Impact of surgical lung biopsy on lung function and survival in patients with idiopathic pulmonary fibrosis in a multi-centre registry cohort.

BACKGROUND AND OBJECTIVE: Establishing an accurate and timely diagnosis of idiopathic pulmonary fibrosis (IPF) is essential for appropriate management and prognostication. In some cases, surgical lung biopsy (SLB) is performed but carries non-negligible risk. The objective of this retrospective study was to determine if SLB is associated with accelerated lung function decline in patients with IPF using the Canadian Registry for Pulmonary Fibrosis. METHODS: Linear mixed models and Cox proportional hazards regression models were used to compare decline in forced vital capacity (FVC)%, diffusion capacity of the lung (DLCO%) and risk of death or lung transplantation between SLB and non-SLB patients. Adjustments were made for baseline age, sex, smoking history, antifibrotic use, and lung function. A similar analysis compared lung function changes 12 months pre- and post-SLB. RESULTS: A total of 81 SLB patients and 468 non-SLB patients were included. In the SLB group, the post-biopsy annual FVC% decline was 2.0% (±0.8) in unadjusted, and 2.1% (±0.8) in adjusted models. There was no difference in FVC% decline, DLCO% decline, or time to death or lung transplantation between the two groups, in adjusted or unadjusted models (all p-values >0.07). In the pre-post SLB group, no differences were identified in FVC% decline in unadjusted or adjusted models (p = 0.07 for both). CONCLUSION: No association between SLB and lung function decline or risk of death or lung transplantation was identified in this multi-centre study of patients with IPF.

Intravascular Large B-cell Lymphoma Presenting as Pulmonary Ground-glass Nodules That Progressed Slowly over Several Months with No Overt Symptoms.

A 74-year-old man with no overt symptoms was referred for a chest computed tomography (CT) that revealed multiple bilaterally pulmonary ground-glass nodules (GGNs) with subtle changes in size over eight months. Surgical lung biopsies were performed in the left upper lobe. A pathologic study confirmed the intravascular large B-cell lymphoma (IVLBCL). This lesion was a nodule-like cluster of atypical cells, meaning that it had been localized for several months. Pulmonary IVLBCL may form focal lesions presenting as GGN on chest CT and progress slowly without apparent symptoms.

Concordance between transbronchial lung cryobiopsy and surgical lung biopsy in patients with idiopathic multicentric Castleman disease: A report of four cases.

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is a rare polyclonal lymphoproliferative disease often associated with pulmonary involvement. Recently, transbronchial lung cryobiopsy (TBLC) has been reported to be useful for the diagnosis of diffuse interstitial lung disease. However, there have been no reports of pathological assessment of TBLC for iMCD. METHOD: To clarify the efficacy of TBLC in the diagnosis of iMCD, we retrospectively reviewed four iMCD patients who had undergone both TBLC and surgical lung biopsy (SLB). RESULTS: The median age was 44 years; 2 males and 2 females. Two or three TBLC specimens were taken from each patient. All patients had no complications other than minimal bleeding. The size of the TBLC specimens was approximately 5-6 × 3-4 mm, and the alveolar region, and centrilobular and perilobular areas were adequately sampled. As with SLB, the extent of lung lesions and inflammatory cell infiltration could be sufficiently evaluated by TBLC. The presence of lymphoid follicles could also be assessed by TBLC; however, the germinal centers with lymphoid follicles were difficult to evaluate. The TBLC specimens could also be evaluated for immunostaining, especially IgG4 immunostaining, to rule out IgG4-related lung disease. Pulmonary pathological grading showed a high concordance rate between major pathological findings of TBLC and SLB. The pathologist's confidence level of TBLC for the diagnosis of iMCD was high in all cases. CONCLUSIONS: TBLC exhibits a high concordance rate with SLB in the pathological evaluation of iMCD, which may be useful for the diagnosis of iMCD.

Safety and efficacy of cryobiopsy for the diagnosis of lymphangioleiomyomatosis compared with forceps biopsy and surgical lung biopsy.

