Bronchoscopic Lung Biopsy Research Articles

A review of the effectiveness of virtual bronchoscopy in biopsy of lung tumors. Evolution of lung tumor diagnosis

Lung cancer remains the leading cause of cancer-related mortality, emphasizing the need for advanced diagnostic methods. This study reviews modern bronchoscopy navigational techniques, focusing on Virtual Bronchoscopic Navigation (VBN) and Electromagnetic Navigation Bronchoscopy (ENB), assessing their efficacy and safety in biopsying pulmonary lesions. Based on literature from 2000 to 2023, VBN demonstrated superior diagnostic accuracy for smaller nodules, with success rates of 93% vs 89% for ENB, while both methods exhibited low complication rates. Despite higher upfront costs, these technologies may offer long-term savings due to improved outcomes. Further research is warranted to optimize lung cancer diagnostics and enhance patient care. Aim of the study This study aims to evaluate the effectiveness and safety of VBN and ENB in diagnosing lung nodules. By comparing diagnostic success rates, complication rates, procedure durations, and cost-effectiveness, we seek to identify the safer and more efficient technique for biopsying neoplastic lesions, ultimately improving patient outcomes. Materials and methods We searched the following databases: PubMed, Web of Science, clinical trial registry platforms, using key terms such as virtual bronchoscopy navigation, navigation system-guided biopsy, bronchoscopic lung biopsy. The results were limited to papers published between 2000 - 2023. Conclusion Navigational bronchoscopy techniques like VBN and ENB are safe and effective, with minimal adverse events and no hospitalization needed. They reduce procedure times and patient burden, offering long-term cost-effectiveness despite higher initial costs. Further research is necessary to enhance these technologies for better lung cancer diagnostics. Key words: lung biopsy, bronchoscopy navigation, lung cancer, bronchoscopic

The importance of Ki-67 proliferation index in small cell lung cancer

BackgroundAs in numerous cancers, the connection between the Ki-67 proliferation index and response to treatment in cellular breakdown in the lungs is underlined. The purpose of this study was to investigate the connection between the Ki-67 proliferation index and radiotherapy’s therapeutic and survival effects in small cell lung cancer.MethodsThe limited-stage small cell lung cancer patients in our hospital were retrospectively reviewed. Patients receiving standard chemoradiotherapy were included in the study. Age, sex, cancer stage, comorbidities, response to treatment, and survival time were recorded. Bronchoscopic or transthoracic lung biopsy specimens which were taken at the time of diagnosis were stained with the Ki-67 immunohistochemical stain. Survival of patients and treatment response were compared statistically with the Ki-67 values.ResultsThe Ki-67 proliferation index (62.29 ± 7.52) was lower in patients with partial response than in patients with complete response (77.08 ± 2.84) (p < 0.001). When the correlation between survival time and Ki-67 was examined, there was a positive correlation between the Ki-67 and survival time (p: 0.019; r: 0.426). The patients were divided into two groups: Ki-67 < 68.70 and Ki-67 ≥ 68.70. In patients with Ki-67 ≥ 68.70, the survival rate was better than that of patients with Ki-67 < 68.70 (p: 0.012). In Cox regression analysis, Ki-67 PI < 68.7 was found that increased mortality by 2742 times independently.ConclusionsPatients with a high Ki-67 had a better survival effect than those with low Ki-67, and patients with complete responses had a higher Ki-67 value.

High Tidal Volume, High Positive End Expiratory Pressure and Apneic Breath Hold Strategies (Lung Navigation Ventilation Protocol) With Cone Beam Computed Tomography Bronchoscopic Biopsy of Peripheral Lung Lesions: Results in 100 Patients.

