Paola Tantalocco

Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases

Background Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited. Objectives To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD. Method Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features. Results Safety: pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm2 (range, 11.94–76.25). Diagnostic yield: among adequate TBLC the pathologists were confident (“high confidence”) that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis–interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident (“low confidence”). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69–0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable. Conclusions TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical-radiological setting of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia. Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD.

Bronchoscopic Lung Cryobiopsy Increases Diagnostic Confidence in the Multidisciplinary Diagnosis of Idiopathic Pulmonary Fibrosis

RATIONALE Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung cryobiopsy (BLC), are highly desirable. OBJECTIVES To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF. METHODS In this cross-sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels. MEASUREMENTS AND MAIN RESULTS We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 to 65%, P = 0.0016 of high confidence IPF diagnosis, in the BLC group and SLB group, respectively). The overall interobserver agreement in IPF diagnosis was similar for both approaches (BLC overall kappa, 0.96; SLB overall kappa, 0.93). IPF was the most frequent diagnosis (50 and 39% in the BLC and SLB group, respectively; P = 0.23). After the addition of histopathologic information, 17% of cases in the BLC group and 19% of cases in the SLB group, mostly idiopathic nonspecific interstitial pneumonia and hypersensitivity pneumonitis, were reclassified as IPF. CONCLUSIONS BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF. This study provides a robust rationale for future studies investigating the diagnostic accuracy of BLC compared with SLB.

The impact of lung cancer on survival of idiopathic pulmonary fibrosis.

BACKGROUND Lung cancer (LC) is frequently associated with idiopathic pulmonary fibrosis (IPF). Despite this well-known association, the outcome of LC in patients with IPF is unclear. The objective of this study was to evaluate the impact of LC on survival of patients with associated IPF. METHODS A total of 260 patients with IPF were reviewed, and 186 IPF cases had complete clinical and follow-up data. Among these, five cases were excluded because LC was radiologically suspected but not histologically proven. The remaining 181 cases were categorized in two groups: 23 patients with biopsy-proven LC and IPF (LC-IPF) and 158 patients with IPF only (IPF). Survival and clinical characteristics of the two groups were compared. RESULTS Prevalence of histologically proven LC was 13%, and among those with LC-IPF cumulative incidence at 1 and 3 years was 41% and 82%. Patients with LC were more frequently smokers (91.3% vs 71.6%, P = .001), with combined pulmonary fibrosis and emphysema (52% vs 32%, P = .052). Survival in patients with LC-IPF was significantly worse than in patients with IPF without LC (median survival, 38.7 months vs 63.9 months; hazard ratio = 5.0; 95% CI, 2.91-8.57; P < .001). Causes of death in the study group were respiratory failure in 43% of patients, LC progression in 13%, and LC treatment-related complications in 17%. CONCLUSIONS In patients with IPF, LC has a significant adverse impact on survival. Diagnosis and treatment of LC in IPF are burdened by an increased incidence of severe complicating events, apparently as lethal as the cancer itself.

Safety and Diagnostic Yield of Transbronchial Lung Cryobiopsy in Diffuse Parenchymal Lung Diseases: A Comparative Study versus Video-Assisted Thoracoscopic Lung Biopsy and a Systematic Review of the Literature.