BACKGROUND: Transbronchial lung forceps biopsy (TBFB) is recommended before a surgical lung biopsy (SLB) when a definitive diagnosis of lymphangioleiomyomatosis (LAM) is required for patients without any additional confirmatory features. Transbronchial lung cryobiopsy (TBCB) has been suggested as replacement test in patients considered eligible to undergo SLB for the diagnosis of interstitial lung diseases. The efficacy and safety of TBCB were compared with that of TBFB and SLB in the diagnosis of LAM. METHODS: A retrospective analysis was conducted on 207 consecutive patients suspected with LAM in the First Affiliated Hospital of Guangzhou Medical University from 2005 to 2020. RESULTS: The difference in diagnostic rate of patients suspected with LAM between TBCB (20/30, 66.7%) and TBFB (70/106, 66.0%) groups was not significant (p = 0.949). One patient performed TBCB with negative pathological results could be diagnosed exclusively after SLB. LAM diagnosis was confirmed by surgical pathological findings in 3 TBFB-negative patients. More patients with minimal cystic profusion were diagnosed with LAM by TBCB (5/19, 26.3%) and SLB (11/39, 28.2%) than by TBFB (3/61, 4.9%) (TBCB vs TBFB: p = 0.04, SLB vs TBFB, p < 0.001). The difference between the severity of cystic lung disease in patients diagnosed with LAM through TBCB and SLB was not significant (p > 0.05). One pneumothorax, 8 mild bleeding and 1 moderate bleeding were observed in TBCB. One pneumothorax, 15 mild bleeding and 1 moderate bleeding occurred after TBFB. CONCLUSION: Compared to TBFB, TBCB is safe and effective in diagnosing LAM at a higher diagnostic rate in patients with minimal cystic profusion.

Transbronchial lung cryobiopsy and pulmonary fibrosis: A never-ending story?

Background: The diagnostic process of pulmonary fibrosis (PF) is often challenging, requires a collaborative effort of several experts, and often requires bioptic material, which can be difficult to obtain, both in terms of quality and technique. The main procedures available to obtain such samples are transbronchial lung cryobiopsy (TBLC) and surgical lung biopsy (SLB). Objective: The purpose of this paper is to review the evidence for the role of TBLC in the diagnostic-therapeutic process of PF. Methods: A comprehensive review was performed to identify articles to date that addressed the role of TBLC in the diagnostic-therapeutic process of PF using the PubMed® database. Results: The reasoned search identified 206 papers, including 21 manuscripts (three reviews, one systematic review, two guidelines, two prospective studies, three retrospective studies, one cross-sectional study, one original article, three editorials, three clinical trials, and two unclassifiable studies), which were included in the final review. Conclusions: TBLC is gaining increasing efficacy and improving safety profile; however, there are currently no clear data demonstrating its superiority over SLB. Therefore, the two techniques should be considered with careful rationalization on a case-by-case basis. Further research is needed to further optimize and standardize the procedure and to thoroughly study the histological and molecular characteristics of PF.

The importance of lung biopsy in a patient with idiopathic pulmonary fibrosis: a case report.

Idiopathic pulmonary fibrosis (IPF) is a severe progressive fibrotic disease of the lung. Its etiology is not yet completely clear. The affected population is exclusively older than 40 years with maximum incidence in the age categories of 60 to 70 years. Its worldwide prevalence varies from 2 to 29/100 000 people (in the Czech Republic 5-6/100 000). Annual incidence is constantly rising, mainly thanks to the ever-improving diagnostic possibilities. Untreated IPF disease causes rapid structural and functional devastation of the lungs with development of respiratory insufficiency and death of the patient within 2 to 3 years after diagnosis, prognosis with IPF is therefore fully (without any exaggeration) comparable to untreated bronchogenic carcinoma. In recent years, the prognosis and quality of life of patients have significantly improved thanks to available specific antifibrotic treatment, which can substantially slow down the disease progression and thus prolong survival. However, a necessary condition for the timely treatment initiation is a quick and accurate diagnosis. The following case report describes a protracted journey to the correct diagnosis in a patient with atypical radiological findings, so that the definitive diagnosis was established only as a result of a surgical lung biopsy.

