was 0.73 in the external validation dataset including 30 patients.ConclusionThe CT radiomics-based model developed in this study provided useful information regarding the cellular infiltration in the ILD with good correlation with SLB specimens.

Expression of HOXB7 in the Lung of Patients with Idiopathic Pulmonary Fibrosis: A Proof-of-Concept Study.

The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50-75%)-measured with high-resolution computer tomography-compared to those with a lower extent (0-25%) (difference between means = 25.74 ± 6.72, p = 0.004). The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF.

Clinical, radiological and histopathological features of patients with familial pulmonary fibrosis

BackgroundIn familial pulmonary fibrosis (FPF) at least two biological relatives are affected. Patients with FPF have diverse clinical features.Research questionWe aimed to characterize demographic and clinical features, re-evaluate high-resolution computed tomography (HRCT) scans and histopathology of surgical lung biopsies, assess survival and investigate the suitability of risk prediction models for FPF patients.Study designA retrospective cohort study.MethodsFPF data (n = 68) were collected from the medical records of Oulu University Hospital (OUH) and Oulaskangas District Hospital between 1 Jan 2000 and 11 Jan 2023. The inclusion criterion was pulmonary fibrosis (PF) (ICD 10-code J84.X) and at least one self-reported relative with PF. Clinical information was gathered from hospital medical records. HRCT scans and histology were re-evaluated.ResultsThirty-seven (54.4%) of the patients were men, and 31 (45.6%) were women. The mean ages of the women and men were 68.6 and 61.7 years, respectively (p = 0.003). Thirty-seven (54.4%) patients were nonsmokers. The most common radiological patterns were usual interstitial pneumonia (UIP) (51/75.0%), unclassifiable (8/11.8%) and nonspecific interstitial pneumonia (NSIP) (3/4.4%). Pleuroparenchymal fibroelastosis (PPFE) was observed as a single or combined pattern in 13.2% of the patients. According to the 2022 guidelines for idiopathic pulmonary fibrosis (IPF), the patients were categorized as UIP (31/45.6%), probable UIP (20/29.4%), indeterminate for UIP (7/10.3%) or alternative diagnosis (10/14.7%). The histopathological patterns were UIP (7/41.2%), probable UIP (1/5.9%), indeterminate for UIP (8/47.2%) and alternative diagnosis (1/5.9%). Rare genetic variants were found in 9 patients; these included telomerase reverse transcriptase (TERT, n = 6), telomerase RNA component (TERC, n = 2) and regulator of telomere elongation helicase 1 (RTEL1, n = 1). Half of the patients died (n = 29) or underwent lung transplantation (n = 5), with a median survival of 39.9 months. The risk prediction models composite physiology index (CPI), hazard ratio (HR) 1.07 (95.0% CI 1.04–1.10), and gender-age-physiology index (GAP) stage I predicted survival statistically significantly (p<0.001) compared to combined stages II and III.ConclusionsThis study confirmed the results of earlier studies showing that FPF patients’ radiological and histopathological patterns are diverse. Moreover, radiological and histological features revealed unusual patterns and their combinations.

Disseminated Granulomatous Lung Disease in Patients with Intravenous Drug Use: Clinical and Morphological Features

Pulmonary dissemination syndrome is a radiological syndrome characterised by the development of multiple focal opacities and/or an increase and reticular deformation of the lung pattern, often bilaterally. It can occur in the development of various pathological processes, with over 200 different lung diseases associated with its development.Key components of differential diagnosis include a thorough study of the patient’s history, evaluation of clinical symptoms, radiological imaging and the dynamics of the process during observation, laboratory indicators and spirometry data. If a diagnosis cannot be established, it is appropriate to perform transbronchial lung biopsy or video thoracoscopy with biopsy of the most affected lung areas.This paper presents current data on the development of a rare variant of disseminated granulomatous process in the lungs, which can occur in drug-dependent individuals who intravenously inject solutions or suspensions of drugs originally manufactured in tablet form and intended for oral use. Literary data and personal observations from practice are provided. Typically, such patients do not have specific complaints or clinical signs, and their laboratory indicators are also non-specific. Radiologically, a disseminated process in the lungs is diagnosed. The main diagnostic measure in such cases is surgical lung biopsy followed by morphological examination. Histological descriptions of peculiar changes in lung tissue and useful additional studies for differential diagnosis are presented. Two cases are detailed, one of which involved a combination of morphological signs of past tuberculosis with manifestations of another giant cell granulomatous process.It is crucial in the diagnosis of this pulmonary pathology to establish and clarify the history—repeated intravenous administration of drugs intended for oral use, as most patients tend to conceal this information.