Background: A diagnosis of interstitial lung diseases (ILDs) may include surgical lung biopsy (SLB), which is associated with significant morbidity and mortality and also appreciable costs. Transbronchial lung cryobiopsy (TBLC) is adopting an important role. Objectives: The aim of this study was to compare the diagnostic yield (DY) and safety of TBLC and SLB in a large cohort of patients and to perform a systematic review of the literature as well as a meta-analysis. Methods: We performed a retrospective analysis of 447 cases with ILD undergoing TBLC and/or SLB and a systematic review of the literature (MEDLINE and Embase for all original articles on the DY and safety of TBLC in ILDs up to July 2015). Results: A total of 150 patients underwent SLB and 297 underwent TBLC. The median time of hospitalization was 6.1 days (SLB) and 2.6 days (TBLC; p < 0.0001). Mortality due to adverse events was observed for 2.7% (SLB) and 0.3% (TBLC) of the patients. Pneumothorax was the most common complication after TBLC (20.2%). No severe bleeding was observed. TBLC was diagnostic for 246 patients (82.8%), SLB for 148 patients (98.7%, p = 0.013). A meta-analysis of 15 investigations including 781 patients revealed an overall DY of 0.81 (0.75-0.87); the overall pooled probability of developing a pneumothorax, as retrieved from 15 studies including 994 patients, was 0.06 (95% CI 0.02-0.11). Conclusion: Cryobiopsy is safe and has lower complication and mortality rates compared to SLB. TBLC might, therefore, be considered the first diagnostic approach for obtaining tissue in ILDs, reserving the surgical approach for cases in which TBLC is not diagnostic.

Transbronchial biopsy is useful in predicting UIP pattern.

BackgroundUsual interstitial pneumonia (UIP), is a necessary feature pathologically or radiologically for the diagnosis of idiopathic pulmonary fibrosis (IPF). The predictive value of transbronchial biopsy (TBB) in identifying UIP is currently unknown. The objective of this study is to assess the accuracy with which histopathologic criteria of usual interstitial pneumonia (UIP) can be identified in transbronchial biopsy (TBB) and to assess the usefulness of TBBx in predicting a the diagnosis of UIP pattern. We conducted a retrospective blinded and controlled analysis of TBB specimens from 40 established cases of UIP and 24 non-UIP interstitial lung diseases.ResultsAdequate TBB specimens were available in 34 UIP cases (85% of all UIP cases). TBB contained histopathologic criteria to suggest a UIP pattern (ie. at least one of three pathologic features of UIP present; patchy interstitial fibrosis, fibroblast foci, honeycomb changes) in 12 cases (30% of all UIP cases). Sensitivity, specificity, positive and negative predictive values for the two pathologists were 30% (12/40), 100% (24/24), 100% (12/12), 46% (24/52) and 30% (12/40), 92% (22/24), 86% (12/14), 55% (22/40) respectively. Kappa coefficient of agreement between pathologists was good (0.61, 95% CI 0.31-0.91). The likelihood of identifying UIP on TBB increased with the number and size of the TBB specimens.ConclusionAlthough sensitivity is low our data suggest that even modest amount of patchy interstitial fibrosis, fibroblast foci, honeycomb changes detected on TBB can be highly predictive of a UIP pattern. Conversely, the absence of UIP histopathologic criteria on TBB does not rule out UIP.

Idiopathic Pulmonary Fibrosis: Diagnosis and Prognostic Evaluation

Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and has a dismal prognosis. Median age at IPF onset is 60-70 years and it is mainly related to cigarette smoke exposure. Its clinical profile is heterogeneous and different clinical phenotypes are now better defined: familial IPF, slow and rapid progressors, combined pulmonary fibrosis and emphysema, anti-neutrophil cytoplasmic antibodies/microscopic polyangiitis and IPF, and IPF associated with lung cancer. Acute exacerbation associated with rapid functional decline is an event that does not happen infrequently and affects survival. Diagnosis requires a typical usual interstitial pneumonia (UIP) pattern on computed tomography in the appropriate clinical setting or morphological confirmation of the UIP pattern when imaging findings are not characteristic enough. Surgical lung biopsy is the gold standard to obtain valuable information for histological analysis. However, less invasive procedures (transbronchial lung biopsy or even improved transbronchial lung biopsy by cryoprobes) are now under consideration. Prognostic indicators are mainly derived by pulmonary function tests. Recently, staging systems have been proposed.