Evaluation of large airway specimens obtained by transbronchial lung cryobiopsy in diffuse parenchymal lung diseases.

BACKGROUND: The difference in diagnostic yield between surgical lung biopsy and transbronchial lung cryobiopsy (TBLC) in diffuse parenchymal lung diseases (DPLD) has been reported to be due to differences in the rate of interpathologist agreement, specimen size, and specimen adequacy. In TBLC, the specimens containing large airway components are generally believed as inadequate specimens for histological evaluation, but the detailed characteristics of TBLC specimens including the large airway and the impact on histological diagnostic rates of DPLD have not been investigated. METHODS: We retrospectively reviewed the specimen characteristics of patients with DPLD who underwent TBLC. RESULTS: Between February 2018 and January 2020, 74 patients and 177 specimens were included. There were 85 (48.0%) large airway specimens (LAS) that contained bronchial gland or bronchial cartilage. The ideal specimen ratio was significantly lower in the LAS-positive group than that in the LAS-negative group (5.8% vs. 45.6%), and the proportion of bronchioles, alveoli, and perilobular area were similarly lower in the LAS-positive group. The presence of traction bronchiectasis and diaphragm overlap sign on high-resolution computed tomography (HRCT) were also significantly higher in the LAS-positive group than those in the LAS-negative group. We observed a statistically significant trend in histological diagnostic yield (40.7% in LAS positive group; 60.8% in LAS positive and negative group; 91.6% in LAS negative group) (Cochran-Armitage trend test). CONCLUSION: LAS is a specimen often collected in TBLC and contains a low percentage of bronchioles, alveoli, and perilobular area. Since the histological diagnostic yield tends to be higher in cases that do not contain LAS, it may be important to determine the biopsy site that reduces the frequency of LAS collection by referring to the HRCT findings in TBLC.

A case of renal cell carcinoma with microscopic pulmonary tumor embolism proven by surgical lung biopsy.

Pulmonary tumor embolism (PTE) is difficult to diagnose before death. We report the case of a 75-year-old man with microscopic PTE of renal cell carcinoma who was diagnosed by surgical lung biopsy. He visited our hospital because of dyspnea on exertion. Chest computed tomography (CT) showed multiple micronodules and ground glass opacities. Steroid therapy was started as therapeutic diagnosis for IgG4-related pulmonary disease. However, he was admitted our hospital due to progressive respiratory failure. Pathological findings of a lung biopsy obtained by video-assisted thoracic surgery showed PTE of renal cell carcinoma without embolization of large pulmonary arteries. He received palliative medicine and died four months after the surgical lung biopsy. In cases of multiple micronodules in chest CT findings and worsened respiratory symptoms, PTE should be considered in the differential diagnosis.

Surgical Lung Biopsy for Interstitial Lung Disease: A Two Center Propensity Score Matching Analysis.

BACKGROUND: Surgical lung biopsy (SLB) is recommended for patients with nonclassified interstitial lung disease (nILD) if high resolution computed tomography and/or transbronchial lung biopsy did not achieve a definitive diagnosis. Current literature suggests better patient tolerability and less postoperative complications if surgery is performed under spontaneous ventilation. OBJECTIVES: We conducted a propensity score matching (PSM) analysis of our nILD patients undergoing SLB under spontaneous ventilation or general anesthesia to investigate postprocedural AE-ILD, 30-/90-day mortality and perioperative variables in two academic high-volume centers (Hannover, Heidelberg). METHODS: All patients undergoing SLB for nILD under general anesthesia (GAVATS) and spontaneous ventilation (NIVATS) at both centers from February 2013 until April 2021 were analyzed retrospectively. Data of 132 patients were used for PSM resulting in 40 pairs. RESULTS: There was one death in the NIVATS group 60 days after SLB and one AE-ILD in each cohort. Chest tube indwelling time, chest tube total effusion, length of hospital stay, and operative time were all in favor of NIVATS. CONCLUSIONS: In our PSM analysis, NIVATS is associated with faster postprocedural recovery. However, a reduction in postoperative AE-ILD or 30-/90-day mortality was not observed.