A dedicated anesthesia protocol for bronchoscopic lung biopsy-lung navigation ventilation protocol (LNVP)-specifically designed to mitigate atelectasis and reduce unnecessary respiratory motion, has been recently described. LNVP demonstrated significantly reduced dependent ground glass, sublobar/lobar atelectasis, and atelectasis obscuring target lesions compared with conventional ventilation. In this retrospective, single-center study, we examine the impact of LNVP on 100 consecutive patients during peripheral lung lesion biopsy. We report the incidence of atelectasis using cone beam computed tomography imaging, observed ventilatory findings, anesthesia medications, and outcomes, including diagnostic yield, radiation exposure, and complications. Atelectasis was observed in a minority of subjects: ground glass opacity atelectasis was seen in 30 patients by reader 1 (28%) and in 18 patients by reader 2 (17%), with good agreement between readers (κ = 0.78). Sublobar/lobar atelectasis was observed in 23 patients by reader 1 and 26 patients by reader 2, also demonstrating good agreement (κ = 0.67). Atelectasis obscured target lesions in very few cases: 0 patients (0%, reader 1) and 3 patients (3%, reader 2). Diagnostic yield was 85.9% based on the AQuIRE definition. Pathology demonstrated 57 of 106 lesions (54%) were malignant, 34 lesions (32%) were benign, and 15 lesions (14%) were nondiagnostic. Cone beam computed tomography images confirmed low rates of atelectasis, high tool-in-lesion confirmation rate, and high diagnostic yield. LNVP has a similar safety profile to conventional bronchoscopy. Most patients will require intravenous fluid and vasopressor support. Further study of LNVP and other ventilation protocols are necessary to understand the impact of ventilation protocols on bronchoscopic peripheral lung biopsy.

Is histological confirmation necessary to avoid futile resections? Comparative of 4 university hospitals.

There is no consensus in the literature on preoperative histological analysis for lung cancer. The objective of this study was to assess 4 diagnostic models used in different hospitals with differing practices regarding preoperative histological diagnosis and the consequences in terms of unnecessary surgery and futile major resection. We carried out a retrospective observational study collected from 4 university hospitals in Spain over 3 years (January 2019 to December 2021). We included all patients with a confirmed diagnosis of primary lung cancer and any patients with suspected primary lung cancer who had undergone surgery. All patients underwent computed tomography and positron emission tomography/computed tomography scans. Each multidisciplinary committee was free to choose whether to perform flexible bronchoscopic or transthoracic lung biopsy. Decisions concerning whether to perform intraoperative sample analysis, the surgical approach and the type of resection were left to the surgical team. We included a total of 1642 patients. The use of flexible endoscopy and its diagnostic performance varied substantially between hospitals (range: 23.8-79.3% and 25-60.7%, respectively); and the same was observed for transthoracic biopsy and its performance (range: 16.9-82.3% and 64.6-97%, respectively). Regarding major resection surgery (lobectomy or more extensive resection), the lowest rate was observed in hospital C (1%) and the highest in hospital B (2.8%), with between-hospital differences not reaching significance (P = 0.173). The rate of histological sampling before lung cancer surgery still varies between hospitals. In spite of very diverse multidisciplinary management, the rate of futile lobectomy is not significantly higher in hospitals with lower rates of preoperative histological analysis.

Establishing a Diagnosis of Pulmonary Sarcoidosis.

Pulmonary sarcoidosis is the most prevalent manifestation of sarcoidosis and the commonest diagnosis in clinics for ILD. Due to the lack of a simple and reliable test, making the diagnosis is often challenging. There are three criteria that must always be considered: (1) compatible clinical presentation; (2) evidence of granuloma formation (usually non-caseating); and (3) exclusion of alternative causes of granulomatous disease. There are various tools available for diagnosis, amongst which serum biomarkers like sACE and sIL-2R, HRCT, BAL, EBUS/EUS and sometimes bronchoscopic or surgical lung biopsy are most contributive. However, the degree of invasiveness of the applied test and associated risk to the patient must be weighed against management consequences. In specific situations (e.g., presentation as Löfgren's syndrome) or when there is high suspicion based on HRCT in the context of supportive clinical findings, it might be justifiable to decide on a "working diagnosis of sarcoidosis" and to refrain from further invasive procedures for the patient. This should, however, preferably be agreed upon after discussion in an experienced multidisciplinary team and requires close follow-up of the patient. In general, it is advisable to always maintain a healthy dose of skepticism when making the diagnosis of sarcoidosis, especially when the clinical course of disease gives rise to this.