The multidisciplinary approach in the diagnosis of idiopathic pulmonary fibrosis: a patient case-based review

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressively fibrosing interstitial pneumonia that is associated with a significantly worse prognosis than other forms of chronic interstitial pneumonia. An early and accurate diagnosis of IPF is important to enable the initiation of disease-specific therapies, which have the potential to reduce disease progression, and the avoidance of inappropriate and potentially harmful drugs. Establishing an accurate diagnosis of IPF can be challenging. Recent studies and international guidelines advocate the importance of a multidisciplinary team (MDT) in the initial diagnostic assessment of patients with suspected IPF. Typical MDT members include a pulmonologist, a radiologist and a pathologist, with further input from a thoracic surgeon, a rheumatologist, a specialist nurse and an occupational physician where appropriate. Multidisciplinary diagnosis is considered the gold standard because it can improve the accuracy of diagnosis of IPF, avoid unnecessary testing (e.g. lung biopsy), and optimise patient management. Here we highlight the strengths and limitations of the multidisciplinary approach to IPF diagnosis through MDT discussion of two patient cases. The strengths and limitations of IPF management by a multidisciplinary team are highlighted in two patient cases http://ow.ly/H04Xe

Transbronchial Lung Cryobiopsy in Diffuse Parenchymal Lung Disease: Comparison between Biopsy from 1 Segment and Biopsy from 2 Segments - Diagnostic Yield and Complications

Background: Transbronchial lung cryobiopsy is an innovative method of obtaining samples from the parenchyma of patients with diffuse parenchymal lung diseases. However, the technique is not yet standardized, and uncertainty exists about the optimal protocol, including the number of samples, the biopsy size, and the choice of the biopsy site. Objectives: To compare the diagnostic yield and complications of cryobiopsy with different strategies adopted to sample lung tissue (number of samples, biopsy site, and sample size). Methods: We prospectively enrolled 46 patients with suspected diffuse parenchymal lung diseases for the diagnosis of which a biopsy was deemed useful. All patients underwent transbronchial lung cryobiopsy, and they were randomly assigned to group A (4 samples obtained from the same segment) or group B (2 samples obtained from one segment and 2 samples obtained from a different segment of the same lobe). Analysis of the samples was performed sequentially (from the first to the last sample), and pathologists reformulated their histopathologic diagnosis with the addition of each sample. Results: The mean diagnostic yield of the procedure combining the 2 groups and performing only the first sampling was 69%. When a second biopsy was performed as well, the mean diagnostic yield improved, but this increase was significant only when the 2 samples were obtained from 2 different segments (96%, group B). Conclusions: This study suggests that the strategy of performing 2 biopsies with a cryoprobe may be associated with an increased diagnostic yield in diffuse parenchymal lung diseases if these samples are obtained from 2 different segments within the same lobe.

Übereinstimmung unterschiedlicher Spirometer: Eine Herausforderung in der langfristigen Beobachtung von Patienten und Patientengruppen?

Hintergrund: Langzeit-Kohortenstudien und Lungenfunktionslabors sehen sich früher oder später damit konfrontiert, dass sie ihre Spirometer ersetzen müssen. Mangelnde Übereinstimmung zwischen den unterschiedlichen Spirometern kann die longitudinale Vergleichbarkeit der Daten beeinträchtigen, insbesondere wenn konventionelle durch portable Spirometer ersetzt werden. Ziele: Vergleich des Handgeräts EasyOne (EO) mit einem konventionellen Spirometer von SensorMedics (SM) und Untersuchung der Reproduzierbarkeit der Messungen mehrerer EO-Geräte untereinander. Methoden: Insgesamt 82 Freiwillige unterzogen sich spirometrischen Untersuchungen mit 1 SM- und 2 der 3 EO-Spirometer gemäß einem lateinischen Quadrat-Design. Für die Analyse der mit den verschiedenen Spirometern gemessenen Unterschiede in der forcierten Vitalkapazität (FVC), der forcierte exspiratorische Einsekundenkapazität (forced expiratory volume in 1 s; FEV1), dem FEV1/FVC-Quotienten und dem mittleren forcierten exspiratorischen Fluss bei 25-75% der FVC wurde ein gemischtes Effektmodell mit einem zufälligen Achsenabschnitt für jeden Probanden und dem Effekt des Geräts als Festeffekt (berichtigt um Geschlecht, Alter, Größe und Reihenfolge der Spirometer) verwendet. Bland-Altman-Plots zeigen die 95%-Grenzen der Übereinstimmung. Ergebnisse: Die Vergleiche zwischen EO und SM ergaben relativ geringe mittlere Unterschiede von <3%, jedoch systematisch niedrigere Werte für FVC und FEV1 bei allen EO-Geräten. Die 95%-Übereinstimmung überschritt bei 2 EO-Spirometern die Grenze für die FEV1 um 50 ml. Die Vergleiche der EO-Geräte untereinander ergaben mittlere Unterschiede und Grenzen der Übereinstimmung innerhalb des festgelegten Rahmens und sprachen somit für recht hohe Genauigkeit der Geräte im Vergleich. Wiederholungsmessungen mit demselben Spirometer ergaben keine statistisch signifikanten Unterschiede. Schlussfolgerungen: Die Studie deutet auf eine recht hohe Übereinstimmung zwischen portablen und konventionellen Spirometern hin. Die bei 2 EO-Geräten ermittelten Unterschiede, die bei der FEV1 geringfügig über den Grenzwerten lagen, dürften für die klinische Praxis als weitgehend irrelevant zu betrachten sein. Die systematisch niedrigeren FVC- und FEV1-Werte, die mit den EO-Geräten gemessen wurden, könnten hingegen für epidemiologische Studien signifikant sein und sprechen für eine Inspektion vor dem Austausch der Geräte.Übersetzung aus Respiration 2013;85:505-514 (DOI:10.1159/000346649)