Efficacy of Pirfenidone vs. Placebo in Unclassifiable Interstitial Lung Disease, by Surgical Lung Biopsy Status: Data From a post-hoc Analysis.

Approximately 12-13% of patients with interstitial lung disease (ILD) are diagnosed with unclassifiable ILD (uILD), often despite thorough evaluation. A recent Phase 2 study (NCT03099187) described a significant effect of pirfenidone vs. placebo on forced vital capacity (FVC) measured by site spirometry in patients with progressive fibrosing uILD (hereafter referred to as the pirfenidone in uILD study). Here, we present the results from a post-hoc analysis of this study to assess patient baseline characteristics and the efficacy of pirfenidone vs. placebo analyzed by surgical lung biopsy (SLB) status. Mean FVC (mL) change over 24 weeks was included as a post-hoc efficacy outcome. Of 253 randomized patients, 88 (34.8%) had a SLB and 165 (65.2%) did not. Baseline characteristics were generally similar between SLB subgroups; however, patients who had a SLB were slightly younger and had a higher 6-min walk distance than those without a SLB. Mean FVC change over 24 weeks for pirfenidone vs. placebo was -90.9 vs. -146.3 mL, respectively, in patients who had a SLB, and 8.2 vs. -85.3 mL, respectively, in patients without a SLB. Overall, the results from the post-hoc analysis identified that pirfenidone may be an effective treatment in progressive fibrosing uILD over 24 weeks, irrespective of SLB status; however, caution should be taken when interpreting these data due to several limitations. There are differences in the treatment effect of pirfenidone between the subgroups that require further pathological and radiological investigation. In this manuscript, we also descriptively compared baseline characteristics from the overall pirfenidone in uILD study population with other uILD populations reported in the literature, with the aim of understanding if there are any similarities or differences within these cohorts. Most baseline characteristics for patients in the pirfenidone in uILD study were within the ranges reported in the literature; however, ranges were wide, highlighting the heterogeneity of uILD populations. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03099187.

Pulmonary amyloidosis diagnosed via transbronchial lung cryobiopsy without surgical lung biopsy: A case series.

Pulmonary amyloidosis is a rare disease characterized by abnormal extracellular deposition of amyloid fibril in the lung tissue, and the identification of amyloid deposits is essential for its diagnosis. Surgical lung biopsy (SLB) is a standard diagnostic method for pulmonary amyloidosis. However, it has a relatively high post-procedural mortality rate. Recently, transbronchial lung cryobiopsy (TBLC) has been gradually used for diagnosing interstitial lung disease. However, its diagnostic efficacy for pulmonary amyloidosis has not yet been validated. Here, we describe two cases of pulmonary amyloidosis with deposition of amyloid light chain detected via TBLC. Since SLB is a high-risk procedure for the patients due to age and complications, TBLC was performed. Both patients presented with Congo red-positive amyloid deposits. One patient with localized pulmonary amyloidosis had a good clinical course without therapeutic intervention and was followed up. The other with systemic amyloidosis received chemotherapy and presented with a stable clinical course. TBLC can collect a larger pulmonary specimen for pulmonary amyloidosis than forceps biopsy and has fewer complications and a lower mortality rate than SLB. Thus, it can be a diagnostic method for pulmonary amyloidosis.

Parsimonious risk model for predicting mortality after surgical lung biopsy for interstitial lung disease.