Pilot study of archimedes virtual bronchoscopic navigation system-guided biopsy to diagnose lung nodules in children.

Peripheral pulmonary lesions are uncommon in children. Bronchoscopy is a minimal invasive method to obtain a diagnostic lung biopsy. However, due to the lack of effective guidance methods, the diagnostic efficacy of transbronchial lung biopsy for peripheral solitary pulmonary diseases is still limited. Is the Archimedes virtual bronchoscopic navigation system safe and effective for the diagnosis of peripheral pulmonary lesions in children? This pilot study retrospectively analyzed the clinical features, radiological characteristics, operation processes, intra-and postoperative complications, and pathological results of five children who underwent Archimedes-guided biopsy of peripheral pulmonary lesions in Beijing Children's Hospital from May 2021 to May 2022. The cohort comprised five children (all males) with age of 7.1-15.8 years. A guide sheath was inserted through the bronchoscope under the guidance of Archimedes combined with radial endobronchial ultrasound to complete the biopsy under general anesthesia. The fused fluoroscopy technique was used to reconfirm the location of the forceps prior to biopsy in all children. The forceps reached the lesion under the guidance of the navigation and the samples were collected successfully in all children. Pathological examination of the biopsy specimens showed Epstein-Barr virus infection-related lymphoproliferative disease in one child, pulmonary metastasis of rhabdomyosarcoma in one child, and pulmonary vasculitis in one child; high-throughput sequencing of the biopsy tissue sample identified Mycobacterium tuberculosis (sequence no. 80) in one child and Aspergillus (sequence no. 40) in another child. All five children tolerated the biopsy procedure without developing postoperative complications, such as pneumothorax and hemoptysis. Archimedes-guided bronchoscopic lung biopsy is a feasible and efficient way to diagnose peripheral pulmonary lesions in children with manageable complications.

Safety and Feasibility of a Sheath Cryoprobe for Bronchoscopic Transbronchial Biopsy: The FROSTBITE Trial

Background: Bronchoscopic lung biopsy is typically performed using transbronchial forceps. However, this method is limited by small sample size and presence of crush artifact. Cryobiopsy offers the potential to overcome these limitations with larger artifact-free samples but has not been widely adopted due to concerns over increased rates of bleeding and pneumothorax. A new, smaller 1.1-mm cryoprobe has been developed that operates in a similar fashion to forceps, though the safety profile of this cryoprobe has not yet been prospectively studied. Objective: The aim of this study was to investigate the safety of transbronchial biopsy using a novel 1.1-mm cryoprobe. Methods: This prospective, single-arm study enrolled patients referred for transbronchial biopsy. All procedures were performed using the 1.1-mm cryoprobe with oversheath. The primary outcome was the composite of significant complications related to the cryobiopsy procedure (bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure). Bleeding and pneumothorax were graded according to previously published scales. Results: Fifty participants from two academic medical centers underwent transbronchial cryobiopsy. Indications for biopsy included evaluation of lung transplant allograft (50%), diffuse lung disease (44%), and pulmonary parenchymal lesion (6%). There were two pneumothoraces (4%), neither of which required aspiration or chest tube placement. There were no Grade 3 or 4 bleeding events. Mild bleeding (Grade ≤2) was observed in 25 cases (50%). No complications occurred that met the a priori primary outcome of bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure. Conclusions: Transbronchial cryobiopsy using a 1.1-mm cryoprobe is feasible with an acceptable safety profile.