Sofortzytologie während der endobronchialen ultraschallgeführten transbronchialen Nadelaspiration zur Diagnose des Lungenkarzinoms: Eine randomisierte Studie

Hintergrund: Die sofort und vor Ort durchgeführte zytologische Untersuchung (rapid on-site cytologic evaluation; ROSE) ist zwar im Rahmen der endobronchialen ultraschallgeführten transbronchialen Nadelaspiration (EBUS-TBNA) sehr gebräuchlich, jedoch ist ihre genaue Rolle nicht geklärt. Ziele: Das Ziel der vorliegenden Studie war die Beurteilung der Wirksamkeit von ROSE im Rahmen der EBUS-TBNA bei der Diagnose von Lungenkrebs. Methoden: 120 Patienten mit dringendem Verdacht auf Lungenkrebs, bei denen eine hiläre/mediastinale Lymphadenopathie oder ein Tumor nahe der zentralen Atemwege vorlag, wurden in die Studie eingeschlossen und auf EBUS-TBNA mit oder ohne ROSE randomisiert. Ergebnisse: Zwölf Patienten mit sichtbaren endobronchialen Läsionen wurden aus der Analyse ausgeschlossen. So wurden insgesamt 108 Patienten (55 in der ROSE-Gruppe, 53 in der Nicht-ROSE-Gruppe) ausgewertet. Weitere Maßnahmen einschließlich einer EBUS-TBNA wegen einer anderen Läsion als der Hauptzielläsion und/oder eine transbronchiale Biopsie in derselben Sitzung wurden bei 11% der Patienten in der ROSE-Gruppe und 57% der Patienten in der Nicht-ROSE-Gruppe durchgeführt (p < 0,001). Die mittlere Anzahl der Punktionen war in der ROSE-Gruppe signifikant niedriger (2,2 vs. 3,1 Punktionen; p < 0,001), die mittlere Dauer der Bronchoskopie aber bei beiden Gruppen vergleichbar (22,3 vs. 22,1 min; p = 0,95). Die Sensitivität bzw. Genauigkeit für die Diagnose von Lungenkrebs betrug in der ROSE-Gruppe 88 bzw. 89% und in der Nicht-ROSE-Gruppe 86 bzw. 89%. Es traten keine Komplikationen auf.Schlussfolgerungen: ROSE im Rahmen der EBUS-TBNA ist mit einem signifikant geringeren Bedarf an zusätzlichen bronchoskopischen Maßnahmen und Punktionsversuchen assoziiert.Übersetzung aus Respiration 2013;85:486-492 (DOI: 10.1159/000346987)