OBJECTIVES: To develop a risk model for predicting postoperative mortality and morbidity in patients with interstitial lung disease undergoing surgical lung biopsy. METHODS: From 2004 to 2019, patients who underwent surgical lung biopsy for interstitial lung disease were included in this study. Based on the findings of the multivariable analysis using preoperative clinical variables, a risk model for predicting postoperative mortality and morbidity was developed. RESULTS: During the study period, 1177 patients were enrolled. Among them, morbidity and mortality occurred in 45 (3.8%) and 29 (2.5%) patients, respectively, which gradually declined over time from 8.9% in 2004-2005 to 0% in 2018-2019. In the final multivariable analysis, the dyspnoea grade, a forced vital capacity of ≤60%, preoperative oxygen therapy and preoperative intensive care unit stay were found to be the independent factors associated with both morbidity and mortality; smoking >40 pack-years was additionally identified as a factor related to mortality. Diffusing capacity of carbon monoxide ≤50%, which was a significant factor in the univariable analysis, became insignificant after adjustment for the forced vital capacity in the multivariable analysis. The risk scoring system based on this model showed a good discriminant ability for both morbidity [area under the receiver operating characteristic curve (95% confidence interval): 0.830 (0.726-0.932)] and mortality [0.887 (0.804-0.975)]. CONCLUSIONS: We developed a scoring system for predicting the risk of morbidity and mortality, which could help determine surgical candidates for lung biopsy among patients with interstitial lung disease.

Outcomes for Elective Open and Thoracoscopic Surgical Lung Biopsies in the United States and Temporal Trends.

Objective: To elucidate the outcomes of surgical lung biopsies (SLBs) performed for indications other than interstitial lung disease (ILD) and stratify outcomes according to procedural approach (open vs thoracoscopic). Patients and Methods: Using the Nationwide Inpatient Sample database (January 1, 2008, through December 31, 2014), we identified elective hospitalizations with International Classification of Diseases, Ninth Revision, Clinical Modification codes for open (33.28) and thoracoscopic (33.20) SLB. We stratified cases by the presence/absence of ILD. Our primary outcome was in-hospital mortality. Results: There were 47,469 hospitalizations for elective SLB (26,540 [55.9%] thoracoscopic) during the study period; 23,930 patients (50.5%) were women, 17,019 (35.9%) had ILD, and the mean ± SD age was 62.6±13.0 years. Over the study period, thoracoscopic increasingly replaced open SLB, and in-hospital mortality declined (3.5% [308 of 8678] in 2008 vs 2.5% [130 of 5215] in 2014; P<.001). Mortality following thoracoscopic SLB was 2.1% (550 of 26,519; 1.9% [214 of 11,513] in ILD and 2.2% [336 of 15,006] in non-ILD), and mean ± SD length of stay was 5.1±6.9 days. Open SLBs had worse outcomes; mortality was 3.7% (782 of 20,914; 3.9% [214 of 5487] in ILD and 3.7% [568 of 15,427] in non-ILD), and mean ± SD length of stay was 8.2±12 days. On multivariable analysis, male sex, advanced age, ILD, and higher comorbidity index correlated with higher mortality. Conversely, lower mortality was observed among individuals with obesity (odds ratio, 0.73; 95% CI, 0.60-0.88) and those who had their thoracoscopic SLBs performed at high-volume centers (top quartile) (odds ratio, 0.73; 95% CI, 0.57-0.94). Conclusion: Surgical lung biopsy is more often performed for non-ILD indications. Interstitial lung disease was an independent predictor of poor outcomes, but the unadjusted outcomes were worse in the non-ILD cohort due to differences in patient characteristics. Thoracoscopic SLBs performed at high-volume centers had superior outcomes.

Safety and accuracy of transbronchial lung cryobiopsy in diagnosing desquamative interstitial pneumonia.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is a new technique to obtain specimens for diagnosis of interstitial lung disease (ILD) in recent years. The objective of this study is to evaluate the safety and the diagnostic accuracy of TBLC in patients of desquamative interstitial pneumonia (DIP). METHODS: In this study twelve patients confirmed with DIP were selected from January 2019 to December 2020 at the department of pulmonary and critical care medicine in China-Japan Friendship Hospital. All cases underwent TBLC in a hybrid cone beam CT (CBCT) operation room with a single general anesthesia. The definitive diagnosis was made by a multidisciplinary team that involved clinicians, radiologists and pathologists. This study analyzed the biopsy sample surface areas, main complications and the consistency between TBLC pathology and multidisciplinary discussion (MDD) diagnosis for DIP. RESULTS: An average of 3.1 ± 1.1 specimens were obtained per patient. The mean surface area of the specimen was 23.7 ± 6.1 mm2 . None of the cases had pneumothorax or massive hemorrhage. Ten cases (83.3%) had no or mild bleeding and two cases (16.7%) had moderate bleeding. All cases had the typical pathologic characteristics of DIP, which was highly consistent with the diagnosis of MDD. CONCLUSION: TBLC can obtain sufficient samples for the pathological diagnosis of DIP, which has high security and accuracy in experienced specialist centers.