A CASE OF RENAL CELL CARCINOMA WITH SMALL INTESTINE METASTASIS DURING NIVOLUMAB PLUS IPILIMUMAB

A 71-year-old man with a history of hoarseness and right upper extremity numbness was referred to our department for evaluation of an intrathoracic mass that was detected on chest radiography and a right kidney tumor observed on computed tomography (CT). Histopathological examination of percutaneous kidney biopsy and bronchoscopic lung biopsy specimens revealed renal clear cell carcinoma with multiple lung metastases. The patient showed a poor risk based on the International Metastatic renal cell carcinoma Database Consortium score, and nivolumab plus ipilimumab were initiated as first-line therapy. His symptoms gradually improved, following four courses of nivolumab plus ipilimumab treatment, and CT revealed shrinkage of all lesions. However, he developed diarrhea, rash, anemia, and elevated serum C-reactive protein levels (CRP) following this therapy. Diarrhea and rash were considered immune-related adverse events, and he was treated with oral prednisolone and topical corticosteroid. Nivolumab administration was discontinued because anemia worsened together with elevated serum CRP levels despite improvement in diarrhea. He subsequently developed constipation and abdominal bloating, following further treatment for 4 months. CT revealed intestinal tumor-induced intussusception, necessitating partial resection of the small intestinal tumor, which was histopathologically diagnosed as metastases. Both anemia and elevated CRP improved postoperatively. Currently, all metastatic lesions other than the resected intestine have continued to respond to treatment over 12 months after initiation of nivolumab plus ipilimumab therapy.

Age as a Risk Factor in the Occurrence of Complications during or after Bronchoscopic Lung Biopsy

Introduction: Bronchoscopic lung biopsy (BLB) is a widely used procedure. As the world’s population is ageing, more BLBs are performed for older people with comorbidities. The aim of the study was to investigate if an older age is a risk factor for BLB related complications. Materials and Methods: A prospective study at the Centre of Pulmonology and Allergology of Vilnius University Hospital Santaros klinikos was conducted. Seven hundred and eighty-six patients (male 60.6%), mean age 57 ± 16, who underwent BLB, were included. The complications that occurred due to BLB were evaluated. Bleeding and pneumothorax were classified into I° or II° grades depending on their severity. Potential determinants, which may increase the risk of complications, emphasizing on age, were analyzed. Results: Fifty-seven (7.2%) BLB-related complications occurred. There were 27 (3.4%) pneumothoraxes, and 19 (70%) of them required thoracic drainage. Thirty (3.8%) bleeding complications occurred, and four (16%) of them were severe. Higher rates of bleeding were found in the age group ≥65 years, p = 0.001. The risk of bleeding in older patients was 3.2 times higher (95% CI 1.51–6.87). Conclusions: Older age is related to a higher incidence of mild bleeding during BLB. However, the risk of life-threatening complications is low despite the age, and older age should not be considered as a contraindication for the procedure if needed.

Commentary on "Diagnostic value of surgical lung biopsies for diffuse parenchymal lung disease: the change of disease spectrum in the past 28 years in a single institution in China"

In the past 30 years, the diagnosis of diffuse interstitial lung disease (DPLD) in China has made great progress,and the understanding of the disease has been significantly improved. More and more diseases have been diagnosed by combining clinical, laboratory examination and typical high-resolution computed tomography(HRCT). In addition, the application of multidisciplinary discussion increased diagnosis rate, and the number of surgical lung biopsies was on a decreasing trend. However, lung biopsy was still required for some DPLD diseases. Different diseases required different lung biopsy methods. Some diseases with characteristic pathological features can be diagnosed by small biopsy specimens. Transbronchial cryobiopsy has a higher diagnostic rate than traditional bronchoscopic lung biopsy. Overall, the number of lung biopsy for DPLD is relatively low in China, and the development of non-tumor respiratory pathology is relatively lagging behind, and there is still the phenomenon of empirical hormone therapy in clinic. So many aspects on diagnosis and standardized treatment of DPLD still require continuous efforts to improve in the future.