Longitudinal changes in serum immunoglobulin G testing in patients with fibrotic avian hypersensitivity pneumonitis

BackgroundEvaluation of the antigen responsible for fibrotic hypersensitivity pneumonitis (HP) is challenging. Serum immunoglobulin (Ig) G testing against HP-associated antigens is performed. Although single-serum IgG testing has been investigated, multiple-serum IgG testing has not yet been studied.MethodsThis study included patients who underwent histopathological examination and positive inhalation challenge test as well as those with moderate or high HP guideline confidence level. Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP. The association between changes in serum IgG antibody titers and changes in forced vital capacity (FVC) and other parameters was investigated.ResultsIn this study, 28 patients (mean age, 64.5 years; mean FVC, 85.3%) with fibrotic avian HP were selected, of whom 20 and 8 underwent surgical lung biopsy and transbronchial lung cryobiopsy, respectively. Of the 28 patients, 19 had been keeping birds for more than 6 months. A correlation was observed between the annual changes in serum IgG antibody titers by ELISA and changes in relative FVC (r = − 0.6221, p < 0.001). Furthermore, there was a correlation between the annual changes in serum IgG antibody titers by ImmunoCAP and changes in relative FVC (r = − 0.4302, p = 0.022). Multiple regression analysis revealed that the change in serum IgG antibody titers by both ELISA and ImmunoCAP also influenced the relative FVC change (p = 0.012 and p = 0.015, respectively). Moreover, 13 patients were given additional treatments between the first and second blood test; however, the additional treatment group was not significantly different in relative FVC change compared to the group with no additional treatment (p = 0.982).ConclusionsIn patients with fibrotic avian HP, the annual changes in serum IgG testing were correlated with FVC changes, highlighting the importance of serum IgG testing over time.

Squamous metaplasia is an indicator of acute exacerbation in patients with usual interstitial pneumonia / idiopathic pulmonary fibrosis

BackgroundAcute exacerbation (AE) is a potentially lethal event in patients with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF). However, to date, no pathological predictors of AE have been identified. This retrospective study aimed to elucidate the pathological features that could predict AE in patients with UIP. MethodsWe reviewed the pathological findings of 91 patients with UIP/IPF and correlated these findings with AE events. Thirteen histological variables related to acute lung injury were evaluated by three independent observers and classified as positive or negative. The patients’ clinical data during follow-up were collected and reviewed for AE. A recursive partition using the Gini index for the prediction of AE was performed, with each pathological finding as a candidate for branching. ResultsTwenty patients (22%) developed AE during the median follow-up duration of 40 months. Thirty-eight patients died (15 due to AE and 23 for other reasons). The median time interval from surgical lung biopsy to AE onset was 497 (interquartile range: 901–1657) days. Histologically, squamous metaplasia was positively associated with AE (odds ratio: 4.7, P = 0.015) and worse event-free survival in patients with UIP (P = 0.04). Leaf scoring based on the Gini index for recursive partition, including five positive findings (squamous metaplasia, neutrophilic infiltration, septal widening, Kuhn's hyaline, and fibrin), showed a sensitivity of 90% with a specificity of 74.7% (area under curve: 0.89). ConclusionsWe found that squamous metaplasia is an important histopathological finding that predicts AE events and tends to unfavorable outcome in patients with UIP/IPF.

Transbronchial Lung Cryobiopsies, Transbronchial Forceps Lung Biopsies, and Surgical Lung Biopsies in Mechanically Ventilated Patients with Acute Hypoxemic Respiratory Failure: A Retrospective Cohort Study.

Lung biopsies are sometimes performed in mechanically ventilated patients with acute hypoxemic respiratory failure (AHRF) of unknown etiology to guide patient management. While surgical lung biopsies (SLB) offer high diagnostic rates, they may also cause significant complications. Transbronchial forceps lung biopsies (TBLB) are less invasive but often produce non-contributive specimens. Transbronchial lung cryobiopsies (TBLC) yield specimens of potentially better quality than TBLB, but due to their novel implementation in the intensive care unit (ICU), their accuracy and safety are still unclear. Our main objective was to evaluate the risk of adverse events in patients with AHRF following the three biopsy techniques. Our secondary objectives were to assess the diagnostic yield and associated modifications of patient management of each technique. We conducted a retrospective cohort study comparing TBLC, TBLB, and SLB in mechanically ventilated patients with AHRF. The primary outcome was the proportion of patients with at least one complication, and secondary outcomes included complication rates, diagnostic yields, treatment modifications, and mortality. Of the 26 patients who underwent lung biopsies from 2018 to 2022, all TBLC and SLB patients and 60% of TBLB patients had at least one complication. TBLC patients had higher unadjusted numbers of total and severe complications, but also worse Sequential Organ Failure Assessment scores and P/F ratios. A total of 25 biopsies (25/26, 96%) provided histopathological diagnoses, 88% (22/25) of which contributed to patient management. ICU mortality was high for all modalities (63% for TBLC, 60% for TBLB and 50% for SLB). All biopsy methods had high diagnostic yields and the great majority contributed to patient management; however, complication rates were elevated. Further research is needed to determine which patients may benefit from lung biopsies and to determine the best biopsy modality.