Lung Biopsy With a Non-intubated VATS Approach in an Obese Population: Indications and Results.

Background: According to the international guidelines, patients affected by interstitial lung disease with unusual clinical presentation and radiological findings that are not classic for usual interstitial pneumonia end up meeting criteria for surgical lung biopsy, preferably performed with video-assisted thoracic surgery. The growing appeal of non-intubated thoracic surgery has shown the benefits in several different procedures, but the strict selection criteria of candidates are often considered a limitation to this approach. Although several authors define obesity as a contraindication for non-intubated thoracoscopic surgery, the assessment of obesity as a dominant risk factor represents a topic of debate when minor tubeless procedures such as lung biopsy are considered. Our study aims to investigate the impact of obesity on morbidity and mortality in non-intubated lung biopsy patients with interstitial lung disease, analyzing the efficacy and safeness of this procedure. Materials and Methods: The study group of 40 obese patients consecutively collected from 202 patients who underwent non-intubated lung biopsy was compared with overweight and normal-weight patients, according to their body mass index. Post-operative complications were identified as the primary endpoint. The other outcomes explored were the early 30-day mortality rate and intraoperative complications, length of surgery, post-operative hospitalization, patient's pain feedback, and diagnostic yield. Results: The overall median age of the patients was 67.4 years (60, 73.5). No 30-day mortality or significant differences in terms of post-operative complications (P = 0.93) were noted between the groups. The length of the surgery was moderately longer in the group of obese patients (P = 0.02). The post-operative pain rating scale was comparable among the three groups (P = 0.45), as well as the post-operative length of stay (P = 0.96). The diagnosis was achieved in 99% of patients without significant difference between groups (P = 0.38). Conclusion: Our analysis showed the safety and efficacy of surgical lung biopsy with a non-intubated approach in patients affected by lung interstitiopathy. In the context of perioperative risk stratification, obesity would not seem to affect the morbidity compared to normal-weight and overweight patients undergoing this kind of diagnostic surgical procedure.

Clinical Utility of Surgical Lung Biopsy for Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Surgical lung biopsy (SLB) is performed in patients with acute respiratory distress syndrome (ARDS); however, its clinical utility remains unclear. OBJECTIVES: We categorized the pathological diagnoses and investigated the predictive value for short-term mortality. METHOD: Three electronic databases (MEDLINE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) were searched for the included studies. The QUADAS-2 was used to evaluate the risk of bias and its applicability. The types and populations of pathological diagnoses were investigated. The pooled sensitivity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) were estimated at a fixed specificity. Hierarchical summary receiver operating characteristic curves were drawn. RESULTS: A total of 16 studies that enrolled 758 patients were included. The pathological diagnoses were as follows: diffuse alveolar damage (DAD) 29.9%; infection 24.7%; interstitial lung disease 17.2%; malignancy 3.6%; cardiovascular disease 3.6%; drug toxicity 2.3%; connective tissue disease 2.2%; allergic disease 1.1%; and nonspecific diagnosis 15.4%. To predict short-term mortality, 13 studies that enrolled 613 patients used DAD as an index test and recorded a mortality rate of 56.9% (349 of 613 patients). A total of 3 studies that used index tests other than DAD were excluded. The pooled sensitivity, fixed specificity, LR+, LR-, and DOR were 0.46 (95% confidence interval [CI]: 0.29-0.56), 0.69, 1.48 (95% CI: 0.92-1.81), 0.78 (95% CI: 0.63-1.03), and 1.90 (95% CI: 0.89-2.86), respectively. CONCLUSIONS: SLB is unlikely to provide a specific diagnosis and should not be recommended for confirming DAD or predicting ARDS prognosis.