Chemotherapy-Associated Pulmonary Toxicity—Case Series from a Single Center

BackgroundPulmonary toxicity due to chemotherapeutic agents can occur with many established and new drugs. Strong clinical suspicion is important as the clinical presentation is usually with nonspecific symptoms like cough, dyspnea, fever, and pulmonary infiltrates. Timely discontinuation of the offending agent alone can improve the condition.MethodsA prospective observational study on patients receiving chemotherapy at an 800-bedded tertiary care hospital was performed from 2014 to 2016. Consecutive patients on chemotherapy, presenting with nonresolving respiratory symptoms were evaluated with contrast-enhanced computerized tomography of chest, diffusion lung capacity for carbon monoxide (DLCO), fiberoptic bronchoscopy with lavage, and biopsy, after excluding all causes for pulmonary infections. Descriptive data has been depicted.ResultsA total of 18 patients were evaluated for persistent symptoms of dry cough, dyspnea, and fever among 624 who received chemotherapy during the study period. Ground-glass opacities on high-resolution CT was the most common imaging finding, others being patchy subpleural consolidation and pleural effusion. Lymphocyte-predominant bronchoalveolar lavage was detected in nine. Eight of the 15 patients who underwent DLCO, had abnormal results. Seven had significant histopathological findings on bronchoscopic lung biopsy, which revealed organizing pneumonia as the most common pattern. Paclitaxel, fluorouracil, gemcitabine, and tyrosine kinase inhibitors were the common culprit drugs. Discontinuation alone of the culprit drug was effective in 15 and 3 needed oral corticosteroids for relief of symptoms. None of the patients died due to the toxicity.ConclusionAn incidence of 2.8% for chemotherapy-induced lung injury was seen in our observational study of 3 years, with parenchymal, interstitial, and pleural involvement due to various chemotherapeutic agents. Oral steroids maybe required in a subset of patients not responding to discontinuation of the culprit agent.

Comparison of the GenCut Core Biopsy System to Transbronchial Biopsy Forceps for Flexible Bronchoscopic Lung Biopsy.

Pulmonary nodules are increasingly detected on screening and routine chest imaging, leading to an increase in diagnostic procedures. Bronchoscopy with transbronchial biopsy (TBBx) is the most common diagnostic modality, with diagnostic yield between 43% and 86%, largely dependent on the use of navigational modalities. In 2015 a new biopsy tool by Medtronic, the GenCut core biopsy system [GenCut transbronchial needle aspiration (TBNA)], was developed with the intention of improving yield in lung nodule biopsies. Our goal was to determine the efficacy of this new device when used in addition to TBBx. This is a prospective observational study of 324 consecutive bronchoscopic lung biopsies in which both TBBx and GenCut TBNA were performed on the same lesion. We recorded patient and nodule characteristics, along with the bronchoscopic modalities used. The primary outcome was the diagnostic yield with the addition of the GenCut TBNA, and the key secondary outcome was the complication rate. Of the 324 nodule biopsies analyzed, 164 (50.6%) were diagnostic via TBBx or GenCut TBNA.In all, 97 (59%) were positive in both TBBx and GenCut TBNA, 43 (26.2%) were positive only in TBBx, and 24 (14.6%) were positive only in GenCut TBNA. Overall, the addition of the GenCut TBNA increased the diagnostic yield by 7.4% (P<0.01). There were 7 complications: 5 pneumothoraxes and 2 episodes of bleeding. The diagnostic yield is improved by using the GenCut core biopsy system in addition to traditional TBBx forceps when performing bronchoscopy for pulmonary nodules, without an increase in complications. These biopsy methods should be used in tandem for the greatest yield.

