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Diagnostic Yield, Safety, and Impact of Transbronchial Lung Biopsy In Ghiani and Neurohr BMC Pulm Med (2021) 21:15 https://doi.org/10.1186/s12890-020-01357-7 RESEARCH ARTICLE Open Access Diagnostic yield, safety, and impact of transbronchial lung biopsy in mechanically ventilated, critically ill patients: a retrospective study Alessandro Ghiani1* and Claus Neurohr1,2 Abstract Background: Pulmonary infltrates of variable etiology are one of the main reasons for hypoxemic respiratory failure leading to invasive mechanical ventilation. If pulmonary infltrates remain unexplained or progress despite treatment, the histopathological result of a lung biopsy could have signifcant impact on change in therapy. Surgical lung biopsy is the commonly used technique, but due to its considerable morbidity and mortality, less invasive bronchoscopic transbronchial lung biopsy (TBLB) may be a valuable alternative. Methods: Retrospective, monocentric, observational study in mechanically ventilated, critically ill patients, subjected to TBLB due to unexplained pulmonary infltrates in the period January 2014 to July 2019. Patients’ medical records were reviewed to obtain data on baseline clinical characteristics, modality and adverse events (AE) of the TBLB, and impact of the histopathological results on treatment decisions. A multivariable binary logistic regression analysis was performed to identify predictors of AE and hospital mortality, and survival curves were generated using the Kaplan- Meier method. Results: Forty-two patients with in total 42 TBLB procedures after a median of 12 days of mechanical ventilation were analyzed, of which 16.7% were immunosuppressed, but there was no patient with prior lung transplantation. Diagnostic yield of TBLB was 88.1%, with AE occurring in 11.9% (most common pneumothorax and minor bleeding). 92.9% of the procedures were performed as a forceps biopsy, with organizing pneumonia (OP) as the most common histological diagnosis (54.8%). Variables independently associated with hospital mortality were age (odds ratio 1.070, 95%CI 1.006–1.138; p 0.031) and the presence of OP (0.182, [0.036–0.926]; p 0.040), the latter being confrmed in the survival analysis (log-rank= p 0.040). In contrast, a change in therapy based= on histopathology alone occurred in 40.5%, and there was no evidence= of improved survival in those patients. Conclusions: Transbronchial lung biopsy remains a valuable alternative to surgical lung biopsy in mechanically ven- tilated critically ill patients. However, the high diagnostic yield must be weighed against potential adverse events and limited consequence of the histopathological result regarding treatment decisions in such patients. *Correspondence: [email protected] 1 Department of Pulmonary and Respiratory Medicine, Schillerhoehe Lung Clinic (Robert-Bosch-Hospital GmbH, Stuttgart), Solitudestr. 18, 70839 Gerlingen, Germany Full list of author information is available at the end of the article © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Ghiani and Neurohr BMC Pulm Med (2021) 21:15 Page 2 of 8 Keywords: Transbronchial lung biopsy, Mechanical ventilation, Critical illness, Safety, Diagnostic yield, Organizing pneumonia Background A06, A07, A09, A11, A13, E40, F43) and the modifed Intubation with mechanical ventilation is a life–saving International Classifcation of Procedures in Medicine procedure for patients with acute severe hypoxemic res- (ICPS) code for the TBLB (OPS 1–430.2). piratory failure due to pulmonary infltrates of variable etiology [1]. If infltrates remain unexplained or progress Data collection despite therapy (e.g. antibiotics), it is almost impossi- Data were collected from the hospitals’ electronic medi- ble to derive a specifc diagnosis based solely on clinical cal record and chart systems (PDMS Metavision ICU, symptoms, radiological fndings, and laboratory values. iMDsoft, Tel Aviv, Israel; iMedOne, Telekom Healthcare Empiric treatment of such patients tends to over–ther- Solutions, Bonn, Germany), and from the prospectively apy, that may have potentially toxic side efects (e.g. for maintained records of the bronchoscopy database (View- unnecessary application of broad-spectrum and long- Point 6, GE Healthcare GmbH, Chalfont St. Giles, Great term antimicrobial