Impact of Lung Biopsy Information on Treatment Strategy of Patients with Interstitial Lung Diseases.

Rationale: Lung biopsy (LBx) has a relevant role in the prediction of prognosis of interstitial lung diseases (ILDs), but its impact on the clinical management of patients remains unexplored. Objectives: This study evaluates whether LBx may change the therapeutic strategy and assesses the effect of diagnostic reclassification after LBx on long-term prognosis. Methods: We evaluated the LBx of 426 consecutive patients with ILDs, without a definite usual interstitial pneumonia pattern on high-resolution computed tomographic imaging. A total of 266 patients underwent transbronchial lung cryobiopsy (TBLC), and 160 patients underwent surgical lung biopsy (SLB). The multidisciplinary team (MDT) determined a diagnosis with high or low confidence, and a management strategy, both before and after the LBx data. Results: Final MDT diagnoses were 189 idiopathic pulmonary fibrosis (IPF), 143 non-IPF fibrotic ILDs, and 94 nonfibrotic ILDs. LBx data changed the management strategy in 145 cases (34%), with similar results for TBLC and SLB (the treatment strategy changed in 31.5% of TBLC cases, 84/266, P < 0.001, and in 38% of SLB, 61/160, P < 0.001). After LBx, the MDT was less inclined to "wait and see" (from 15% to 4% of cases, P < 0.001) or to prescribe steroids only (from 54% to 37%, P < 0.001) and was more confident to treat with antifibrotics (from 23% to 44%, P < 0.001) or immunosuppressive drugs (from 7% to 14%, P < 0.001). The therapeutic strategy changed in 70% of reclassified cases (60/85) and in 59% of cases in which LBx increased the MDT confidence (84/142). Reclassification significantly impacted the outcome. The cases classified as non-IPF by clinician and radiologist and then reclassified to be IPF after LBx showed a significantly worse survival compared with non-IPF confirmed cases (adjusted hazard ratio [HR], 3.8; 95% confidence interval [CI], 1.75-8.3); P = 0.001. Cases initially classified as IPF and then reclassified as non-IPF after LBx showed a better prognosis compared with IPF confirmed cases (HR, 0.41; 95% CI, 0.18-0.94; P = 0.03). Conclusions: Reclassification of cases with LBx data increased diagnostic confidence and changed the therapeutic strategy in one-third of cases. Pathologic reclassification of cases refined prognosis prediction. Patients classified as non-IPF by clinician and radiologist and then reclassified IPF after LBx had worse prognosis compared with the non-IPF confirmed cases.

The Impact of the Envisia Genomic Classifier in the Diagnosis and Management of Patients with Idiopathic Pulmonary Fibrosis.

Rationale: The diagnosis of idiopathic pulmonary fibrosis (IPF) remains challenging and can result in delayed or misdiagnosis. IPF diagnosis is based on the presence of either a radiographic or histologic usual interstitial pneumonia (UIP) pattern in the absence of an identifiable etiology. The Envisia Genomic Classifier is a clinically validated molecular diagnostic test that identifies UIP in transbronchial biopsies. Objectives: To determine the impact of the Envisia Genomic Classifier on physicians' clinical decision-making in the diagnosis and management of IPF. Methods: This prospective randomized decision impact survey was designed to test the hypothesis that including an Envisia UIP-positive result will increase IPF diagnoses, diagnostic confidence, and the recommendation for antifibrotic therapy. The survey included patients from the BRAVE (Bronchial Sample Collection for a Novel Genomic Test) study who had a high-resolution computed tomographic scan without a typical UIP pattern, an Envisia UIP-positive result, and a final diagnosis of IPF by multidisciplinary team discussion. Each case was presented in three different formats: a pre-post cohort, where each case is presented initially without and then with Envisia, and two independent cohorts, where each case is presented without and with Envisia, respectively. Results: U.S.-based pulmonologists from community and academic centers in geographically diverse practices were approached for inclusion in this study. 103 (65%) U.S.-based pulmonologists met the inclusion criteria and provided 605 case reviews of 11 patient cases. The number of IPF diagnoses increased with Envisia by an absolute difference of 39% from 47 (30%) before Envisia to 107 (69%) after Envisia in the pre-post cohort and by 13% in the independent cohorts. High confidence (⩾90%) of interstitial lung disease diagnoses was more commonly seen with Envisia in both the pre-post cohort and in the independent cohorts. Recommendation for antifibrotic treatment increased with Envisia by an absolute difference of 36% from 15 (10%) before Envisia to 72 (46.4%) after Envisia in the pre-post cohort and by 11% in the independent cohorts. Conclusions: This decision impact survey suggests the clinical utility of the Envisia Classifier by demonstrating a significant increase in IPF diagnoses, diagnostic confidence, and recommendation for antifibrotic therapies to assist physicians in effectively managing patients to improve outcomes of patients with IPF.