ROLE OF TRANSBRONCHIAL LUNG BIOPSY AND BRONCHOALVEOLAR LAVAGE IN DIAGNOSIS OF DIFFUSE PARENCHYMAL LUNG DISEASE

Background: Diffuse parenchymal lung diseases (DPLD) constitute a group of over 200 diverse etiologic entities which present with respiratory symptoms and diffuse lung infiltrates and account for 15% of patients seen by a pulmonary physician. Objective: To evaluate the role of transbronchial lung biopsy and bronchoalveolar lavage in diagnosis of diffuse parenchymal lung disease. Patients and Methods: This prospective cross-sectional study was carried out at the Department of Chest, Al-Hussein University Hospital, during the period from October 2019 to October 2020, and included sixty patients admitted in the inpatient wards with undiagnosed DPLD, after detailed history taking, physical examinations, routine labs, chest X-ray PA view, HRCT chest, pulmonary function tests (PFTs) as simple spirometry, ECG, echocardiography and Arterial blood gases evaluation. All of them were subjected to fibrooptic bronchoscope, transbronchial lung biopsy and bronchoalveolar lavage. Results: As regard comparison between bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) diagnostic yield there was a statistical significant difference between TBLB positive and negative patients, as regard BAL predominant cells and BAL microbiology. the comparison of histopathology as regard TBLB diagnostic yield showed a statistical significant difference between TBLB positive and TBLB negative patients. Conclusion: Bronchoalveolar lavage was a minimally invasive procedure performed during flexible bronchoscopy. BAL cellular analysis alone was insufficient to diagnose the specific type of DPLD, except in malignancies and some rare interstitial lung diseases (ILDs), and the yield of bronchoscopic lung biopsy was high in diseases where the lesions were peri bronchial in distribution such as in sarcoidosis, hypersensitivity pneumonitis and organizing pneumonias.

Interstitial lung disease in a veterans affairs regional network; a retrospective cohort study

BackgroundThe epidemiology of Interstitial Lung Diseases (ILD) in the Veterans Health Administration (VHA) is presently unknown.Research questionDescribe the incidence/prevalence, clinical characteristics, and outcomes of ILD patients within the Veteran’s Administration Mid-Atlantic Health Care Network (VISN6).Study design and methodsA multi-center retrospective cohort study was performed of veterans receiving hospital or outpatient ILD care from January 1, 2008 to December 31st, 2015 in six VISN6 facilities. Patients were identified by at least one visit encounter with a 515, 516, or other ILD ICD-9 code. Demographic and clinical characteristics were summarized using median, 25th and 75th percentile for continuous variables and count/percentage for categorical variables. Characteristics and incidence/prevalence rates were summarized, and stratified by ILD ICD-9 code. Kaplan Meier curves were generated to define overall survival.Results3293 subjects met the inclusion criteria. 879 subjects (26%) had no evidence of ILD following manual medical record review. Overall estimated prevalence in verified ILD subjects was 256 per 100,000 people with a mean incidence across the years of 70 per 100,000 person-years (0.07%). The prevalence and mean incidence when focusing on people with an ILD diagnostic code who had a HRCT scan or a bronchoscopic or surgical lung biopsy was 237 per 100,000 people (0.237%) and 63 per 100,000 person-years respectively (0.063%). The median survival was 76.9 months for 515 codes, 103.4 months for 516 codes, and 83.6 months for 516.31.InterpretationThis retrospective cohort study defines high ILD incidence/prevalence within the VA. Therefore, ILD is an important VA health concern.

Interstitial lung disease in a veterans affairs regional network; a retrospective cohort study.

The epidemiology of Interstitial Lung Diseases (ILD) in the Veterans Health Administration (VHA) is presently unknown. Describe the incidence/prevalence, clinical characteristics, and outcomes of ILD patients within the Veteran's Administration Mid-Atlantic Health Care Network (VISN6). A multi-center retrospective cohort study was performed of veterans receiving hospital or outpatient ILD care from January 1, 2008 to December 31st, 2015 in six VISN6 facilities. Patients were identified by at least one visit encounter with a 515, 516, or other ILD ICD-9 code. Demographic and clinical characteristics were summarized using median, 25th and 75th percentile for continuous variables and count/percentage for categorical variables. Characteristics and incidence/prevalence rates were summarized, and stratified by ILD ICD-9 code. Kaplan Meier curves were generated to define overall survival. 3293 subjects met the inclusion criteria. 879 subjects (26%) had no evidence of ILD following manual medical record review. Overall estimated prevalence in verified ILD subjects was 256 per 100,000 people with a mean incidence across the years of 70 per 100,000 person-years (0.07%). The prevalence and mean incidence when focusing on people with an ILD diagnostic code who had a HRCT scan or a bronchoscopic or surgical lung biopsy was 237 per 100,000 people (0.237%) and 63 per 100,000 person-years respectively (0.063%). The median survival was 76.9 months for 515 codes, 103.4 months for 516 codes, and 83.6 months for 516.31. This retrospective cohort study defines high ILD incidence/prevalence within the VA. Therefore, ILD is an important VA health concern.