agents). Tis also generates high costs Britain). Tese data included patient’s baseline character- and rare and potentially reversible causes of pulmonary istics on ICU admission, such as demographic data, lead- infltrates remain undetected and untreated. In contrast, ing cause for intubation, presence of acute respiratory the histopathological result of a lung biopsy may provide distress syndrome (ARDS) defned by the Berlin criteria important information on the underlying disease and [10], and comorbidities, as well as modalities and adverse could have signifcant impact on treatment decisions. events (AE) of TBLB. Surgical lung biopsy (SLB) is the commonly used tech- AE assessed were pneumothorax, minor and major nique in such patients [2, 3], but hypoxemia may worsen bleeding, hemodynamic instability (defned as either dramatically with single–lung ventilation, and the proce- a start or increase in dosage of vasopressors during the dure usually requires a transfer from the intensive care procedure), and death. Minor bleeding was defned as unit (ICU) to the operating theater. Alternatively, bron- bleeding control by means of segmental wedging and/ choscopic, transbronchial lung biopsy (TBLB, by means or topical administration of cold saline or adrenaline, of forceps biopsy or cryobiopsy) is available, which also whereas major bleeding required an additional hemo- can be performed at the bedside in the ICU in the event static agent (e.g. oxidized regenerated cellulose [ORC] of mechanical ventilation [4–9]. mesh), pulmonary isolation (using selective endobron- Te present study aims to assess the diagnostic yield, chial intubation, a bronchus blocker or a double-lumen safety, and therapeutic consequences of transbronchial tube), bronchial artery embolization or surgery [11]. lung biopsy in a cohort of mechanically ventilated, criti- Te histopathological results of TBLB were assessed cally ill patients. for specifc histological diagnoses. Furthermore, sub- groups of patients depending on histological fndings Methods (e.g. patients with organizing pneumonia [OP], either cryptogenic [COP] or secondary to an underlying dis- Exploratory, retrospective, monocentric, observational ease [SOP]) were separately analyzed. Changes in therapy study on mechanically ventilated, critically ill patients, based on the histopathological result (e.g. commence- treated at the Schillerhoehe Lung Clinic (Gerlingen, Ger- ment of corticosteroid treatment or immunosuppression) many) from January 2014 to July 2019, and subjected were recorded. We defned responsiveness to corticos- to transbronchial lung biopsy due to unexplained pul- teroids as an increase in the ratio of partial pressure of monary infltrates. Te study was approved by the local oxygen to fraction of inspired oxygen (P/F ratio) of more ethics committee, the need for informed consent was than 100 mmHg within one week of therapy, as previ- waived (Ethics Committee of the State Chamber of Phy- ously described [12, 13]. sicians of Baden-Wuerttemberg, Germany, fle number F–2019–096). Transbronchial lung biopsy All bronchoscopies were carried out by an experienced Patient selection interventional pulmonologist who was familiar with both Patients were identifed using the 2019 Diagnosis Related the fexible and the rigid bronchoscopy technique. TBLB Groups (DRG) codes for mechanical ventilation (DRG was performed either at the bedside in the ICU or in the bronchoscopy unit. Target lobes and lung segments were Ghiani and Neurohr BMC Pulm Med (2021) 21:15 Page 3 of 8 selected based on a current chest CT scan. TBLB was using MedCalc statistical software version 19.2.5 (Med- always performed unilaterally to avoid bilateral pneu- Calc software Ltd., Ostend, Belgium). mothorax. Te main criterion for exclusion was severe coagulopathy with thrombocytopenia < 50/nL, activated Results partial thromboplastin time (aPTT) > 50 s, an Interna- Forty-two patients with in total 42 TBLB procedures were tional Normalized Ratio (INR) > 1.5, and the presence of assessed, of which seven patients (16.7%) were immu- anticoagulants or antiaggregants (with the exception of nosuppressed, but there was no patient with prior lung acetylsalicylic acid [14]). Biopsies were always performed transplantation. Tree patients were on
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