Comparison of Forceps, Cryoprobe, and Thoracoscopic Lung Biopsy for the Diagnosis of Interstitial Lung Disease - The CHILL Study.

RATIONALE: Transbronchial lung cryobiopsy (TBLC) has emerged as a less invasive method to obtain a tissue diagnosis in patients with interstitial lung disease (ILD). The diagnostic yield of TBLC compared to surgical lung biopsy (SLB) remains uncertain. OBJECTIVES: The aim of this study was to determine the diagnostic accuracy of forceps transbronchial lung biopsy (TBLB) and TBLC compared to SLB when making the final diagnosis based on multidisciplinary discussion (MDD). METHODS: Patients enrolled in the study underwent sequential TBLB and TBLC followed immediately by SLB. De-identified cases, with blinding of the biopsy method, were reviewed by a blinded pathologist and then discussed at a multidisciplinary conference. MAIN RESULTS: Between August 2013 and October 2017, we enrolled 16 patients. The raw agreement between TBLC and SLB for the MDD final diagnosis was 68.75% with a Cohen's kappa of 0.6 (95% CI 0.39, 0.81). Raw agreement and Cohen's kappa of TBLB versus TBLC and TBLB versus SLB for the MDD final diagnosis were much lower (50%, 0.21 [95% CI 0, 0.42] and 18.75%, 0.08 [95% CI -0.03, 0.19], respectively). TBLC was associated with mild bleeding (grade 1 bleeding requiring suction to clear) in 56.2% of patients. CONCLUSIONS: In patients with ILD who have an uncertain type based on clinical and radiographic data and require tissue sampling to obtain a specific diagnosis, TBLC showed moderate correlation with SLB when making the diagnosis with MDD guidance. TBLB showed poor concordance with both TBLC and SLB MDD diagnoses.

Idiopathic pulmonary fibrosis diagnosed concomitantly with diffuse squamous cell lung cancer on surgical lung biopsy: a case report.

BACKGROUND: Idiopathic pulmonary fibrosis is a disease with a poor prognosis and has been associated with increased lung cancer incidence. CASE PRESENTATION: We report the case of a Caucasian 75-year-old woman, a former smoker, hospitalized for breathlessness with a chest computed tomography scan showing an interstitial lung disease. A surgical lung biopsy was performed, confirming a pattern of usual interstitial pneumonia but also numerous disseminated foci of well-differentiated focally invasive squamous cell carcinoma without hypermetabolic lung nodule, mass, or enlarged lymph node visualized on chest computed tomography or positron emission tomography scan. Nintedanib was started for its antifibrotic and antitumor properties, without any other antineoplastic treatment. Three years after initiation of nintedanib, clinical, functional, and computed tomography scan evaluations were stable, and there was no evidence for evolution of the squamous cell carcinoma. CONCLUSIONS: Data are scarce regarding the benefit of nintedanib in patients with idiopathic pulmonary fibrosis-associated lung cancer, and it is unclear whether nintedanib could have a preventive role in lung carcinogenesis in idiopathic pulmonary fibrosis patients. This experience could help the scientific community in case of similar incidental findings.