The spectrum of pathogens in 187 cases of pulmonary fungal disease diagnosed by histopathology-a retrospective analysis

Objective: To investigate the spectrum of pathogens causing lung fungal disease diagnosed by histopathology through histochemical special staining, compared to the fungal culture results, and to further evaluate the diagnostic value of histochemical special staining in pulmonary fungal disease. Methods: We performed a retrospective analysis of 187 cases of pulmonary fungal disease diagnosed by histopathology in Peking Union Medical College Hospital from 2001 to 2015 (including 92 cases with pulmonary resection or open lung biopsy, 33 with percutaneous lung biopsy and 62 ones with fiberoptic bronchoscopic lung biopsy). All cases were treated with hexamine silver, PAS, mucus carmine and acid-fast staining in addition to conventional HE staining. The clinical records and the fungal culture results were reviewed. Results: There were 103 male and 84 female patients, aged from 12 to 70 years [average (48±14) years]. There were 85 cases(45.5%) of pulmonary aspergillosis(including 60 cases of invasive infection and 25 cases of aspergilloma), 51 cases(27.3%) of pulmonary cryptococosis, 6 cases (3.2%)of pulmonary mucormycosis, 3 cases(1.6%) of pulmonary histoplasmosis, 3 cases (1.6%)of pulmonary candidiasis, and 2 cases (1.1%) of pneumocystosis, while in the remaining 37 cases (19.8%) the pathogens could not be clearly classified by microscopy due to limited tissue or degeneration. Among the 88 patients with pulmonary fungal disease diagnosed by histopathology from 2011 to 2015, 35 ones (39.9%) were detected by fungal culture (including lung biopsy, intraoperative swab, blood, bronchoalveolar lavage fluid and sputum, etc.). The diagnostic results of 18 cases were completely consistent between histopathological examination and fungal culture (18/35, 51.4%), while 13 cases (13/35, 37.1%) were diagnosed by histopathology but no fungi were cultured, and in 3 cases (3/35,8.6%) the culture was positive for fungi which could not be classified clearly by histopathology. In another case the pathogen was found to be Cryptococcus histopathologically but the lavage culture grew"candida", but the patient's blood cryptococcal antigen was positive. Conclusions: Among patients with histopathological diagnosis of pulmonary fungal disease, pulmonary aspergillosis was the most common, followed by pulmonary cryptococcosis, pulmonary mucormycosis, pulmonary histoplasmosis, pulmonary candidiasis and pneumocystosis. A small number of cases could not be classified by histopathology through histochemical special staining. There was a high consistency in discovering fungal pathogens between pathological histochemical special staining and culture method, but 37% pulmonary fungal disease diagnosed by histopathology were culture negative. In practice, the role of histochemical special staining in diagnosing pulmonary fungal disease should be paid more attention.

Diagnostic yield, safety, and impact of transbronchial lung biopsy in mechanically ventilated, critically ill patients: a retrospective study

BackgroundPulmonary infiltrates of variable etiology are one of the main reasons for hypoxemic respiratory failure leading to invasive mechanical ventilation. If pulmonary infiltrates remain unexplained or progress despite treatment, the histopathological result of a lung biopsy could have significant 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.MethodsRetrospective, monocentric, observational study in mechanically ventilated, critically ill patients, subjected to TBLB due to unexplained pulmonary infiltrates 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.ResultsForty-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 confirmed 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.ConclusionsTransbronchial lung biopsy remains a valuable alternative to surgical lung biopsy in mechanically ventilated 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.