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

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. 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. 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. 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. Netherlands Organisation for Health Research and Development (ZonMW) and Amsterdam University Medical Centers.

Particle analysis of surgical lung biopsies from deployed and non-deployed US service members during the Global War on Terrorism.

The role that inhaled particulate matter plays in the development of post-deployment lung disease among US service members deployed to Southwest Asia during the Global War on Terrorism has been difficult to define. There is a persistent gap in data addressing the relationship between relatively short-term (months to a few years) exposures to high levels of particulate matter during deployment and the subsequent development of adverse pulmonary outcomes. Surgical lung biopsies from deployed service members and veterans (DSMs) and non-deployed service members and veterans (NDSMs) who develop lung diseases can be analyzed to potentially identify residual deployment-specific particles and develop associations with pulmonary pathological diagnoses. We examined 52 surgical lung biopsies from 25 DSMs and 27 NDSMs using field emission scanning electron microscopy (FE-SEM) with energy dispersive x-ray spectroscopy (EDS) to identify any between-group differences in the number and composition of retained inorganic particles, then compared the particle analysis results with the original histopathologic diagnoses. We recorded a higher number of total particles in biopsies from DSMs than from NDSMs, and this difference was mainly accounted for by geologic clays (illite, kaolinite), feldspars, quartz/silica, and titanium-rich silicate mixtures. Biopsies from DSMs deployed to other Southwest Asia regions (SWA-Other) had higher particle counts than those from DSMs primarily deployed to Iraq or Afghanistan, due mainly to illite. Distinct deployment-specific particles were not identified. Particles did not qualitatively associate with country of deployment. The individual diagnoses of the DSMs and NDSMs were not associated with elevated levels of total particles, metals, cerium oxide, or titanium dioxide particles. These results support the examination of particle-related lung disease in DSMs in the context of comparison groups, such as NDSMs, to assist in determining the strength of associations between specific pulmonary pathology diagnoses and deployment-specific inorganic particulate matter exposure.

Abstract 3747: Bronchial washing fluid sequencing is useful in the diagnosis of lung cancer with necrotic tumor

Abstract Lung cancers identified with low-dose CT are typically early stage without endobronchial lesions, and most require a pathological diagnosis using invasive procedures. We conducted a study analyzing bronchial washing (BW) fluid using targeted panel sequencing to evaluate its diagnostic performance. And we aimed to elucidate the characteristics of patients group in which this method could be effectively applied. We prospectively enrolled patients with an incidental lung lesion suspected of early-stage lung cancer on chest CT and no visible endobronchial lesion on bronchoscopy from June 2017 to March 2018 at two independent hospitals. Lung cancer was histologically diagnosed using a diagnostic work-up including surgical lung biopsy, percutaneous needle biopsy, endobronchial ultrasound, and other biopsies. BW was performed on each patient in the subsegmental bronchus where the lung lesion was suspected to be located. Among shared genes between the panels for each cohort, we selected 8 genes that are frequently mutated known oncogenes/tumor suppressor genes in lung cancer not to consider passenger mutations for diagnosis. In addition, several filtering criteria were considered to differentiate cancer. Since criterion d considered definitive somatic mutations [known hotspot mutations or loss of function mutations with variant allele fraction (VAF) ≥ 2%] with criterion c (≥ 2 COSMIC11 variants with VAF ≥ 1%), the sensitivity was increased without loss of precision and the sensitivity of sequencing was higher than BW cytology. In total, 164 subjects (114 with lung cancer and 50 with benign) were enrolled. Of lung cancer patients, necrosis was observed on chest CT in 44 (38.6%) patients and malignant cells were identified upon BW cytological examination in 33 (28.9%) patients. Of total, 33 (20.1%) patients had complications related to invasive diagnostic test. By the panel with the criterion d, 42 patients (25.6%) were classified as cancer. The panel showed 100% of specificity, 100% of positive predictive value for diagnosing cancer whereas it had relatively low sensitivity. Twenty patients who were classified as cancer by sequencing despite of negative cytology. In the group with necrosis, the proportion of patients with positive for sequencing only was significantly higher than that of patients with positive for cytology only. In addition, the sensitivity of BW sequencing reached 75% in patients with necrotic tumors. The prevalence of necrotic tumors was significantly higher in SQC than in ADC. The significant proportion (66.7%) of primary tumors with positive for sequencing only and located in outer area had necrosis. This study demonstrated that BW sequencing could be applied for diagnosis in patients with necrotic lung lesion suspected of early-stage lung cancer in chest CT. It would be possible to reduce the frequency of unnecessary invasive procedures and subsequent complications. Citation Format: Jun Hyeok Lim, Hyun-Tae Shin, Sunmin Park, Woo Kyung Ryu, Lucia Kim, Kyung-Hee Lee, Sung Min Ko, Seung Jae Lee, Jung Soo Kim, Jeong-Seon Ryu. Bronchial washing fluid sequencing is useful in the diagnosis of lung cancer with necrotic tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3747.