Constrictive (Obliterative) Bronchiolitis as Presenting Manifestation of Connective Tissue Diseases.

Constrictive (obliterative) bronchiolitis (CB) is an uncommon form of obstructive lung disease that can occur in patients with identifiable causes including connective tissue diseases (CTDs) as a form of lung involvement. We explored whether CB can be the presenting manifestation of CTD. We identified 44 patients with cryptogenic CB and examined the presenting clinical, laboratory, and radiologic features, as well as their clinical course. The mean age at presentation was 60.5 (SD, 13.8) years and included 38 women (86%); 32 (73%) were never smokers. All patients presented for evaluation of dyspnea, commonly associated with cough. An obstructive pattern on pulmonary function testing was demonstrated in 86% of patients. On chest high-resolution computed tomography, nearly all patients manifested a mosaic attenuation pattern with air trapping on expiratory views, characteristic of CB. Bronchoscopic lung biopsy (n = 10) was usually nondiagnostic (90%), whereas all 5 surgical lung biopsies yielded evidence of CB. Serologic testing for CTD was positive in 19 patients (43%) and most commonly included antinuclear antibody, rheumatoid factor, and anti-cyclic citrullinated antibodies. Seven of these patients with positive serologic results were eventually diagnosed to have CTD. Connective tissue diseases included rheumatoid arthritis in 4 patients, Sjögren syndrome in 2, and undifferentiated CTD in 1 patient. Nearly one-half of patients with cryptogenic CB manifest positive CTD serology, and some of these patients have CTD not previously diagnosed. These results suggest that CB can be the presenting manifestation of a CTD.

Direct-from-blood RNA sequencing identifies the cause of post-bronchoscopy fever

BackgroundAntibiotic resistance is rising at disturbing rates and contributes to the deaths of millions of people yearly. Antibiotic resistant infections disproportionately affect those with immunocompromising conditions, chronic colonization, and frequent antibiotic use such as transplant patients or those with cystic fibrosis. However, clinicians lack the diagnostic tools to confidently diagnose and treat infections, leading to widespread use of empiric broad spectrum antimicrobials, often for prolonged duration.Case presentationA 22 year-old Caucasian female with cystic fibrosis received a bilateral orthotopic lung transplantation 5 months prior to the index hospitalization. She underwent routine surveillance bronchoscopy and was admitted for post-procedure fever. A clear cause of infection was not identified by routine methods. Imaging and bronchoscopic lung biopsy did not identify an infectious agent or rejection. She was treated with a prolonged course of antimicrobials targeting known colonizing organisms from prior bronchoalveolar lavage cultures (Pseudomonas, Staphylococcus aureus, and Aspergillus). However, we identified Stenotrophomonas maltophilia in two independent whole blood samples using direct-pathogen sequencing, which was not identified by other methods.ConclusionsThis case represents a common clinical conundrum: identification of infection in a high-risk, complex patient. Here, direct-pathogen sequencing identified a pathogen that would not otherwise have been identified by common techniques. Had results been clinically available, treatment could have been customized, avoiding a prolonged course of broad spectrum antimicrobials that would only exacerbate resistance. Direct-pathogen sequencing is poised to fill a diagnostic gap for pathogen identification, allowing early identification and customization of treatment in a culture-independent, pathogen-agnostic manner.

ELECTROMAGNETIC NAVIGATIONAL (EMN) BRONCHOSCOPY AND EMN PERCUTANEOUS TRANSTHORACIC NEEDLE BIOPSY OF THE CHEST LESION: THE FIRST 102 CONSECUTIVE EARLY EXPERIENCE CASES

ELECTROMAGNETIC NAVIGATIONAL (EMN) BRONCHOSCOPY AND EMN PERCUTANEOUS TRANSTHORACIC NEEDLE BIOPSY OF THE CHEST LESION: THE FIRST 102 CONSECUTIVE EARLY EXPERIENCE CASES